Microbiology Devices; Reclassification of Cytomegalovirus Deoxyribonucleic Acid Quantitative Assay Devices Intended for Transplant Patient Management

<RULE> DEPARTMENT OF HEALTH AND HUMAN SERVICES <SUBAGY>Food and Drug Administration</SUBAGY> <CFR>21 CFR Part 866</CFR> <DEPDOC>[Docket No. FDA-2016-N-2880]</DEPDOC> <SUBJECT>Microbiology Devices; Reclassification of Cytomegalovirus Deoxyribonucleic Acid Quantitative Assay Devices Intended for Transplant Patient Management</SUBJECT> <HD SOURCE="HED">AGENCY:</HD> Food and Drug Administration (FDA), Department of Health and Human Services (HHS). <HD SOURCE="HED">ACTION:</HD> Final amendment; final order. <SUM> <HD SOURCE="HED">SUMMARY:</HD> The Food and Drug Administration (FDA or the Agency) is issuing a final order to reclassify cytomegalovirus (CMV) deoxyribonucleic acid (DNA) quantitative assay devices intended for transplant patient management, a postamendments class III device (product code PAB) into class II (general controls and special controls), subject to premarket notification. </SUM> <EFFDATE> <HD SOURCE="HED">DATES:</HD> This order is effective October 23, 2024. </EFFDATE> <HD SOURCE="HED">ADDRESSES:</HD> For access to the docket to read background documents or the electronic and-written/paper 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 document, 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> Silke Schlottmann, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 3258, Silver Spring, MD 20993-0002, 301-796-9551, <E T="03">Silke.Schlottmann@fda.hhs.gov.</E> </FURINF> <SUPLINF> <HD SOURCE="HED">SUPPLEMENTARY INFORMATION:</HD> <HD SOURCE="HD1">I. Background—Regulatory Authorities</HD> The Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended, by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L. 94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), the Food and Drug Administration Modernization Act of 1997 (Pub. L. 105-115), the Medical Device User Fee and Modernization Act of 2002 (Pub. L. 107-250), the Medical Devices Technical Corrections Act (Pub. L. 108-214), the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85), and the Food and Drug Administration Safety and Innovation Act (Pub. L. 112-144), among other amendments, establishes a comprehensive system for the regulation of medical devices intended for human use. Section 513 of the FD&C Act (21 U.S.C. 360c) established three classes of devices, reflecting the regulatory controls needed to provide reasonable assurance of their safety and effectiveness. The three classes of devices are class I (general controls), class II (general controls and special controls), and class III (general controls and premarket approval). Devices that were not in commercial distribution prior to May 28, 1976 (generally referred to as postamendments devices) are automatically classified by section 513(f)(1) of the FD&C Act into class III without any FDA rulemaking process. Those devices remain in class III and require premarket approval, unless and until: (1) FDA reclassifies the device into class I or class II or (2) FDA issues an order finding the device to be substantially equivalent, in accordance with section 513(i) of the FD&C Act, to a predicate device that does not require premarket approval. FDA determines whether new devices are substantially equivalent to predicate devices by means of premarket notification procedures in section 510(k) of the FD&C Act (21 U.S.C. 360(k)) and part 807 (21 CFR part 807), subpart E, of FDA's regulations. A postamendments device that has been initially classified in class III under section 513(f)(1) of the FD&C Act may be reclassified into class I or II under section 513(f)(3) of the FD&C Act. Section 513(f)(3) of the FD&C Act provides that FDA, acting by administrative order, can reclassify the device into class I or class II on its own initiative, or in response to a petition from the manufacturer or importer of the device. To change the classification of the device, the proposed new class must have sufficient regulatory controls to provide a reasonable assurance of the safety and effectiveness of the device for its intended use. In the <E T="04">Federal Register</E> of September 18, 2020 (85 FR 58300), FDA published a proposed order to reclassify CMV DNA quantitative assay devices intended for transplant patient management (“CMV transplant assays”) from class III into class II (general and special controls), subject to premarket notification. The comment period on the proposed order closed on November 17, 2020. FDA received two comments on the proposed order, both of which were supportive of the reclassification from Class III to Class II and agreed with FDA that CMV transplant assays should be subject to premarket notification. <HD SOURCE="HD1">II. The Final Order</HD> Based on the information discussed in the preamble to the proposed order (85 FR 58300), the supportive comments received on the proposed order, and FDA's experience over the years with this device type, FDA concludes that special controls, in conjunction with general controls, will provide reasonable assurance of the safety and effectiveness of CMV transplant assays. Therefore, in accordance with section 513(f)(3) of the FD&C Act, FDA is issuing this final order to reclassify CMV transplant assays from class III into class II, subject to premarket notification. This final order will be codified at 21 CFR 866.3180. <SU>1</SU> <FTREF/> In this final order, FDA has identified special controls under section 513(a)(1)(B) of the FD&C Act, which in addition to general controls, will provide reasonable assurance of the safety and effectiveness of the device. FDA is reclassifying these devices and establishing the special controls as published in the proposed order without change. <FTNT> <SU>1</SU>  In December 2019, FDA began adding the term “Final amendment” to the “ACTION” caption for these documents, typically styled “Final order,” to indicate an amendment to the Code of Federal Regulations. This editorial change was made in accordance with the Office of Federal Register's interpretations of the Federal Register Act (44 U.S.C. chapter 15), its implementing regulations (1 CFR 5.9 and parts 21 and 22), and the Document Drafting Handbook. </FTNT> Section 510(m) of the FD&C Act provides that a class II device may be exempted from the premarket notification requirements under section 510(k) of the FD&C Act, if the Agency determines that premarket notification is not necessary to reasonably assure the safety and effectiveness of the device. FDA has determined that premarket notification is necessary to reasonably assure the safety and effectiveness of CMV transplant assays. Therefore, the Agency does not intend to exempt these class II devices from premarket notification (510(k)) submission as provided under section 510(m) of the FD&C Act. The devices that are the subject of this reclassification are assigned the generic name “quantitative CMV nucleic acid tests for transplant patient management.” These devices are identified as a quantitative CMV nucleic acid test for transplant patient management, a device intended for prescription use in the detection of CMV and as an aid in the management of transplant patients to measure CMV DNA levels in human plasma and/or whole blood using specified specimen processing, amplification, and detection instrumentation. The test is intended for use as an aid in the management of transplant patients with active CMV infection or at risk for developing CMV infection. The test results are intended to be interpreted by qualified healthcare professionals in conjunction with other relevant clinical and laboratory findings. Under this final order, CMV transplant assays are prescription devices requiring the supervision of a practitioner licensed by law to direct the use of the devices in order to ensure accurate interpretation of results, ensuring the devices provide a reasonable assurance of safety and effectiveness. As such, the prescription device must satisfy prescription labeling requirements for in vitro diagnostic products (see 21 CFR 809.10(a)(4) and (b)(5)(ii)). In addition, the Agency believes that certain changes could be made to CMV transplant assays that could significantly affect the safety and effectiveness of those devices and for which a new 510(k) is likely required. <SU>2</SU> <FTREF/> Based on FDA's accumulated experience with these devices, changes that likely could significantly affect the safety and effectiveness of these devices include, but are not limited to, changes to critical reagents, changes to final release specifications, and changes in shelf life of the device. For more information about when to submit a new 510(k), manufacturers should refer to FDA's guidance entitled “Deciding When to Submit at 510(k) for a Change to an Existing Device” (Ref. 3). <FTNT> <SU>2</SU>  See 21 CFR 807.81(a)(3)(i). </FTNT> <HD SOURCE="HD1">III. Implementation Strategy</HD> The order is effective 30 days after its date of publication in the <E T="04">Federal Register</E> . <HD SOURCE="HD1">IV. Analysis of Environmental Impact</HD> The Agency has determined under 21 CFR 25.34(b) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required. <HD SOURCE="HD1">V. Paperwork Reduction Act of 1995</HD> This final order establishes special controls that refer to previously approved collections of information found in other FDA regulations and guidance. Those collections of information ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Preview showing 10k of 21k characters. Full document text is stored and available for version comparison. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━