Navigating your molecular lab’s test selection and development over the next two years

With the FDA’s publication of the final rule on laboratory developed tests (LDTs) on May 6, 2024, clinical molecular laboratories are beginning to chart a course through the next five years. As described in the rule and in our first post of this series, the final of five stages of enforcement rollout will go into effect in May of 2028. It will require that qualifying low- and moderate-risk in vitro diagnostics (IVDs) run as LDTs meet FDA premarket review requirements, like tests developed by other manufacturers. The requirements laid out in the previous four stages will apply, such that for applicable tests, labs will have to have already complied with reporting, registration, listing, and labeling requirements, and will need to have established a quality system that meets FDA requirements. 

How, then, should your laboratory prepare? Will all of these requirements apply to your lab? What does it mean for the tests you are developing now or had planned to develop to meet the needs of the clinicians and patients you serve? 

First, evaluate whether kitted IVD solutions with FDA clearance or approval exist for the test indications that you serve today or intend to serve in the future. Most labs that perform molecular testing for oncology and inherited disease using NGS have chosen to develop and validate their own tests over the past decade rather than adopt available kitted IVDs. Indeed, options for NGS IVDs that are cleared or approved by the FDA for distribution are very limited or unavailable. 

However, such tests are theoretically attractive because the manufacturer has met the FDA requirements already. These tests can be verified in a CLIA-certified laboratory and run in the same manner today (and, we anticipate, in 2028 and beyond) as they were in 2023. Some labs may find that kitted IVDs give them the necessary tools to serve local patient populations without the need for send out testing and without needing to comply with FDA requirements that pertain to device manufacturers. We can anticipate that the market will respond to this demand over the next few years and increase the kitted IVD options available to molecular NGS laboratories. 

Labs whose patient care mandate cannot be served by adopting kitted IVDs in the foreseeable future must instead examine the final rule closely. We at Velsera anticipate that most such clinical NGS laboratories with test menus that cater to common disease indications will need to comply with most or all FDA requirements, even if not every offering on the lab’s menu will be subject to premarket review. There are exceptions: the FDA has outlined several scenarios in which it will exercise enforcement discretion to avoid disrupting critical patient care testing, and within institutions that have other risk mitigating oversight in place. 

1. If your laboratory performs testing within the Veterans Affairs Administration (VAA) or Department of Defense (DoD), it is exempt from all requirements. 
2. If your lab receives New York State Clinical Laboratory Evaluation Program (NYS CLEP) approval for its tests, it is exempt only from the premarket review requirements. 
3. Certain labs that are part of an integrated health system and offer tests that serve unmet needs are exempt from most quality system requirements and from premarket review requirements with respect to those tests. However, as we will discuss in an upcoming post, a lab must tread a narrow path to remain exempt for its full test menu over time. 
4. An LDT that was marketed prior to May 6, 2024 (the date of issuance of the final rule) is exempt from both quality system and premarket review requirements as long as it is not modified in certain significant ways. 

Other than VAA or DoD labs, all labs that intend to continue running LDTs must comply with the reporting, registration, labeling, and listing requirements of Stages 1 and 2, including in scenarios B-D above. It’s prudent to start planning this summer to comply with Stage 1 medical device reporting requirements before next May. 

Over time, we anticipate that most labs will eventually need to either adopt kitted IVDs or comply with FDA’s Quality System Regulations according to Stage 3. Even if a lab decides to continue running their existing LDTs in an unmodified fashion over the next 5-6 years, most such tests will eventually need to be modified or replaced. Except for VAA and DoD labs and integrated health system labs whose tests serve unmet needs, any NGS LDT not being run today must be developed and launched under a compliant quality system. It will also require NYS CLEP or FDA premarket review. 

Many labs have decisions to make over the next months to determine how they will adhere to FDA’s requirements. Is your lab in search of a partner to evaluate your options? Velsera has deep experience supporting analytical and clinical validations consistent with CLIA and FDA requirements and is confident that its customer labs can succeed at receiving regulatory clearance or approval where warranted. We’re prepared to guide our community and help labs learn from each other during this time. Please get in touch by signing up for our newsletter at the bottom of this page or by writing us at marketing@velsera.com. 

Next time, we’ll take a closer look at compliance with Stages 1 and 2, with an eye towards labs that  will continue running existing LDTs and anticipate launching new ones in 2024 and 2025. 

The information presented here is not intended as legal or regulatory advice but rather as a brief introduction to the subject matter. Compliance with the FDA’s final rule may rely on factors and requirements not listed here, and any person or entity subject to the final rule is encouraged to obtain professional advice specific to their situation.