Devices

FDA Discussion Paper on New LDT Oversight Proposal

David McFarland

— 2 min read
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An FDA discussion paper on laboratory developed tests (LDTs) outlines a new proposal to provide oversight of such devices. Recently, the agency announced that it would not issue a final guidance on LDT oversight at the request of various stakeholders to allow for further public discussion on an appropriate oversight approach, and to give congressional authorizing committees an opportunity to develop a legislative solution.

 

In the meantime, the paper seeks to advance dialog on an approach that would use a prospective oversight framework focusing on new and significantly modified high and moderate risk LDTs. Under such an approach, previously marketed LDTs would not be expected to comply with most or all FDA regulatory requirements, including premarket review, quality systems, and registration and listing, unless necessary to protect the public health. Additionally, new and significantly modified LDTs in the following categories would not be expected to comply with premarket review, quality systems, and registration and listing requirementsunless necessary to protect the public health:

  • Low risk LDTs;
  • LDTs for rare diseases;
  • Traditional LDTs (i.e., tests that use components that are legally marketed for clinical use23and whose output is the result of manual interpretation by a qualified laboratory professional, without the use of automated instrumentation or software for intermediate or final interpretation);
  • LDTs intended solely for public health surveillance (i.e., intended solely for use on systematically collected samples for analysis and interpretation of health data that are essential to the planning, implementation and evaluation of public health practice, which is closely integrated with the dissemination of these data to public health officials and linked to disease prevention and control24);
  • LDTs used in CLIA-certified, high-complexity histocompatibility labs to perform allele typing, antibody screening and monitoring, or crossmatching in connection with organ, stem cell, and tissue transplantation; and
  • LDTs intended solely for forensic use.

To protect patients from tests that could lead to harm, the proposal would allow the agency would retain its ability to enforce premarket review, quality systems, and other applicable requirements for any LDT if the agency identified one or more of the following:

  • The LDT is not analytically and clinically valid or there is an absence of sufficient data to support its analytical and clinical validity;
  • The manufacturer of an LDT has engaged in deceptive promotion; or
  • There is a reasonable probability that the LDT will cause death or serious adverse health consequences

Additionally, FDA proposes to leverage certification to Clinical Laboratory Improvement Amendments (CLIA) requirements, even though they are not fully consistent with FDA quality system requirements, and, for LDTs made within a CLIA-certified laboratory, narrowly focus its assessment on only three FDA QS requirements that address aspects of the test development process not covered by CLIA: design controls; acceptance activities (i.e., mechanisms to ensure that products meet specified requirements coming into the laboratory and throughout testing); and procedures for implementing corrective and preventive actions (CAPA). The discussion paper cautions: “Laboratories may need to expand their existing CAPA activities to cover the design and development phase, and this will help them offer improved tests over time FDA would also expand its third party inspection program for LDTs so that postmarket inspections could be conducted by FDA-accredited third parties.

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