NEW YORK – The US Food and Drug Administration has issued a draft guidance detailing its proposed policies for predetermined change control plans (PCCPs) for medical devices.
The guidance will likely prove of interest to the clinical laboratory industry, which has identified PCCPs as potential source of flexibility for modifying and updating laboratory-developed tests (LDTs) following the FDA's recently issued final rule on regulating these assays.
Codified in the Food and Drug Omnibus Reform Act of 2022 (FDORA), PCCPs allow manufacturers to make certain changes and updates to FDA-cleared or approved devices without having to take them back through the regulatory process.
A PCCP is documentation submitted as part of a device's larger regulatory package that details future changes or updates a manufacturer may want to make to the device as well as how those changes will be implemented and validated. If approved, the PCCP allows the manufacturer to make those changes without having to take the device back through premarket review.
PCCPs have commonly been discussed as a tool for updating software and AI-based devices, but they are applicable to diagnostics more broadly, and FDA's move to exert authority over LDTs has driven interest in PCCPs among some clinical labs and laboratorians.
Examples of where PCCPs might be used include a manufacturer adding a new strain to a previously cleared flu test or a new genetic variant to a genetic test. Exactly what the scope of PCCPs will be has remained uncertain, however.
The new draft guidance remains somewhat vague on exactly what modifications might be covered under a PCCP, but it does provide some details. For instance, "certain changes in the labeling and/or the indications for use to specify use of the device with an additional device, component, or human genetic variant" may be appropriate for inclusion in a PCCP. On the other hand, "changes in the labeling and/or the indications for use to include a new patient population" are "generally not appropriate," for inclusion, the guidance states. Broadly speaking, the guidance indicates that modifications are not appropriate for inclusion in a PCCP if they introduce a "major change" to a device's intended use, "significantly affect" its safety or effectiveness, or introduce a new risk.
The guidance also provides a number of examples of specific devices and modifications that would and would not be appropriate for inclusion in a PCCP. One example concerns a microarray-based IVD cancer predisposition risk assessment system for over-the-counter use intended to detect five single-nucleotide variants in BRCA1 and three SNVs in BRCA2 in saliva to describe if a person is at increased risk of breast cancer, ovarian cancer, or prostate cancer.
Examples of appropriate modifications include addition of new SNVs, addition of insertion and deletion variants up to 20 base pairs, and labeling updates to provide information on potentially cross-reactive polymorphisms. Inappropriate modifications include adding new copy number variants, new genes, changing the collection device and sample type, and moving from a manual to an automated process.
In addition to providing details on what kinds of modifications may be included in a PCCP, the draft guidance lays out processes for establishing and writing PCCPs as well as for implementing modifications based on authorized PCCPs.
The draft guidance will be open for public comment for 90 days following its official issuance on Aug. 22.