DANA-FARBER / HARVARD CANCER CENTER STANDARD OPERATING PROCEDURES FOR CLINICAL RESEARCH

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1 DANA-FARBER / HARVARD CANCER CENTER STANDARD OPERATING PROCEDURES FOR CLINICAL RESEARCH TITLE: SOP #: QA-706 Page: 1 of 7 Applicable Regulations & Guidelines: 21 CFR General Responsibilities of Investigators 21 CFR Investigator Recordkeeping and Record Retention 21 CFR Investigator Reports 21 CFR Assurance of IRB Review September 1993 FDA Internal Compliance Program Guidance Manual, 17348: 811 Clinical Investigators FDA Sheets, October 1998 May 1997 FDA Clinical Investigator Inspections International Conference on Harmonisation; Good Clinical Practice: Consolidated Guideline (E6), sections 3, 4, 5 and 8 Other References: QA-719 Audit Preparation and Response QA-701 Responsibilities of the Clinical Investigations Leadership Committee (CLC) QA-702 Responsibilities of the Audit Committee Attachments: A. DF/HCC External Audit Contact List B. Sample IND/IDE Responsibility Checklist C. QACT Audit Manual: Appendix A, Audit Review Form Responsible Personnel: Overall Principal Investigator (PI), Site Principal Investigators, Study Coordinators (CRCs/CRAs), Clinical Trials Offices (CTOs), Quality Assurance Office for Clinical Trials (QACT), Office for Human Research Studies (OHRS), Institutional Officials (IOs), Research Pharmacy, DF/HCC Audit Committee Policy Statement: It is the responsibility of the Overall PI and the Lead Clinical Trials Office (CTO) to manage the external audit process. They will work together to ensure that communication and logistics related to the audit are appropriate, complete, and timely. Background: All audits/inspections strive to ensure the protection of human subjects and the quality and integrity of the data and information submitted to the Institutional Review Board (IRB), Sponsor, and the FDA. DF/HCC has a vested interest in the quality of the research that is performed at the facility and in maintaining its collective reputation as an outstanding research community. Because of the center s complicated structure and many sources of funding and support, it is critical for it to have an overall understanding of the workings and results of any external audits/inspections. This allows DF/HCC to develop systems to resolve problems when necessary.

2 SOP #: QA-706 Page: 2 of 7 Definitions: External Audit: An independent examination of trial-related activities and documents to determine whether the trial-related activities were conducted, recorded, and accurately reported according to the protocol, sponsor s procedures, and the applicable regulatory requirements. This may include but is not limited to examinations requested or directed by NIH, an NCI/Cooperative Group, the FDA, the study s sponsor, or their representatives. Institutional Official (IO): The individual at a research facility who is authorized to legally commit on behalf of the research facility that the requirements of the Code of Federal Regulations will be met. Lead CTO: The clinical trials office at the same physical location as the DF/HCC Overall PI. Lead Study Team: The study team at the same physical location as the DF/HCC Overall PI. Procedures: A. Roles and Responsibilities: Overall Principal Investigator (PI) Has the ultimate responsibility for the conduct of the protocol. May delegate responsibility for audit preparation to the study team but must be aware of all issues. Must have one-on-one instruction from the Lead CTO about audit expectations. Lead Study Team Works with Overall PI and Lead CTO to prepare for the external audit. Maintains the master regulatory binder for the protocol. Lead CTO Takes a leadership role in coordinating the external audit with the Overall PI (Attachment A, DF/HCC External Audit Contact List). Meets with the Overall PI and study teams to review their responsibilities for the audit and DF/HCC expectations.

3 SOP #: QA-706 Page: 3 of 7 Site PI Responsible for communicating with the Overall PI and may need to be present at the exit interview. Site Study Team Works with the Lead Study Team, Site PI and Site CTO to prepare for external audits. Maintains a site-specific regulatory binder. Site CTO Works with the Site Study Team to ensure that audit preparation is on track and that the Site PI is aware of his/her responsibilities. Works with the Lead CTO to ensure a coordinated effort. OHRS Will ensure regulatory files are available for the study team to review and will support the study team as needed. QACT Will perform a mock audit prior to all FDA audits, and attempt a mock audit prior to other external audits, to assist the study team with preparations and ensure regulatory compliance. Must receive a copy of the final audit result and PI s response, if applicable, in order to present the information to the DF/HCC Audit Committee. Research Pharmacy Maintain original drug accountability forms. Ensure that the study drug is properly accounted for, storage is appropriate and that drug returns are managed. DFCI Institutional Official Must always be notified of results since DFCI is the IRB of record.

4 SOP #: QA-706 Page: 4 of 7 B. Initial Notification: It is the responsibility of the Lead PI or designee to communicate with study teams, Site PIs, and the CTO at his/her institution. The Overall PI or designee will notify the Lead CTO within 24 hours of notification of any external group s plans to audit a protocol at DF/HCC, providing the following details: date, time, location, and purpose of the audit, as well as the identity of the auditors and the principal DF/HCC study contact. The Lead CTO will notify the OHRS, QACT, and the appropriate Institutional Officials, Site CTOs, and the Research Pharmacies involved in the study within 24 hours of notification of the impending audit and which study is being reviewed. Note: This notification process does not apply to routine sponsor monitoring visits. C. Preparing for the Audit: Overall PI If notified of an FDA audit, notify the sponsor as soon as possible. Schedule one-on-one with Lead CTO. Lead CTO Schedule the mock audit with QACT. Finalize roles prior to the audit. Site CTO Work with the Lead CTO to coordinate and plan roles for the audit. Reserve a conference room in a private area for the mock and actual audits.

5 SOP #: QA-706 Page: 5 of 7 Study Teams Request the medical records for all subjects enrolled in the study identified as the focus of the external audit. Work with QACT to ensure that all documentation, including informed consent forms, source documents, case report forms (CRFs), and the regulatory binder for the identified study are accurate, complete and available for review by the external auditor (Attachment B, Sample IND/IDE Responsibility Checklist; Attachment C, QACT Audit Manual: Appendix A, Audit Review Form). Ensure that records of staff qualifications and training are available for review by the external auditor or inspector. QACT Perform an internal review of the study files (Attachment C, QACT Audit Manual: Appendix A, Audit Review Form). Research Pharmacy Ensure that all drug accountability forms and documents relating to the receipt, distribution and return/destruction of the study drug are accurate, complete and available for review. If there were any instances in which emergency breaking of the blind was required, have that documentation available. Institutional Officials Provide necessary support for the study teams being audited

6 SOP #: QA-706 Page: 6 of 7 D. During the External Audit: Overall PI Meet with the auditor or inspector. Request to see identification, and if this is an FDA audit, request Form FDA 482 Notice of Inspection. Ensure that questions posed by the auditor or inspector are answered promptly, directly, and honestly by appropriate study personnel. Lead CTO Meet with the auditor or inspector. Assign someone to meet and escort the auditor or inspector. Ensure all information is made available. Notify the Site CTOs as applicable, OHRS, QACT and Research Pharmacy of audit plans. Continue to communicate with all involved DF/HCC parties during the audit. Provide a summary of key information, as needed, to OHRS, QACT, appropriate IOs and Site CTOs. Communicate final audit results within 24 hours of being available to Site PIs, study teams, QACT, OHRS, and the applicable CTOs and IOs. Study Teams Provide orientation and access to the study records and files. Be available to the auditor or inspector at all times. If the auditor or inspector requests a tour of the facility where the research took place, immediately notify staff in those areas and accompany the auditor or inspector at all times. Keep in mind that FDA inspectors should not be in/around patient care and research staff workspaces. Provide copies of requested studyrelated documents, retaining a photocopy of what was requested.

7 SOP #: QA-706 Page: 7 of 7 E. During the Exit Interview: The following individuals will participate in the exit interview: Overall PI, Site PI (as applicable), a DF/HCC representative (OHRS or QACT), and the Lead CTO representative. The Lead CTO representative will determine if others need to be present for the findings. If a Form FDA 483 is generated, the Overall PI will request a copy. F. Following-up after the Audit: The Overall PI and Lead Site Study Team will draft the preliminary response within 10 business days of the exit interview. The Lead CTO will review and approve the preliminary response before sending it to the reviewing sponsor/agency. o Note: Responses to Form FDA 483 are due at the FDA no later than 15 business days after the exit interview. Any results, corrective action plans or follow-up correspondence must be communicated to the Lead CTO and through them to the necessary offices (e.g., OHRS, QACT, etc.). The DF/HCC Audit Committee will review findings from all external audits. Original Approval Date: CLINPOC 11/16/04 Last Review Date: 2/1/11 Revision Dates: 10/31/07, 6/21/09, 2/1/11 (QA-706 & OV-1001 merged) Effective Date: 11/16/04, 11/30/07, 7/21/09, 2/1/11