On July 14, 2016, the U.S. Food and Drug Administration (FDA) released draft guidance on the codevelopment of therapeutic products (such as pharmaceuticals) and companion tests that are used to determine if the therapeutic products will be safe and effective.

The codevelopment of therapeutic products and companion tests, known as in vitro companion diagnostic devices (“IVD companion diagnostics”), is not new. In 1998, the FDA approved both the cancer drug Herceptin along with an IVD companion diagnostic called HercepTest. HercepTest measures the expression of human epidural growth factor receptor 2  (HER-2) in breast cancer tissue. Some breast cancer cells have too many copies of the HER-2 gene, which can lead to an overproduction of proteins that cause cell growth. Herceptin works by attaching itself to the HER-2 receptor, thereby reducing the overproduction of these proteins.  However, only 25 to 30% of those with breast cancer overexpress the HER-2 gene. As an IVD companion diagnostic, HercepTest allows physicians to determine whether their patients overexpress the HER-2 gene and would benefit from Herceptin. 

The FDA defines an IVD companion diagnostic as an in vitro device that provides information that is essential to the safe and effective use of its corresponding therapeutic product. According to the draft guidance, IVD companion diagnostics can be used to:

1. identify patients who are most likely to benefit from the therapeutic product;

2. identify patients likely to be at increased risk for serious adverse reactions as a result of treatment with the therapeutic product;

3. monitor response to treatment with the therapeutic product for the purpose of adjusting treatment (e.g., schedule, dose, discontinuation) to achieve improved safety or effectiveness; or

4. identify patients in the population for whom the therapeutic product has been adequately studied and found to be safe and effective (i.e., there is insufficient information about the safety and effectiveness of the therapeutic product in any other population).

The above list illustrates the extraordinary power of IVD companion diagnostics to inform the development and use of therapeutic products. It is therefore not surprising that the FDA generally believes that IVD companion diagnostics should be either approved, granted a de novo request or cleared by FDA contemporaneously with the approval of the corresponding therapeutic product.

The discovery of “biomarkers” like HER-2 have increased tremendously, and, as the FDA notes in the draft guidance, the codevelopment of IVD companion diagnostics and therapeutic products is critical to the advancement of precision medicine. To facilitate these advances, the FDA’s draft guidance provides developers with principles that can help them effectively codevelop the products while satisfying FDA’s regulatory requirements. The draft guidance specifically focuses on the following four topics:

• general principles to guide codevelopment to support obtaining contemporaneous marketing authorization for a therapeutic product and its corresponding IVD companion diagnostic,

• certain regulatory requirements that sponsors should be aware of as they develop such products,

• considerations for planning and executing a therapeutic product clinical trial that also includes the investigation of an IVD companion diagnostic, and

• administrative issues in the submission process for the therapeutic product and IVD companion diagnostic.

The codevelopment of these products presents unique challenges given that therapeutic products and IVDs companion diagnostics are typically developed on different schedules, are subject to different regulatory requirements, and have different points of interaction with the appropriate review review centers at FDA. Cooperation–both among the codevelopers and between the codevelopers and the FDA–is a crucial part of the navigating the codevelopment process.

Comments on the draft guidance can be submitted here. They are due by October 13, 2016.