Next-generation sequencing (NGS)-based tests, complex laboratory-developed tests (LDTs), and companion diagnostics are all challenging the conventional regulatory process at the U.S. Food and Drug Administration (FDA). In an October report, “Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development,” the agency details how it is responding to and anticipating challenges related to review of personalized medicine (PM) products and the measures it plans to take to ensure the regulatory processes are properly suited to address these rapid innovations. The FDA says the era of PM is definitely here and cites internal evidence that of the new drugs approved since 2011, approximately one-third included some form of genetic or other biomarker data in the submission to characterize the drug’s efficacy, safety, or pharmacokinetics. Additionally, more than 100 approved drugs contain labeling information on genomic biomarkers. “The FDA has worked to bridge developments in genomics and other relevant sciences to clinical practice by advancing the tools necessary for evaluating targeted therapeutics and bringing them to market more efficiently, collaborating in key research, defining and streamlining regulatory pathways and policies, and applying new knowledge in product reviews,” the report says. Core to the FDA’s responsibilities is […]
Next-generation sequencing (NGS)-based tests, complex laboratory-developed tests (LDTs), and companion diagnostics are all challenging the conventional regulatory process at the U.S. Food and Drug Administration (FDA).
In an October report, “Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development,” the agency details how it is responding to and anticipating challenges related to review of personalized medicine (PM) products and the measures it plans to take to ensure the regulatory processes are properly suited to address these rapid innovations.
The FDA says the era of PM is definitely here and cites internal evidence that of the new drugs approved since 2011, approximately one-third included some form of genetic or other biomarker data in the submission to characterize the drug’s efficacy, safety, or pharmacokinetics. Additionally, more than 100 approved drugs contain labeling information on genomic biomarkers.
“The FDA has worked to bridge developments in genomics and other relevant sciences to clinical practice by advancing the tools necessary for evaluating targeted therapeutics and bringing them to market more efficiently, collaborating in key research, defining and streamlining regulatory pathways and policies, and applying new knowledge in product reviews,” the report says.
Core to the FDA’s responsibilities is consideration of the benefits and risks during evaluation of medical products. The agency believes that PM should increase benefits and reduce risks for patients by improving both the safety and efficacy of therapeutics. It adds, though, that in this early stage of PM it has the additional responsibility to “provide clarity, predictability, and guidance to industry in order to help encourage development” and to identify “opportunities for streamlining regulatory processes and advancing the science and tools that will help drive innovation.”
But in this time of transition, there are challenges in determining how to evaluate PM products, including appropriate evidentiary standards with an emphasis on examination of clinical trial design and statistical methods to analyze genomic data. Logistical and organizational considerations are also being reviewed to better coordinate the review of companion or combination products.
“Reviews of co-developed products pose a number of challenges to the Agency, since they require expertise from and careful coordination between the Centers to ensure consistent reviews and contemporaneous approval of the two products. Challenges stem from the co-developed products falling within the purview of multiple FDA centers each operating under different laws, regulations, systems for tracking submissions, and timelines,” the report explains.
What’s more, the explosion of emerging evidence documenting genetic associations, and the volume of emerging diagnostics and their increasing complexity, are posing challenges to the review process. This can be seen particularly in the area of NGS-based tests and complex LDTs, where the FDA has taken a number of steps toward developing new methods for evaluating these tests.
“The Agency has since started to assess sequence-based tests using a strategy that focuses on validating the analytical performance of the sequencing platform—whether it measures what it is supposed to measure accurately and reliably and precisely,” the report says. “While it will be impossible for the Agency to assess the platform’s performance for every single variant, the Agency is looking at possibilities for identifying a representative set of markers that could be assessed in order to develop an understanding of the performance of the platform as a whole.”
When it comes to LDTs the FDA has generally withheld enforcement, but with the “product interdependency” created by tailored treatments, the FDA has begun to reconsider its regulatory position on some LDTs, where the test results impact the ability of a specific therapeutic product to achieve its established safety and effectiveness, the agency says.
“FDA has been developing a risk-based framework for regulatory oversight of LDTs that would assure that tests, regardless of the manufacturer, have the proper levels of control to provide a reasonable assurance of safety and effectiveness, while also fostering innovation and progress in PM,” says the report.
Takeaway: Advanced diagnostic testing, central to the application of personalized medicine strategies, poses a challenge to the traditional regulatory review process. But the FDA is evaluating modifications to the review processes to meet the challenges posed by these innovations.
