On December 6, FDA Commissioner Gottlieb announced in a press release the availability of a new draft guidance entitled, “Developing and Labeling In vitro Companion Diagnostic Devices for a Specific Group or Class of Oncology Therapeutic Products” (Draft Guidance). The agency also published the Draft Guidance announcement in the December 7 Federal Register. FDA issued the Draft Guidance in an effort to “make it easier to get class labeling on diagnostic tests for oncology therapeutic products, where scientifically appropriate.” The Draft Guidance is part of a broader agency focus on personalized medicine.

FDA explains that the Draft Guidance expands on “existing policy” established in the agency’s final guidance entitled, “In Vitro Companion Diagnostic Devices” (Aug. 2014). That particular guidance states: “In some cases, if evidence is sufficient to conclude that the IVD companion diagnostic device is appropriate for use with a class of therapeutic products, the intended use/indications for use should name the therapeutic class, rather than each specific product within the class.” Here, in the Draft Guidance, FDA seeks to provide more detailed recommendations regarding broader labeling while cautioning that broader labeling is “not as simple as just matching diagnostic targets with therapeutic targets.” In particular, the agency provides the following considerations:

  • A sponsor should first identify the specific group or class of oncology therapeutic products to be included in a companion diagnostic’s labeling. A specific group or class of oncology therapeutic products are those approved for the same indication, including the same mutation(s) and disease for which clinical evidence has been developed with at least one device for the same specimen type of each therapeutic product.
  • The sponsor should have a detailed understanding of the mechanism of action of the specific group or class of oncology therapeutic products and the interactions between the therapeutic products and the biomarker(s), at the mutation level, detected by the diagnostic. For this information, sponsors may rely on valid scientific evidence, including therapeutic product labeling, therapeutic product study data, or peer-reviewed scientific literature, or the sponsor could perform clinical studies (as needed).
  • A sponsor should be able to show that there is sufficient and consistent clinical experience with the group or class of therapeutic products for the same biomarker-informed indications. Generally, there should be experience with at least two FDA-approved therapeutic products that would make up the group or class for the broader indication.
  • The sponsor should demonstrate analytical validity of the companion diagnostic across the range of biomarkers that inform that indication and clinical validation with the therapeutic products in the disease of interest. Currently cleared or approved tests for use with a therapeutic product can “generally leverage the information in their cleared or approved submission….” For analytical validation, FDA does caution that difference in technology should be studied, as certain mutations may not be detectable by all technological forms. For clinical validation, the agency notes that it is important to consider the defined cut-off for a specific companion diagnostic, as different cut-offs may identify different groups of patients.
  • The agency is interested in meeting with sponsors seeking class labeling. FDA states that the pre-submission process can assist a sponsor in determining the appropriate pathway to achieve class labeling. The agency also notes that pursuing class labeling may require collaboration with therapeutic product developers.

FDA has established a docket for a 60-day public comment period. Comments are due by February 5, 2019. Specifically, the agency is soliciting comments on four questions/issues:

  • Please describe any specific challenges with developing the evidence needed to identify in labeling a companion diagnostic for use with a specific group or class of oncology therapeutic products, rather than a specific therapeutic product. For example, please describe any challenges resulting from industry or business practices, including business agreements. What actions can FDA take to address the challenge(s)?
  • Please describe any specific challenges with submitting a premarket approval (PMA) supplement to FDA to expand the labeling for an approved companion diagnostic for use with a specific group or class of oncology therapeutic products. What actions can FDA take to address the challenge(s)?
  • Please describe any additional actions FDA can take to facilitate or encourage broader, evidence-based labeling that supports the use of a specific group or class of oncology therapeutic products with a companion diagnostic.
  • The guidance notes that variations in defined cut-points established for specific biomarkers for companion diagnostics can lead to challenges in implementing broader labeling for a specific group or class of oncology therapeutic products. Are there actions that FDA, or the broader scientific community, can take to facilitate standardization in this area?