RUOs and FDA Approval
Although laboratory tests using RUO products are not generally subject to FDA regulation, there are situations where RUO assays do intersect with the premarket review process. One area of overlap involves the use of RUO assays or instruments in support of a marketing application by an IVD manufacturer. FDA has not yet publicly and formally articulated its policy on marketing applications that incorporate an RUO product. Applicants do need to be aware that, at a minimum, they will need to bring the RUO product into their own quality system. Because RUO products are not subject to the Quality System Regulation, the applicant will need to develop appropriate quality oversight for the RUO component.
In some circumstances, it may even be necessary to obtain FDA clearance for the RUO product in order for the application to succeed. For other lower risk products sold as RUO, FDA’s concerns sometimes can be satisfied by having the third-party supplier relabel its product as an “in vitro diagnostic” and list it with FDA as a device. IVD companies incorporating RUO products into their product should consult with FDA at an early stage to address potential issues involving the use of an RUO product. This is particularly important if the RUO product plays a fundamental role in the potential diagnostic product.
Pharmaceutical companies also need to be alert to the issues stemming from the use of RUO products in clinical trials. There is no bar against the use of RUOs during a clinical investigation. An RUO product could, for example, be used to help evaluate changes in a novel biomarker in a Phase II study. One major problem, though, is whether the resulting data would be acceptable to FDA reviewers to support approval. Using an RUO test to help explore and understand biomarker relationships is fine, but relying on this data in a regulatory submission can be problematic. If a companion diagnostic is needed for approval of the drug, an RUO product will not be acceptable.
FDA has recognized that more detailed guidance involving RUOs would be helpful. In the early 1990s, FDA proposed several draft guidance documents. That effort was eventually abandoned. More recently, FDA has indicated that it is planning to issue a draft guidance soon. When that draft document will be released or what it will say remains uncertain.
RUOs are an important class of products. Over the years, they have raised many questions and provoked considerable regulatory controversy. FDA’s pending draft guidance document is unlikely to answer all the questions or end the controversies.