Overhaul of the FDA Medical Device Pre-Market Approval Program: What Does It Means for Diagnostics

On October 19^th, the FDA Center for Devices and Radiation Health (CDRH) released its Medical Device Pre-Market Programs: An Overview of FDA Actions (link).  This document presents the center’s review of the processes of pre-market approval of all medical devices, and articulates solutions to the problems identified in this review.

First, CDRH wants to dispel the misperception that safety/effectiveness and innovation are incompatible.  Their solution is not to focus on whether more or less regulations are needed but rather to focus on smart regulation: effectively achieve both aspects of the center’s mission as a regulator and facilitator.

Second, the number one problem identified from discussions with key stakeholders (i.e. industry, academia, and payers) is insufficient predictability in the pre-market program.  This lack of clarity has resulted in inefficiencies, increased cost for both the industry and the FDA, and delays in bringing safe and effective innovative products to the market.  At the root of these problems, CDRH identified excessive staff turnover, insufficient training (FDA and industry), rapidly increasing workload associated with the growing complexity and number of submissions, inconsistent data requirements, insufficient guidance for the industry, and poor quality of industry submissions.

To address these issues, CDRH is proposing a set actions centered on three areas of emphasis:

1. Create a culture change toward greater transparency, interaction, collaboration, and the appropriate balancing of benefits and risks
1. Better engagement with industry
1. Improve Interactive Review (informal call to the submitter) to accelerate review time
2. Improve pre-submission meetings to specify consistent and stable submission expectations
2. Greater use of external experts
3. Implementing flexible, risk-based policies that appropriately balance benefits and risks and apply a more patient-centric approach
4. Establishing new ways of doing business that add value
1. Create an innovation pathway (an entirely novel approach) to enable the timely review of ground-breaking technologies
5. Setting clear expectations for CDRH staff
2. Assure predictable and consistent recommendations, decision making, and application of the least burdensome principle
1. Providing adequate management oversight and staffing
2. Enhancing training
3. Improving internal processes
4. Adopting smarter policies and issuing more guidance
5. Developing new communication tools
3. Implement efficient processes and use of resources
1. Making existing processes more efficient
2. Using our resources more effectively
3. Improving our ability to rely on data from outside the U.S. and actions by regulatory bodies of other countries

For regulatory purposes, diagnostics are medical devices.  Therefore, the changes proposed by CDRH will affect the submission and approval of novel diagnostics.  Specifically, the development and approval of diagnostics will most likely benefit from the improved review process with greater predictability and transparency.  The commitment of CDRH to actively interact with the sponsors will most likely provide greater efficiency and reduced review time.  The call for enrolling experts in the relevant fields should streamline the process of defining the requirements for successful submissions.

While these improvements are promising, CDRH makes no secret that a significant number of these solutions will require additional funding.  The ongoing negotiations of the reauthorization of user fees will therefore most likely result in higher cost for the sponsors.  In keeping with this move, CDRH emphasizes the concept of shared responsibilities by stating: “We must fully embrace the paradigm that assuring the safety and effectiveness of devices is everyone’s job and the responsibility resides as much with industry, practitioners and patients as with the Agency”.

The specific aspect of review of approval of companion diagnostics is not specifically addressed in this report.  The sometime chaotic relationship between CDRH and its drug reviewing counterpart CDER would certainly benefit from a similar review.

Thierry Sornasse for Integrated Biomarker Strategy