At the latest MedTech conference held in Boston, MA from October 24-26, we heard from FDA officials and industry representatives on a range of topics. Below, we provide a snapshot of the three-day event:
Update on the International Medical Device Regulators Forum (IMDRF)
The IMDRF conference was held in early September where Associate Director for International Affairs at CDRH, Melissa Torres, summarized actions members were taking, including working on harmonizing premarket review requirements. She indicated the requirements went out for comments and expects the group to finalize the document by early next year.
Harmonizing different regulatory requirements is difficult both because of a lack of resources and differences in how each country’s laws and regulations are written. Recognizing this, moderator Diane Wurzburger, a regulatory affairs executive at GE, asked whether industry could assist in advancing hot areas such as artificial intelligence/machine learning (AI/ML). In response, Ms. Torres shared that on the heels of the MDUFA V announcement, the international affairs team will be able to hire another five employees on top of the two existing ones. This allows FDA to further engage with international members, address harmonization of international standards, develop multilateral agreements and cross agency documents around AI/ML and a predetermined control plan (PCCP), and converge on topics such as AI/ML.
Ms. Torres also shared that the eSTAR program, which we most recently blogged about here, is being developed with Health Canada. The goal is to permit sponsors to submit their device applications through eSTAR to both US and Canadian regulators and reduce administrative burden. Fellow panelist, August Bencke Geyer, who serves as Deputy General Manager of the Medical Devices Office at ANVISA (Brazilian Health Regulatory Agency) expressed enthusiasm and indicated that Brazilian regulators are watching closely to see how the program unfolds. We are too!
Understanding FDA Emergency Use Authorization (EUA) Transition Plan
Last month, we advised planning for the end of the Covid-19 public health emergency (PHE) and highlighted that transition plans for Covid-19 products are amongst CDRH FY2023 priorities. In one of the conference’s well-attended sessions, Dr. William Maisel, Chief Medical Officer and Director at CDRH’s Office of Product Evaluation and Quality, shared FDA’s experience with EUAs over the last two and a half years as well as more detail on transition planning for those devices marketed under an EUA or enforcement policy (EP).
CDRH’s pandemic responses included more than 4,000 medical devices authorized. This includes EUAs and full marketing authorizations. To put it into perspective, these were the numbers (so far) for in vitro diagnostics EUAs: 304 molecular, 84 antibody, 51 antigen, and 5 other. FDA also authorized the following medical devices: 279 personal protective equipment (PPE), 119 ventilators, and 52 others.
To paraphrase from our blog post, EUAs are triggered by an EUA declaration; FDA will publish advanced notice for an EUA declaration and provide a 180 day notice before the implementation of the transition plan. Section 319 of the Public Health Service Act is a declaration by the Health and Human Services (HHS) Secretary that a PHE exists; these declarations generally last 90 days but may be extended by the HHS Secretary. EPs are triggered by an expiration of Section 319 or at least 45 days after guidance is finalized, whichever is later.
Dr. Maisel reaffirmed that an EUA may remain in effect beyond the duration of the declared PHE, unless FDA chooses to revoke an EUA. Below, we re-create information shared by Dr. Maisel that summarizes transition planning and what has been outlined in a guidance document and our blog post:
|Device Marketed Under||Implementation Start|
(Days 1 – 179)
|Premarket Submission Due|
|EUA||FR (Federal Register) publication of Advance Notice of Termination for each EUA declaration termination||Continue marketing under terms of EUA||Upon EUA Declaration Termination|
|EP||Expiration of section 319 PHE declaration OR ≥ 45 days after guidance finalization whichever is later||Continue marketing under terms of EP|
+ Beginning Day 1:
21 CFR 803 (AE Reporting)
+ Beginning Day 90:
21 CFR 806 (Reports of Removals and Corrections)
21 CFR 807 Subparts B – D (Registration and Listing)
|Upon Withdrawal of EP Guidances|
|Device Marketed Under||Premarket Submission Due|
|Submission Submitted||Discontinue Distribution|
|EUA||Upon EUA Declaration Termination||FDA doesn’t intend to object to continued distribution of devices IF:|
1) Marketing submission submitted and accepted before applicate date
2) Final FDA action on submission not yet taken
Should follow all other applicable statutory and regulatory requirements
21 CFR 801 Subpart B
21 CFR 803
21 CFR 806
21 CFR 807 Subparts B – D
21 CFR 820
21 CFR Part 830
|Manufacturer expected to discontinue distribution IF:|
1) Required marketing submission not submitted and accepted before applicable date
2) Manufacturer receives negative FDA decision, withdraws submission, or fails to provide a complete response
|EP||Upon Withdrawal of EP Guidances|
Dr. Maisel’s short and sweet takeaway: “focus on getting your application accepted, not even cleared or approved. It’s an easy way to manage the transition.”
Accepted means through the Refuse to Accept (RTA) process. As we noted previously, eSTAR 510(k)s are exempt from RTA – one more advantage to submitting a 510(k) via eSTAR.
If you have a good relationship with the review team, Dr. Maisel encourages a brief phone call or quick email to obtain informal feedback.
Dr. Maisel also discussed disposition of already distributed devices. For whose manufacturers who do not intend to continue device distribution, FDA generally does not intend to request market removal of those devices distributed before the applicable EUA termination or guidance withdrawal date. However, he cautioned that manufacturers should be aware of any applicable Food, Drug, and Cosmetic Act (FD&C Act) requirements for their specific device and continue to comply with these requirements for as long as they are applicable.
In closing, he advised manufacturers who plan to market their products beyond the public health emergency to plan to submit marketing applications. He signaled that MDUFA V will impact pre-submissions with their goal of completing 90% within 70 days. In other words, for those wishing to obtain FDA feedback on their transition plan or marketing submission, they should plan to do it soon and ensure enough time to comply with regulatory requirements.
Getting Serious About Women’s Health in Medtech
On the second day of the conference, we heard from Dr. Terri Cornelison, Chief Medical Officer and Director of Health of Women at CDRH. She described the CDRH Health of Women Strategic Plan to Better Inform Medical Device Research and Regulation for Women and summarized three priorities:
- Sex and gender specific analysis and reporting,
- Integrated approach for current and emerging issues related to women’s health, and
- Research roadmap.
Under the first priority, CDRH practices for sex and gender specific data collection, analysis, and reporting would be optimized. Priority 2 will result in CDRH coordinating and leading a center-wide integrated approach to current and emerging issues as they relate to women. Under priority 3, CDRH will continue to promote advancement of regulatory science; strategize gap areas; discover and improve understanding; better understand women’s experience; facilitate sex and gender analyses; and identify areas where clinical trial enrollment can be better balanced for women.
We also heard from Dr. Suzanne Baron, Director of Interventional Cardiology Research at Lahey Hospital and Medical Center. Dr. Baron spoke to specific actions sponsors can take to improve representation of women in cardiac clinical trials. These include, but are not limited to, ensuring inclusion/exclusion criteria addresses how women present with disease, obtaining input on protocol design from women, and including women on steering committees, advisory boards, and as principal investigators. These are important considerations as FDA routinely asks sponsors to ensure their protocols are diverse, not just in the subjects recruited, screened, and enrolled, but also in users and those who carry out the protocols.
CDRH Town Hall
In the last session of the conference, aptly described as a super session, CDRH officials led the standing room only presentation and discussion around the CDRH strategic plan and priorities, Covid-19 impact on workload and attrition, and the total product life cycle (TPLC) Advisory Program (TAP).
CDRH Strategic Plan and Priorities
Dr. Jeff Shuren, Director of CDRH, kicked off the super session by acknowledging that increasing cybersecurity vulnerabilities to medical devices and the risks that are imposed such that patient care is compromised represent a national security. To that end, Dr. Shuren shared that there was a 17-fold increase in device related vulnerabilities from 2016 to 2020 and said FDA requires more funding and authority to fight the issue.
As part of his introductory remarks, Dr. Shuren touted the digital health activities CDRH has undertaken: establishing the Digital Health Center of Excellence and the pre-certification program and publishing guidance on clinical decision support and AI/ML.
He also shared that the three 2022 – 2025 priorities are:
- Promote a modern and diverse workforce,
- Enhance organizational agility and resilience, and
- Advance health equity.
FDA’s recent pre-certification report, which we blogged about here, would enable FDA to create a new pathway for those products considered software as a medical device (SaMD). The report illuminated the fact that FDA is currently only allowed to grant a de novo application through such a pathway. Dr. Shuren acknowledged this highlights a major shortcoming in that the regulatory regime will be behind evolving digital health technologies.
Dr. Shuren praised the administrations of both President Biden and former President Trump in their commitment to streamline guidance documents, citing the first Covid-19 guidance was cleared within 36 hours.
He signaled that 2023 will be a transition year as FDA aims to “return to normal” after an unprecedented workload, speaking to a slide that showed a nearly 70% increase in submission volume in FY2020, 35% in FY2021, and 20% in FY2022 as compared to FY2019. The FY2022 data is through October 17, 2022 and includes more than 1,400 EUAs and pre-EUAs. As discussed above in the session with Dr. Maisel, Dr. Shuren reinforced plans to publish guidance on transition plans for devices marketed under EUAs and EPs.
Dr. Shuren also remarked that this year was busy for those submitting and reviewing breakthrough designations, which are granted about 40% of the time.
For those unfamiliar, Dr. Douglas Kelly, Deputy Director for Science, Chief Scientist at CDRH introduced the Total Product Life Cycle (TPLC) Advisory Program (TAP) Pilot.
The TAP program is a voluntary program intended to leverage experts “who provide dynamic, strategic advice” and is a new component of MDUFA V. The program will include FDA review teams, patients, providers, and payors and is designed to incorporate input from these stakeholders to “improve various aspects of medical device development and to increase the predictability and reduce the time from concept to commercialization.” One goal of the program is to provide for more timely premarket interactions. Another is to improve submission quality.
Dr. Kelly shared that the TAP Pilot will be introduced in a phased approach with the first phase set to launch on January 1, 2023. During this time, fifteen cardiovascular devices from the Office of Health Technology 2 (OHT2) will be enrolled. OHT2 was chosen based on their history of granting breakthrough device designations, workload, and experience with programs that involve rapid interactions. Dr. Kelly indicated that an additional 45 devices will be enrolled in FY2024 and an additional 65 in FY2025. Because these additional devices have not been identified, Dr. Kelly welcomed feedback on areas to target next.
In closing, we appreciated hearing from an impressive slate of speakers and enjoyed meeting and reuniting with friends and colleagues. We return energized with new perspectives and work ahead!