SOP #: AUD-102 (formerly QA-706) Page: 1 of 8 Effective Date: 1/14/2016 1. POLICY STATEMENT: Prompt notification is required to inform key associated leadership and study personnel of pending inspections and audits. The Overall Principal Investigator (PI) and the responsible Clinical Trials Office will manage the notifications and logistics to ensure appropriate, complete and timely alert. In the event of an audit from the Food and Drug Administration (FDA) or European Medical Association (EMA), for trials in which a Partners institution was involved in the study, PIs must ensure that the Partners designated officials (see section 6) are notified in addition to the DF/HCC officials. 2. 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 regulatory authorities. 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 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. 3. RESPONSIBLE PERSONNEL: 3.1. Overall Principal Investigator (PI) 3.2. Site Principal Investigator 3.3. Study Coordinator 3.4. Clinical Trials Office Director 3.5. The Office of Data Quality (ODQ) Data and Safety Monitoring Manager 3.6. Institutional Official (IO) 4. DEFINITIONS: 4.1. Clinical Trial Office: The institutional entity that provides centralized administrative services that help move cancer clinical trials from initial proposal through study completion. 4.2. External Audit: An independent examination of research related activities and documents to determine whether the research 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 the Food and Drug Administration (FDA), European Medical Association (EMA), National Institutes of Health (NIH), a National Cancer Institute (NCI)/Cooperative Group, regulatory authorities, a research sponsor, or their representatives.
SOP #: AUD-102 (formerly QA-706) Page: 2 of 8 Effective Date 1/14/2016 4.3. Institutional Official (IO): A senior official who, on behalf of a research institution, has the authority and responsibility for the oversight and administration of the institution s human subject research program. 4.4. Lead Research Team: The research team at the same physical location as the DF/HCC Overall PI. 5. PROCEDURE: 5.1. This notification and follow-up process does not apply to routine sponsor monitoring visits. 5.2. Initial Notification: 5.2.1. It is the responsibility of the Overall PI or responsible clinical trials office to communicate impending inspections to DF/HCC as outlined in Section 6 below. 5.2.1.1.The Overall PI or designated research team member will notify the responsible clinical trials office within 1 business day of notification of any external group s plans to inspect or 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 Overall PI or designated research team member should also confirm which DF/HCC sites are to be reviewed as part of the audit or inspection. 5.2.1.2.The Overall PI or designated research team member will notify the Sponsor as soon as possible if notified of an inspection by regulatory authorities, such as the Food and Drug Administration (FDA). 5.2.1.3.The responsible clinical trials office will notify the Office of Human Research Studies (OHRS), the Office of Data Quality (ODQ)Site clinical trials offices, and the Research Pharmacies involved in the study within 1 business day of notification 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.
SOP #: AUD-102 (formerly QA-706) Page: 3 of 8 Effective Date: 1/14/2016 5.2.1.4.In the event of a regulatory agency inspection, the responsible clinical trials office must also notify the DF/HCC Associate Director of Administration, and the appropriate IO and IRB at the site of the Overall PI. 5.2.1.5.For any regulatory audit, OHRS and ODQ are to be included in all communications and meetings unless otherwise notified by either office that their participation will be limited. 5.3. Preparing for the Inspection or Audit: 5.3.1. The responsible clinical trials office will schedule a one-on-one meeting with the Overall PI and lead site research team, or affected Site Responsible Investigator and research team in the case of site-based Cooperative Group or sponsor audits, to review trial status, coordinate and plan roles for the inspection and audit, including: 5.3.1.1.Coordinating with Site Responsible Investigators, research teams and applicable clinical trial offices 5.3.1.2.Reserving appropriate space 5.3.1.3.Requesting any required documents (i.e. medical records, off-site storage) 5.3.1.4.Ensuring all regulatory, pharmacy and subject records are accurate, complete and available for review by the external inspector/auditor 5.3.2. A mock audit or review will be scheduled as deemed appropriate by the ODQ. Trials audited in the past six months may not be scheduled for a full ODQ mock audit. 5.4. During the Inspection or Audit: 5.4.1. The responsible clinical trials office must communicate with all involved DF/HCC parities during the audit, including providing summaries of key information, as needed, to ODQ, OHRS, appropriate IOs and Site clinical trials offices.
SOP #: AUD-102 (formerly QA-706) Page: 4 of 8 Effective Date: 1/14/2016 5.5. During the Exit Interview: 5.5.1. The following individuals will participate in the exit interview: Overall PI (as applicable), Site Responsible Investigators (as applicable), an ODQ representative, an OHRS representative (if it is a regulatory audit) and a responsible clinical trials office representative. 5.5.2. The responsible clinical trials office representative will determine if others need to be present for the findings. 5.5.3. The responsible clinical trials office representative, in collaboration with the ODQrepresentative, will record discussion points during the exit interview and will provide summaries of key findings to the involved research team and the Audit Committee. Any significant findings, such as the issuing of a Form FDA 483, clinical hold, suspension or other actionable finding, from regulatory agencies or external sponsors will be communicated the next business day (Monday Friday) to the OHRS, ODQ, appropriate IOs and the DF/HCC Associate Director of Administration. 5.5.4. If a Form FDA 483 is generated, the Overall PI will request a copy. 5.6. Following-up after the Inspection or Audit: 5.6.1. The Overall PI and designated research team member will draft the preliminary response within 10 business days of the exit interview and send it to the responsible clinical trials office for review. 5.6.2. Any results, corrective action plans or follow-up correspondence must be communicated to the responsible clinical trials office and through them to the ODQ for Audit Committee review and other applicable offices or entities (e.g., OHRS, pharmacy, etc.). 5.6.3. The responsible clinical trials office and other applicable offices will review and approve the preliminary response before sending it to the reviewing sponsor/agency. 5.6.4. Responses to Form FDA 483 are due at the FDA no later than 15 business days after the exit interview.
SOP #: AUD-102 (formerly QA-706) Page: 5 of 8 Effective Date: 1/14/16 6. DF/HCC External Audit Contact List DF/HCC EXTERNAL AUDIT CONTACT LIST It is the responsibility of the Overall Principal Investigator to notify DF/HCC entities in advance of an external audit. This checklist is intended for use in determining who needs to be notified of an external audit. DF/HCC ODQ Nicholas Farley Director, ODQ nfarley@partners.org Nareg Grigorian Data&Safety Monitoring Manager ngrigorian@partners.org OHRS Michele Russell-Einhorn, JD Senior Director, OHRS mrussell-einhorn@partners.org DF/HCC Research Pharmacy Sylvia Bartel Director, Research Pharmacy sbartel@partners.org Dana-Farber Cancer Institute* *Includes Dana-Farber Cancer Institute, Dana-Farber/Brigham and Women s Cancer Care and Dana-Farber/Boston Children s Cancer and Blood Disorders Center DFCI Clinical Trials Office DFCI Main Pharmacy Pediatric Pharmacy Anne Daoust Director Clinical Trials Compliance, DFCI CTO adaoust@partner.org Caroline Harvey Supervisor, Research Pharmacy charvey@partners.org Caroline Harvey Supervisor, Research Pharmacy charvey@partners.org
SOP #: AUD-102 (formerly QA-706) Page: 6 of 8 Effective Date: 1/14/16 Beth Israel Deaconess Medical Center BIDMC Cancer Clinical Trials Office Jonathan Dinsmore, PhD Director, BIDMC CCTO jdinsmor@bidmc.harvard.edu BIDMC Pharmacy Michael Mosny Research Pharmacy mmosny@bidmc.harvard.edu Heena Patel Research Pharmacy hpatel@bidmc.harvard.edu Hina Jolin Research Pharmacy ljoshi@partners.org Massachusetts General Hospital MGH Cancer Center Protocol Office Robert Herman Director, MGH CCPO rherman1@partners.org Shannon Himber Associate Director, CCPO shimber@mgh.harvard.edu MGH Pharmacy Lalit Joshi Research Pharmacy ljoshi@partners.org In the Event of an Audit from the FDA: The Overall PI must notify Partners Contacts Listed Below: Elizabeth Hohmann, MD Chair, Partners IRB ehohmann@mgh.harvard.edu AND Rosalyn Gray Director of Human Research Review and Compliance Rgray1@partners.org
SOP #: AUD-102 (formerly QA-706) Page: 7 of 8 Effective Date1/14/2016 7. Hosting Audits with the FDA 7.1. In preparation for the FDA Audit: The Primary Investigator should prepare a list of all active and inactive studies where he/she is the Principal Investigator. The FDA will request to see this list when they arrive. It should include: protocol #s, protocol titles, product names, names of sponsors and study start and end dates 7.2. In preparation for the FDA Audit: The Primary Investigator should assure that the FDA inspector will have access to any electronic research records that will be needed. This may involve requesting access to the Patient electronic medical records system from the Partners IT department. This should be done in advance of the inspector s visit if possible. 7.3. When the FDA Inspector arrives at the site, the Primary Investigator should be available to meet and greet the auditor, and accept and sign the Form FDA 482 (Notice of Intent to Audit) 7.4. The PI should ask to view the inspector s credentials, but do not photocopy them 7.5. Provide the auditor or inspector with a comfortable place to work with ample space to organize materials. Keep the room free of non-protocol materials or subject information. Lock any cabinets and drawers in the room. 7.6. The FDA inspector should be escorted by a designated member of the study team at all times they are within the institution. 7.7. Gather key study personnel and introduce them to the FDA auditor 7.8. It is recommended that all study documents be stored in a separate room from where the inspector is conducting the audit. Only those documents that are requested by the inspectorshould be brought into the conference room/office. 7.9. Copying Documents: During the course of the audit, FDA inspectors may make copies of documents as necessary, but are not permitted to remove original documents from the institution grounds. If the inspector requests copies of study documents, make sure to clearly document what was copied, and keep a log of the date of the request, the name of the document and the name of the staff member providing the document. 7.10. During the Inspection: The Overall PI should adjust his or her schedule and be available to address questions or requests the auditor or inspector may have during the audit. The Overall PI or designee designate should plan on checking-in at least three times during each day, once in the morning, mid-day and towards late afternoon or at the timeframes agreed upon with the auditor or inspector. If the Overall PI tells the auditor or inspector that he or she will be available at a given time, be sure to keep the time. Do not make the auditor or inspector wait.
SOP #: AUD-102 (formerly QA-706) Page: 8 of 8 Effective Date: 1/14/16 7.10.1. The Overall PI will designate a research team member as a liaison to facilitate the auditor or inspector. This designated liaison (or point person) will function as the auditor or inspector s escort. The designated liaison/escort will act as the coordinator for the audit and will keep written record of all audit related activities, including all document requests or requests for personnel interviews. Upon request, all research team members should be available to answer questions of which they have direct knowledge. 7.10.2. Confirm with the auditor or inspector his or her preference for handling issues and queries. Provide the appropriate pager number and paging instructions in case he or she needs to reach the Overall PI or the designee prior to the agreed meeting time. Remember to track all requests from the auditor or inspector and make photocopies, if appropriate. 7.10.3. During the audit, it is likely the auditor or inspector will make observations relating to the conduct of the trial, documentation, etc. The designated liaison/escort should work with the research team to make every effort to address and correct these observations while the audit or inspection is taking place 7.10.4. Do not volunteer information; answer all questions briefly, honestly and accurately. Do not elaborate on a question unless questioned further for detail. When appropriate, limit responses to yes or no answers. Only answer questions of which you have direct knowledge. Be confident that your response is accurate and factual and be prepared to supply supporting documentation. 7.10.5. Limit offers of hospitality to simple beverages such as water, coffee, tea or juice. It is not appropriate to provide food items. 7.11. The Exit Interview: At the end of the inspection, the FDA inspector will conduct an exit interview. Refer to section 5.5 above for a list of required attendees. Interactions during the exit interview should take place primarily between the Overall PI and the inspector. If an FDA Form 483 is issued, make sure to obtain a copy before the inspector leaves. Refer to section 5.6 above for response guidance. 8. APPLICABLE REGULATIONS & GUIDELINES: 21 CFR 50 Protection of Human Research Subjects 21 CFR 54 Financial Disclosure by Clinical Investigators 21 CFR 56 Institutional Review Boards 21 CFR 312 - Investigational New Drugs Drugs for Human Use 21 CFR 812 - Investigational Device Exemptions 45 CFR 46 Protection of Human Subjects FDA Industry Guidelines and Information Sheets FDA Compliance Policy Guidance Programs: 7348.809, 7348.810, and 7348.811 9. RELATED REFERENCES: International Conference on Harmonisation E6 Version: 8 Effective Date: 1/14/2016 Last Reviewed Date: 12/08/2015