Audience Q&A: From Legal Considerations when Interacting with the FDA Webinar

This article covers additional questions submitted from the webinar, Legal Considerations | Interacting with the FDA Before, During, and After Inspections, presented by FDA Law Partner Neil DiSpirito.

In the webinar, Neil discussed the legal concept of the FDA inspection as a Warrantless Search. Removing the 4th and 5th Amendments’ due process clauses in gathering evidence of both an administrative and civil and criminal nature and your rights.

Q&A with Neil DiSpirito

1. Where does legal counsel new to the FDA-regulated industry get reliable, in-depth information?

• • Redica Systems is certainly one place to obtain reliable and accessible data. Redica does a good job of providing FOIA materials. FDLI (Food & Drug Law Institute) is where I learned a lot in my early days of practice. FDLI’s symposia meetings, publications, mentoring, and networking opportunities really provided good insight into the practical aspects of FDA practice that one cannot get from a standard text. FDLI also provides timely updates for new laws and regulations to FDLI’s members. RAPS is another excellent resource for the “nuts and bolts” of regulatory work. RAPS provides a lot of very practical insight. Both organizations are non-profits. Non-profit educational organizations are the best way to learn FDA practice.

2. How can firms balance protecting their rights and confidential data without incurring an event which FDA would consider to constitute delaying, denying, or limiting an inspection?

• • The organization needs to understand what information FDA is entitled to and what they are not. Certainly, you want to provide FDA with all the information they are entitled to by law and regulations, but not what they are not entitled to have. For example, Internal audits, financials, R & D, and non-job-related personnel pages in employee’s files are not in the FDA’s purview or jurisdiction. You can reach out to me or one of my colleagues to have us talk to the FDA if there is an item in contention. You are allowed to consult with a lawyer for legal issues. Once a firm turns over information willingly to the FDA, whether the FDA is entitled to it or not, that information can and will be used against the company.

3. Can FDA “legally” take photos or videos as evidence of violations during inspections (despite the IOM guidance to FDA investigators)?

• • No. Anything in the background of a photo that is deleterious to the firm can be used by the FDA, even if it is not the focus of the photo. At one time, denying the FDA photo-taking opportunities was very easy. Now the investigators are aggressive in pursuing photos. They will cite two legal cases that they suggest are precedents, which allow them to take photos. One case discusses an open-air chemical facility with its operations in plain site that allowed the government to take aerial photos, and one case talks about photos that were taken previously after the company gave permission to the FDA to take the pictures. Neither case applies to a new inspection in a closed-roof building where the company did not give permission for the FDA to take photos. If you agree to allow the FDA to take pictures, take pictures of what the FDA is photographing (do not put the investigator in the picture, as that is not allowed.)

4. Can you record the investigation?

• • The FDA generally does not object to videotaping the inspection; however, if the company videotapes the inspection, the FDA will also videotape the inspection, which never turns out well for the company.

5. What is the FMD-145 requirement for sending EIR’s to the establishment?

• • The FDA will release an EIR if the inspection is deemed closed (no further issues) in accordance with 21 CFR 20.64(d)(3). Inspections requiring further FDA action (i.e., Warning Letters, etc.) are not eligible for release under the same CFR regulation. In practice, if there are issues with the inspection the FDA will not release the EIR to the company until the inspection is closed. As the EIR is the investigators true impressions and assessment of the situation, the FDA for enforcement strategy reasons does not want to release the EIR. A legal consult with an FDA law practitioner is advised in cases with issues.

6. Do you encourage your customers to utilize the QSIT and Preamble?

• • Ensuring the company’s Quality Systems are compliant with FDA regulations is the company’s primary obligation. Organizing your approach under the QSIT methodology the FDA investigators will use during the inspection may lead to a more efficient inspection. The preamble provides the reason “why” the regulation exists or will exist. Compliance can often depend on achieving the “why.” But one thing to remember is that QSIT is not legally binding on the FDA. The FDA has room for interpretation and discretion.

7. If an investigator asks for an affidavit at the end of the inspection what should be the action plan?

• • Most FDA practitioners advise their clients to never sign affidavits. We generally agree with that philosophy. If a situation arises where it is necessary to sign an affidavit, it should only be signed with the legal advice and input of an FDA practice attorney (including edits and modifications to the language.) Otherwise (without legal input) it is never advisable to sign affidavits (especially if they have not been reviewed by an attorney). Also, do not allow the investigator to read you the affidavit and ask you if you agree. It will count as if you have read and signed the affidavit.

8. Is the FDA allowed to request confidential human resources-related records?

• • For example, records detailing disciplinary action against personnel who intentionally didn’t follow procedures.Only if the violation of procedures affected the product or the job, for example, if the procedures violated were GMP procedures, then the FDA can see them. If the procedure violated was not punching in/out for lunch break, then no.

9. If certain FDA 483 observations are inconsistent with the evidence provided during inspections, what is your advice on challenging FDA investigators during the inspections or responding to the observations?

• • The wrap-up meeting is the best place to produce evidence or data that shows why the observation is incorrect or does not rise to the legal level of being included on the Form 483. The company should include its dissent and evidence of the contrary to the observation in the reply (received by FDA within 15 business days after the inspection.)  This is an area where you may want to reach out to me. We may be able to assist you and work this out with FDA compliance/legal.

10. What are the best practices for what to include in responses to the FDA?

• • Include the issue, and talk about how the company has or will correct the issue. Cite any CAPAs or investigations you have opened to find the root cause of the problem and correct it. Also, answer in a way that includes how you modified the system, SOP, or practice to prevent this type of issue from occurring again. Be concise and succinct, and be careful not to open any “new doors” or issues with your response. If it is an ongoing process, offer to update the FDA monthly or quarterly on your progress and let them know when the issue has been resolved.

11. Can FDA legally hold back publishing a warning letter for six months on their website? (Example: Abbott Point of Care Warning Letter issued on Nov 8, 2022, but posted on 4/18/2023)

• • In reality, it happens. Sometimes it happens because of an overload on the FDA system or because they are considering more enforcement action, or because subsequent communications with the company change the status of the issue. More importantly, the company wants to be sure the FDA publishes timely the close-out letter when the company has resolved all its issues, and the matter is closed by the FDA.

12. An inspection agenda is generally not shared by the FDA. Any specific reasons that we should be aware of? Is there a timeline to distribute the EIR after completion of the inspection?

• • Inspection formats will vary depending on the type of inspection and the facility’s regulatory compliance history. For example, a GMP inspection will generally be much more detailed than a pre-approval inspection. A facility with a history of good compliance will experience a faster and smoother inspection generally. Most of us who have dealt with the FDA for any length of time can give our clients a very good approximation of what the FDA will be examining. We can include a discussion of agendas in our next webinar with Redica Systems if you would like. As to EIR distribution, the requirements state that the EIR can be sent after the inspection is closed. If the FDA alleges the company has regulatory compliance issues, then the FDA will not close the inspection, and the Agency will not release the EIR until it is closed. This is another area where I would urge companies to consult legal counsel like us (who can possibly resolve the issue with FDA legal.)

13. From the FDA perspective, please provide case studies and reasons why it’s important for biologics and cell therapy R&D and Preclinical companies to qualify suppliers used (based on a risk-based approach) for Preclinical, Phase 1, and Phase 2 studies.

• • In general, to assess aspects of the biological activity of an investigational product for safety in human and animal use. Assuring the integrity and adequacy of the supply is important in determining whether the product can be used in clinical and pre-clinical testing. Please contact us for case studies, case law, and specific regulatory schemes regarding the FDA’s approach and a more specific answer.

14, In the case of litigation which country law takes precedent?

• • It depends on many factors. What we have to determine with our clients is the location of the company and the facility, jurisdiction, incorporation, foreign or domestic corporate registration, where the products are being used, and a plethora of many other factors. To answer this question specifically, a specific legal analysis applying the law to the facts involved is required.

15. Is there any guidance/regulation specifying the rights of the FDA and the inspected company? Are questions and requests always allowed or forbidden, or must there be a rationale for every demand?

• • Yes, there are regulations and caselaw that determine the reasonableness, times for inspection, what the FDA is allowed to request, and what they are not. The regulations and cases are included in various slides in my Redica Systems webinar presentation.

16. What are your thoughts about the timeliness or lack thereof of FDA 483 to the registered entity post-inspection?

• • Generally, the FDA will give you a copy of the Form 483 to read and discuss with the investigators at the close-out meeting. If you presented additional information at the close out meeting, they may have to edit the copy. Generally, the FDA will send you a formal final copy within a week or two.

17. Can you speak about the voluntary 15-day response time after receiving a 483?

• • We, as FDA practitioners, do not like to think of the 15-day response as “voluntary.” Although there is no requirement to answer the FDA, you are inviting further disciplinary proceedings if you don’t answer promptly. In fact, this is your best chance to convince the FDA you have taken this seriously and are making corrections to thwart any further enforcement. If your response will take more than 15 days, you need to contact the compliance officer assigned and get in writing (an email will do) an extension of time.

18. Does the Quality Assurance (QA) report to Manufacturing if the company is still in drug development and has no drug on the market?

• • Generally, QA should never report to manufacturing. It is against FDA regulation and policy. QA must be an independent organization that can stop production if an issue arises.

19. What is the key difference between an FDA audit & EU audit apart from their own regulations?

• • Both are designed to ensure compliance with their own regulations. There may be some technical differences, but the goal is the same, to ensure safe and effective products and regulatory compliance.

About the speaker

Neil DiSpirito is an FDA law partner in Brown Rudnick’s Corporate and Global Life Sciences Practice Groups.

Clients call Neil when complex government regulations or decisions threaten their company’s future by jeopardizing transactions, mergers, acquisitions, licenses, new product applications enforcement proceedings, administrative actions, litigation, stalled applications or civil and criminal investigations and complaints.

Neil’s practice focuses on a wide array of regulatory and compliance issues in the pharmaceutical, biologic, supplement, and medical device industries (and related data privacy and security regulatory issues). Neil also advises on many business transactions and filings for FDA-regulated products and companies.

For over two decades, Neil has helped his clients navigate complex government regulations or decisions that impact their future. He has advised all types of life sciences companies on a broad range of U.S. and international regulatory compliance challenges and issues that arise in government regulatory approvals and actions, transactions, mergers, acquisitions, licensing, products liability litigation, and other disputes.