By Phil Crooker, VP – Technical, Regulatory & Access, Parexel
Despite the best efforts of the pandemic, the FDLI delayed but did not cancel its annual meeting for 2020 and hosted the event through a virtual platform. You can find the lineup of topics and speakers for the event on the FDLI website here - https://www.fdli.org/2020/10/2020-annual-agenda/. As you’ll see from the bulleted highlights of the meeting, the early demise of the FDA has been greatly exaggerated.
In this blog, I’ll walk through the points that resonated as nuggets of important new information or that showcased important elements of the agency’s culture that colors its actions and decision-making.
- The agency’s current chief counsel, Stacy Cline Amin, mentioned:
- The final rule recently published for the state importation plan for certain prescription drugs from Canada, noting that there was extraordinary legal effort put into creating the final rule using novel interpretations of existing statutory authorities. You can find the FDA press release here - https://www.fda.gov/news-events/press-announcements/fda-takes-actions-help-lower-us-prescription-drug-prices.
- Sometime during 2020 the agency expects to publish an interim report on work process enhancements and optimizations for conducting inspections based in its collective experience in managing the effects of COVID-19. The final report is scheduled to be published in 2021.
- The agency is using its statutory authorities under Section 704 of the FDCA (Section 706 of FDASIA) requesting information in advance of inspections to prioritize and triage the backlog of manufacturing inspections for drugs. So far, FDA has conducted approximately 200 mission critical inspections during the pandemic.
- There is a process underway to examine the utility of remote or “virtual” inspections and work is being done to create work procedures for remote inspections.
There was a panel discussion of former chief counsels that yielded some excellent perspective and insight into the legal culture permeating the agency. Here is a flavor of the discussion:
- Guidance has provided an important mechanism for the agency to implement its authorities and levels the playing field of information so that individual companies don’t get an advantage of case-by-case communications.
- A word of caution is also in order when discussing guidance – it’s a mixed bag for striking the right balance of vigilance with utility. There are instances at the review level where there have been efforts to implement guidance as if it were a regulation. This results in pressure and belief that require industry to act in a proscribed approach.
- The “Brand Memo” was a good reminder to federal agencies to use discipline in a vigilant approach to how guidance is used contrasted with the standards for a violation of law.
- One of the key roles of OCC has to been to advise the agency about the limits of its authority as a check against urges to act more broadly using a sweeping rationale of protection of public health. Previous chief counsels, in particular Peter Barton Hutt, have advocated for an approach that essentially argues that the FDA has the authority to take actions that are not prohibited in the FDCA. There are limits but the existing legislation has plenty of opportunity for creative arguments that are not constrained by a very limited reading of the bare text of the FDCA.
- In situations where the chief counsel believes that the agency’s authority is limited, the agency can cooperate with other government agencies such as CPSC and FTC.
- In the past, such as tobacco and pediatric initiatives, the agency created a theory of authority that was not accepted by the courts. This opens the door for potential loss of credibility with the courts for the over-reach, but also ultimately resulted in spurring Congress to grant FDA legislative authority in these areas.
- The FDA is on a clock with the various COVID-19 products and expect a transition to be needed for marketing the articles. The pandemic can act as a catalyst for FDA to get more comfortable much more quickly with novel issues, such as real-world evidence and making a shift towards greater reliance on risk-based management of pre-approval inspections – including implementing virtual inspections.
- Expect a gradual winding down of using EUA – FDA has discretion to set a deliberative pace for the process, and some EUA may persist.
- Products marketed with the authority of an EUA are being scrutinized - the FDA just issued its first Warning Letter for failures to comply with medical device reporting requirements.
- Any number of different possibilities or mix of combinations for how FDA conducts inspections in the future are feasible – hybrid models that combine elements of “virtual” and “conventional” inspections; wider use of the FDCA Section 704 (FDASIA Section 706) authorities, as well as more targeted risk-based on-site inspections. But FDA will look for approaches to implement new policies first before trying to revise or request new authorities or rulemaking.
- Dr. Marks, Office Director for the Center for Biologics Evaluation and Research (CBER), was available for a break-out session that focused on the emerging vaccines for COVID-19. He made these points in his roundtable:
- The advisory committee meeting for Vaccines and Related Biological Products that will meet on October 22 will provide an introduction to vaccine development, various challenges facing the FDA, post-market surveillance but will not include any sponsor presentations.
- If the FDA receives information from a sponsor up until about a week before the advisory committee meeting, it has the flexibility to include that information and move the date of the committee meeting if necessary.
- Some of the challenges faced by the FDA include how to manage the effects of any EUA for a vaccine on the enrollment and unblinding of clinical trials that are underway. Also, if a candidate vaccine were to show greater than 95% efficacy with an adequate safety profile then any such vaccine authorized using an EUA could become the standard of care if there is a dramatic decrease in participation in clinical trials.
- The FDA has the bandwidth to host 50,000 viewers on Adobe Connect® but also expects that at least one network news organization will carry the video feed live.
- The FDA expects that there will be tremendous public pressure for consolidated manufacture by multiple companies for the same vaccine if there is a candidate vaccine that reports data with greater than 95% efficacy. This was actually the premise behind “Operation Warp Speed.”
- CBER has only missed a few PDUFA dates because manufacturing inspections could not be performed. But if the pandemic persists then the challenges to meet PDUFA dates will increase significantly for approaching PDUFA dates – particularly for foreign sites – and the public should expect to see some drop-off in meeting goal dates.
- CDER recognizes that there are innovative approaches that have been used during COVID-19 that could also be used post-pandemic with increasing flexibility, including:
- De-centralized clinical trials.
- Remote monitoring of clinical trials.
- Use of inspection alternatives – primarily wider use of FDCA Section 704 (FDASIA Section 706) authorities and greater reliance on the MRA and cooperative agreements rather than “virtual” inspections.
- The essential medicines list that FDA was required to develop in consultation with other government agencies as part of the Executive Order (EO) on Ensuring Essential Medicines, Medical Countermeasures, and Critical Inputs Are Made in the United States is in progress (for more information about the Executive Order read my earlier blog here - https://www.parexel.com/news-events-resources/blog/overview-recent-executive-order-critical-drugs-made-america). The FDA has created the process and criteria to identify drugs, medical-counter measures and in some cases devices as well as critical components. The list will be finalized, and the agency is discussing whether there are mechanisms to engage the public, but no decisions have been made.
- Finally, here are some statistics shared during the meeting about FDA activity during the pandemic:
- More than 590 drug development programs in the planning stage through CTAP.
- More than 310 trials reviewed through CTAP.
- 5 EUA for drugs.
- More than 90 Warning Letters issued to sellers of fraudulent products.
- Almost 50,000 inquires from the public between January 1 – September 3-, 2020 – 15,600 related to COVID-19.
Although the FDA remarked that the operational pace of COVID-19 is not sustainable long term, the early demise of the FDA has been exaggerated.
During the event, Parexel also showcased its Compliance Consulting Services in the virtual exhibition space which includes a team of over 80 former regulators / inspectors who, alongside seasoned industry experts, help companies mitigate compliance risks, manage remediations, and restore confidence. I encourage you reach out to me or visit our website to learn more.