83 FR 8355 - Medical Devices; Hematology and Pathology Devices; Classification of Lynch Syndrome Test Systems
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 39 (February 27, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 39 (February 27, 2018)
| Page Range | 8355-8357 | |
| FR Document | 2018-03924 |
[Federal Register Volume 83, Number 39 (Tuesday, February 27, 2018)] [Rules and Regulations] [Pages 8355-8357] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-03924] ======================================================================= ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 864 [Docket No. FDA 2018-N-0339] Medical Devices; Hematology and Pathology Devices; Classification of Lynch Syndrome Test Systems AGENCY: Food and Drug Administration, HHS. ACTION: Final order. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or we) is classifying Lynch syndrome test systems into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the Lynch syndrome test systems' classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens. DATES: This order is effective February 27, 2018. The classification was applicable on October 27, 2017. FOR FURTHER INFORMATION CONTACT: Scott McFarland, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 4676, Silver Spring, [[Page 8356]] MD 20993-0002, 301-796-5866, [email protected]. SUPPLEMENTARY INFORMATION: I. Background Upon request, FDA has classified Lynch syndrome test systems as class II (special controls), which we have determined will provide a reasonable assurance of safety and effectiveness. In addition, we believe this action will enhance patients' access to beneficial innovation, in part by reducing regulatory burdens by placing the device into a lower device class than the automatic class III assignment. The automatic assignment of class III occurs by operation of law and without any action by FDA, regardless of the level of risk posed by the new device. Any device that was not in commercial distribution before May 28, 1976, is automatically classified as, and remains within, class III and requires premarket approval unless and until FDA takes an action to classify or reclassify the device (see 21 U.S.C. 360c(f)(1)). We refer to these devices as ``postamendments devices'' because they were not in commercial distribution prior to the date of enactment of the Medical Device Amendments of 1976, which amended the Federal Food, Drug, and Cosmetic Act (FD&C Act). FDA may take a variety of actions in appropriate circumstances to classify or reclassify a device into class I or II. We may issue an order finding a new device to be substantially equivalent under section 513(i) of the FD&C Act to a predicate device that does not require premarket approval (see 21 U.S.C. 360c(i)). We determine whether a new device is substantially equivalent to a predicate by means of the procedures for premarket notification under section 510(k) of the FD&C Act and part 807 (21 U.S.C. 360(k) and 21 CFR part 807, respectively). FDA may also classify a device through ``De Novo'' classification, a common name for the process authorized under section 513(f)(2) of the FD&C Act. Section 207 of the Food and Drug Administration Modernization Act of 1997 established the first procedure for De Novo classification (Pub. L. 105-115). Section 607 of the Food and Drug Administration Safety and Innovation Act modified the De Novo application process by adding a second procedure (Pub. L. 112-144). A device sponsor may utilize either procedure for De Novo classification. Under the first procedure, the person submits a 510(k) for a device that has not previously been classified. After receiving an order from FDA classifying the device into class III under section 513(f)(1) of the FD&C Act, the person then requests a classification under section 513(f)(2). Under the second procedure, rather than first submitting a 510(k) and then a request for classification, if the person determines that there is no legally marketed device upon which to base a determination of substantial equivalence, that person requests a classification under section 513(f)(2) of the FD&C Act. Under either procedure for De Novo classification, FDA is required to classify the device by written order within 120 days. The classification will be according to the criteria under section 513(a)(1) of the FD&C Act. Although the device was automatically within class III, the De Novo classification is considered to be the initial classification of the device. We believe this De Novo classification will enhance patients' access to beneficial innovation, in part by reducing regulatory burdens. When FDA classifies a device into class I or II via the De Novo process, the device can serve as a predicate for future devices of that type, including for 510(k)s (see 21 U.S.C. 360c(f)(2)(B)(i)). As a result, other device sponsors do not have to submit a De Novo request or premarket approval application in order to market a substantially equivalent device (see 21 U.S.C. 360c(i), defining ``substantial equivalence''). Instead, sponsors can use the less-burdensome 510(k) process, when necessary, to market their device. II. De Novo Classification On May 31, 2017, Ventana Medical Systems, Inc. submitted a request for De Novo classification of the Ventana MMR IHC Panel. FDA reviewed the request in order to classify the device under the criteria for classification set forth in section 513(a)(1) of the FD&C Act. We classify devices into class II if general controls by themselves are insufficient to provide reasonable assurance of safety and effectiveness, but there is sufficient information to establish special controls that, in combination with the general controls, provide reasonable assurance of the safety and effectiveness of the device for its intended use (see 21 U.S.C. 360c(a)(1)(B)). After review of the information submitted in the request, we determined that the device can be classified into class II with the establishment of special controls. FDA has determined that these special controls, in addition to the general controls, will provide reasonable assurance of the safety and effectiveness of the device. Therefore, on October 27, 2017, FDA issued an order to the requester classifying the device into class II. FDA is codifying the classification of the device by adding 21 CFR 864.1866. We have named the generic type of device Lynch syndrome test systems, and it is identified as in vitro diagnostic tests for use with tumor tissue to identify previously diagnosed cancer patients at risk for having Lynch syndrome. FDA has identified the following risks to health associated specifically with this type of device and the measures required to mitigate these risks in table 1. Table 1--Lynch Syndrome Test Systems Risks and Mitigation Measures ------------------------------------------------------------------------ Identified risk Mitigation measures ------------------------------------------------------------------------ False positive test result........ General controls; Special controls (1) and (2) (21 CFR 864.1866(b)(1) and (2)). False negative test result........ General controls; Special control (1) and (2) (21 CFR 864.1866(b)(1) and(2)). ------------------------------------------------------------------------ FDA has determined that special controls, in combination with the general controls, address these risks to health and provide reasonable assurance of safety and effectiveness. For a device to fall within this classification, and thus avoid automatic classification in class III, it would have to comply with the special controls named in this final order. The necessary special controls appear in the regulation codified by this order. This device is subject to premarket notification requirements under section 510(k). III. Analysis of Environmental Impact 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 [[Page 8357]] nor an environmental impact statement is required. IV. Paperwork Reduction Act of 1995 This final order establishes special controls that refer to previously approved collections of information found in other FDA regulations and guidance. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections of information in the guidance document ``De Novo Classification Process (Evaluation of Automatic Class III Designation)'' have been approved under OMB control number 0910-0844; the collections of information in part 814, subparts A through E, regarding premarket approval, have been approved under OMB control number 0910-0231; the collections of information in part 807, subpart E, regarding premarket notification submissions, have been approved under OMB control number 0910-0120; and the collections of information in 21 CFR parts 801 and 809, regarding labeling, have been approved under OMB control number 0910-0485. List of Subjects in 21 CFR Part 864 Blood, Medical devices, Packaging and containers. Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, 21 CFR part 864 is amended as follows: PART 864--HEMATOLOGY AND PATHOLOGY DEVICES 0 1. The authority citation for part 864 continues to read as follows: Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371. 0 2. Add Sec. 864.1866 to subpart B to read as follows: Sec. 864.1866 Lynch syndrome test systems. (a) Identification. Lynch syndrome test systems are in vitro diagnostic tests for use with tumor tissue to identify previously diagnosed cancer patients at risk for having Lynch syndrome. (b) Classification. Class II (special controls). The special controls for this device are: (1) Premarket notification submissions must include the following information, as appropriate: (i) A detailed description of all test components, including all provided reagents, and required but not provided, ancillary reagents. (ii) A detailed description of instrumentation and equipment, including illustrations or photographs of non-standard equipment or manuals. (iii) Detailed documentation of the device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (iv) A detailed description of quality controls including appropriate positive and negative controls that are recommended or provided. (v) Detailed specifications for sample collection, processing, and storage. (vi) A detailed description of methodology and assay procedure. (vii) A description of the assay cut-off (i.e., the medical decision point between positive and negative results) or other relevant criteria that distinguishes positive and negative results, or ordinal classes of marker expression, including the rationale for the chosen cut-off or other relevant criteria and results supporting validation of the cut-off. (viii) Detailed specification of the criteria for test result interpretation and reporting. (ix) Detailed information demonstrating the performance characteristics of the device, including: (A) Data from an appropriate study demonstrating clinical accuracy using well-characterized clinical specimens representative of the intended use population (i.e., concordance to Deoxyribonucleic Acid (DNA) sequencing results of the Lynch syndrome associated genes or method comparison to the predicate device using samples with known alterations in genes representative of Lynch syndrome). Pre-specified acceptance criteria must be provided and followed. (B) Appropriate device reproducibility data investigating all sources of variance (e.g., for distributed tests, data generated using a minimum of three sites, of which at least two sites must be external sites). Each site must perform testing over a minimum of 5 nonconsecutive days evaluating a sample panel that spans the claimed measuring range, and includes the clinical threshold. Pre-specified acceptance criteria must be provided and followed. (C) Data demonstrating reader reproducibility, both within-reader and between-reader, assessed by three readers over 3 nonconsecutive days at each site, including a 2 week washout period between reads, as appropriate. (D) Device precision data using clinical samples spanning the measuring range and controls to evaluate the within-lot, between-lot, within-run, between run, and total variation. (E) Analytical specificity studies including as appropriate, western blots, peptide inhibition, testing in normal tissues and neoplastic tissues, interference by endogenous and exogenous substances, and cross-reactivity and cross contamination testing. (F) Device analytical sensitivity data generated by testing an adequate number of samples from individuals with the target condition such that prevalence of the biomarker in the target population is established. (G) Device stability data, including real-time stability and in-use stability, and stability evaluating various storage times, temperatures, and freeze-thaw conditions, as appropriate. (H) The staining performance criteria assessed must include overall staining acceptability, background staining acceptability, and morphology acceptability, as appropriate. (I) Appropriate training requirements for users, including interpretation manual, as applicable. (J) Identification of risk mitigation elements used by the device, including a description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing. (2) The device's Sec. 809.10(b) of this chapter compliant labeling must include a detailed description of the protocol, including the information described in paragraphs (b)(1)(i) through (viii) of this section, as appropriate, and a detailed description of the performance studies performed and the summary of the results, including those that relate to paragraph (b)(1)(ix) of this section, as appropriate. Dated: February 21, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-03924 Filed 2-26-18; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 83, No. 39 / Tuesday, February 27, 2018 / Rules and Regulations 8355
Background Accordingly, CBP is amending 19 CFR Authority: 5 U.S.C. 301; 19 U.S.C. 66, 1202
12.104g(a) in order to reflect the (General Note 3(i), Harmonized Tariff
Pursuant to the provisions of the Schedule of the United States (HTSUS)),
Convention on Cultural Property extension of the import restrictions
pursuant to the agreement. 1624;
Implementation Act (hereafter, the
The Designated List of Archaeological * * * * *
Cultural Property Implementation Act
or the Act) (Pub. L. 97–446, 19 U.S.C. Material originating in Belize covered Sections 12.104 through 12.104i also issued
2601 et seq.), which implements the by these import restrictions is set forth under 19 U.S.C. 2612;
1970 United Nations Educational, in CBP Dec. 13–05, which can be found * * * * *
Scientific and Cultural Organization online at: https://eca.state.gov/files/
bureau/bz2013dlfrn.pdf. § 12.104g [Amended]
(UNESCO) Convention on the Means of
Prohibiting and Preventing the Illicit The restrictions on the importation of ■ 2. In § 12.104g, the table in paragraph
Import, Export and Transfer of this archaeological material originating (a) is amended in the entry for Belize by
Ownership of Cultural Property in Belize are to continue in effect for an adding the words ‘‘extended by ‘‘CBP
(hereinafter, the Convention), in U.S. additional five years. Importation of Dec. 18–02’’ after the words ‘‘CBP Dec.
law, the United States may enter into an such material continues to be restricted 13–05’’ in the column headed ‘‘Decision
international agreement with another unless the conditions set forth in 19 No.’’.
State Party to the Convention to impose U.S.C. 2606 and 19 CFR 12.104c are
met. Kevin K. McAleenan,
import restrictions on eligible
Acting Commissioner, U.S. Customs and
archaeological and ethnological Inapplicability of Notice and Delayed Border Protection.
materials under procedures and Effective Date Approved: February 21, 2018.
requirements prescribed by the Act.
This amendment involves a foreign Timothy E. Skud,
Under the Act and applicable CBP
regulations (19 CFR 12.104g), the affairs function of the United States and Deputy Assistant Secretary of the Treasury.
restrictions are effective for no more is, therefore, being made without notice [FR Doc. 2018–03946 Filed 2–26–18; 8:45 am]
than five years beginning on the date on or public procedure (5 U.S.C. 553(a)(1)). BILLING CODE 9111–14–P
which the agreement enters into force In addition, CBP has determined that
with respect to the United States (19 such notice or public procedure would
U.S.C. 2602(b)). This period may be be impracticable and contrary to the DEPARTMENT OF HEALTH AND
extended for additional periods, not to public interest because the action being HUMAN SERVICES
exceed five years, if it is determined that taken is essential to avoid interruption
the factors justifying the initial of the application of the existing import Food and Drug Administration
agreement still pertain and no cause for restrictions (5 U.S.C. 553(b)(B)). For the
suspension of the agreement exists (19 same reason, a delayed effective date is 21 CFR Part 864
U.S.C. 2602(e); 19 CFR 12.104g(a)). not required under 5 U.S.C 553(d)(3).
[Docket No. FDA 2018–N–0339]
On February 27, 2013, the United Regulatory Flexibility Act
States entered into a bilateral agreement Medical Devices; Hematology and
with the Government of Belize Because no notice of proposed Pathology Devices; Classification of
concerning the imposition of import rulemaking is required, the provisions Lynch Syndrome Test Systems
restrictions on certain categories of of the Regulatory Flexibility Act (5
archaeological material originating in U.S.C. 601 et seq.) do not apply. AGENCY: Food and Drug Administration,
Belize, pursuant to the Act. (The HHS.
Executive Orders 12866 and 13771
agreement can be found online at ACTION: Final order.
https://eca.state.gov/files/bureau/ Because this rule involves a foreign
bzmou2013.pdf.) On March 5, 2013, affairs function of the United States, it SUMMARY: The Food and Drug
CBP published CBP Dec. 13–05 in the is not subject to either Executive Order Administration (FDA or we) is
Federal Register (78 FR 14183), which 12866 or Executive Order 13771. classifying Lynch syndrome test systems
amended 19 CFR 12.104g(a) to reflect into class II (special controls). The
Signing Authority
the imposition of restrictions on this special controls that apply to the device
This regulation is being issued in type are identified in this order and will
material and included a list designating
accordance with 19 CFR 0.1(a)(1). be part of the codified language for the
the types of archaeological material
covered by the restrictions. These List of Subjects in 19 CFR Part 12 Lynch syndrome test systems’
restrictions were to be effective through classification. We are taking this action
Cultural property, Customs duties and because we have determined that
February 27, 2018. inspection, Imports, Prohibited
On January 12, 2018, after reviewing classifying the device into class II
merchandise. (special controls) will provide a
the findings and recommendations of
the Cultural Property Advisory Amendment to CBP Regulations reasonable assurance of safety and
Committee, the Acting Assistant effectiveness of the device. We believe
For the reasons set forth above, part this action will also enhance patients’
Secretary for Educational and Cultural 12 of Title 19 of the Code of Federal
Affairs, Department of State, concluding access to beneficial innovative devices,
Regulations (19 CFR part 12), is in part by reducing regulatory burdens.
that the cultural heritage of Belize amended as set forth below.
continues to be in jeopardy from pillage DATES: This order is effective February
of certain archaeological material, made 27, 2018. The classification was
daltland on DSKBBV9HB2PROD with RULES
PART 12—SPECIAL CLASSES OF
the necessary statutory determinations, MERCHANDISE applicable on October 27, 2017.
and decided to extend the agreement FOR FURTHER INFORMATION CONTACT:
with Belize for an additional five-year ■ 1. The general authority citation for Scott McFarland, Center for Devices and
period to February 27, 2023. Diplomatic part 12 and the specific authority Radiological Health, Food and Drug
notes have been exchanged that reflect citation for § 12.104g continue to read as Administration, 10903 New Hampshire
the extension of the agreement. follows: Ave., Bldg. 66, Rm. 4676, Silver Spring,
VerDate Sep<11>2014 18:04 Feb 26, 2018 Jkt 244001 PO 00000 Frm 00035 Fmt 4700 Sfmt 4700 E:\FR\FM\27FER1.SGM 27FER1](https://thefederalregister.org/doc/83_FR_8394/page/1.svg)
![Federal Register / Vol. 83, No. 39 / Tuesday, February 27, 2018 / Rules and Regulations 8357
nor an environmental impact statement (ii) A detailed description of within-run, between run, and total
is required. instrumentation and equipment, variation.
including illustrations or photographs of (E) Analytical specificity studies
IV. Paperwork Reduction Act of 1995
non-standard equipment or manuals. including as appropriate, western blots,
This final order establishes special (iii) Detailed documentation of the peptide inhibition, testing in normal
controls that refer to previously device software, including, but not tissues and neoplastic tissues,
approved collections of information limited to, standalone software interference by endogenous and
found in other FDA regulations and applications and hardware-based exogenous substances, and cross-
guidance. These collections of devices that incorporate software. reactivity and cross contamination
information are subject to review by the (iv) A detailed description of quality testing.
Office of Management and Budget controls including appropriate positive (F) Device analytical sensitivity data
(OMB) under the Paperwork Reduction and negative controls that are generated by testing an adequate
Act of 1995 (44 U.S.C. 3501–3520). The recommended or provided. number of samples from individuals
collections of information in the (v) Detailed specifications for sample with the target condition such that
guidance document ‘‘De Novo collection, processing, and storage. prevalence of the biomarker in the target
Classification Process (Evaluation of (vi) A detailed description of population is established.
Automatic Class III Designation)’’ have methodology and assay procedure. (G) Device stability data, including
been approved under OMB control (vii) A description of the assay cut-off real-time stability and in-use stability,
number 0910–0844; the collections of (i.e., the medical decision point between and stability evaluating various storage
information in part 814, subparts A positive and negative results) or other times, temperatures, and freeze-thaw
through E, regarding premarket relevant criteria that distinguishes conditions, as appropriate.
approval, have been approved under positive and negative results, or ordinal (H) The staining performance criteria
OMB control number 0910–0231; the classes of marker expression, including assessed must include overall staining
collections of information in part 807, the rationale for the chosen cut-off or acceptability, background staining
subpart E, regarding premarket other relevant criteria and results acceptability, and morphology
notification submissions, have been supporting validation of the cut-off. acceptability, as appropriate.
approved under OMB control number (viii) Detailed specification of the (I) Appropriate training requirements
0910–0120; and the collections of criteria for test result interpretation and for users, including interpretation
information in 21 CFR parts 801 and reporting. manual, as applicable.
809, regarding labeling, have been (ix) Detailed information (J) Identification of risk mitigation
approved under OMB control number demonstrating the performance elements used by the device, including
0910–0485. characteristics of the device, including: a description of all additional
(A) Data from an appropriate study procedures, methods, and practices
List of Subjects in 21 CFR Part 864
demonstrating clinical accuracy using incorporated into the instructions for
Blood, Medical devices, Packaging well-characterized clinical specimens use that mitigate risks associated with
and containers. representative of the intended use testing.
Therefore, under the Federal Food, population (i.e., concordance to (2) The device’s § 809.10(b) of this
Drug, and Cosmetic Act and under Deoxyribonucleic Acid (DNA) chapter compliant labeling must include
authority delegated to the Commissioner sequencing results of the Lynch a detailed description of the protocol,
of Food and Drugs, 21 CFR part 864 is syndrome associated genes or method including the information described in
amended as follows: comparison to the predicate device paragraphs (b)(1)(i) through (viii) of this
using samples with known alterations in section, as appropriate, and a detailed
PART 864—HEMATOLOGY AND genes representative of Lynch description of the performance studies
PATHOLOGY DEVICES syndrome). Pre-specified acceptance performed and the summary of the
criteria must be provided and followed. results, including those that relate to
■ 1. The authority citation for part 864 paragraph (b)(1)(ix) of this section, as
continues to read as follows: (B) Appropriate device
reproducibility data investigating all appropriate.
Authority: 21 U.S.C. 351, 360, 360c, 360e, sources of variance (e.g., for distributed Dated: February 21, 2018.
360j, 360l, 371. tests, data generated using a minimum Leslie Kux,
■ 2. Add § 864.1866 to subpart B to read of three sites, of which at least two sites Associate Commissioner for Policy.
as follows: must be external sites). Each site must [FR Doc. 2018–03924 Filed 2–26–18; 8:45 am]
perform testing over a minimum of 5
§ 864.1866 Lynch syndrome test systems. nonconsecutive days evaluating a
BILLING CODE 4164–01–P
(a) Identification. Lynch syndrome sample panel that spans the claimed
test systems are in vitro diagnostic tests measuring range, and includes the
for use with tumor tissue to identify clinical threshold. Pre-specified DEPARTMENT OF HOMELAND
previously diagnosed cancer patients at acceptance criteria must be provided SECURITY
risk for having Lynch syndrome. and followed.
(b) Classification. Class II (special Coast Guard
(C) Data demonstrating reader
controls). The special controls for this reproducibility, both within-reader and
device are: 33 CFR Part 165
between-reader, assessed by three
(1) Premarket notification readers over 3 nonconsecutive days at
daltland on DSKBBV9HB2PROD with RULES
[Docket Number USCG–2018–0074]
submissions must include the following each site, including a 2 week washout
information, as appropriate: period between reads, as appropriate. RIN 1625–AA00
(i) A detailed description of all test (D) Device precision data using Safety Zone; Wando Terminal Crane
components, including all provided clinical samples spanning the Movement; Charleston, SC
reagents, and required but not provided, measuring range and controls to
ancillary reagents. evaluate the within-lot, between-lot, AGENCY: Coast Guard, DHS.
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Document Created: 2018-02-27 01:14:58
Document Modified: 2018-02-27 01:14:58
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Rules and Regulations | |
| Action | Final order. | |
| Dates | This order is effective February 27, 2018. The classification was applicable on October 27, 2017. | |
| Contact | Scott McFarland, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 4676, Silver Spring, MD 20993-0002, 301-796-5866, [email protected] | |
| FR Citation | 83 FR 8355 | |
| CFR Associated | Blood; Medical Devices and Packaging and Containers |
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