Source: https://www.federalregister.gov/articles/2014/05/22/2014-11635/microbiology-devices-reclassification-of-influenza-virus-antigen-detection-test-systems-intended-for
Timestamp: 2015-10-13 11:56:50
Document Index: 309503631

Matched Legal Cases: ['art 807', 'art 807', 'art 807', '§ 866', '§ 866', '§ 866', '§ 866', '§ 866', '§ 866', '§ 866', '§ 866', '§ 866', '§ 866', '§ 866', '§ 809', '§ 809', '§ 866', 'art 866', '§ 866', '§ 866', '§ 809', '§ 809']

Federal Register | Microbiology Devices; Reclassification of Influenza Virus Antigen Detection Test Systems Intended for Use Directly With Clinical Specimens
Dates: Submit either electronic or written comments on the proposed order by August 20, 2014. See section XI for the proposed effective date of any final order that may publish based on this proposed order.
Comments Close: 08/20/2014
-29392 (6 pages)
Document Number: 2014-11635
Shorter URL: https://federalregister.gov/a/2014-11635 Related Topics
Table 1—Identified Risks to Health and Required Mitigation Measures
I. Regulatory Authorities Back to Top
The Federal Food, Drug, and Cosmetic Act (the FD Act), as amended by the Medical Device Amendments of 1976 (the 1976 amendments) (94), the Safe Medical Devices Act of 1990 (101), and the Food and Drug Administration Modernization Act of 1997 (FDAMA) (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 (FDASIA) (Pub. L. 112-144), among other amendments, established a comprehensive system for the regulation of medical devices intended for human use. Section 513 of the FD Act (21 U.S.C. 360c) established three categories (classes) of devices, reflecting the regulatory controls needed to provide reasonable assurance of their safety and effectiveness. The three categories of devices are class I (general controls), class II (special controls), and class III (premarket approval).
FDA determines whether new devices are substantially equivalent to previously offered devices by means of premarket notification procedures in section 510(k) of the FD Act (21 U.S.C. 360(k)) and part 807 of the regulations (21 CFR part 807). Section 510(k) of the FD Act and the implementing regulations in part 807, subpart E, require a person who intends to market a medical device to submit a premarket notification submission to FDA before proposing to begin the introduction, or delivery for introduction into interstate commerce, for commercial distribution of a device intended for human use.
Section 513(f)(2) of the FD&C Act establishes procedures for “de novo” risk-based review and classification of postamendment devices automatically classified into class III by section 513(f)(1). Under these procedures, any person whose device is automatically classified into class III by section 513(f)(1) of the FD&C Act may seek reclassification into class I or II, either after receipt of an order finding the device to be not substantially equivalent, in accordance with section 513(i), to a predicate device that does not require premarket approval, or at any time after determining there is no legally marketed device upon which to base a determination of substantial equivalence. In addition, under section 513(f)(3) of the FD&C Act, FDA may initiate, or the manufacturer or importer of a device may petition for, the reclassification of a device classified into class III under section 513(f)(1).
On July 9, 2012, FDASIA was enacted. Section 608(a) of FDASIA (126 Stat. 1056) amended section 513(e) of the FD Act, changing the process for reclassifying a device from rulemaking to an administrative order. Section 608(b) of FDASIA (126 Stat. 1056) amended section 515(b) of the FD Act (21 U.S.C. 360e(b)), changing the process for requiring premarket approval for a preamendments class III device from rulemaking to an administrative order.
FDA is publishing this document to propose the reclassification of antigen based rapid influenza detection test (RIDT) systems intended to detect influenza virus antigen directly from clinical specimens that are currently regulated as influenza virus serological reagents under § 866.3330 (21 CFR 866.3330) from class I into class II with special controls and into a new device classification regulation.
Reevaluation of the data previously before the Agency is an appropriate basis for subsequent action where the reevaluation is made in light of newly available authority (see Bell, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 F.Supp. 382, 388-391 (D.D.C. 1991)), or in light of changes in “medical science” (Upjohn, 422 F.2d at 951). Whether data before the Agency are old or new data, the “new information” to support reclassification under section 513(e) of the FD Act must be “valid scientific evidence,” as defined in section 513(a)(3) and 21 CFR 860.7(c)(2). (See, e.g., General Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Association v. FDA, 766 F.2d 592 (D.C. Cir.), cert. denied, 474 U.S. 1062 (1986).)
II. Regulatory Background of the Device Back to Top
In the Federal Register of April 22, 1980 (45 FR 27204), FDA published proposed regulations containing general provisions applicable to the classification of immunology and microbiology devices and individual proposed regulations to classify 161 immunology and microbiology devices into one or more of three regulatory classes: Class I (general controls), class II (performance standards), and class III (premarket approval). These regulations included the April 22, 1980, proposed rule (45 FR 27204 at 27261) to classify influenza virus serological reagents into class I under § 866.3330 (21 CFR 866.3330) Influenza virus serological reagents. In a final rule, on November 9, 1982 (47 FR 50814 at 50823), under the authority of the Medical Device Amendments of 1976, FDA classified influenza virus serological reagents into class I under § 866.3330. At that time, influenza tests conceived to fall under this regulation were laboratory methods to detect antibodies that develop in response to influenza infection while the detection of the influenza virus itself was done primarily by viral culture. As enzyme immunoassay technology developed, tests capable of detecting viral proteins (antigens) directly in human respiratory samples began to come to FDA for clearance. Since then, numerous influenza detection tests based on antigen-antibody binding properties have been developed and cleared for the market. The first RIDT for use directly from clinical specimens was cleared in 1990 and followed by others in the late 1990s. To date, methods utilizing antigens and antibodies as components of an influenza detection device have been regulated under § 866.3330 as class I devices exempt from the premarket notification (510(k)) requirement subject to the limitations in § 866.9 (21 CFR 866.9). RIDTs found under § 866.3330 exceed the limitations to the exemption from premarket notification for influenza virus serological reagents under § 866.9(c)(6) and thus require a 510(k) submission.
There are approximately 12 RIDTs classified under § 866.3330 actively marketed today. Because these devices are easy to use and provide results within 15 to 30 minutes, they are widely used in point-of-care settings where rapid diagnosis of influenza is important for early case identification. III. Identification Back to Top
We are proposing that RIDTs classified under § 866.3330 be identified under the new name of influenza virus antigen detection test system. An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time that may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.
IV. Background for Proposed Reclassification Decision Back to Top
V. Classification Recommendation Back to Top
FDA is proposing that all RIDTs currently regulated under § 866.3330 be reclassified into class II with special controls under the new device name “influenza virus antigen detection test system.” FDA believes that special controls that: (1) Identify the minimum acceptable performance criteria; (2) identify the appropriate comparator for establishing performance of new assays; and (3) call for mandatory annual analytical reactivity testing of contemporary influenza strains, including testing of newly emerging strains that pose a danger of public health emergency, would provide reasonable assurance of safety and effectiveness of these devices.
VI. Risks to Health Back to Top
VII. Summary of the Reasons for Reclassification Back to Top
Due to the mounting evidence and reports from the scientific community about the poor sensitivity of the RIDTs currently on the market and the corresponding risks to health associated with low sensitivity in combination with a rapidly evolving influenza genome with the potential for a public health emergency, FDA convened a meeting of the Microbiology Devices Panel of the Medical Devices Advisory Committee in order to discuss a proposal to reclassify RIDTs in § 866.3330 from class I to class II with special controls. Consistent with the opinions expressed by the experts on the panel, FDA believes that the establishment of special controls, in addition to general controls, is necessary to mitigate the risks to health not mitigated by the general controls and provide a reasonable assurance of safety and effectiveness for these devices. While we believe that general controls continue to adequately address the risk to health caused by a lack of result due to a device malfunction we believe special controls, in addition to general controls, are needed to control the other risks of this device, which are: (1) A false negative result may lead to failure to provide a correct diagnosis and the appropriate treatment of infection caused by influenza virus and may contribute to unnecessary treatment for another suspected condition; (2) a false negative result will also provide incorrect epidemiological information leading to failure to initiate appropriate corrective measures to control and prevent additional infections; (3) a false positive result on the other hand may lead to delayed treatment of a respiratory infection caused by another etiologic agent, which could potentially result in a more serious patient outcome; and (4) a false positive result will also provide incorrect epidemiological information on the presence of influenza in a community, which may result in unnecessary patient isolation or contact limitations and in unnecessary close contact investigations.
VIII. Special Controls Back to Top
○ Placing the results directly in the device's § 809.10(b) (21 CFR 809.10(b)) compliant labeling in a section of the labeling devoted to annual analytical reactivity testing; or
○ Placing the table directly in the device's § 809.10(b) compliant labeling in the section of the labeling devoted to annual analytical reactivity testing and influenza emergency analytical reactivity testing but separate from the annual analytical reactivity testing tables; or
Table 1 shows the special controls set forth in this order that are needed to address the identified risks for this device not sufficiently addressed by the general controls to provide a reasonable assurance of safety and effectiveness of the device. Table 1—Identified Risks to Health and Required Mitigation Measures Back to Top
1. A false negative result may lead to failure to provide a correct diagnosis and the appropriate treatment of infection caused by influenza virus and may contribute to unnecessary treatment for another suspected condition.
Special Controls 1-4.
2. A false negative result will also provide incorrect epidemiological information leading to failure to initiate appropriate corrective measures to control and prevent additional infections.
3. A false positive result on the other hand may lead to delayed treatment of a respiratory infection caused by another etiologic agent, which could potentially result in a more serious patient outcome.
4. A false positive result will also provide incorrect epidemiological information on the presence of influenza in a community, which may result in unnecessary patient isolation or contact limitations and in unnecessary close contact investigations.
If this proposed order is finalized, RIDTs in § 866.3330 will be reclassified into class II with special controls in a new classification regulation at 21 CFR 866.3328. Adherence to the special controls, when finalized, in addition to the general controls, is necessary to provide a reasonable assurance of the safety and effectiveness of the device.
XIII. Reference Back to Top
1. Transcript of FDA's Microbiology Devices Panel Meeting, June 13, 2013. (Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/MicrobiologyDevicesPanel/UCM359554.pdf.)
1.The authority citation for part 866 continues to read as follows: Authority:
2.Add § 866.3328 to subpart D to read as follows: § 866.3328 Influenza virus antigen detection test system.
(ii) If the manufacturer chooses to compare the device to an appropriate molecular comparator method: (A) The positive percent agreement for the device when testing for Influenza A and Influenza B must be at least at the 80 percent point estimate with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling in a section of the labeling devoted to annual analytical reactivity testing; or
(A) Placing the table directly in the device's § 809.10(b) of this chapter compliant labeling in the section of the labeling devoted to annual analytical reactivity testing and influenza emergency analytical reactivity testing but separate from the annual analytical reactivity testing tables; or