83 FR 28994 - Medical Devices; Immunology and Microbiology Devices; Classification of the Next Generation Sequencing Based Tumor Profiling Test
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 121 (June 22, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 121 (June 22, 2018)
| Page Range | 28994-28996 | |
| FR Document | 2018-13406 |
[Federal Register Volume 83, Number 121 (Friday, June 22, 2018)] [Rules and Regulations] [Pages 28994-28996] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-13406] ======================================================================= ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 [Docket No. FDA-2018-N-1929] Medical Devices; Immunology and Microbiology Devices; Classification of the Next Generation Sequencing Based Tumor Profiling Test AGENCY: Food and Drug Administration, HHS. ACTION: Final order. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or we) is classifying the next generation sequencing based tumor profiling test 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 next generation sequencing based tumor profiling test's 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 June 22, 2018. The classification was applicable on November 15, 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, MD, 20993-0002, 301- 796-6217, [email protected]. SUPPLEMENTARY INFORMATION: I. Background Upon request, FDA has classified the next generation sequencing based tumor profiling test 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) & 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 (21 U.S.C. 360c(f)(2)). 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 (21 U.S.C. 360c(a)(1)). 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 PMA 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 September 25, 2017, Memorial Sloan-Kettering Cancer Center Department of Pathology submitted a request for De Novo classification of the MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets). 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 November 15, 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 866.6080. We have named the generic type of device next generation sequencing (NGS) based tumor profiling test, and it is identified as a qualitative in vitro diagnostic test intended for NGS analysis of tissue [[Page 28995]] specimens from malignant solid neoplasms to detect somatic mutations in a broad panel of targeted genes to aid in the management of previously diagnosed cancer patients by qualified health care professionals. 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--Next Generation Sequencing Based Tumor Profiling Test Risks and Mitigation Measures ------------------------------------------------------------------------ Identified risk Mitigation measures ------------------------------------------------------------------------ Incorrect performance of the test General controls and Special leading to false positives, false control (1) (21 CFR negatives. 866.6080(b)(1)). Incorrect interpretation of test General controls; Special results. control (1)(21 CFR 866.6080(b)(1)(iii)(E)); and Special control (2) (21 CFR 866.6080(b)(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. In order 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 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 collection of information in part 814, subparts A through E, regarding premarket approval, have been approved under OMB control number 0910-0231; the collection 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 866 Biologics, Laboratories, Medical devices. Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, 21 CFR part 866 is amended as follows: PART 866--IMMUNOLOGY AND MICROBIOLOGY DEVICES 0 1. The authority citation for part 866 continues to read as follows: Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371. 0 2. Add Sec. 866.6080 to subpart G to read as follows: Sec. 866.6080 Next generation sequencing based tumor profiling test. (a) Identification. A next generation sequencing (NGS) based tumor profiling test is a qualitative in vitro diagnostic test intended for NGS analysis of tissue specimens from malignant solid neoplasms to detect somatic mutations in a broad panel of targeted genes to aid in the management of previously diagnosed cancer patients by qualified health care professionals. (b) Classification. Class II (special controls). The special controls for this device are: (1) Premarket notification submissions must include the following information: (i) A detailed description of all somatic mutations that are intended to be detected by the test and that are adequately supported in accordance with paragraph (b)(1)(v) of this section and reported in the test results in accordance with paragraph (b)(2)(iv) of this section, including: (A) A listing of mutations that are cancer mutations with evidence of clinical significance. (B) As appropriate, a listing of mutations that are cancer mutations with potential clinical significance. (ii) The indications for use must specify the following: (A) The test is indicated for previously diagnosed cancer patients. (B) The intended specimen type(s) and matrix (e.g., formalin-fixed, paraffin-embedded tumor tissue). (C) The mutation types (e.g., single nucleotide variant, insertion, deletion, copy number variation or gene rearrangement) for which validation data has been provided. (D) The name of the testing facility or facilities, as applicable. (iii) A detailed device description including the following: (A) A description of the test in terms of genomic coverage, as follows: (1) Tabulated summary of all mutations reported, grouped according to gene and target region within each gene, along with the specific cDNA and amino acid positions for each mutation. (2) A description of any within-gene targeted regions that cannot be reported and the data behind such conclusion. (B) Specifications for specimen requirements including any specimen collection devices and preservatives, specimen volume, minimum tumor content, specimen handling, DNA extraction, and criteria for DNA quality and quantity metrics that are prerequisite to performing the assay. (C) A detailed description of all test components, reagents, instrumentation, and software required. Detailed documentation of the device software including but not limited to, software applications and hardware-based devices that incorporate software. (D) A detailed description of the methodology and protocols for each step of the test, including description of the quality metrics, thresholds, and filters at each step of the test that are implemented for final result reporting and a description of the metrics for run- failures, specimen-failures, invalids, as applicable. (E) A list of links provided by the device to the user or accessed by the device for internal or external information (e.g., decision rules or databases) supporting clinical significance of test results for the panel [[Page 28996]] or its elements in accordance with paragraphs (b)(1)(v) and (b)(2)(vi) of this section. (F) A description of internal and external controls that are recommended or provided and control procedures. The description must identify those control elements that are incorporated into the testing procedure. (iv) Information demonstrating analytical validity of the device according to analytical performance characteristics, evaluated either specifically for each gene/mutation or, when clinically and practically justified, using a representative approach based on other mutations of the same type, including: (A) Data that adequately supports the intended specimen type (e.g., formalin-fixed, paraffin-embedded tumor tissue), specimen handling protocol, and nucleic acid purification for specific tumor types or for a pan-tumor claim. (B) A summary of the empirical evidence obtained to demonstrate how the analytical quality metrics and thresholds were optimized. (C) Device precision data using clinical samples to adequately evaluate intra-run, inter-run, and total variability. The samples must cover all mutation types tested (both positive and negative samples) and include samples near the limit of detection of the device. Precision must be assessed by agreement within replicates on the assay final result for each representative mutation, as applicable, and also supported by sequencing quality metrics for targeted regions across the panel. (D) Description of the protocols and/or data adequately demonstrating the interchangeability of reagent lots and multiplexing barcodes. (E) A description of the nucleic acid assay input concentration range and the evidence to adequately support the range. (F) A description of the data adequately supporting the limit of detection of the device. (G) A description of the data to adequately support device accuracy using clinical specimens representing the intended specimen type and range of tumor types, as applicable. (1) Clinical specimens tested to support device accuracy must adequately represent the list of cancer mutations with evidence of clinical significance to be detected by the device. (2) For mutations that are designated as cancer mutations with evidence of clinical significance and that are based on evidence established in the intended specimen type (e.g., tumor tissues) but for a different analyte type (e.g., protein, RNA) and/or a measurement (e.g., incorporating a score or copy number) and/or with an alternative technology (e.g., IHC, RT-qPCR, FISH), evidence of accuracy must include clinically adequate concordance between results for the mutation and the medically established biomarker test (e.g., evidence generated from an appropriately sized method comparison study using clinical specimens from the target population). (3) For qualitative DNA mutations not described in paragraph (b)(1)(iv)(G)(2) of this section, accuracy studies must include both mutation-positive and wild-type results. (H) Adequate device stability information. (v) Information that adequately supports the clinical significance of the panel must include: (A) Criteria established on what types and levels of evidence will clinically validate a mutation as a cancer mutation with evidence of clinical significance versus a cancer mutation with potential clinical significance. (B) For representative mutations of those designated as cancer mutations with evidence of clinical significance, a description of the clinical evidence associated with such mutations, such as clinical evidence presented in professional guidelines, as appropriate, with method comparison performance data as described in paragraph (b)(1)(iv)(G) of this section. (C) For all other mutations designated as cancer mutations with potential clinical significance, a description of the rationale for reporting. (2) The 21 CFR 809.10 compliant labeling and any product information and test report generated, must include the following, as applicable: (i) The intended use statement must specify the following: (A) The test is indicated for previously diagnosed cancer patients. (B) The intended specimen type(s) and matrix (e.g., formalin-fixed, paraffin-embedded tumor tissue). (C) The mutation types (e.g., single nucleotide variant, insertion, deletion, copy number variation or gene rearrangement) for which validation data has been provided. (D) The name of the testing facility or facilities, as applicable. (ii) A description of the device and summary of the results of the performance studies performed in accordance with paragraphs (b)(1)(iii), (b)(1)(iv), and (b)(1)(v) of this section. (iii) A description of applicable test limitations, including, for device specific mutations validated with method comparison data to a medically established test in the same intended specimen type, appropriate description of the level of evidence and/or the differences between next generation sequencing results and results from the medically established test (e.g., as described in professional guidelines). (iv) A listing of all somatic mutations that are intended to be detected by the device and that are reported in the test results under the following two categories or equivalent designations, as appropriate: ``cancer mutations panel with evidence of clinical significance'' or ``cancer mutations panel with potential clinical significance.'' (v) For mutations reported under the category of ``cancer mutations panel with potential clinical significance,'' a limiting statement that states ``For the mutations listed in [cancer mutations panel with potential clinical significance or equivalent designation], the clinical significance has not been demonstrated [with adequate clinical evidence (e.g., by professional guidelines) in accordance with paragraph (b)(1)(v) of this section] or with this test.'' (vi) For mutations under the category of ``cancer mutations panel with evidence of clinical significance,'' or equivalent designation, link(s) for physicians to access internal or external information concerning decision rules or conclusions about the level of evidence for clinical significance that is associated with the marker in accordance with paragraph (b)(1)(v) of this section. Dated: June 18, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-13406 Filed 6-21-18; 8:45 am] BILLING CODE 4164-01-P
![28994 Federal Register / Vol. 83, No. 121 / Friday, June 22, 2018 / Rules and Regulations
(g) Sunset provision. The provisions by placing the device into a lower Under either procedure for De Novo
of this section will no longer be effective device class than the automatic class III classification, FDA is required to
on August 2, 2019, unless we terminate assignment. classify the device by written order
them earlier or extend them beyond that The automatic assignment of class III within 120 days. The classification will
date by notice of a final rule in the occurs by operation of law and without be according to the criteria under
Federal Register. any action by FDA, regardless of the section 513(a)(1) of the FD&C Act (21
[FR Doc. 2018–13359 Filed 6–21–18; 8:45 am] level of risk posed by the new device. U.S.C. 360c(a)(1)). Although the device
BILLING CODE 4191–02–P
Any device that was not in commercial was automatically within class III, the
distribution before May 28, 1976, is De Novo classification is considered to
automatically classified as, and remains be the initial classification of the device.
within, class III and requires premarket We believe this De Novo classification
DEPARTMENT OF HEALTH AND approval unless and until FDA takes an will enhance patients’ access to
HUMAN SERVICES action to classify or reclassify the device beneficial innovation, in part by
Food and Drug Administration (see 21 U.S.C. 360c(f)(1)). We refer to reducing regulatory burdens. When FDA
these devices as ‘‘postamendments classifies a device into class I or II via
21 CFR Part 866 devices’’ because they were not in the De Novo process, the device can
commercial distribution prior to the serve as a predicate for future devices of
[Docket No. FDA–2018–N–1929] date of enactment of the Medical Device that type, including for 510(k)s (see 21
Amendments of 1976, which amended U.S.C. 360c(f)(2)(B)(i)). As a result, other
Medical Devices; Immunology and the Federal Food, Drug, and Cosmetic device sponsors do not have to submit
Microbiology Devices; Classification of Act (FD&C Act). a De Novo request or PMA in order to
the Next Generation Sequencing FDA may take a variety of actions in market a substantially equivalent device
Based Tumor Profiling Test appropriate circumstances to classify or (see 21 U.S.C. 360c(i), defining
AGENCY: Food and Drug Administration, reclassify a device into class I or II. We ‘‘substantial equivalence’’). Instead,
HHS. may issue an order finding a new device sponsors can use the less-burdensome
to be substantially equivalent under 510(k) process, when necessary, to
ACTION: Final order. section 513(i) of the FD&C Act to a market their device.
SUMMARY: The Food and Drug predicate device that does not require
premarket approval (see 21 U.S.C. II. De Novo Classification
Administration (FDA or we) is
classifying the next generation 360c(i)). We determine whether a new On September 25, 2017, Memorial
sequencing based tumor profiling test device is substantially equivalent to a Sloan-Kettering Cancer Center
into class II (special controls). The predicate by means of the procedures Department of Pathology submitted a
special controls that apply to the device for premarket notification under section request for De Novo classification of the
type are identified in this order and will 510(k) of the FD&C Act and Part 807 (21 MSK–IMPACT (Integrated Mutation
be part of the codified language for the U.S.C. 360(k) & 21 CFR part 807, Profiling of Actionable Cancer Targets).
next generation sequencing based tumor respectively). FDA reviewed the request in order to
profiling test’s classification. We are FDA may also classify a device classify the device under the criteria for
through ‘‘De Novo’’ classification, a classification set forth in section
taking this action because we have
common name for the process 513(a)(1) of the FD&C Act.
determined that classifying the device
authorized under section 513(f)(2) of the We classify devices into class II if
into class II (special controls) will general controls by themselves are
FD&C Act (21 U.S.C. 360c(f)(2)). Section
provide a reasonable assurance of safety insufficient to provide reasonable
207 of the Food and Drug
and effectiveness of the device. We assurance of safety and effectiveness,
Administration Modernization Act of
believe this action will also enhance but there is sufficient information to
1997 established the first procedure for
patients’ access to beneficial innovative establish special controls that, in
De Novo classification (Pub. L. 105–
devices, in part by reducing regulatory combination with the general controls,
115). Section 607 of the Food and Drug
burdens. provide reasonable assurance of the
Administration Safety and Innovation
DATES: This order is effective June 22, Act modified the De Novo application safety and effectiveness of the device for
2018. The classification was applicable process by adding a second procedure its intended use (see 21 U.S.C.
on November 15, 2017. (Pub. L. 112–144). A device sponsor 360c(a)(1)(B)). After review of the
FOR FURTHER INFORMATION CONTACT: may utilize either procedure for De information submitted in the request,
Scott McFarland, Center for Devices and Novo classification. we determined that the device can be
Radiological Health, Food and Drug Under the first procedure, the person classified into class II with the
Administration, 10903 New Hampshire submits a 510(k) for a device that has establishment of special controls. FDA
Ave., Bldg. 66, Rm. 4676, Silver Spring, not previously been classified. After has determined that these special
MD, 20993–0002, 301–796–6217, receiving an order from FDA classifying controls, in addition to the general
Scott.McFarland@fda.hhs.gov. the device into class III under section controls, will provide reasonable
SUPPLEMENTARY INFORMATION: 513(f)(1) of the FD&C Act, the person assurance of the safety and effectiveness
then requests a classification under of the device.
I. Background section 513(f)(2). Therefore, on November 15, 2017,
Upon request, FDA has classified the Under the second procedure, rather FDA issued an order to the requester
next generation sequencing based tumor than first submitting a 510(k) and then classifying the device into class II. FDA
profiling test as class II (special a request for classification, if the person is codifying the classification of the
daltland on DSKBBV9HB2PROD with RULES
controls), which we have determined determines that there is no legally device by adding 21 CFR 866.6080. We
will provide a reasonable assurance of marketed device upon which to base a have named the generic type of device
safety and effectiveness. In addition, we determination of substantial next generation sequencing (NGS) based
believe this action will enhance equivalence, that person requests a tumor profiling test, and it is identified
patients’ access to beneficial innovation, classification under section 513(f)(2) of as a qualitative in vitro diagnostic test
in part by reducing regulatory burdens the FD&C Act. intended for NGS analysis of tissue
VerDate Sep<11>2014 16:09 Jun 21, 2018 Jkt 244001 PO 00000 Frm 00018 Fmt 4700 Sfmt 4700 E:\FR\FM\22JNR1.SGM 22JNR1](https://thefederalregister.org/doc/83_FR_29115/page/1.svg)
![28996 Federal Register / Vol. 83, No. 121 / Friday, June 22, 2018 / Rules and Regulations
or its elements in accordance with RNA) and/or a measurement (e.g., established test in the same intended
paragraphs (b)(1)(v) and (b)(2)(vi) of this incorporating a score or copy number) specimen type, appropriate description
section. and/or with an alternative technology of the level of evidence and/or the
(F) A description of internal and (e.g., IHC, RT-qPCR, FISH), evidence of differences between next generation
external controls that are recommended accuracy must include clinically sequencing results and results from the
or provided and control procedures. The adequate concordance between results medically established test (e.g., as
description must identify those control for the mutation and the medically described in professional guidelines).
elements that are incorporated into the established biomarker test (e.g., (iv) A listing of all somatic mutations
testing procedure. evidence generated from an that are intended to be detected by the
(iv) Information demonstrating appropriately sized method comparison device and that are reported in the test
analytical validity of the device study using clinical specimens from the results under the following two
according to analytical performance target population). categories or equivalent designations, as
characteristics, evaluated either (3) For qualitative DNA mutations not appropriate: ‘‘cancer mutations panel
specifically for each gene/mutation or, described in paragraph (b)(1)(iv)(G)(2) of with evidence of clinical significance’’
when clinically and practically justified, this section, accuracy studies must or ‘‘cancer mutations panel with
using a representative approach based include both mutation-positive and potential clinical significance.’’
on other mutations of the same type, wild-type results. (v) For mutations reported under the
including: (H) Adequate device stability category of ‘‘cancer mutations panel
(A) Data that adequately supports the information. with potential clinical significance,’’ a
intended specimen type (e.g., formalin- (v) Information that adequately limiting statement that states ‘‘For the
fixed, paraffin-embedded tumor tissue), supports the clinical significance of the mutations listed in [cancer mutations
specimen handling protocol, and panel must include: panel with potential clinical
nucleic acid purification for specific (A) Criteria established on what types significance or equivalent designation],
tumor types or for a pan-tumor claim. and levels of evidence will clinically the clinical significance has not been
(B) A summary of the empirical validate a mutation as a cancer mutation demonstrated [with adequate clinical
evidence obtained to demonstrate how with evidence of clinical significance evidence (e.g., by professional
the analytical quality metrics and versus a cancer mutation with potential guidelines) in accordance with
thresholds were optimized. clinical significance. paragraph (b)(1)(v) of this section] or
(C) Device precision data using (B) For representative mutations of with this test.’’
clinical samples to adequately evaluate those designated as cancer mutations (vi) For mutations under the category
intra-run, inter-run, and total variability. with evidence of clinical significance, a of ‘‘cancer mutations panel with
The samples must cover all mutation description of the clinical evidence evidence of clinical significance,’’ or
types tested (both positive and negative associated with such mutations, such as equivalent designation, link(s) for
samples) and include samples near the clinical evidence presented in physicians to access internal or external
limit of detection of the device. professional guidelines, as appropriate, information concerning decision rules
Precision must be assessed by with method comparison performance or conclusions about the level of
agreement within replicates on the assay data as described in paragraph evidence for clinical significance that is
final result for each representative (b)(1)(iv)(G) of this section. associated with the marker in
mutation, as applicable, and also (C) For all other mutations designated accordance with paragraph (b)(1)(v) of
supported by sequencing quality metrics as cancer mutations with potential this section.
for targeted regions across the panel. clinical significance, a description of the
(D) Description of the protocols and/ rationale for reporting. Dated: June 18, 2018.
or data adequately demonstrating the (2) The 21 CFR 809.10 compliant Leslie Kux,
interchangeability of reagent lots and labeling and any product information Associate Commissioner for Policy.
multiplexing barcodes. and test report generated, must include [FR Doc. 2018–13406 Filed 6–21–18; 8:45 am]
(E) A description of the nucleic acid the following, as applicable: BILLING CODE 4164–01–P
assay input concentration range and the (i) The intended use statement must
evidence to adequately support the specify the following:
range. (A) The test is indicated for DEPARTMENT OF THE INTERIOR
(F) A description of the data previously diagnosed cancer patients.
adequately supporting the limit of (B) The intended specimen type(s) Office of Surface Mining Reclamation
detection of the device. and matrix (e.g., formalin-fixed, and Enforcement
(G) A description of the data to paraffin-embedded tumor tissue).
adequately support device accuracy (C) The mutation types (e.g., single 30 CFR Part 901
using clinical specimens representing nucleotide variant, insertion, deletion,
the intended specimen type and range copy number variation or gene [SATS No. AL–080–FOR; Docket ID: OSM–
of tumor types, as applicable. rearrangement) for which validation 2016–0011; S1D1S SS08011000 SX064A000
(1) Clinical specimens tested to data has been provided. 189S180110; S2D2S SS08011000
support device accuracy must SX064A000 18XS501520]
(D) The name of the testing facility or
adequately represent the list of cancer facilities, as applicable. Alabama Abandoned Mine Land
mutations with evidence of clinical (ii) A description of the device and Reclamation Plan
significance to be detected by the summary of the results of the
daltland on DSKBBV9HB2PROD with RULES
device. performance studies performed in AGENCY: Office of Surface Mining
(2) For mutations that are designated accordance with paragraphs (b)(1)(iii), Reclamation and Enforcement, Interior.
as cancer mutations with evidence of (b)(1)(iv), and (b)(1)(v) of this section. ACTION: Final rule; approval of
clinical significance and that are based (iii) A description of applicable test amendment.
on evidence established in the intended limitations, including, for device
specimen type (e.g., tumor tissues) but specific mutations validated with SUMMARY: We, the Office of Surface
for a different analyte type (e.g., protein, method comparison data to a medically Mining Reclamation and Enforcement
VerDate Sep<11>2014 16:09 Jun 21, 2018 Jkt 244001 PO 00000 Frm 00020 Fmt 4700 Sfmt 4700 E:\FR\FM\22JNR1.SGM 22JNR1](https://thefederalregister.org/doc/83_FR_29115/page/3.svg)
Document Created: 2018-11-06 09:50:40
Document Modified: 2018-11-06 09:50:40
| 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 June 22, 2018. The classification was applicable on November 15, 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- 796-6217, [email protected] | |
| FR Citation | 83 FR 28994 | |
| CFR Associated | Biologics; Laboratories and Medical Devices |
2025 Federal Register | Disclaimer | Privacy Policy
USC | CFR | eCFR