Aligning drugs and diagnostics

SILVER SPRING. Md.—Precision medicine has already been steadily on the rise in popularity, but it got a boost earlier this year when U.S. President Barack Obama launched a Precision Medicine Initiative. Obviously, companion diagnostics are critical to advancing precision medicine and that, too, got a boost recently with the issuance of draft guidance from the U.S. Food and Drug Administration (FDA) regarding the principles of drug and diagnostic codevelopment.

The document is titled, simply and lengthily enough, as “Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product: Draft Guidance for Industry and Food and Drug Administration Staff.” And, at 48 pages long, we can’t do much more than hit the generalities and high points.

But let’s start with some of the FDA’s own words on the subject of in-vitro diagnostics (IVD) with regard to companion diagnostics (CDx) codevelopment, from the draft guidance document:

“Codevelopment of IVD companion diagnostics and therapeutic products is critical to the advancement of precision medicine. FDA seeks to facilitate innovations in precision medicine by providing sponsors with a set of principles that may be helpful for effective codevelopment and in fulfilling FDA’s applicable regulatory requirements.”

From the FDA’s standpoint—and, probably, the industry’s as well—the best-case scenario for drug-CDx codevelopment is when the need for a CDx test is identified at the earliest parts of the drug development process and the therapeutic and CDx are developed and launched at the same time. This isn’t new, of course—such policy was stated by the FDA in 2014 draft guidance as well.

But the FDA elucidates this approach a bit more in the newer draft guidance, providing specific steps for the sponsors of the drug and the IVD companion diagnostic, including advice to “meet with the appropriate FDA review centers prior to launching a trial intended to advance the development of the therapeutic product and the IVD companion diagnostic.”

The reason for contemporaneous development is in part “so that an analytically validated test can be prospectively incorporated into the design of the therapeutic product trials.”

“Although codevelopment as a process does not require simultaneous development of the IVD companion diagnostic and the therapeutic product from beginning to end, the availability of an IVD with ‘market-ready’ analytical performance characteristics (i.e., a test that is completely specified with complete analytical validation and meets the therapeutic product sponsor’s expectations for performance) is highly recommended at the time of initiation of clinical trial(s) intended to support approval of the therapeutic product,” wrote the FDA.

It also noted: “Although there is significant flexibility in the type of test to be used, and test design changes are permissible between therapeutic product clinical trial phases, it is still important to understand the critical analytical performance characteristics of early prototype tests. The analytical validation studies that evaluate critical performance parameters should be completed in advance of using the test in a trial that is intended to provide the clinical evidence in support of IVD companion diagnostic claims. Using an analytically validated test is important to protect clinical trial subjects, to be able to interpret trial results when a prototype test is used, and to help to define acceptable performance characteristics for the development of the candidate IVD companion diagnostic.”

FDA has also provided a hint in the document that it may be less strenuous about classification of companion diagnostics, which are typically considered Class III, high-risk devices that require premarket approval. The new draft documentation indicates, though, that there may be situations under which a CDx test could be seen as a Class II, moderate-risk device that can come to market following 510(k) clearance or a de-novo request.

FDA also notes that many of the principles discussed in the draft guidance “may also be relevant to the codevelopment of therapeutic products with IVDs that do not meet the definition of an IVD companion diagnostic but that are nonetheless beneficial for therapeutic product development or clinical decision making.”

As of press time for this issue, FDA was set to hosting a webinar to answer questions about the draft guidance document on Aug. 18. Stakeholders may submit comments electronically by October 13.