Originally published Sept. 30.
NEW YORK (GenomeWeb) – The US Food and Drug Administration has officially released two draft guidances on its regulatory framework for laboratory-developed tests.
The first draft guidance outlines FDA's overarching risk-based plan and another lays out requirements to labs for reporting information to the agency about their LDTs and adverse events due to testing. These documents will become available for public comment upon publication in the federal register Oct. 3.
The FDA released these guidances after notifying the US Congress on July 31 of its intent to regulate LDTs. According to a provision in the Food and Drug Administration Safety and Innovation Act, the FDA was required to inform legislators of its intent to release the LDT draft guidances, along with a copy of the "anticipated" documents, 60 days ahead of their release for public comment. In September, the House Energy and Commerce Committee's subcommittee on health held a hearing to question the agency about the impact of its proposed guidance.
The draft LDT oversight framework describes a risk-based system that the FDA plans to phase in over nine years. The agency for 40 years practiced "enforcement discretion" over LDTs, leaving oversight in the hands of the Centers for Medicare & Medicaid Services. However, these tests are no longer limited only to testing small, local patient populations and those with rare disease, and are increasingly being marketed to broader populations and employing complex technologies and algorithms, the FDA says.
Under its new oversight plan, the FDA plans to continue to exercise "enforcement discretion", for Class I devices, as well as for LDTs for rare diseases and for unmet medical needs. For these types of tests, the agency will not require premarket or quality systems review, but labs will have to register and list these tests. Additionally, the agency will extend enforcement discretion for LDTs used in forensics and tests for transplantation performed in CLIA-certified, high-complexity histocompatibility labs.
For Class II and Class III LDTs, or moderate-to-high risk tests, FDA will phase in registration, listing, adverse events reporting, as well as 510(k) and premarket review requirements. A year after the LDT guidance is finalized, labs developing the highest-risk tests – those with the same indication as FDA-approved companion diagnostics, as well as screening tools meant to be used in asymptomatic patients and high-risk diagnostics for infectious diseases — will have to submit documents for premarket review a year after the LDT guidance is finalized.
Then, LDTs with the same intended use as FDA-approved Class III devices and blood products will have to comply with regulatory requirements. Hoping to wrap up regulation of high-risk LDTs five years after finalizing the guidance, the FDA will then focus on moderate-risk devices for the last four years.
FDA spokesperson Stephanie Yao told PGx Reporter that the released drafts are pretty much identical to the proposed documents sent to Congress over the summer, with a few technical amendments. For example, the FDA has updated the definition of companion diagnostic to be consistent with the final guidance on "In Vitro Companion Diagnostic Devices" issued on August 6.
Additionally, the released version also tweaked a section outlining the conditions under which the agency will continue to practice enforcement discretion over "traditional LDTs" – defined as devices that are manufactured, developed, and used at a single lab. The proposed document to Congress stated that a traditional LDT must comprise only components and instruments (i.e. analyte-specific reagents) that are legally marketed. The released version now specifies that that the components and instruments of a traditional LDT must be "legally marketed for clinical use."
The FDA made these technical changes to the LDT regulatory framework guidance based on "informal comments and questions regarding the anticipated details of this draft guidance provided in the notification to Congress," Yao said. The public can comment on the two guidances for 120 days from the publication date of Oct. 3.