Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the High Throughput Genomic Sequence Analyzer for Clinical Use, 13551-13553 [2017-04941]
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Federal Register / Vol. 82, No. 48 / Tuesday, March 14, 2017 / Rules and Regulations
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. FDA–2017–N–1142]
Medical Devices; Clinical Chemistry
and Clinical Toxicology Devices;
Classification of the High Throughput
Genomic Sequence Analyzer for
Clinical Use
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Final order.
The Food and Drug
Administration (FDA) is classifying the
high throughput genomic sequence
analyzer for clinical use into class II
(special controls). The special controls
that will apply to the device are
identified in this order and will be part
of the codified language for the
classification of the high throughput
genomic sequence analyzer for clinical
use device. The Agency is classifying
the device into class II (special controls)
in order to provide a reasonable
assurance of safety and effectiveness of
the device.
DATES: This order is effective March 14,
2017. The classification was applicable
on November 19, 2013.
FOR FURTHER INFORMATION CONTACT:
Steven Tjoe, Center for Devices and
Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4550, Silver Spring,
MD, 20993–0002, 301–796–5866,
steven.tjoe@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
rmajette on DSK30RV082PROD with RULES
SUMMARY:
I. Background
In accordance with section 513(f)(1) of
the Federal Food, Drug, and Cosmetic
Act (the FD&C Act) (21 U.S.C.
360c(f)(1)), devices that were not in
commercial distribution before May 28,
1976 (the date of enactment of the
Medical Device Amendments of 1976),
generally referred to as postamendments
devices, are classified automatically by
statute into class III without any FDA
rulemaking process. These devices
remain in class III and require
premarket approval unless and until the
device is classified or reclassified into
class I or II, or FDA issues an order
finding the device to be substantially
equivalent, in accordance with section
513(i) of the FD&C Act, to a predicate
device that does not require premarket
approval. The Agency determines
whether new devices are substantially
equivalent to predicate devices by
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means of premarket notification
procedures in section 510(k) of the
FD&C Act (21 U.S.C. 360(k)) and part
807 (21 CFR part 807) of the regulations.
Section 513(f)(2) of the FD&C Act,
also known as De Novo classification, as
amended by section 607 of the Food and
Drug Administration Safety and
Innovation Act (Pub. L. 112–144),
provides two procedures by which a
person may request FDA to classify a
device under the criteria set forth in
section 513(a)(1) of the FD&C Act.
Under the first procedure, the person
submits a premarket notification under
section 510(k) of the FD&C Act for a
device that has not previously been
classified and, within 30 days of
receiving an order classifying the device
into class III under section 513(f)(1) of
the FD&C Act, the person requests a
classification under section 513(f)(2).
Under the second procedure, rather than
first submitting a premarket notification
under section 510(k) of the FD&C Act
and then a request for classification
under the first procedure, the person
determines that there is no legally
marketed device upon which to base a
determination of substantial
equivalence and requests a classification
under section 513(f)(2) of the FD&C Act.
If the person submits a request to
classify the device under this second
procedure, FDA may decline to
undertake the classification request if
FDA identifies a legally marketed device
that could provide a reasonable basis for
review of substantial equivalence with
the device or if FDA determines that the
device submitted is not of ‘‘lowmoderate risk’’ or that general controls
would be inadequate to control the risks
and special controls to mitigate the risks
cannot be developed.
In response to a request to classify a
device under either procedure provided
by section 513(f)(2) of the FD&C Act,
FDA shall classify the device by written
order within 120 days. This
classification will be the initial
classification of the device. In
accordance with section 513(f)(1) of the
FD&C Act, FDA issued an order on
September 13, 2013, classifying the
Illumina MiSeqDx Platform into class
III, because it was not substantially
equivalent to a device that was
introduced or delivered for introduction
into interstate commerce for commercial
distribution before May 28, 1976, or a
device which was subsequently
reclassified into class I or class II.
On September 23, 2013, FDA received
from Illumina, Inc., a request for
classification of the Illumina MiSeqDx
Platform submitted under section
513(f)(2) of the FD&C Act. In accordance
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Sfmt 4700
13551
with section 513(f)(2) of the FD&C Act,
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. FDA
classifies 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 to provide reasonable
assurance of the safety and effectiveness
of the device for its intended use. After
review of the information submitted in
the request, FDA determined that the
device can be classified into class II
with the establishment of special
controls. FDA believes these special
controls, in addition to general controls,
will provide reasonable assurance of the
safety and effectiveness of the device.
Therefore, on November 19, 2013,
FDA issued an order to the requestor
classifying the device into class II. FDA
is codifying the classification of the
device by adding 21 CFR 862.2265.
Following the effective date of this
final classification order, any firm
intending to market a high throughput
genomic sequence analyzer for clinical
use will need to comply with the special
controls named in this final order. A De
Novo classification decreases regulatory
burdens. When FDA classifies a device
type as class I or II via the De Novo
pathway, other manufacturers do not
have to submit a De Novo request or
PMA in order to market the same type
of device, unless the device has a new
intended use or technological
characteristics that raise different
questions of safety or effectiveness.
Instead, manufacturers can use the less
burdensome pathway of 510(k), when
necessary, to market their device, and
the device that was the subject of the
original De Novo classification can serve
as a predicate device for additional
510(k)s from other manufacturers.
The device is assigned the generic
name high throughput genomic
sequence analyzer for clinical use, and
it is identified as an analytical
instrument system intended to generate,
measure and sort signals in order to
analyze nucleic acid sequences in a
clinical sample. The device may include
a signal reader unit; reagent handling,
dedicated instrument control, and other
hardware components; raw data storage
mechanisms; data acquisition software;
and software to process detected signals.
FDA has identified the following risks
to health associated specifically with
this type of device and the measures
required to mitigate these risks:
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Federal Register / Vol. 82, No. 48 / Tuesday, March 14, 2017 / Rules and Regulations
TABLE 1—HIGH THROUGHPUT GENOMIC SEQUENCE ANALYZER FOR CLINICAL USE RISKS AND MITIGATION MEASURES
Identified risks to health
Required mitigations
Inaccurate test results due to unavailability of necessary components of the instrument system
Inaccurate results due to unknown performance of the instrument system ...................................
rmajette on DSK30RV082PROD with RULES
FDA believes that the special controls,
in combination with the general
controls, address these risks to health
and provide reasonable assurance of the
safety and effectiveness. The special
controls for a high throughput genomic
sequence analyzer for clinical use
include a detailed outline of analytical
performance information that must be
generated for the instrument system
(i.e., platform and all associated
software). This includes analytical
validation using well characterized
samples (i.e., well characterized or
reference materials) to demonstrate the
system’s capabilities and to identify
limitations.
The validation testing, as required by
the special controls, only establishes the
instrument’s general capabilities and
does not establish the instrument’s
capabilities or suitability with respect to
any specific claims. Instruments
indicated for a specific diagnostic test,
including those that make claims for a
specific test, (e.g., hematology panel;
oncology panel) require additional
independent validation and are not high
throughput genomic sequence analyzers
for clinical use under 21 CFR 862.2265.
Section 510(m) of the FD&C Act
provides that FDA may exempt a class
II device from the premarket notification
requirements under section 510(k), if
FDA determines that premarket
notification is not necessary to provide
reasonable assurance of the safety and
effectiveness of the device. For this type
of device, FDA believes premarket
notification is not necessary to provide
reasonable assurance of the safety and
effectiveness of the device type and,
therefore, is planning to exempt the
device from the premarket notification
requirements under section 510(m) of
the FD&C Act. Once finalized, persons
who intend to market this device type
need not submit a 510(k) premarket
notification containing information on
the high throughput genomic sequence
analyzer for clinical use prior to
marketing the device.
II. Analysis of Environmental Impact
We have 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
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environmental impact statement is
required.
III. Paperwork Reduction Act of 1995
This final order establishes special
controls that refer to previously
approved collections of information
found in other FDA regulations. 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
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 862
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 862 is
amended as follows:
PART 862—CLINICAL CHEMISTRY
AND CLINICAL TOXICOLOGY
DEVICES
1. The authority citation for part 862
is revised to read as follows:
■
Authority: 21 U.S.C. 351, 360, 360c, 360e,
360j, 360l, 371.
2. Add § 862.2265 to subpart C to read
as follows:
■
§ 862.2265 High throughput genomic
sequence analyzer for clinical use.
(a) Identification. A high throughput
genomic sequence analyzer for clinical
use is an analytical instrument system
intended to generate, measure and sort
signals in order to analyze nucleic acid
sequences in a clinical sample. The
device may include a signal reader unit;
reagent handling, dedicated instrument
control, and other hardware
components; raw data storage
mechanisms; data acquisition software;
and software to process detected signals.
(b) Classification. Class II (special
controls). The special controls for this
device are:
(1) The labeling for the instrument
system must reference legally marketed
pre-analytical and analytical reagents to
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Fmt 4700
Sfmt 4700
Special Control (1) (21 CFR 862.2265(b)(1)).
Special Control (2) (21 CFR 862.2265(b)(2)).
be used with the instrument system and
include or reference legally marketed
analytical software that includes
sequence alignment and variant calling
functions, to be used with the
instrument system.
(2) The labeling for the instrument
system must include a description of the
following information:
(i) The specimen type(s) validated as
an appropriate source of nucleic acid for
this instrument.
(ii) The type(s) of nucleic acids (e.g.,
germline DNA, tumor DNA) validated
with this instrument.
(iii) The type(s) of sequence variations
(e.g. single nucleotide variants,
insertions, deletions) validated with this
instrument.
(iv) The type(s) of sequencing (e.g.,
targeted sequencing) validated with this
instrument.
(v) The appropriate read depth for the
sensitivity claimed and validation
information supporting those claims.
(vi) The nucleic acid extraction
method(s) validated for use with the
instrument system.
(vii) Limitations must specify the
types of sequence variations that the
instrument cannot detect with the
claimed accuracy and precision (e.g.,
insertions or deletions larger than a
certain size, translocations).
(viii) Performance characteristics of
the instrument system must include:
(A) Reproducibility data generated
using multiple instruments and
multiple operators, and at multiple
sites. Samples tested must include all
claimed specimen types, nucleic acid
types, sequence variation types, and
types of sequencing. Variants queried
shall be located in varying sequence
context (e.g., different chromosomes,
GC-rich regions). Device results shall be
compared to reference sequence data
with high confidence.
(B) Accuracy data for all claimed
specimen types and nucleic acid types
generated by testing a panel of well
characterized samples to query all
claimed sequence variation types, types
of sequencing, and sequences located in
varying sequence context (e.g., different
chromosomes, GC-rich regions). The
well-characterized sample panel shall
include samples from at least two
sources that have highly confident
sequence based on well-validated
sequencing methods. At least one
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Federal Register / Vol. 82, No. 48 / Tuesday, March 14, 2017 / Rules and Regulations
reference source shall have sequence
generated independently of the
manufacturer with respect to technology
and analysis. Percent agreement and
percent disagreement with the reference
sequences must be described for all
regions queried by the instrument.
(C) If applicable, data describing
endogenous or exogenous substances
that may interfere with the instrument
system.
(D) If applicable, data demonstrating
the ability of the system to consistently
generate an accurate result for a given
sample across different indexing primer
combinations.
(ix) The upper and lower limit of
input nucleic acid that will achieve the
claimed accuracy and reproducibility.
Data supporting such claims must also
be summarized.
Dated: March 8, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017–04941 Filed 3–13–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 882
[Docket No. FDA–2017–N–1123]
Medical Devices; Neurological
Devices, Classification of the Vibratory
Counter-Stimulation Device
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Final order.
The Food and Drug
Administration (FDA) is classifying the
vibratory counter-stimulation device
into class II (special controls). The
special controls that will apply to the
device are identified in this order and
will be part of the codified language for
the vibratory counter-stimulation
device’s classification. The Agency is
classifying the device into class II
(special controls) in order to provide a
reasonable assurance of safety and
effectiveness of the device.
DATES: This order is effective March 14,
2017. The classification was applicable
on December 18, 2013.
FOR FURTHER INFORMATION CONTACT:
Michael Hoffmann, Center for Devices
and Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 2640, Silver Spring,
MD 20993–0002, 301–796–6476,
michael.hoffmann@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
rmajette on DSK30RV082PROD with RULES
SUMMARY:
VerDate Sep<11>2014
15:10 Mar 13, 2017
Jkt 241001
I. Background
In accordance with section 513(f)(1) of
the Federal Food, Drug, and Cosmetic
Act (the FD&C Act) (21 U.S.C.
360c(f)(1)), devices that were not in
commercial distribution before May 28,
1976 (the date of enactment of the
Medical Device Amendments of 1976),
generally referred to as postamendments
devices, are classified automatically by
statute into class III without any FDA
rulemaking process. These devices
remain in class III and require
premarket approval unless and until the
device is classified or reclassified into
class I or II, or FDA issues an order
finding the device to be substantially
equivalent, in accordance with section
513(i) of the FD&C Act, to a predicate
device that does not require premarket
approval. The Agency determines
whether new devices are substantially
equivalent to predicate devices by
means of premarket notification
procedures in section 510(k) of the
FD&C Act (21 U.S.C. 360(k)) and part
807 (21 CFR part 807) of the regulations.
Section 513(f)(2) of the FD&C Act,
also known as De Novo classification, as
amended by section 607 of the Food and
Drug Administration Safety and
Innovation Act (Pub. L. 112–144),
provides two procedures by which a
person may request FDA to classify a
device under the criteria set forth in
section 513(a)(1). Under the first
procedure, the person submits a
premarket notification under section
510(k) of the FD&C Act for a device that
has not previously been classified and,
within 30 days of receiving an order
classifying the device into class III
under section 513(f)(1) of the FD&C Act,
the person requests a classification
under section 513(f)(2). Under the
second procedure, rather than first
submitting a premarket notification
under section 510(k) of the FD&C Act
and then a request for classification
under the first procedure, the person
determines that there is no legally
marketed device upon which to base a
determination of substantial
equivalence and requests a classification
under section 513(f)(2) of the FD&C Act.
If the person submits a request to
classify the device under this second
procedure, FDA may decline to
undertake the classification request if
FDA identifies a legally marketed device
that could provide a reasonable basis for
review of substantial equivalence with
the device or if FDA determines that the
device submitted is not of ‘‘lowmoderate risk’’ or that general controls
would be inadequate to control the risks
and special controls to mitigate the risks
cannot be developed.
PO 00000
Frm 00005
Fmt 4700
Sfmt 4700
13553
In response to a request to classify a
device under either procedure provided
by section 513(f)(2) of the FD&C Act,
FDA shall classify the device by written
order within 120 days. This
classification will be the initial
classification of the device. In
accordance with section 513(f)(1) of the
FD&C Act, FDA issued an order on June
14, 2011, classifying the Symphony
Device into class III, because it was not
substantially equivalent to a device that
was introduced or delivered for
introduction into interstate commerce
for commercial distribution before May
28, 1976, or a device which was
subsequently reclassified into class I or
class II.
On July 13, 2011, Sensory Medical,
Inc. submitted a request for
classification of the Symphony Device
under section 513(f)(2) of the FD&C Act.
In accordance with section 513(f)(2) of
the FD&C Act, FDA reviewed the
request in order to classify the device
under the criteria for classification set
forth in section 513(a)(1). FDA classifies
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
to provide reasonable assurance of the
safety and effectiveness of the device for
its intended use. After review of the
information submitted in the request,
FDA determined that the device can be
classified into class II with the
establishment of special controls. FDA
believes these special controls, in
addition to general controls, will
provide reasonable assurance of the
safety and effectiveness of the device.
Therefore, on December 18, 2013,
FDA issued an order to the requestor
classifying the device into class II. FDA
is codifying the classification of the
device by adding 21 CFR 882.5895.
Following the effective date of this
final classification order, any firm
submitting a premarket notification
(510(k)) for a vibratory counterstimulation device will need to comply
with the special controls named in this
final order. A De Novo classification
decreases regulatory burdens. When
FDA classifies a device type as class I
or II via the De Novo pathway, other
manufacturers do not have to submit a
De Novo request or PMA in order to
market the same type of device, unless
the device has a new intended use or
technological characteristics that raise
different questions of safety or
effectiveness. Instead, manufacturers
can use the less burdensome pathway of
510(k), when necessary, to market their
device, and the device that was the
subject of the original De Novo
E:\FR\FM\14MRR1.SGM
14MRR1
Agencies
[Federal Register Volume 82, Number 48 (Tuesday, March 14, 2017)]
[Rules and Regulations]
[Pages 13551-13553]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-04941]
[[Page 13551]]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 862
[Docket No. FDA-2017-N-1142]
Medical Devices; Clinical Chemistry and Clinical Toxicology
Devices; Classification of the High Throughput Genomic Sequence
Analyzer for Clinical Use
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is classifying the high
throughput genomic sequence analyzer for clinical use into class II
(special controls). The special controls that will apply to the device
are identified in this order and will be part of the codified language
for the classification of the high throughput genomic sequence analyzer
for clinical use device. The Agency is classifying the device into
class II (special controls) in order to provide a reasonable assurance
of safety and effectiveness of the device.
DATES: This order is effective March 14, 2017. The classification was
applicable on November 19, 2013.
FOR FURTHER INFORMATION CONTACT: Steven Tjoe, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4550, Silver Spring, MD, 20993-0002, 301-796-5866,
steven.tjoe@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
In accordance with section 513(f)(1) of the Federal Food, Drug, and
Cosmetic Act (the FD&C Act) (21 U.S.C. 360c(f)(1)), devices that were
not in commercial distribution before May 28, 1976 (the date of
enactment of the Medical Device Amendments of 1976), generally referred
to as postamendments devices, are classified automatically by statute
into class III without any FDA rulemaking process. These devices remain
in class III and require premarket approval unless and until the device
is classified or reclassified into class I or II, or FDA issues an
order finding the device to be substantially equivalent, in accordance
with section 513(i) of the FD&C Act, to a predicate device that does
not require premarket approval. The Agency determines whether new
devices are substantially equivalent to predicate devices by means of
premarket notification procedures in section 510(k) of the FD&C Act (21
U.S.C. 360(k)) and part 807 (21 CFR part 807) of the regulations.
Section 513(f)(2) of the FD&C Act, also known as De Novo
classification, as amended by section 607 of the Food and Drug
Administration Safety and Innovation Act (Pub. L. 112-144), provides
two procedures by which a person may request FDA to classify a device
under the criteria set forth in section 513(a)(1) of the FD&C Act.
Under the first procedure, the person submits a premarket notification
under section 510(k) of the FD&C Act for a device that has not
previously been classified and, within 30 days of receiving an order
classifying the device into class III under section 513(f)(1) of the
FD&C Act, the person requests a classification under section 513(f)(2).
Under the second procedure, rather than first submitting a premarket
notification under section 510(k) of the FD&C Act and then a request
for classification under the first procedure, the person determines
that there is no legally marketed device upon which to base a
determination of substantial equivalence and requests a classification
under section 513(f)(2) of the FD&C Act. If the person submits a
request to classify the device under this second procedure, FDA may
decline to undertake the classification request if FDA identifies a
legally marketed device that could provide a reasonable basis for
review of substantial equivalence with the device or if FDA determines
that the device submitted is not of ``low-moderate risk'' or that
general controls would be inadequate to control the risks and special
controls to mitigate the risks cannot be developed.
In response to a request to classify a device under either
procedure provided by section 513(f)(2) of the FD&C Act, FDA shall
classify the device by written order within 120 days. This
classification will be the initial classification of the device. In
accordance with section 513(f)(1) of the FD&C Act, FDA issued an order
on September 13, 2013, classifying the Illumina MiSeqDx Platform into
class III, because it was not substantially equivalent to a device that
was introduced or delivered for introduction into interstate commerce
for commercial distribution before May 28, 1976, or a device which was
subsequently reclassified into class I or class II.
On September 23, 2013, FDA received from Illumina, Inc., a request
for classification of the Illumina MiSeqDx Platform submitted under
section 513(f)(2) of the FD&C Act. In accordance with section 513(f)(2)
of the FD&C Act, 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. FDA classifies 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 to provide reasonable
assurance of the safety and effectiveness of the device for its
intended use. After review of the information submitted in the request,
FDA determined that the device can be classified into class II with the
establishment of special controls. FDA believes these special controls,
in addition to general controls, will provide reasonable assurance of
the safety and effectiveness of the device.
Therefore, on November 19, 2013, FDA issued an order to the
requestor classifying the device into class II. FDA is codifying the
classification of the device by adding 21 CFR 862.2265.
Following the effective date of this final classification order,
any firm intending to market a high throughput genomic sequence
analyzer for clinical use will need to comply with the special controls
named in this final order. A De Novo classification decreases
regulatory burdens. When FDA classifies a device type as class I or II
via the De Novo pathway, other manufacturers do not have to submit a De
Novo request or PMA in order to market the same type of device, unless
the device has a new intended use or technological characteristics that
raise different questions of safety or effectiveness. Instead,
manufacturers can use the less burdensome pathway of 510(k), when
necessary, to market their device, and the device that was the subject
of the original De Novo classification can serve as a predicate device
for additional 510(k)s from other manufacturers.
The device is assigned the generic name high throughput genomic
sequence analyzer for clinical use, and it is identified as an
analytical instrument system intended to generate, measure and sort
signals in order to analyze nucleic acid sequences in a clinical
sample. The device may include a signal reader unit; reagent handling,
dedicated instrument control, and other hardware components; raw data
storage mechanisms; data acquisition software; and software to process
detected signals.
FDA has identified the following risks to health associated
specifically with this type of device and the measures required to
mitigate these risks:
[[Page 13552]]
Table 1--High Throughput Genomic Sequence Analyzer for Clinical Use
Risks and Mitigation Measures
------------------------------------------------------------------------
Identified risks to health Required mitigations
------------------------------------------------------------------------
Inaccurate test results due to Special Control (1) (21 CFR
unavailability of necessary components of 862.2265(b)(1)).
the instrument system.
Inaccurate results due to unknown Special Control (2) (21 CFR
performance of the instrument system. 862.2265(b)(2)).
------------------------------------------------------------------------
FDA believes that the special controls, in combination with the
general controls, address these risks to health and provide reasonable
assurance of the safety and effectiveness. The special controls for a
high throughput genomic sequence analyzer for clinical use include a
detailed outline of analytical performance information that must be
generated for the instrument system (i.e., platform and all associated
software). This includes analytical validation using well characterized
samples (i.e., well characterized or reference materials) to
demonstrate the system's capabilities and to identify limitations.
The validation testing, as required by the special controls, only
establishes the instrument's general capabilities and does not
establish the instrument's capabilities or suitability with respect to
any specific claims. Instruments indicated for a specific diagnostic
test, including those that make claims for a specific test, (e.g.,
hematology panel; oncology panel) require additional independent
validation and are not high throughput genomic sequence analyzers for
clinical use under 21 CFR 862.2265.
Section 510(m) of the FD&C Act provides that FDA may exempt a class
II device from the premarket notification requirements under section
510(k), if FDA determines that premarket notification is not necessary
to provide reasonable assurance of the safety and effectiveness of the
device. For this type of device, FDA believes premarket notification is
not necessary to provide reasonable assurance of the safety and
effectiveness of the device type and, therefore, is planning to exempt
the device from the premarket notification requirements under section
510(m) of the FD&C Act. Once finalized, persons who intend to market
this device type need not submit a 510(k) premarket notification
containing information on the high throughput genomic sequence analyzer
for clinical use prior to marketing the device.
II. Analysis of Environmental Impact
We have 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.
III. Paperwork Reduction Act of 1995
This final order establishes special controls that refer to
previously approved collections of information found in other FDA
regulations. 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
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 862
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
862 is amended as follows:
PART 862--CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES
0
1. The authority citation for part 862 is revised to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 862.2265 to subpart C to read as follows:
Sec. 862.2265 High throughput genomic sequence analyzer for clinical
use.
(a) Identification. A high throughput genomic sequence analyzer for
clinical use is an analytical instrument system intended to generate,
measure and sort signals in order to analyze nucleic acid sequences in
a clinical sample. The device may include a signal reader unit; reagent
handling, dedicated instrument control, and other hardware components;
raw data storage mechanisms; data acquisition software; and software to
process detected signals.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) The labeling for the instrument system must reference legally
marketed pre-analytical and analytical reagents to be used with the
instrument system and include or reference legally marketed analytical
software that includes sequence alignment and variant calling
functions, to be used with the instrument system.
(2) The labeling for the instrument system must include a
description of the following information:
(i) The specimen type(s) validated as an appropriate source of
nucleic acid for this instrument.
(ii) The type(s) of nucleic acids (e.g., germline DNA, tumor DNA)
validated with this instrument.
(iii) The type(s) of sequence variations (e.g. single nucleotide
variants, insertions, deletions) validated with this instrument.
(iv) The type(s) of sequencing (e.g., targeted sequencing)
validated with this instrument.
(v) The appropriate read depth for the sensitivity claimed and
validation information supporting those claims.
(vi) The nucleic acid extraction method(s) validated for use with
the instrument system.
(vii) Limitations must specify the types of sequence variations
that the instrument cannot detect with the claimed accuracy and
precision (e.g., insertions or deletions larger than a certain size,
translocations).
(viii) Performance characteristics of the instrument system must
include:
(A) Reproducibility data generated using multiple instruments and
multiple operators, and at multiple sites. Samples tested must include
all claimed specimen types, nucleic acid types, sequence variation
types, and types of sequencing. Variants queried shall be located in
varying sequence context (e.g., different chromosomes, GC-rich
regions). Device results shall be compared to reference sequence data
with high confidence.
(B) Accuracy data for all claimed specimen types and nucleic acid
types generated by testing a panel of well characterized samples to
query all claimed sequence variation types, types of sequencing, and
sequences located in varying sequence context (e.g., different
chromosomes, GC-rich regions). The well-characterized sample panel
shall include samples from at least two sources that have highly
confident sequence based on well-validated sequencing methods. At least
one
[[Page 13553]]
reference source shall have sequence generated independently of the
manufacturer with respect to technology and analysis. Percent agreement
and percent disagreement with the reference sequences must be described
for all regions queried by the instrument.
(C) If applicable, data describing endogenous or exogenous
substances that may interfere with the instrument system.
(D) If applicable, data demonstrating the ability of the system to
consistently generate an accurate result for a given sample across
different indexing primer combinations.
(ix) The upper and lower limit of input nucleic acid that will
achieve the claimed accuracy and reproducibility. Data supporting such
claims must also be summarized.
Dated: March 8, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-04941 Filed 3-13-17; 8:45 am]
BILLING CODE 4164-01-P