The release is the culmination of a multi-year process in which FDA has built the case for its regulatory authority over LDTs. It is initially being released as “anticipated details of the draft guidance,” in response to a letter from Senators, concurrent with the Agency’s 60-day notification of release.
On Nov. 25, 2013, FDA issued a final guidance on in vitro diagnostics (IVD) for research use only (RUO) or investigational use only (IUO). The guidance was intended to clarify the requirements applicable to RUO or IUO IVD products, mandate consistency of labeling with the intended use of such devices and hold manufacturers accountable for distribution practices by warning of possible enforcement actions if they encouraged the use of RUO-labeled products for clinical diagnostic purposes. Days earlier, FDA issued a stern warning letter to 23andMe, Inc., on the grounds that the company did not have marketing clearance or approval for its Saliva Collection Kit and Personal Genome Service Kit.
FDA maintains and clarifies further in this “anticipated guidance” that demonstration of accuracy and validity is outside the scope of the Clinical Laboratory Improvements Amendments Act (CLIA) regulation, which is administered by CMS. The guidance identifies LDTs as IVDs intended for clinical use that are designed, manufactured and used within a single laboratory. It provides extensive background and justification for the Agency’s regulation of such tests, including regulatory history, the evolution of LDT complexity and gaps in regulatory oversight.
FDA proposes a risk-based framework for oversight based upon the existing device classification system. The Agency states that it will issue draft guidance to describe how LDTs will fall into this system within 18 months of finalization of this guidance, but notes as of now it will continue to exercise enforcement discretion for low-risk LDTs.
FDA says that the oversight framework will be phased in gradually, in order to take differential risks of LDTs into account and mitigate unintended consequences of immediate broad enforcement. The elements of the framework according to the guidance are:
• Notification to FDA of LDTs manufactured by a laboratory or Registration and Listing • Medical Device Reporting Requirements (MDR) for LDTs (e.g., adverse event reporting)
- Notification data will be publically available, and used for advisory panel recommendations on risk
- Notifications are due within six months of final guidance publication
• Continued enforcement discretion with respect to premarket review requirements for low-risk LDTs, “Traditional LDTs,” LDTs used for rare diseases and “LDTs for Unmet Needs”
• Risk-based, phased-in approach to enforcing the premarket review requirements for other high-risk and moderate-risk LDTs
• Use of clinical literature to support a demonstration of clinical validity
• Facilitation of third-party review for many moderate risk LDTs
• Phased-in approach to enforcing the Quality System regulation
• Continued enforcement discretion for premarket review of Class I LDTs
In addition to the Framework for regulating LDTs, the Agency also issued a “pre-draft” guidance on medical device reporting requirements for LDT owners/operators. Starting six months after publication of the final version of the LDT Framework guidance, the Agency intends to continue to exercise enforcement discretion with respect to registration and listing requirements, provided that these laboratory owners/operators notify the Agency and provide basic information regarding the new LDTs prior to offering them for clinical use. Laboratories that do not provide notification will not be within the scope of FDA’s enforcement discretion policy and would fall within the Agency’s normal enforcement approach with respect to registration and listing requirements.
Certain categories of LDTs, prime among them those with the same intended use as a cleared or approved companion diagnostic, will be impacted sooner than others. Upon issuance of the final guidance, all LDTs will gradually come under FDA’s regulatory purview according to the proposed phase-in schedule. FDA intends to enforce the notification requirements for testing laboratories, and these LDT manufacturers will be subject to specific medical device reporting requirements per 21CFR803.
The comment period for the draft guidances released will open in 60 days, as FDA is statutorily required to provide a 60-day notice of guidance release to Congress, and the details released today are a courtesy in response to the urging of Senate members.
These guidance documents and FDA’s approach to regulatory oversight of diagnostics will be addressed in detail at Avalere’s upcoming diagnostics conference on Sept. 18.
Please contact Lakshman Ramamurthy with any LDT related questions, at LRamamurthy@Avalere.com
Attached, please find previous Avalere research on regulatory and reimbursement trends in diagnostics.
View the FDA’s draft LDT guidance.