Na An, MJLST Article Editor
In July 2016, the US Food and Drug Administration (FDA) published a draft guidance document titled “Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product.” The new draft guidance aims to serve as a “practical guide” and assist sponsors of drugs and in vitro diagnostics (IVD) in developing these two products simultaneously. So far, FDA has received six public comments on the draft guide which are mostly positive, with Illumina calling the document “worth the wait,” and Genentech claiming it “crucial for the advancement of personalized medicine.”
A companion diagnostic includes a medical device, in this case an in vitro device, which provides safety and efficacy information of a corresponding drug or biological product. It is a critical component of precision medicine, the cornerstone of which is the ability to identify and measure biomarkers indicative of the patient’s response to a particular therapy. Approximately, a quarter of new drugs approved over the past two years were a drug-IVD companion. However, the codevelopment process is complicated by the fact that these two products may be developed on different schedules, subject to different regulatory requirements, and reviewed by different center at the FDA. The long-awaited draft guidance was in the works for more than a decade and intended to help sponsors and the FDA reviewers navigate these challenges.
In this draft guidance, FDA reiterates its general policy that IVD devices should receive marketing approval contemporaneously with the authorization of the corresponding therapeutic product. FDA states that “the availability of an IVD with ‘market-ready’ analytical performance characteristics . . . is highly recommended at the time of initiation of clinical trials intended to support approval of the therapeutic product.” FDA also recommends: “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.” The new draft guidance provides much more information about the technical and scientific aspects of the development process. For example, the draft guidance details the use of IVD prototype tests for the purpose of testing the drug early in the development, considerations for planning and executing a therapeutic product clinical trial that also includes the investigation of an IVD companion diagnostic, the use of a prospective-retrospective study approach, the use of training and validation sample sets, and the use of a master file for the therapeutic product to provide data in support of the IVD companion diagnostic marketing application.
The draft guidance has received high marks from industry giants. Illumina said the draft “has been a long time coming, eagerly anticipated, but worth the wait.” Yet, the gene sequencing giant also seeks more clarity from FDA on risk assessments and expectations for analytical validation prior to investigational IVD use in trials. “There is an opportunity here for FDA to add clarity on this important decision making process. We suggest this discussion on significant risk versus nonsignificant risk determinations be expanded and put into an appendix with examples. This is a unique opportunity for FDA to help sponsors get this process right,” Illumina says. On a similarly positive note, Genentech called the draft “crucial for the advancement of personalized medicine,” and supplementary to two previous guidance documents on next generation sequencing. In addition, Genentech notes that the scope of this IVD and drug co-development draft guidance “is limited, and therefore it does not address the requirements for development of complementary diagnostics or the challenges of co-development using high-throughput technologies such as Next-Generation Sequencing (NGS) based test panels, which are an increasingly attractive tool for both developers and providers.” AstraZeneca, on the other hand, seeks more clarity on guidance on complementary diagnostics and clarifying between “patient enrichment” and “patient selection” and the resulting considerations on determination of significant risk uses of investigational devices.
We eagerly wait for FDA’s view of these comments and impacts of the guidance on the codevelopment of a drug-IVD companion.