Bill to Regulate LDTs Advances, but Is No Slam Dunk for Final Passage

On June 17, members of the Senate Committee on Health, Education, Labor and Pensions (HELP) put the finishing touches on a game-changing piece of legislation called the Food and Drug Administration Safety and Landmark Advancements (FDASLA) Act of 2022 (S. 4348), which would, among other things, establish a risk-based system for FDA regulation of laboratory developed tests (LDTs). Here’s a briefing of the latest developments and prospects for ultimate passage.

The New VALID Act 

The LDT provisions of the FDASLA are a revised version of the Verifying Accurate Leading-edge IVCT Development (VALID) Act designed to replace the current haphazard and arbitrary FDA regulatory regime with an orderly system for FDA oversight of LDTs based on risk. The new version of VALID would treat LDTs like 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. 

While enjoying the support of the American Clinical Laboratory Association (ACLA), VALID has drawn criticism from other groups who feel it is too stringent and that it shouldn’t be rushed through as part of a larger legislative package.

The Senate Markup

Given the controversy over VALID, the markup—i.e., process in which the congressional committee responsible for a proposed bill debates and adopts amendments—that took place in the Senate on June 14 assumed added importance. The HELP Committee considered two amendments.

Under the bill, companies that develop LDTs would pay user fees for IVCT review. While justifiable for large commercial test developers, there are concerns that user fees would impose undue financial burdens on individual, nonprofit labs at academic and other medical centers that develop LDTs. So, during markup, Sen. Tommy Tuberville (R-Ala.) proposed an amendment that would exempt academic medical centers from the VALID Act. While acknowledging the concern, HELP Committee chair Patty Murray (D-Wash.) characterized the proposed amendment as being too broad and moved to table, i.e., postpone consideration of it. The motion passed by a vote of 12 to 10.

However, the committee did adopt an amendment from Sen. Roger Marshall (R-KS) to require a General Accounting Office (GAO) report to evaluate VALID’s impact on academic medical centers, hospital-based labs, and other providers. And the marked up FDASLA, including the amended VALID Act, passed the committee by a 13 to 9 vote.

What Happens Next

The VALID Act is enmeshed in the FDA Medical Device User Fee Amendments (MDUFA) user fee situation. Explanation: The current user fees system, MDUFA IV, is due to expire and Congress must pass new MDUFA V legislation by Sept. 1 to keep the system going. The House has already passed its version of user fee reauthorization which doesn’t address LDTs. In addition, the Senate FDASLA bill also includes other major FDA changes not covered by the House, including biosimilars, infant formula, and importation of prescription drugs.

So, FDASLA must now go to the full Senate for a vote. If it passes, the bill will go to what’s called a conference committee made up of members of both chambers to negotiate the differences and adopt a final FDA user fee reauthorization bill. It’s far from clear whether the VALID provisions will survive the conference process. Even if the final bill does address LDT regulation, it will then have to pass both the House and Senate and be signed into law by the president.

Bottom Line: While legislation to regulate LDTs has advanced farther than it ever has before, the VALID Act remains the subject of major controversy. The political strategy of attaching it to legislation that must pass, i.e., the FDA user fee reauthorization bill, may backfire to the extent that VALID must be sacrificed in the interest of gathering the needed votes for final approval before the September deadline.  

****

Here are some of the key new FDA EUAs and clearances that were announced in June 2022:

New FDA Emergency Use Authorizations (EUAs) & Approvals

Manufacturer(s)	Product
Roche	EUA for Cobas SARS-CoV-2 Duo assay for use with Cobas 6800/8800 systems
Foundation Medicine (Roche subsidiary)	Approval for FoundationOne CDx test as companion diagnostic with Roche's Rozlytrek (entrectinib) to identify patients with ROS1 fusion-positive non-small cell lung cancer or NTRK fusion-positive solid tumors that could benefit from Rozlytrek
LabCorp	EUA for VirSeq SARS-CoV-2 NGS Test, first to get EUA for identifying and differentiating SARS-CoV-2 strains
Rune Labs	510(k) clearance to use StrivePD app to monitor Parkinson's disease patients' symptoms via the Apple Watch
Sysmex America, Inc.	Clearance for addition of residual white blood cell counting to its XN-10 Automated Hematology Analyzer with Blood Bank mode
Scopio Labs	510(k) clearance for X100HT device with Full-Field Peripheral Blood Smear (PBS) Application to improve accuracy and speed of hematological tests
Thermo Fisher Scientific	Clearance for Thermo Scientific EliA RNA Pol III and EliA Rib-P tests for diagnosis of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE)
Angle	De novo clearance of Parsortix system for gathering cancer cells and analyzing blood samples from metastatic breast cancer patients
DxLab	EUA for molecular DxLab COVID-19 RT-LAMP test run on company's DxHub instrument
LG Chem	EUA for AdvanSure SARS-CoV-2 IgG(S1), an ELISA-based SARS-CoV-2 antibody test

New CE Marks & Global Certifications

Notable European CE certifications announced during the period: 

New CE Markings in Europe

Manufacturer(s)	Product(s)
ProtonDx Ltd	Dragonfly in vitro diagnostic system
Biocartis	Idylla GeneFusion Panel for lung cancer
Nonagen Bioscience	Oncuria bladder cancer immunoassay
Pictor	PictArray SARS-CoV-2 IgG antibody test
Imagia Canexia Health	Imagia Canexia Health Insights Platform (ICHIP)
Thermo Fisher Scientific	Ion Torrent Reporter Software Aneuploidy Dx Workflows
Becton Dickinson	BD SARS-CoV-2/Flu assay
AnchorDx	PulmoSeek lung cancer early detection assay
Ibex Medical Analytics	Galen Gastric, software which uses artificial intelligence to detect gastric cancers
Sophia Genetics	Sophia Data Driven Medicine (DDM) software platform
Bosch Healthcare Solutions	Vivalytic MG, MH, UP/UU test
Aiforia Technologies	Aiforia Clinical Suite Viewer
Genomtec	Genomtec ID Respiratory Panel 5-Plex point-of-care molecular diagnostic panel for 5 respiratory infections
Innova	Innova SARS-CoV-2 Antigen Rapid Qualitative Self-Test
LumiraDx	Blood test for diabetes that measures level of hemoglobin (Hb) A1c
LumiraDx	Amira Analyzer portable instrument for rapid COVID-19 testing
LumiraDx	Dual-Target SARS-CoV-2 STAR Complete test
LumiraDx	LumiraDx SARS-CoV-2 & Flu A/B RNA STAR Complete
LumiraDx	NT-proBNP test for diagnosing congestive heart failure (CHF)
LumiraDx	D-Dimer test to quantify D-dimer levels in fingerstick blood and plasma at point of care
CorDx	Influenza A/B+COVID-19/RSV Combo Ag Test for simultaneous detection of influenza A, influenza B, COVID-19, and respiratory syncytial virus (RSV)
Genetron Holdings	FusionScan Plus Kit
Burning Rock	OverC Multi-Cancer Detection Blood Test
Stratipath	AI-based Stratipath Breast software for prognostic risk stratification of breast cancers
Novacyt	PathFlow COVID-19 Rapid Antigen Self-Test
Beroni Group	COVID-19 Antigen Rapid Test Kit – Colloidal Gold Method
Nalagenetics	Nala CDS Module – PGx Core
VolitionRx	Nu.Q NETs test for NETosis
DoMore Diagnostics	Histotype Px Colorectal deep-learning algorithm to predict colorectal cancer patient outcomes
QuantuMDx	Q-POC SARS-CoV-2, Flu A/B & RSV Assay
ViroGates	SuPARnostic POC+ point-of-care test for a biomarker of inflammation

Other international clearances announced during the period:

Manufacturer(s)	Country(ies)	Product(s)
Ainos	Taiwan	Ainos SARS-CoV-2 Antigen Rapid Self-Test