As IVD manufacturers and clinical laboratories gathered at the American Association for Clinical Chemistry's (AACC) annual meeting and clinical lab expo in Chicago, FDA made a major announcement that will likely test the relationship between these two groups. The agency notified "Congress of its intention to publish a proposed risk-based oversight framework for laboratory-developed tests (LDT)."

Along with this notification, FDA sent the preliminary drafts of two guidance documents that describe the framework for regulating LDTs. The first draft guidance, "Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)," discusses the proposed regulatory framework. The second guidance, "FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)," spells out the methods that industry may be able to use to address the requirements the agency is proposing.

As expected, the reactions to FDA's announcement were on completely polar opposite ends of the spectrum. On one end, IVD industry groups applauded the agency's proposed regulatory framework.

"We welcome the publication of the draft framework on a risk-based approach to the regulation of LDTs and look forward to reviewing the draft guidance when it is issued," said Andrew Fish, executive director of AdvaMedDx, a division of the Advanced Medical Technology Association (AdvaMed) dedicated to issues facing IVD manufacturers. "These types of tests are increasingly being used to diagnose and guide the treatment of potentially life-threatening conditions, and FDA oversight of higher risk diagnostic tests including companion diagnostics, regardless of the manufacturers, is essential to patient safety."

But on the other end, the clinical laboratory community's reactions were not so sanguine. The American Clinical Laboratory Association (ACLA) urged FDA to exercise caution and expressed concern that another layer of regulation could stifle diagnostic innovation and ultimately jeopardize patient access to timely and effective treatments.

"The massive leaps in scientific and medical advancement that have occurred over the last quarter century have yielded a bounty of new tests created by highly trained physicians and clinicians that were not even imagined when the Clinical Laboratory Improvement Amendments (CLIA) was last updated in 1988," said Alan Mertz, president of ACLA. "To the extent that stakeholders have concerns about possible regulatory gaps under CLIA, ACLA has long supported enhancing the CLIA regulatory framework, rather than impose an additional layer of regulation based upon a different statute designed for manufactured products rather than laboratory testing."

“The CLIA program, in combination with laboratory accreditation programs and professional certification, provides the level of rigor, as well as the flexibility necessary, for ensuring high-quality laboratory testing in the U.S.,” said Elain Lyon, PhD, president of the Association for Molecular Pathology (AMP; Bethesda, MD). “Over-regulation or inappropriate regulation has the potential to negatively impact patient care and limit the availability of medically necessary laboratory developed procedures.”

I asked several attorneys who have closely followed the contentious LDT issue for their thoughts and opinions on FDA’s proposed regulations for LDTs. Jonathan S. Kahn, a partner at Hogan Lovells, offered the following key takeaways from the initial draft guidance documents:

  • The proposed framework reasserts FDA’s view that it has jurisdiction over IVDs made by both IVD companies and clinical laboratories. This position has been very controversial in the past and is likely to spark heated debate and possible legal actions in the coming months.
  • FDA also explicitly states that LDTs developed at academic medical centers will not be treated any differently, although this is listed as a factor for consideration for certain types (e.g., traditional LDTs).
  • For LDTs already on the market when the guidance is finalized, grace periods for premarket submissions will be allowed, but not for new LDTs introduced after that time.
  • FDA elected to forgo requiring registration and listing in exchange for notification and medical device reporting (MDR). This also presumably may mean, for now, that there will be no routine inspections of laboratories that comply with notification.
  • FDA is proposing to require CLIA-certified laboratories currently marketing tests that do not meet the agency’s technical definition for an LDT to comply with the same risk-based framework as “true” LDTs.
  • Although premarket review requirements would be phased in and provide for a grace period for all tests already on the market, new tests not yet marketed would be subject to those requirements immediately upon guidance finalization.

Some attorneys took the IVD industry’s side and applauded FDA’s actions.

“The guidance that FDA issued is impressive and thorough. FDA obviously spent quite a bit of time thinking through these issues and appears committed to taking a risk-based approach,” said Bradley M. Thompson, an attorney at Epstein Becker Green. “Clearly, FDA worked through the issues such as how to develop a program that is practical with regard to the agency and industry resources. Indeed, FDA’s focus is not just on the risk associated with the clinical use of a test and the resources required, but also more broadly on such public health concerns as unmet medical need and rare conditions.”

Thompson suggested that Congress should direct the federal agencies involved, including FDA, the Centers for Medicare and Medicaid Services (CMS), and others, to develop a holistic federal government strategy for diagnostic tests, particularly companion diagnostics.

“As a part of the process of developing that holistic federal strategy, FDA should get input from a working group of diverse stakeholders,” said Thompson. “This is very complicated and requires weighing the need for innovation in new diagnostic test development and timely access to new technologies on the one hand, with the assurance of safety and effectiveness on the other. Accomplishing that will require much good-faith discussion among many stakeholders.”

But other attorneys brought up concerns that echoed those raised by clinical laboratories.

“We believe that these guidances present unsettling questions for the approximately 2,000 laboratories estimated to be affected by these guidance documents, not only with respect to their current LDTs, but to future innovation as well,” wrote Allyson B. Mullen and Jeffrey N. Gibbs, attorneys at Hyman, Phelps & McNamara, in their firm’s blog. “In addition, the documents do not address the costs that will be incurred. And while FDA talks about the perceived risks associated with LDTs, it essentially ignores the benefits. Thus, the new documents present questions not just for laboratories, but for the entire healthcare system. These issues, as well as the legality of FDA’s proposed actions, are sure to be the subject of intense debate in the upcoming months.”