MDUFA V, A New Step from 2023

Last week, USFDA released on their website the proposed recommendations that the administration negotiated with the representatives of the medical devices industry. It marks an important transition, passing through public comments and the legislative before the 5th amendment of the MDUFA, in other words, Medical Device User Fee Amendments 2023 running up to 2027, becomes force of law.

MDUFA V public meeting will be held virtually April 19, 2022, to provide the public an opportunity to learn more about and provide their views on the proposed recommendations. The final recommendations are scheduled to be delivered to Congress in April 2022, after FDA considers public input on the proposed recommendations and revises them as necessary.

A new vision for RWE/RWD

Beyond the mere aspect of "re-authorizing" the fee structures for various applications, this revision and update process is above all the opportunity to redefine, or newly establish new guidelines and principles. I find it particularly revealing in the field of RWD and digital technologies. Knowing how influential the US regulatory agency is around the world, I am keen to keep a close look at those guidelines, as it may influence the approach that other countries will adopt, not least in the fields of RWD and DX, both of them at the forefront of many speculations, expectations, and sometime frustrations.

Among the many ways that the FDA carries out its public health mission, their usage of data from prospective randomized controlled trials has long been considered the gold standard to demonstrate the safety and efficacy of a regulated product. However, for many medical devices, practical limitations related to the device or disease condition require alternative approaches to prospective randomized controlled trials and increased flexibility in trial design and statistical analysis.?

That is why they announced ground-breaking measures taking full advantage of the advances in the availability of real-world data (RWD) sources – such as electronic health records, registries, medical claims, pharmacy data and feedback from wearables and mobile technology to support FDA regulatory decisions. The real-life clinical performance of a medical product might be more clearly demonstrated through RWD/RWE because a controlled clinical trial often cannot evaluate all applications of a product in clinical practice across the full range of potential users.

RWE can be leveraged to bring new products to market, evaluate the safety and effectiveness of existing products for new uses, and assess the continued performance and safety of products once on the market. The experience of FDA’s Center for Devices and Radiological Health (CDRH), exemplified by a recent analysis, illustrates the wide range of RWE that has been used in regulatory decisions. Today, CDRH published the results of that analysis, which include 90 publicly available examples of different types of regulatory submissions supported by RWE. These examples come from the full continuum of clinical and device areas throughout CDRH and across the medical device total product life cycle but do not comprise an exhaustive list of all submissions that have relied on RWE.

Beside RWE/RWD new position, there are other meaningful changes that would likely pass through the public comments and Congress review unscathed:

Pre-Submissions

The process and timing for requesting a pre-submission meeting, scheduling the meeting, and receiving feedback from FDA is remaining the same.?However, FDA is significantly increasing (more than double) the number of pre-submission sponsors that will receive feedback within the review goal of 70 calendar days from receipt date or 5 calendar days before the date of the scheduled meeting, whichever is sooner.?Many companies have experienced delays in receiving pre-submission feedback due to FDA’s resource constraints during COVID-19, so this increased goal will be welcome news to companies with devices in development.?As those who have had pre-submission meetings with CDRH understand, preparing for the pre-submission meeting cannot, practically, begin until the written feedback is received.?Having greater certainty as to when written feedback will arrive will allow sponsors consistent time to prepare for the meeting, thereby making the best use of its and FDA’s time.

De Novo Requests

The draft MDUFA V commitment letter sets the goal of 70% goal in FY 2023, but if the de novo decision goal is met in FY 2023 and the fee revenue amount provided for FY 2026 and 2027 is adequate to support performance improvements, FDA plans to increase the goal to 80% in FY 2026.?Similarly, if the 70% goal is met in FY 2024 and adequate fee revenue is provided, the goal will be adjusted to 90% in FY 2027.

Deficiency Letters

By January 1, 2023, FDA plans to update the 2017 guidance document on “Developing and Responding to Deficiencies in Accordance with Least Burdensome Provisions” to clarify what constitutes a statement of the basis for the deficiency.?FDA has set performance goals related to providing a statement of the basis for a deficiency in at least 75% of deficiencies in FY 2023, and that goal will increase each fiscal year.

Enhanced Use of Consensus Standards

In continuity with MDUFA IV, FDA established a voluntary pilot program called the Accreditation Scheme for Conformity Assessment (ASCA), which grants ASCA accreditation to qualified accreditation bodies to accredit testing laboratories that perform premarket testing for medical device companies.?During the pilot, over 85 testing laboratories have become ASCA accredited.?The draft MDUFA V commitment letter states that FDA plans to transition the pilot program to a “sustainable and expanded program” by the end of FY 2023, incorporating lessons learned from the pilot program.?While many laboratories have received ASCA accreditation during the pilot, in our experience, FDA does not inquire about the ASCA status of testing laboratories during premarket reviews.?It is possible that with transition to a more established program, FDA will become more interested in whether testing laboratories have ASCA accreditation when reviewing a device premarket application.

Patient Engagement:?

The draft commitment letter notes the following plans to increase patient engagement in device premarket reviews: issue a draft guidance to provide best practices on incorporating?clinical outcome assessments (i.e., an assessment that reflects how a person feels, functions, or survives) into premarket studies; support use of innovative technologies to reduce barriers to patient participation in studies; and hold a public meeting by the end of FY 2024 to explore ways to use patient-generated health data to advance remote clinical trial data collection and support clinical outcome assessments.?The feedback received during the planned public meeting on remote data collection could potentially impact FDA’s draft guidance document on “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations.”

Digital Health

The draft commitment letter states that FDA will finalize the draft guidance document on “Content of Premarket Submissions for Device Software Functions” by 18 months from the close of the comment period.?FDA will also publish a draft guidance document describing a process to evaluate a predetermined change control plan for digital health devices.

International Harmonization

FDA plans to “support regulatory convergence” by developing a mechanism for FDA to communicate confidentially with regulatory partners to align international regulatory strategy (e.g., regarding scientific, clinical, or technical information).?By the end of FY 2023, FDA plans to issue for public comment a draft strategic plan with details and timelines on achieving international harmonization objectives.?Starting in FY 2024, FDA will publish an annual assessment of international harmonization activities described in the strategic plan.?Notably, this section of the draft commitment letter did not make any mention of FDA’s proposed rule to harmonize the Quality System Regulation with ISO 13485, which is one of CDRH’s most significant steps to-date to harmonize its requirements with international regulatory requirements.

Total Product Life Cycle (TPLC) Advisory Program (TAP)

FDA will establish the TAP pilot during the course of MDUFA V.?The goal of this program is to provide for more timely premarket interactions, enhance the experience of all participants in device development and review processes, facilitate improved strategic decision-making by identifying and mitigating product development risks earlier, facilitate regular engagement with FDA review teams, and collaborate to better align expectations regarding generation of evidence and submission quality.?Each fiscal year, FDA will enroll increasing numbers of products in the TAP pilot, starting with 15 in FY 2023, and ending with at least 325 through FY 2027.