Stakeholders Seek Clarification of Investigational IVD Draft Guidance

Stakeholders lauded the FDA’s efforts in developing draft guidance on the use of investigational in vitro diagnostic devices in clinical trials but said the agency needs to provide more specific examples for the guidance to be useful.

AdvaMed commended the agency on developing the draft and described it as a positive step in supporting innovators bringing new diagnostics to the U.S. to advance personalized medicine.

The FDA issued the draft guidance in December 2017, noting the growing interest in personalized medicine that relies on the use of IVDs to detect and measure biomarkers and other individual characteristics of diseases or other conditions to better manage patient treatment (IDDM, Jan. 1).

CDRH said it was concerned that study sponsors and Institutional Review Boards are unaware that many IVDs are investigational and their safety and effectiveness are still being assessed.

Extended List

In its comments, AdvaMed said it would like to see an “extended, comprehensive list of the known types of uses of IVDs in therapeutic product trials and clear instruction as to whether certain uses are considered investigational.”

Examples of each type of IVD use and whether it falls within the scope of the guidance would be helpful, the industry group said.

AdvaMed said it supports allowing submission of all investigational device exemption components to an investigational new drug application rather than requiring both an IDE and an IND. It said this approach would promote efficiency and speed the review process. It also supported pre-submission meetings with the FDA to help coordinate reviews among the FDA centers and to agree on study designs that support validation of the IVD.

The Biotechnology Innovation Organization also asked the FDA to provide a comprehensive list of “known, potential and/or most common uses of IVDs in therapeutic product trials and provide explanation as to why it is considered investigational vs. non-investigational.”

BIO pressed the agency to clarify that if the intended use of a cleared IVD is unchanged, then the IVD would not be considered investigational. It also sought clarification on what steps a sponsor should take when a change in risk status of an investigational IVD is noted. The association said risk determinations are not consistent, and more clarification was needed.

On the question of whether the agency should require both an IDE and an IND or one or the other, BIO said the process should remain flexible depending on circumstances, because sometimes it would be more beneficial to submit the IDE as part of an IND.

Three Categories

In its comments, Ilumina also welcomed the guidance and it commended the agency on the three categories of device studies outlined for significant risk studies, non-significant risk studies and exempt studies.

However, the company said the descriptions for making significant risk determinations are “terse and fail to recognize how difficult these risk determinations can be.” It suggested that the FDA provide concrete examples from its regulatory review experience.

PerkinElmer said in its comments that although it appreciated FDA’s effort to clarify when an IVD is investigational, “we believe the document is ambiguous as to whether laboratory-developed tests are by default considered to be investigational based on the definition of ‘an IVD that is legally marketed’.”

The devicemaker asked the agency to clarify where it stood on the applicability of laboratory-developed tests in the final guidance document, particularly since many clinical trials rely on the testing of samples submitted to labs in the absence of an available IVD.

PerkinElmer also pointed out that the guidance assumes that the IVD maker would have knowledge of the clinical study, but the device maker stressed that this is not always so clear.