Test Driving VALID2021
October 28 Meeting
Download the slide deck from the meeting.
September 23 Meeting
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September 2 Meeting
The group had a productive first meeting. Please find the meeting recording along with the powerpoint slides below.
Download the slide deck.
Project Overview
Title: Test Driving VALID2021
Authors: Shannon Bennett & Joe Lennerz
Addressed Parties: We are looking for stakeholders to examine practical implications of the VALID Act of 2021.
Background: On June 24, 2021, bipartisan members of both the House and Senate reintroduced a revised version of the Verifying Accurate Leading-edge IVCT Development (VALID) Act, following up on its initial introduction in March 2020 in the prior session of Congress. The general framework for the proposed new system for FDA’s regulation of in vitro clinical tests (IVCTs) has been slightly modified and still revolves around a concept called “technology certification”.
Approach & Objectives: The aim of this project is to select three use cases from pathology practice and discuss these against the anticipated legislative framework proposed in the VALID act of 2021. Specifically, we will focus on which submission pathway would be appropriate (low-/high-/high- with mitigating measures) and then the potential for technology certification.
Deliverables: The key deliverables is a website entry on the PIcc/Alliance webpage that will serve as a discussion basis and resources for interested stakeholders.
Currently proposed test driving scenarios for laboratory-developed tests are:
1) a whole slide imaging based artificial intelligence application to predict combined Gleason grade from H&E stained routine FFPE sections
2) PD-L1 immunohistochemical staining for a solid tumor (CoDx) that is cross-referencing another approved test
3) a Next-generation sequencing assay (multiple established biomarkers)
Value proposition:
“How will the proposed project be valuable from each of these categories?” Address each in detail:
· Clinical: Oversight of high-complexity molecular diagnostic tests developed in laboratories will affect patient care
· Regulatory: Providing a concrete basis for regulatory discussions is an important basis to provide input into regulatory decision making.
· R&D: Outlining some of the challenges will reveal potential gaps and or approaches to provide new evidence regarding meaningful legislation
Funding sources: N/A
Benefit to patients: technical advance, increased quality, outcome, access, affordability
References: N/A
Useful Resources
AACC-ACMG-AMP-APC Joint Webinar on “The Regulatory Landscape of Laboratory Developed Testing Procedures: How we got here, why it’s important, where we’re going, and how you can get involved”. Slides and recordings of presentations are available.
VALID 2021 Definitions
IN VITRO CLINICAL TEST. A test intended by its developer to be used in the collection, preparation, analysis, or in vitro clinical examination of specimens taken or derived from the human body for the purpose of—
(i) identifying or diagnosing a disease or condition;
(ii) providing information for diagnosing, screening, measuring, detecting, predicting, prognosing, analyzing, or monitoring a disease or condition, including by making a determination of an individual’s state of health; or
(iii) selecting, monitoring, or informing therapy or treatment for a disease or condition; and
(B) may include—
(i) a test protocol or laboratory test protocol;
(ii) an instrument (as defined in section 587(11));
(iii) a specimen receptacle;
(iv) software, excluding software that is excluded by section 520(o) from the definition of a device under section 201(h), and excluding modifications that are exempt in accordance with section 587A(l)(2)(A); and
(v) subject to subparagraph (2), a component or part of a test, a test protocol, an instrument, an article, or software described in any of clauses (A) through (D) of such subparagraph, whether alone or in combination, including reagents, calibrators, and controls.
LOW-RISK. The term ‘low-risk’, with respect to an in vitro clinical test or category of in vitro clinical tests, means that an undetected inaccurate result from such in vitro clinical test, or such category of in vitro clinical tests, when used as in15 tended by the developer—
(A) would cause minimal or no harm, or minimal or no disability, or immediately reversible harm, or would lead to only a remote risk of adverse patient impact or adverse public health impact, taking into account the degree to which the technology for the intended use of an in vitro clinical test or category of tests is well characterized and the criteria for performance of the test or category of tests are well-established for the intended use, the clinical circumstances under which the in vitro clinical test or category of tests is used, and the availability of other tests (such as confirmatory or adjunctive tests); or
(B) would cause a serious adverse health consequence, harm that is reversible, a delay in necessary treatment that is not life-supporting or life-sustaining, or would lead to a serious risk of adverse patient experience or adverse public health impact, but applied mitigating measures have the capacity to ensure the test meets the standard described in subparagraph 13 (A).
HIGH-RISK. the term ‘high-risk’, with respect to an in vitro clinical test or category of in vitro clinical tests—
(i) means that, when used as intended by the developer, an undetected inaccurate result from such test or category—
(I) presents unreasonable risk for serious or irreversible harm or death to a patient or patients, or would otherwise cause serious harm to the public health; or
(II) is potentially likely to result in the absence, significant delay, or discontinuation of life-supporting or life-sustaining medical treatment;
(ii) shall account for the degree to which the technology for the intended use of an in vitro clinical test or tests is well characterized and the criteria for performance of the test or tests are well-established for the intended use, the clinical circumstances under which the in vitro clinical test is used, and the availability of other tests (such as confirmatory or adjunctive tests).
(B) EXCEPTION.—The term ‘high-risk’ does not include an in vitro clinical test de19
scribed in subparagraph (A) if—
(i) mitigating measures are established to prevent, detect, or otherwise mitigate the risk of inaccurate results as described in subparagraph (A), or—
(ii) an exemption from the definition of such term applies under section 587A.
MITIGATING MEASURES. The term ‘mitigating measures’—
(A) means controls, standards, or requirements that the Secretary determines, based on available evidence—
(i) are necessary for an in vitro clinical test, or a category of in vitro clinical tests, to meet the applicable standard; or
(ii) to mitigate the risk of harm ensuing from an inaccurate result such that a test or category of tests subject to such mitigating measures does not meet the definition of high risk, or such that a test or category of tests subject to such mitigating measures is low risk; and
(B) includes, as appropriate, applicable requirements regarding labeling, conformance to performance standards or guidance, performance testing, submission of clinical data, advertising, website posting of information, clinical studies, postmarket surveillance, user comprehension studies, training, and availability of confirmatory laboratory or clinical findings.
