Anatomy of an FDA Audit Trigger Prevention and Process

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1 Robert S. Walsh, MD, MBA, FAHA, FCCP Walsh Medical Consulting 15 th Annual Product Complaints Congress Crystal City, VA 14 June 2017

2 How many here are from Pharma? Medical Device Industry? Biotechnology? CROs? Clinical Sites?

3 What does the FDA inspect? FDA inspects manufacturers or processors of FDA-regulated products to verify that they comply with relevant regulations. Those inspected include vaccine and drug manufacturers blood banks food processing facilities dairy farms animal feed processors compounding pharmacies FDA also inspects facilities that conduct studies in people (clinical trials) laboratories that conduct studies in animals or microorganisms when these studies are used to apply for FDA approval of a medical product foreign manufacturing and processing sites for FDA-regulated products that are sold in the United States imported regulated products at the border FDA conducts several types of inspections to help protect consumers from unsafe products: pre-approval inspection after a company submits an application to FDA to market a new product routine inspection of a regulated facility for-cause inspection to investigate a specific problem that has come to FDA s attention

4 What does the FDA inspect? FDA inspects manufacturers or processors of FDA- regulated products to verify that they comply with relevant regulations. Those inspected include: vaccine and drug manufacturers blood banks food processing facilities dairy farms animal feed processors compounding pharmacies

5 FDA also inspects: facilities that conduct studies in people (clinical trials) laboratories that conduct studies in animals or microorganisms when these studies are used to apply for FDA approval of a medical product foreign manufacturing and processing sites for FDA-regulated products that are sold in the United States imported regulated products at the border

6 What does the FDA inspect? FDA conducts several types of inspections to help protect consumers from unsafe products: pre-approval inspection after a company submits an application to FDA to market a new product routine inspection of a regulated facility for-cause inspection to investigate a specific problem that has come to FDA s attention

7 What does the FDA inspect? FDA conducts several types of inspections to help protect consumers from unsafe products: pre-approval inspection after a company submits an application to FDA to market a new product routine inspection of a regulated facility for-cause inspection to investigate a specific problem that has come to FDA s attention

8 FDA responds to information that it receives from whatever the source might be. -- Typically this is from the company itself - MDRs - interim reports -- Sometimes it may be from patients, doctors or health facilities

9 Basically, there are two different kinds of FDA audits that can be triggered here to discuss 1. Manufacturing sites/headquarters 2. Clinical sites (BIMO = Bioresearch Monitoring Program)

10 Manufacturing Sites/Headquarters: 1. Field Actions Number Failed corrections Inadequate response Failure to close in a timely fashion 2. MDRs Increase in numbers Increase in severity/change in the Risk Benefit UADEs Complaints from the field Journal articles/lay press 3. Findings on Routine Audits Failure to follow SOPs or Regulations Failure to Open/Close CAPAs Failure to correctly file/timeliness on MDRs

11 What can one do proactively? Follow the regulations and SOPs!

12 Triggers of a for-cause BIMO audit by the FDA include: 1. A complaint 2. Sponsor concerns 3. IRB concerns 4. Termination of a clinical site 5. During ongoing clinical trials to provide realtime assessment of the investigator s conduct of the trial and protection of human subjects 6. Multiple protocol deviations or AEs 7. FDA identified a special interest 8. at the request of an FDA review division (fasttracked)

13 BIMO Audit Triggers: -- Marketing application will trigger a response -- Top three enrolling sites -- PI with previous problems -- Evidence that an investigator has a significant financial interest in the product -- Having apparent access to too many patients with a specific disease state for the locale or practice setting -- Reporting significantly better efficacy, fewer adverse effects, or different laboratory results than other investigators studying the same drug -- Conducting clinical studies outside of one s field of specialization -- Conducting a large volume of clinical trials

14 Most Common Findings: 1. Failure to follow the Investigational Plan 2. Protocol Deviations 3. Inadequate Recordkeeping 4. Failure to control the investigational devices 5. Inadequate communication with the IRB 6. Inadequate protection of subjects 1. Failure to report AEs 2. Informed consent issues

15 TIPS Develop compliance plans to ensure proper trial management: 1. SOPs to ensure consistency 2. Follow them! 3. Source documentation: keep everything! Maintain all original source documents, data and records that correspond to the CRFs, including all s. 4. Check list logs: verify completion. 5. Use Notes-to-file to explain any aberrations. 6. Use mock audits! Hire outside people with auditing experience.

16 REFERENCES 1. Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors FDA Inspections of Clinical Investigators, June Retrieved from pdf 2. An FDA audit is no reason to panic: These 10 steps can help you prepare. April 1, AHC Media. Retrieved from: 3. Li et al. Common Reasons for For-Cause Inspections in Bioequivalence Studies Submitted to the Food and Drug Administration. AAPS J Jan; 15(1):

17 Any question? Rob Walsh, MD