On January 13, 2017, the Food and Drug Administration (FDA) released a discussion paper concerning an updated proposed framework for oversight of laboratory developed tests (LDTs). According to FDA, the updated proposal is the result of ongoing engagement with industry stakeholders. Under the proposal, the FDA generally stands by its position that a complementary risk-based oversight framework that involves both the FDA and the CMS Clinical Laboratory Improvements Amendments (CLIA) program is the preferable alternative to a CMS-only framework. However, the updated proposal generally scales back FDA’s involvement in the framework and emphasizes the need for regulatory flexibility.

FDA’s new discussion paper does not represent the formal position of FDA, nor is it enforceable. The paper is meant merely to “advance the public discussion” by providing “a possible approach to spur further dialogue.”

Do not let this disclaimer (or the upcoming change in White House administration) dissuade you from reading the new paper. Change is coming for LDTs and diagnostics generally, regardless of who is in the White House. If your business relates in any way to LDTs and diagnostic tests currently regulated by FDA, then we suggest taking the time to read FDA’s updated proposed oversight framework and considering how this could impact your business operations and projections over the next decade and beyond.

Focused Oversight

FDA now proposes a prospective oversight framework that focuses on new and significantly modified high- and moderate-risk LDTs. Under this framework, previously marketed LDTs would be grandfathered – that is, they would not be expected to comply with most, if not all, of the FDA regulatory requirements. Additionally, certain new and significantly modified LDTs would likewise be exempt from a range of FDA requirements. Specifically, these exempt LDTs would be: (1) low-risk LDTs, (2) LDTs for rare diseases, (3) traditional LDTs, (4) LDTs intended solely for public health surveillance, (5) certain LDTs used in CLIA-certified, high-complexity histocompatibility labs, and (6) LDTs intended solely for forensic use.

However, the FDA would retain the ability to enforce regulatory requirements for any LDT, including these generally exempted LDTs, if the agency identifies any of the following issues: (1) the LDT is not analytically or clinically valid, (2) the LDT manufacturer has been engaged in deceptive promotion, or (3) there is reasonable probability that the LDT will cause death or serious adverse health consequences.

Risk-Based, Phased-In Oversight

FDA’s new discussion paper contemplates a shorter phase-in period than was proposed in the Agency’s 2014 draft guidance; specifically, premarket review for new and significantly modified LDTS could be phased in over four years, rather than nine. This four-year phase-in would first focus on the highest-risk tests and move on to other less-risky tests by year four. The FDA would allow tests introduced between the effective date of the finalized framework and the phase-in date for said date to continue to be offered for clinical use during the premarket review period, in order to ensure that patient access is not disrupted. Additionally, FDA’s new discussion paper contemplates a more broadly defined “unmet need” category that would allow greater flexibility for LDTs that address unmet need than was originally proposed in 2014.

Evidence Standards

FDA intends for the premarket review process, where required, to be complementary to, and not duplicative of, CMS’ postmarket oversight. Under this approach, FDA contemplates engaging with industry to determine how existing review programs could be leveraged to reduce the burden of conducting premarket review.

Third-Party Review

FDA contemplates expanding its third-party premarket review program to include eligible LDTs. For example, FDA is exploring whether to accept New York Department of Health’s Clinical Laboratory Evaluation Program determinations in lieu of the FDA’s own determinations.

Clinical Collaboratives

The FDA contemplates expanding its collaboration with industry to develop measurement and review standards, and to promote efficiency with regard to any future oversight framework.

Transparency

The FDA would make evidence of analytical and clinical validity for all LDTs available to the public to ensure transparency.

Modifications

The FDA emphasizes the need for regulatory flexibility to enable laboratories to make modifications to LDTs without undue burden, while still providing assurances to users that these modifications do not affect validity. To this end, the FDA would encourage laboratories to submit prospective change protocols in their premarket submissions. Subsequent modifications made in accordance with this change policy could then be made without the need for a new submission.

Leveraging CMS/CLIA: Quality System Requirements for LDTs

With regard to current quality system (QS) requirements, the FDA now proposes leveraging certification to CLIA requirements, even though these requirements are not fully consistent with the FDA QS requirements. For LDTs made in a CLIA-certified laboratory, the FDA would narrowly focus its assessment on only three FDA QS requirements that address aspects of test development not covered by CLIA: (1) design controls, (2) acceptance activities, and (3) procedures for implementing corrective and preventive actions. To this end, the FDA would also expand its third-party inspection program for LDTs so that many of these QS inspections could be conducted by FDA-accredited third parties.

Postmarket Surveillance

The updated proposed framework would initially require laboratories to report serious adverse events to the FDA with certain exceptions. The FDA indicates that, in the future, it may be able to decrease or discontinue such reporting as monitoring efforts mature.

With the release of this new discussion paper, FDA has signaled its intent to continue to drive the LDT discussion through transparency and additional engagement with all interested parties. Although FDA has not requested written comments to the new discussion guide, that fact should not stop you from informing the Agency about the feasibility of this new (or updated) proposed framework for regulating LDTs.