The Proposed Framework
Because all LDTs are deemed devices by FDA, all labs that make LDTs are subject to regulation under the FDC Act. FDA, however, does not intend to regulate all LDTs in the same manner. Rather, the agency has proposed a tiered, risk-based structure.
If the guidance is finalized, all labs with LDTs—except for those doing forensic testing or certain LDTs for transplantation—will need to comply with some basic statutory requirements, regardless of risks. These will include registering with FDA (or providing a special notification in lieu of registering), submitting Medical Device Reports (MDRs), and submitting notices to FDA in the event the laboratory initiates corrections or removals. These are nontrivial obligations, but significantly less burdensome than what will follow for many labs. All labs with LDTs will need to establish procedures to comply with the MDR and reporting regulations. They will also need to evaluate the complaints they receive and corrective actions they take to determine whether they need to submit reports to FDA.
Some LDTs will be subject to only these basic requirements. One such group consists of low-risk LDTs. Those will be well-established tests, and thus new markers or new technologies generally will not fall within this category. FDA will also exempt “Traditional LDTs.” FDA identified four criteria that it will consider, including that the LDT is used to test patients only at the facility that made the LDT.
Another group consists of LDTs for “rare diseases.” However, that nomenclature is really a misnomer. The category is based on rarity of testing, not the rarity of the disease. It applies only if fewer than “4,000 patients a year . . . would be subject to testing using this device.” As a practical matter, this exemption is likely to be of little utility, since it may take hundreds or thousands, or even tens of thousands, of tests to identify one patient with a rare disease.
The final low regulation category is “LDTs for Unmet Needs.” FDA lists several factors it will consider, including that there is no FDA-cleared or approved test “for that specific intended use” and the LDT “is both manufactured and used by a healthcare facility laboratory” that is treating the patient. Although FDA does not say so explicitly, it appears that FDA would not accord "Unmet Need" status to an LDT unless it is offered only to patients of the facility where the test is conducted. If all of these elements must be met, this exemption would likely be of limited significance due to the geographic restrictions. Thus, while some LDTs will be exempt, those exemptions, as drafted, may be fairly narrow in scope.
All other LDTs will face the full panoply of FDA regulation. This includes registration or notification, MDRs and recall reporting, premarket review, and compliance with the Quality System Regulation. Implementation of these provisions will be phased in.
The first LDTs that will need to comply with these requirements are the high-risk LDTs. FDA plans to require that companies with the highest risk devices submit marketing applications within 12 months of the finalization of the guidance. These first-in-line LDTs include ones that have the same intended use as a companion diagnostic that has been cleared or approved by FDA, and LDTs that have the same intended use as kits that have been approved by the premarket approval (PMA) process. One of the many details that will need to be ironed out is what exactly “the same intended use” is in this context.
The second batch of LDTs that will undergo FDA review are those high-risk devices that do not fall into the first tranche. It is unclear which of these LDTs will be the first to be the subject of a marketing application. FDA says it will develop a plan to decide the sequence in which this next tranche gets called, and will solicit public feedback in developing this prioritization scheme.
FDA expects that it will take five years to work through the process with the high-risk LDTs. The agency then intends to proceed with moderate risk devices. That phase is expected to last four more years. Thus, the framework contemplates a very long process, lasting nine years from initiation to completion.
Under the framework, labs that create high-risk LDTs will be grandfathered for existing tests if they submit their marketing applications when called for. (Presumably, grandfathering will extend to moderate risk tests as well.) On the other hand, labs that want to offer new LDTs will need “to comply with premarket review requirements before marketing of such LDTs” (emphasis added). This grandfathering may well spur labs to introduce new tests ahead of any call for submissions.