In late November, FDA announced that it would not be finalizing the 2014 draft LDT Guidance. The Agency had, however, done a significant amount of work regarding the draft guidance and evaluating the regulatory framework for lab tests. In an effort to document the work that it had done and further the public discussion regarding LDTs, FDA issued a discussion paper on Friday (the 13th) laying out key elements of a possible revised future LDT regulatory framework.
Released in the last week of the Obama administration, the discussion paper is in no way a formal proposal by FDA. We think, however, it is worth noting a few key elements that could potentially appear in a renewed attempt to regulate LDTs in a new administration. The discussion paper states the following:
- LDTs on the market at the time a final guidance is issued would not be expected to comply with any FDA regulatory requirements except for MDR reporting, unless necessary to protect the public health;
- Certain categories of LDTs entering the market after issuance of a final guidance would be exempt from regulation, unless necessary to protect the public health. These categories are consistent with the proposed LDT guidance and included, among others, low risk LDTs, LDTs for rare diseases, and Traditional LDTs;
- FDA has the ability to regulate any of the exempt LDTs if it concludes that the test is not analytically or clinically valid or there is insufficient data to support analytical or clinical validity, the LDT manufacturer has engaged in deceptive promotion, or there is a reasonable probability that an LDT will cause death or serious adverse health consequences (in other words, FDA believes it can regulate selected LDTs);
- For the remaining tests that will be subject to FDA regulatory oversight, the requirements would be phased in using a risk-based approach in four years rather than nine years as proposed in the draft guidance;
- Tests that enter the market after a final guidance is issued but before their phase-in date could be offered commercially during its premarket review, and manufacturers would have two years to comply with the Quality System Regulation (QSR);
- The third-party premarket review program could be expanded to accept certain LDT approvals, including, for example New York Department of Health (note: the discussion paper does not consider the statutory limitations to having a third-party reviewer evaluate clinical data related to an LDT);
- FDA could accept compliance with the Clinical Laboratory Improvement Amendments quality requirements to satisfy the QSR, with the exception of design controls, acceptance activities, and corrective and preventive actions (CAPA);
- Evidence of clinical validity should be made publicly available; and
- Changes to LDTs would require premarket review if the change significantly changes the performance specifications or intended use of the test.
As we discussed in our last LDT post (see here), there are a number of ways FDA could still attempt to regulate LDTs even without a final guidance. The discussion paper does not allude to how FDA could proceed to indirectly regulate LDTs until it puts forth a new LDT proposal, beyond noting that FDA reserves the right to attack LDT tests it considers invalid.
The discussion paper does, however, make clear that FDA believes compliance wouldn’t be too burdensome for laboratories. Whether that assessment is correct is debatable. For example, the discussion paper says that “clinical validity, especially of established tests, can often be supported by literature, well-curated databases, or other appropriate sources that meet the valid scientific evidence standard.” As we have previously noted, FDA rarely accepts data other than prospective clinical studies; even performing studies using banked samples can be difficult. It is possible that third-party reviewers may be more accepting of alternative forms of clinical data; however, we do not expect FDA would change its standards.
As is so often the case, the devil is in the details. Assuming FDA does resume its quest to regulate LDTs, we will have to wait quite a while to learn the details.