CRC Reference Manual_September2022 Flipbook PDF

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Clinical Research Coordinator

Reference Binder Name:

August 2022

Table of Content 1.

Clinical Operating Guidelines

2. Standard Operating procedures Handbook 3. Clinical Research Reference Manual 4. Acronyms & Initialisms 5. Supplemental Binder Table of Content 6. CRC Checklist (Daily) 7. Study Startup Checklist in CTMS 8. Site Signature & Delegation of Duties Log 9. Source Document Request Form 10. Adding or Removing a Staff Member 11. Training Log Instructions 12. Master ICF Log 13. MCR Forms 14. MCR Logs 15. Chart Labels

Section 1

Clinical Operating Guidelines

Clinical Operating Guidelines STUDY SCREENING VISITS This guideline describes the methods for recruitment and prescreening of subjects for clinical studies at all Meridian Clinical Research (MCR) sites It is intended to meet FDA regulations, ICH/GCP Guidelines, industry standards and MCR policies and procedures for screening of study volunteers. The Patient Recruitment team, study staff and the investigators are responsible for appropriate recruitment of subjects. The study staff will communicate with the volunteers to collect accurate information during the recruitment and prescreening process. It is permissible to ask a potential subject to fast prior to signing the Informed Consent Form (ICF) as this is considered non-invasive and routine/SOC. If a protocol requires a subject to be fasting for a visit, they will be advised of this requirement prior to their scheduled appointment. The MCR Demographic Form is to be completed and placed in the study chart and uploaded to the site CTMS for each person presenting for a screening visit if paper chart is unitized. If electronic source chart is used the demographic form will be completed and uploaded to the electronic chart. Prior to any study procedures being performed, an IRB approved informed consent must be signed and dated by the subject and person explaining the consent. Under no circumstances shall a potential subject be told to withhold any medication without first signing an approved informed consent document that describes the potential benefits and risks. Eligibility for study participation must be determined by a Principal Investigator (PI) or Sub-Investigator (SI) after the required ICF has been signed and prior to randomization. MCR requires all subjects be given a physical exam prior to randomization and/or at initial investigational product (IP) administration/dispensation to ensure eligibility criteria is met. Once the ICF has been administered, a health history is obtained and carefully documented with complete dates whenever possible. The participant may be asked to obtain validation if dates or conditions are unclear. If the study or investigator requires medical records a medical release form should be signed by subject and records requested. For potential participants who fail to meet entry criteria for current clinical studies, permission may be given to store the data in the CTMS to contact them at a later date for participation in other studies. Subjects who demonstrate chronic poor compliance with study procedures (visits, medications, or diary completion) may not be considered for future study participation.

Guideline #01 Version date: August 2021

Page 1 of 2

Clinical Operating Guidelines Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 50.25 Elements of informed consent 21 CFR 312.60 General responsibilities of investigators 21 CFR 312.62 Investigator recordkeeping and record retention 21 CFR 50.20 General requirements for informed consent 21 CFR 50.27 Documentation of Informed Consent FDA Information Sheets, January 1998

A Guide to Informed Consent Document; Institutional Review Boards Frequently Asked Questions

Guidance for Industry October 2009

Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects

March 2018

Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2)

Meridian Clinical Research SOP # 2/3, January 2021

Informed Consent Process for Adults or Informed Consent Process for Pediatric Subjects

Meridian Clinical Research Guideline #10, January 2021

Medical Records

Guideline #01 Version date: August 2021

Page 2 of 2

Clinical Operating Guidelines MONITORING VISITS This guideline provides the methods of preparing for and conducting monitoring visits for clinical studies at all Meridian Clinical Research (MCR) sites. It is intended to meet FDA regulations, ICH/GCP Guidelines, industry standards and MCR policies and procedures for monitor visits. The purpose of a CRA/monitor visit is to verify that the rights and well-being of human subjects are protected, the trial data are accurate, complete, and verifiable from source documents, the conduct of the trial is in compliance with currently approved protocol/amendment(s). The four main types of monitoring visits are: Pre-study visit (PSV), Site initiation visit (SIV), Interim monitoring visit (IMV), and Close out visit (COV). A sponsor/CRO may also choose to have remote or phone monitoring visits in addition to or in place of on-site visits. A sign-in log must be completed at each visit by CRA/monitor with date and purpose of visit. The clinical research coordinator (CRC) or site representative and the CRA must sign the log at the end of each visit to verify visit date and time. For remote/phone visits, the CRC must complete a Remote Visit Log and enter the date and time of the visit with the designation as a remote visit. Prior to a monitoring visit (IMV or COV), the Lead CRC (LCRC/ACRC) or Assistant CRC (ACRC) assigned to the study or delegated staff will prepare a monitoring room with the Trial Master File (TMF) to include the site supplementary binder, logs, and subject charts. Access to the e-Regulatory Portal TMF should be arranged in advance of the visit. The LCRC/ACRC is also to review pertinent areas (lab, drug room, etc) to make certain that all areas are clean and organized prior to the monitor’s arrival. PREPARING FOR A MONITOR VISIT • The LCRC/ACRC/ACRA will ensure that all case report forms (CRFs), and source documents are complete and signed as required. The LCRC/ACRC/ACRC should collect and have readily accessible all CRFs (electronic or paper), all subject charts and source documents including the results of any diagnostic testing required by the protocol • The updated TMF and supplementary binder will contain documents that verify previous communications between the site and sponsor/CRO, all study and drug accountability logs • Queries are to be checked twice weekly and have all resolved by Friday of each week so there are no outstanding queries at time of monitor visit • The LCRC/ACRC will ensure that the drug accountability and temperature logs are complete and up to date • The LCRC/ACRC will arrange for a quiet area where the monitor can work effectively, preferably away from subject care areas • The LCRC/ACRC will schedule for time to meet with the monitor to make all necessary corrections during the visit so that pertinent issues can be addressed and resolved • If not received within 5 days prior to visit, a confirmation letter should be requested from the sponsor/CRO with agenda for visit or an email sent to the CRA confirming the visit.

Guideline #02 Version date: August 2021

Page 1 of 3

Clinical Operating Guidelines DURING THE MONITOR VISIT • The monitor should meet with the Principal Investigator (PI) at each visit. Should the PI be unavailable on the day of the visit a phone visit should be scheduled with documentation of the call to be placed in the TMF. • Reserve time during the monitor’s day to review study progress and forms. The LCRC/ACRC should ask about the status of study enrollment, if the initial study timelines for completion will be maintained, and if enrollment might be extended • As soon as possible, the next monitoring visit should be scheduled with a date agreed upon mutually. The visit is to be entered into the site calendar in CTMS and the PI’s schedule. The investigator and QA representative should also be made aware of the date of the next visit via email • To maintain confidentiality, discussions not related to the study should not be held within the hearing of monitors. This may include personnel issues, subject issues, information related to other studies, etc. VISIT FOLLOW UP • Monitor follow-up letter/report should be received within 14 business days of completion of the visit. If not received, site should request letter from CRA. (Attachment #1 – correspondence template) • Response to follow-up letters/reports with open items should be completed and returned to the monitor within 14 business days • All communication between the sponsor and the site should be documented with copies in the TMF or supplementary binder; All telephone conversations regarding the trial should be documented and filed in the correspondence section of the TMF • Notify the monitor/sponsor and IRB, as required when there is a study participant exception/protocol deviation • Notify the monitor, sponsor, and IRB of all Serious Adverse Events

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.60 General responsibilities of investigators Guideline #02 Version date: August 2021

Page 2 of 3

Clinical Operating Guidelines 21 CFR 312.62

Investigator recordkeeping and record retention

March 2015 Guidance for Industry October 2009 March 2018

Compliance Program Guidance Manual For FDA Staff Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) SOP #15: Electronic Regulatory Documents

Meridian Clinical Research January 2021

Attachment #1 – Correspondence template for monitoring visits

Guideline #02 Version date: August 2021

Page 3 of 3

Clinical Operating Guidelines QUALITY ASSURANCE This Guideline describes the methods and procedures for quality assurance for clinical studies conducted at all Meridian Clinical Research (MCR) sites. It is intended to meet industry standards, FDA Regulations and ICH/GCP Guidelines. The Principal Investigator (PI), clinical research coordinator (CRC), and Quality Assurance staff are responsible for maintaining high quality data collection and complying with all GCP procedures during the conduct of a clinical study. Quality Assurance (QA) consists of all planned and systematic actions that are established to ensure that the trial is performed, and data are generated, documented (recorded) and reported in compliance with ICH/GCP and the applicable regulatory requirements, industry standards, and MCR policies and procedures. The following are in place at MCR sites to ensure quality of clinical studies: • • • • • •

Standard Operating Procedures (SOPs) to ensure quality and consistency which are reviewed and updated annually Staff training The use of checklists, source documents, and other forms to ensure that documentation is complete and accurate Periodic internal audits to ensure compliance with SOPs, FDA Regulations, ICH/GCPs, and protocols, as well as accuracy of data Correction of deficiencies found through internal audits, inspections, or sponsor monitoring visits: protocol deviations, regulatory non-compliance, AE/SAE reporting CAPA plans generated when required to ensure compliance, corrective action taken, preventive measures taken, and additional training if necessary

Each study may be reviewed by the sponsor/monitor and is reviewed by the CRC during the course of the study to ensure that the study will pass an FDA inspection. The following areas may be audited: • • • • • • • •

Informed consent forms: complete and accurate Source documents with appropriate signatures and dates Maintenance of study drug accountability and subject compliance All communications between the sponsor, CRO, IRB and the site IRB submissions, correspondence, and approvals AE/SAE reporting and follow-up Verification of adherence to the protocol Documentation and reporting of protocol deviations

Guideline #03 Version date: August 2021

Page 1 of 2

Clinical Operating Guidelines Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES March 2015 Compliance Program Guidance Manual for FDA Staff Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2)

Guideline #03 Version date: August 2021

Page 2 of 2

Clinical Operating Guidelines HIPAA NON-COVERED ENTITY SUBJECT CONFIDENTIALITY Meridian Clinical Research (MCR) does not furnish, bill, or receive payment for health care in the normal course of business. Therefore, MCR sites are not a covered entity under the Health Insurance Portability & Accountability Act of 1996. For the MCR sites embedded in a private practice, HIPAA Privacy Rules will be adhered to as set forth for practice-related charts and documents. Taking Study Documents Off-Site • • • • •

Study documents may be removed from an MCR site when deemed necessary for review at a remote location. Approval from Regional Manager (or Leadership) for removal of study documents from the site must be received prior to taking the documents off-site. Only designated employee(s) of MCR will have access to documents/charts removed from the site. A sign-out log will be maintained at the main office and all documents/charts will be logged out with subject number, initials/date of individual taking chart and logged back in upon return. Transport of charts will be by personal vehicle, courier or rental car as needed.

Subject Confidentiality • • • • •



Study-related assessments and procedures are conducted in a private room located within the clinic. No one other than the subject, parent/guardian/LAR when required, and research staff will be allowed into the examination room during study visits unless the subject gives consent to have others (friends, family members) present in the room. No personal information will be collected from the subject other than what is necessary for study purposes and with permission from subject. Access to Protected Health Information is limited solely to investigators and MCR staff. Paper records (screening logs, lab reports, source documentation, paper CRFs, etc.) and individual subject charts are kept in the research staff offices. The office doors are all equipped with locks for the protection of subject and study information. Charts may be taken off-site as noted above. Protected Health Information may be entered into an electronic database (CTMS) which is Part 11 compliant.

Guideline #04 Version date: January 2021

Page 1 of 2

Clinical Operating Guidelines Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

12-1-2021

_______________________________________________ Signature

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES FDA Information Sheet Recruiting Study Subjects: Guidance for Institutional Review Boards Updated March 2018 and Clinical Investigators Guidance for Industry October 2009

Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects

ICH Guideline E6 (R2) November 2016

Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2)

Public Law 104-191 The HIPAA Privacy Rule

Health Insurance Portability and Accountability Act of 1996 (HIPAA) 45 CFR Part 160 and Subparts A and E of Part 164

Changes made Clarified parent/guardian/LAR language Added section “Taking Study Documents Off-Site Added “practice-related charts and documents” to first paragraph for clarity Added “Charts may be taken off-site as noted above” to 5th bullet in Subject Confidentiality section

Guideline #04 Version date: January 2021

Date 22Jan2020 02Nov2020 02Nov2020 02Nov2020

Page 2 of 2

Clinical Operating Guidelines SUBJECT STIPENDS Stipends are paid at the conclusion of each study visit to compensate for the subject’s time and travel unless otherwise designated by sponsor. Payment will be either by a subject payment card or by check. All stipends must be approved by the IRB as part of the Informed Consent Form (ICF). The IRB determines if the amount of compensation is reasonable and not coercive as approved in the ICF. Payment of stipends is not contingent upon completion of the study. When a visit is completed, funds will be approved and loaded directly onto the payment card. The funds are available on the day of visit after being loaded. The subject will be issued one card for the duration of participation. The subject/parent may be charged for replacement cards. Should a check be written for payment of the study stipend, the checks for adult studies may only be written in the name of the subject. Stipend checks written for pediatric studies may be written in the name of the parent or legal guardian. The study and the visit number should be documented in the “memo” section of the check. The copy of the check will be kept with Meridian Clinical Research’s financial documents. There may be studies in which the sponsor provides study payment therefore the above process may not be followed. Standard Customer Service/Client Reimbursement Process A preloaded $25 gift card may be offered to customers/clients of Meridian Clinical Research (MCR) across all MCR sites/locations. This is done to maintain positive community relations when situations cause inconvenience for MCR’s current and/or potential subjects. Approval must be obtained prior to distribution. This general practice process applies to all subjects regardless of status, (e.g., if they were consented for a specific study, screen failed, did not qualify for a study) such as: waited too long for visit, experienced inconvenience when MCR sites participate in large enrolling studies, needed rescheduling, needed to return to the research office.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

Attachment #1 – Meridian General Reimbursement Process

Guideline #05 Version date: August 2021

Page 1 of 2

Clinical Operating Guidelines APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 56.109 IRB review of research 21 CFR 312.60 General responsibilities of investigators 21 CFR 50.20 General requirements for informed consent FDA Information Sheets, A Guide to Informed Consent Document; Institutional Review Boards January 1998 Frequently Asked Questions FDA Information Sheet Recruiting Study Subjects: Guidance for Institutional Review Boards Updated March 2018 and Clinical Investigators Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2)

Changes made Added “Standard Customer Service/Client Reimbursement Process” paragraph

Date October 2018

Revised first paragraph to include “Compensation provided to subjects is not to be presented in a manner that may be coercive. Payment of stipends is not contingent upon completion of the study.” Added: “The IRB determines if the amount of compensation is reasonable and not coercive as approved in the informed consent form”; deleted “Compensation provided to subjects…”

June 2019

Guideline #05 Version date: August 2021

August 2021

Page 2 of 2

Clinical Operating Guidelines TIME DOCUMENTATION Meridian Clinical Research (MCR), in order to ensure timing accuracy and consistency for study protocol requirements at all MCR sites for time entries on study source documentation will document time using the time from the atomic clocks that may be located in patient examination rooms in MCR offices. If atomic clock is not available or in working condition, the use of research staff cell phones is acceptable.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.62 Investigator recordkeeping and record retention Guidance for Industry October 2009

Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects

March 2018

Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2)

Guideline #06 Version date: August 2021

Page 1 of 1

Clinical Operating Guidelines SENDING FORMS IN ADVANCE OF A STUDY Meridian Clinical Research (MCR) sites may send certain forms to potential participants interested in a clinical trial in advance of their first visit. These forms may include but are not limited to the following: • IRB approved Informed Consent/Assent for review; this copy is only sent for review and does not change the MCR existing informed consent policy - the subject is not to sign this form but will be given a new ICF to read, ask questions and sign at their first/screening visit after questions are answered and prior to any study-related procedures to be performed • Demographic Form (to be included in the subject’s chart and uploaded to CTMS) • Medical Release Authorization Form • Medical history and concomitant medication memory aids • IRB approved ads or study related materials, flyer/information sheet

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.60 General responsibilities of investigators 21 CFR 312.62 Investigator recordkeeping and record retention 21 CFR 50.20 General requirements for informed consent 21 CFR 50.27 Documentation of Informed Consent FDA Information Sheets, January 1998 Guidance for Industry October 2009 March 2018

Guideline #07 Version date: August 2021

A Guide to Informed Consent Document; Institutional Review Boards Frequently Asked Questions Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2)

Page 1 of 1

Clinical Operating Guidelines EQUIPMENT CALIBRATION All medical and other equipment required and/or used in clinical trials at Meridian Clinical Research (MCR) sites requiring calibration will be calibrated annually or per manufacturer instructions unless otherwise required by the sponsor. Calibration receipts and/or records are filled in the MCR calibration binder/file for each site. Copies of these records will be placed in each Trial Master File at study closeout, as required by study sponsor.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects ICH Guideline E6 (R2) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical March 2018 Practice E6 (R2)

Guideline #08 Version date: August 2021

Page 1 of 1

Clinical Operating Guidelines URINE PREGNANCY TESTING All female subjects must have a urine pregnancy test (UTP) performed based upon protocol-specific and sponsor requirements. A subject’s urine pregnancy test information will be documented in source documents and pregnancy test log. The test must be negative prior to randomization and dispensation of investigational product. Information to be recorded: brand name, lot number, date/time of test results, and expiration date of kit. If required by protocol, pregnancy test will be repeated throughout study participation. All manufacture directions will be followed when performing testing.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2)

Guideline #09 Version date: August 2021

Page 1 of 1

Clinical Operating Guidelines MEDICAL RECORDS Meridian Clinical Research (MCR) does not require medical records from potential participants prior to or during a subject’s participation in a clinical trial. Medical records are requested from study subjects if they are required by protocol, to establish a definitive diagnosis, to support the criteria for study participation or if requested by the investigator. If medical records are required for study participation a medical records release form must be signed by subject for the specific records needed (e.g., 6 months, 1 year prior, vaccine only, etc.). If the staff is unsure that the subject is providing accurate or complete information, medical records may be requested. Once the records are received, they must be stamped with certified receipt stamp. Records received by MCR are certified with “Certified Receipt” stamp to indicate that is an accurate and complete representation of the medical records as received by MCR. Certification of receipt should be accomplished by having the person who makes/prints the copy initial/date the copy with number of pages received to indicate it meets the requirements of certified as described above. The records should be reviewed to compare with verbal medical history provided by the subject to ensure accuracy and to ensure study eligibility criteria has been met by the study subject. The source document medical history is to be updated as needed and medical records may be maintained in the subject’s study chart.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_________ Date

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.60 General responsibilities of investigators 21 CFR 312.62 Investigator recordkeeping and record retention Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2)

Changes made Added paragraph #3 regarding using Certified Receipt stamp Guideline #10 Version date: August 2021

Date January 2021

Page 1 of 2

Clinical Operating Guidelines Added : “…and medical records may be maintained in the subject’s study chart”

Guideline #10 Version date: August 2021

August 2021

Page 2 of 2

Clinical Operating Guidelines REGULATORY DOCUMENTS This Guideline describes the procedures for the creation, collection, and storage of complete Trial Master File (TMF) regulatory documents for clinical studies at Meridian Clinical Research (MCR) sites. It is intended to meet FDA regulations, ICH/GCP Guidelines and industry standards for documents required for clinical studies. The TMF may be either a paper/hard copy file, an electronic file of documents or a combination of the two. The Principal Investigator (PI) and research staff are responsible for maintaining all required TMF regulatory documents for clinical studies to meet sponsor, ICH/GCP and FDA compliance. The delegated staff person is responsible for obtaining and filing all required regulatory documents for each study. The lead Clinical Research Coordinator (LCRC) and regulatory staff are responsible for maintaining records of study administrative and regulatory activities as well as data from each study participant. When a study is being planned, a TMF regulatory binder is started for each study by the assigned staff person so that all documents are collected properly for the study. Copies of ALL documents relating to clinical studies will be kept in the TMF and/or supplemental binder. Copies or originals may be sent to the Sponsor/IRB, as appropriate; any original documents sent off site should be documented to whom they were send with signature/date of person sending. The LCRC or delegated staff will continue to file additional documents created or received in appropriate sections of the TMF. At the end of the study, the LCRC will audit the TMF documents and discrepancies will be noted; missing documents will be obtained from sponsor and filed. After the study is completed, and audited to determine that the TMF is complete, it will be archived as outlined in SOP #9, Document Storage. The TMF will be maintained in a secure location and made available for Sponsor or FDA inspection. When completing the initial Form FDA 1572 (1572), Section #6, MCR lists medical doctors, PAs or NPs as subinvestigators. All other CRCs and/or RAs who may perform specific protocol procedures are listed on the site Delegation Log unless otherwise required by the Sponsor/CRO. (See section VII, #33 page 14 of FAQs for Form FDA 1572) When study staff changes (e.g., subinvestigators are added or removed) a new 1572 may not generated but Note to File may be created to document the changes and inform the sponsor of these changes unless otherwise required by Sponsor/CRO. This is done so that the sponsor can appropriately update the IND. (See Section I, #7 of FAQs for Form FDA 1572)

Guideline #11 Version date: August 2021

Page 1 of 2

Clinical Operating Guidelines Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.60 General responsibilities of investigators 21 CFR 312.62 Investigator recordkeeping and record retention Information Sheet Guidance for Frequently Asked Questions – Statement of investigator (Form FDA Sponsors, Clinical Investigators, 1572) and IRBs May 2010 Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2) Meridian Clinical Research SOP #15: Electronic Regulatory Documents January 2021

Changes made Added two paragraphs regarding Form FDA 1572 (paragraphs 7 & 8) Added to paragraph one “and industry standards” Added to paragraph one “The TMF may be either a paper/hard copy file, an electronic file of documents or a combination of the two” Combined paragraph 5 and 7 Added in Paragraph 4: and/or supplemental binder” and “; any original documents sent off site should be documented to whom they were send with signature/date of person sending.”

Guideline #11 Version date: August 2021

Date 6.25.18 May 2019 May 2019 January 2021 August 2021

Page 2 of 2

Clinical Operating Guidelines HIV TESTING AND REPORTING Meridian Clinical Research (MCR) will allow any subject requiring HIV testing to first read the procedure consent form, at their own pace, in a private setting. The delegated staff will review the sponsor provided and IRB approved HIV testing consent with the subject and provide answers to questions. The subject will also have the opportunity to ask questions of an investigator who is available at the site. Once the subject’s questions/concerns have been adequately answered, they can make the decision to consent or not, to the given test. The consent will be witnessed by the site staff and/or investigator and a fully executed copy of the consent given to the subject. This process will be clearly documented in the subject’s research chart. Employees of MCR will follow all testing guidelines provided by the lab and/or test manufacturer. All results will be sent to Meridian Clinical Research to be placed in the subject’s chart, reviewed, and assessed by an Investigator. Subjects will receive results at their next scheduled appointment or contacted by telephone to establish an appointment. If three phone calls are made unsuccessfully, MCR will send a certified letter stating the importance of reaching the subject (no results will be provided over the phone). Subjects receiving a positive first lab result will be contacted to have a Western Blot test. The initial test results will be given to the subject, in a private setting, by a physician, physician’s assistant, or nurse practitioner. An explanation of further testing will be discussed. If the confirmatory test comes back positive, MCR will contact the subject and comply with all state required reporting guidelines. The site will comply with the CDC’s Guidelines for HIV Counseling, Testing, and Referral. The subject will be referred to the appropriate health program/facility for further care and counseling. All MCR staff will adhere to strict subject confidentiality.

Approved by Nicole Osborn, MD Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES CDC Guidelines for HIV Testing https://www.cdc.gov/hiv/guidelines/testing.html 21 CFR 312.62 Investigator recordkeeping and record retention FDA Information Sheets Screening Tests Prior to Study Enrollment (January 1998) Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects November 2016 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2)

Guideline #12 Version date: January 2021

Page 1 of 1

Clinical Operating Guidelines TRANSPORTING SPECIMENS This Guideline establishes the policy and procedures for the transport of specimens from the location where the subject was seen and the specimen was collected to the location where it will be processed and packaged for shipment. The specimens will be handled as follows: •

• • • • • •



Universal precautions will be observed to prevent any contact with potentially infected bodily fluids - information at: https://www.osha.gov/bloodborne-pathogens/workerprotections Specimens will be collected per protocol or standard of care (SOC) procedures After collection, specimens will be placed in a container provided by MCR which prevents leakage during transport. The container will be labeled with an orange-red biohazard emblem and closed prior to being transported Specimens that require specific temperatures prior to and during processing will be placed in coolers or on dry ice to maintain the necessary temperature. Temperatures may be tracked, as required (Use Specimen Transport Log) Ambient specimens will be transported immediately in insulated bags provided by MCR directly from collection location to the processing location (site) to avoid exposure to heat or cold. A courier may be used for transporting specimens to clinical research site for processing and packaged for shipment to clinical trial lab. Should a courier be used, the site will adhere to the policy/procedure set forth by the courier service or as dictated by protocol.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

Guideline #13 Version date: August 2021

12-1-2021

_____________ Date

Page 1 of 2

Clinical Operating Guidelines APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.60 General responsibilities of investigators 29 CFR 1910.1030 OSHA Bloodborne Pathogens Standard Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2) Meridian Clinical Research January 2021

SOP #05: Handling of Investigational Product

OSHA Standards

https://www.osha.gov/bloodborne-pathogens/worker-protections

Guideline #13 Version date: August 2021

Page 2 of 2

Clinical Operating Guidelines BIOHAZARD DISPOSAL Meridian Clinical Research (MCR) requires all bio-hazardous material to be disposed of in the provided, approved Biohazard containers. MCR staff is trained on and follow OSHA standards for disposal of medical waste, termed “regulated waste”. This includes blood and items contaminated with blood or other potentially infectious materials. Universal precautions are observed to prevent any exposure to infectious materials. Biohazardous material includes, but is not limited to the following items: • Used vacutainer vials • Investigational Product (IP) to include but not limited to: investigational medication, vials/packages (if disposed of at site) • Sharps: Needles, Lancets, and Syringes • Blood and blood products • Personal Protective Equipment (PPE) as required In accordance with FDA regulations, all IP will be returned to sponsor for destruction. MCR will only destroy on-site if required and adequate documentation with instructions is obtained from sponsor. Delegated site personnel will complete the MCR On-Site Destruction Record (available on the MCR intranet). All IP awaiting destruction will be put in a biohazard container and housed in a secure location until retrieved by an independent contractor hired for this purpose. It is disposed of per local and federal laws/regulations. It will be hand delivered to vendor pick-up staff and site will be notified of destruction.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

__________________________________ Signature

Guideline #14 Version date: August 2021

12-1-2021

_____________ Date

Page 1 of 2

Clinical Operating Guidelines

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.60 General responsibilities of investigators 29 CFR 1910.1030 OSHA Bloodborne Pathogens Standard Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) Meridian Clinical Research January 2021

SOP #05: Handling of Investigational Product

OSHA Standards

https://www.osha.gov/bloodborne-pathogens/worker-protections

Guideline #14 Version date: August 2021

Page 2 of 2

Clinical Operating Guidelines Transport of Study/Source Documents Between Meridian Offices All Meridian Clinical Research (MCR) sites will use the following process to transport original source document study charts between main MCR office (at any given location) and MCR satellite offices at the same site location as required for study visits or study/source documents created at an MCR call center to the site for which they are required as part of the subject study chart: • • • • • • •

Original study charts/source documents will be created and maintained at the main office Original source created at a call center will be transported to study site and copy maintained at call center A sign-out log will be maintained at main office or call center All charts to be transported from one office/call center to another will be logged out with subject number, initials/date of individual taking charts and logged back in upon return Transport of documents will be by personal vehicle, courier or rental car as needed Approval from Regional Manager (or Leadership) for removal of study documents from the site must be received prior to taking the documents off-site. Only designated employee(s) of MCR will have access to documents/charts removed from the site.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

___________________________________ Signature

12-1-2021

______________ Date

APPLICABLE REGULATIONS AND GUIDELINES 21 CFR 312.60 General responsibilities of investigators 21 CFR 312.62 Investigator recordkeeping and record retention Guidance for Industry Investigator Responsibilities – Protecting the Rights, Safety, and October 2009 Welfare of Study Subjects March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) Public Law 104-191 Health Insurance Portability and Accountability Act of 1996 (HIPAA) HIPAA Privacy Rule 45 CFR Part 160 and Subparts A and E of Part 164 MCR Clinical Operating HIPAA Non-Covered Entity Subject Confidentiality Guideline #04

Guideline #15 Version date: August 2021

Page 1 of 1

Clinical Operating Guidelines Maintenance of Emergency Medical Kit and Supplies Meridian Clinical Research (MCR), in order to ensure adequate materials to respond to an in-office emergency appropriately, requires each MCR site to have in place an Emergency Medical Kit. Kits should be stored in a location that is safe from exposure to heat, cold or other damage. The location should be easily accessible and known to all staff with instructions on how to access and use them. Each site will maintain an inventory of the supplies and kit checked monthly for expired drugs and/or devices. Comprehensive review of the supplies will be performed on an annual basis at minimum, to ensure all supplies and medications are current. Expired items will be replaced within two (2) weeks of inventory. To be documented: • Date of content review completed • Staff delegated responsibility for daily check • Monthly review/documentation of expired supplies • Lock is broken: document reason and contents of kit The following supplies may be contained in each kit: AIRWAY INJECTION SUPPLIES • Bag-Valve-Mask (AMBU bag)-1 • 5 ml luer lock syringes • Adult Simple Oxygen Mask-1 • 1 ml luer lock syringes • Pediatric Simple Oxygen Mask-1 • 25 ga 1 in needles • Nasal trumpet-1 • 21 ga 1.5 in needles • Oral airway-1 • Alcohol swabs • Band-Aids MEDICATIONS GENERAL SUPPLIES (NOT IN KIT) • Acetaminophen • Glucometer and strips • Albuterol MDI • Adult blood pressure cuff • Aspirin-chewable • Pediatric blood pressure cuff • Solumedrol IM • AED • Diphenhydramine IM • Personal protection equipment-gloves and face mask • Diphenhydramine liquid • Oxygen tank (Stand-alone sites only) • Diphenhydramine tablet • Epi-Pen or vial with IM supplies • Naloxone IM/SC • Nitroglycerin-dissolvable tablets or spray OTHER EQUIPMENT • Broselow tape

Guideline #16 Version date: January 2021

Page 1 of 2

Clinical Operating Guidelines Approved by Nicole Osborn Signed by Kathryn Stoddard

Kathy Stoddard

_______________________________________________ Signature

Guideline #16 Version date: January 2021

12-1-2021

_____________ Date

Page 2 of 2

Clinical Operating Guidelines Health Screening Guideline is to be used for routine health screening of people who may be interested as volunteers for clinical trials at all Meridian Clinical Research (MCR) sites. The IRB approved Meridian Health Screening Form may be completed for each person presenting for a health screening. (Attachment #2) Prior to any health screening procedures being performed the IRB approved Consent for Health Screening (Attachment #1) must be signed and dated by the subject and staff person explaining the consent. Once the consent form has been signed and copy given to the person consenting, a health history may be obtained, and procedures performed. For potential volunteers who fail screening tests, permission may be obtained for site to store the data in CTMS for future contact for participation in upcoming studies.

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

Attachment #1 IRB approval and Health Screening Informed Consent Attachment #2 Meridian Health Screening Form

Guideline #17 Version date: August 2021

Page 1 of 1

Clinical Operating Guidelines DUCTLESS PCR WORKSTATION Meridian Clinical Research (MCR), in order to ensure the correct and safe use of the PCR Workstation Model Number AC632LFUVC the following guidance will be provided to staff using the workstation in addition to the Operator’s Manual: • A properly grounded line cord and receptacle will be provided for use • Filters must be in place prior to any use • System must be properly installed before use • The workstation is not to be used for purposes other than nucleic acid preparation and amplification of non-biological substances • Staff is not to look directly at the UV light • If display is blank or hard to read, do not operate the unit, call customer service The workstation will be located in the Investigational Product (IP) preparation room in those sites where it is being used. The Operator’s Manual will be located in the IP prep room in an easily visible location. The Site Director or Director of Laboratory Services will be responsible for ensuring training of staff and proper maintenance of the unit as outlined in the Operator’s Manual. A maintenance log will be maintained to document any parts required or any other maintenance needed during the study. All staff using the workstation or responsible for maintenance of the workstation will read and acknowledge understanding of the instructions contained in the Operator’s Manual. The training (selfdirected or otherwise) will be documented on a training log with name, signature, and completion date of training for each person. IP will be prepared using the PCR Workstation according to the clinical trial Pharmacy Manual and protocol instructions. During IP preparation staff must use appropriate Person Protective Equipment (PPE) at all times. This may include but is not limited to: gown, face mask, face shield and gloves. Study-related forms/documentation will be completed as required by protocol and/or sponsor. A certified copy of all forms will be maintained in the Trial Master File. The site is responsible for ensuring accurate accountability of IP and placebo, if applicable and maintaining accurate records from the time of receipt through dosing and any subsequent destruction or return. All records must be available for inspection by the Sponsor and are subject to inspection by the FDA at any time.

Guideline #18 Version date: August 2021

Page 1 of 2

Clinical Operating Guidelines Approved by Nicole Osborn Signed by Kathryn Stoddard

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE GUIDELINES Ductless PCR Workstation Operator’s Manual, 2009

Guideline #18 Version date: August 2021

AirClean Systems Raleigh, NC27604 800.849.0472 www.aircleansystems.com [email protected]

Page 2 of 2

Clinical Operating Guidelines Conduct of Clinical Trials Remote Visits and/or Home Visits Meridian Clinical Research (MCR) guidance regarding remote subject visits and/or home visits by MCR employees to work with challenges that may arise due to quarantines, site closures, travel limitations, interruptions to the supply chain for investigational product (IP), or potential hazards to participants and study staff. This guidance is to assist the MCR sites in assuring the safety of trial participants and MCR employees while maintaining compliance with good clinical practice (GCP) and minimizing risks to trial integrity. At all times patient safety will be the forefront of considerations. Therefore, changes may be implemented to mitigate potential hazards to participants and study staff while ensuring participant safety and maintaining data integrity. Remote Study Visits • Per sponsor instructions, investigators and/or appropriately designated study staff will be allowed to perform study visits as remote study visits (e.g. conducted by phone contact, virtual visit, video conference) if patients are unable to attend in-person visits and to assure the safety of patients. • Safety Assessments – documentation to include but not limited to: adverse events, concomitant medications and procedures, diary review, pregnancy test results and other assessments as required by protocol. All assessments not able to be completed remotely will be performed at next in-person office visit. • Urine Pregnancy Testing – per sponsor instructions, site may provide participants with study supplied urine pregnancy test kits and written instructions to be used at-home by participants for remote study visits. Site staff will verbally review testing instructions and test results with all participants. • Investigational Product Dispensation for Remote Visits – per sponsor instructions, IP may be shipped to participants via an overnight courier or provided curbside. Documented written process with approval from sponsor prior to dispensing/shipping IP must be obtained. • An investigator will be available as needed during all remote visits • Revised Informed Consent – if patients are unable to attend in-person visits the MCR SOP for Adult or Pediatric informed consent should be followed in addition to the following: o Revised IRB approved Informed Consent Form (ICF) will be mailed, faxed, or emailed to patients prior to remote visit for review. If mailed; a self-addressed stamped envelope will be included in the mailing; method of transmission will be documented in patient’s source. o Study staff will review and discuss ICF with patient at time of remote visit, clearly documenting the process o Patient should be instructed to sign and date the ICF and email, fax or mail to the site, if they choose to continue in the study. An electronic signature system may be use; returned e-signature document will be filed in patient chart o A fully executed copy of the ICF will be mailed to the patient Guideline #19 Version date: August 2021

Page 1 of 3

Clinical Operating Guidelines Home Study Visits • All home visits will involve two (2) employees • All home visits will take place between 7:30 am and 5:00 pm Monday – Friday unless weekend visits are required per protocol • Per protocol and sponsor instructions, investigators and/or appropriately designated study staff will be allowed to perform study visits at patients’ homes if patients are unable to attend inperson visits and to assure the safety of patients and study staff during study participation • Urine Pregnancy Testing – per sponsor instructions, site may provide participants with study supplied urine pregnancy test kits and written instructions to be used at-home by participants for home study visits; site staff will verbally review testing instructions and test results with all participants. • Investigational Product Dispensation for Home Visits – per sponsor instructions, IP may be transported to patients’ home or shipped to participants via an overnight courier or provided curbside. Documented written process with approval from sponsor prior to dispensing/shipping IP must be obtained • Original study chart will not to be taken from the study site; a copy may be taken to the home visit along with next visit source documents • All assessments not able to be completed at home visits will be performed at next in-person office visit • An investigator will be available by phone if necessary, during the visit • Revised Informed Consent – if patients are unable to attend in-person office visits the MCR SOP for Adult or Pediatric informed consent should be followed in addition to the following: o Revised IRB approved ICF is to be mailed, faxed, or emailed to patients prior to home visit for review; method of transmission will be documented in the patient’s source o Study staff will review and discuss ICF with patient at time of home visit, clearly documenting the process o Patient and study staff will sign the ICF, if the patient chooses to continue in the study o A fully executed copy of the ICF will be mailed to the patient o Should Sponsor/CRO provide additional guidance for re-consenting participants and/or their legally authorize representatives (LAR) during COVID-19 restrictions and/or when there is no follow-up onsite visit to be scheduled the sites will comply with the guidance as provided by the Sponsor/CRO in addition to the MCR process for informed consent as documented above. Approved by Nicole Osborn Signed by Kathryn Stoddard

Kathy Stoddard

___________________________________________ Signature

Guideline #19 Version date: August 2021

12-1-2021

_____________ Date

Page 2 of 3

Clinical Operating Guidelines APPLICABLE REGULATIONS AND GUIDELINES March 27, 2020 FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Pandemic March 18, 2020 Coronavirus (COVID-19) Update FDA Issues Guidance for Conducting Clinical Trials Meridian Clinical Research, January 2021 March 2018

Clinical Operating Guideline #23: IP Transport Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2)

Changes made Added bullet #6 under Revised Informed Consent

Guideline #19 Version date: August 2021

Date August 2021

Page 3 of 3

Clinical Operating Guidelines Conduct of Clinical Trials During The Coronavirus (COVID-19) Pandemic Meridian Clinical Research (MCR) policy regarding protocol changes that may be implemented for Investigative Sites to deal with challenges that may arise due to quarantines, site closures, travel limitations, interruptions to the supply chain for investigational product (IP), or potential hazards to participants and study staff. This guidance is to assist the MCR sites in assuring the safety of trial participants, and site staff, maintaining compliance with good clinical practice (GCP) and minimizing risks to trial integrity during the COVID-19 pandemic. At all times patient safety will be the forefront of considerations. Therefore, changes may be implemented to mitigate potential hazards to participants and study staff while ensuring participant safety and maintaining data integrity. •







• •

Remote Study Visits – per sponsor instructions, investigators and/or appropriately delegated study staff will be allowed to perform study visits as remote study visits (e.g. conducted by phone contact, virtual visit, video conference) if patients are unable to attend in-person visits due to COVID-19 pandemic and to assure the safety of patients. Safety Assessments – documentation to include but not limited to: adverse events, concomitant medications and procedures, diary review, pregnancy test results and other assessments as required by protocol. All assessments not able to be completed remotely will be performed at next in-person visit. Urine Pregnancy Testing – per sponsor instructions, site may provide participants with study supplied urine pregnancy test kits and written instructions to be used at-home by participants for remote study visits. Site staff will verbally review testing instructions and test results with all participants. Investigational Product Dispensation for Remote Visits – per sponsor instructions, IP may be shipped to participants via an overnight courier or provided curbside. Documented written process with approval from sponsor prior to dispensing/shipping IP must be obtained. (See Investigational Product Transport Accountability Log) Training on Protocol Changes – to be provided by the sponsor and documented by site staff on Training Log. Providing Source Documents for Remote Visits It is important to maintain subject confidentiality in all email communication. When sending an email of scanned documents o Do not include any subject identifying information. o When sending source documents please ensure that all subject identifying information is permanently redacted. The only information that should be contained in the email and in the source documents that are sent should be the Subject’s Study Identifier. o The Subject’s Study Identifier should be on each page of the source document sent. o Information to be redacted includes but is not limited to: Subject name Guardian/LAR name, if applicable Initials

Guideline #20 Version date: August 2021

Page 1 of 3

Clinical Operating Guidelines •



Phone number Date of birth Revised Informed Consent – if patients are unable to attend in-person visits the following process should be followed: o Revised, IRB approved ICF are to be mailed to patients with Self Addressed Stamped Envelope (SASE) for ICF return o Study staff is to set up phone call appointment to review ICF with patient, clearly documenting phone conversation o Patient should be instructed to sign the ICF, if they choose to continue in the study and mail back to site in SASE o Upon receipt of signed consent, the staff member who conducted the phone consent should sign the ICF and place original in study binder with a copy in patient study chart o A fully executed copy of the ICF is to be mailed/emailed to the patient o Should Sponsor/CRO provide additional guidance for re-consenting participants and/or their legally authorize representatives (LAR) during COVID-19 restrictions and/or when there is no follow-up onsite visit to be scheduled the sites will comply with the guidance as provided by the Sponsor/CRO in addition to the MCR process for informed consent as documented above. Due to office closures and staff in quarantine beginning in April 2020, the following may apply: o PI oversight may be accomplished as virtual visits via phone, video conference (example: Teams, Zoom) or other means available to the research staff o The virtual visits may be documented in study chart notes as necessary o PI oversight signatures may be extended therefore may not be completed within three (3) days of visit

Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

___________________________________________ Signature

Guideline #20 Version date: August 2021

12-1-2021

_____________ Date

Page 2 of 3

Clinical Operating Guidelines APPLICABLE REGULATIONS AND GUIDELINES March 27, 2020 FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Pandemic March 18, 2020 Coronavirus (COVID-19) Update FDA Issues Guidance for Conducting Clinical Trials Meridian Clinical Research January 2021 March 2018

Clinical Operating Guideline #23: IP Transport Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2)

Changes made Added: Conduct of Clinical Trials During The Coronavirus (COVID-19) Pandemic – Addendum

Date January 2021

Added bullet #6 under Revised Informed Consent Corrected Guideline #

August 2021 August 2021

Guideline #20 Version date: August 2021

Page 3 of 3

Clinical Operating Guidelines Vendor Oversight Guideline This process is to assess newly contracted Vendors for ability to carry out requested assessments and/or procedures for Meridian Clinical Research (MCR) clinical trials and to ensure that active Vendors are maintaining necessary standards to perform contracted duties in an acceptable manner. It is intended to meet FDA regulations, ICH/GCP Guidelines, industry standards and MCR policies and procedures for vetting and contracting with Vendors needed for the clinical trials conducted at all MCR sites.

Newly Contracted Vendor Assessment • • • • • • • • • •

Review Sponsor requirements for Vendor assessments/procedures Ensure Vendor can fulfill requirements Ensure Virtual Study Vendors agree to be included on Delegation of Duties (DOA) log if required by MCR/Sponsor Ensure Vendor completes all required training (by sponsor and by MCR) Obtain required Vendor certifications, calibration records and licenses File Vendor documents in Complion Inspect Vendor facility if needed and/or facilitate Sponsor/CRO inspection of Vendor facility Ensure that Vendor contract includes specific requirements as above Provide Vendor with related MCR guidelines if indicated Work with Vendor to create process flow for subject visits o Scheduling procedure o Documentation/reporting requirements o Billing

Ongoing Vendor Oversight • • •

Obtain and file updated/revised Vendor documents as required by sponsor If Vendor facility inspection was required at onset of services, reinspect Vendor facility annually to ensure that facility is being maintained properly and Sponsor requirements are being met Discuss with Vendor and update Vendor contract if changes are made by Sponsor to Vendor requirements

Guideline #21 Version date: October 2021

Page 1 of 2

Clinical Operating Guidelines Approved by Nicole Osborn, CEO Signed by Kathryn Stoddard, VP, Clinical Operations

Kathy Stoddard

_______________________________________________ Signature

12-1-2021

_____________ Date

APPLICABLE REGULATIONS AND GUIDELINES March 2018 Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6 (R2) 21 CFR 312.50 Responsibilities of Sponsors and Investigators

Guideline #21 Version date: October 2021

Page 2 of 2

IP Transport Log Version Date: July 2021

Page __ of __

Reason for Transfer: Office relocation Emergency (i.e. weather conditions) Other (Specify):__________________________________________________________________________________________________

Delivery Container & Storage Conditions : Box (Ambient Temperature) Cooler with dry ice Cooler without dry ice Other (Specify):_________________________________________________________________________________________________

Method of Transport: Personal Vehicle: Courier Name: ______________________________ Hand delivered by Site Employee: Name:_______________________________________________

Location/Address to which IP is to be/was transferred: __________________________________________________________________________________________________________

Location/Address of Main site: _________________________________________________________________________________________________________

Did the investigational product remain within the temperature ranges specified by the protocol? Pre____C/F Post______C/F YES NO (If no, please report the deviation to the Sponsor/CRO, and the IRB if required)

Do we need the lines above if we have the one below or should we cut out the one below?

Minimum Temperature During Transport:__________C/F Maximum Temperature During Transport:__________C/F Temperature Prior To Transport:_________________C/F Temperature At End Of Transport:________________C/F

Protocol #:__________________________________ Principal Investigator: ___________________________________ Site #:_________________________ Sponsor/CRO:____________________________

INVESTIGATIONAL PRODUCT TRANSPORT ACCOUNTABILITY LOG

COMMENTS

.No, explain why_________________________

# Units Transported

Yes, Attach copy of approval

Subject Number if Known and Applicable

IP Transport Log Version Date: July 2021

Page __ of __

Signature on Arrival at Site:____________________________________Date/Time IP Received: _______________

Signature of Individual Transporting IP:____________________________Date/Time IP Shipped:________________

Approval from Sponsor/CRO

Bottle/Kit/Lot Number

RECEIVED BY INTE

I NTEG1R-fV-1f-W-I RB ,

3815 S. Capital of Texas Highway, Suite 320 Austin, Texas 78704 , Phone (512) 326-3001 Fax (512) 697-0085 Email: [email protected] Web: www.integreview.com

GENERIC MATERIALS REQUEST FORM NOTE: UTILIZE THIS FORM FOR ALL REQUESTS NOT ASSOCIATED WITH A PARTICULAR PROTOCOL (i.e. generic recruitment, pre-screening IC, etc.)

REQUEST'J)ETAILS Name of Company Submitting: Meridian Clinical Research

l:gj New material

D Revised material

Description of request: one generic screening information and consent doqument, one health screen form NOTE: For eneric ads be sure to include the total number of ads bein submitted

· .. ··

INVOICING DETAILS

Name of person submitting request: Yvonne McCracken Phone Number: 704.996.4798 Email address for invoicing: [email protected] PQ Number, when appl.:

I INTEGREVIEW IRB ACTION

Approved by Full Board

D Reviewed by Expedited .D Acknowledgement of Receipt Only . D Reviewed by Full Board

D With modifications required by Reviewer(s) (see attached) D Disapproved by Full Board (modify as noted and resubmit for review)

D Jami Brackeen, Co-Chair D Charles Ryan, Ph. D., Chair

D Matthew Pfeiffer, Ph.D. ,D Christina Walker, M.D.

D Karen Haslund, M.D.

D Angelica Martinez, Co-Chair

D Francine Lopez, Co-Chair D Bridget Briseno, Co-Chair 1

By signing below I certify that I do not have a

D Tonya Reed, Co-Chair

D Christopher Martin, Pharm.D. D Mary Ruwart, Ph.D.

tified · IntegReview' s SOP 3 5.

OF CHAIR OR DESIGNEE

Page 1of1

DATE

Approved April 8, 2019 IntegReview IRB

INFORMATION AND CONSENT FOR HEALTH SCREENING I am volunteering for a general health screening to provide Meridian Clinical Research with information for possible inclusion in clinical trials Health Screening Procedures If you agree to a health screening, we may include the following: • • • • • •

Brief health history Discuss the list of medicines you take Brief physical exam (including height, weight, blood pressure, temperature and heart rate) Electrocardiogram (to measure the electrical activity of your heart) Chest X-rays, tests to determine how well your lungs work Urine sample will be used for the purpose of screening for one or more of the following drugs: □ Cannabinoids (THC) □ Benzodiazepines □ Ectasy (MDMA) □ Amphetamines □ Methamphetamines □ Methadone □ Opiates □ Barbiturates □ Phencyclidine (PCP) □ Cocaine □ Opioids

I understand that this testing is completely voluntary and that I may decline this testing. I understand that there will be no cost to me for this testing. I understand that I will not be compensated for these tests and that this testing has no direct medical benefit to me. These tests will not be shared or provided to any other person or company for any reason outside of Meridian Clinical Research. They will not be shared or provided to any other company or person for any reason and is not for legal or employment purposes. I understand that the results of these tests will be kept confidential in accordance with applicable privacy laws and to the extent permitted by law. I understand that I will be told the results of these tests today. I understand that if the results of some of these tests are positive, I may not be eligible for entry into Meridian Clinical Research’s clinical trials. STATEMENT: I have read the above information and have had an opportunity to ask questions. By signing this consent form below, I hereby give my permission for Meridian Clinical Research to do a health screening as explained above. ____________________________________________ Printed Name of Person Consenting to Testing

_____________________________________________ Signature of Person Consenting to Testing

________________ Date

____________________________________________ Printed Name of Person Performing Consent

_____________________________________________ Signature of Person Performing Consent Meridian Clinical Research, LLC

www.mcrmed.com

Date

__________________

1 of 1

Today’s Date: _________________

Patient Demographics Name: _______________________________________________________________________________ First

Middle

Last

_____________________________________________________________________________________ Address

City

State

Zip Code

_____________________________________________________________________________________ Home Phone

Cell Phone

Alternate Phone

_____________________________________________________________________________________ E-mail address

May we have your permission to use your information to contact you for future studies?

Yes

No

Race/Ethnicity: ☐ African American

☐ Caucasian

Sex: ☐ Male ☐Female

☐ American-Indian

☐ Chinese

Date of Birth: ____________________

☐ Asian

☐ Hispanic

SSN: ________ - ______ - ________

Medical History [Check all that apply]

Skin ☐ Eczema ☐ Psoriasis ☐ Acne

Cardiovascular ☐ High Cholesterol ☐ High Blood Pressure ☐ Heart attack

Respiratory ☐ Asthma ☐ COPD ☐ Allergies*

Musculoskeletal ☐ Arthritis ☐ Pain** ☐ Fibromyalgia

Gastrointestinal ☐ Irritable Bowel ☐ Chron’s disease ☐ Acid reflux ☐ Constipation

Urinary ☐Urinary incontinence ☐Overactive bladder

Neurological ☐ Stroke ☐ Anxiety ☐ Depression ☐ Bipolar ☐ Migraines

Endocrine ☐ Diabetes Type I ☐ Diabetes Type II ☐ Hyper/Hypo thyroid ☐ Obesity

☐ HIV ☐ AIDS ☐ Cancer _______________

*List Allergies: _________________________________ **List Areas of pain: ____________________________ _____________________________________________

Current Medications

Meridian Clinical Research, LLC

www.mcrmed.com

1 of 1

Section 2

Standard Operating Procedure Handbook

"'� ,,, MERIDIAN

Standard Operating Procedures

��

Isolation, Cryopreservation, And Shipment of Peripheral Blood Mononuclear Cells (PBMCs) Using Ficoll-Paque© Gradient Method 1.

OBJECTIVE 1.1. This Standard Operating Procedure (SOP) describes the equipment and methodology necessary for the isolation, cryopreservation, and shipment of peripheral blood mononuclear cells (PBMCs) using the Ficoll-Paque ® gradient method.

2.

SCOPE 2.1. Sodium Heparin, Sodium Citrate, or EDTA anticoagulation tubes will be used to collect whole blood samples. This SOP will be utilized by laboratory staff of Meridian Clinical Research to complete PBMC processes. Protocol-specific requirements of the client may be substituted wherever necessary.

3.

SAFETY AND RESPONSIBILITIES 3.1. Managers and supervisors are responsible for making sure all PBMC processors are thoroughly trained on this SOP before they work on a study- specific protocol, and that all equipment is cleaned and maintained according to manufacturer instructions 3.2. All laboratory staff who perform this procedure must do so with proper aseptic technique, personal protective equipment (PPE), and in accordance with applicable guidelines and regulations (see below) 3.2.1. 21 CFR 58 {Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies 3.2.2. Good Clinical Laboratory Practices

3.2.3. OSHA Bloodborne Pathogen Standards All PBMC processors will document pertinent information from this procedure in real 3.3. time on PBMC processing worksheets. This information will include subject numbers, blood collection times, processing times, freezing times, all calculations, and the time/date when samples are transferred from -80 ° C to LN2 (as applicable). 3.3.1. These worksheets must be reviewed for correctness and completion by another laboratory staff member, who will sign and date the completed worksheet after reviewing it 4.

ABBREVIATIONS AOPI Acridine Orange Propidium Iodide Biosafety Cabinet (Class II) BSC CPS Cryopreservation Solution (Freezing Media) CSTFB Cell Separation Tubes with Frit Barrier

SOP #17 Version Date: August 2022

Page 1 of 9

"',, ,,, MERIDIAN eluucal� 6.

7.

Standard Operating Procedures

EQUIPMENT AND MATERIALS 6.1. Class II BSC 6.2. Refrigerated centrifuge (up to 1800xg) with ambient capacity and swinging bucket rotor 6.3. Automated serological pipettor with assorted individually wrapped pipette tips (1ml, 2ml, 5ml, 10ml, 25ml, 50ml) 6.4. Micropipettes (p20, p200, plO00) with associated micropipette tips (20µL, 200µL, l000µL). Sterile (if required by protocol) 6.5. Refrigerator (2-8°C) 6.6. -80°C Freezer for FBS and short-term PBMC storage LN2 tank, freezer, and IATA-approved dry shipper (as required by protocol) 6.7. 6.8. Automated Cell Counter (Nexcelom Cellometer Auto 2000 or equivalent) with accompanying hemocytometer slides 6.9. 15ml disposable graduated polypropylene, conical bottom centrifuge tubes (as applicable) 6.10. 50ml disposable graduated polypropylene, conical bottom centrifuge tubes 6.11. Cell separation tubes with frit barrier (CSTFB - as allowed by protocol 6.12. Cryogenic polypropylene vials (1.8-2mL), screw cap with O-ring, sterile, for vapor phase LN2 storage 6.13. Cryoboxes for storage of cryogenic vials in LN2 6.14. Mr. Frosty™ by Nalgene, CoolCell® by BioCision, StrataCooler by Agilent, or equivalent cell freezing containers 6.15. Sodium Heparin, Sodium Citrate, or EDTA blood collection tubes (as applicable) 6.16. Personal Protective Equipment 6.16.1. Powder-free gloves (latex or nitrite) 6.] 6.2.

Cryo-gloves for handling of froz:en samples

6.16.3.

Biohazard bags and sharps containers

PREPARATIONS

7.1.

Collected blood should be stored upright at ambient temperature until processing start time 7.2. Collection time refers to the time the blood to be processed was drawn from the subject. Processing time begins at the start of the first centrifugation of collected samples, and ends when the samples are put into the -80°C freezer for storage 7.2.1. Total time refers to the time elapsed from the collection time until the end of the processing time. This should ideally be no more than 8 hours. In the event that more than 8 hours have passed, the sample(s) should still be processed with a note indicating that this occurred 7.3. FBS should be aliquoted and thawed at the end of each week based on the number of samples expected for the following week (see section 5.4 above) 7.4. BSC should be cleaned at the beginning and end of each day using IPA and UV SOP #17

Version Date: August 2022

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Section 3

Clinical Research Reference Manual ALCOA-C

Clinical Research Reference Manual **Internal MCR (Meridian Clinical Research) document, not to be shared externally**

Contents (alphabetical order) 1572 ...................................................................................................................................................................... 3 Access to CRIO (Granting access to CRA’s) ........................................................................................................... 3 Acronyms .............................................................................................................................................................. 4 Activation / Greenlight email template for notifications ..................................................................................... 5 ALCOA-C ................................................................................................................................................................ 6 Awarded Study Email Template............................................................................................................................ 7 Chart Set-up (Paper Charts) .................................................................................................................................. 8 Check-in Process (Front desk / Patient intake) ..................................................................................................... 9 Communicating with CRA’s / Monitors onsite.................................................................................................... 10 Complion (E-regulatory)...................................................................................................................................... 11 Confidential Disclosure Agreements (CDA’s) ...................................................................................................... 12 Consenting – Paper Consents/CRIO (E-Source) .................................................................................................. 13 CRIO – Comments from CRA within e-source ..................................................................................................... 14 CRIO – Outage Procedure ................................................................................................................................... 15 CRIO – Paper documents loaded to e-source ..................................................................................................... 16 CTMS / Clinical Conductor .................................................................................................................................. 16 Delegation Log .................................................................................................................................................... 17 Destroying IP onsite Vs. Returning to sponsor ................................................................................................... 18 Deviations ........................................................................................................................................................... 18 Diaries (Collecting, Reviewing, and Storage of participant Diaries) ................................................................... 19 E-mail Groups...................................................................................................................................................... 21 Enrolling Patients in two studies ........................................................................................................................ 22

FDA Inspection Calls............................................................................................................................................ 23 Feasibilities ......................................................................................................................................................... 24 Generators on site / maintenance ...................................................................................................................... 24 How to QC Participant Charts ............................................................................................................................. 25 Intranet ............................................................................................................................................................... 33 IRB Documents.................................................................................................................................................... 34 Lab Reports ......................................................................................................................................................... 34 Late Entry – Clarification ..................................................................................................................................... 34 Lost to Follow up (Participants that cannot be reached) ................................................................................... 35 Medical Record Releases .................................................................................................................................... 35 Monitoring Visits................................................................................................................................................. 36 Note to File ......................................................................................................................................................... 38 [email protected]............................................................................................................................... 39 Offsite Storage of Study Documents................................................................................................................... 40 Out of Office – Email Automatic Replies............................................................................................................. 40 Patient Health Information (PHI) ........................................................................................................................ 41 Peer to Peer Chart Review (Paper/E-Source) ..................................................................................................... 42 PI Oversight Responsibilities ............................................................................................................................... 43 Post-Dose Vitals .................................................................................................................................................. 44 Primary Care Physician (PCP) Notifications ........................................................................................................ 46 PSSV’s (Pre-Site Selection visits) ......................................................................................................................... 47 Redaction of Medical Records ............................................................................................................................ 48 Regulatory Compliance Reports ......................................................................................................................... 49 Safety Committee ............................................................................................................................................... 50 Serious Adverse Events (SAE’s) ........................................................................................................................... 51 Short Form Informed Consent Process ............................................................................................................... 52 Smart Sense (temperature monitoring) ............................................................................................................. 53 Spanish Translation Process................................................................................................................................ 55 Spin Logs (Sample processing logs)..................................................................................................................... 56 Supplemental Binder .......................................................................................................................................... 57 Target Dates (managed in Clinical Conductor) ................................................................................................... 59 Unblinded IP storage areas ................................................................................................................................. 60 Unblinded Labels ................................................................................................................................................ 60 Unblinded Treatment Lists ................................................................................................................................. 60 Unblinded Verification of IP ................................................................................................................................ 61 CRC Quick Reference Guide // V3-10Aug2022

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Unblinded Process for Dispensing Investigational Product ................................................................................ 63 Weekly Site Meetings ......................................................................................................................................... 64 Appendix A – CRIO Document Filing and Naming Convention .......................................................................... 65

1572 This is also referred to as the “Statement of Investigator.” It is an agreement signed by the investigator to provide certain information to the sponsor and assure that they will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic. These forms are created at study start by the regulatory team. They are also updated by the regulatory team when the site notifies them of a new investigator being added to the study delegation. When a new investigator is added to a study as a sub-I, they must first be added to the 1572 before adding to the delegation log. When an investigator is removed from the delegation log, regulatory must also be notified so that the 1572 can be updated signifying that an investigator has been removed from the study delegation. Adding or Removing Staff from a study - Instructions on adding or removing staff on a study can be found on the MCR intranet. This form is to be used by the site whenever adding or removing a staff member from a study so that no steps are missed. You can also search on the meridian intranet for this for by typing “Adding or removing staff members” into the search bar. Section Updated: 8/4/2022

Access to CRIO (Granting access to CRA’s) CRA Access in CRIO is Given by the Lead CRC (Clinical Research Coordinator) for the study: The Lead CRC is responsible for providing, maintaining, and ending access for the CRA in CRIO. Below are the steps for setting up access. It is essential that access is not open ended. Site Managers and Site Directors should be making sure that this access is maintained and monitored. Regional Directors should set up a calendar reminder to run a report to check CRIO access and update as needed. ▪ Go to the trial, overview section, external users ▪ Add email and name, role defaults to “monitor” ▪ Invite ▪ Recipient will get a link to activate their account. ▪ Deactivate after visit, they will remain on the list for you to reactivate later ▪ If you add them to another study or site, they will not get a new email / link, they will see the new study on their CRIO home page ▪ external users do not have to navigate from one site to another like we do. They have a home page with their trials in tile format same as we see, and the site name is in the tile ▪ when you deactivate them, the trial does not appear on their home page. ▪ Training video for external users: https://www.youtube.com/watch?v=cWfEjXA77Oo ▪ If an external user finds CRIO and sets up an account without waiting for an external user invitation, the system defaults to setting them up as an internal user (not tied to any organization) and you will get an error message. Contact [email protected] to resolve. Section Updated: 8/4/2022 CRC Quick Reference Guide // V3-10Aug2022

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Acronyms Whether you are new to the clinical research world or need a refresher, here is a condensed list of common acronyms and abbreviations you may come across: ACRC: Assistant Clinical Research Coordinator ADR: Adverse Drug Reaction AE: Adverse Event AESI: Adverse Event of Special Interest ALCOA-C: Attributable, Legible, Contemporaneous, Original, Accurate, and Complete CAPA: Corrective and Preventive Action CFR: Code of Federal Regulations CRA: Clinical Research Associate (aka Study Monitor) CRC: Clinical Research Coordinator CCRC: Certified Clinical Research Coordinator COV: Close-out Visit CRF: Case Report Form CRO: Contract Research Organization/Clinical Research Organization CTM: Clinical Trial Manager (Sponsor/CRO) CTMS: Clinical Trial Management System DM: Data Manager DMC: Data Monitoring Committee DSMB: Data Safety Monitoring Board eCRF: Electronic Case Report Form EDC: Electronic Data Capture EHR: Electronic Health Record EMR: Electronic Medical Record ePRO: Electronic Patient-Reported Outcomes eTMF: Electronic Trial Master File FDA: Food and Drug Administration FDA Form 483: Official FDA inspectional observation sheet FDF: Financial Disclosure Form GCP: Good Clinical Practices HIPAA: Health Insurance Portability and Accountability Act IBC: Institutional Biosafety Committee ICF: Informed Consent Form ICH: International Conference on Harmonization IDB: Investigational Drug Brochure (aka Investigator’s Brochure) IM: Investigator Meeting IMV: Interim Monitoring Visit IND: Investigational New Drug (Application) INV: Investigator (Sub-I/PI) IRB: Institutional Review Board IRT: Interactive Response Technology IVRS: Interactive Voice Response System IWRS: Interactive Web Response System NDA: New Drug Application OSV: Over-site Visit CRC Quick Reference Guide // V3-10Aug2022

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PD: Protocol Deviation PHI: Protected Health Information PI: Principal Investigator PM: Project Manager PSV: Pre-Study Visit PSSV: Pre-Study Site Visit QA: Quality Assurance QC: Quality Control or Quality Check RBM: Risk Based Monitoring RMV: Remote Monitoring Visit SAE: Serious Adverse Event SOE: Schedule of Events SC: Study Coordinator SD: Source Document(s) SDV: Source Document Verification SIF: Site Investigator File (aka Study Binder, Essential Documents Binder, Complion Binder) SIV: Site Initiation Visit SOP: Standard Operating Procedure Sub-I: Sub-Investigator SUSAR: Suspected Unexpected Serious Adverse Reaction TMF: Trial Master File UIMV: Unblinded Interim Monitoring Visit Section Updated: 8/10/2022

Activation / Greenlight email template for notifications

When a green light / activation notification is sent from a site to [email protected] , please include what the plan is for that greenlight. For example: • plan to screen within 24hours or not possible/why? o Example: Don’t have all supplies, pending IP delivery, and/or access to EDC/IRT • # Prescreened and ready to schedule o Example: Include enrollment plan for the week, weekend, and/or late-night enrollment visits • Or onsite referrals only o Example: PI referral only due to study requires symptoms reported at the time of the screening visit. This is helpful for all departments to see when the greenlight to enroll comes through, any little notes help plan and prepare from all angles. Section added: 8/10/2022

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ALCOA-C Clinical Research Good Documentation Practices

“If it is not documented, it did not happen”

A ttributable It should be obvious who documented or did what; traceable to a person, date, and participant visit. If a record is changed it should be obvious who made the change, when the change was made, and why.

L egible The Record should be easy to read and signatures identifiable (if not then print name also).

C ontemporaneous The information should be documented as it happens. If a clinical observation cannot be entered when made, chronology should be recorded. An acceptable amount of delay (within one month) should be defined and justified. E.g., "late entry". All signatures or initials should be attached to a date indicating when the signature was added to the document.

O riginal First record of the information or certified copy. The investigator should have the original source document, not photocopies.

A ccurate Consistent and real representation of facts. Study records should have the highest level of integrity and honesty to what was truly observed; give a full accounting of the research process. Work should be double checked for unintentional errors. +

C omplete

The information should be complete (i.e., to answer who, what, when, where, why, and how). All the elements of the acronym ALCOA must be applied to both paper and electronic source data, and the records that hold that data. Serving as evidence of the events that took place during a study, source documents need to paint the full picture of what happened. Using ALCOA as a guide to collect quality data in clinical trials can help justify that a test article is safe and effective.

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Awarded Study Email Template Awarded study emails should be forwarded to [email protected] and the site director or the lead CRC as soon as it is received. Please include the following information when forwarding: Subject: New Study Award: [SITE (ex: SAV-IM) / STUDY PHASE AND PROTOCOL NUMBER (ex: P2 COVID mRNA1273-P201)] Draft Protocol Title: [DRAFT TITLE (ex: A Phase 2, Randomized, Observer-Blind, Placebo-Controlled, DoseFinding Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older)] Sponsor: [NAME OF SPONSOR] CRO: [NAME OF CRO] PI: [FIRST and LAST of PI] Sub Is: [First and Last Name of Sub-I’s] CRC primary: [First and Last name of Lead CRC] CRC backup: [First and Last name of backup CRC] Unblinded CRC: [First and Last name of Unblinded CRC] CRA Contact: [First and Last name of CRA, email, and phone number] Date of PSSV: [DATE of Pre-Site Selection Visit if applicable] Date of receipt of regulatory start up documents: [DATE or PENDING] Contact info for [SITE REGULATORY CONTACT] was sent to [CRA] on [DATE] Estimated start of enrollment: [ENROLLMENT DATE] Enrollment Goal: [#of PATIENTS TO BE ENROLLED] *It is advisable to save this template as an outlook email template to utilize each time an award is received.

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Chart Set-up (Paper Charts) Left Side (Bottom to Top) Demographics Sheet Informed Consent/Subject Level ICF Log *In order of Version with most recent on top and ICF log on top listing all versions signed Medical Records (Release on Top) *Records must be signed by PI or Sub-I X-Rays, Mammograms, and other Diagnostics *If required EKG *Original EKG must be signed by PI prior to copying Labs *Lab Req underneath* with results on top. IVRS, Diary Print Outs (Diary printout signed by PI) Additional Source *Any clinical note should be undersigned by an investigator

Right Side (Bottom to Top) AE Log *PI should sign all AE’s and SAE’s Con Procedure Log *If required Con Med Log Visit Source *Chronological order with most recent on top

Section Updated: 8/10/2022

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Check-in Process (Front desk / Patient intake) Participant is given Demographics Form, Medical Release (if applicable per the protocol), and Patient Health Information Form to complete upon check-in. Participants are to also provide photo identification at check-in to confirm their identity. Parents of the participants might need to provide a birth certificate and/or adoption papers in some situations when the last names do not match for verification of guardianship.

Demographics Form: Front desk staff Verifies completion and accuracy of the demographic form, double checking box 4 regarding contacting patient by text or social media (as it is missed often). The administrative staff scans the demographic into the patients account in clinical conductor. The original signed paper form is placed in the participants’ chart. If the participant is pediatric, please ensure all parents and/or caregivers are added to the demographics form. Medical Release Form:  Do not routinely collect Medical Record Release forms unless a study specifically asks for past medical records at the time of the screening visit. CRC/ACRC Verify that they have signed this form at the bottom, and they are releasing records from the correct party. (i.e.: if they are a patient of the embedded practice, it must be a release for that practice to utilize the office records. If they are releasing records from their primary care, they need to list that physician. If they are releasing vaccination records ONLY in the instance of a vaccine trial the required record per protocol, then only the “Immunization records” box needs to be checked rather than complete medical record, etc.) Only fully completed authorizations are to be used. Medical Record Releases without an end date are not allowed. We need to add an end date, so that the release is issued for a certain period of time as well as what records are being requested and from what facility. *Please check CC (Clinical Conductor) first to see if we already have a current medical release * **Please verify with your site director if medical records are required for your specific study.** Patient Health Information Form: All patients are to complete the patient health information form upon arrival to their first visit. The completed form is given to the ACRC/CRC who is completing the visit to utilize. It is returned to the administrative desk upon completion of the visit along with the encounter form. The patient health information form is entered into CC utilizing the "custom" groups and once entered this sheet is to be shredded. *This form makes our CTMS system searchable for potential patients by medical condition, which is how we recruit for all studies. Driver’s License: Driver’s licenses are to be scanned into the CTMS system to the participants’ file prior to the start of their visit. These are scanned so identity can be verified in CC at subsequent appointments. These are not to be filed in participants’ paper charts, only in the CTMS. Section updated: 8/10/2022

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Communicating with CRA’s / Monitors onsite Professionalism • The goal is to develop a healthy & friendly working relationship with your CRA, while remaining professional. Always remain professional when communicating with the CRA. • Know your protocol, know what issues you have had at the site that are specific to the protocol (PDs) • Have documents, charts, binders ready when CRA arrives (should be prepared and reviewed the night before) • Set 1-2 hours aside each day while CRA is at site to go over their findings, ask your site director/manager to block time on the schedule for you to allow for this. Remember • Monitors are not your friends. This Does not mean they are your enemy. If you want to talk extensively about personal things, do so after work. • Only express the typical niceties - shouldn't be more than 2-5 mins ("How was your flight?”; "Hope your child is doing well!") • They are here to WORK and HELP - This means they should be focused on our site the entire time they are onsite reviewing our study materials. If they are not doing this, we are at risk of FDA 483s The More eyes on the materials, the better. Studies should always be audit ready. • They are not here to get us in trouble or to be at odds with us Do Not Do • Do not provide food or drink. Let them know they have access to the break room for water or coffee • When they arrive for the first time at our site, show them where the break room and bathrooms are located. • Monitors are not to have free access to the clinic; they must be escorted for a tour. • Breakroom & Bathrooms are always accessible to them • Must be escorted to IP room, labs, etc., and they should not be left alone in the IP room at any time. What Not to Say • Do not admit fault until you have investigated the issue. Do not challenge CRA on findings until you have investigated the issue thoroughly and know the details. • Absolutely do not throw coworkers under the bus • Do not mention staff changes or role changes until those changes have been finalized. This Should be done via email to entire study team, including site team. When Speaking to Monitors • Make sure you and they stay focused on the biggest issues rather than only minor issues • If CRA asks a question & you do not know the answer do NOT speculate/make assumptions. Go back to your desk, figure out the entire story first, and then report back. • If you do not know the answer, do not say that you do not know. Say "Let me look into this". • CRAs (Clinical Research Associates) are human - they make mistakes too. There are times when they are wrong, even when it comes to reading/interpreting the protocol. If interpretation is

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• •



different from ours, we need to get clarification from the study team (CRO/Sponsor) in email format. There are times when we can push back on their recommendations. Many "recommendations" are a CRAs individual opinions, not necessarily industry standard. Sometimes these recommendations are in direct opposition to MCR policy/procedure. Know your SOP’s and if you are unsure if a CRA’s recommendations align with company policy – ask your site management. Do not take their findings at face value. They are not MCR employees and are not aware of all company policies and procedures. To maintain confidentiality, discussions not related to the study should not be held within the hearing of monitors. This may include personnel issues, participant issues, information related to other studies, etc. (Reference: MCR Guideline #2)

Site Directors need to be meeting with each CRA onsite before they leave for the day to see if there are any issues / outstanding action items that should be expected. Many issues can be resolved prior to CRA departing and avoid being listed as deviation in a follow up letter that will be generated and received at the site days or weeks later. Section added: 3/16/2022

Complion (E-regulatory) Each study has an electronic regulatory binder where study documents are stored in “Complion”. Each study has its own Complion specific email address in which you can add to your address book and easily forward study information to the study binder. Forwarding Documents to Complion from your email • To comply with federal regulations, ICH Guidelines and MCR SOPs for PI oversight, documents need to be sent to Complion daily. • Regulatory staff are responsible for sending for signatures (unless otherwise requested) • Protocol amendments and ICFs (informed consent forms) sent to Notifications when sent to Complion • In Complion, documents are date stamped when uploaded therefore we need to get documents signed in real time to match the uploaded date. • When time-sensitive materials are uploaded please let your regulatory contact know ASAP o Prior to SIV (Study Initiation Visits), Monitoring visits, oversight visits, audits, etc. o Anything that needs PI signatures • No subject-specific emails should be uploaded to Complion for example: o Lab requisitions o Data entry o Randomization emails o Response to monitor requests for completed tasks regarding subjects (ie: If a CRA emails asking you to drop a specific subject in IVRS, that email should be filed in the subject chart, not Complion, as it would be difficult to locate there. Patient specific documents belong in the patient chart.) • Blinded documents to be uploaded to Complion • Unblinded documents not uploaded to Complion - to be kept in site binder CRC Quick Reference Guide // V3-10Aug2022

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All headers & footers completed prior to uploading to Complion

Regulatory has assigned one person to be the primary point of contact. This person will be responsible for the day-to-day Complion regulatory filing, assist with IRB filings, as necessary, and assist with study start-up documents. In addition, they will be responsible for the regulatory start-up for newly awarded studies for their assigned sites. As a team we are dedicated to supporting all sites and the regulatory team will be providing back-up coverage as well as assisting each other to ensure all binders are current. Please do not hesitate to contact your regulatory person if you have questions or need assistance. **All Documents, User Manuals, Checklists etc. regarding Complion are available on the Meridian Intranet on Microsoft Office (located In the Operations Folder titled “Complion Instructions and Guidelines”) Section updated: 8/5/2022

Confidential Disclosure Agreements (CDA’s) A “Confidential Disclosure Agreement” (CDA), also referred to as “non-disclosure agreement” (NDA) or secrecy agreement, is a legal agreement between two parties which outlines information the parties wish to share with one another but wish to restrict from wider use and dissemination. The parties agree not to disclose the non-public information covered by the agreement. CDA’s are used by CRO’s and Sponsors (pharmaceutical companies) that we partner with to share protocols and study information with MCR, and to prevent MCR from sharing that information with any outside sources. These are legally binding contracts. The Business Development department is responsible for all CDA’s. If any staff receive a CDA from a CRO (Contract Research Organization) or a sponsor, they are to forward it to [email protected] for completion and are not to sign or return it themselves. MCR has several Master CDA’s in place with large groups and CRA’s/Monitors are not often aware of this and therefore they do not need to be completed. If they DO need to be completed, often they need to be edited to include the correct information – Which BD will evaluate and edit if necessary. Once that is completed BD will often send to the site for the PI to sign – and then BD will sign as the company signatory. Any CDA not signed by a company signatory is not legally binding. Section Added: 3/22/2022

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Consenting – Paper Consents/CRIO (E-Source) When an initial or a new Informed Consent form is received the regulatory department does the first check to make sure information is accurate. The second check should be done by the Lead CRC for that study. Review the information, phone numbers, address, visit breakdown, etc. for accuracy and reach out to regulatory if anything seems inconsistent. The IRB approved consent(s) are to be uploaded to CRIO and the Complion Binder. **Please note that the most recent IRB approved consent should be uploaded to CRIO upon approval to ensure accurate consenting process at the time of the next on-site visit.**

Consenting is one of the key tasks you perform as a CRC. It is important to ensure all information on the consent is correct and verified once a participant has signed. Dates must be complete and all signatures, selection boxes, and initial lines completed. Progress consent notes in the charts (Which are done EVERYTIME a consent is signed) should include that the patient had adequate time to read and sign ICF. A copy of the signed/fully executed ICF was given to the participant and that no procedures were done prior to signing. (And a form of some of the following questions in red) ** A new progress consent note must be written each time a participant signs any new version of the ICF during their participation in a study. ** “No questions at this time” “Questions regarding study visits answered to participants satisfaction at this time” “Stipend question answered”

Any medical related question MUST be answered and by an investigator. These 3 items must be answered in EVERY consent note: 1. Was the participant given ample time to read the informed consent? 2. Was the participant given a copy of the signed/fully executed ICF? 3. Were any procedures performed prior to the signing of the ICF? Consent Version Colors Informed consent forms are color coded in the following order: Green, Purple, Blue, Pink, Yellow *The order starts over if necessary. So, the 6th Version used would be Green again. **The first consent that is signed by the first participant is always GREEN regardless of version (They can change many times before a study really starts) Consents must be second verified and initialed/dated by another staff member once signed. E-consents must be 2nd verified per MCR Guidelines (#2 and #3) like any other ICF.

Process for ICF Verification, required for every consent: • •

Informed Consent Form (ICF) is to be fully executed by the delegated staff member obtaining consent The completed ICF is presented to a second Meridian staff person for review (prior to participant leaving the office) of the following items on the form: o Correct/current version is being used o All pages are present o All signatures are present and correct o All dates are present and correct o Check all pages of the form to ensure any check boxes, initials, or information (for example, PCP name and address) have been completed

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Participant Number and Participant Initials are documented on the top right corner on the 1st page of the consent Verifier is to initial/date on bottom of final page of ICF on the day ICF is signed o Please note the verifier is to confirm all above steps are completed at the time of verification ICF Progress note is documented in the source visit for initial ICF and/or updated ICF Site QA Specialist will review all ICFs to check for this verification All staff are to be trained in this process at Orientation Training and re-trained as needed o

• • • •

**If any pages with signature lines are confirmed NOT APPLICABLE: MCR does not mark through ICF pages as N/A, this is not industry standard. A signature that may be needed might accidentally get marked as "NA" in error if this process were used - and if was a signature line just missed in error (which again should not happen with a trained verifier) but in that case, the signature would be able to be obtained at the next visit rather than "NA" being marked and a new ICF needed or error corrections and/ or notes of clarification needed. Also, the ICF would look very sloppy making the site look sloppy to an inspector... Of course, if everyone is reading ICF's (as they should) before obtaining consent and they are being verified (as they should) they will know where it needs to be signed, where it would be left blank if not applicable, and this will result in cleaner ICF's.**

Reconsenting Onsite: Avoid remote reconsenting if possible. The informed consent process is best done in person. Additionally, this is important when the budget indicates onsite consenting as part of the process for reimbursement to MCR. Please ensure that the ICF approval notification is reviewed entirely before determining if new and/or already consented participants need to sign the newly approved consent form at the next on-site visit. When a new ICF is approved for on-site use the LCRC is responsible for ensuring that the “Orange ICF Alert” flag and ICF Progress Note documentation page is placed into the participants chart the day of approval. If the study is being conducted in CRIO then the LCRC is responsible for uploading the newly approved ICF to the correct study page in CRIO the day of approval. Uploading the ICF “triggers” the procedure in eSource, which captures the date/time of consent as well as any specific questions in the consent. Section updated: 8/10/2022

CRIO – Comments from CRA within e-source When queries are issued by monitors to Coordinators in CRIO they should be treated no differently than an action item in a follow-up letter. If a query requires multiple actions to resolve, it should be noted in the comment back to the CRA just as it would be addressed in the CRC response to follow-up letters. For example, if a protocol deviation is noted, the CRC should not just comment back "Done" or "Resolved". They should list what action was taken to resolve the protocol deviation. Commenting back to the CRA is like the CRC completing a resolution letter for action items after an IMV. This will go a long way to keep action items off the f/u letter if the CRA can see and get notification it has been resolved. We would rather not see these queries end up as action items on the follow-up letters when they can be addressed and resolved on both the sites end as well as the CRAs at the time the query is issued. Section added: 8/4/2022

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CRIO – Outage Procedure Site Instructions: If a user or site is having an issue with the functioning of CRIO, such as crashing, inaccessibility, load times that are excessive or fail to resolve, contact the Meridian CRIO Admin team at [email protected] or Michael Pierre on Teams. The CRIO Admin team will determine the nature of the problem, and you will be advised on the actions to take. Internal Process: o o

o o

If Michael is out of office, he will set his Teams away message to direct staff to notify another member of the CRIO team. Internet down  CRIO Admin team will notify Operations, Clinical Data and Administrator of outage  If applicable, instruct site to use a hotspot if available • If no hotspot, Operations will advise if site is to use cell phone to complete visit • Website: https://app.clinicalresearch.io/login Internet and cellular down  CRIO admin will notify Operations, Clinical Data and Administrator team of outage and seek solutions  Operations will determine what actions to take regarding subjects CRIO down  CRIO Admin will notify Operations, Administrator and Clinical Data of outage  CRIO Admin will notify sites affected and potentially affected that there is an issue and are working to repair it  CRIO Admin will find out predicted length of outage from CRIO and any other issues causing the problem • Operations will determine what actions to take regarding subjects  CRIO Admin will pull looker report Operations / appointments to see what visits are scheduled and send to Clinical Data, who will send them the pdf of the source. • Clinical Data will instruct site on how to upload paper source to CRIO • Recommend CRIO have a company wide report in case person with looker access is not available. • If a visit is simple and needs to be completed on that day, a paper source (progress note) can be used to complete the visit. This documentation would not be provided by clinical data in the event of a systemwide failure, so the CRC would have to rely on referencing the protocol for the visit schedule and details.

Notes: o

eSource outages are usually short, and no longer than 24 hours.

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o o

o

Outages seem to move, meaning that one site may be down, but another location is not. If this is the case, a member of the clinical data team can email a pdf of the visit/s the site needs. Preventative: if a site is starting a trial with high expected enrollment, clinical data team can email a pdf of the visit/s needed. Sites are not to store the blank source when the outage is resolved.

CRIO – Paper documents loaded to e-source Because CRIO migration is an ongoing process, and we have not completed full transition – we are continuing to keep the paper documents we are loading there. (EKGs, etc.). These should be kept in a separate binder tabbed out by patient for each study. CRAs do not review these. They are our backup documents should CRIO glitch. We are new to CRIO, and we are being protective of this data until full migration is complete. Once a paper document is loaded into CRIO, it must be signed as a true and complete copy in CRIO, tagged for an investigator review if required, and then filed in this backup paper binder tabbed out by patient. These are not filed in the ICF binder. This is for site CRIO backup only – it is not provided to anyone. Section added: 8/4/2022

CTMS / Clinical Conductor CTMS stands for “Clinical Trial Management System” The CTMS MCR currently uses is “Clinical Conductor” – this will change in 2023, more to come on that. We have video resources available on Learning Central and “Stream” through Teams to show you how to do a variety of Clinical Conductor tasks. To access Stream, go to Teams and on the left-hand side click the three dots under files. In the popup window select Stream and in the groups window select Clinical Conductor. “STREAM” is also an application on your Microsoft office account. When you login to Microsoft Office type “stream” in the search bar to access here as well. Additional Clinical Conductor training can be found on the Learning Central Website. (https://meridian.3ec.com/course/index.php?categoryid=48) The CTMS system tracks all participants through their visits for each study. Most visits will have a protocol directed “window” of time they have to be completed within. During Study Start-up it will be the LCRC and Site Directors responsibility to ensure the CC Admin windows are correct in the CTMS. If there are changes to original visit windows the coordinator must print requested changes, sign and date the required form, and the Site Director will sign and date the requested changes. All changes are emailed to [email protected] and Regional Director.

Section updated: 8/10/2022

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Delegation Log The purpose of the DOA (Delegation of Authority) is for the PI to delegate tasks to staff members. It gives approval for staff members to complete tasks on a study. Site Directors and the lead CRC should work together on the initial creation of a DOA for a new study before sending to QA for review. The Delegation Log is referred to as a Delegation of Authority Log (or DOA), some companies may also refer to as an “SSDL” or Site Signature Delegation Log. Key Items to remember: 1. You may only perform tasks for which you have been delegated 2. Training must be completed prior to staff being added to a delegation log 4. Delegation logs need to be current and uploaded to Complion with the original kept in the supplemental binder. SPECIFIC INSTRUCTIONS on how to complete the Delegation Log correctly is titled “DOA Log Training” and there is also a training video in the Operations folder. There is also an extremely helpful checklist for all the various steps involved when adding or removing a staff member to a study on the intranet as well. This should be utilized anytime a staff member is added or removed from a study to not miss any steps. It is on the MCR intranet in the operations folder > Clinical Forms and Logs > Adding or Removing Staff Members DOA APPROVAL PROCESS: MCR sites are required to use the Meridian Delegation log unless otherwise required by the Sponsor/CRO and documented in writing to the site. Staff should push hard to utilize the Meridian log and escalate any requirement for a different log to your manager. Consistency prevents errors. • Lead CRC and SD (Site Director) will create a draft paper log (utilizing the paper DOA form located on the intranet that is watermarked “draft” based on needs of the site/staffing, and requirements of the protocol. This protocol must be reviewed carefully to identify which tasks are needed. Not all tasks on key are applicable to every study. This process should begin as soon as possible. • Once this paper log is completed, reviewed again against the protocol, and verified that the correct staff are assigned the correct tasks, the site will send it to their assigned regulatory specialist for their site who will create the official e-DOA in Complion. *IF there are any questions regarding who should be delegated tasks please consult your onsite QA, your regional clinical trial director for the study, etc. For assistance in assigning tasks **Please CC: Michael Pierre in this email to activate study in CRIO. • Regulatory specialists will build the e-DOA based on this information from the site. Staff will be able to e-sign through complion. • FOR DOA CHANGES DURING STUDY: Site will complete the "add/remove staff" form and send it to the assigned regulatory specialist for review and to update e-DOA. Section updated: 8/4/2022

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Destroying IP onsite Vs. Returning to sponsor Change to SOP (Standard Operating Procedure) IP Destruction Language (see attachment-SOP #05 Handling of IP dated June 22): The previous SOP on IP destruction contained the following language: “FDA recommends all IP is returned to sponsor for destruction. MCR will only destroy IP on site if required and adequate documentation with instructions is obtained from sponsor. Delegated site personnel will complete the MCR On-Site Destruction Record. All IP awaiting destruction will be housed in a secure location until retrieved by an independent contractor hired for this purpose and is disposed of per local and federal laws/regulations. It will be hand delivered to pick-up staff and site will be notified of destruction.” A change has been made so that Meridian returns IP to the sponsor / CRO for destruction unless absolutely required to be destroyed at the site. The change SOP IP Destruction Language now reads as follows: “Will return all IP (unused and returned drug to include empty containers) to the Sponsor/CRO for destruction. The site will only destroy IP on site only if absolutely required to destroy by the Sponsor/CRO” Section added: 8/4/2022

Deviations Anything that deviates from the protocol (i.e.: an “out of window visit”) is considered a Protocol Deviation. There should be a protocol deviation log for all studies. Even if a CRA creates their own Deviation log, Meridian is responsible for theirs and it is required to be maintained throughout the study. These should be captured in real time and not added to a log at the end of a study. If any of the deviations need to be reported to the IRB, then that report also needs to be loaded to Complion. It is mandatory for you to notify your Site Director and the safety committee immediately if there are major deviations in a study. (Please see the Safety Committee Section for the process) Your Site Director will notify your Regional Director of these types of issues at the time of reporting. Examples of these Major Deviations include but are not limited to: 1. Dosing errors / wrong IP given 2. Major deviations from study that are reportable to the IRB per the IRB guidelines 3. Lab errors causing a major deviation / safety risk for the participant It is rare that a deviation is significant enough to be reported to the IRB under a category of anything but “other” and no IRB report should be done for a major deviation or Safety Risk without including your SD, RD, QA and Regulatory in the reporting process. If you have any questions, please reach out to your SD or RD especially if you need help determining if it’s a major deviation.

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Things such as out of window visits and other minor deviations are normally not reportable by the IRB guidelines, but at times some sponsors will request they be reported anyway. If this is the case, we report those under the category of “other” as they do not require IRB review. Pro tip: Some monitors/CRA’s will ask you to record things as protocol deviations that are not actually things written in the protocol. These are Not protocol deviations. If there is ANY question on if a protocol deviation should be captured ASK before doing so.

IF YOU EVER BELIEVE A BOX OTHER THAN THE “OTHER” CATEGORY SHOULD BE CHECKED YOU MUST REVIEW THIS WITH YOUR SITE DIRECTOR, REGIONAL DIRECTOR, QA AND REGULATORY TEAMS – NEVER SUBMIT A DEVIATION TO THE IRB THAT HAS NOT BEEN REVIEWED. THESE FORMS ARE TRICKY AND ONCE SUBMITTED CANNOT BE TAKEN BACK. Section updated: 8/10/2022

Diaries (Collecting, Reviewing, and Storage of participant Diaries) • • •

Protocol/Sponsor process for diaries is to be followed if one is outlined in protocol or provided by sponsor/CRO Log of all eDiary devices received will be maintained to track receipt, dispensation and return of all devices (device accountability log located on MCR intranet to be used) If the Protocol does not include a process for collecting, reviewing and storage of the diaries or if it is less than that required by MCR process the following should be adhered to: o If the diary is electronic: Print the reactogenicity eDiary from portal upon completion of each diary time frame (Example, a 7-day diary after vaccination should be printed upon completion of day 7, for each time a diary is required) and include the diary review sheet on top of the diary print out for the PI to review and sign. The diary and the review form are to be filed in the participants’ chart per MCR requirement. o If the study utilizes paper or card diary to be completed by hand: The site staff should collect diary cards as required at each visit designated by the protocol. Even if there are no symptoms to report, the diary must be collected as it is source and must be included in the participants’ chart. o Review diary at visit or on telephone visit with participant (as protocol dictates) for any signs/symptoms, changes in con meds or AEs. The eDiary review log (available in complion and/or CRIO) is to be completed for each diary (daily, weekly or monthly per protocol) o Check each page for completeness and compliance - to ensure any check boxes, initials or information is complete for paper diaries. o If corrections need to be made to a paper diary, the participant should make them and initial/date. Please refer to the protocol to determine if corrections are allowed to be made for that study.

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o o

o o

Document in source the diary review and any relevant info contained in the diary (con meds, AEs) PI is to review diaries and/or diary reports and initial/date to indicate review and acceptance and PI is to sign off on eDiary review log (protocol specific source and MCR form) – this form is used in all cases, even if the diary portal does not allow the eDiary results to be printed. Long term diary check-ins are typically not printed, as these are not reactogenicity. A log is maintained in source to ensure the participant is continuing to check-in as instructed and has not experienced any significant events. Tip for Medidata Rave EDC: Many diaries can be printed by utilizing the “landscape” view and resizing to 35% in settings.

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E-mail Groups Email Address [email protected] [email protected] [email protected] [email protected] [email protected]

Purpose

Company IT Administrator For e-mails regarding Feasibilities, CDA's. potential new studies. This inbox goes to the entire Business Development team. For emails regarding clinical conductor, set-up of studies, etc. This inbox goes to the entire Clinical Conductor team. For Source documents (both eSource and Paper) for office building facilities questions, project updates, and site-building issues. Please allow 24-48 hours for a response. In case of an emergency or in need of immediate assistance contact Jonathan Whelan via Teams.

[email protected] [email protected]

For e-mails regarding study billing See page re: "notifications" for complete details COO, Operations Vice Presidents, Senior Regional Directors, Regional [email protected] Directors, Site Directors and Site Managers. [email protected] Payroll & Benefits [email protected] Quality Assurance Team [email protected] Recruitment Team [email protected] Regulatory team [email protected]

For communication regarding periodic reviews completed by the risk management team. This team is responsible for assessing issues and research compliance with ICH/GCP associated within all areas of Clinical Research

[email protected]

for all safety related assessments (Quick turnaround) for Protocol Deviations, SAE's, Dosing issues, Patient Safety review, etc. All must be reviewed by this group before any protocol deviations are reported.

[email protected] [email protected]

Group e-mail to all Site Directors company-wide Travel requests / scheduling

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Enrolling Patients in two studies It is (in rare cases) possible to enroll a patient in two studies simultaneously. However, this will need to be discussed with your Site Director and Regional Director prior to proceeding. Always refer to both study protocols to determine eligibility related to dual enrollment as typically this is not allowed.   Examples of patients enrolled in two studies might be: 1. An observational study when a participant is in a study with IP 2. A study when IP had been given but it’s been months since the injection and the participant is only in follow-up phase 3. Determining if a 28 day or 30 days allowance is required between studies The only time our CTMS administrator would allow this would be if the direction came from one of the Regional Directors who will reach out to the COO Kathy Stoddard, MCR President Laura Falcone, and / or Dr. Essink as needed to make this decision prior to letting the CTMS administrator know they can proceed. If you have any patents who you want to duel enroll, please discuss with your Site Director so they can get a decision from the ops team. If approved the CTMS team would have to override the participant into the study in CC.

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FDA Inspection Calls FDA Inspection Calls: What information you must gather should the FDA call your site for inspection. This initial phone call is vital for us to obtain the details necessary to begin FDA prep and scheduling. Once the information is obtained, your Site Director and Regional Director be immediately notified – do not leave voicemails or send emails. Instead, ensure you speak directly to someone who will handle it accordingly. The Regional Director is to then notify the leadership team immediately. Information to obtain on the call: A.

FDA inspector’s first and last name

B.

FDA inspector’s phone number, including area code

C.

Name of PI having the inspection

D.

Name/Title and Protocol number of the Clinical Trial they are coming to inspect

E.

Is this a “routine” or “for cause” audit

F.

Date and time they would like to start the inspection and length of anticipated time they will be on site

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Feasibilities Also referred to as “FQ’s” these are the submissions MCR must complete in order to win new study awards. These allow sponsors and CRO’s to evaluate if a study is a good fit for a site and if the site has the capabilities to run their project. It is MCR’s chance to shine and show off! Normally a feasibility will come in the format of a questionnaire, but at times they are as simple as one graph to just submit the PI’s name if interested. Business Development will share these with sites they believe may want the study and ask for feedback. These are on VERY QUICK turnaround times and are a PRIORITY each day for site directors and site managers. The process for feasibilities is as follows: • • • • •

• • •

BD is tracking metrics on Feasibility Questionnaires (FQs) beginning this week – metrics to include: o Timeliness of FQ submissions o Completion thoroughness Because BD is currently short staffed, for the next 60 days, all sites will assist BD by thoroughly completing FQs, including site demographics and other well know site information until our new BD specialist is up and running Site Directors who are out of office, must assign FQ completion to the Site Managers in their absence All FQs must be discussed with the PI prior to submission All sites should have a database of information to be utilized in completing FQs which has been gleaned from previous FQs that were completed o Please reference this information in order to provide accurate numbers o Update the database when changes occur o Recommend utilizing an excel spreadsheet to keep this information in one place – reach out if assistance is needed in building this Going forward, when BD is notified that PSSVs will be omitted by sponsors, sites will be notified immediately so that appropriate action can be taken (obtain full protocol and request clarifications, etc.) In June 2022, FQs will be built into Microsoft Forms for ease of completion and communication Sites must provide 3 valid reasons for declining a study and Regional Directors must sign off on all study declinations going forward

REMINDER: Please forward any potential new study opportunities to the [email protected] email, and not just an individual on the BD team. It is imperative that ANY new potential opportunity (whether we want it or not) be sent to [email protected]. Every single opportunity we receive is tracked in salesforce. Sending to one member of the BD team can result in a lag time that costs sites the trial. Section added: 4/6/2022

Generators on site / maintenance All sites are required to maintain their generators. (For Battery operated generators, you need to plug this in monthly to ensure it has a full charge.) This should be done on the first business day of the month every month and be logged to show documentation of this maintenance. Site management should have this on a calendar alert set as a reminder to complete this. The Generator Maintenance log is on the MCR intranet and tracks the entire year. Section added 8/4/2022

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How to QC Participant Charts The Lead CRC will be responsible for ensuring that every chart will be 100% QC’d throughout the study and at the time of close out for every participant that signed an ICF. Please see the below steps on how to properly QC a chart. Items needed prior to reviewing Participant Charts: • •

Print the Schedule of Events to ensure understanding of the required assessments and protocol windows for each visit Print a copy of the Study Level ICF log to be able to reference when an ICF must signed by the participant at the screening visit and/or follow-up visits

Steps on how to QC a Participants Screening Visit and/or Randomization Visit: •

Review source starting with the Screening Visit o Ensure Correct Initial ICF was signed by the Patient at the 1st Visit  Ensure ICF Progress Note Documentation Completed  Ensure all dates are correct per the date format on the ICF  Ensure Participant/Parent and the Person Consenting signed the ICF – on all applicable pages (including initials, check boxes, etc.)  Ensure Copy of the ICF is in the paper chart and/or uploaded to CRIO  Ensure ICF was verified by another employee  Ensure Subject Level ICF Log was updated as applicable  Please note that some studies require an assent to be signed by adolescents. Please ensure the above requirements are followed as well. ICF progress note will be documented together for both consents on the ICF process note page in source o Ensure Patient meets ALL Eligibility Criteria for Randomization  Ensure Patient Demographics documented • Ensure correct date of birth compared to the Patient Demographics form completed by the patient o Ensure the MCR Patient Demographics form is completed entirely by the participant/parent • Ensure correct gender, race, and ethnicity completed • Ensure Alcohol History was obtained o If current and/or former include amount/frequency • Ensure Smoking History was obtained o If current and/or former include frequency/method • If participant disclosed Drug and/or alcohol abuse, please confirm how long ago and whether the Sub-I and/or PI discussed abuse with participant to confirm eligibility • eligibility • Ensure Screening Number documented and previous screening number if applicable  Verify Medical History was obtained • Start and Stops dates documented correctly, or Ongoing checked • Procedures have a corresponding Medical Indication documented in the Source as applicable (i.e., Total Right Knee Replacement would have Right Knee Pain documented on a separate line) CRC Quick Reference Guide // V3-10Aug2022

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If patient has an allergy, ensure reactions are documented in the details section • If a patient discloses, they are not taking medication for a medical indication that more than likely would be please ensure we have something documented (i.e., controlled with diet or exercise etc.)  Verify Concomitant Meds and Concomitant Procedure Logs are completed if applicable and patient meets inclusion criteria. • Ensure each concomitant medication and/or concomitant procedure has the appropriate medical indication documented from the indications listed on the Medical History page o If prophylaxis, please include general health or nutritional supplement dependent on the eCRF guidelines and/or sponsor requirements • Ensure each concomitant medication has the correct amount, route, frequency, and Start/Stop dates • Ensure each concomitant procedure has the correct procedure name, correct indication, and date.  Female: Childbearing or Non-Childbearing Potential • If childbearing potential, verify contraception check and/or abstinence documented if acceptable per protocol. *Please note that transgender participants that are born as a female are consider Childbearing and will require a UPT per protocol** o Verify IUD and prescription hormonal contraception was documented on the concomitant medication log o Verify required Urine Pregnancy Test and/or Serum Pregnancy Test obtained at the visit. Ensure results from the UPT was documented in the chart. • If non-childbearing, verify eligibility for inclusion criteria. o Ensure Post-Menopausal status document on the Med History  Confirm date of last menses  Confirm if a FSH was required prior to randomizations o Ensure Surgical History (Hysterectomy, tubal ligation, bilateral oophorectomy as allowed per protocol) documented on the Med History  Ensure why the patient had a surgical sterilization was documented on the Med History page. For the next several assessments please ensure they are completed in order per protocol as applicable. **Please note that blood and/biological swabs are generally collected after Vitals and/or ECG, however some sponsor might require blood after randomization. Please always reference the protocol**  Verify Vitals were obtained and meet inclusion criteria • Ensure Vital seat time was documented appropriately per protocol • Vitals sign seat time should be after the time the ICF was signed. o Example: ICF signed at 11:30 vitals seat time 11:31) • BMI calculated correctly per protocol • All Vitals within range and/or Vitals repeated per MCR Policy •

o

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Ensure abnormal vitals are assess for Clinical Significance or Non-Clinical Significance Verify ECG was obtained per protocol • Ensure supine time was documented appropriately per protocol • If paper chart, ensure the Sub-I and PI have reviewed the ECG for normal and abnormal findings • If CRIO please ensure its upload to the visit level file for the participants chart for the Sub-I and PI to assess the ECG for normal and abnormal findings • Ensure abnormal ECG findings are assessed for Clinical Significance or NonClinical Significance Verify Physical Exam performed per protocol • Ensure all abnormal findings are noted as applicable per protocol. **Please note if PE finding(s) are noted at screening, then please add the abnormal finding(s) to Med HX with the correct start** Verify all applicable blood, urine, and/or biological samples are collected per protocol • Ensure to document time of specimen and/or location of the collected sample if applicable per protocol. o Ensure Lab Req are filled out completely and uploaded in to CRIO if applicable Verify all applicable Sub-I/PI assessments completed per protocol • Please note this can be for more indication base studies and/or vaccine studies that require the Investigator Only performing the required assessments Verify Inclusion/Exclusion review was done with Study Personnel and Investigator with documenting their Initials/Date for the review/confirmation o Please note that this is the last step prior to the Sub-I/PI confirm eligibility in source. Inclusion/Exclusion is a working review during the screening process prior to confirm patient meets eligibility criteria for randomization. Verify the Sub-I and/or PI have signed off on eligibility • Please note that if the PI was not on-site during the visit, then the PI needs to Initial/Date eligibility showing his PI oversite during the PI oversite visit process. Verify the person confirming randomization was a different employee than the person that conducted the visit. • Employee confirming randomization will confirm they meet all Inclusion and Exclusion criteria by reviewing the chart entirely prior to randomizing them. Verify the participant was randomized in the appropriate IRT/IWRS portal per protocol • Ensure printout was placed into the paper chart and/or CRIO chart • Ensure the DOB, Initials, Cohort/Arm, Screening Number is correct per protocol requirements •

















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Verify the Unblinded and/or Blinded CRC performing the IP dispensing and/or administration verified participant meets eligibility requirements prior to dispensing and/or administering the IP (Please note if it is a unblinded study only unblinded employees will have access to IP container numbers, IP accountability Logs, Unblinded IWRS/IRT confirmation pages, and IP worksheets. Only thing to verify will be the administration page within the participants chart) • Ensure the proper IP dispensing criteria was followed per MCR and/or Protocol Requirements. o IP process documented on IP worksheet as applicable  Ensure Verifier confirmed IP container number per IWRS/IRT worksheet  Ensure IP was given within the correct time frame since dispensing and/or completed IP preparation time o IP and/or diluent documented on IP accountability log o IWRS/IRT randomization confirmation page in participants chart as applicable per Protocol o IP administration completed as required by protocol  Including Time and Location  Please ensure that proper documentation is noted if administering a different way then as described per protocol. (ie dominant arm due to…, tattoos on both locations, etc..) Verify ediary was setup and participant training was completed as applicable per protocol • Verify if the employee dispensed a diary to the participant and the serial number was documented in source and on device log as applicable per protocol Verify Post-Dose ediary review was completed by the participant. (ie typically 30 min or 60 min ediary symptom/temperature review) • Verify correct documentation in source for any AESI, AEs, severe grade unsolicited Aes as documented in the ediary Verify Post-Dose vitals completed as applicable per protocol • Ensure Vital seat time was documented appropriately per protocol • Vitals sign seat time should be after the administration time. (Cannot be at beginning of post-dose observation unless being watched entire time during post-dose) • All Vitals within range and/or Vitals repeated per MCR Policy • Ensure abnormal vitals are assess for Clinical Significance or Non-Clinical Significance. (Please note if CS please ensure we document the appropriate AE per protocol) Verify End of visit reminders completed and/or all required participant material given to the participant before leaving • Vitals sign seat time should be after the administration time • All Vitals within range and/or Vitals repeated per MCR Policy

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Ensure abnormal vitals are assess for Clinical Significance or Non-Clinical Significance. (Please note if CS please ensure we document the appropriate AE per protocol)  Verify end of visit reminders were completed and/or all required participant material given to the participant before leaving  Verify Next visit was scheduled appropriately per protocol windows  Please note if the participant is not randomized the same day as the screening visit please verify that everything was completed up to the randomization procedure, participant was given all required participant materials and/or reminders prior to the visit completed. Verify subject was scheduled correctly for the next appropriate visit per protocol. Verify Progress note was documented as appropriate per Protocol and/or MCR Policy •

o

Steps on how to QC a Participants Follow-up Visits as applicable per protocol o

o

o o o o o

Verify participant signed appropriate current approved ICF/Assent ICF prior to the employee conducting the visit.  Ensure ICF Progress Note Documentation Completed  Ensure all dates are correct per the date format on the ICF  Ensure Participant/Parent and the Person Consenting signed the ICF  Ensure Copy of the ICF is in the paper chart and/or uploaded to CRIO.  Ensure ICF was verified by another employee  Ensure Subject Level ICF Log was updated and completed as applicable Verify any new and/or ongoing AEs were addressed/documented appropriately per protocol  Please note that if a participant disclosed any signs and/or symptoms during the visit the employee documented the appropriate AE, Con-Med/Con-Procedure and/or performed additional procedures as necessary per protocol • (I.e. signs/symptoms vs confirmed diagnosis)  Ensure PI has completed PI oversite for all AEs. (SAEs, AESI, and AEs)  Ensure all AEs have been ended if realistically should not be still ongoing at EOS Verify any new and/or ongoing Con Meds were addressed/documented appropriately per protocol  Verify Con-Meds taken for AEs are ended if AE has a stop date Verify any new and/or ongoing Con Meds were addressed/documented appropriately per protocol  Ensure the indication matches the AE and/or Medical History Indication Verify any new con procedures were documented appropriately per protocol  Ensure the indication matches the AE and/or Medical History Indication Verify e-diary was reviewed and any findings on the e-diary was documented appropriately per protocol  Ensure e-dairy was collected as applicable Verify all appropriate procedures completed as outlined in the protocol and that the employee followed MCR policies as described in QC’ing a screening visit.  Verify all previous Lab reports reviewed and assessed by the Investigator including PI oversite. • Verify labs were printed and/or uploaded into CRIO for review as applicable • Please note that some protocols will require elevated lab reporting as an AE and repeat of labs as applicable for protocol CRC Quick Reference Guide // V3-10Aug2022

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Urine Pregnancy Test Vitals ECG • Verify ECG was printed and/or uploaded into CRIO for review as applicable  Symptom Directed Physical or Directed Physical • Ensure anything reported on the physical was documented as Med HX or AE as applicable per protocol  Investigator Assessment as applicable  Lab Specimens collected as applicable  Confirming Eligibility if applicable  Re-dispensing and/or dispensing of IP if applicable • Collected IP Container or IP if applicable per protocol  Unblinded/Blinded IP Verification and Dispensing requirements  Post-Dose e-Diary assessment  Post-Dose Vitals and/or Investigator Assessments  Appropriate participant reminders and participant materials given at the visit  Appropriate visit schedule according to the protocol and/or MCR policy Verify all AEs, Con-Med Logs, Con Procedure logs, and e-diary logs completed entirely as applicable per protocol and MCR policies Verify e-diary logs are printed and/or uploaded into CRIO for PI oversite as applicable  Verify PI has signed for PI oversite Verify Progress note was documented as appropriate per Protocol and/or MCR Policy   

o o o

Steps on how to QC a Participants End of Study Visits as applicable per protocol o

o

o o o

Verify participant signed appropriate current approved ICF/Assent ICF prior to the employee conducting the visit.  Ensure ICF Progress Note Documentation Completed  Ensure all dates are correct per the date format on the ICF  Ensure Participant/Parent and the Person Consenting signed the ICF  Ensure Copy of the ICF is in the paper chart and/or uploaded to CRIO.  Ensure ICF was verified by another employee  Ensure Subject Level ICF Log was updated and completed as applicable Verify any new and/or ongoing AEs were addressed/documented appropriately per protocol  Please note that if a participant disclosed any signs and/or symptoms during the visit the employee documented the appropriate AE, Con-Med/Con-Procedure and/or performed additional procedures as necessary per protocol • (I.e. signs/symptoms vs confirmed diagnosis)  Ensure PI has completed PI oversite for all AEs. (SAEs, AESI, and AEs) Verify any new and/or ongoing Con Meds were addressed/documented appropriately per protocol  Ensure the indication matches the AE and/or Medical History Indication Verify any new con procedures were documented appropriately per protocol  Ensure the indication matches the AE and/or Medical History Indication Verify e-diary was reviewed and any findings on the e-diary was documented appropriately per protocol  Ensure e-dairy was collected as applicable CRC Quick Reference Guide // V3-10Aug2022

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o

o o o

Verify all appropriate procedures completed as outlined in the protocol and that the employee followed MCR policies as described in QC’ing a screening visit.  Verify all previous Lab reports reviewed and assessed by the Investigator including PI oversite. • Verify labs were printed and/or uploaded into CRIO for review as applicable • Please note that some protocols will require elevated lab reporting as an AE and repeat of labs as applicable for protocol  Urine Pregnancy Test  Vitals  ECG • Verify ECG was printed and/or uploaded into CRIO for review as applicable  Symptom Directed Physical or Directed Physical • Ensure anything reported on the physical was documented as Med HX or AE as applicable per protocol  Investigator Assessment as applicable  Lab Specimens Collected as applicable  Collecting IP/IP container if applicable Verify all AEs, Con-Med Logs, Con Procedure logs, and e-diary logs completed entirely as applicable per protocol and MCR policies  Ensure indications are documented Verify e-diary logs are printed and/or uploaded into CRIO for PI oversite as applicable  Verify PI has signed for PI oversite Verify Progress note was documented as appropriate per Protocol and/or MCR Policy

Steps on how to QC Medical Records • • • • • •

Verify Medical Release was filled out correctly per participant/parent Verify Medical Records received was stamped with “received” with Initials/Date Verify Sub-I and/or PI initial/dated the records confirming they have reviewed the medical records Verify and confirm all Med HX, Con Meds, and Con-Procedures documented/verified as applicable per protocol Verify if any AEs, Con Meds, and Con Procedures were documented as applicable per protocol Verify records are stored in the participants chart and/or uploaded into CRIO

Steps on how to QC SAEs •





Verify clear documentation was noted in the participants chart on how the site was informed about the SAE o Please note this can be from a visit, telephone call, and/or receipt of medicals records o Verify the time and date when the site became aware of the SAE Verify SAE form was completed within the 24hour notification policy per FDA requirements o Notification can be done by direct EDC entry and/or Sponsor provided paper forms o Verify SAE was documented on the required AE form per MCR source requirements  Please note that participants and/or site might not have the correct AE term and/or know all applicable information to document on the sponsor SAE form and all required fields in the EDC at the time of notification Verify the Sponsor/CRO/CRA was notified via email at the time of SAE notification

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• • • • • • • •

Verify Medical Release was filled out correctly per participant/parent for the required information on the SAE Verify Medical Records received was stamped with “received” with Initials/Date Verify Sub-I and/or PI initial/dated the records confirming they have reviewed the medical records Verify and confirm all Med HX, Con Meds, and Con-Procedures documented/verified as applicable per protocol Verify if any additional AEs, Con Meds, and Con Procedures were documented as applicable per protocol Verify records are stored in the participants chart and/or uploaded into CRIO Ensure SAE form was updated as applicable per the medical records and/or participant/parent confirmation Ensure SAE was documented in CC for tracking purposes

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Intranet The Meridian Intranet houses many documents necessary for the day-to-day operations of our clinical trial sites. These are updated and typically version controlled – so these documents shouldn’t be printed out and kept onsite for future use, but rather accessed on the intranet as needed. Clinical Forms and Logs (FOLDER)

Complion Instructions and Guidelines (FOLDER)

PBMC Forms and Logs (FOLDER)

1.0 Complion User Manual Nov 2020

Adding or Removing Staff Members

1.1 Research Regulatory Binder Template - Updated 11_06_20

Communications Log

1.2 Supplemental Paper Binder 16 OCT 2020

CRC Study Transition Training Form

1.3 Complion Guidance Checklist

Daily Oxygen Monitoring Log

1.4 Regional_Regulatory_QA Contacts 08 OCT 2020

Device Accountability Log

1.5 Central Binder Onboarding 16 OCT 2020

DOA Log Bullet Point Instructions 2021

1.6 Site Investigator List_V2 Blank

DOA STOP Instructions 14 JAN 2021

1.7 Complion Signature Guidelines_MCR_Oct_2019 (00000004)

Dry Ice Log

1.8 CRA Complion Access Guide

Emergency Kit and Supplies

1.9 Complion Validation Questions FAQ

Hood Cleaning Log

2.0 Complion Part 11 Compliance Letter

Investigative Product Accountability Log

Quality Assurance (QA) (FOLDER)

Master Informed Consent Log

Adding or Removing Staff Members

Phone Correspondence Form

Corrective Action Response Form (PDF)

Pregnancy Test Log

Corrective Action Response Form

Protocol Deviation Log

Correspondence for Monitoring Visits

Remote Monitor Visit Log

CRC Study Transition Training Form

SAE Adverse Event Intake Form

FDA Inspection Checklist

Site Signature and Delegation of Responsibilities Log

Fridge Sign

Spin Log Form

Note to File Form - 1572 Change

SSDL-Guidance-Document Sep2020 V1.2

Note to File

Study Level Consent Form Log

Patient Query Review Form (Condensed Version)

Supply Destruction Record

Patient Query Review Form (One Subject Per Page)

Temperature Log Form (2021)

Patient Query Review Form (Condensed Version)

Temperature Log Form

Post-Dose Vitals

Training Log Specific to Each Task (Instructions Only)

Redacted Records Log

Training Log Specific to Each Task (Multi-Page)

Redaction reminder sign

Weekly Eyewash Inspection Form

Source Document Creation Process

Site Director (FOLDER)

Source Document Request Form

CRC Study Transition Training Form

Study Closeout (FOLDER)

Meeting Minutes Form

IP Destruction Record

Pre Site Selection Visit Form

Monitor Closeout Visit Checklist

Pre-Site Selection Visit Form (Word Version)

Storage Transfer Form

Training Log

Supply Destruction Record Word

Weekly Site Director Checklist

Supply Destruction Record PDF

Do not edit the originals on the intranet – rather download to your computer and then edit them (or else the whole company will see your edits on the originals!) An example (Not all inclusive as these forms are added to frequently) of forms on the Intranet: *Please see the following page containing the current OneDrive files as of 23Sep2021. These are subject to change and are updated frequently in this live folder. There are other folders, this is just a list of the most frequently used documents. This section will be updated during the next review in Q4 2022 CRC Quick Reference Guide // V3-10Aug2022

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IRB Documents IRB documents are documents that have been approved by the IRB such as: the consent, protocol, advertisement/recruitment materials, patient materials, continuing reviews, etc. IRB documents need to be uploaded directly to the study binder in Complion since not all documents are sent to Notifications. The lead coordinator is responsible for making sure all IRB approved documents are uploaded into their study binders. All CRCs are also expected to check their IRB portals daily to ensure no new ICF has been released to prevent any consenting with an incorrect ICF version. The main IRB’s used are: • • •

Advarra WCG Sterling

Lab Reports Lab reports should be routed immediately for review signature by a delegated investigator (Sub-I and/or PI) to ensure participant safety. These should be reviewed in a timely manner. The lead CRC is responsible for this for their assigned studies. All lab reports with values reported should also be reviewed and signed by the PI for the study.

Late Entry – Clarification When late entry is made the date of the note is the documentation of the late entry. There is no need to add an additional note at the date of documentation signifying the late entry. In CRIO late notes need to be added to ADDITIONAL SOURCE in CRIO. Adding "Late entry" note does not clarify anything. If a signature is significantly late the person signing could note "missed line at time of visit". There is no value in adding the note of “late entry”; it does not clarify anything. Section added: 8/4/2022

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Lost to Follow up (Participants that cannot be reached) No participant in a study should be dropped citing the reason of “Lost to Follow-up” without reviewing the chart and all documentation with Site Director/Regional Director showing that all avenues to reach the participant have been exhausted. Participants must have a minimum of 3 documented attempts to reach them in their chart which can included reaching out to their emergency contacts. If at least 3 minimum failed attempts are documented, then a certified letter must be sent to the participant after the last attempt with no response. With all documentation clearly captured in source of these attempts. A participant that is lost to follow up is a huge loss of revenue, and a concern due to not having long term safety data from the subject. The staff all work very hard to enroll each participant, that same effort must be shown to retain them – and approval from Site Director and Regional Director must be granted before a participant is dropped for this reason. Please follow the below steps on how to document this process in the CTMS/Clinical Conductor: 1. 2. 3. 4.

1st attempt should be scheduled at 6am 2nd attempt should be re-scheduled for 615am 3rd attempt should be re-scheduled for 630am Certified letter should be re-scheduled for the following day at 645am to indicate a certified letter needs to be sent to the participant if no response from the 3rd attempt 5. After Certified Letter is created and shipping documents are finalized a copy of both documents will be uploaded into the CTMS/Clinical conductor for tracking and invoicing purposes for the Finance team 6. The appointment will be canceled and participants status will be changed to “Dropped/Screen Failed” in the CTMS when they are officially deemed lost to follow-up from the sponsor and/or site. Please ensure a “Note” is added to the note section in the participants chart in the CTMS and participants chart for PI oversite 7. A copy of the certified letter and shipping documents will be uploaded into the CRIO chart or placed into the participant paper chart

Medical Record Releases MCR does not routinely collect Medical Record Release forms unless a study specifically asks for past medical records upon screening, and MCR has confirmed this is required by protocol. Patient report of medical history is frequently accepted. This is protocol driven. Only fully completed authorizations for release of medical records are to be used if a specific protocol requires records. Medical Record Releases without an end date are not allowed. We need to add an end date, so that the release is issued for a certain period as well as what records are being requested and from what facility. We do not have all participants sign blank releases “in case of” SAE’s. If we have a release signed, it is for a specific set of records from a specific identified location. *Please note that when Medical Records are received, they need to be stamped received with the Principal Investigator and/or Sub-Investigator confirming they have reviewed them. * Section added: 8/4/2022

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Monitoring Visits Monitoring visits can also be referred to as IMV’s or Interim Monitoring Visits. These visits are to ensure ethical conduct, proper collection of data, appropriate records of study procedures, and compliance with the approved protocol. Monitoring visits should be placed on the CTMS calendar when they are scheduled so they can be viewed by all departments (Video on Stream on how to enter these). QA and Regulatory should be notified so they can ensure charts are reviewed and all items are current in the binder. *Pro Tip – send an outlook calendar invite to your QA and Regulatory specialist with the protocol number listed so they are aware and able to help prepare for the visit. Please also notify QA and Regulatory of all your scheduled IMV’s, RMV’s, SIV’s, COV’s etc. to allow both the Regulatory and QA Teams to confirm all binders are up to date prior to your visit date. Please email your Regulatory Specialist the following information for all upcoming monitoring visits: • Sponsor • Protocol • CRA/Monitor Name • What type of Monitor Visit • PI • Site • Lead Coordinator Resolve all issues that can be resolved while the monitor is onsite. You want to have as few action items as possible – preferably none. Please meet with them first thing upon their arrival to express that you will resolve any issues they find and follow up once items are completed. It is expected all CRCs are prepared for their monitoring visits. There is a Monitor visit preparation checklist to assist with this. When a study monitor arrives onsite the CRC should present them with the monitor sign-in log for that study immediately upon their arrival so that the monitor completes this as their first task. Monitor Follow-Up Letters If you don’t receive a follow-up letter from a monitor in a timely manner you should send an email requesting it. Follow-up letters need to be resolved, responded to (if any action items), and uploaded to Complion with resolution of each item stated within 14 days. An email with the resolution should be sent to QA, Regional Director, Site Director, and uploaded to Complion. There is a CRA response letter template available on the Intranet as an example of how to follow up in writing to any action items listed on the follow-up letter.

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Monitor letters should be signed and dated when they are received at the site. Sometimes monitor letters are compiled but not sent out the same day so the CRA’s date on the letter is not always accurate. We need to signify the date we received it at the site. Site Directors need to follow up with CRCs to make sure all monitoring follow-up letters are received. This is a requirement and some cases the CRA may be delinquent or delayed. CRC’s need to be persistent in requesting these follow up letters in a timely manner. The Site Director needs to get involved if the CRC is not getting their letters back after multiple requests. CRCs need to address all actions listed in the follow up letter in a timely manner, not just simply submitting the letter into Complion when it is received. The CRC ideally should print the letter out and work on each action item until completed. These action items are to be completed prior to the next monitor visit at a minimum, ideally within 2 weeks of receiving the letter from the monitor. Site Directors need to track these tasks on their calendars to make sure these tasks are being done. The follow-up letter to the CRA confirming each action item is completed should utilize the template on the MCR intranet located by searching: “Monitor follow up letter” and the basic outline is below and should be on MCR logo / letterhead:



RE: Dear , Thank you for the follow up letter dated from your recent monitoring visit. As always, we strive to provide high quality, clean data for all studies. In your letter, you have listed the following items to be addressed by the site prior to your next scheduled visit. I have reviewed all items along with the PI and QA specialist for resolution. Beside each item is the status and date resolved, if appropriate. 1. - 2. If you have any questions or need additional information about any of these items, please do not hesitate to contact me at or . I have the next monitoring visit scheduled for . I look forward to seeing you at that time. Best regards,

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Note to File MCR limits NTFs to administrative issues (e.g., location of forms, etc.), issues of that same nature that are for the most part one-time occurrences. There is nothing in FDA regulations or guidance documents that requires sponsors and clinical sites to use NTFs. A NTF is not meant to identify a corrective action. The FDA does not approve of after-the-fact memos nor does an NTF negate a site’s responsibility for their error(s). Once an NTF is written and becomes a study record, it cannot be retracted. NTF provides a “roadmap” for an auditor or the FDA that a mistake was made. MCR sites should refrain from writing NTFs for items that can be or already have been clearly documented within source documents/subject charts, correspondence or otherwise in a manner that resolves the issue without additional paperwork or calling undue attention to an issue. A NTF should not replace good documentation practices (GDP), GCP adherence, and human subject protection (HSP). In a Warning Letter (www.fda.gov/foi/warning_letters/s6551c.htm), FDA wrote: "Our investigation found (the sponsor) failed to take any action except to generate numerous memos to file after all the subjects completed the study." The Warning Letter then noted at least 89 memos were generated after a monitoring visit. Process for writing a NTF •

• • • •

Using criteria above, determine if a NTF is needed for the issue in question with the Site Director, Regional Manager and QAS. Submit to the safety committee for review once narrative is written for approval. If needed, draft NTF using NTF form located on the MCR intranet. Work with SD to write draft and have QAS review initial draft Clearly state the issue (for example lost diaries, missing documents, etc.) After final review and approval through safety committee, the NTF will be returned to the site for PI signature Once PI has signed, upload to Complion for filing and alert sponsor/CRO of finalized NTF.

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[email protected] The Notifications email is a way of sharing important documents with all the necessary departments. There are specific items that should be sent to this email address by each site for all studies: What to send to [email protected]: New ICF’s – Please include explanation of changes • Protocols and Protocol Amendments (Include IRB site level approval status and include synopsis if available) – Please include explanation of changes. Departments need to know if this is approved at the site level. • Protocol Clarifications (state if site has received site level IRB approval for these) – Please include explanation of changes • Study Changes: Green light/Activation, enrollment hold, early enrollment closure, major enrollment changes – Please include explanation of changes. • Study Award Notifications – include template on page 6 for study award notifications • FDA and Sponsor Audit Notifications and Sponsor Oversight Visits – Notify if site is prepared or any audit preparation plans • PSSV reports, PSSV scheduled dates (include protocol if possible) • SIV scheduled dates •

If updating about an existing study please include where we are on enrollment, alert anyone who needs to be alerted, state where we need help, and the enrollment goal. Notifications emails auto forward to leadership, Business development, Regional Directors, Source Team, and CC team among others. They do not go to individual sites, as these emails are coming FROM the sites to these departments. Please make sure to always include in the Email subject line: Sponsor, FULL Protocol number, PI, and Site location when sending items to [email protected]. Please also CC: your site’s assigned QA staff on these notifications. Section updated: 6/29/2022

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Offsite Storage of Study Documents Moving study documents offsite should only be done with the assistance of the Site Director and Regional director for the site as it is a many-step process. When moving charts off site to storage an email needs to be sent to the Sponsor notifying them of our intent. Here is an e-mail Example: Protocol: CP-PRO-QVLP-014 Site # 240 PI: Paul Bradley, MD Per our sites procedures we are notifying study staff of intent to move study documents for the abovementioned study to our offsite document storage location.  Offsite storage documents are tracked in the CTMS system as either “on-site” or “off-site”. The status of documents should only be updated by SD’s or RD’s. Note: There is a general note to file (NTF) that covers storage of documents which is filed in every study binder. Section updated: 8/4/2022

Out of Office – Email Automatic Replies When you will be out of the office for more than two consecutive business days, turn on e-mail automatic replies and use the following message (copy/paste the below and complete as applicable): I am away from the office and may not have access to email until I return on (). For immediate assistance, please contact: · : // · : // Contacting Out of Office Employees for Urgent Matters: If a Meridian employee or external client requires your immediate/emergency assistance while you’re absent, a Meridian employee will call or text you to refer to an email with “URGENT” listed in the subject line.

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Patient Health Information (PHI) To protect participants and their privacy, Meridian must adhere to Health Insurance Portability and Accountability Act (HIPAA) guidelines. To stay compliant, we must ensure the safe and secure management of patient information, especially through email. Microsoft Office 365 is the suite of software Meridian uses for email (Exchange) and includes file- and datasharing tools such as OneDrive and SharePoint. Your “@mcrmed.com” account is a Microsoft Office 365 account. Email encryption helps ensure the private, secure transfer of email content among intended parties. Protected Health Information (PHI) is any medical information that can potentially identify an individual. This includes information about health conditions (past or present), treatment/exams provided, and even name, address, initials, DOB, and/or SSN when associated with any health information. Quick Steps to Protect PHI • Do not share PHI via Teams • Always lock your computer when you step away from it • Ensure participant files are not visible through open doors or windows, even when attended • Ensure participant and non-Meridian parties cannot overhear discussions involving PHI • When not in use, ensure PHI is locked in a room or file cabinet • Do not store unencrypted PHI on any electronic device (e.g., laptop, thumb drive) that will be taken outside of Meridian Emailing PHI • Use participant ID numbers instead of participant names • Never log into a third-party email app with your @mcrmed.com account • Do not manage emails on any personal, non-Meridian device (such as your personal smartphone) • Stop, Think, and Review emails before forwarding them or sharing with an external party, especially if they contain PHI or sensitive employee, business, or financial information Emailing PHI Within Meridian If you send an email ONLY to users with an @mcrmed.com account, the email will automatically be encrypted. No further action is necessary to protect the email. Emailing PHI Outside of Meridian Certain Meridian users can send encrypted emails containing PHI outside of the system as needed. If you have not received information about doing this with your account, DO NOT send PHI to any external accounts (e.g., addresses that don’t end in @mcrmed.com). Staff at all sites can upload source documents and other documents containing PHI into Complion.

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Peer to Peer Chart Review (Paper/E-Source) Informed consent form • If a new version of ICF has been approved, has subject signed at next visit • Is the most current version being used • Are all page’s present • Are all signature lines signed, initialed/checked, and dated as required by subject and staff conducting consent process • If an error was made, was it corrected appropriately • Has the ICF been verified by a second person Inclusion/Exclusion Criteria • For any visits following a visit with labs: lab results uploaded and e-signed. Reviewed by PI and/ or Sub – Investigator • CS or NCS checked where required and any follow-up documented in chart (i.e.: shared results with participant, redraw planned, etc.) • For Screening labs: Was applicable inclusion/exclusion lab review visit completed? • Does protocol require site to have medical records, vaccine records or any other study specific information. Meet eligibility criteria? • If screen fail, is the reason clearly documented Randomization • Were all procedures completed as required per protocol prior to randomization and clearly documented as such in the source • All (Blinded) information pertaining to randomization documented and filed • Verify parameters for cohorts per protocol. Is subject randomized to correct Cohort. Has the subjects' profile been updated with the correct cohort/arm if applicable Source Documentation • All tasks completed, fully filled out source. • All subject related documents filed are e-signed • Progress note completed for each visit as required • Medical history completed using correct medical terminology – surgeries should have corresponding condition • ConMeds are completed using correct drug name, route, dose and indication – meds should match medical conditions on history, PE/medical assessment and medical records • BP (for adults) above 140/90 must be retaken. If above 140/90 a second time, the PI/Sub PI must document even if NCS is checked • All AE/SAEs must have follow-up with resolution date, and have signature or progress note from PI showing their oversight on each of the AE’s. • Copies of ECGs, Lab reports, MRI report, any applicable paper documentation is filed at the visit level and e-signed. • All chart logs completed pertaining to visit (protocol deviations, AE, Con meds) Diaries (paper or eDiaries) • Training/dispensation of diary is documented • Ensure diary entry completed and review documented prior to subject discharge, if required by protocol CRC Quick Reference Guide // V3-10Aug2022

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Diary review log is completed If a severe reaction is documented in the diary, it must be addressed (with documentation) by the PI/Sub PI. It is not necessarily an AE or an SAE unless protocol defines it as an AE/SAE

• •

Investigational Product (IP) • All information pertaining to dispensation of IP documented in source (blinded documentation only) • Where required, subject compliance rate documented in source and if required, additional training given • IP instructions and/or any requirements for reporting side effects given to subjects and documented in source

PI Oversight Responsibilities • • • • • • •

Review and sign EKGs (or any other study specific diagnostics) and decide if significant. *Abnormal EKG requires PI signature, Normal EKG Can be Sub-I Review and sign off on all labs and decide if significant. *Abnormal can be signed by Sub-I but requires PI over-sign for confirmation * Determine AE and SAE severity and causality (Can be determined by Sub-I but requires PI oversign on all.) Review and sign eligibility *Can be signed by Sub-I but requires PI over-sign for confirmation * Review and sign (or over sign) any clinical “additional source” notes Review and sign off on printed diaries *Can be signed by Sub-I but requires PI over-sign of review as well* DOA log review and signatures

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Post-Dose Vitals "Why are we checking post-dose vital signs?" There has been some question as to why we are doing post-dose vital signs when the protocol doesn't specifically require it. Meridian implemented the strategy of using post-dose vitals as a relatively simple method of determining subject stability prior to discharge from the clinic after receiving an investigational product or comparator/placebo. This was for two reasons. After experiencing multiple FDA audits and reviewing regulatory documents (GCP), the question of "subject stability/safety" has been broached multiple times. FDA auditors routinely ask the Principal Investigator the following questions: "How did you determine the subject is stabile to receive investigational product? How did you determine the subject was stable to be discharged from the clinic?" in their initial interviews. The first question is fairly easy to answer as there is medical history, a physical, maybe labs, etc. performed before randomization. In addition, we have implemented pre-dose vitals in all IP-administering visits. Most, but not all, are required by protocol. Most trials also have post-dose vitals or observation period designated by protocol. However, if not required by the protocol, the PI must be able to explain how stability was determined and source documentation must support this. Therefore, Meridian, under my guidance, has required pre- and post-dose vitals whenever IP or equivalent has been administered as the simplest, and probably most effective, screening tool to determine current stability. Checking vital signs and having an observation period also allows for the determination of immediate, dosing-related adverse events. These are generally captured in diaries which can be reviewed with the subject. It also gives the subject time to see if they have any questions about next steps and their responsibilities and an opportunity for us to express protocol compliance. Determining stability is also a general medical practice in most (should be all!) clinics. In addition, we have seen a shift to this in vaccineadministering places of business such as pharmacies as well. This is more for legal purposes as there have been numerous cases of injury shortly after leaving a practice and receiving medication or a procedure. Documentation of stability helps protect you as a medical entity in these cases. Therefore, it's just good medical practice! "When should we do post-dose vitals?" The simple answer is "any visit IP or equivalent is being dosed in clinic". This is regardless of route administered (e.g., oral, intramuscular, intravenous, subcutaneous, topical, intraocular, transdermal, inhaled, etc.). I think we can have a discussion prior to the protocol if the route is topical (i.e., applied to the skin) and the investigational brochure expresses minimal risk of systemic effects. Giving a foreign substance via any route can cause an adverse reaction. As an example, some of the worse post-dose, systemic reactions I have seen in my career have involved eye drops! "How will we do post-dose vitals?" Most protocols will have post-dose vitals and observation built in via the schedule of events. Protocol specified times will be followed. These are generally based on information found in the Investigator Brochure if you want more information on why these have been set forth. Occasionally, the FDA requires a specific timeframe for checking of vitals and other stability procedures such as ECGs when they are reviewing the sponsor's protocol. However, when post-dose vitals are not part of the protocol, our team, including source writers, will add a section for post-dose vitals to be completed. This is NOT an optional activity and should not be crossed out or have "NA" written on it just because it "is not in the protocol". Please contact your clinic director, regional manager or myself if there is a concern that the requirement cannot be followed. It is noted that there are CRC Quick Reference Guide // V3-10Aug2022

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times that a subject may refuse to cooperate with post-dose vitals. It happens at all the clinics. If this is the case, this should be documented thoroughly in the source documents and, when possible, the subject should sign this stating they are refusing and for what reason. This would be similar to an "Against Medical Advice" form provided at the hospital. Site personnel telling the subject it is optional and they "really don't have to stay and do this" in order to not have to perform the vitals are possibly committing medical malpractice and putting themselves and site at legal risk and risk for FDA noncompliance. If part of the protocol, a protocol deviation will also need to be documented. We are currently working with multiple Meridian PIs to come up with a set of "Normal" vital signs for different age groups in order to make this process easier. Previous recommendations have only been mine based on industry standards and using some guidance from other documents such as JNC 8. Many protocols have individual "Normal" values stated and these should be followed in those instances. Our goal here is subject safety as a priority. Therefore, when ranges are outside the "Normal" value, rechecks should be performed and an investigator notified if they continue out of range. The investigator should document whether stability exists, and whether the subject is safe to be discharged or other arrangements made (e.g., follow-up with primary care, go to the emergency department, call ambulance, etc.). Please don't hesitate to contact me with any questions or concerns. Again, we don't want this to be a burden on the site but instead are protecting subject safety and following regulatory agency recommendations in the process of performing our amazing research! Bandon J. Essink, MD, CPI Medical Director, Principal Investigator

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Primary Care Physician (PCP) Notifications Paper Charts • • •

• • •

• • •

Lead CRC creates and signs a letter for each study using the PCP notification template from the MCR intranet Site administrative assistant or delegated staff places a copy of the letter in each chart for each screening/randomization visit Letter remains in the chart if subject agrees to notifying their PCP of study participation either on the ICF or verbally as recorded in source document. Otherwise, the letter template is removed from the chart if the subject declines If the subject meets all eligibility criteria and is randomized, at that time the letter is completed The Lead CRC or delegated staff is responsible for filling in the subject name, DOB, date and the PCP information The admin assistant or delegated staff may fax the letter and include the Fax confirmation page with the letter; if it is sent via email, then that can be documented on the letter or the email itself printed and filed. Otherwise, the letter may be sent by mail to the PCP – this is done within 5 days of randomization. A copy of the letter and the front of the envelope with a stamp is placed in the chart. If the PI is the PCP they can be notified by email or verbally; notification is documented in subject’s chart If the subject agrees, notify the PI’s practice utilizing the PCP notification template from the MCR intranet

E-source/CRIO • •

The CRC at Screening tags the person who is delegated to send the PCP notification letters for the site (this will vary at each site), that will remain as an unresolved comment (all can see it) until it is sent. QA will be able to see this easily. It will be noted who sent the letter through the comment. This will be left as an action item. The coordinator could also use their own name in the tag to ensure this is done for "their study."

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PSSV’s (Pre-Site Selection visits) PSSV’s (or Pre-Site Selection Visits) are also referred to by some in the industry as PQV’s (PreQualification visits). These are assessments of the site to establish if we could effectively run a study at the site. PSSV’s are how studies are awarded – and are therefore one of the most pivotal moments in the process of a study at the site. These visits are TIME SENSITIVE and must be scheduled URGENTLY once a sponsor or CRO reaches out to schedule. Studies move quickly at this phase, and if the site is not evaluated quickly, the site may not be chosen to participate in the study. The sponsors/CRO’s are monitoring how long it takes for a site to respond and schedule these visits as indicators of how the site will perform and communicate during a study. A sponsor or CRO requesting a PSSV should always be responded to within 24 hours, even if it's to say that you are working with the PI to get a date scheduled and will get right back to them. It should take no longer than 48 hours (about 2 days) to get the date set. During the PSSV there will be a presentation (typically slides) about the study design. A brief meeting with the PI will take place to discuss if he/she believes they will be able to enroll the study based on the review of the criteria. There will also be a tour of the office to ensure the site has adequate space and equipment to run the study. This is the site's opportunity to highlight themselves and their abilities. The staff leading this PSSV (Typically Site Director/Manager/Lead CRC) will complete the MCR PSSV form in its entirety. There are many questions on this form that other departments use to set up the study in our systems. Once completed both the PI and regional directors review and sign these forms. The site submits these to [email protected] Allow the CRA to complete their presentation – be professional and avoid interrupting. Any questions on the PSSV form that were not answered by the presentation can be asked of the CRA after they have completed their slide presentation and review. Please have printed and available for reference the submitted feasibility (BD sends this to the site upon completion) to ensure we are not stating different enrollment expectations at the time of PSSV than was listed at the time of the feasibility being submitted. If after reviewing the slides as PSSV the PI and site think these enrollment expectation numbers should be different that those submitted at feasibility – please note this on the PSSV form with reasons so the departments receiving this form are aware. If for any reason the regional director is unavailable, the MCR PSSV form can also be signed by a Senior Regional Director or VP of Operations. These forms should be submitted within 48 hours (about 2 days) of a PSSV being completed. If a Sponsor/CRO wants to schedule an “SQW” or “Site Qualification Waiver” call – this is the exact same thing as a PSSV and a PSSV form still needs to be completed and submitted just as if this call is a PSSV. This form initiates the study being set up in our CTMS so this is always needed even when a PSSV is only a formality and site knows they will be selected. Section added: 3/16/2022

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Redaction of Medical Records It is our job to protect the privacy of our subjects. Any time medical records need to be sent out they must have all identifying information redacted. Name, Date of birth, hospital account number/record number, etc. These MUST be reviewed by the Site Director after initial redaction by the CRC. If there’s anything questionable, please run it by your site assigned QA staff prior to sending out records. Make sure any marker being used cannot be seen-through – there are redaction pens for this purpose that can be ordered at any time. Review of redacted Medical Records will be documented on the “Redacted Review Log” by the Site Director. How to Redact Medical Records - Process

1. 2. 3. 4. 5. 6. 7. 8. 9.

Make a copy of the medical records to be redacted. Thoroughly redact all medical records using the checklist below. Scan a copy to yourself after redaction. Review the scanned copy to be sure that no redacted information is visible. If you can still see the information, print a copy and re-redact. Scan to yourself a second time and re-review. If all information is redacted to the best of your knowledge/ability, forward to QA/Reg for review. QA/Reg will forward it to Site Director for a final review. Site Director reviews for approval and sends back to CRC giving the okay to send or providing updates that need to be made. 10. If additional redaction is required, repeat steps 2-9.

Ensure EVERY page of medical record has the following identifiers redacted • • • • • • • • • • • •

Patient Name, Parent/Guardian name DOB SSN Patient Account #, Hospital patient ID# Hospital name, address, logo Lab name, address, logo Patient address Patient pharmacy Attending physicians, Attending staff names (nursing staff, physical therapy staff) Author/editor name if transcribed from dictation Electronic signatures Any/All other patient identifying information as needed

Section Updated: 8/10/2022

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Regulatory Compliance Reports MCR is extremely fortunate to have a Regulatory department. This team completes regular compliance reviews of ongoing studies to ensure quality data and compliance by MCR employees. As part of this review, compliance reports are sent to Lead CRCs for the study noting potentials issues or deficiencies to be addressed. These require a response by the Lead CRC to each item listed. Instructions for response to compliance reports: • • • • •

• •

Lead CRC is responsible for response and return of the completed report If you need an extension, please contact the requestor for additional allotted time Send response after all action items have been completed. Documentation of “pending resolution” does not resolve an outstanding action item. The Compliance report is not considered resolved until all action items are completely resolved. Please keep the same email items with all responses (this is for tracking purposes) Write the completion date with any responses/notes on the report received in the “resolved” column so that it can be uploaded If you are having an issue obtaining needed documents from the sponsor or CRO to complete a report, please ask for assistance from your Site Director, Regional Director, or Senior Regional Director to resolve it.

Compliance reports are due one week from the time they are issued to the Lead CRC.

Section Added: 8/10/2022

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Safety Committee What goes to the safety committee: All Protocol deviations the CRA requests the site to send to the IRB, SAEs, Dosing errors, CAPPA requests, NTFs, and any pertinent safety issues –There is a Microsoft form to utilize to submit these, the link is on the main page of the Meridian Intranet. This type of information needs to be reviewed by the safety committee before reporting to the IRB, so the committee can evaluate and assist with the reporting process, should they determine reporting is warranted. (SAEs do not need to go through safety committee before sponsor reporting. This is done immediately within 24 hours of site awareness. We only ask that the IRB report for the SAE be sent before submission.) The assigned Senior Regional of the site that is reporting the issue to Safety Committee will take it from there and push forward to resolution (decide if QA is to be roped in, if a CAPA should be done, If a NTF is appropriate, if the IRB should get a report, etc.) Submissions are required to be made utilizing the Microsoft form only. Please note that SAEs and CAPAs will be reviewed for final approval by the assigned Vice President of the site reporting the issue. Required information to be submitted on the Microsoft form: • Type of Submission • Site Location • Full Protocol Number • Principal Investigator Name • Please describe event details. In order to review, specifics will be required such as: Subject numbers, dates, any details on current documentation of event. (For SAE's please enter the date event was reported to site, date reported to sponsor, etc.) o Complete Narrative of the Event (reminder no he/she in the narrative) o Who, What, When, Where, Why, and How this happened o What MCR process was not followed o Singular Subject vs Multiple Subjects • Attached IRB Pending Submission Form and/or appropriate supporting documents (Please consider PHI prior to attaching items to the form) Please include the documentation from the Sponsor/CRO requesting the NTF and/or CAPA being requested. Link: Microsoft Forms Section Updated: 8/10/2022

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Serious Adverse Events (SAE’s) SAEs are any event resulting in death, a life-threatening situation, hospitalization or prolonged hospitalization, disability, incapacity, or congenital defect identified during a study. SAEs must be reported to the sponsor within 24 hours of site staff becoming aware of the event. Most sponsors will have either an SAE reporting form they require for use and/or specific forms to be completed in the EDC system for reporting. Please follow ALL sponsor required forms for SAE reporting and review the instructions carefully on how to report. Again – this MUST be done in 24 hours (not working hours, but 24 consecutive hours) from site knowledge of event. SAEs need to be entered in Clinical conductor so MCR can bill appropriately. Entering an SAE can be done in CC under each study. If you need assistance on how to enter these, let your Site Director or Regional director know. This is how we bill the sponsors for all the work involved in getting these reported within 24 hours, so do not skip this step. Additionally, entering these in the CTMS makes it possible for you to easily export an SAE log from CC for the study rather than having to hand write out an SAE log. Currently MCR requires all SAEs to also be reported to the IRB, even though normally IRB guidelines only require related SAE’s to be reported. For your assistance in the process of reporting SAE’s there is an SAE intake form that will guide you through the steps and help you collect the correct information when taking in an SAE report – which saves you valuable time. This is an internal Meridian form to help guide you through the process and it is advised to utilize it whenever taking in SAE information. When an SAE is reported the Site Director must be informed immediately. Before reporting any SAE to the IRB, the draft of the IRB report must be sent for approval to Safety Committee via the Microsoft Link: Microsoft Forms *Please review the Safety Committee section for proper steps on submitting the pending IRB SAE report* The SAE intake form is located on the Meridian Intranet: Documents > Operations > Clinical Forms and Logs > SAE Adverse Event Intake Form Section Updated: 8/10/2022

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Short Form Informed Consent Process A Short Form is a consent document written in a language understandable to a non-English speaking individual [or his/her legally authorized representative (LAR)] in their preferred language. It summarizes the required elements of informed consent outlined in the federal regulations, but it does not contain specific study information. It is to be presented orally to the subject or LAR. • • •





• • •

A Short Form Consent must be approved by the IRB prior to use Subjects who do not speak English should be presented with an IRB approved ICF written in a language understandable to them Alternatively, oral presentation of informed consent information in conjunction with a short form written consent document (stating that the elements of consent have been presented orally) and a written summary of what is presented orally is permitted At the time of consent, the short form document should be signed by the subject (or the subject's LAR); the summary (i.e., the English language ICF) should be signed by the person obtaining consent as authorized under the protocol; A witness is required to be present during the entire consent process, not just for signing the documents. The subject or the subject's LAR must sign and date the short form. The witness must sign both the short form and a copy of the summary, and the person obtaining the consent must sign a copy of the summary. When the person obtaining consent is assisted by a translator, the translator may serve as the witness The subject must be given copies of the short form document, the summary and the ICF in their language The entire process must be clearly documented in the participant’s source documents

Reference: HHS Regulations and Policy Guidance: Informed Consent of Subjects Who Do Not Speak English / 21 CRF 50.27 Documentation of Informed Consent Section added: 3/16/2022

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Smart Sense (temperature monitoring) “Smart Sense” by Digi is the 24-hour temperature monitoring system that all MCR sites use for any location that IP (investigational Products) or samples would possibly be stored. Generally, this includes ambient storage, any refrigerators, freezers, etc. These monitor 24 hours a day / 7 days a week and are set up with alert ranges. If a device reaches alert range it will email, text, and call (depending on settings) the appropriate staff to let them know that a temperature is getting close to an excursion. -Alert ranges for devices are set by industry standards, but some sponsors have stricter requirement. Please notify your Site Director of requirements for IP or lab sample storage on a given study so that alert ranges can be set appropriately SmartSense temperature monitors do NOT get calibrated at the site. These systems come already calibrated with their own calibration certificates which are good for 2 years and should not be calibrated onsite. New ones are to be ordered when they come close to calibration expiration. The calibration reports should be housed in Complion and can be downloaded from the SmartSense site. The flow of temperature data in our system goes Probe > Sensor > Gateway > Cloud PROBES: These are the devices that read the temperature. • • •

For our refrigerators and freezers, the probe is enclosed in a glycol buffer vial to mimic the actual temperature of products stored, rather than the temperature of the air. For our -80 Freezers, the probes are long stainless-steel rods. (We will be getting glass bead buffer vials for these in the near future) For ambient readings, we use sensor “nubs”, which are tiny NIST-calibrated sensor probes attached to the wireless sensor. They are white with a black protrusion and usually have a tag on them.

SENSORS: These are the white boxes with antennae that the sensor probes are attached to. These devices record the temperature data from the probe, and transmit it via wifi to the GATEWAY. These sensors are battery powered and MUST use ONLY Lithium AAs. We should check the battery level on these frequently, as battery death is the most common cause of missed temperature readings. If the sensor loses connection to the Gateway, it will store up to 24 hours of temperature data ad upload it to the gateway once the connection is re-established. DISPLAY SCREEN: The wireless display screens are paired to a particular sensor, and display the current temperature reading for all probes attached to that sensor, as well as a min/max for that day. They also display the battery level of the sensor. It’s a good idea to check these once a day to ensure batteries are good and no temp excursions have occurred. GATEWAY: All of the wireless sensors transmit their data to the Gateway at the site. The Gateway has a 4G connection (like a cell phone) which transmits all of this data to the web. In the event it loses connection due to a downed cell tower or something, it will store up to 24 hours of temp data and upload it to the cloud once it is reconnected. SMARTSENSE: This is the web portal used to access all of our temp alert data, run reports, and check on the current status of devices.

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Running Reports in SmartSense by Digi 1. Got to app.smartsense.co to access the TempAlert portal a. Log in with username and PW b. If you do not have access to the portal, request access from your Site Director 2. At the top left, click REPORTS

3. There are a variety of different report options

a. The COMPLIANCE REPORT gives you a good overview of all of the devices at your site over a set time range, whether any incidents occurred on a given day, and a daily min/max for each device. b. The ASSET SUMMARY report is a great way to view trends for each of your devices over time (ie- is the drug room getting warmer at a certain time of day? Is the freezer slowly getting colder over time?). Checking on this regularly can help you spot issues before they arise, like identifying a misplaced probe or a freezer that may need maintenance. c. 4. At the top right of the reports screen, you will find a link to LEGACY REPORTS, which provides even more reporting options:

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a. DAILY SUMMARY REPORT gives a daily min/max for each device at the location you select, as well as one additional temperature reading per day at a time you select. This is a great report to run weekly/monthly and upload to Complion for your CRAs to be able to view. b. DEVICE REPORT will give you every reading from an individual device in a given time span. This is a great report to run when you have a temp excursion, so that you can identify exactly how long a device was out of range. This is the perfect report to provide to your monitors in the case of a temp excursion so that they can quickly evaluate the severity of the excursion. (Remember, all of our devices record temps every 5 minutes, so if you are running a DEVICE REPORT for a period longer than 1 day, it will have A LOT of readings to dig through.) 5. After generating a report, you can download it as a PDF and save it/upload it/print it as you like. Note that some of the legacy reports print small and light, so using your printer setting to darken or magnify the page before printing can help. Also, this website can help to answer a lot of questions: https://helpcenter.smartsense.co/ Section added: 28Apr2022

Spanish Translation Process This process is to be followed for each visit with Spanish speaking participant: • • • • • • •

• • •

Document that the subject is Spanish speaking Document within the source that the CRC/ACRC conducting the visit is interpreting the visit or that an interpreter is used in conducting the visit Document at each visit that an interpreter is used or is present at the visit and who the interpreter is If blinding is required by the study, an unblinded interpreter will be needed in addition to the blinded staff Interpreter’s qualifications are documented on their CV and should include Spanish translation certification The interpreter is to be listed on the Delegation of Authority log and delegated this task Document if the subject: o Reads only Spanish but can speak English o Reads and speaks Spanish only o Reads and speaks Spanish and English Same interpreter to be used at each successive visit, if possible Document clearly all Spanish study materials that are dispensed to the subject at each visit Should any part of the visit be conducted virtually (Zoom, Teams, etc.) that should be clearly documented in the source

**Please note that the CRC/ACRC interpreting the visit needs to be certified per MCR Policies. Please reach out the Site Director and/or HR to confirm if the interpreter meets the requirements** Section Added: 3/22/20

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Spin Logs (Sample processing logs) Spin logs are created to document the processing of a subject’s blood sample from the time it was drawn, to the time it is frozen on a site level. The quality of the study’s scientific data is dependent on the accurate processing of blood samples; therefore, processing documentation is essential. Spin logs can be provided by the sponsor, but if allowed we always prefer to use MCR spin log. They can be created either by onsite lab staff or by the laboratory director. To create these logs, download the template provided on the MCR intranet and edit it to make the template both site and study specific. A spin log needs to be created for each sample that is processed differently; whether it be a different clot time, spin speed, spin time, or storage. These site-specific logs should be filed into Complion under each study binder. Section added: 8/8/2022

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Supplemental Binder For all Complion studies there will be a single physical supplemental binder containing the following: Delegation of Authority Log - This log is a “Meridian” Log, available on the Intranet, and the Meridian version should always be used unless a sponsor requires the site in writing to use theirs. The Delegation of Authority Log should be reviewed and approved by QA at the start of the study to ensure it is completed correctly, ideally at the time of SIV. It is typed initially (Any additions after SIV are handwritten) and always hand-signed (not electronically signed) and will be kept in the supplemental site binder for the duration of the trial and scanned/loaded into Complion prior to each Monitoring visit and at the close-out of the study. •

Training Log and documents - Training logs are typically provided by the study sponsor and begin with SIV training. This document can be added to throughout the duration of the study documenting additional training. This should be loaded into Complion before each monitoring visit and the original kept in the supplemental binder. Two additional Meridian training forms are available on the Intranet: There is a blank/General training log that can be used for any supplemental training that occurs after the initial training log. Also, the protocol specific training Log can be utilized for one person at a time to detail their training on the study including the version of protocol, version of consent, etc. These two training documents should be loaded to Complion each time they are used. They can be hand or electronically signed. Every person on the Delegation of Authority log must also have a completed training log showing they have been trained on the current protocol, and on any additional protocol amendments that are received. •

Monitor Visit Log - This form is typically sponsor-provided to be handwritten and signed by the monitor for each visit. These will be scanned and loaded into Complion at the study closeout. Additionally, Meridian has a remote monitoring log for any remote visits to be documented as well. •

Protocol Deviation log - This is a Meridian log available on the intranet and is used to track all protocol deviations. These will be scanned and loaded into Complion at the study closeout. If the study team/CRA tracks protocol deviation logs on their own log the Meridian log should still be kept, and these should always have the same deviations logged on both. •

Device ID log - if applicable, to track any diaries or devices supplied to study subjects. These will be scanned and loaded into Complion at the study closeout. •

Study Level ICF log - This is the overall ICF log of all versions of consent approved to be used by the IRB for the study by version, along with the date they were received by the site. These will be scanned and loaded into Complion or made sure current before each monitoring visit and at study closeout. •

Master ICF Log – Consent log for all subjects noting the date that every subject signed consent and the version they signed throughout the study. •

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Subject screening and Enrollment log - This log will be exported from CC. These will be scanned and loaded into Complion at the study closeout. These can be exported for any monitoring visit from CC as needed. •

Subject ID log - This log will be exported from CC. These will be scanned and loaded into Complion at the study closeout. These can be exported for the monitor at any monitoring visit from CC as needed. •

IP log - if the study has unblinded staff, this will be kept in separate unblinded binder by the designated unblinded team. If there is no blind, the IPAL (Investigational Product Accountability log) will be kept in the supplemental study binder until closeout. •

Pregnancy test and spin log - These are often kept as a running log in the laboratory. This can also be kept in the supplemental study binder. These will be scanned and loaded into Complion at the study closeout. A pregnancy log is to be used for any study that completes pregnancy tests. A spin log should be used for any study that processes labs. •

Notes to file - Any NTFs that are not general regulatory (filed in Complion) or subject specific (filed in the subjects’ chart) will be hand signed by the PI and filed in the supplemental binder. For example, any NTF explaining an issue, deviation, or CAPA should be filed in the supplemental binder. •

Correspondence - If the correspondence is from an external entity such as CRO, Sponsor, etc. this should all go immediately to Complion. If the correspondence is generated internally such as NTFs and CAPA's, these should be in print and go into the physical supplemental binder. Then this should be filed at end of study to Complion. •



Supplemental Binders should be kept in the chart room or a centrally secured location. Not to be left on employee desks. All must be stored in a centrally secured location each night.

Section updated: 6/29/2022

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Target Dates (managed in Clinical Conductor) • Pre-Site Selection Visit: “PSSV” When you have a PSSV, you should be filling out the PSSV form and sending to [email protected] (This is how the study gets entered into CC as a potential trial for the site. Once the study is awarded, please enter the PSSV date into the CC target dates for that study. • PI Meeting: Also called the “Investigator Meeting” or “IM”. Please list the date of attendance. If Meeting was more than one day, just list the first day in the Target Dates. Please enter this as soon as the study team notifies you of when the IM will be held. • Close Out Visit: The date that the site is closed out. The IRB close out should be completed on this day as well once the sponsor approves the site to submit it. • First Patient First Visit: or “FPFV” This is the based on the first patient completing the first visit as your site in CC. This is MCR Specific. This is NOT the projected FPFV that the Sponsor provides us for the overall study. This date is entered by the finance team. • CTA Effective: this is something that is automatically loaded based on the effective date of the contract. Site does not enter this information. • Site Initiation Visit: Date of the “SIV” should be entered into Target Dates as soon as it is scheduled. • Enrollment Start – Expected: this is an estimate of when we think that a study will open to enrollment. It will be a moving target that we update as we learn more. • Enrollment Start – Actual: This is the date that we officially have permission to start seeing patients. There is usually a letter from the Sponsor saying that we can start (Sponsor and IRB approved) that can be forwarded to [email protected]. • Enrollment Closed – Actual: the date that enrollment has officially closed to enrollment. Please forward confirmation communication that enrollment has officially closed to [email protected] • IRB Approval: the date listed in the IRB portal and on the initial IRB approval letter. • Enrollment Closed – Anticipated: The projected date that enrollment will close. This is an estimate, and will be adjusted as we find out more. • Database lock: reflects the date of Database lock for the study. This is a date utilized by the finance team to send bills to the sponsor. The Database lock dates for the study are often found on the study newsletters as they draw near. This means all the data in EDC is locked for the study and can no longer be changed. • LPLV: or “Last Patient Last Visit” date is based on the last patient completing the last visit in CC. This is MCR Specific at study end. THIS IS NOT the LPLV date that the sponsor provides us for the study overall. This date is automatically entered by the finance team. • IRB Expiration: This date is listed in the IRB portal and on the IRB approval document. All IRB approvals have an expiration, and if the study is still ongoing at that time a “continuing review form” must be completed with the IRB. Once the continuing review is approved there will be a new expiration date on this approval and this new date should be entered in the CC target dates. **If at any time one of these dates will not occur (for instance if there will be no PI meeting for the study) Please enter 01/01/1900 to indicate it will not happen. **Please note that the Site Director is to ensure these are updated on a bi-weekly status**

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Unblinded IP storage areas Investigational products can be stored frozen, refrigerated, or in ambient storage locations. All IP storage locations must be locked, and temperature monitored. On the front of all refrigerators, freezers, or ambient cabinets the unblinded staff should maintain a document (Excel template available on the MCR intranet) outlining the protocol numbers, temperature ranges, and directives should there be an excursion as per the IP manual for each product inside the storage location. Section added: 8/5/2022

Unblinded Labels Not all trials include the step of wrapping a label around a syringe in the pharmacy manual or the study procedures manual. MCR has added this step to the handling of investigational products to include the use of a standardized MCR label (Unless labels are sponsor provided) to include: Protocol #____________ Subject ID____________ Date/Exp time________ Syringe identifier______

A syringe label template and big label template is available on the MCR intranet. Use Avery labels #5160 (1” x 2 5/8”) for the syringe labels and Avery Label #5360 (1 ½” x 2 13/16”) for the big labels Section added: 8/3/2022

Unblinded Treatment Lists At the end of a trial, once all data is complete, a sponsor or CRO may release a final list of treatment assignments so that participants can be unblinded to their assigned treatment arm. If this is received for a study, the site director should be notified. Once participants are allowed to be given their treatment arm assignment, MCR will reach out to them and often this is a great opportunity to discuss future studies with the participant. If this is a paper document study, the document should be filed in the regulatory binder. If the study is a Complion binder study (e-regulatory) the document should be loaded there at study closure.

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Unblinded Verification of IP Reminder: IP temperatures need to be verified each morning prior to any medication being dispensed. Investigational Product (IP) should never be dispensed to a participant in a clinical trial without verification that the correct IP has been allocated by a second individual. This will always involve 2 staff members. One to get the IVRS allocation of IP Kit number and pull the referenced IP from its storage, and a second staff member to confirm the correct IP / Kit number was pulled for the subject and sign any corresponding print out that contains the number to be pulled. TWO signatures should be on each IVRS printout or IP allocation sheet. This confirms that both individuals are actually looking at both the allocation sheet and the actual kit number on the kit itself to confirm these match. This sheet cannot be signed without looking at the kit itself as well. IP verification is also done on IP prep forms (should those be required for a protocol). In this case the unblinded staff AND the verifier are signing and dating BOTH the IVRS IP allocation print out and the IP prep form. Both should be filed in the unblinded dosing binder. When preparing IP, it is important to think about what you are doing and what your signature means. On the IVRS sheet, (or whatever form tells you what kit to pull for the subject, sometimes even a screenshot from EDC is used to show the Kit number) – two people are signing because one has pulled the kit as they read it from the sheet, and a second person to read the kit number from the IP and then verify with the sheet. This way there are TWO sets of eyes confirming the right IP number is being used. Both staff members then sign this form because IF IT ISNT DOCUMENTED IT DIDN’T HAPPEN. We can say that the IP kit number was verified, but unless both are signing and dating there is no proof of that. This step should be done before any IP preparation begins – right at the time it is removed from storage – in real time. This is not something that can be verified after the fact, at the end of the day, etc. That defeats the purpose of checking the kit number. Less frequently, some studies using placebo or a multi-dose vial do not always have an IVRS print out, but it is captured and signed-off by the unblinded staff and the verifier on the dispensing logs. This would be the case if there was no IVRS printout or email sheet with a kit number to be printed and signed (which is not typical). Please confirm at study start with the team if you believe there will not be a confirmation sheet for a study to confirm this is the case before any dosing. As a rule, there is almost always a way to verify the correct kit outside of only a prep form.

eSource (CRIO): Prior to preparation/administration, the vaccinator will confirm in eSource that the vaccination/randomization criteria have been confirmed prior to vaccinating. This includes, but is not limited to, inclusion/exclusion criteria review, pregnancy test resulted as negative, lab samples collected, INV signed eligibility statement. It must be confirmed to be documented in source before it is "marked as confirmed." No documents that have unblinding information are to be uploaded to CRIO (IP Prep Forms, IVRS printouts, etc.)! Those will be housed in the IP binder (just like with paper source). CRIO will not have a verifier signature in source in the IP administration section unless protocol requires. The verification required is of the IP and the prep of that IP – therefore it will be documented in the unblinded source. As stated above, this will be in the form of IP prep sheets with 2 staff signatures as well as any IVRS print outs, email with IP allocation print outs, or screen shots of IP allocation kit numbers if necessary to have this documented. Moving forward, the IP Administration section in paper source will match the format of eSource. In other words, unless the IP administration is required to be verified, there will not be a "verifier signature" of the administration but rather it will also be documented as verified on the IP Prep Forms, IVRS printouts, etc. CRC Quick Reference Guide // V3-10Aug2022

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Notes and nuances: If a study does not have a blind, there is still typically an IP allocation number that the site receives for each subject. This should still be printed and signed by two individuals that both checked that the allocated IP is the one being given to the subject prior to distribution. If a specific study is utilizing a countdown in sequential order to distribute IP there should still be a second person verifying the correct kit in sequential order was pulled for the subject. This should be documented. If you are unsure how to document verification that the correct IP was pulled please reach out to management. There should be no cases where IP distribution is not double verified prior to distribution to a study participant. Correct IP dosing, management, and verification are the most important aspects of ensuring patient safety. Any staff member responsible for pulling an allocated dose is REQUIRED to have a second verifier documented and is prohibited from moving forward with dosing until the dose is verified as correct by a second delegated staff member. Staff tasked with verifying are to understand this task should be taken very seriously, as they are the final set of eyes before an investigational medicine is given to a human being. Please treat this task with the gravity you would if this were your own family member. Section added: 3/16/2022

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Unblinded Process for Dispensing Investigational Product Please follow the below process to ensure accurate documentation of IP dispensing and proper storage of used IP 1. 2.

3. 4.

5.

6.

7.

8.

Dispense Investigational Product per IRT and/or protocol requirements. *Please note this process is completely done differently from a double-blind protocol vs observer-blind protocol. (Blinded vs unblinded) * MCR requires two employees to verify IP prior to mix and/or administering/dispensing the IP to the participant. Appropriate delegated personnel per the DOA will pull the investigational product from the appropriate storage, both will verify the IP matches the printout from the IRT and/appropriate documentation to the container number listed on the IP Both delegated personnel will initial and date the IRT printout and/or appropriate documentation to confirm the verification process was completed One of the delegated personnel to perform the IP process will grab a Ziplock bag. They will document the protocol number, participant number, date of dispensation, vial number/container number, and dosage if the protocol has different dosages available. *Please note you can create a protocol specific label IP label for the Ziplock bags vs writing on the bag. If dispensing a tube or bottle to the participant please ensure that the site keeps the IP container for accountability purposes*

(Multiple Participants) (Single Participant) One of the delegated personnel to perform the IP process will document on the Master Investigational Product Accountability log of the Vial/Container number that was dispensed to the participant. Please ensure the person verifying the process also documents their initials on the IP log. *Please note that some protocols require a diluent to be used which would have its own separate accountability log to ensure accountability* One of the delegated personnel to perform the IP process will document on the IP mixing and/or administration worksheet to ensure we are following the protocol requirements. **Please note the person verifying the process is to watch every step as its being completed during the mixing procedures** Once the IP is correctly mixed, please ensure the expiration time is added to the Ziplock bag and IP documentation worksheet. Please ensure all required documentation is completed on the IP administration pages and/or participants chart. Once the IP administration process is completed for either the single participant and/or multiple participants the Ziplock bag with the used vials/containers will be stored in a marked bin for reconciliation at a monitor’s visit. On the outside of the container please label it with the Protocol Number/Used IP *Please note if this is a unblinded study please ensure that no one can see the Ziplock bags to ensure the blind was maintained with all staff on-site*

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Weekly Site Meetings Each Clinical Research site at MCR must hold a weekly staff meeting. There is a template that is required to be used to collect these meeting minutes. These weekly meeting minutes are tracked to show oversite, training, etc. as required by our industry. Query updates need to be a part of the weekly meeting. Site Directors should list the number of queries per study and identify areas of concern and where support is needed. Site Directors are encouraged to schedule weekly meetings with embedded QA, regulatory, and recruiters, and lab staff. The priority is to increase communication and awareness across departments, early identification of issues, and create strong team relationships. Site Directors are to upload the signed copy into Operations-Weekly Team Meeting folder on the intranet on a weekly basis. The template is on the Meridian intranet, titled “Meeting Minutes Form” Link: https://meridianmedical.sharepoint.com/:w:/s/MeridianInternal/EVMMunZcdBtMgxrG78ZyLXABvSpG2 pNDbJxsVsiYeu9vpw?e=xdCDBn

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Appendix A – CRIO Document Filing and Naming Convention v1; 04MAY2022 1. IRB approved Informed Consent(s) a. Save blank (unsigned) IRB approved ICF(s) as PDF documents to a work computer i. Title document as: DocumentType_ProtocolNumber_SiteApprovalVersionDate (e.g. ICF_mRNA-1189-P101_07JAN2022) b. Upload saved ICF(s) to the study level in CRIO: i. Select study → Click “Files” tab → Click “Informed Consents” (in blue) 1. Click the pencil icon at the end of the row (far right) to open the “Update Document” dialogue box a. Studies with multiple consents will have multiple ICF rows b. Ensure you are uploading the ICF to the row with a matching “Category" description e.g., “(For procedure MAIN ICF)” or “(For procedure Pregnant Partner ICF)” ii. Enter information in the dialogue box as follows: 1. “Custom Name (optional)” – Leave this field blank 2. “Version #” - Entry in this field is mandatory and MUST be completed in order to upload and update the ICF document in the system (initial entry or updated data in this field triggers the procedure to populate in source). a. Version # field MUST be different each time a document is uploaded. b. If version # is available on the ICF, the version # should be entered into this field. i. This is the Version # of consent applicable to the individual MCR site, NOT the sponsor Version #. c. If version # is not included, the IRB Approved or IRB Revised date should be entered in the Version # box in DDMMMYYYY format (without spaces/dashes) i. The date entered should be the date of consent approval for the individual MCR site. This date (depending on the IRB) is typically: • In the upper right corner, preceded by “IRB approved” or “IRB approved as modified” OR • In the lower right corner of each page listed as “Revised DDMMMYYYY” ii. This may vary consent to consent and IRB to IRB; CRC’s/QA/regulatory should work together to determine the appropriate date to use if there are questions. 3. “Version Date (optional)” – Entry in this field is mandatory and MUST be entered each time a document is uploaded (initial or updates). a. Date format must follow CRIO date requirements e.g., DDMMM-YYYY (dashes and capital letters for month, are both required), alternatively use calendar for auto-format entry. CRC Quick Reference Guide // V3-10Aug2022

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b. If consent DOES NOT have an IRB Version # listed, then this date will be the same date as was entered into the “Version #” field. 4. “Approval Date (optional)” – Leave this field blank 5. “Description (optional)” – Entry in this field mandatory and MUST be entered each time a document is uploaded (initial or updates). a. Enter the date the ICF was received by the site in DDMMMYYYY format (without spaces/dashes) iii. Click “Choose File” to open computer documents 1. Locate and select the previously saved PDF version of the document and attach to CRIO iv. Click “Upload Document” 2. Subject Documents a. Save all subject documents as PDF documents to a work computer BEFORE uploading to CRIO i. Documents that require signature will be saved to the computer WITHOUT a “wet-ink" signature. All documents will be e-signed through CRIO (reference section ‘iv.’ below) ii. Title document: Document type_Subject ID_Visit # (if appl.) e.g. Consent, IVRS Screening confirmation, and Labs at Visit 0 would be saved as: • Informed Consent_123456 • IVRS Screening Confirmation_123456_Visit 0 • Laboratory results_123456_Visit 0 b. Upload saved subject documents into CRIO i. ALL subject documents that are typically filed in a subject’s paper chart are required to be uploaded as either a subject level OR visit level document (see list on page 3 to review where to upload common documents) 1. To upload to the subject level: a. On the subject page, located just above the Visit schedule, you will see: “##files attached to SubjectName at subject level (Add)” → Click “Add” 2. To upload to the visit level: a. While on the subject page scroll down to visit schedule b. Locate the applicable visit row i. Visit must at least be started to add a document (Includes: paused, in progress, partially completed, completed, screenfail) c. Click the # (in blue) located to the right/end of row for that visit (under “Files” column) i. this will say “0” prior to documents being added and will increase as documents are added d. Click “Add New Document” to open the uploading dialogue box ii. Choose category and document type CRC Quick Reference Guide // V3-10Aug2022

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1. If there is not an appropriately matching category and/or document type choose “Other” iii. Click “Choose File” to open computer documents 1. Locate and select the previously saved PDF version of the document and attach to CRIO 2. You will NOT enter a custom name or a description. The naming convention you used when the document was saved to your computer is how it will be reflected within the subject’s CRIO chart iv. E-sign vs. Assign – Subject documents 1. E-sign every document when uploaded a. This will certify that the document is a true and correct copy of the original 2. Assign the document if it requires Investigator review and signature a. This will be any document you would typically get a wet-ink signature on, e.g. lab results). i. If investigator makes NO mark-ups to the document and only e-signs, the Inv. Signature statement will certify the document (again) as a true and correct copy ii. If investigator makes mark-ups (eg. adds CS/NCS to labs) prior to e-signing, it will attest to the veracity of all statements they made, and certify the document as a true and correct original **IMPORTANT INFORMATION REGARDING SUBJECT DOCUMENTS** Once the above steps are followed and the document is uploaded into CRIO, the subject document MUST be deleted from the work computer! When referring to “subject documents” within this document, the direction is for BLINDED subject documents ONLY. UNBLINDED documents (e.g., Unblinding IVRS IP confirmation, IP Prep Forms) will NOT be saved to a work computer or uploaded into CRIO. Unblinded documents should be maintained ONLY in the Pharmacy Binder

Filing Level of Common Subject Documents in CRIO SUBJECT Level Documents • Signed ICF’s • Records release & Medical Records • Demographic form • Deviation forms submitted to IRB & IRB Acknowledgement • SAE, AESI, Pregnancy reports • Correspondence NOT related to a visit (e.g. sponsor emails/emails regarding medical history, con meds, AE’s) • Visit Calculators • eDiary reports reviewed between visits CRC Quick Reference Guide // V3-10Aug2022

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VISIT Level Documents • Blinded IVRS Confirmations – any that would typically be filed in subjects BLINDED chart (eg. Screening, screenfail, randomization, visit registration, IP assignment [only blinded information], IP return, discontinuation, completion) • Laboratory requisitions • Laboratory results • • •

ECG tracings & ECG over-reads Wet-ink questionnaires and Assessments Wet-ink Diaries (medication, symptoms, etc.) returned at the visit



eDiary reports that were reviewed during the visit



Visit Procedures (Spirometry, ultrasound, x-ray reports)

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Section 4

Acronyms & Initialisms

Acronyms and Initialisms Abbreviation..................................Definition ADR................................................... Adverse Drug Reaction AE ..................................................... Adverse Event AUC .................................................. Area Under the Curve BLA ................................................... Biologic Licensing Application BUN .................................................. Blood Urea Nitrogen CAP ................................................... College of American Pathologists CBER ................................................. Center for Biologics Evaluation and Research (FDA) CDER ................................................. Center for Drug Evaluation and Research (FDA) CDRH ................................................ Center for Devices and Radiological Health (FDA) CFR ................................................... Code of Federal Regulations CI ...................................................... Confidence Interval CLIA .................................................. Clinical Laboratory Improvements Amendments Cmax ................................................ Maximum Plasma Concentration Cmin ................................................. Minimum Plasma Concentration CNT ................................................... Consented but Not Treated Cr ...................................................... Serum Creatinine CRA ................................................... Clinical Research Associate CRC ................................................... Clinical Research Coordinator CRF ................................................... Case Report Form CRO................................................... Contract Research Organization CT ..................................................... Computed Tomography CTA ................................................... Clinical Trials Agreement CTC ................................................... Circulating Tumor Cell Count CTCAE ............................................... Common Terminology Criteria for Adverse Events CYP ................................................... Cytochrome P450 Meridian Clinical Research, LLC

www.mcrmed.com

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DAR................................................... Drug or Device Accountability Records DHEA ................................................ Dihydroepiandrosterone DLT ................................................... Dose Limiting Toxicity DNA .................................................. Deoxyribonucleic Acid DSMB................................................ Data Safety Monitoring Board DSMP ................................................ Data Safety Monitoring Plan EC ..................................................... Ethics Committee ECG ................................................... Electrocardiogram ECOG ................................................ Eastern Cooperative Oncology Group (Used to determine Performance Status) EDC ................................................... Electronic Data Capture EMEA ................................................ European Agency for the Evaluation of Medicinal Products FDA ................................................... Food and Drug Administration FWA number .................................... Federal Wide Assurance number (number assigned to IRB) GCP ................................................... Good Clinical Practices GLP ................................................... Good Laboratory Practices GMP ................................................. Good Manufacturing Practices HAQ .................................................. Health Assessment Questionnaire HDE................................................... Humanitarian Device Exemption (must be in place to use a HUD) HUD .................................................. Humanitarian Use Device (for less than 4, 000 subjects) IB ...................................................... Investigator’s Brochure ICF .................................................... Informed Consent Form ICH .................................................... International Conference on Harmonization IC50 .................................................. Inhibitory Concentration 50% IDE .................................................... Investigational Device Exemption IEC .................................................... Independent Ethics Committee IND ................................................... Investigational New Drug IRB .................................................... Institutional Review Board ISR .................................................... Injection Site Reaction ITT..................................................... Intent-to-Treat

www.mcrmed.com

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IVRS .................................................. Interactive Voice Recognition System Ki ...................................................... Inhibition Constant LDH ................................................... Lactate Dehydrogenase MDR ................................................. Medical Device Reporting MedDRA ........................................... Medical Dictionary for Regulatory Activities mmHg ............................................... Millimeters of Mercury MOS.................................................. Medical Outcomes Study MTD.................................................. Maximum Tolerated Dose NDA .................................................. New Drug Application NSR ................................................... Non-Significant Risk ( usually refers to device research ) OHRP ................................................ Office for Human Re-search Protection PD ..................................................... Pharmacodynamics PFS .................................................... Progression-Free Survival PI ...................................................... Principal Investigator PK ..................................................... Pharmacokinetic PMA.................................................. Pre- Market Approval PMS .................................................. Post Marketing Surveillance prn .................................................... As Needed QOL .................................................. Quality of Life QTcF ................................................. QT Interval Corrected by the Fridericia Correction Formula RECIST .............................................. Response Evaluation Criteria in Solid Tumors (Oncology ) SAE ................................................... Serious Adverse Event SD ..................................................... Standard Deviation SDV ................................................... Source Document Verification SEM .................................................. Standard Error for the Mean SEV ................................................... Site Evaluation Visit SIV .................................................... Site Initiation Visit SR ..................................................... Significant Risk (usually refers to device research) Tbili ................................................... Total Bilirubin TK ..................................................... Toxicokinetics www.mcrmed.com

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t1/2................................................... Half-Life TTP ................................................... Time To Progression WBC.................................................. White Blood Cell Count WHO ................................................. World Health Organization WMA ................................................ World Medical Association

www.mcrmed.com

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Section 5

Supplemental Binder Table of Contents Complion Guidance & Checklist

MCR Regulatory Binder Template Document Spreadsheet

Supplemental Binder For all Complion studies there will be a single physical supplemental binder containing the following:



Delegation of Authority Log - This log is a “Meridian” Log, available on the Intranet, and the Meridian version should always be used unless a sponsor requires the site in writing to use theirs. The Delegation of Authority Log should be reviewed and approved by QA at the study start to ensure it is completed correctly, ideally at the time of SIV. It is typed initially (Any additions after SIV are handwritten) and always hand-signed (not electronically signed) and will be kept in the supplemental site binder for the duration of the trial and scanned/loaded into Complion prior to each Monitoring visit and at the close-out of the study.



Training Log and documents - Training logs are typically provided by the study sponsor and begin with SIV training. This document can be added to throughout the duration of the study documenting additional training. This should be loaded into Complion before each monitoring visit and the original kept in the supplemental binder. Two additional Meridian training forms are available in the Intranet: There is a blank/General training log that can be used for any supplemental training that occurs after the initial training log. Also, the protocol specific training Log can be utilized for one person at a time to detail their training on the study including the version of protocol, version of consent, etc. These two training documents should be loaded to Complion each time they are used. They can be hand or electronically signed. Every person on the Delegation of Authority log must also have a completed training log showing they have been trained on the current protocol, and on any additional protocol amendments that are received. 



Monitor Visit Log - This form is typically sponsor-provided to be handwritten and signed by the monitor for each visit. These will be scanned and loaded into Complion at the study closeout. Additionally, Meridian has a remote monitoring log for any remote visits to be documented as well. 



Protocol Deviation log - This is a Meridian log available on the intranet and is used to track all protocol deviations. These will be scanned and loaded into Complion at the study closeout. If the study team/CRA tracks protocol deviation logs on their own log the Meridian log should still be kept and these should always have the same deviations logged on both. 



Device ID log - if applicable, to track any diaries or devices supplied to study subjects. These will be scanned and loaded into Complion at the study closeout. 

Supplemental Binder



Study Level ICF log - This is the overall ICF log of all versions of consent approved to be used by the IRB for the study by version, along with the date they were received by the site. These will be scanned and loaded into Complion or made sure current before each monitoring visit and at study closeout. 



Master ICF Log – Consent log for all subjects noting the date that every subject signed consent and the version they signed throughout the study.



Subject screening and Enrollment log - This log will be exported from CC. These will be scanned and loaded into Complion at the study closeout. These can be exported for any monitoring visit from CC as needed. 



Subject ID log - This log will be exported from CC. These will be scanned and loaded into Complion at the study closeout. These can be exported for the monitor at any monitoring visit from CC as needed.



IP log - if the study has unblinded staff, this will be kept in separate unblinded binder by the designated unblinded team. If there is no blind, the IPAL (Investigational Product Accountability log) will be kept in the supplemental study binder until closeout. 



Pregnancy test and spin log - These are often kept as a running log in the laboratory. This can also be kept in the supplemental study binder. These will be scanned and loaded into Complion at the study closeout. A pregnancy log is to be used for any study that completes pregnancy tests. A spin log should be used for any study that processes labs. 



Notes to file - Any NTFs that are not general regulatory (filed in Complion) or subject specific (filed in the subjects’ chart) will be hand signed by the PI and filed in the supplemental binder. For example, any NTF explaining an issue, deviation, or CAPA should be filed in the supplemental binder. 

Supplemental Binder •

Correspondence - If the correspondence is from an external entity such as CRO, Sponsor, etc. this should all go immediately to Complion. If the correspondence is generated internally such as NTFs and CAPA's, these should be in print and go into the physical supplemental binder. Then this should be filed at end of study to Complion.



Supplemental Binders should be kept in the chart room or a central secured location. Not to be left on employee desks. Must be replaces in central secured location each night.

Section updated: 6/29/2022

Complion Guidance and Checklist

Forwarding Documents to Complion from your email • • • • • • •

• • •

In order to comply with federal regulations, ICH Guidelines and MCR SOPs for PI oversight, documents need to be sent to Complion daily. Regulatory staff is responsible for sending for signatures (unless otherwise requested) Protocol amendments and ICFs sent to Notifications when sent to Complion In Complion, documents are date stamped when uploaded therefore we need to get documents signed in real time to match the uploaded date. When time-sensitive materials are uploaded please let your regulatory contact know ASAP o Prior to SIV, Monitoring visits, oversight visits, audits, etc. o Anything that needs PI signatures The checklist is your reference and a copy kept for each study (it does not need to be sent to anyone else) No subject-specific emails should be uploaded to Complion (anything that has subject # on it) for example: o Lab requisitions o Data entry o Randomization emails o Response to monitor requests for completed tasks regarding subjects Blinded documents to be uploaded to Complion Unblinded documents not uploaded to Complion - to be kept in site binder All headers & footers completed prior to uploading to Complion

Regulatory has assigned one person to be the primary point of contact. This person will be responsible for the day to day Complion regulatory filing, assist with IRB filings, as necessary, and assist with study start-up documents. In addition, they will be responsible for the regulatory start-up for newly awarded studies for their assigned sites. As a team we are dedicated to supporting all of the sites and the regulatory team will be providing back-up coverage as well as assisting each other to ensure all binders are current. Please do not hesitate to contact your regulatory person if you have questions or need assistance. The current assignments are as follows: Ginny McNew maintain the regulatory responsibilities for the following locations: Norfolk, NE – OB/GYN

Norfolk, NE – IM

Savannah, GA – IM

Savannah, GA – Dermatology

Savannah, GA – Plastics

Savannah, GA – Urology

Courtney Heisey will maintain the regulatory responsibilities for the following locations: Omaha, NE Dakota Dunes, SD / Sioux City, IA Baton Rouge – Peds Baton Rouge – Dermatology Savannah, GA – Neurology Grand Island, NE – Pediatrics Grand Island, NE – OB/GYN Version date: 17Feb2020

Grand Island, NE – Family Practice Hastings, NE – OB/GYN Hastings, NE - Pediatrics Jessica Fellows will maintain the regulatory responsibilities for the following locations: New York sites

Rockville, MD – IM

Rockville, MD – Neurology

Norfolk, VA – Neurology

Macon, GA - Pediatrics Lorita Johnson *** – will maintain the regulatory responsibilities for maintaining the Meridian Central Binder: Adding/Granting Access to new staff for Complion CVs (Full CVs for Investigators, Abbreviated MCR, Pfizer One Page and Transcelerate) Medical Licenses/licenses GCP Certificates IATA Certificates Calibration Logs Temperature Logs SOPs *** Any updates to these documents needed to be forwarded to Lorita.

Monitoring Visits: Initial Preparation/Ongoing External Users: please notify Regulatory Specialists all CRAs who will need access to the study specific binder in Complion: Information needed: Name of CRA and email address Please email your Regulatory Specialist the following information for all upcoming monitor visits: Sponsor Protocol CRA/Monitor Name What type of Monitor Visit PI Site Lead Coordinator

Version date: 17Feb2020

Checklist

Protocol #: ____________

All Pre-Study Site Visit (PSSV) correspondence and documents Initial Regulatory packet received Site Selection Letter (with email received) SIV documentation ❖ Training Slides and other training documents ❖ Sponsor Forms completed at SIV ❖ Examples ▪ Source Document Locator ▪ Site-Specific Blinding Plan ▪ Sponsor Recruitment Plan Site Visit Log for both Remote and On-site visits Site Visit Reports for SIV Site Training Logs – Protocol, ICF and IB please list version and date for each ❖ Training Certificates per staff member if training is done in portal ❖ Protocol Overview Certificates – send directly to binder (ex: Firecrest) Delegation of Authority Log – to be uploaded immediately after SIV All training must be completed before staff is delegated any tasks. ❖ Please review for completion: Headers and footers, pages numbers, no blanks, all tasked delegated and all staff listed. All staff to sign and PI sign-off (after QA approval) – keep original in Supplemental Binder ❖ Page for regulatory staff (Courtney, Ginny and Jessica) to be incorporated in DOA General Correspondence – monitor correspondence back and forth that does not contain subject information • Do not send any unblinded monitor letters to Complion • Send only Final email of chain/thread of messages - PLEASE Request of documents from Sponsor Confirmation emails of Site Monitoring visits – along with letter that is attached Follow-up email/reports from Site Monitoring visits – along with letter if attached ❖ Email Blast pertaining to Trial ❖ Newsletters ❖ Study Weekly Updates ❖ Recruitment/Enrollment Updates ❖ Webinars include invitation, slides, attendance log ❖ Memos/Note to Files Subject Materials (IRB approved) Examples ❖ Telephone scripts ❖ Questionnaires ❖ Diaries ❖ Reminder Email Notifications ❖ Appointment Cards Recruitment Materials (IRB approved) Sponsor Contact Lists IND Safety Reports – if not acknowledged in portal by PI Ask sponsor if disk will be provided at close-out Protocol Amendments (email from the sponsor that we received it and any response back) Informed Consents - all versions and templates Version date: 17Feb2020

Uploaded day of receipt AOR (acknowledgement of receipt) for IRB Submissions Initial Submission AOR Continuing Review/Close-out AOR Protocol Deviation AOR Serious Adverse Events AOR IRB Approvals with all corresponding documents listed on the IRB approval letter Uploaded day of receipt Example: Notice of Approval Letters stated Ads, Questionnaires and Subject Materials – make sure all documents are uploaded to Complion Investigator Brochure (email from the sponsor regarding receipt of IB) Uploaded day of receipt – notified Regulatory Specialist to ensure Protocol Signature Page is created/routed for signature Version of Investigator Brochure AOR of Investigator Brochure (not all sponsor use) Summary of Changes/ Tracked Changes (not all sponsors use) Protocol (email regarding receipt of new Protocol) Uploaded day of receipt – notified Regulatory Specialist to ensure Protocol Signature Page is created/routed for signature Version of Protocol/Amendments Protocol Signature page Tracked changes/Summary of changes (not all sponsor use) Protocol clarification memo Laboratory (emails relating to Lab Documents) Laboratory Manual CV for Lab director CLIA and/or CAP Certificates Study Manuals (emails along with Manuals) EDC certificates – send directly to Trial binder Guidelines for EDC, etc. Screen Shots of EDC Logs Temp logs to be uploaded the first of each month for the prior month All logs kept in site binder need to be uploaded at Study close-out unless requested by monitor otherwise Documents in Sponsor Portals need to be downloaded and sent to Complion Examples: Training modules and certificates

Version date: 17Feb2020

To Whom Document will be Routed

Action requested in Complion

• PI - Review W/Signature • Lead CRC - Review W/Signature • Alicia - Read (No Signature) • PI - Trained W/Signature • Unblinded Staff - Trained W/Signature • Alicia High - Read (No Signature) • Embedded Regulatory - Read (No Signature)

Review W/Signature

• Principal Investigator • All Unblinded staff • Alicia High • Embedded Regulatory Specialist (or lead CRC if no ER at site) will route to PI and all unblinded staff

• Principal Investigator • Lead CRC

Newsletters

Pharmacy Manual (IP Manual)

Protocol

Monitor Follow-up Letter • Principal Investigator • Lead CRC • Alicia High (review Only)

• PI - Trained W/Signature • Sub-I - Trained W/Signature • Delegated staff - Trained W/Signature • Alicia High / Avery Dunn - Read (No Signature) • Embedded Regulatory - Read (No Signature)

Review W/Signature Review W/Signature Review W/Signature Review W/Signature Review W/Signature

Trained W/Signature

Review W/Signature

Review W/Signature

• PI - Trained W/Signature • Sub-I - Trained W/Signature • Staff Delegated EDC - Trained W/Signature • Alicia High - Read (No Signature) • Embedded Regulatory - Read (No Signature)

Review W/Signature • PI - Review W/Signature • QA - Read (No Signature)

ER at site)

• Principal Investigator • Principal Investigator • Principal Investigator • Principal Investigator • Principal Investigator • Principal Investigator • Sub-I's • Lead CRC • Any staff delegated to Labs • Alicia High / Avery Dunn • Embedded Regulatory Specialist (or lead CRC if no

• All CRC's for Boehring Ingelheim Studies only

• Principal Investigator • Sub-I's

• Principal Investigator • Lead CRC

• Principal Investigator • Sub-I's • Any staff delegated to EDC • Alicia High • Embedded Regulatory Specialist • Principal Investigator • Lead CRC

• Principal Investigator • Principal Investigator • Site embedded QA Specialist

Monitor Confirmation Letter

Lab Manuals

IRB Approval – Continuing Review IRB Approval – Informed Consent IRB Approval – Initial Investigator Approval IRB Approval – New Protocol or PACL

Investigator Brochure Acknowledgment

Investigator Brochure

Informed Consent & ICF Amendments

Email Blasts (Specific Study Update Information)

eCRF Guidelines

Document Type

Complion Signature Guidelines

*Note: PI is trainer for all Pfizer Protocols

Paper Training Log Required •PI •Sub-I's •All staff on DOA

Paper Training Log Required •PI •All Unblinded Staff *Frequently kept in the unblinded binder

Only Complion signature required. This is routed by regulatory using the current DOA

No Training log required

N/A

N/A

Only Complion signature required. This is routed by regulatory using the current DOA

No Training log required

N/A N/A N/A N/A N/A

Only Complion signature required. This is routed by regulatory using the current DOA

No Training log required

Paper Training Log Required •PI •Sub-I's •All staff delegated to Consent

N/A

Only Complion signature required. This is routed by regulatory using the current DOA

No Training log required

Training Log Requirement

Site Selection /Site Initiation Letter

Safety Letter/Reports/Acknowledgment

Protocol Signature Page

Protocol Amendments and/or Summary of Changes

Document Type

Approve W/Signature

Review W/Signature

Action requested in Complion

• Principal Investigator

Sub-I's)

Review W/Signature

• PI - Review W/Signature • ER - Read (No signature) ER at site) • Sub-I's (Embedded regulatory or Lead CRC will route to • Sub-I's - Review W/Signature

• Principal Investigator • Principal Investigator • Embedded Regulatory Specialist (or lead CRC if no

• Principal Investigator • Lead CRC

To Whom Document will be Routed

Complion Signature Guidelines

Training Log Requirement

N/A

Only Complion signature required. This is routed by regulatory using the current DOA

No Training log required

N/A

*Note: PI is trainer for all Pfizer Protocols

Paper Training Log Required •PI •Sub-I's •All staff on DOA

Meridian Clinical Research Regulatory Binder Template •

Current Documents • • • • •



Current Protocol {Protocol Number Color Key and Site} • Study Specific Document Current Protocol Training Materials • Centrally Managed Document {Protocol Number and Site} Current FDA 1572 {Protocol Number and Site} Current Investigational Brochure {Protocol Number and Site} Current Delegation of Authority Log {Protocol Number and Site}

Study Documents o Protocol Documents ▪ Current • Current Protocol {Protocol Number and Site} • Current Protocol Documents {Protocol Number and Site} • Current Protocol Signature Page {Protocol Number and Site} • Current Protocol Summary of Changes {Protocol Number and Site} ▪ Archived • Archived Protocol {Protocol Number and Site} • Archived Protocol Documents {Protocol Number and Site} • Archived Protocol Signature Page {Protocol Number and Site} • Archived Protocol Summary of Changes {Protocol Number and Site} ▪ Pending • Pending Approval Protocol {Protocol Number and Site} o Training Materials & Logs ▪ Current • Current Training Log {Protocol Number and Site} • Current Training Materials {Protocol Number and Site} • Current Protocol Training Materials {Protocol Number and Site} ▪ Archived • Archived Training Log {Protocol Number and Site} • Archived Training Materials {Protocol Number and Site} ▪ Templates • Training Log Template {Protocol Number and Site} o EDC / IRT / IWRS ▪ Current • Current EDC Training {Name of Researcher, EDC, EDC Certificate Type} ▪ Archived • Archived EDC Training {Name of Researcher, EDC, EDC Certificate Type} ▪ EDC Misc • EDC Misc {Protocol Number and Site} ▪ Guidelines / Screenshots • Current o Current Guidelines / Screenshots {Protocol Number and Site} • Archived

o

o

o

o

o

o

o o

o Archived Guidelines / Screenshots {Protocol Number and Site} Study Correspondence ▪ General Correspondence • General Correspondence {Protocol Number and Site} ▪ Newsletters • Newsletters {Protocol Number and Site} End of Study Documents • Master Subject Log {Protocol Number and Site} • IRB Closeout / Termination Report {Protocol Number and Site} Informed Consent ▪ Current • Current Informed Consent Form {Protocol Number and Site} • Current Informed Consent Form Certificate of Translation {Protocol Number and Site} ▪ Archived • Archived Informed Consent Form {Protocol Number and Site} • Archived Informed Consent Form Certificate of Translation {Protocol Number and Site} Study Manuals ▪ Current • Current Study Manual {Protocol Number and Site} • Current Coordinator Manual {Protocol Number and Site} ▪ Archived • Archived Study Manual {Protocol Number and Site} • Archived Coordinator Manual {Protocol Number and Site} ▪ Coordinator Quick Reference Guides • Coordinator Quick Reference Guide {Protocol Number and Site} Delegation of Authority ▪ Current • Current Team Member List {Protocol Number and Site} • Current Team Member Profile {Name of Researcher and Site} • Current Delegation of Responsibility {Protocol Number and Site} • Delegation of Authority Log {Protocol Number and Site} ▪ Archived • Archived Team Member List {Protocol Number and Site} • Archived Team Member Profile {Name of Researcher and Site} • Archived Delegation of Responsibility {Protocol Number and Site} ▪ Templates • Delegation of Authority Sponsor Template {Protocol Number and Site} Personal Data Privacy Consent Form ▪ Current • Current Personal Data Privacy Consent Form {Protocol Number and Site} ▪ Archived • Archived Personal Data Privacy Consent Form {Protocol Number and Site} Site Data Protection Consent Form • Site Data Protection Consent Form {Protocol Number and Site] Financial Disclosure Form ▪ Current





• Current FDF {Protocol Number and Site} ▪ Archived • Archived FDF {Protocol Number and Site} o FDA 1572 ▪ Current • Current FDA 1572 {Protocol Number and Site} ▪ Archived • Archived FDA 1572 {Protocol Number and Site} ▪ Notes to File • Note to File FDA 1572 {Protocol Number and Site} o End of Study Documents • End of Study Document {Protocol Number and Site} • IRB Closeout/Termination Report {Protocol Number and Site} • Master Subject Log {Protocol Number and Site} Note To File ▪ Study • Note to File {Protocol Number and Site} ▪ FDA 1572 • Note to File FDA 1572 {Protocol Number and Site} Investigational Documents o Investigational Brochure Documents ▪ Current • Current Investigator’s Brochure {Protocol Number and Site} • Current Investigator’s Brochure Addendum Letter {Protocol Number and Site} • Current Investigator’s Brochure Signature Page {Protocol Number and Site} • Current Investigator’s Brochure Summary of Changes {Protocol Number and Site} ▪ Archived • Archived Investigator’s Brochure {Protocol Number and Site} • Archived Investigator’s Brochure Addendum Letter {Protocol Number and Site} • Archived Investigator’s Brochure Signature Page {Protocol Number and Site} • Archived Investigator’s Brochure Summary of Changes {Protocol Number and Site} o Package Insert ▪ Current • Current Packet Insert {Protocol Number and Site} ▪ Archived • Archived Packet Insert {Protocol Number and Site} o Investigational Product ▪ Current o Current IP Documentation {Protocol Number and Site} o Current Temperature Log {Storage Area} o Current Temperature Deviation Reports {Protocol Number and Site}



Archived o o o

Pharmacy Manuals • Pharmacy Forms {Protocol Number and Site} • Pharmacy Manuals {Protocol Number and Site} • Pharmacy Signature Page {Protocol Number and Site} o Accountability Log • Accountability Log {Protocol Number and Site} Staff Credentials o CVs ▪ Current • Current CV {Name of Researcher and CV Type} ▪ Archived • Archived CV {Name of Researcher and CV Type} o GCP Training ▪ Current • Current GCP Training {Name of Researcher} ▪ Archived • Archived GCP Training {Name of Researcher} o IATA Training ▪ Current • Current IATA Training {Name of Researcher and IATA Certificate} ▪ Archived • Archived IATA Training {Name of Researcher and IATA Certificate} o Licenses ▪ Medical Licenses • Current o Current Medical License {Name of Researcher} • Archived o Archived Medical License {Name of Researcher} ▪ Licenses • Current o Current License {Name of Researcher} • Archived o Archived License {Name of Researcher} ▪ DEA Licenses • Current o Current DEA License {Name of Researcher} • Archived o Archived DEA License {Name of Researcher} o Training Certificates ▪ Current • Current Training Certificate {Name of Researcher} ▪ Archived • Archived Training Certificate {Name of Researcher} o



Archived IP Documentation {Protocol Number and Site} Archived Temperature Log {Storage Area} Archived Temperature Deviation Reports {Protocol Number and Site}







Study Specific • Study Specific Training {Protocol Number and Name of Researcher}

Central Lab Documents o Lab Credentials ▪ Current • Current Central Lab Director CV {Protocol Number and Site} • Current Central Lab Director Medical License {Protocol Number and Site} ▪ Archived • Archived Central Lab Director CV {Protocol Number and Site} • Archived Central Lab Director Medical License {Protocol Number and Site} o Lab Certifications ▪ Current • Current Central Lab CLIA/CAP {Protocol Number and Site} • Current Central Lab CLIA/CAP Waiver {Protocol Number and Site} ▪ Archived • Archived Central Lab CLIA/CAP {Protocol Number and Site} • Archived Central Lab CLIA/CAP Waiver {Protocol Number and Site} o Lab Documents ▪ Current • Current Central Lab Manual {Protocol Number and Site} • Current Central Lab Document {Protocol Number and Site} • Current Central Lab Guidelines {Protocol Number and Site} • Current Central Lab Reference Range {Protocol Number and Site} ▪ Archived • Archived Central Lab Manual {Protocol Number and Site} • Archived Central Lab Document {Protocol Number and Site} • Archived Central Lab Guidelines {Protocol Number and Site} • Archived Central Lab Reference Range {Protocol Number and Site} o Lab Correspondence • Central Lab Correspondence {Protocol Number and Site} Local Lab Documents o Lab Credentials ▪ Current • Current Local Lab Director CV {Lab} • Current Local Lab Director Medical License {Lab} ▪ Archived • Archived Local Lab Director CV {Lab} • Archived Local Lab Director Medical License {Lab} o Lab Certifications ▪ Current • Current Local Lab CLIA/CAP {Lab} • Current Local Lab CLIA/CAP Waiver {Lab} ▪ Archived • Archived Local Lab CLIA/CAP {Lab} • Archived Local Lab CLIA/CAP Waiver {Lab} o Local Lab Documents ▪ Current









• Current Local Lab Manual {Lab} • Current Local Lab Document {Lab} • Current Local Lab Guidelines {Lab} • Current Local Lab Reference Range {Lab} ▪ Archived • Archived Local Lab Manual {Lab} • Archived Local Lab Document {Lab} • Archived Local Lab Guidelines {Lab} • Archived Local Reference Range {Lab} o Lab Correspondence • Local Lab Correspondence {Protocol Number and Site} Site Documents o Calibration ▪ Current • Current Calibration Certification {Equipment and Site} ▪ Archived • Archived Calibration Certificate {Equipment and Site} o Standard Operating Procedures • Current Standard Operating Procedure {Standard Operating Procedure} • Archived Standard Operating Procedure {Standard Operating Procedure} o Guidelines ▪ Guidelines {Protocol Number and Site} o Temperature Logs ▪ Current • Current Temperature Log {Storage Area} ▪ Archived • Archived Temperature Log {Storage Area} Source Documents ▪ Pending • Pending Source Document {Protocol Number and Site} ▪ Current • Current Source Document {Protocol Number and Site} ▪ Archived • Archived Source Document {Protocol Number and Site} ▪ Source Document Request Form • Source Document Request Form {Protocol Number and Site} Event Reporting o Adverse Events ▪ Adverse Event {Protocol Number and Site} ▪ Adverse Event Document {Protocol Number and Site} o Serious Adverse Events ▪ Serious Adverse Event {Protocol Number and Site} ▪ Serious Adverse Event Document {Protocol Number and Site} o Safety Reports ▪ Safety Report {Protocol Number and Site} ▪ Safety Report Document {Protocol Number and Site} IRB Documents o IRB Submission Documents

Current • Current IRB Submission {Protocol Number and Site} ▪ Archived • Archived IRB Submission {Protocol Number and Site} IRB Approval Documents ▪ Current • Current IRB Approval/Acknowledgement {Protocol Number and Site} ▪ Archived • Archived IRB Approval/Acknowledgement {Protocol Number and Site} IRB Documents ▪ Current • Current IRB Document {Protocol Number and Site} ▪ Archived • Archived IRB Document {Protocol Number and Site} IRB Roster ▪ Current • Current IRB Roster {IRB} • Current IRB Handbook {IRB} ▪ Archived • Archived IRB Roster {IRB} • Archived IRB Handbook {IRB} IRB Correspondence • IRB Correspondence {Protocol Number and Site} IND Safety Report Acknowledgements • IND Safety Report Acknowledgement {Protocol Number and Site} IRB Protocol Deviation Reports • IRB Protocol Deviation Report {Protocol Number and Site} Advertisements ▪ Current Advertising Material • Current Advertising Material {Protocol Number and Site} • Current Advertising Material Certificate of Translation {Protocol Number and Site} ▪ Current Sponsor Advertising Material • Current Sponsor Advertising Material {Protocol Number and Site} ▪ Current Site Advertising Material • Current Site Advertising Material {Protocol Number and Site} ▪ Archived Advertising Material • Archived Advertising Material {Protocol Number and Site} • Archived Advertising Material Certificate of Translation {Protocol Number and Site} ▪ Archived Sponsor Advertising Material • Archived Sponsor Advertising Material {Protocol Number and Site} ▪ Archived Site Advertising Material • Archived Site Advertising Material {Protocol Number and Site} IRB Continuing Review/Close-Out Reports • Continuing Review {Protocol Number and Site} • IRB Closeout / Termination Report {Protocol Number and Site} Coordinator Materials ▪

o

o

o

o o o o

o

o

Current • Current Coordinator Material {Protocol Number and Site} ▪ Archived • Archived Coordinator Material {Protocol Number and Site} ▪ IRB Approved Advertisements • IRB Approved Coordinator Material {Protocol Number and Site} o Subject Materials ▪ Current • Current Subject Material {Protocol Number and Site} • Current Subject Material Certificate of Translation {Protocol Number and Site} ▪ Archived • Archived Subject Material {Protocol Number and Site} • Archived Subject Material Certificate of Translation {Protocol Number and Site} o IBC Documents ▪ IBC Document {Protocol Number and Site} Study Agreements o Agreements • Clinical Trial Authorization (CTA) {Protocol Number and Site} • Other Study Agreement {Protocol Number and Site} Sponsor Documents o Sponsor/CRO Contact List • Sponsor/CRO Contact List {Protocol Number and Site} o Site Blinding Plan ▪ Current • Current Site Blinding Plan {Protocol Number and Site} ▪ Archived • Archived Site Blinding Plan {Protocol Number and Site} o Sponsor Documents ▪ Sponsor Document {Protocol Number and Site} o Investigator Meeting ▪ Investigator Meeting {Protocol Number and Site} o Pregnancy Forms ▪ Pregnancy Form {Protocol Number and Site} o Sponsor Correspondence ▪ Sponsor Correspondence {Protocol Number and Site} ▪ Current Sponsor/CRO Approval {Protocol Number and Site} o Protocol Deviation Reports ▪ Protocol Deviation Reports {Protocol Number and Site} o Coordinator Quick Reference Guides ▪ Coordinator Quick Reference Guide {Protocol Number and Site} o Subject Quick Reference Guides ▪ Subject Quick Reference Guide {Protocol Number and Site} Monitoring o Monitor Visits ▪ Monitor Confirmation Letter {Protocol Number and Site} ▪ Monitor Visit Log {Protocol Number and Site} ▪







o

o o •

• •

Site Initiation Visit ▪ Site Initiation Visit Letter {Protocol Number and Site} ▪ Site Initiation Visit Log {Protocol Number and Site} ▪ Site Initiation Visit Report {Protocol Number and Site} ▪ Site Initiation Visit Training Material {Protocol Number and Site} ▪ Site Initiation Visit Log Template {Protocol Number and Site} Newsletters ▪ Newsletters {Protocol Number and Site} Follow Up ▪ Monitor Visit Follow-Up Report {Protocol Number and Site}

Vendor o Vendor Manual ▪ Current • Current Vendor Manual {Protocol Number and Site} ▪ Archived • Archived Vendor Manual {Protocol Number and Site} o Vendor Training Materials • Vendor Training Materials {Protocol Number and Site} o Vendor Shipping Receipts • Vendor Shipping Receipts {Protocol Number and Site} o Vendor Other Documents • Vendor Other Documents {Protocol Number and Site} o Vendor Correspondence • Vendor Correspondence {Protocol Number and Site} Miscellaneous • Miscellaneous {Protocol Number and Site} Logs o Delegation of Authority Logs ▪ Current • Current Delegation of Responsibility {Protocol Number and Site} • Delegation of Authority Log {Protocol Number and Site} ▪ Archived • Archived Delegation of Responsibility {Protocol Number and Site} o Training ▪ Current • Current Training Log {Protocol Number and Site} ▪ Archived • Archived Training Log {Protocol Number and Site} o Site Initiation Visit • Current Site Initiation Visit Log {Protocol Number and Site} o Monitor Visits • Current Monitor Visit Log {Protocol Number and Site} o Sponsor Visits • Sponsor/CRO Visit Log {Protocol Number and Site} o Temperature Logs ▪ Current • Current Temperature Log {Storage Area} ▪ Archived



• •



• Archived Temperature Log {Storage Area} o Deviation Logs ▪ Current • Current Deviation Log {Protocol Number and Site} ▪ Archived • Archived Deviation Log {Protocol Number and Site} o Master Subject Log • Master Subject Log {Protocol Number and Site} o Screening/Enrollment/Randomization Logs • Screening/Enrollment/Randomization Logs {Protocol Number and Site} o Informed Consent Log ▪ Logs • Informed Consent Log {Protocol Number and Site} ▪ Templates • Informed Consent Log Template {Protocol Number and Site} o Other Logs • Other Study Log {Protocol Number and Site} Correspondence o Study Correspondence • General Correspondence {Protocol Number and Site} o IRB Documents • IRB Correspondence {Protocol Number and Site} o Central Lab Documents • Central Lab Correspondence {Protocol Number and Site} o Local Lab Documents • Local Lab Correspondence {Protocol Number and Site} o Sponsor Correspondence • Sponsor Correspondence {Protocol Number and Site} • Current Sponsor/CRO Approval {Protocol Number and Site} o Vendor Correspondence • Vendor Correspondence {Protocol Number and Site} Feasibility Review • Feasibility Review {Protocol Number and Site} CDA ▪ Current • Current Master CDA {Sponsor} • Current Study Specific CDA {Protocol Number and Site} ▪ Archived • Archived Master CDA {Sponsor} • Archived Study Specific CDA {Protocol Number and Site} Study Contracts ▪ Current • Current Fully Executed Budget {Protocol Number and Site} • Current Fully Executed Contract {Protocol Number and Site} • Current Fully Executed Contract Amendment {Protocol Number and Site} • Current Fully Executed Contract Supporting Documentation {Protocol Number and Site} • Current Master CTA {Sponsor}

Archived • Archived Fully Executed Budget {Protocol Number and Site} • Archived Fully Executed Contract {Protocol Number and Site} • Archived Fully Executed Contract Amendment {Protocol Number and Site} • Archived Fully Executed Contract Supporting Documentation {Protocol Number and Site} • Archived Master CTA {Sponsor} Financial Documents • Payment Intake {Protocol Number and Site} Vendor Agreements ▪ Current • Current Laboratory Services Agreement {Protocol Number and Site} • Current Imaging Services {Protocol Number and Site} • Current Sub Agreements {Protocol Number and Site} • Current Compassionate Usage Agreement {Protocol Number and Site} • Current Data Usage Agreement {Protocol Number and Site} • Current Material Transfer Agreement {Protocol Number and Site} ▪ Archived • Archived Laboratory Services Agreement {Protocol Number and Site} • Archived Imaging Services {Protocol Number and Site} • Archived Sub Agreements {Protocol Number and Site} • Archived Compassionate Usage Agreement {Protocol Number and Site} • Archived Data Usage Agreement {Protocol Number and Site} • Archived Material Transfer Agreement {Protocol Number and Site} Study Expenses o Budget Summary • Budget Summary {Protocol Number and Site} o Study Receipts/Invoices • Study Receipt/Invoice {Protocol Number and Site} • Advertising Invoice {Protocol Number and Site} Study Invoices o Submitted • Submitted Study Invoice {Protocol Number and Site} o Revision Required • Revision Required Study Invoice {Protocol Number and Site} o Archived • Archived Study Invoice {Protocol Number and Site} Study Payments o Pending Verification • Study Payment Pending Verification {Protocol Number and Site} o Completed • Completed Study Payment {Protocol Number and Site} ▪

• •







Section 6

CRC Daily Checklist

Clinical Research Coordinator Daily Checklist AM Verify Temperatures are within range prior to seeing patients Check email for IRB Approvals/Notifications Ensure all Approved and/or Updated Consents are printed and filed for the Subject to sign at screening and/or next visit if applicable Ensure Monitor Visit is setup if applicable • Ensure the PI is aware of the Monitoring Visit and a time the PI can meet with the Monitor is setup • Ensure Monitor has Complion access Check Emails from Sponsors/MCR Employees to ensure all important communications are handled in a timely manner Ensure sure all required applicable notifications are sent to the notifications email group • • • • • • •

All informed consents - new, updates, etc. All protocols All major status updates - green light, on hold, closing early, enrollment changes, study canceled, etc. All protocol amendments All study synopsis or summaries All audit notifications - CRO, sponsor and FDA All emails clarifying anything to do with the study that are important communications

Check Queries in EDC for each protocol your assigned to and prioritize query resolution with Data Entry Team Ensure all protocol specific shipments are unpacked correctly accounted for in SLOPE and/or Device accountability log Ensure all IP shipments are stored and documented accordingly to Sponsor and/or MCR Policy Ensure all subject charts are pulled and approved source is place into the chart if applicable for the next day/week- (i.e. Screening, Follow-ups, Diaries, Phone Calls) Ensure Lab reports are getting printed for PI Review/Signature Ensure all applicable filling is up to date Ensure Site Delegation Log is updated for any addition or deletion of staff members • Ensure updated Site Delegation Log is sent to the CTMS Team • Ensure updated Site Delegation Log is sent to the CRIO Team Ensure all applicable documents are forward to the appropriate Regulatory Binder for filing Ensure all trainings are completed and/or started for any protocol/sponsor specific training as applicable Ensure all Diaries/Follow-up phone calls are getting completed accurately according to the protocol • •

Diaries Printed for PI signature Follow-ups documented appropriately with PI signature if applicable

Prepare New Supplemental Binder and/or New Study documents if applicable – •

Ensure all appropriate documents are sent to the correct department for approval • Draft Site Delegation Log • Draft Training Log • Screening Tool Sheet • Study Specific Site Information Sheet

**NA any task if not applicable at Site. Please confirm with Site Management prior to marking NA** Meridian Clinical Research, LLC

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• •

Blinding Plan Recruitment Plan

Ensure Site Start-Up Checklist is complete in the CTMS Ensure all target dates are correct/updated in the CTMS PM Ensure all corrections and/or queries from the Monitor is completed prior to the monitoring leaving for the day •

Ensure all outstanding action items are completed from previous monitoring visits

Check email for IRB Approvals/Notifications Ensure all Approved Consents are printed and filed for subject to sign at screening and/or next visit if applicable Check Emails from Sponsors/MCR Employees to ensure all important communications are handled in a timely manner Ensure Source Request was sent to the Data Team if applicable Ensure any outstanding task from CC Admin was completed (i.e. study start up windows/reminders, invoicing questions, and/or other communication) Ensure Subject Charts are getting entered into EDC Ensure Chart Corrections are Completed Ensure Master ICF log is up to date Ensure Supplemental binder is up to date with all applicable documents per MCR Policy Ensure all filing is completed for Patient Charts Ensure SAEs are submitted per Sponsor/MCR Policy • • •

Ensure all SAEs required to be submitted to the IRB was sent to QA for Review/Approval Submit Approved SAE Notifications to the IRB Ensure all SAEs are entered into CC for Payments/Tracking

______ Ensure Protocol Deviations are documented on the log as applicable • •

Ensure all protocol deviations required to be submitted to the IRB was sent to QA for review/approval Submit Approved Protocol Deviations to the IRB

Ensure the visit summary for each assigned protocol is accurate and up to date- (i.e. All visits competed in CC, confirm 3 visits are scheduled out within window, ensure payments are complete, ensure all screening/randomization numbers are complete) Ensure all no-shows are called and rescheduled per MCR policy ______ Ensure all Certified letters were sent out if applicable •

Ensure certified letter is uploaded into CC per MCR Policy

Ensure all applicable documents are forward to the appropriate Regulatory Binder for filing Ensure all charts are flagged for PI signature Ensure sure all required applicable notifications are sent to the notifications email group Request for Additional Study Supplies if applicable (i.e. devices, lab kits, and/or recruitment material)

**NA any task if not applicable at Site. Please confirm with Site Management prior to marking NA** V1.0 – 30Jul2021

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Section 7

Study Startup Checklist in CTMS Guide

Study Start-up Checklist in CTMS-Guide ______ PSSV Form-send to [email protected] o Regional/Site Management will send in this form ______ Award Letter-send to [email protected] o Regional/Site Management will send in this form ______ Update Target Dates and Assign Lead Coordinator in CTMS o Site Management will ensure the dates are entered and Lead Coordinator assigned ______ Confirm Initial Recruitment Meeting for Study Start Up- (i.e. advertising material, database list, patient engagement advertising material) o Site Management will setup the meeting with the Recruitment team members as applicable ______ Confirm Regulatory Packet Received o Lead CRC/Site Management will Ensure Regulatory has received the packet ______ Protocol-Send to [email protected] o Lead CRC to send the protocol to notifications ______ Source Request to Data Team-1st Request with Applicable Documents o Lead CRC to send the 1st request will all applicable documents received at this point ______ Pharmacy Manual-Send to [email protected] o Lead CRC to send to Data Team once received ______ Lab Manual-Send to [email protected] o Lead CRC to send to Data Team once received ______ eCRF Guidelines-Send to [email protected] o Lead CRC to send to Data Team once received ______ Source Request to Clinical Data Team-2nd Request with Applicable Documents (only if applicable) o Lead CRC to send the 2st request will all applicable documents received at this point if needed ______ Draft DOA sent to Embedded QA 1st for Approval (once approved send to QA for Final Approval) o Lead CRC/Site Management to create Draft DOA for Review ______ Draft Training Log Created for SIV o Lead CRC to create Training log ______ Confirm Supplemental Binder Created o Lead CRC/Embedded Regulatory to create binder ______ Confirm Lab Binder Created- (i.e. spin log, UPT log, etc) o Lead CRC/Lab Staff to create binder ______ Confirm ICF Binder Created o Lead CRC to create binder ______ Confirm if applicable Unblinded Binder o Unblinded staff to create binder ______ Confirm Prescreening Script and/or Screening Tool Sheet Created in CTMS o Lead CRC to Create Screening Tool Sheet if applicable for site. o Lead CRC to confirm Prescreening Script loaded into the CTMS ______ Final Approved DOA draft sent to QA, Regulatory, and CC Admin o Lead CRC to send approved draft to appropriate departments ______ SIV Date updated in CTMS Study List o Lead CRC/Site Management to ensure SIV date is entered into the CTMS Target Dates ________Confirm all applicable access information received for all study personnel (i.e. IWRS, EDC, E-Diary, etc.) o Lead CRC/Site Management to ensure all staff has received access emails _______ Confirm PI has activated IWRS and EDC accounts

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o Lead CRC/Site Management to ensure PI has logged in to their account and activated the account ______ Confirm Complion Binder Create o Lead CRC/Embedded Reg to ensure complion binder created and confirm correct staff members assigned to the binder ______ Confirm Complion Access Request sent to SIV CRA o Lead CRC to provide correct CRA contact information to Embedded Regulatory for access information to be sent ______ Confirm IRB and/IBC approval Received o Lead CRC to ensure IRB approval is received ______ Confirm Approved ICF received and ICF List Updated for Staff White Board o Lead CRC/Site Management to ensure approved ICF received and staff white board updated ______ Review ICF and Compare to Protocol for Stipend Accuracy o Lead CRC is to review the above to ensure accuracy ______ Confirm Study Start Date, Cohorts, and Enrollment Goal to [email protected] o Lead CRC/Site management is to ensure all the above is sent to Notifications ______ Source Request to Clinical Data Team-Final Request if only applicable o Lead CRC to send the #st request will all applicable documents received at this point if needed ______ Confirm 2nd Recruitment Meeting for the Study Start-Up and Projected 1st Patient 1st Visit in CTMSUpdate on Database List and/or Advertising Packet o Site Management will setup the meeting with the Recruitment team members as applicable ______ Send CTMS Admin the Visit Template and Confirmed Subject Stipend with Additional Reminder Notes o Lead CRC to complete the above and send to CC Admin ______ Send Final and Signed DOA to QA, Regulatory, and CC Admin o Lead CRC to send DOA to the appropriate departments ______ Confirm Signed DOA and Training Documents are Uploaded into the Complion Binder o Lead CRC to confirm ______ Confirm Green Light letter sent to [email protected] o Lead CRC to send letter ______ Confirm 3rd Recruitment Meeting for Study Start-up if needed. (i.e. database follow-up and/or advertising packet. o Site Management will setup the meeting with the Recruitment team members as applicable ______ Confirm Complion has regulatory filed: o Source documents o Protocol o ICF o Signature page of Protocol o DOA Training and Logs ▪ Lead CRC will ensure all is filed ______ Lead CRC to Confirm Acknowledgement of what goes to [email protected] after Study Start-Up o All informed consents - new, updates, etc. o All protocols and protocol amendments o All major status updates - green light, on hold, closing early, enrollment changes, study cx’d, etc. o All audit notifications - CRO, sponsor and FDA o All Monitoring Visits and Monitoring Visit Follow-ups to QA and Regulatory Team o Notify QA and Regulatory Team of all monitoring visits via outlook invite

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Section 8

Site Signature & Delegation of Duties Log

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Principal Investigator:

CRO: Site #:

PI Signature

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Initials

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Study Tasks

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Start Date (dd/Mmm/yyyy)

End Date (dd/Mmm/yyyy)

Delegation of Duties Log, 4.0 – 09Nov2021

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CHANGE IN PI INSTRUCTIONS: In the event that the Principal Investigator changes use Page 1A (located on Meridian Intranet), follow the process to document changes

*My signature confirms/acknowledges that the information contained here is accurate and that: • I will remain responsible for the overall study conduct and reported data. • I will ensure study oversight. • I will authorize the delegation of study-related tasks to each individual as listed. • The study tasks listed will only be delegated by me to skilled and qualified staff appropriately trained for the role. • I will ensure that all personnel assisting in the conduct of the study are informed about their obligations and will not have performed any delegated study-related tasks prior to appropriate delegation and completion of study training appropriate to the role. • I will ensure that site staff receives, in a timely manner, the appropriate information and training for delegated tasks. • I will ensure that any and all changes in staff or delegated study-related task will be recorded in a timely manner.

Name of PI

THE STUDY SITE IS REQUIRED TO MAINTAIN AN UP-TO-DATE VERSION OF THIS FORM IN ACCORDANCE WITH SPONSOR REQUIREMENTS.

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THE PRINCIPAL INVESTIGATOR MUST ENSURE PERSONNEL DO NOT START THE DELEGATED STUDY-RELATED TASKS UNTIL CONFIRMING THAT THEY HAVE COMPLETED STUDY RELATED TRAINING APPROPRIATE TO THE ROLE AND TASK.

THIS FORM IS TO BE COMPLETED FOR SITE PERSONNEL INVOLVED IN THE STUDY TO WHOM THE INVESTIGATOR HAS DELEGATED SIGNIFICANT STUDY-RELATED DUTIES. THE FORM IS TO BE COMPLETED PRIOR TO CONDUCTING STUDY RELATED TASKS.

Protocol #:

Sponsor:

Delegation of Duties Log

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30. Safety/surveillance calls 31. Other*: 32.Other *: ______________________________ 33.Other *: ______________________________ 34. Other *: ______________________________ 35. Other *:______________________________ 36. Other *:______________________________ 37. Other *: ______________________________ 38. Other *:______________________________ 39. Other *:______________________________ 40. Other *: ______________________________ 41. Other *: ______________________________ 42. Other *: ______________________________ 43. Other *: ______________________________ 44. Other *: ______________________________

Site #:

Delegation of Duties Log, Version 4.0 – 09Nov2021

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Study Role Key: Enter the research staff’s study-specific role next to their name on each line. Examples of roles may include: SI – Sub-investigator CRC – Clinical Research Coordinator ACRC – Assistant Clinical Research Coordinator EDC - Data Entry Specialist Regulatory Specialist Lab Coordinator Diary Specialist UCRC - Unblinded CRC Administrative Assistant

Page ____ of ____

Bolded tasks should only be delegated to site staff who are qualified by educational background to make medical or diagnostic decisions in patient care (M.D., D.O., NP, PA, etc.). (*) Other tasks may be those that are study specific or are local regulatory requirements and have been identified by the Study Sponsor. (**) PI initials and date indicate that PI confirms/ approves start date of tasks in column “Start of task(s)”

on ly

CRO:

16. Perform protocol required procedures/assessments (may include ECG, vital signs, med hx & con meds) 17. SAE report documentation, review & submission 18. Collect biological samples 19. Process and/or ship biological samples (IATA required) 20. Manage IP receipt & storage 21. Prepare and dispense IP 22. Perform IP accountability 23. IP Verification 24. Administer IP 25. Post dose observation 26. Diary dispense & training 27. Diary collection & Review 28. Make (e)CRF entries, corrections, & queries 29. Staff training

Principal Investigator:

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Ex

Study Task Key: 1. Break Blind (PI only) 2. Sign off on (e)CRF visit data (PI only) 3. Perform physical exam 4. Confirm eligibility criteria (inclusion/exclusion) 5. Make study related medical decisions 6. Evaluate study related test results 7. Assess AE/SAE causality 8. Manage IRB/EC communications & submissions 9. Maintain essential documents 10. Receive/Review safety notifications 11. Recruit/Screen study subjects 12. Source document completion 13. Informed consent process 14. Obtain consent 15. Use IWRS/IVRS

Protocol #:

Sponsor:

Delegation of Duties Log

Signature My signature below indicates that I accept the study task.

Clair Coordinator

Name /Credentials

Example Clair Coordinator, RN

Protocol #:

Sponsor:

CMC

CRC

(Select from key)

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Study Role

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1, 2, 3, 5, 7

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Study Task(s) (Select from key)

Principal Investigator:

Site #:

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DMG 31/MAY/2016

30/JUN/2017

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PI initials/ date Start of task(s) End of task(s) PI initials /date ** (dd/Mmm/YYYY) (dd/Mmm/yyyy) (dd/Mmm/yyyy) (dd/Mmm/yyyy)

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Site #:

x Principal Investigator’s Signature*

Delegation of Duties Log, Version 4.0 – 09Nov2021

INSTRUCTIONS: This is a duplicate of the prior page Only use/print this page to add more site staff for delegation.

Date

I confirm that the information contained in this document is accurate and complete. (To be completed by the Principal Investigator at study close-out).

am pl e

Ex on ly

Principal Investigator:

Comments (Or, please check box if there are no comments ☐)

Protocol #:

Sponsor:

Delegation of Duties Log

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STOP !!!! Updating the Delegation of Authority ❖ Contact QA to discuss Study Tasks prior to adding staff ❖ Contact your Regulatory Specialist – provide start date of delegated task ❖ Complete Add/Drop Form

Do NOT add Staff to DOA: The following Documents are needed before staff can be delegated. • Abbreviated CV and/or Pfizer One Page CV- esign • License – certified staff • GCP Certificate • IATA Certificate – make sure signed by staff • Site Training Logs - staff has completed training on the current version of the Protocol and all delegated tasks • Access to Complion – to sign electronically • Personal Data Privacy Consent form is sponsor requires, create and sent for e-signature (Pfizer)

Before you add an Investigator Regulatory will need to complete

✓ Update 1572 – remove staff that have left ✓ Financial Disclosure created and routed for e-signature ✓ Personal Data Privacy Consent Form if sponsor requires, created and sent for e-signature (Pfizer)

Section 9

Source Document Request Form

Source Document Request Form

CHECK ONE: ☐ Initial Request ☐ Updated Request – reason: _______________________________ STUDY & SITE DETAILS:

Sponsor/CRO Name:

Protocol Number:

Study Indication:

Date of Request:

Lead CRC:

Lead Unblinded: ☐ NA

Anticipated Date Initial Source Documents Needed: Site Location & Principal Investigator: PROTOCOL DETAILS:

Current Protocol Version #/Date:

Is a protocol amendment anticipated? ☐ No ☐ Yes

Site-Specific Participation in Study: (e.g., Cohorts, Phase, Period, Part, Optional Assessments, Sub-Study, PBMC Collection, Sentinel Group) ☐ NA

Specify: ___________________________________________________________________________________________________

SPONSOR SOURCE:

Is the Sponsor providing source? ☐ Yes (send upon receipt) ☐ No

Is the site required to use Sponsor source? ☐Yes ☐ No ☐ NA

Can Sponsor source be supplemented? ☐Yes ☐ No ☐ NA

STUDY DOCUMENTS (IF NOT CONFIRMED TO BE FILED IN eREGULATORY BINDER, SEND WITH REQUEST):

Mark all applicable study documents: ☐ Protocol: ☐ Available ☐ Requested ☐ eCRF Completion Guidelines: ☐ Available ☐ Requested ☐ eCRF Blank Casebook: ☐ Available ☐ Requested ☐ IRB Approved Informed Consent/Assent, specify: ☐ Main ☐ Parental ☐ Assent ☐ Optional Sub-Study or Addendum  Will eConsent be utilized? ☐ Yes ☐ No ☐ Pharmacy Manual: ☐ Available ☐ Requested ☐ NA  Are IP Prep Forms provided by the Sponsor? ☐ Yes (send) ☐ No ☐ NA ☐ Study/Operational Manual: ☐ Available ☐ Requested ☐ NA ☐ Lab Manual: ☐ Available ☐ Requested ☐ IRB Approved Telephone Script: ☐ Available ☐ NA ☐ SIV Slides: ☐ Available ☐ Requested ☐ IM Slides/FAQ: ☐ Available ☐ Requested ☐ Sponsor Provided Source: ☐ Available ☐ Requested ☐ NA ☐ Diary, specify type: ☐ Paper ☐ Memory Aid ☐ eDiary ☐ Other: _______________________________________________________________________________________________________________ Comments:

TIMELINE FOR SITE: Study Startup (Estimated): Regulatory packet received on date: ________________ or ☐ pending receipt SIV: ☐ Date: __________________________ or ☐Not currently scheduled ☐None

Investigator’s Meeting: Date(s): ________________________________ ☐ In-Person ☐Virtual (send invite) ☐None First Subject First Visit (at site): Green Light (anticipated):

Please email the completed form and all updates to [email protected]. Include “Source Request: Protocol Number (XXX), Sponsor (XXX), Site Location (XXX)” in email subject line. Clinical Data Notes:

Meridian Clinical Research, LLC

Source Document Request Form // V3; 04JUN2021

Page 1 of 1

Section 10

Adding or Removing a Staff Member Lead CRC Study Transfer Checklist

Adding or Removing a Staff Member Protocol ID: Click or tap here to enter text. Principal Investigator: Click or tap here to enter text.

Site ID: Click or tap here to enter text.

Adding or Removing Staff Member?

Date

☐ Adding (Complete Checklist #1) ☐ Removing (Complete Checklist #2 [Page 2])

Click or tap here to enter text.

Staff Member Name

Staff Member Position/Title

Click or tap here to enter text.

Click or tap here to enter text.

Checklist #1 (Complete if ADDING a Staff Member) Task

Done?

Sponsor notified of new staff member being added

☐ Yes ☐ No

Study access to relevant portals requested

☐ Yes ☐ No ☐ n/a

Date Completed

Staff Initials Comment

Staff added to Complion binder ☐ Yes (Confirm CV, License, GCP, and IATA if ☐ No ☐ n/a required have pulled into binder) Regulatory specialist for site notified ☐ Yes that staff member has been added to ☐ No ☐ n/a study Staff added to 1572 box 6 or NTF created (Only if lead CRC or SubInvestigator)

☐ Yes ☐ No ☐ n/a

Financial disclosure form completed (Only if lead CRC or Sub-Investigator)

☐ Yes ☐ No ☐ n/a

IRB access requested for new staff member

☐ Yes ☐ No ☐ n/a

Current protocol, informed consent, and lab manual training completed, documented, and sent to Complion binder

☐ Yes ☐ No ☐ n/a

EDC and IVRS Training completed, documented, and sent to Complion binder

☐ Yes ☐ No ☐ n/a

Added to delegation log and signed off on by PI once training completed

☐ Yes ☐ No

Upload the updated Delegation log to ☐ Yes ☐ No Complion binder and copy [email protected] in the email ☐ n/a

Meridian Clinical Research, LLC

Adding or Removing a Staff Member, Version 1.0 — 14Jul2020

Page 1 of 2

Checklist #2 (Complete if REMOVING a Staff Member) Task

Done?

Sponsor notified that staff is no longer participating on study and to remove access to portals

☐ Yes ☐ No

IRB access to study removed from portal

☐ Yes ☐ No ☐ n/a

If lead CRC is being removed, study transfer to new lead CRC form completed

☐ Yes ☐ No ☐ n/a

End date of participation added to delegation log and signed off by PI

☐ Yes ☐ No ☐ n/a

Upload the updated Delegation log to complion binder and copy [email protected] in the email

☐ Yes ☐ No ☐ n/a

Sponsor notified that staff is no longer participating on study and to remove access to portals

☐ Yes ☐ No ☐ n/a

Date Completed Staff Initials Comment

Adding or Removing a Staff Member, Version 1.0 — 14Jul2020

Page 2 of 2

Lead CRC Study Transfer Checklist Protocol Number

New Lead CRC

Training CRC

Training CRC (Initials + Date)

Training Topics

New CRC (Initials + Date)

Protocol review (also review study slides if available). ICF review. IP manual review. Lab Manual review. Lab supplies accounted for and show new lead where all is stored (shipping boxes, labels, etc.). New lead CRC delegated correctly on DOA. EDC access and training. IVRS access and training. Patient diary review (if applicable) and portal access. IRB access and training on portal and documents (Ensure all communication is going to the new lead CRC). Visit review in CC, review current subjects’ statuses and charts with new CRC. Complion binder access for study given to new lead CRC. Spin log and pregnancy test log for study (if applicable) given to new CRC. CRA Email introduction to new CRC. Review Protocol Deviation Log with new CRC Notify all internal Meridian parties of lead CRC change by sending an email with protocol number, new Lead name, and effective date to [email protected] + [email protected] and attaching this completed form. Add new lead to Teams study chat. If study is taking place at another Meridian site, please contact lead CRC at the associated site, notify them that the study has a new CRC and connect them / assign that lead as the new coordinators mentor for the study. Mentor name: Training on study specific questionnaires (if applicable) Study specific training (add details, or note N/A): Site Director Signature (Upon Form Completion)

Meridian Clinical Research, LLC

Lead CRC Study Transfer Checklist | V5 | 23Mar2022

Page 1 of 1

Section 11

Training Log Instructions Training Log Operational Training Log

Training Log Instructions V2-27Apr2021

When complete, please send to your QA specialist for review prior to PI signature. If you have any questions, please refer them to Renee Barbato, QA specialist.

Others as applicable

Lab procedures

AE/SAE reporting

Unblinded procedures

Blinded procedures

Consenting process

IB with version/date for PIs and Sub-Is only

ICF with version/date for those who did not attend the SIV

Protocol Amendment with version/date

Initial protocol with version/date for those who did not attend the SIV

SIV (with Protocol version/date)

Training Topics: (to include but not limited to/or as directed by Sponsor)

1. First enter the trainer’s information and how they were trained. This means there must be some documentation on who/when the trainer was originally trained on the topic 2. List all individuals as they are trained with the date clearly noted along with the method of training. ie: trained vs. self-review 3. Enter trainers signature or NA as applicable 4. Have the PI sign/date as directed on log 5. This form should not be filled out in advance but at the time of training or after training has been completed

Use this log when training is needed for multiple people on a specific topic. Use the key below to enter the topic being trained on. Be specific to include the protocol version number/date, IB version number/date, and ICF version/date

Training Log Instructions

Trainee Name

Trainee Signature

Trainer Name/Self Review (As on Delegation Log)

Trainer Signature/NA

Meridian Clinical Research

Training Log V2-27Apr2021

PI Signature (As page is completed or at end of study)

Date

Page ___ of___

Instructions: Document training provided to staff during the study. Version of study documents (protocol, ICF) covered during training should be clearly recorded. I authorize the delegation of training to qualified staff trained for the study role as on delegation log.

Training Date

Study Role

PI/Site Number:

Protocol #:

Training Topic (be sure to include version and date where applicable):

CRO:

Sponsor:

Training Log

PI/Site Number:

Protocol #:

Meridian Clinical Research

Training Log V2-27Apr2021

PI Signature (As page is completed or at end of study)

Date

Page ___ of___

Instructions: Document training provided to staff during the study. Version of study documents (protocol, ICF) covered during training should be clearly recorded. I authorize the delegation of training to qualified staff trained for the study role as on delegation log.

Training Topic (be sure to include version and date where applicable):

CRO:

Sponsor:

Training Log

Operational Training Log Training Topic(s)/Item(s) Reviewed

Date of Training/Review Trainer Site

Name (Print)

x Trainer Signature Meridian Clinical Research

Signature

Date Operational Training Log | Version 1.0 | 23Mar2022

1

Section 12

Master ICF Log Subject Level ICF Log

ICF Tracking Log

MCR Version 5.0 – 27Apr2021

ICF Version Number/Version Date

Subject ID #

Meridian Clinical Research, LLC

Site Number

Protocol Number Date Informed Consent Signed

Principal Investigator

Sponsor

The log should be completed each time a subject signs an informed consent for the duration of trial.

Master Informed Consent Form (ICF) Tracking Log

Comments

Page ____ of ____

Meridian Clinical Research, LLC

Current ICF Date/Version

Subject ID

Sponsor

MCR Version 4.1 – 17Mar2021

Specify ICF Type (Main, sub-study, etc.)

Principal Investigator Site Number

The log should be completed each time a subject signs an informed consent for the duration of trial.

Subject Level Informed Consent Form (ICF) Tracking Log

Date Subject Signed ICF

Protocol Number

Page ____ of ____

MCR Version 4.0 – 27Apr2021

IRB approval date

Current ICF Date/Version

Meridian Clinical Research, LLC

Site Number

Protocol Number

Specify ICF Type (Main, sub-study, etc.)

Investigator

Sponsor

Date Received by Site

Page ____ of ____

The log should be completed each time a significant change is made by the sponsor ICF. Rationale for the revision and significant summary of change should include enough information to give the site a sufficient overview of the ICF changes to date.

Informed Consent Form (ICF) Tracking Log

Section 13

MCR Logs Daily Temperature Log Investigator Product Accountability Log Dry Ice Log Device Accountability Log

Pregnancy Test Log Spin Log Remote Visit Log Protocol Deviation Log

Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

*01-Jan-2022 *02-Jan-2022 03-Jan-2022 04-Jan-2022 05-Jan-2022 06-Jan-2022 07-Jan-2022 *08-Jan-2022 *09-Jan-2022 10-Jan-2022 11-Jan-2022 12-Jan-2022 13-Jan-2022 14-Jan-2022 *15-Jan-2022 *16-Jan-2022 17-Jan-2022 18-Jan-2022 19-Jan-2022 20-Jan-2022 21-Jan-2022 *22-Jan-2022 *23-Jan-2022 24-Jan-2022 25-Jan-2022 26-Jan-2022 27-Jan-2022 28-Jan-2022 *29-Jan-2022 *30-Jan-2022 31-Jan-2022 Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

Daily Temperature Log (Morning Only) | V4-2Dec2021 | *Denotes site is closed

Page 1 of 12

Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Feb-2022 02-Feb-2022 03-Feb-2022 04-Feb-2022 *05-Feb-2022 *06-Feb-2022 07-Feb-2022 08-Feb-2022 09-Feb-2022 10-Feb-2022 11-Feb-2022 *12-Feb-2022 *13-Feb-2022 14-Feb-2022 15-Feb-2022 16-Feb-2022 17-Feb-2022 18-Feb-2022 *19-Feb-2022 *20-Feb-2022 21-Feb-2022 22-Feb-2022 23-Feb-2022 24-Feb-2022 25-Feb-2022 *26-Feb-2022 *27-Feb-2022 28-Feb-2022

Comments: __________________________________________________________________________________________________

Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Mar-2022 02-Mar-2022 03-Mar-2022 04-Mar-2022 *05-Mar-2022 *06-Mar-2022 07-Mar-2022 08-Mar-2022 09-Mar-2022 10-Mar-2022 11-Mar-2022 *12-Mar-2022 *13-Mar-2022 14-Mar-2022 15-Mar-2022 16-Mar-2022 17-Mar-2022 18-Mar-2022 *19-Mar-2022 *20-Mar-2022 21-Mar-2022 22-Mar-2022 23-Mar-2022 24-Mar-2022 25-Mar-2022 *26-Mar-2022 *27-Mar-2022 28-Mar-2022 29-Mar-2022 30-Mar-2022 31-Mar-2022 Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Apr-2022 *02-Apr-2022 *03-Apr-2022 04-Apr-2022 05-Apr-2022 06-Apr-2022 07-Apr-2022 08-Apr-2022 *09-Apr-2022 *10-Apr-2022 11-Apr-2022 12-Apr-2022 13-Apr-2022 14-Apr-2022 15-Apr-2022 *16-Apr-2022 *17-Apr-2022 18-Apr-2022 19-Apr-2022 20-Apr-2022 21-Apr-2022 22-Apr-2022 *23-Apr-2022 *24-Apr-2022 25-Apr-2022 26-Apr-2022 27-Apr-2022 28-Apr-2022 29-Apr-2022 *30-Apr-2022 Comments: __________________________________________________________________________________________________

Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

*01-May-2022 02-May-2022 03-May-2022 04-May-2022 05-May-2022 06-May-2022 *07-May-2022 *08-May-2022 09-May-2022 10-May-2022 11-May-2022 12-May-2022 13-May-2022 *14-May-2022 *15-May-2022 16-May-2022 17-May-2022 18-May-2022 19-May-2022 20-May-2022 *21-May-2022 *22-May-2022 23-May-2022 24-May-2022 25-May-2022 26-May-2022 27-May-2022 *28-May-2022 *29-May-2022 *30-May-2022 31-May-2022 Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Jun-2022 02-Jun-2022 03-Jun-2022 *04-Jun-2022 *05-Jun-2022 06-Jun-2022 07-Jun-2022 08-Jun-2022 09-Jun-2022 10-Jun-2022 *11-Jun-2022 *12-Jun-2022 13-Jun-2022 14-Jun-2022 15-Jun-2022 16-Jun-2022 17-Jun-2022 *18-Jun-2022 *19-Jun-2022 20-Jun-2022 21-Jun-2022 22-Jun-2022 23-Jun-2022 24-Jun-2022 *25-Jun-2022 *26-Jun-2022 27-Jun-2022 28-Jun-2022 29-Jun-2022 30-Jun-2022

Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Jul-2022 *02-Jul-2022 *03-Jul-2022 *04-Jul-2022 05-Jul-2022 06-Jul-2022 07-Jul-2022 08-Jul-2022 *09-Jul-2022 *10-Jul-2022 11-Jul-2022 12-Jul-2022 13-Jul-2022 14-Jul-2022 15-Jul-2022 *16-Jul-2022 *17-Jul-2022 18-Jul-2022 19-Jul-2022 20-Jul-2022 21-Jul-2022 22-Jul-2022 *23-Jul-2022 *24-Jul-2022 25-Jul-2022 26-Jul-2022 27-Jul-2022 28-Jul-2022 29-Jul-2022 *30-Jul-2022 *31-Jul-2022 Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Aug-2022 02-Aug-2022 03-Aug-2022 04-Aug-2022 05-Aug-2022 *06-Aug-2022 *07-Aug-2022 08-Aug-2022 09-Aug-2022 10-Aug-2022 11-Aug-2022 12-Aug-2022 *13-Aug-2022 *14-Aug-2022 15-Aug-2022 16-Aug-2022 17-Aug-2022 18-Aug-2022 19-Aug-2022 *20-Aug-2022 *21-Aug-2022 22-Aug-2022 23-Aug-2022 24-Aug-2022 25-Aug-2022 26-Aug-2022 *27-Aug-2022 *28-Aug-2022 29-Aug-2022 30-Aug-2022 31-Aug-2022 Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Sep-2022 02-Sep-2022 *03-Sep-2022 *04-Sep-2022 *05-Sep-2022 06-Sep-2022 07-Sep-2022 08-Sep-2022 09-Sep-2022 *10-Sep-2022 *11-Sep-2022 12-Sep-2022 13-Sep-2022 14-Sep-2022 15-Sep-2022 16-Sep-2022 *17-Sep-2022 *18-Sep-2022 19-Sep-2022 20-Sep-2022 21-Sep-2022 22-Sep-2022 23-Sep-2022 *24-Sep-2022 *25-Sep-2022 26-Sep-2022 27-Sep-2022 28-Sep-2022 29-Sep-2022 30-Sep-2022 Comments: __________________________________________________________________________________________________

Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

*01-Oct-2022 *02-Oct-2022 03-Oct-2022 04-Oct-2022 05-Oct-2022 06-Oct-2022 07-Oct-2022 *08-Oct-2022 *09-Oct-2022 10-Oct-2022 11-Oct-2022 12-Oct-2022 13-Oct-2022 14-Oct-2022 *15-Oct-2022 *16-Oct-2022 17-Oct-2022 18-Oct-2022 19-Oct-2022 20-Oct-2022 21-Oct-2022 *22-Oct-2022 *23-Oct-2022 24-Oct-2022 25-Oct-2022 26-Oct-2022 27-Oct-2022 28-Oct-2022 *29-Oct-2022 *30-Oct-2022 31-Oct-2022 Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Nov-2022 02-Nov-2022 03-Nov-2022 04-Nov-2022 *05-Nov-2022 *06-Nov-2022 07-Nov-2022 08-Nov-2022 09-Nov-2022 10-Nov-2022 11-Nov-2022 *12-Nov-2022 *13-Nov-2022 14-Nov-2022 15-Nov-2022 16-Nov-2022 17-Nov-2022 18-Nov-2022 *19-Nov-2022 *20-Nov-2022 21-Nov-2022 22-Nov-2022 23-Nov-2022 *24-Nov-2022 25-Nov-2022 *26-Nov-2022 *27-Nov-2022 28-Nov-2022 29-Nov-2022 30-Nov-2022 Comments: __________________________________________________________________________________________________

Meridian Clinical Research, LLC

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Daily Temperature Log (Double-click this area to edit header; changes will affect all pages.) DEVICE NAME: ☐ -80° Freezer ☐ -70°C Freezer ☐ -20°C Freezer ☐ Refrigerator ☐ Ambient DEVICE ID

Date

TEMPERATURE RANGE (°C) to °C

STORAGE UNIT SERIAL NUMBER (S/N)

Time (24hr)

Morning Temperature (XX.X°C) Min Max Actual

SITE ADDRESS

Comments

Initials/Date

01-Dec-2022 02-Dec-2022 *03-Dec-2022 *04-Dec-2022 05-Dec-2022 06-Dec-2022 07-Dec-2022 08-Dec-2022 09-Dec-2022 *10-Dec-2022 *11-Dec-2022 12-Dec-2022 13-Dec-2022 14-Dec-2022 15-Dec-2022 16-Dec-2022 *17-Dec-2022 *18-Dec-2022 19-Dec-2022 20-Dec-2022 21-Dec-2022 22-Dec-2022 23-Dec-2022 *24-Dec-2022 *25-Dec-2022 *26-Dec-2022 27-Dec-2022 28-Dec-2022 29-Dec-2022 30-Dec-2022 *31-Dec-2022 Comments: __________________________________________________________________________________________________ Meridian Clinical Research, LLC

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Use only blue or black ballpoint pens. If an error is made, draw one line through the incorrect entry, initial, date and enter correction. NEVER USE CORRECTION FLUID. For any fields where data is not applicable; write N/A (not applicable). Perform data entry at the time of occurrence. If late entry of data is necessary, provide both the date of entry and date of occurrence, (e.g., 11-Feb-2016 for 09Feb-2016). The entry of a future date is not allowed.

Meridian Clinical Research, LLC

1.

IP Accountability Log – V2.0 - 18Mar2019

Blinded or Unblinded Document: (Pre-populated by study manager or designee). In a blinded study, if unblinded document box is checked, this document is only accessible to unblinded site personnel and requires unblinded site monitor. 2. Storage Requirement: (pre-populated by study manager or designee). Enter appropriate storage requirement (refer to product label). 3. Receipt or Dispense Date: dd/Mmm/yyyy. 4. Lot, Kit, Container Number, Other or Shipment ID #: Check appropriate box (if other, specify). For shipments received, enter shipment ID number (do not list individual container/kit numbers); when dispensing, enter only one kit or container number per line. 5. Study Subject ID Number: Subject’s assigned study number (in some cases this will be randomization number). 6. Quantity of Containers Received (R) or Dispensed (D): Indicate as R +10 (for received 10 containers), D -1 (for dispensed 1 container). 7. Balance (Containers): Write container balance calculated at each receipt of investigational product or dispensation to a subject (this number should always reflect the number of undispensed containers available at site); in cases where a bulk bottle is received and dispensing of single units is required from that bottle, change “(containers)” to “(units)” as appropriate (all changes should be indicated by drawing one line through incorrect entry, initial, date and enter correction). 8. Site Staff Initials: Two designated site staff members document dispensing of investigational product and one or two staff member(s) document receipt of investigational product by initialing the form. 9. Site Monitor Initials: Monitor initials as verification that accountability was performed at site monitoring visit (this confirms that monitor has verified inventory). 10. Subject Returns: Site staff completes when subject returns unused investigational product (open bottles, partial blister packs, etc.). • Quantity of Units Returned: This is number of “units” (e.g. 31 tablets), not containers OR if product was prepared but not administered to subject and is returned to pharmacy, this should be indicated here (additional comments, if needed may be placed in comment section). • Date Returned: dd/Mmm/yyyy (this is the date the subject physically returns the investigational product to the site). • Staff Initials: Site staff performing reconciliation (number of units returned) initials the form. 11. Disposition: The site monitor completes this at time of investigational product return or destruction. • Indicate “R” for return to sponsor/designee or “D” for destruction at site • Date of Disposition: dd/Mmm/yyyy (for investigational product returns, date of disposition is the date that return has been initiated [investigational product is packed and prepared for shipment]). • Staff Initials. • Monitor Initials (acknowledgment that investigational product was destroyed at site or return to sponsor/designee for destruction was initiated). 12. Comments: Use this section to comment on any problems or deviations. * Page ___ of ____: Number pages consecutively; do not fill in “of ____” until study completion. Note: Any undispensed containers that are returned or destroyed should be entered on the IPAL. Enter the individual kit, container or lot number as applicable.



• • • •

Instructions for completing Investigational Product Accountability Log (IPAL)

Investigational Product Accountability Log

Comments: 12

Receipt or Dispense Date 3 dd/Mmm/yyyy or Shipment ID #4

☐ Lot # ☐ Kit # ☐ Container # ☐ Other (specify): Balance (Containers) Staff 7 Initials8

IP Accountability Log – V2.0 - 18Mar2019

Study Subject ID Number (SSID)5

Quantity of Containers Received (R) or Dispensed (D)6

Storage Requirement (refer to product label)

Strength

Investigational Product Name (SIIV)

Units Per Container

Site ID

Site Principal Investigator

Protocol Title

Monitor Initials9

Quantity of Units Returned (NR for not returned) Date Returned dd/Mmm/yyyy

SUBJECT RETURNS10

DISPOSITION11 Return (R) to Sponsor/ Staff Designee or Initials Destroy (D)

Dosage Form

Protocol #

Staff Monitor Initials Initials

*Page ____ of ____

Date of Disposition dd/Mmm/ yyyy

☐ Blinded Document ☐ Unblinded Document1

Date:

Sponsor + Protocol

am pl e

Ex

6

g

Lo

Full or split?

y.

O nl

Total Pounds Ordered

le d

fil

ou to nl in e.

Total Pounds used (If split amount studies) Notes

Dry Ice Log (Example)

Meridian Clinical Research, LLC

Device Accountability Log | V2 – 4Feb2019

Subject ID #

Device #

Date Rec’d or Dispensed (dd/mmm/yyyy)

Quantity Rec’d, Dispensed, or Returned

Protocol #

Device

Device Accountability Log Date Dispensed Balance Total (ddmmmyyyy)

Site #

Notes

Page ___ of ___

Pregnancy Test Log Principal Investigator

Subject Initials/Subject Number

Sponsor/Protocol Number

Date/Time of Results

Test Results

Site Number

Pregnancy Test Test by Expiration Date Initials Brand/Lot Number (ddmmmyyyy)

☐ Negative ☐ Positive

☐ Negative ☐ Positive

☐ Negative ☐ Positive

☐Negative ☐ Positive

☐Negative

☐ Positive

☐Negative ☐ Positive

☐Negative

☐ Positive

☐Negative ☐ Positive

☐Negative

☐ Positive

☐Negative ☐ Positive

☐Negative

☐ Positive

☐Negative ☐ Positive

☐Negative

☐ Positive

☐Negative ☐ Positive

☐Negative

☐ Positive

Meridian Clinical Research, LLC

Pregancy Test Log | V2 – 23Sep2021

Page 1 of 1

Spin Log SPONSOR …

SUBJECT #

PROTOCOL …

VISIT

DRAW DATE DDMmmYYYY

SITE # …

DRAW TIME 24hr

SPIN START TIME …

PRINCIPAL INVESTIGATOR …

SPIN STOP TIME …

TIME SAMPLE STAFF IN FREEZER INITIALS + … DATE

COMMENTS: …

Meridian Clinical Research

V1.0/26Aug2019

Page 1 of 1

Meridian Clinical Research, LLC

MONITOR NAME

Site:

Principal Investigator (PI):

Protocol Number:

CALL TIME

SITE STAFF SIGNATURE

Remote Monitor Visit Log // V1-03Dec2019

CALL DATE

Remote Monitor Visit Log

PI SIGNATURE

Date of Deviation

Meridian Clinical Research, LLC

Subject Number

Protocol Deviation Log | V2.2 – 18Nov2020

☐ Yes, date:

☐ No

`

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes ☐ No

☐ Yes ☐ No

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

Principal Investigator Name

Page

of

7. Drug Storage/Preparation 10. Diary Noncompliance 8. Drug Administration 11. Noncompliance, Specify (e.g., Trends, 9. Visit Schedule (e.g., Visit Out of Missed Assessments) Window) 12. Other, Specify Does Event Principal Reported to Meet IRB Reported to Staff Initials Inv. Initials the Sponsor? Reporting IRB? and Date and Date Criteria?

Site Number

Deviation Type/Brief Description

4. Prohibited Concomitant Medications/Therapies 5. AE/SAE Reporting 6. Regulatory

Time/Date Deviation Identified

Deviation Type 1. Informed Consent 2. Inclusion Criteria (Specify Criteria #) 3. Exclusion Criteria (Specify Criteria #)

Sponsor/Protocol Number

Protocol Deviation Log

Subject Number

Date of Deviation

Sponsor/Protocol Number

Deviation Type/Brief Description

Protocol Deviation Log | V2.2 – 18Nov2020

Time/Date Deviation Identified

Site Number

☐ Yes, date:

☐ No `

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes ☐ No

☐ Yes ☐ No

☐ Yes ☐ No

☐ Yes ☐ No

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

☐ No

☐ Yes, date:

Page

of

Does Event Principal Reported to Meet IRB Reported to Staff Initials Inv. Initials the Sponsor? Reporting IRB? and Date and Date Criteria?

Principal Investigator Name

Section 14 MCR Forms Safety Committee Review Request PCP Notification Letter

Certified Letter Template Additional Source Page Investigator Diary Review AE Intake Form On-site Destruction Record On-site IP Destruction Record

Health Screening Form Patient Demographic Form Authorization to Release Medical Information Communication Documentation

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Address City

State

Phone

Fax

Include Full Address, Physician Name, and Phone if Possible

ZIP

>

Email

☐ Fax my records to:

☐ Email* my records to:

*Emailed records must be delivered to a secure address.

3: Information to be Shared At the request of the patient named above, the person/organization listed shall receive access to the following protected health information (which may include records relating to mental healthcare, communicable diseases, HIV or AIDS, and alcohol or drug abuse treatment): ☐ Complete Medical Record (All Information) ☐ Immunization History ☐ Hospital Reports, Discharge Summary ☐ History and Physical ☐ X-Ray, Diagnostic Study ☐ Lab ☐ Consultation Reports ☐ EKG, Cardiac Study ☐ Other: Reason for Request ☐ Personal/Request of the Patient ☐ Treatment/Referral ☐ Other:

4: Patient Rights, Authorization, and Signature The above named person has the following rights:  This statement of consent can be revoked at any time before the disclosure of the information via a written request to this clinic, and it expires at the end of the research study. A copy of this authorization shall be valid as the original.  This authorization is effective for the requested and authorized health care information only. You may ask for and receive a copy of this authorization form. (There may be a fee associated with copying records. If for personal use, you are entitled to one copy of your personal health information record free of charge.

Additional copies for you, future releases to you, or releases to other providers, persons, or facilities may be subject to a reasonable charge. Please contact a clinic office manager or site administrator for additional information about applicable copying fees.)  You may refuse to sign this authorization. Such refusal will not affect your ability to obtain treatment except to the extent that the information being requested may assist your health care provider in determining appropriate treatment.  You have the right to inspect the information you are authorizing to be re-released.

 The information you are authorizing to be released could be re-released or disclosed by the recipient. Such additional disclosures or releases may not be prohibited by law. We are not responsible for the actions of others who may be provided with information released as a result of this authorization. PLEASE NOTE: Unless otherwise specified by law, we will release only that information created by our employees or agents, including chart notes, lab results, summaries, and consultation reports. Records created by and available from other providers, hospitals, or other care facilities must be obtained directly from those other providers or facilities.

By signing below, the patient hereby authorizes the Person/Organization Releasing Information and the Person/Organization Receiving Information to 1) request health information from, 2) send health information to, and/or 3) discuss health information with one another. I request and authorize the sharing of my complete medical records to the organization(s) or individual(s) named on this request. I understand that the information to be released includes information regarding the following condition(s). x Signature of Patient, Parent, or Legal Authorized Representative†

Date

†Relationship to Patient (if Applicable) Meridian Clinical Research, LLC

Medical Information Release Authorization Form: V3.0 Updated 8July2021

Page 1 of 1

Communication Documentation Date and Time Sponsor Protocol PI Name Site Number Call To/From Topic Discussed Document the Discussion

Call Outcome

Signature

Date

To be filed in regulatory binder in Correspondence Tab

Meridian Clinical Research

Communication Documentation // V1.0 5May2020

Page 1 of 1

Section 15

Chart Labels

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

 HARD STICK-CRC: ____________  RIGHT ARM  LEFT ARM  HOH  PASS-OUT POTENTIAL  ALLERGIES ______________  SPANISH SPEAKING ONLY OR OTHER LANGUAGE  DEVICE PROVIDED TO PATIENT-REMIND TO BRING  GENERAL: ____________________________________ ________________________________________________

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Sponsor Indication Protocol Number PI

Visit

QC

EDC

Visit

QC

EDC

Visit

QC

EDC

Visit

QC

EDC

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

CHILDBEARING POTENTIAL UPT REQUIRED

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