Medical Devices; Hematology and Pathology Devices; Classification of the Flow Cytometric Test System for Hematopoietic Neoplasms, 61163-61166 [2017-27855]
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Federal Register / Vol. 82, No. 247 / Wednesday, December 27, 2017 / Rules and Regulations
Therefore, on November 19, 2013,
FDA issued an order to the requestor
classifying the device into class I. FDA
is codifying the classification of the
device by adding 21 CFR 862.3800. We
have named the generic type of device
reagents for molecular diagnostic
instrument test systems, and it is
identified as reagents other than analyte
specific reagents used as part of
molecular diagnostic test systems, such
as polymerases, nucleotides and
nucleotide mixes, master mixes in
which individual reagents are optimized
61163
to be used together, and labeled nucleic
acid molecules.
FDA has identified the following risks
to health associated specifically with
this type of device in table 1.
TABLE 1—REAGENTS FOR MOLECULAR DIAGNOSTIC INSTRUMENT TEST SYSTEMS RISKS AND MITIGATION MEASURES
Identified risks
Mitigation measures
Inaccurate test results due to inconsistently manufactured test system
reagents.
General controls, including current good manufacturing practices.
the collections of information in 21 CFR
part 820, regarding current good
manufacturing practices, have been
approved under OMB control number
0910–0073.
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.
daltland on DSKBBV9HB2PROD with RULES
Section 510(l)(1) of the FD&C Act
provides that a device within a type that
has been classified into class I under
section 513 of the FD&C Act is exempt
from premarket notification under
section 510(k), unless the device is of
substantial importance in preventing
impairment of human health or presents
a potentially unreasonable risk of illness
or injury (21 U.S.C. 360(l)(1)). Devices
within this type are exempt from the
premarket notification requirements
under section 510(k), subject to the
limitations of exemptions in 21 CFR
862.9.
PART 862—CLINICAL CHEMISTRY
AND CLINICAL TOXICOLOGY
DEVICES
IV. Paperwork Reduction Act of 1995
This final order refers 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
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 21 CFR parts 801 and
809, regarding labeling, have been
approved under OMB control number
0910–0485; the collections of
information in 21 CFR 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
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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:
1. The authority citation for part 862
continues to read as follows:
■
Authority: 21 U.S.C. 351, 360, 360c, 360e,
360j, 360l, 371.
2. Add § 862.3800 to subpart D to read
as follows:
■
§ 862.3800 Reagents for molecular
diagnostic instrument test systems.
(a) Identification. Reagents for
molecular diagnostic test systems are
reagents other than analyte specific
reagents used as part of molecular
diagnostic test systems, such as
polymerases, nucleotides and
nucleotide mixes, master mixes in
which individual reagents are optimized
to be used together, and labeled nucleic
acid molecules.
(b) Classification. Class I (general
controls). The device is exempt from the
premarket notification procedure in
subpart E of part 807 of this chapter,
subject to the limitations in § 862.9.
Dated: December 20, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017–27853 Filed 12–26–17; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 864
[Docket No. FDA–2017–N–6643]
Medical Devices; Hematology and
Pathology Devices; Classification of
the Flow Cytometric Test System for
Hematopoietic Neoplasms
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Final order.
The Food and Drug
Administration (FDA or we) is
classifying the flow cytometric test
system for hematopoietic neoplasms
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
flow cytometric test system for
hematopoietic neoplasms’ 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 December
27, 2017. The classification was
applicable on June 29, 2017.
FOR FURTHER INFORMATION CONTACT:
Ryan Lubert, Center for Devices and
Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4545, Silver Spring,
MD 20993–0002, 240–402–6357,
ryan.lubert@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
SUMMARY:
I. Background
Upon request, FDA has classified the
flow cytometric test system for
hematopoietic neoplasms as class II
(special controls), which we have
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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 (21
U.S.C. 360c(i)) to a predicate device that
does not require premarket approval.
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 shall 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 placed 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 October 3, 2016, Beckman Coulter
submitted a request for De Novo
classification of the ClearLLab Reagents
(T1, T2, B1, B2, M). 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 June 29, 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 864.7010. We
have named the generic type of device
flow cytometric test system for
hematopoietic neoplasms, and it is
identified as a device that consists of
reagents for immunophenotyping of
human cells in relation to the level of
expression, antigen density, and
distribution of specific cellular markers.
These reagents are used as an aid in the
differential diagnosis or monitoring of
hematologically abnormal patients
having or suspected of having
hematopoietic neoplasms. The results
should be interpreted by a pathologist or
equivalent professional in conjunction
with other clinical and laboratory
findings.
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—FLOW CYTOMETRIC TEST FOR HEMATOPOIETIC NEOPLASMS RISKS AND MITIGATION MEASURES
Identified risks
Mitigation measures/21 CFR section
Incorrect test results (false negatives or false positives) .........................
General Controls and Special Controls (1) and (2) (21 CFR
864.7010(b)(1) and (2)).
General Controls and Special Controls (1), (2), and (3) (21 CFR
864.7010(b)(1), (2), and (3)).
General Controls and Special Control (1) (21 CFR 864.7010(b)(1)).
Incorrect interpretation of device results by the end user .......................
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Patient harm from specimen(s) collection ................................................
FDA has determined that special
controls, in combination with the
general controls, address these risks to
health and provide reasonable assurance
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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
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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
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premarket notification requirements
under section 510(k) of the FD&C Act.
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. 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 21 CFR 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; the
collections of information in 21 CFR
part 820 have been approved under
OMB control number 0910–0073; 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
1. The authority citation for part 864
is revised to read as follows:
■
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Authority: 21 U.S.C. 351, 360, 360c, 360e,
360j, 360l, 371.
2. Add § 864.7010 to subpart H to read
as follows:
■
§ 864.7010 Flow cytometric test system for
hematopoietic neoplasms.
(a) Identification. A flow cytometric
test for hematopoietic neoplasms is a
device that consists of reagents for
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immunophenotyping of human cells in
relation to the level of expression,
antigen density, and distribution of
specific cellular markers. These reagents
are used as an aid in the differential
diagnosis or monitoring of
hematologically abnormal patients
having or suspected of having
hematopoietic neoplasms. The results
should be interpreted by a pathologist or
equivalent professional in conjunction
with other clinical and laboratory
findings.
(b) Classification. Class II (special
controls). The special controls for this
device are:
(1) Premarket notification
submissions must include the following
information:
(i) The indications for use must
indicate the clinical hematopoietic
neoplasms for which the assay was
designed and validated, for example,
chronic leukemia or lymphoma.
(ii) A detailed device description
including the following:
(A) A detailed description of all test
components, all required reagents, and
all instrumentation and equipment,
including illustrations or photographs of
nonstandard equipment or methods.
(B) Detailed documentation of the
device software including, but not
limited to, standalone software
applications and hardware-based
devices that incorporate software.
(C) A detailed description of
methodology and assay procedure.
(D) A description of appropriate
internal and external quality control
materials that are recommended or
provided. The description must identify
those control elements that are
incorporated into the testing procedure,
if applicable.
(E) Detailed specifications for sample
collection, processing, and storage.
(F) Detailed specification of the
criteria for test results interpretation and
reporting including pre-established
templates.
(G) If applicable, based on the output
of the results, a description of the
specific number of events to collect,
result outputs, and analytical sensitivity
of the assay that will be reported.
(iii) Information that demonstrates the
performance characteristics of the test,
including:
(A) Device performance data from
either a method comparison study
comparing the specific lymphocyte cell
markers to a predicate device or data
collected through a clinical study
demonstrating clinical validity using
well-characterized clinical specimens.
Samples must be representative of the
intended use population of the device
including hematologic neoplasms and
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61165
the specific sample types for which the
test is indicated for use.
(B) If applicable, device performance
data from a clinical study demonstrating
clinical validity for parameters not
established in a predicate device of this
generic type using well-characterized
prospectively obtained clinical
specimens including all hematologic
neoplasms and the specific sample
types for which the device is indicated
for use.
(C) Device precision data using
clinical samples to evaluate the withinlot, between-lot, within-run, between
run, site-to-site and total variation using
a minimum of three sites, of which at
least two sites must be external sites.
Results shall be reported as the standard
deviation and percentage coefficient of
variation for each level tested.
(D) Reproducibility data generated
using a minimum of three lots of
reagents to evaluate mean fluorescence
intensity and variability of the recovery
of the different markers and/or cell
populations.
(E) Data from specimen and reagent
carryover testing performed using wellestablished methods (e.g., CLSI H26–
A2).
(F) Specimen and prepared sample
stability data established for each
specimen matrix in the anticoagulant
combinations and storage/use
conditions that will be indicated.
(G) A study testing anticoagulant
equivalency in all claimed specimen
type/anticoagulant combinations using
clinical specimens that are
representative of the intended use
population of the device.
(H) Analytic sensitivity data using a
dilution panel created from clinical
samples.
(I) Analytical specificity data,
including interference and crosscontamination.
(J) Device stability data, including
real-time stability of reagents under
various storage times and temperatures.
(K) For devices that include
polyclonal antibodies, Fluorescence
Minus One (FMO) studies to evaluate
non-specific binding for all polyclonal
antibodies. Each FMO tube is compared
to reagent reference to demonstrate that
no additional population appears when
one marker is absent. Pre-specified
acceptance criteria must be provided
and followed.
(L) For devices indicated for use as a
semi-quantitative test, linearity data
using a dilution panel created from
clinical samples.
(M) For devices indicated for use as
a semi-quantitative test, clinically
relevant analytical sensitivity data,
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including limit of blank, limit of
detection, and limit of quantification.
(iv) Identification of risk mitigation
elements used by the device, including
a detailed description of all additional
procedures, methods, and practices
incorporated into the instructions for
use that mitigate risks associated with
testing the device.
(2) The 21 CFR 809.10 compliant
labeling must include the following:
(i) The intended use statement in the
21 CFR 809.10(a)(2) and (b)(2)
compliant labeling must include a
statement that the results should be
interpreted by a pathologist or
equivalent professional in conjunction
with other clinical and laboratory
findings. The intended use statement
must also include information on what
the device detects and measures,
whether the device is qualitative, semiquantitative, and/or quantitative, the
clinical indications for which the device
is to be used, and the specific
population(s) for which the device is
intended.
(ii) A detailed description of the
performance studies conducted to
comply with paragraph (b)(1)(iii) of this
section and a summary of the results.
(3) As part of the risk management
activities performed under 21 CFR
820.30 design controls, product labeling
and instruction manuals must include
clear examples of all expected
phenotypic patterns and gating
strategies using well-defined clinical
samples representative of both abnormal
and normal cellular populations. These
samples must be selected based upon
the indications described in paragraph
(b)(1)(i) of this section.
Dated: December 20, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017–27855 Filed 12–26–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 882
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[Docket No. FDA–2017–N–6642]
Medical Devices; Neurological
Devices; Classification of the
Computerized Behavioral Therapy
Device for Psychiatric Disorders
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Final order.
The Food and Drug
Administration (FDA or we) is
SUMMARY:
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classifying the computerized behavioral
therapy device for psychiatric disorders
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
computerized behavioral therapy device
for psychiatric disorders’ 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 December
27, 2017. The classification was
applicable on September 14, 2017.
FOR FURTHER INFORMATION CONTACT:
Patrick Antkowiak, Center for Devices
and Radiological Health, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 2663, Silver Spring,
MD 20993–0002, 240–402–3705,
Patrick.Antkowiak@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the
computerized behavioral therapy device
for psychiatric disorders 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 (21
U.S.C. 360c(i)) to a predicate device that
does not require premarket approval.
PO 00000
Frm 00038
Fmt 4700
Sfmt 4700
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 shall 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 placed 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.
E:\FR\FM\27DER1.SGM
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]]>Agencies
[Federal Register Volume 82, Number 247 (Wednesday, December 27, 2017)]
[Rules and Regulations]
[Pages 61163-61166]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-27855]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 864
[Docket No. FDA-2017-N-6643]
Medical Devices; Hematology and Pathology Devices; Classification
of the Flow Cytometric Test System for Hematopoietic Neoplasms
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or we) is classifying
the flow cytometric test system for hematopoietic neoplasms 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 flow cytometric test system for hematopoietic
neoplasms' 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 December 27, 2017. The classification
was applicable on June 29, 2017.
FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 4545, Silver Spring, MD 20993-0002, 240-402-6357,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
Upon request, FDA has classified the flow cytometric test system
for hematopoietic neoplasms as class II (special controls), which we
have
[[Page 61164]]
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 (21 U.S.C. 360c(i)) to a predicate device that
does not require premarket approval. 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 shall
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 placed
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 October 3, 2016, Beckman Coulter submitted a request for De Novo
classification of the ClearLLab Reagents (T1, T2, B1, B2, M). 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 June 29, 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 864.7010. We have named
the generic type of device flow cytometric test system for
hematopoietic neoplasms, and it is identified as a device that consists
of reagents for immunophenotyping of human cells in relation to the
level of expression, antigen density, and distribution of specific
cellular markers. These reagents are used as an aid in the differential
diagnosis or monitoring of hematologically abnormal patients having or
suspected of having hematopoietic neoplasms. The results should be
interpreted by a pathologist or equivalent professional in conjunction
with other clinical and laboratory findings.
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--Flow Cytometric Test for Hematopoietic Neoplasms Risks and
Mitigation Measures
------------------------------------------------------------------------
Mitigation measures/21 CFR
Identified risks section
------------------------------------------------------------------------
Incorrect test results (false negatives General Controls and Special
or false positives). Controls (1) and (2) (21 CFR
864.7010(b)(1) and (2)).
Incorrect interpretation of device General Controls and Special
results by the end user. Controls (1), (2), and (3) (21
CFR 864.7010(b)(1), (2), and
(3)).
Patient harm from specimen(s) General Controls and Special
collection. Control (1) (21 CFR
864.7010(b)(1)).
------------------------------------------------------------------------
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
[[Page 61165]]
premarket notification requirements under section 510(k) of the FD&C
Act.
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. 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 21 CFR 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; the collections of
information in 21 CFR part 820 have been approved under OMB control
number 0910-0073; 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 is revised to read as follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.
0
2. Add Sec. 864.7010 to subpart H to read as follows:
Sec. 864.7010 Flow cytometric test system for hematopoietic
neoplasms.
(a) Identification. A flow cytometric test for hematopoietic
neoplasms is a device that consists of reagents for immunophenotyping
of human cells in relation to the level of expression, antigen density,
and distribution of specific cellular markers. These reagents are used
as an aid in the differential diagnosis or monitoring of
hematologically abnormal patients having or suspected of having
hematopoietic neoplasms. The results should be interpreted by a
pathologist or equivalent professional in conjunction with other
clinical and laboratory findings.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Premarket notification submissions must include the following
information:
(i) The indications for use must indicate the clinical
hematopoietic neoplasms for which the assay was designed and validated,
for example, chronic leukemia or lymphoma.
(ii) A detailed device description including the following:
(A) A detailed description of all test components, all required
reagents, and all instrumentation and equipment, including
illustrations or photographs of nonstandard equipment or methods.
(B) Detailed documentation of the device software including, but
not limited to, standalone software applications and hardware-based
devices that incorporate software.
(C) A detailed description of methodology and assay procedure.
(D) A description of appropriate internal and external quality
control materials that are recommended or provided. The description
must identify those control elements that are incorporated into the
testing procedure, if applicable.
(E) Detailed specifications for sample collection, processing, and
storage.
(F) Detailed specification of the criteria for test results
interpretation and reporting including pre-established templates.
(G) If applicable, based on the output of the results, a
description of the specific number of events to collect, result
outputs, and analytical sensitivity of the assay that will be reported.
(iii) Information that demonstrates the performance characteristics
of the test, including:
(A) Device performance data from either a method comparison study
comparing the specific lymphocyte cell markers to a predicate device or
data collected through a clinical study demonstrating clinical validity
using well-characterized clinical specimens. Samples must be
representative of the intended use population of the device including
hematologic neoplasms and the specific sample types for which the test
is indicated for use.
(B) If applicable, device performance data from a clinical study
demonstrating clinical validity for parameters not established in a
predicate device of this generic type using well-characterized
prospectively obtained clinical specimens including all hematologic
neoplasms and the specific sample types for which the device is
indicated for use.
(C) Device precision data using clinical samples to evaluate the
within-lot, between-lot, within-run, between run, site-to-site and
total variation using a minimum of three sites, of which at least two
sites must be external sites. Results shall be reported as the standard
deviation and percentage coefficient of variation for each level
tested.
(D) Reproducibility data generated using a minimum of three lots of
reagents to evaluate mean fluorescence intensity and variability of the
recovery of the different markers and/or cell populations.
(E) Data from specimen and reagent carryover testing performed
using well-established methods (e.g., CLSI H26-A2).
(F) Specimen and prepared sample stability data established for
each specimen matrix in the anticoagulant combinations and storage/use
conditions that will be indicated.
(G) A study testing anticoagulant equivalency in all claimed
specimen type/anticoagulant combinations using clinical specimens that
are representative of the intended use population of the device.
(H) Analytic sensitivity data using a dilution panel created from
clinical samples.
(I) Analytical specificity data, including interference and cross-
contamination.
(J) Device stability data, including real-time stability of
reagents under various storage times and temperatures.
(K) For devices that include polyclonal antibodies, Fluorescence
Minus One (FMO) studies to evaluate non-specific binding for all
polyclonal antibodies. Each FMO tube is compared to reagent reference
to demonstrate that no additional population appears when one marker is
absent. Pre-specified acceptance criteria must be provided and
followed.
(L) For devices indicated for use as a semi-quantitative test,
linearity data using a dilution panel created from clinical samples.
(M) For devices indicated for use as a semi-quantitative test,
clinically relevant analytical sensitivity data,
[[Page 61166]]
including limit of blank, limit of detection, and limit of
quantification.
(iv) Identification of risk mitigation elements used by the device,
including a detailed description of all additional procedures, methods,
and practices incorporated into the instructions for use that mitigate
risks associated with testing the device.
(2) The 21 CFR 809.10 compliant labeling must include the
following:
(i) The intended use statement in the 21 CFR 809.10(a)(2) and
(b)(2) compliant labeling must include a statement that the results
should be interpreted by a pathologist or equivalent professional in
conjunction with other clinical and laboratory findings. The intended
use statement must also include information on what the device detects
and measures, whether the device is qualitative, semi-quantitative,
and/or quantitative, the clinical indications for which the device is
to be used, and the specific population(s) for which the device is
intended.
(ii) A detailed description of the performance studies conducted to
comply with paragraph (b)(1)(iii) of this section and a summary of the
results.
(3) As part of the risk management activities performed under 21
CFR 820.30 design controls, product labeling and instruction manuals
must include clear examples of all expected phenotypic patterns and
gating strategies using well-defined clinical samples representative of
both abnormal and normal cellular populations. These samples must be
selected based upon the indications described in paragraph (b)(1)(i) of
this section.
Dated: December 20, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-27855 Filed 12-26-17; 8:45 am]
BILLING CODE 4164-01-P
