A Sea-Change is Coming in How Laboratory-Developed Tests are Regulated – Is your Lab Ready?

As originally published by Health IT Answers

On May 6, FDA published a final rule that will change the way laboratory-developed tests (LDTs) are regulated. The rule phases out the agency’s general policy of “enforcement discretion” and mandates that, across five stages within the next four years, LDTs will be beholden to the same regulatory requirements as in vitro diagnostics (IVDs).

While FDA has long defined LDTs as IVDs that are intended for clinical use and are designed, manufactured, and used within laboratories (and as such, devices), LDTs have traditionally been regulated by agencies such as Clinical Laboratory Improvement Amendments (CLIA) program or College of American Pathologists (CAP). However, the wording of the new Final Rule clarifies that IVDs – including those manufactured by laboratories – are “devices” under the Federal Food, Drug, and Cosmetic (FD&C) Act. This language shift means that, because the definition of devices in the FD&C Act does not differentiate based on where devices are manufactured, LDTs are subject to FDA regulation as medical devices.

“FDA is correcting the imbalance in its oversight between non-laboratory and laboratory IVD manufacturers—an imbalance that harms American patients,” the agency said. “The public will benefit from laboratory manufacturer compliance with basic FDA requirements that protect and promote public health.”

However, not everyone shares this sentiment. The American Clinical Laboratory Association (ACLA) called the ruling an “ill-fitting device regime,” stating, “Laboratory testing services are often created to address unmet patient needs … Forcing [LDTs] into the rigid regulatory framework designed for manufactured medical devices will undermine the dynamic and patient-centered nature of clinical laboratory services.” And the Association for Molecular Pathology (AMP) filed a lawsuit against FDA to challenge the ruling, saying that it “imposes billions of dollars in unnecessary healthcare mandates, threatens patient access to essential medical procedures, and stifles … innovation.

Despite the pushback, the reality is that laboratories need to start preparing now. While the four-year grace period might sound like a long time, building up the procedures and expertise necessary for compliance is not a simple flip of a switch.

Here are five tips for how labs can prepare.

Getting Your Ducks (Test Tubes) in a Row

1. Ramp up your documentation game. Hopefully, your lab already has a Quality Management System (QMS) and software in place to help you comply with CAP/CLIA requirements. While your existing QMS may not have all the pieces you’ll need, it’s a good starting point. Once LDTs are regulated by FDA, documentation requirements will significantly increase – from the development phase to risk analysis, QC metrics, process controls, and more. The first step in understanding what you’ll need to document is to understand the requirements with which you must comply. Do your research and come up with a plan of attack. FDA’s regulatory framework is vast and intricate, and the amount of documentation required is massive; mere compliance with CAP/CLIA will not be enough.
2. Bring in the experts. Ensuring compliance will mean not just hiring individual experts but building entire teams with the right knowledge and experience. Compliance will require experts in several areas – PMA/510(k) submission, statisticians, a dedicated quality team consisting of quality assurance, quality control, supplier management, process engineers, software validation, bioinformatics, and more. Consider working with contractors with specialized knowledge; they bring extensive expertise in niche areas and can be an objective partner to keep you on track, mitigate conflict, and keep costs down.
3. Plan for the increased cost and time commitment. It’s easy to underestimate the increase in cost and time that will be required. This new level of documentation and associated processes can’t be tackled with a couple hours of overtime or a few more staff meetings. There’s also the added cost of submission fees and the additional samples required for validation (more about this in tip #5). Like every home reno project in history, it’s going to take longer and cost more than anticipated.
4. Prepare to lock down your test. In the CLIA/CAP world, there are relatively easy paths for continual optimization of tests following clinical launch. But for FDA, any desired change to workflow will require a new submission and a receipt of approval. This is one of the most challenging and potentially harmful impacts of the new ruling, as without the proper forethought and planning, the inability to make adjustments during clinical testing can stifle the smooth and steady pace of innovation. Labs will need to keep this in mind as they design all aspects of their assays and work even harder to plan for the foreseen (and unforeseen) needs of the tests’ end users.
5. Be ready to scale specimen procurement. The quality – and sheer quantity – of specimens needed for FDA PMA/510(k) submission may come as a shock to labs. Where traditionally LDTs might need dozens or hundreds of specimens for validation, labs will need to validate their tests with thousands or tens of thousands of specimens under the new ruling. FDA will also want more documented information: Were the specimens ethically sourced? Did patients provide consent? Does your validation set align with any diversity within your target patient population? The only way to meet these requirements is to have a trusted partner who can deliver high-quality specimens quickly, meet necessary quantity demands, and be transparent – from beginning to end – to make things as easy as possible. Your specimen provider should be a true partner, not just a vendor.

Preparation is the key to success

We recognize the immensity of this shift and its impact on diagnostic labs and startup organizations across the country – not to mention the impact on patients who are depending on life-saving innovations.

Change isn’t easy. Labs will need to increase their labor force, partner with the right experts, and document with extreme diligence. This shift won’t happen overnight. But the time to begin the work is now. It’s only through planning ahead and looking at the long game that labs will be able to successfully come out the other side, stay the course, and continue pursuing the science that patients are counting on.