Regulation of Laboratory-Developed Products: What Next?

Katie M. Smith

FDA continued its march to restrict or regulate laboratory-developed tests (LDTs). Even though the recently issued draft guidance, “Commercially Distributed In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions” speaks to RUO- and IUO-labeled IVD products, it appears to target RUO and IUO IVD products that are adapted by small and large CLIA-certified labs into LDTs offered as clinical lab services. The timing of this guidance comes when new genomic and proteomic technologies are emerging, and clinical molecular labs are blossoming. These technologies find use in disease risk assessment and are of intense interest to pharmaceutical companies for identifying patients who will or will not benefit from therapies. Due to the rigors and uncertainties of FDA reviews of IVD products using new technologies, genomic mutation testing, for example, is often emerging as an LDT derived from RUO or IUO products.

Manufacturers of RUO and IUO IVDs offer products based on customer needs for reagents and/or tests emerging in research and clinical arenas. The evidence is often in published literature and points to a need to investigate the clinical utility of new biological entities. For such manufacturers to intend or even have knowledge of their customer’s initial or future use of an RUO or IUO product is limited or incidental at best. If the RUO or IUO product performs well in the hands of the laboratory customer and the customer is technically astute in using the product, there may be little communication or interaction between a manufacturer and a customer on the latter’s short- or long-term use of the product. Per the FDA guidance document, these business entities would have to take explicit action to “halt the sales for such use,” described as “non-investigational diagnostic use.” For manufacturers to gather now customer practice information or stop sales would undermine their business, create combative customer interactions, and downstream, discourage the development or use of clinically useful tests.

Individuals providing comments on the guidance offered serious concerns. Some also suggested positive changes to existing regulations such as expanding ASR regulations to include combination ASRs, or enhancing inspections of clinical labs under CLIA rather than an FDA focus on product labeling.

This guidance has created significant controversy. When FDA issues a revised guidance, it needs to strike the right balance between regulation and good business practices for RUO/IUO IVD manufacturers, CLIA-certified labs, research laboratories, and pharmaceutical companies.

Katie M. Smith, PhD, is principal at Katie Smith Consulting (San Diego). She can be reached via email at