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range of age and educational levels and lead to prophylactic screening, SUPPLEMENTARY INFORMATION: have no prior experience with the test confirmatory procedures, or treatments I. Statutory Background or its manufacturer. These factors shall that may incur morbidity or mortality to be well defined in the inclusion and the patient; Section 510(k) of the Federal Food, exclusion criteria. (iii) Assessing the presence of genetic Drug, and Cosmetic Act (the FD&C Act) (ii) All sources of bias must be variants that impact the metabolism, (21 U.S.C. 360(k)) and the implementing predefined and accounted for in the exposure, response, risk of adverse regulations, 21 CFR part 807 subpart E, study results with regard to both events, dosing, or mechanisms of require persons who intend to market a responders and non-responders. prescription or over-the-counter device to submit and obtain FDA (iii) The testing must follow a format medications; or clearance of a premarket notification where users have limited time to (iv) Assessing the presence of (510(k)) containing information that complete the studies (such as an onsite deterministic autosomal dominant allows FDA to determine whether the survey format and a one-time visit with variants. new device is ‘‘substantially equivalent’’ a cap on the maximum amount of time within the meaning of section 513(i) of Dated: November 1, 2017. that a participant has to complete the the FD&C Act (21 U.S.C. 360c(i)) to a tests). Lauren Silvis, legally marketed device that does not (iv) Users must be randomly assigned Chief of Staff. require premarket approval. to study arms. Test reports in the user [FR Doc. 2017–24159 Filed 11–6–17; 8:45 am] On December 13, 2016, the 21st comprehension study given to users BILLING CODE 4164–01–P Century Cures Act (Pub. L. 114–255) must define the target condition being (Cures Act) was signed into law. Section tested and related symptoms, explain 3054 of the Cures Act amended section the intended use and limitations of the DEPARTMENT OF HEALTH AND 510(m) of the FD&C Act. As amended, test, explain the relevant ethnicities in HUMAN SERVICES section 510(m)(2) provides that, 1 regard to the variant tested, explain calendar day after the date of Food and Drug Administration genetic health risks and relevance to the publication of the final list under user’s ethnicity, and assess participants’ paragraph (1)(B), FDA may exempt a 21 CFR Part 866 ability to understand the following class II device from the requirement to comprehension concepts: The test’s [Docket No. FDA–2015–N–3455] submit a report under section 510(k) of limitations, purpose, appropriate action, the FD&C Act, upon its own initiative or test results, and other factors that may Medical Devices; Exemption From a petition of an interested person, if have an impact on the test results. Premarket Notification; Class II FDA determines that a 510(k) is not (v) Study participants must be Devices; Autosomal Recessive Carrier necessary to provide reasonable untrained, be naı¨ve to the test subject of Screening Gene Mutation Detection assurance of the safety and effectiveness the study, and be provided the labeling System of the device. This section requires FDA prior to the start of the user to publish in the Federal Register a AGENCY: Food and Drug Administration, comprehension study. HHS. notice of intent to exempt a device, or (vi) The user comprehension study of the petition, and to provide a 60- must meet the predefined primary ACTION: Final order. calendar-day comment period. Within endpoint criteria, including a minimum SUMMARY: The Food and Drug 120 days of publication of such notice, of a 90 percent or greater overall Administration (FDA or Agency) is FDA must publish an order in the comprehension rate (i.e., selection of the publishing an order to exempt Federal Register that sets forth its final correct answer) for each comprehension autosomal recessive carrier screening determination regarding the exemption concept. Other acceptance criteria may gene mutation detection systems from of the device that was the subject of the be acceptable depending on the concept the premarket notification requirements, notice. If FDA fails to respond to a being tested. Meeting or exceeding this subject to certain limitations. This petition under this section within 180 overall comprehension rate exemption from 510(k), subject to days of receiving it, the petition shall be demonstrates that the materials certain limitations, is immediately in deemed granted. presented to the user are adequate for effect for autosomal recessive carrier II. Criteria for Exemption over-the-counter use. screening gene mutation detection There are a number of factors FDA (vii) The analysis of the user systems. This exemption will decrease may consider to determine whether a comprehension results must include regulatory burdens on the medical 510(k) is necessary to provide results regarding reports that are device industry and will eliminate reasonable assurance of the safety and provided for each gene/variant/ethnicity private costs and expenditures required effectiveness of a class II device. These tested, statistical methods used to to comply with certain Federal factors are discussed in the January 21, analyze all data sets, and completion regulations. FDA is also amending the 1998, Federal Register notice (63 FR rate, non-responder rate, and reasons for codified language for the autosomal 3142) and subsequently in the guidance nonresponse/data exclusion. A recessive carrier screening gene the Agency issued on February 19, 1998, summary table of comprehension rates mutation detection system devices entitled ‘‘Procedures for Class II Device regarding comprehension concepts (e.g., classification regulation to reflect this Exemptions from Premarket purpose of test, test results, test final determination. limitations, ethnicity relevance for the Notification, Guidance for Industry and test results, etc.) for each study report DATES: This order is effective November CDRH Staff’’ (referred to herein as the must be included. 7, 2017. Class II 510(k) Exemption Guidance) (4) The intended use of the device FOR FURTHER INFORMATION CONTACT: (Ref. 1). must not include the following Steven Tjoe, Center for Devices and III. Device Description indications for use: Radiological Health, Food and Drug (i) Prenatal testing; Administration, 10903 New Hampshire On February 19, 2015, FDA (ii) Determining predisposition for Ave., Bldg. 66, Rm. 4550, Silver Spring, completed its review of a De Novo cancer where the result of the test may MD 20993–0002, 301–796–5866. request for classification of the 23andMe

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Personal Genome Service (PGS) Carrier IV. Comments on the Proposed based upon scientific and clinical Screening Test for Bloom syndrome. Exemption and FDA Response literature as to the autosomal recessive FDA classified the 23andMe PGS Carrier In response to the October 2015 notice nature of a particular disease or Screening Test for Bloom syndrome, announcing FDA’s intent to exempt condition, we are not providing a and substantially equivalent devices of autosomal recessive carrier screening revised list in this final order. (Comment 2) One commenter this generic type, into class II (special gene mutation detection system devices requested clarification that § 866.5940 controls) under the generic name from premarket notification applies to OTC carrier detection devices ‘‘Autosomal recessive carrier screening requirements, FDA received for the determination of carrier status by gene mutation detection system.’’ This submissions from three commenters—a detection of clinically relevant gene type of device is a qualitative in vitro device industry manufacturer, a mutations associated with cystic molecular diagnostic system used for professional organization, and a health fibrosis. genotyping of clinically relevant care organization—supporting an variants in genomic DNA isolated from (Response) In the October 2015 exemption from premarket notification notice, FDA stated ‘‘[a] gene mutation human specimens intended for for this type of device. prescription use or over-the-counter detection system indicated for the To make it easier to identify determination of carrier status by (OTC) use. The device is intended for comments and our responses, the word autosomal recessive disease carrier detection of clinically relevant gene ‘‘Comment’’ and a comment number mutations associated with Cystic screening in adults of reproductive age. appear in parentheses before each The device is not intended for copy Fibrosis is not 510(k)-exempt since it is comment’s description, and the word a class II device subject to premarket number variation, cytogenetic, or ‘‘Response’’ in parentheses precedes biochemical testing. notification and special controls under each response. Similar comments are 21 CFR 866.5900—Cystic fibrosis FDA believes that De Novo grouped together under the same transmembrane conductance regulator classification will enhance patients’ number. Specific issues raised by the (CFTR) gene mutation detection access to beneficial innovation, in part comments and the Agency’s responses system.’’ Similarly, in the final order by reducing regulatory burdens. When follow. announcing the classification of an FDA classifies a device into class I or II (Comment 1) Two commenters autosomal recessive carrier screening via the De Novo process, the device can requested that FDA clarify that the list gene mutation detection system into serve as a predicate for determining of autosomal recessive carrier diseases class II (80 FR 65626, October 27, 2015), substantial equivalence for future included in the October 2015 notice is FDA stated ‘‘A gene mutation detection devices within that type (see 21 U.S.C. not exhaustive or expand the list of system indicated for the determination 360c(f)(2)(B)(i)). As a result, other diseases and conditions covered by the of carrier status by detection of device sponsors do not have to submit exemption to include all diseases and clinically relevant gene mutations a De Novo request or a premarket conditions described in the scientific associated with cystic fibrosis is approval application in order to market literature as inherited in an autosomal separately classified under 21 CFR a substantially equivalent device (see 21 recessive manner. One commenter 866.5900—Cystic fibrosis U.S.C. 360c(i), defining ‘‘substantial further requested that FDA clarify that transmembrane conductance regulator equivalence’’). Instead, sponsors can use the determination of the applicability of (CFTR) gene mutation detection system the less-burdensome 510(k) process, § 866.5940 (21 CFR 866.5940) should be (class II, special controls), and is thus when necessary, to market their device. based upon scientific and clinical not included in the de novo In the Federal Register of October 27, literature as to the autosomal recessive classification.’’ 2015 (80 FR 65774), FDA published a nature of the disease or condition. However, after considering the notice (‘‘October 2015 notice’’) (Response) The diseases and comments regarding this exemption announcing its intent to exempt conditions listed in table 1 of the action, and after reviewing the devices autosomal recessive carrier screening October 2015 notice were based upon a that are classified as CTFR gene gene mutation detection system devices limited review of the scientific and mutation detection systems under from premarket notification clinical literature at that time. After § 866.5900 (21 CFR 866.5900), FDA is requirements, subject to certain consideration of the public comments, now clarifying that an OTC gene limitations, and provided opportunity FDA agrees that the autosomal recessive mutation detection system indicated for for interested persons to submit diseases and conditions listed in that the determination of autosomal comments by November 27, 2015. After table should be treated as illustrative, recessive carrier status by detection of reviewing comments received and not an exhaustive list. Based on clinically relevant gene mutations (summarized in section IV), FDA is now FDA’s review of current scientific and associated with cystic fibrosis (‘‘OTC providing its final determination for clinical literature, FDA would not Cystic Fibrosis carrier screening test’’) is autosomal recessive carrier screening consider screening for autosomal included within the scope of the gene mutation detection system devices recessive carrier status by detection of classification regulation for an by exempting this type of device from clinically relevant gene mutations autosomal recessive carrier screening premarket notification requirements, associated with a large variety of gene mutation detection system subject to certain limitations as diseases and conditions, in addition to (§ 866.5940) and this exemption action. identified in this notice. FDA is also those listed in table 1 of the October At the time FDA classified a CFTR amending the codified language for the 2015 notice, to constitute a different gene mutation detection system under autosomal recessive carrier screening intended use from that of a legally § 866.5900, we were not aware of any gene mutation detection system devices marketed device in the generic type OTC Cystic Fibrosis carrier screening classification regulation to reflect this under § 866.5940 for purposes of § 866.9 tests, and it was not our intent at the final determination. Persons with (21 CFR 866.9). Because FDA agrees that time to classify this test for OTC use. We pending 510(k) submissions for devices the list of diseases and conditions also note that, to date, the only Cystic that are now exempt from premarket provided in the October 2015 notice is Fibrosis carrier screening tests that have notification, subject to the limitations, not comprehensive, and that been cleared by FDA under § 866.5900 should withdraw their submissions. applicability of § 866.5940 should be are for prescription use only. Finally,

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FDA does not believe that the special gene mutation detection systems in the determined that premarket notification controls under § 866.5900(b) would generic type § 866.5940. Devices within is not necessary to assure the safety and reasonably assure the safety and the scope of the § 866.5940 regulation effectiveness of autosomal recessive effectiveness of OTC Cystic Fibrosis for autosomal recessive carrier screening carrier screening gene detection carrier screening tests, as such special gene mutation detection systems are systems, so long as the limitations on controls were developed to be intended for autosomal recessive carrier exemption described later in this applicable to prescription use only tests. screening in adults of reproductive age. document are not met. For example, when classifying a CFTR The requested indications for carrier VI. Limitations on Exemption gene mutation detection system into screening for X-linked conditions and class II, FDA determined that the special for reporting of diagnostic results are This exemption from 510(k) for an controls under § 866.5900(b), in outside the scope of the § 866.5940 autosomal recessive carrier screening conjunction with general controls, regulation. As this final order concerns gene mutation detection system applies provided a reasonable assurance of the only exemption of devices within the only to those devices that have existing safety and effectiveness of the device. § 866.5940 regulation, the request to or reasonably foreseeable characteristics One risk to health that FDA identified expand the exemption to include carrier of commercially distributed devices was that ‘‘errors in interpretation of screening for X-linked conditions or for within that generic type, or, in the case results may lead to improper clinical the reporting of diagnostic results is of in vitro diagnostic devices, for which recommendations and medical patient outside the scope of this action. a misdiagnosis, as a result of using the management.’’ The special controls (Comment 4) The three commenters device, would not be associated with concerning generation of test results, were generally supportive of the high morbidity or mortality. Therefore, interpretation of test results, and regulation and special controls a manufacturer of an autosomal precautions for interpretation of the test established for the device type, recessive carrier screening gene results were developed only for including for the special controls that mutation detection system would still prescription use only tests with health relate to genetic counseling (e.g., be required to submit a premarket care providers in mind (see Section 6— § 866.5940(b)(1) and (b)(4)(iii)(A)). Two notification to FDA before introducing a Device Description; Test Results/ commenters requested FDA provide device or delivering it for introduction Reporting, Section 10—Labeling; additional recommendations that relate into commercial distribution when the Interpretation of Results, and Section to the special control requirements device meets any of the conditions 10—Labeling; Precautions for related to genetic counseling. described in § 866.9, except § 866.9(c)(2) interpretations of the ‘‘Class II Special (Response) FDA appreciates the to the extent it may include an Controls Guidance Document: CFTR comments supporting the regulation and autosomal recessive carrier screening Gene Mutation Detection Systems’’ special controls established for the gene mutation detection system, for the (October 26, 2005) (Ref. 2). device type. FDA believes that the class reasons explained in the October 2015 Therefore, FDA is clarifying that with II special controls established for the notice. regard to gene mutation detection device type, along with the applicable Specifically, an autosomal recessive systems indicated for the determination general controls, provides reasonable carrier screening gene mutation of carrier status by detection of assurance of the safety and effectiveness detection system is not exempt from the clinically relevant gene mutations of the device type. FDA notes that while premarket notification requirement if associated with cystic fibrosis, the the comments received did not propose such device: (1) Has an intended use classification regulation § 866.5900 is specific amendments to the special that is different from the intended use only applicable to prescription use only control requirements, such discussion is of a legally marketed device in that tests. FDA is further clarifying that we outside the scope of the October 2015 generic type; e.g., the device is intended would not consider a gene mutation notice and this final order, which for a different medical purpose, or the detection system indicated for use as an concerns the exemption from premarket device is intended for lay use where the OTC device for the determination of notification of autosomal recessive former intended use was by health care carrier status by detection of clinically carrier screening gene mutation professionals only; or (2) operates using relevant gene mutations associated with detection systems in the generic type a different fundamental scientific cystic fibrosis to constitute a different § 866.5940. technology than that used by a legally marketed device in that generic type; intended use from that of a legally V. Exemption for Autosomal Recessive marketed device in the generic type e.g., a surgical instrument cuts tissue Carrier Screening Gene Mutation with a laser beam rather than with a § 866.5940 for purposes of § 866.9(a). As Detection System Devices such, OTC Cystic Fibrosis carrier sharpened metal blade, or an in vitro screening tests are within the scope of FDA has assessed the need for 510(k) diagnostic device detects or identifies the classification regulation for an clearance for this type of device by infectious agents by using a DNA probe autosomal recessive carrier screening considering the factors discussed in the or nucleic acid hybridization or gene mutation detection system January 21, 1998, Federal Register amplification technology rather than (§ 866.5940) and are included within the notice (63 FR 3142) and subsequently in culture or immunoassay technology; or scope of this action. the Class II 510(k) Exemption Guidance, (3) is an in vitro device that is intended: (Comment 3) One commenter as previously discussed in the October for use in the diagnosis, monitoring or requested that the exemption be 2015 notice, and has determined they screening of neoplastic diseases with expanded to include carrier screening weigh in favor of 510(k) exemption, the exception of immunohistochemical for X-linked conditions. The commenter subject to certain limitations discussed devices; for measuring an analyte which further requested that the exemption be later in this order. Therefore, for the serves as a surrogate marker for expanded to allow for the reporting of reasons set forth in the Federal Register screening, diagnosis, or monitoring of diagnostic results. of October 27, 2015, and as informed by life threatening diseases, such as (Response) The October 2015 notice the comments received and FDA’s acquired immune deficiency syndrome and this final order concern the understanding and experience with (AIDS), chronic or active hepatitis, exemption from premarket notification autosomal recessive carrier screening tuberculosis, or myocardial infarction, of autosomal recessive carrier screening gene detection systems, FDA has or to monitor therapy; for assessing the

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risk of cardiovascular diseases; for use 809 have been approved under OMB Dated: November 1, 2017. in diabetes management; for identifying control number 0910–0485. Lauren Silvis, or inferring the identity of a Chief of Staff. IX. References microorganism directly from clinical [FR Doc. 2017–24162 Filed 11–6–17; 8:45 am] material; for detection of antibodies to The following references are on BILLING CODE 4164–01–P microorganisms other than display in the Dockets Management immunoglobulin G (IgG) and IgG assays Staff (see ADDRESSES) and are available when the results are not qualitative, or for viewing by interested persons DEPARTMENT OF COMMERCE are used to determine immunity, or the between 9 a.m. and 4 p.m., Monday assay is intended for use in matrices through Friday; they are also available United States Patent and Trademark other than serum or plasma; for electronically at https:// Office noninvasive testing; or for near-patient www.regulations.gov. FDA has verified testing (point of care). 37 CFR Part 42 Exemption from the requirement of the Web site addresses, as of the date premarket notification does not exempt this document publishes in the Federal [Docket No. PTO–P–2016–0029] a device from other applicable Register, but Web sites are subject to regulatory controls under the FD&C Act, change over time. RIN 0651–AD10 including the applicable general and 1. FDA Guidance, ‘‘Procedures for Class II Rule on Attorney-Client Privilege for special controls. Indeed, FDA’s decision Device Exemptions from Premarket Trials Before the Patent Trial and to grant 510(k) exemption for these Notification, Guidance for Industry and Appeal Board devices is based, in part, on the special CDRH Staff,’’ February 19, 1998, controls, in combination with general available at https://www.fda.gov/ AGENCY: Patent Trial and Appeal Board, controls, providing sufficiently rigorous downloads/MedicalDevices/ United States Patent and Trademark mitigations for the risks identified for DeviceRegulationandGuidance/ Office, U.S. Department of Commerce. this generic type. GuidanceDocuments/UCM080199.pdf. ACTION: Final rule. This exemption from 510(k), subject 2. FDA Guidance for Industry and FDA Staff to the limitations described above, is ‘‘Class II Special Controls Guidance SUMMARY: This final rule on attorney- immediately in effect for autosomal Document: CFTR Gene Mutation client privilege amends the existing recessive carrier screening gene Detection Systems,’’ October 26, 2005, rules relating to the United States Patent mutation detection systems. This available at: https://www.fda.gov/ and Trademark Office (Office or exemption will decrease regulatory downloads/MedicalDevices/ USPTO) trial practice for inter partes burdens on the medical device industry DeviceRegulationandGuidance/ review, post-grant review, the and will eliminate private costs and GuidanceDocuments/ucm071104.pdf. transitional program for covered expenditures required to comply with business method patents, and derivation List of Subjects in 21 CFR Part 866 Federal regulation. Specifically, proceedings that implemented regulated industry will no longer have Biologics, Laboratories, Medical provisions of the Leahy-Smith America to invest time and resources in devices. Invents Act (‘‘AIA’’) providing for trials premarket notifications, including before the Office. Therefore, under the Federal Food, preparation of documents and data for DATES: This rule is effective on submission to FDA, payment of user Drug, and Cosmetic Act and under December 7, 2017. fees associated with 510(k) submissions, authority delegated to the Commissioner FOR FURTHER INFORMATION CONTACT: and responding to questions and of Food and Drugs, 21 CFR part 866 is Edward Elliott, Attorney Advisor, by requests for additional information from amended as follows: telephone at (571) 272–7024 or by email FDA during 510(k) review for devices in at [email protected]. this exempted type. PART 866—IMMUNOLOGY AND MICROBIOLOGY DEVICES SUPPLEMENTARY INFORMATION: VII. Analysis of Environmental Impact Executive Summary: Purpose: This We have determined under 21 CFR ■ 1. The authority citation for part 866 final rule clarifies situations where 25.34(b) that this action is of a type that continues to read as follows: privilege is recognized for does not individually or cumulatively communications between clients and have a significant effect on the human Authority: 21 U.S.C. 351, 360, 360c, 360e, their domestic or foreign patent 360j, 360l, 371. environment. Therefore, neither an attorneys and patent agents. environmental assessment nor an ■ 2. In § 866.5940, revise paragraph (b) Background environmental impact statement is introductory text to read as follows: required. In February 2015, the USPTO held a § 866.5940 Autosomal recessive carrier roundtable and solicited comments on VIII. Paperwork Reduction Act of 1995 screening gene mutation detection system. attorney-client privilege issues. See This notice refers to previously * * * * * Notice of Roundtable and Request for approved collections of information Comments on Domestic and found in FDA regulations. These (b) Classification. Class II (special International Issues Related to collections of information are subject to controls). The device is exempt from the Privileged Communications Between review by the Office of Management and premarket notification procedures in Patent Practitioners and Their Clients, Budget (OMB) under the Paperwork subpart E of part 807 of this chapter 80 FR 3953 (Jan. 26, 2015). As part of Reduction Act of 1995 (44 U.S.C. 3501– subject to the limitations in § 866.9, that process, the USPTO requested 3520). The collections of information in except § 866.9(c)(2). Autosomal comments on whether communications 21 CFR part 807, subpart, E have been recessive carrier screening gene between patent applicants or owners approved under OMB control number mutation detection system must comply with their U.S. patent agents or foreign 0910–0120 and the collections of with the following special controls: patent practitioners should be information in 21 CFR parts 801 and * * * * * recognized as privileged to the same

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