New VALID Act Would Establish Risk-Based System for LDTs Regulation

After months of dormancy, Congress has resumed its efforts to clean up the mess over regulation of laboratory-developed tests (LDTs). As part of the FDA user-fee bill that’s working its way through the Senate, members of the Senate Committee on Health, Education, Labor and Pensions (HELP) have proposed a modified version of legislation that would allow the FDA to continue to regulate LDTs on a risk-tiered basis.

The New VALID Act

The Senate bill is a revised version of the Verifying Accurate Leading-edge IVCT Development (VALID) Act, that’s been around in several different incarnations for a number of years, most recently in 2020. VALID would treat LDTs the same as tests developed by commercial companies with all in vitro clinical tests to be grouped into three tiers:

• High-Risk tests, i.e., those whose inaccurate results would be likely to cause death, serious harm or other negative outcomes, would be subject to FDA premarket review;
• Moderate-Risk tests whose inaccurate results would cause only non-life threatening or medically reversible injury or treatment delay, could be brought to market via a voluntary “technology certification” program requiring companies to demonstrate merely that they have appropriate internal test validation processes; and
• Low-Risk tests would be exempt from premarket review.

Labs and test makers would also be allowed to make changes to moderate-risk tests that reach the market without undergoing premarket FDA review, unless those changes have a potentially significant impact on the product’s safety and effectiveness.

The VALID Act Controversy

While all acknowledge the need for reforming LDT regulation, the new VALID Act has received mixed reviews. The first controversy is in regard to tactics, namely, attempting to use the FDA user-fees bill to push through systematic changes to lab test regulation, an issue that has been subject to longstanding debate across industry, Congress, the FDA, and other stakeholders. “The VALID Act remains a complex bill that will have far reaching implications for clinical microbiology laboratories and infectious disease diagnostic testing,” stated the American Society for Microbiology (ASM), while urging lawmakers “to address these concerns before advancing the bill as part of [the user-fees bill], which is a fast-moving legislative package.”

But the really divisive aspect of the new VALID is its regulatory leniency. The American Clinical Laboratory Association (ACLA), which has advocated for a risk-based regulatory framework, has embraced the bill, characterizing it as a “pivotal moment in the multiyear effort on diagnostic regulatory reform.”

But others expressed concern about the implications of allowing labs and test makers to have such easy access to the market. The bill’s exemptions “need to be narrowed to ensure that high-risk tests are subject to the appropriate oversight,” wrote the Pew Charitable Trusts. The nonprofit called for giving the FDA discretion to evaluate tests when it deems it necessary.

Others have criticized the bill for its provisions imposing user-fees for IVCT review and the financial burdens it would cause to labs. There are “vast differences between large commercial test developers and individual, nonprofit laboratories at academic and other medical centers that develop LDTs,” wrote the ASM. “Clinical microbiology laboratories already operate on a thin margin within the health care facilities and are not profit centers.” Lumping them together with big commercial entities for user-fees purposes is “unreasonable,” it added.

And, of course, there’s also the issue of whether the FDA should be in the business of regulating LDTs at all. Many believe that the agency’s assertion of control over LDTs exceeds its legal authority under the Food, Drugs and Cosmetics Act. Thus, rival legislation called the Verified Innovative Testing in American Laboratories (VITAL) Act of 2021 would strip the FDA of any oversight of LDTs and give HHS sole jurisdiction to regulate such tests under the Clinical Laboratory Improvements Act (CLIA).

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Here are some of the key new FDA EUAs and clearances that were announced in late April and May, 2022:

New FDA Emergency Use Authorizations (EUAs) & Approvals

Manufacturer(s)	Product
Angle	Clearance for Parsortix cell sorting system for isolation of circulating metastatic breast cancer cells for liquid biopsy testing
LabCorp	EUA for Labcorp Seasonal Respiratory Virus RT-PCR Test for simultaneous qualitative detection and differentiation of SARS-CoV-2, influenza viruses A and B, and respiratory syncytial virus, including for OTC use
Nexus Medical Labs	EUA for High Throughput SARS-CoV-2 Assay
Abbott	EUA for ID Now COVID-19 2.0 rapid point-of-care test
Becton Dickinson	510(k) clearance for MX molecular diagnostics module and triplex assay for chlamydia, gonorrhea, and trichomonas
Hologic	Approval for Aptima CMV Quant assay to quantify viral load of cytomegalovirus in patients who’ve had solid organ or stem cell transplants
BioFire Diagnostics (part of BioMérieux)	De novo approval for Joint Infection (JI) in vitro diagnostic panel
Mirvie	Breakthrough device designation for test to assess woman’s risk of developing preeclampsia before symptoms occur
Fujirebio Diagnostics	De novo approval for Lumipulse G β-Amyloid Ratio (1-42/1-40) test for Alzheimer's disease
Abbott	Approval for Alinity m STI Assay to detect and differentiate between Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium for use on Abbott's Alinity m PCR platform
Audere	EUA for HealthPulse@home Fusion collection kit
LGC Biosearch Technologies	EUA for SARS-CoV-2 ultra-high-throughput End-Point RT-PCR Test

New CE Marks & Global Certifications

Notable European CE certifications announced during the period:

New CE Markings in Europe

Manufacturer(s)	Product(s)
Hologic	Panther Fusion EBV Quant Assay and Panther Fusion BKV Quant Assay
SeekIn	SeekInClarity Cancer Treatment Response Monitoring Kit
Centogene	CentoCloud cloud-based software-as-a-service platform
Genes2Me	Over 25 NGS-based panels for oncology, pharmacogenomics, and hereditary diseases
Genomic Testing Cooperative (GTC)	Hematology Profile Plus, Solid Tumor Plus, and liquid biopsy profiles for both solid tumors and hematology
CareDx	AlloSeq HCT chimerism testing kit and AlloSeq HCT interpretation software
Precipio	HemeScreen panels for hematologic malignancies
Gradientech	QuickMIC system and Gram-negative panel for antibiotic susceptibility testing (AST) of samples from sepsis patients
Indica Labs	HALO Prostate AI, a deep learning-based screening tool designed to assist pathologists in identifying and grading prostate cancer in core needle biopsies
Luminex (part of DiaSorin)	Aries Flu A/B & RSV+SARS-CoV-2 Assay
LumiraDx	Five-minute SARS-CoV-2 Ag Ultra Test
Cepheid (part of Danaher)	Xpert Xpress CoV-2 plus, rapid molecular diagnostic test adding a third gene target for detecting future viral variants
Cytek Biosciences	Series of single-color cFluor reagents and a six-color T-cell, B-cell, and NK-cell (TBNK) kit
Gemina Laboratories	Gemina Legio X COVID-19 Rapid Antigen Test
Achiko	COVID-19 AptameX test and system
Qiagen	Therascreen EGFR Plus RGQ PCR Kit
Qiagen	QiaStat-Dx automated syndromic testing system
Qiagen	NeuMoDx HSV 1/2 Quant Assay on the NeuMoDx 96 and 288 Molecular Systems
BioMérieux	2 immunoassays to detect Chikungunya virus infection
Paige	Prostate Biomarker Suite AI software detecting 4 prostate cancer biomarkers on digitized tissue images stained with hematoxylin and eosin (H&E)
Biomerica	Hp+detect Helicobacter pylori test
MedMira	Multiplo Complete Syphilis (TP/nTP) Antibody Test
Inex Innovate	Point-of-care OvaCis Rapid Test
Agilent Technologies	PD-L1 IHC 22C3 pharmDx companion diagnostic assay for use in cervical cancer
Lucira Health	COVID-19 and combination COVID-19 and influenza A/B molecular tests
NGeneBio	MTBaccuPanel quantitative NGS assay for Mycobacterium tuberculosis and nontuberculous mycobacteria
NGeneBio	OncoaccuPanel NGS-based comprehensive genomic profiling panel for cancer

Other international clearances announced during the period:

Manufacturer(s)	Country(ies)	Product(s)
Qiagen	South Korea	Therascreen KRAS RGQ PCR Kit as CDx to identify patients with KRAS G12C-mutated non-small cell lung cancer eligible for Amgen's KRAS inhibitor Lumakras (sotorasib)
BioMérieux	Canada	BioFire Blood Culture Identification 2 panel for rapid identification of bloodstream infections
LumiraDx	World Health Organization	SARS-CoV-2 Ag Test