Medical Devices; Laboratory Developed Tests

<RULE> DEPARTMENT OF HEALTH AND HUMAN SERVICES <SUBAGY>Food and Drug Administration</SUBAGY> <CFR>21 CFR Part 809</CFR> <DEPDOC>[Docket No. FDA-2023-N-2177]</DEPDOC> <RIN>RIN 0910-AI85</RIN> <SUBJECT>Medical Devices; Laboratory Developed Tests</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Food and Drug Administration, HHS. <HD SOURCE="HED">ACTION:</HD> Final rule. <SUM> <HD SOURCE="HED">SUMMARY:</HD> The Food and Drug Administration is issuing a final rule to amend its regulations to make explicit that in vitro diagnostic products (IVDs) are devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act) including when the manufacturer of the IVD is a laboratory. In conjunction with this amendment, the Food and Drug Administration is phasing out its general enforcement discretion approach for laboratory developed tests (LDTs) so that IVDs manufactured by a laboratory will generally fall under the same enforcement approach as other IVDs. This phaseout policy includes enforcement discretion policies for specific categories of IVDs manufactured by a laboratory, including currently marketed IVDs offered as LDTs and LDTs for unmet needs. This phaseout policy is intended to better protect the public health by helping to assure the safety and effectiveness of IVDs offered as LDTs, while also accounting for other important public health considerations such as patient access and reliance. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> This rule is effective July 5, 2024. </EFFDATE> <HD SOURCE="HED">ADDRESSES:</HD> For access to the docket to read background documents or comments received, go to <E T="03">https://www.regulations.gov</E> and insert the docket number found in brackets in the heading of this final rule into the “Search” box and follow the prompts, and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500. <FURINF> <HD SOURCE="HED">FOR FURTHER INFORMATION CONTACT:</HD> Toby Lowe, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, 301-796-6512, <E T="03">LDTFinalRule@fda.hhs.gov.</E> </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> <HD SOURCE="HD1">Table of Contents </HD> <EXTRACT> <FP SOURCE="FP-2">I. Executive Summary</FP> <FP SOURCE="FP1-2">A. Purpose of the Final Rule</FP> <FP SOURCE="FP1-2">B. Summary of Select Provisions of the Final Rule</FP> <FP SOURCE="FP1-2">C. Legal Authority</FP> <FP SOURCE="FP1-2">D. Costs and Benefits</FP> <FP SOURCE="FP-2">II. Table of Abbreviations/Commonly Used Acronyms in This Document</FP> <FP SOURCE="FP-2">III. Background</FP> <FP SOURCE="FP1-2">A. FDA's Current Regulatory Framework</FP> <FP SOURCE="FP1-2">B. Need for the Rule</FP> <FP SOURCE="FP1-2">C. Summary of Comments on the Notice of Proposed Rulemaking</FP> <FP SOURCE="FP1-2">D. General Overview of the Final Amendment to the Definition of In Vitro Diagnostic Products</FP> <FP SOURCE="FP1-2">E. General Overview of the Final Phaseout Policy</FP> <FP SOURCE="FP-2">IV. Legal Authority</FP> <FP SOURCE="FP-2">V. Phaseout Policy</FP> <FP SOURCE="FP1-2">A. Scope</FP> <FP SOURCE="FP1-2">B. Enforcement Discretion Policies</FP> <FP SOURCE="FP1-2">C. Stages</FP> <FP SOURCE="FP-2">VI. Comments on the Notice of Proposed Rulemaking and FDA Responses</FP> <FP SOURCE="FP1-2">A. General Comments on the Notice of Proposed Rulemaking</FP> <FP SOURCE="FP1-2">B. Definitions</FP> <FP SOURCE="FP1-2">C. Need for the Rule</FP> <FP SOURCE="FP1-2">D. FDA Authority To Regulate LDTs</FP> <FP SOURCE="FP1-2">E. Other Legal Comments</FP> <FP SOURCE="FP1-2">F. Phaseout Policy</FP> <FP SOURCE="FP1-2">G. Impact on Small Businesses</FP> <FP SOURCE="FP1-2">H. Impact on Pricing</FP> <FP SOURCE="FP1-2">I. Impact on Access and Innovation</FP> <FP SOURCE="FP1-2">J. Level Playing Field</FP> <FP SOURCE="FP1-2">K. Impact to Specific Patient Populations</FP> <FP SOURCE="FP1-2">L. Specific Types of IVDs</FP> <FP SOURCE="FP1-2">M. IVD Modifications</FP> <FP SOURCE="FP1-2">N. FDA Resources</FP> <FP SOURCE="FP1-2">O. 510(k) Third Party Review Program</FP> <FP SOURCE="FP1-2">P. Implementation</FP> <FP SOURCE="FP1-2">Q. Interplay With Oncology Drug Products Used With Certain In Vitro Diagnostic Tests Pilot Program</FP> <FP SOURCE="FP1-2">R. Miscellaneous</FP> <FP SOURCE="FP-2">VII. Effective Date</FP> <FP SOURCE="FP-2">VIII. Economic Analysis of Impacts</FP> <FP SOURCE="FP-2">IX. Analysis of Environmental Impact</FP> <FP SOURCE="FP-2">X. Paperwork Reduction Act of 1995</FP> <FP SOURCE="FP-2">XI. Federalism</FP> <FP SOURCE="FP-2">XII. Consultation and Coordination With Indian Tribal Governments</FP> <FP SOURCE="FP-2">XIII. References</FP> </EXTRACT> <HD SOURCE="HD1">I. Executive Summary</HD> <HD SOURCE="HD2">A. Purpose of the Final Rule</HD> The Food and Drug Administration (FDA, the Agency, or we) is amending its regulations to make explicit that IVDs are devices under the FD&C Act including when the manufacturer of the IVD is a laboratory. This amendment reflects that the device definition in the FD&C Act does not differentiate between entities manufacturing the device. In connection with amending the regulation, FDA is phasing out its general enforcement discretion approach for LDTs so that IVDs manufactured by a laboratory will generally fall under the same enforcement approach as other IVDs ( <E T="03">i.e.,</E> FDA's expectations for compliance will generally be the same). This phaseout policy includes enforcement discretion policies for specific categories of IVDs manufactured by a laboratory, including currently marketed IVDs offered as LDTs  <SU>1</SU> <FTREF/> and LDTs for unmet needs. For purposes of this document, we use “manufacture” and related terms as a shorthand for the various activities that constitute manufacturing as described in FDA regulations ( <E T="03">e.g.,</E> design, preparation, propagation, assembly, and processing). <FTNT> <SU>1</SU>  As discussed in section V.A.1, FDA uses the phrase “IVDs offered as LDTs” throughout this preamble to refer to IVDs that are manufactured and offered as LDTs by laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and that meet the regulatory requirements under CLIA to perform high complexity testing, and used within such laboratories, even if those IVDs do not fall within FDA's traditional understanding of an LDT because they are not designed, manufactured, and used within a single laboratory. </FTNT> In 1976, the Medical Device Amendments of 1976 (the MDA) amended the FD&C Act to create a comprehensive system for the regulation of devices intended for human use. In implementing the MDA, FDA has exercised enforcement discretion such that it generally has not enforced applicable requirements with respect to most LDTs. Enforcement discretion for LDTs developed as a matter of practice. However, the risks associated with LDTs are much greater today than they were at the time of enactment of the MDA. As discussed more fully in the notice of proposed rulemaking (NPRM) (88 FR 68006, October 3, 2023) and this preamble, today's LDTs are, among other things, used more widely, by a more diverse population, with an increasing reliance on high-tech instrumentation and software, and more frequently for the purpose of guiding critical healthcare decisions. In this regard, today's LDTs are similar to other IVDs that have not come within FDA's general enforcement discretion approach. Given these changes, and for the additional reasons discussed in the NPRM and this preamble, FDA is phasing out the general enforcement discretion approach for LDTs. By phasing out this approach, FDA intends to better protect the public health by helping to assure the safety and effectiveness of IVDs offered as LDTs, while also accounting for other important public health considerations such as patient access and reliance. <HD SOURCE="HD2">B. Summary of Select Provisions of the Final Rule</HD> FDA is amending the definition of “in vitro diagnostic products” in its regulations to state that IVDs are devices under the FD&C Act “including when the manufacturer of these products is a laboratory.” In conjunction with this amendment, FDA is phasing out the general enforcement discretion approach for LDTs. As discussed further in this preamble, however, FDA is adopting targeted enforcement discretion policies for several categories of IVDs manufactured by a laboratory in certain circumstances. As with any enforcement discretion policy, FDA may update any of these enforcement discretion policies as circumstances warrant or if the circumstances that inform these policies change, consistent with FDA's good guidance practices (21 U.S.C. 371(h), § 10.115 (21 CFR 10.115)). Additional details regarding the phaseout policy are discussed further in section V of this preamble. <HD SOURCE="HD2">C. Legal Authority</HD> FDA is issuing this rule under the Agency's general rulemaking authorities and statutory authorities relating to devices. These authorities include sections 201(h)(1), 301, 501, 502, 510, 513, 514, 515, 518, 519, 520, 701, 702, 704, and 801 of the FD&C Act (21 U.S.C. 321(h)(1), 331, 351, 352, 360, 360c, 360d, 360e, 360h, 360i, 360j, 371, 372, 374, and 381) and section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262). <HD SOURCE="HD2">D. Costs and Benefits</HD> We quantify benefits to patients from averted health losses due to problematic IVDs offered as LDTs. We focus mainly on certain broad disease categories associated with the majority of misdiagnosis-related harms in the United States. Additional benefits include averted non-health losses from reduced spending on problematic IVDs offered as LDTs and unquantified reduction in costs from lawsuits. We quantify costs to affected laboratories for co ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 1225k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━