The Road to Personalized Medicine: FDA's Proposed Guidelines on Companion Diagnostics

Posted by Johannes Gross on Feb 11, 2015 11:00:00 AM


While regulation of diagnostic tests by the Food and Drug Administration (FDA) may not directly impact the biobanking industry, it does have an impact on the development of new therapies, particularly personalized medicine, and all of us have a stake in the future of personalized medicine.

The FDA is actively encouraging the development of personalized medicine and regenerative therapies, and has taken a significant step on behalf of companies that are developing these products by enforcing regulatory oversight of the corresponding diagnostic tests. The FDA's August 2014 announcement,  In Vitro Companion Diagnostic Devices / Guidance for Industry and Food and Drug Administration Staff, provided further guidance to those companies developing therapeutic products and/or in vitro companion diagnostics.  Shortly after this announcement was made the FDA sent a proposed risk-based framework for regulatory oversight to Congress for approval.

The FDA also held a conference call on July 31, 2014 with the media to announce the issuance of the guidance document and their intent to provide regulatory oversight. According to former FDA Commissioner Dr. Margaret Hamburg, “Personalized medicine is built on two fundamentals. First, the reliability and accuracy of tests used to diagnose the nature of a patient's disease or condition and/or identify whether a patient is likely to respond to a specific treatment. And second, the safety and efficacy of therapies used to treat a given disease or condition.”

Dr. Hamburg noted that the FDA is aware of problems with a number of laboratory developed tests (LDTs) and is deeply concerned that critical medical decisions are being made based on diagnostic tests that have not been reviewed by the FDA. Problems include claims that are not supported with sufficient evidence, lack of controls resulting in erroneous results, and other issues. These problems in turn lead to misdiagnoses, under- or over-treatment, and other events.

Dr. Hamburg also noted that “The FDA has historically exercised enforcement discretion over LDTs, meaning the agency generally did not enforce applicable regulatory requirements on these tests because they were generally considered lower risk and used on a limited basis with any given institution. Today they may be marketed and used more broadly and compete with FDA-approved tests without clinical studies to support their use.”

Thus a primary focus of the regulatory oversight is the protection of patients. The proposed framework will also benefit those companies that are developing new therapies and accompanying diagnostics. During the July 31st media call, Dr. Jeff Shuren, Director of the FDA’s Center for Devices and Radiological Health (CDRH), explained that new therapies and accompanying tests are reviewed simultaneously, and because the test will also be approved, a company’s investment in the data and development process will be protected; once an FDA-approved test is available, other entities that want to market an equivalent test will also have to get FDA approval. Like the original developer, they will have to invest in collecting and submitting the required data to establish that the test meets its intended use, and that it is appropriately manufactured for that specific use.

Other laboratories or entities interested in marketing an equivalent test will also have to generate and submit the required data, establishing that the test meets its intended use, and that it is appropriately manufactured for that specific use. The FDA will look for strong links between a biomarker or set of biomarkers and clinical endpoints.

Not every LDT will be subject to the same level of regulatory oversight.  For instance, FDA does not intend to enforce regulatory oversight for forensic/law enforcement purposes, or certain specific tests used in CLIA-certified medical center labs for procedures performed within the institution, such as transplants. However, any test intended for the same use as a cleared or approved companion diagnostic test will be subject to regulatory oversight, as will tests with the same intended use as an approved Class III medical device and certain tests used to determine the safety and/or efficacy of blood/blood products.

Dr. Shuren explained that release of a new therapy in the market will not necessarily be tied to the approval of an accompanying diagnostic. He emphasized that the safety and efficacy of a new therapy depends on having an accurate and reliable test available, and that the approval process for both the therapy and companion diagnostic are indeed bound together.  However, there are always exceptions, and according to Shuren, the FDA will not hold up a decision on a therapy for a life threatening illness for which nothing else exists, because the diagnostic tests are not ready. 

The FDA held a public workshop at the NIH campus in Bethesda, MD on January 8-9, 2015 to obtain feedback from all stakeholders regarding the proposed risk-based framework.  Proponents and opponents of the proposal voiced their opinions and discussed LDT labeling considerations, clinical validity/intended use, categories for continued enforcement discretion, and other topics in the best interest of public health.  Additional information from the workshop, including the agenda, webcasts, transcripts, and presentations, can be found on the event website.

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The guidance document can be found at: 

The FDA’s proposed framework for regulatory oversight of LDTs can be found at: 

A transcript of the news media call can be found at: