TEMPLATE FOR CLINICAL RESEARCH Sponsor-Investigator to adopt for use as applicable See Policy VI.

01

Standard Operating Procedure FDA 001 Facilitating FDA Inspections Adopted: 07/2008 Rev. Date: Rev. No: Page 1 of 4

FACILITATING FDA INSPECTIONS I. PURPOSE To outline the process of a FDA inspection at a clinical site and describe activities that should be done to facilitate the inspection. II. SCOPE Applies to all personnel involved in the implementation and coordination of clinical investigations. Personnel responsible: Investigator/Co-investigator(s) and, when delegated by the investigator, sub-investigator(s) and clinical research coordinators. III. BACKGROUND FDA inspections are typically conducted at clinical sites to determine compliance with federal regulations and adherence to guidelines, to verify the validity and integrity of clinical data submitted in applications for approval, and to assure that the rights and welfare of subjects participating in clinical studies have been protected. In accordance with: Title 21 CFR 312.62 - Investigator Record Keeping and Record Retention for Clinical Drug or Biological Trials Title 21 CFR 812.140 - Investigator Record Keeping and Record Retention for Device Trials ICH GCP Consolidated Guideline - Part 4.9 Records and Reports ICH GCP Consolidated Guideline'- Part 5.15 Record Access FDA Compliance Program Guidance Manuals 7348.811 Investigators IV. PROCEDURE

Upon request of a FDA investigator, the principal investigator will obtain and have readily available all requested trial-related records. a. The Lead study coordinator or Research Manager will contact Medical Records for the original clinic or hospital chart(s) for any episode of care for all CRFs associated with the trial.

University of Cincinnati Compliance Program

TEMPLATE FOR CLINICAL RESEARCH Sponsor-Investigator to adopt for use as applicable See Policy VI.01

Standard Operating Procedure FDA 001 Facilitating FDA Inspections Adopted: 07/2008 Rev. Date: Rev. No: Page 2 of 4

b.

c.

Medical Records off site will be requested in writing and will be couriered or sent to the audit site within (insert time frame here) days of the request. The Research Manager will communicate any difficulty in obtaining charts to the PI and / or legal in order to facilitate collection of required materials.

2. Upon notification of an impending FDA audit, the clinical site research personnel who first received notification will inform the principal investigator, Sponsor, lead study coordinator and/or site manager, regulatory, including the Office of Research Compliance and legal. (see attached telephone tree or contact list template Appendix 020) 3. The principal investigator will be available during the FDA inspection. If the proposed date of the audit is inconvenient for the principal investigator, the principal investigator or designee may contact the FDA investigator to request rescheduling at a mutually convenient time. 4. The principal investigator will inform the study personnel and the sponsor of the impending inspection. The principal investigator will encourage the study personnel to cooperate with the FDA investigator(s). All study personnel will be available to answer questions of which they have direct knowledge. 5. In preparation for the audit, the lead study coordinator, designee or site manager will gather all study-related records including CRFs, source documents and regulatory files. These documents will be kept in a separate room near the room where FDA will be working. 6. The principal investigators staff will designate a documents person to obtain any requested items for the FDA inspector. 7. The lead study coordinator or site manager will organize all study-related files, arrange logistics and prepare for the audit according to the FDA investigator's request. a. The Principal Investigator will designate a clinical site research person as a liaison to facilitate the audit. This designated liaison (or point person) will function as the escort for the FDA investigator(s) and will take all document requests or requests for personnel interviews to the document person.

University of Cincinnati Compliance Program

TEMPLATE FOR CLINICAL RESEARCH Sponsor-Investigator to adopt for use as applicable See Policy VI.01

Standard Operating Procedure FDA 001 Facilitating FDA Inspections Adopted: 07/2008 Rev. Date: Rev. No: Page 3 of 4

8. During the audit, the person in authority will: a. Greet the FDA investigator(s) and verify identification/credentials. This should be the Principal Investigator. The FDA will provide the PI with the FDA 482 (Notice of Inspection). FDA regulations require the FDA Investigator to give the FDA 482 to the most responsible individual. b. Provide requested records c. Assist in assuring that each question is answered by person(s) knowledgeable about the issue. d. Accompany FDA investigator(s) during tours and interviews e. Assist the FDA investigator(s) as needed f. Arrange for follow-up if required to any unanswered questions or unfulfilled document reports. Note: FDA Compliance Program Guidance Manuals 7348.811 provides a list of information that will be requested during every inspection. This reference may be of substantial use in preparing for the inspection. 9. During the audit, the designated liaison will take notes concerning the progress of the audit. These notes shall include those described in items 10-12 and 14. A form may be used to assist in this task, with spaces for the Investigators name (if a team inspection), document requested, date and time of request, date and time delivered. 10. Pass along requests to the document person who will obtain requested records and make photocopies for the FDA and clinical site. 11. The liaison will pass along requests from FDA to interview research personnel to the documents person who will arrange such meetings. 12. The liaison will document any line of questioning pursued by the Investigator(s) should be summarized, including significant information provided in response. 13. The principal investigator and those he or she designates should request an end of day session with the FDA to review any findings. 14. The liaison will document any questions whose answer could not be provided, along with appropriate follow-up to obtain the requested information

University of Cincinnati Compliance Program

TEMPLATE FOR CLINICAL RESEARCH Sponsor-Investigator to adopt for use as applicable See Policy VI.01

Standard Operating Procedure FDA 001 Facilitating FDA Inspections Adopted: 07/2008 Rev. Date: Rev. No: Page 4 of 4

15. If possible, the principal investigator will meet with the FDA Investigator(s) at the conclusion of the audit to discuss any questions or findings. 16. If the principal investigator receives a Form FDA 483 (report of observations) after the audit, he/she should consult the sponsor and/or legal on how to respond. 17. The principal investigator or designee should send a copy of the Form FDA 483 to the sponsor's project manager and to the Office of Research Compliance. 18. The principal investigator will prepare a written response to any observations noted in the Form FDA 483 and send the response to the FDA within approximately ten days of receiving the report. The written response should: Address each observation and explain what steps have been or are being taken to remedy the observation and prevent future occurrences of similar observations. a. Be factual, professional and cooperative. (be sure to insert here language that addresses legal counsels involvement per your sites policy) 19. The principal investigator or designee should attempt to obtain a copy of the official FDA investigator's field audit report [Establishment Inspection Report (EIR)] under the Freedom of Information Act.

University of Cincinnati Compliance Program