As we have previously blogged on numerous times (for example, here and here), FDA has released a framework for regulation of laboratory developed tests (LDTs). FDA’s proposed framework has sparked much controversy, receiving support from diagnostic test manufacturers and some patient groups, while other patient groups and the laboratory community have strongly opposed the draft framework. Numerous comments on the proposed framework were submitted to FDA earlier this year.
Recently, a different approach to LDT regulation has been floated. The Diagnostic Test Working Group (DTWG), an independent group consisting of representatives from diagnostic manufacturers and clinical laboratories, released an alternative to FDA’s LDT Framework (executive summary and full proposal are available here and here).
The DTWG proposal offers a compromise for those on both sides of the LDT debate. For laboratories, it would mean greater regulation of LDTs while not trying to fit LDTs into the traditional medical device regulatory framework, and for IVD manufacturers, it would result in significant changes to the current regulatory model. A few key points of interest in the DTWG proposal:
- The proposal would apply to all in vitro diagnostic tests – both kits and LDTs, and components of the same (collectively IVDs) and calls for establishment of a new center within FDA.
- The proposal allocates responsibility for oversight of IVDs across FDA, CMS and the individual states. FDA would be responsible for IVD development, CMS would be responsible for laboratory operations, and the states would be responsible for medical applications (e.g., test result interpretation and consultation). This allocation is designed to address the concern about overlapping regulation.
- IVDs will be classified as high risk, moderate risk and low risk, and the proposal sets out criteria for classification into each category. Developers of a new IVD will propose a classification to FDA, and FDA will have 60 days to object.
- • IVDs can move from high risk to low risk when the test and/or analyte become well characterized.
- • The proposal sets a new standard for IVDs: the developer must “establish a reasonable assurance of analytical validity and clinical validity for the intended use.” Reasonable assurance would be established through competent and reliable evidence, which includes a number of different types of information such as published literature and clinical guidelines. There would be a presumption that clinical trials would not be required to demonstrate clinical validity.
- The premarket requirements for each of the three classifications are different. High and moderate risk IVDs require premarket submissions and low risk IVDs merely require notification to FDA.
- New submissions would be required for test modifications to high and moderate risk IVDs, if the modification has a “meaningful clinical impact” or changes the intended use of the IVD. A submission would be required for a low risk IVD, if the modification changes the intended use, purpose of the assay or the target disease or condition.
- The proposal includes special pathways for IVDs for rare diseases, emergency use IVDs, and IVDs for unmet needs.
- Post-market quality system and recall reporting will be generally the same as FDA’s current medical device requirements. Adverse event reporting would be clarified to better fit IVDs.
- There is a proposed three or four year transition period for LDTs currently on the market and those that would enter the market after the proposal goes into effect.
- Instrument platforms will be automatically classified as low risk. Platform manufacturers would also be granted a safe harbor for discussion of off-label uses.
- Paralleling a relatively new program for pharmaceuticals, the proposal also includes priority vouchers for innovative IVDs.
In our view, this proposal is an intriguing start towards a potential LDT compromise. There are certainly many areas of clarification and development that are still required and many key details will still need to be worked out. We expect that many laboratories will prefer the DTWG’s proposal as it would mean less onerous regulation compared to FDA’s proposed LDT framework. Manufacturers may also find the change to IVD regulation to be attractive. This proposal could form the basis of legislation that may be released in the near future. We will keep readers apprised of any legislative developments.