Proposal highlights
Differences from 2014 draft guidance


In an unusual move, the Food and Drug Administration (FDA) published a discussion paper on January 13 2017 entitled "Discussion Paper on Laboratory Developed Tests", which proposes a new regulatory framework for laboratory-developed tests. The discussion paper describes a risk-based approach that differs significantly from the FDA's initial proposal in a draft guidance document issued in 2014 and reflects a lighter touch for most laboratory-developed tests.


The discussion paper is not enforceable and does not represent the formal position of the FDA, nor does it constitute a final version of the draft guidance. Rather, issuing the paper allows the FDA to publicise, gauge and build support for its proposals on a controversial topic while avoiding the requirement that the FDA provide notice to Congress 60 days before issuing any final or draft guidance on laboratory-developed tests.

Although the FDA's issuance of a discussion paper on laboratory-developed tests is unexpected, the move is not unprecedented. For example, the FDA first vetted its potential policy approach to next generation sequencing with a preliminary discussion paper in 2014. The FDA then published additional discussion papers and held public workshops to gather stakeholder input before releasing two draft guidance documents in July 2016. The proposals announced in the next generation sequencing draft guidance documents tracked certain key provisions that were advanced in the discussion papers.

Proposal highlights

The FDA's proposal for regulatory oversight of laboratory-developed tests reflects a risk-based, phased-in approach, but backs away from many provisions of the draft guidance.

There are a number of key provisions in the FDA's proposal:

  • Prospective oversight – the proposed framework focuses on new and significantly modified high and moderate-risk products and exempts 'grandfathered' products from most FDA regulatory controls.
  • Grandfathered products – while grandfathered products would be subject to serious adverse event and malfunction reporting, the prospective oversight approach means that products already on the market would not have to comply with FDA regulatory requirements, including:
    • pre-market review;
    • quality system regulation; or
    • registration and listing requirements (although the FDA would retain the ability to enforce these requirements under certain circumstances).
  • Traditional, low-risk and other laboratory-developed tests – certain new or significantly modified laboratory-developed tests, including low-risk laboratory-developed tests and laboratory-developed tests for rare diseases, would be subject to serious adverse event and malfunction reporting, but would not be subject to other regulatory requirements.
  • Premarket evidence – the FDA would review clinical and analytical data in pre-market submissions and expand its third-party pre-market review programme.
  • Laboratory-developed test modifications – the FDA would have limited pre-market review of changes to cleared laboratory-developed tests.
  • Quality system requirements – the FDA would leverage Clinical Laboratory Improvement Amendments (CLIA) certification requirements and focus on only three quality system requirements:
    • design controls;(1)
    • acceptance activities (ie, mechanisms to ensure a product meets specifications throughout testing);(2) and
    • procedures for corrective and preventive actions.(3)
  • Conventional in vitro diagnostic (IVD) kits – the paper addresses only laboratory-developed tests that are designed, manufactured and used in a CLIA-certified laboratory and does not apply to conventional IVD kits, which would require pre-market review.

Differences from 2014 draft guidance

Notable differences from the proposal outlined in the 2014 draft guidance include the following:

  • Instead of being phased in, currently marketed high and moderate-risk laboratory-developed tests would not be subject to pre-market review, unless necessary to protect public health.
  • The phased-in review of new and significantly modified laboratory-developed tests could be accomplished over a shorter period (four years rather than the nine years proposed in the draft guidance) because of the high number of grandfathered products, and would begin with the tests that could pose the greatest risk to patients in the event of a false result.
  • The FDA would take measures to expedite the pre-market review process by:
    • collaborating with healthcare professionals, industry and other stakeholder groups to leverage accepted reference and review standards for analytical validity;
    • expanding its third-party pre-market review programme to include laboratory-developed tests that are eligible under existing programmes (eg, the New York State Clinical Laboratory Evaluation Programme and programmes run by CLIA-accrediting organisations); and
    • permitting clinical validity to be established by sources, such as literature and 'well-curated' databases, that meet the valid scientific evidence standard.
  • A 'traditional' laboratory-developed test – which under the discussion paper, as according to the draft guidance, would be grandfathered – is defined differently than it was in the 2014 draft guidance to mean "tests that use components that are legally marketed for clinical use and whose output is the result of manual interpretation by a qualified laboratory professional", which excludes tests that use automated instrumentation or software to interpret the results. The intent of the new definition seems to be to exclude tests that utilise research use only components, as well as multi-analyte algorithm-based assays tests from grandfathering.
  • The discussion paper proposal broadened the category of laboratory-developed tests for unmet needs so that it is no longer limited to tests that are manufactured and used by a healthcare system laboratory for patients treated within that facility's healthcare system. Rather than exercising enforcement discretion for pre-market review and quality systems requirements, the new approach would require laboratory-developed tests that address unmet needs to send a pre-market submission to the FDA or to a third-party reviewer within 90 days after entering the market, and the laboratory-developed test would be permitted to remain on the market during the review.

The FDA will likely solicit further stakeholder participation regarding the new proposals outlined in the discussion paper, possibly by holding a public workshop. Industry should carefully consider the proposals made in the discussion paper and be prepared to provide meaningful input.

For further information on this topic please contact Nancy K Stade, Allison Fulton or Tina Papagiannopoulos at Sidley Austin LLP by telephone (+1 202 736 8000) or email ([email protected], [email protected] or [email protected]). The Sidley Austin website can be accessed at


(1) 21 CFR Section 820.30.

(2) 21 CFR Section 820.80.

(3) 21 CFR Section 820.100.