Office of Human Research
Page Title

SOP No.: 503    DOCUMENTATION AND RECORDS RETENTION

Author:    Office of Human Research

Effective Date:  October 1, 2007

Supercedes document dated:              N/A

Last Reviewed on:     N/A                                 

Results of Review:               N/A

This SOP pertains to:  the documents and records that are accumulated during the conduct of all FDA-regulated human subject research within Thomas Jefferson University. It also applies to the Investigator, Monitors, and key study personnel who develop, review and archive research-related documents and records.

Responsibility for executing this SOP:  Investigator and Designated Research Personnel

Approved By:

 

J. Bruce Smith, MD

 

Associate Vice President for Research

 

(signature on file at OHR)

Approved By:

 

Steven E. McKenzie, MD, Ph.D.

 

Vice President for Research

 

(signature on file at OHR)

 

1. INTRODUCTION AND PURPOSE

This procedure describes the processes followed by the Investigator and all participating Co-Investigators for the creation, management, review and maintenance of files pertaining to the conduct of FDA-regulated human subject research.

2. GENERAL INSTRUCTIONS AND RESPONSIBILITIES

  1. The Investigator and all participating Co-Investigators are responsible for ensuring that complete and precise data are collected, documented, and maintained throughout the course of an investigation involving human participants.
  2. The Monitor is responsible for verifying that the files are complete, accurate and securely maintained by the Investigator and participating Investigators.
  3. The Investigator is responsible for terminating the participation of and discontinuing shipments of investigational product to, any participating Investigator who has failed to maintain or make available required records or reports of the study.
  4. The Investigator should maintain site specific files to best facilitate oversight of participating investigators

3. SPECIFIC PROCEDURES

3.1 Creating the Investigator Regulatory Master File (RMF)

The Investigator should create a protocol specific RMF for each protocol that contains the following:

  1. FDA Form 1571 (if applicable)
  2. FDA Form 1572 for Investigator and all participating investigators (if applicable)
  3. Investigator Brochure (drug/biologic studies) and/or an FDA approved package insert, or Investigational Plan and Report of Prior Investigations (medical device studies).
  4. Signed protocol and amendments, if any and sample case report form(s) (CRF).
  5. Information given to study participant:
    • Informed consent form
    • Any other written information
    • Advertisements for participant recruitment
  6. Financial disclosure information. Specific financial and contractual information should be retained in a separate secure file.
  7. Dated, documented approval from the Institutional Review Boards (IRB) of record for the following:
    • The protocol and any amendments
    • CRF (if applicable)
    • Informed consent form(s)
    • Any other written information to be provided to participant(s)
    • Advertisement for participant recruitment (if used)
    • Any other documents given IRB approval
  8. Committee composition of IRB(s) of record or Federal Wide Assurance (FWA).
  9. Regulatory authorities' authorizations/approvals/notifications of protocol (where required) including copies of all submissions such as the Investigational New Drug (IND) submission, Investigational Device Exemption (IDE) submission, protocols, amendments, supplements, and other related correspondence.
  10. Curricula Vitae (CV) and/or other relevant documents evidencing qualifications of Investigator(s) and Sub-investigator(s).
  11. Normal value(s)/range(s) for medical/laboratory/technical procedure(s) and/or test(s) included in the protocol.
  12. For any medical/laboratory/technical procedures and/or tests, secure and file the following, as available:
    • Certification
    • Accreditation
    • Established quality control and/or external quality assessment
    • Other validation
  13. Sample of label(s) attached to investigational product container(s).
  14. Instructions for handling of investigational product(s) and any other study-related labeling (if not included in protocol or Investigator Brochure).
  15. Shipping records for:
    • Investigational product(s)
    • Study-related materials and incidentals
  16. Certificate(s) of analysis of investigational product(s) shipped.
  17. Record of retained reserve samples (if applicable) of investigational products (quantity, location, etc.).
  18. Decoding procedures for blinded studies.
  19. Master randomization list.
  20. Pre-study site qualification report(s).
  21. Site initiation report(s).

3.2 RMF Maintenance during Study Conduct

The Investigator should add documents listed in A through Y to the RMF, as evidence that all new and relevant information is documented as it becomes available.

  1. Investigator Brochure, FDA approved package insert, or Investigational Plan updates.
  2. Any revision to:
    • 1571 and 1572
    • Protocol/amendment(s) and CRF
    • Informed consent form
    • Any other written information provided to participants
    • Advertisement for participant recruitment (if used)
  3. Dated, documented approval from the IRB(s) of record, of revisions to the following:
    • Protocol amendment(s)
    • Informed consent form
    • Any other written information to be provided to participant
    • Advertisement for participant recruitment
    • Any other documents given approval
  4. Dated, documented evidence of continuing review and approval of study by the IRB(s).
  5. Regulatory authorities' authorizations/approvals/notifications where required for protocol amendment(s) and other documents including copies of all submissions such as IND, IDE, amendments, supplements, and other related correspondence.
  6. CVs for new Investigators and/or Sub-investigator(s).
  7. Updates to normal value(s)/range(s) for medical/laboratory/technical procedure(s)/test(s) included in the protocol.
  8. Updates of medical/laboratory/technical procedures/tests:
    • Certification
    • Accreditation
    • Established quality control and/or external quality assessment
    • Other validation
  9. Documentation of investigational product(s) and study-related materials shipment.
  10. Certificate(s) of analysis for new batches of investigational products.
  11. Routine site monitoring visit report(s).
  12. Relevant communications other than site visits, such as:
    • Letters
    • Meeting notes
    • Notes of telephone calls
  13. Sample informed consent forms including original and all revised and updated versions.
  14. Original signed, dated and completed CRFs.
  15. Original documentation of CRF corrections.
  16. Copies of relevant source documents, if sent by or requested from the site, with participant identifiers redacted.
  17. Notifications by originating Investigator to Investigator of serious adverse events and related reports.
  18. Notification by Investigator and/or participating Investigators, if needed, to regulatory authorities and all IRB(s) of record of unexpected and serious adverse events and of other safety information.
  19. Notification by Investigator to participating Investigators of safety information.
  20. Interim or annual reports to IRB(s) of record and other authorities.
  21. Subject Screening and Enrollment Logs.
  22. Subject identification code list.
  23. Investigational products accountability at the site.
  24. Study Staff Signature Log.
  25. Record of retained subject body fluids/tissue samples (if any).

3.3 RMF Closure after Study Completion/Termination

The Investigator should confirm that all documents listed above, are in the RMF together with the documents listed below:

  1. Investigational product(s) accountability at site(s).
  2. Documentation of investigational product destruction (if applicable).
  3. Completed participant identification code list.
  4. Audit certificates and reports/FDA inspection reports.
  5. Final study closeout monitoring report(s).
  6. Treatment allocation and decoding documentation.
  7. Final study report by Investigator to Thomas Jefferson University IRB, and where applicable, to the regulatory authorities.
  8. Final study report by participating Investigators to their IRB(s) of record, the Investigator and where applicable, to the regulatory authorities.
  9. Clinical study report.
  10. All RMF contents will be maintained by the Investigator for a minimum of 2 years after the conclusion of the study or FDA marketing approval, whichever is the longer of the two periods.
  11. After that period of time, files may be archived to a secure location.
  12. Archiving procedures must ensure that original records are available within a 24-hour period, if needed.

3.4 Creating the Participating Investigator's Site File

The Sponsor will review the participating Investigator's site file to ensure it contains the documents listed below.

  1. Investigator Brochure (drug/biologic studies) and/or an FDA approved package insert, or Investigational Plan and Report of Prior Investigations (medical device studies).
  2. Signed protocol, amendments, if any, and sample CRF.
  3. Information given to study participants:
    • Informed consent form
    • Any other written information
    • Advertisement for participant recruitment
  4. Financial Disclosure Statement, FDA Form (If applicable)
  5. Signed Investigator Agreement
  6. Dated, documented approval from the local IRB of record for the following:
    • Protocol and any amendments
    • CRF (if applicable)
    • Informed consent form(s)
    • Any other written information to be provided to the participant(s)
    • Advertisement for participant recruitment (if used)
    • Subject compensation (if any)
    • Any other documents given IRB approval
  7. IRB committee composition.
  8. Copies of correspondence of involved parties (eg. Investigator, local IRB, federal regulatory authorities, etc.) and other related correspondence).
  9. CV and/or other relevant document(s) evidencing qualifications of Investigator(s) and Sub-investigator(s).
  10. Normal value(s)/range(s) for medical/laboratory/technical procedure(s) and/or test(s) included in the protocol.
  11. For any medical/laboratory/technical procedures and/or tests, secure and file the following:
    • Certification
    • Accreditation
    • Established quality control and/or external quality assessment
    • Other validation
  12. Sample of label(s) attached to investigational product container(s).
  13. Instructions for handling of investigational product(s) and study-related labeling (if not included in protocol or Investigator Brochure).
  14. Shipping records for:
    • Investigational product(s)
    • Study-related materials and incidentals
  15. Decoding procedures for blinded studies.
  16. Pre-study qualification report (if provided by Investigator).
  17. Study initiation report (if provided by Investigator).

3.5 Site File Maintenance during Study Conduct

The Sponsor will verify that the participating Investigator has added the documents listed below to the site file and individual participant files, as evidence that all new relevant information is documented as it becomes available.

  1. Investigator Brochure and/or an FDA approved package insert, or Investigational Plan updates.
  2. Any revision to:
    • 1572
    • Protocol/amendment(s) and CRF
    • Informed consent form
    • Any other written information provided to participants
    • Advertisement for participant recruitment (if used)
  3. Dated, documented approval from the IRB of record of revisions to the following:
    • Protocol amendment(s)
    • Informed consent form
    • Any other written information to be provided to the participant
    • Advertisement for participant recruitment
    • Any other documents given approval
  4. Dated, documented evidence of continuing review and approval of study by the IRB of record.
  5. Regulatory authorities' authorizations/approvals/notifications where required for protocol amendment(s) and other documents.
  6. CVs for new Investigator(s) and/or Sub-investigator(s).
  7. Updates to normal value(s)/range(s) for medical/laboratory/technical procedure(s)/test(s) included in the protocol.
  8. Updates of medical/laboratory/technical procedures/tests:
    • Certification
    • Accreditation
    • Established quality control and/or external quality assessment
    • Other validation
  9. Documentation of investigational product(s) and study-related materials shipment.
  10. Routine monitoring visit reports (if provided by Investigator).
  11. Relevant communications other than site visits, such as:
    • Letters
    • Meeting notes
    • Notes of telephone calls
  12. Original, signed informed consent forms including original informed consent form and all revised and updated versions.
  13. Original, complete source documentation to verify data reported in CRF, adverse event reports, etc.
  14. Copies of signed, dated and completed CRF.
  15. Copies of documentation of CRF corrections.
  16. Notifications by originating Investigator to Investigator of serious adverse events and related reports.
  17. Notifications by participating Investigators to applicable regulatory authorities and local IRB of unexpected serious adverse drug reactions and of other safety information.
  18. Notification by Investigator to participating Investigators of safety information.
  19. Interim or annual reports to local IRB and other authorities.
  20. Subject Screening and Enrollment Logs.
  21. Subject identification code list.
  22. Investigational products accountability at the site.
  23. Study Staff Signature Log.
  24. Record of retained body fluids/tissue samples (if any).
  25. Original source documents as required.

3.6 Site File Closure after Study Completion/Termination

The designated Monitor will confirm that all documents listed above are in the participating PI's file together with the documents listed below:

  1. Investigational product(s) accountability at site.
  2. Documentation of investigational product destruction.
  3. Completed participant identification code list.
  4. Audit reports/FDA inspection reports (if applicable).
  5. Final study closeout monitoring report.
  6. Treatment allocation and decoding documentation.
  7. Final report by the participating Investigator to the local IRB, the Investigator and where applicable, to the regulatory authorities.
  8. Clinical study report (if required).
  • All site and participant file contents will be maintained by the participating Investigator for a minimum of two (2) years after the conclusion of the study or FDA marketing approval, whichever is the longer of the two periods.
  • After that period of time, files may be archived to a secure location.
  • Archiving procedures must ensure that original records are available within a 24-hour period, if needed.

4. APPLICABLE REGULATIONS AND GUIDELINES

21 CFR 312.50

General responsibilities of sponsors

21 CFR 312.56

Review of ongoing investigations

21 CFR 312.59

Disposition of unused supply of investigational drug

21 CFR 312.60

General responsibilities of investigators

21 CFR 312.62

Investigator recordkeeping and record retention

21 CFR 312.64

Investigator reports

21 CFR 312.66

Assurance of IRB review

21 CFR 312.68

Inspection of investigator's records and reports

September 1993

FDA Compliance Program Guidance Manual 7348.811: Clinical Investigators

September 1994

FDA Compliance Program Guidance Manual 7348.810: Sponsors, Contract Research Organizations and Monitors

January 1988

Guidelines for the Monitoring of Clinical Investigations

May 1997

International Conference on Harmonisation; Good Clinical Practice: Consolidated Guideline

5. REFERENCES TO OTHER APPLICABLE SOPs

GA-102

Responsibilities of the Research Team

SS-203

Investigator and Site Initiation Meetings

PM-301

Site-Sponsor/CRO Communications

PM-303

Regulatory Files and Subject Records

PM-305

Study Termination Visit

PM-306

Investigational Drug Accountability, Storage, Dispensing and Return

DM-501

Data Management

6. ATTACHMENTS

A. Summary of ICH Essential Documents

7. DEFINITIONS AND GLOSSARY

The following definitions from the International Conference on Harmonisation, Good Clinical Practice: Consolidated Guideline apply to this SOP.

The following definitions the International Conference on Harmonisation, Good Clinical Practice: Consolidated Guideline apply to this SOP.

Case Report Form (CRF): A printed, optical, or electronic document designed to record all of the protocol-required information to be reported to the sponsor on each trial subject.

Compliance (in relation to trials): Adherence to all the trial-related requirements, good clinical practice (GCP) requirements, and the applicable regulatory requirements.

 Contract: A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.

Direct Access: Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsors, monitors, and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects’ identities and sponsor’s proprietary information.

Documentation: All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records; and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

Essential Documents: Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.

Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

Investigator: A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.

Monitoring: The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and the applicable regulatory requirement(s).

Protocol: A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents.

Protocol Amendment: A written description of a change(s) to or formal clarification of a protocol.

Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial).

Sponsor: An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

armacy, at the laboratories, and at medico-technical departments involved in the clinical trial).

 

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