[Federal Register Volume 79, Number 170 (Wednesday, September 3, 2014)]
[Rules and Regulations]
[Pages 52195-52197]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-20882]
[[Page 52195]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 864
[Docket No. FDA-2014-N-1176]
Medical Devices; Hematology and Pathology Devices; Classification
of Early Growth Response 1 Gene Fluorescence In-Situ Hybridization Test
System for Specimen Characterization
AGENCY: Food and Drug Administration, HHS.
ACTION: Final order.
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SUMMARY: The Food and Drug Administration (FDA) is classifying early
growth response 1 (EGR1) gene fluorescence in-situ hybridization (FISH)
test system for specimen characterization into class II (special
controls). The special controls that will apply to this device are
identified in this order and will be part of the codified language for
the early growth response 1 (EGR1) gene fluorescence in-site
hybridization (FISH) test system for specimen characterization
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 October 3, 2014. The classification was
applicable July 29, 2013.
FOR FURTHER INFORMATION CONTACT: Shyam Kalavar, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 5568, Silver Spring, MD 20993-0002, 301-796-6807.
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, as amended by section 607 of the
Food and Drug Administration Safety and Innovation Act (Public Law 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 ``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 will
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 March 20, 2013, classifying the Vysis EGR1 FISH Probe Kit--SC
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
that was subsequently reclassified into class I or class II. On April
9, 2013, Abbott Molecular, Inc., submitted a request for classification
of Vysis EGR1 FISH Probe Kit--SC under section 513(f)(2) of the FD&C
Act. The manufacturer recommended that the device be classified into
class II.
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 de novo 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 July 29, 2013, FDA issued an order to the requestor
classifying the device into class II. FDA is codifying the
classification of the device by adding Sec. 864.1870.
Following the effective date of this final classification
administrative order, any firm submitting a premarket notification
(510(k)) for an early growth response 1 (EGR1) gene fluorescence in-
situ hybridization (FISH) test system for specimen characterization
will need to comply with the special controls named in the final
administrative order.
The device is assigned the generic name early growth response 1
(EGR1) gene fluorescence in-situ hybridization (FISH) test system for
specimen characterization, and it is identified as a device intended to
detect the EGR1 probe target on chromosome 5q in bone marrow specimens
from patients with acute myeloid leukemia (AML) or myelodysplastic
syndrome (MDS). The assay results are intended to be interpreted only
by a qualified pathologist or cytogeneticist. These devices do not
include automated systems that directly report results without review
and interpretation by a qualified pathologist or cytogeneticist. These
devices also do not include any device intended for use to select
patient therapy, predict patient response to therapy, or to screen for
disease as well as any device with a claim for a particular diagnosis,
prognosis, monitoring, or risk assessment.
FDA has identified the following risks to health associated with
this type of device and the measures required to mitigate these risks
in table 1:
[[Page 52196]]
Table 1--Identified Risks and Required Mitigations
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Identified risks Required mitigations
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False negative result..................... Special controls (1), (2),
and (3).
False positive result..................... Special controls (1), (2),
and (3).
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FDA believes that the following special controls, in addition to
the general controls, address these risks to health and provide
reasonable assurance of safety and effectiveness:
1. Premarket notification submissions must also include the
following information:
a. A detailed description of all probes included in the kit;
b. Purpose of each probe;
c. Probe molecular specificity;
d. Probe specificity;
e. Probe limits;
f. Probe sensitivity;
g. Specification of required ancillary reagents, instrumentation,
and equipment;
h. Specification of the specimen collection, processing, storage,
and slide preparation methods;
i. Specification of the assay procedure;
j. Specification of control elements that are incorporated into the
recommended testing procedures;
k. Specification of risk mitigation elements: Description of all
additional procedures, methods, and practices incorporated into the
directions for use that mitigate risks associated with testing;
l. Specification of the criteria for test result interpretation and
reporting;
m. Device analytical sensitivity data;
n. Device analytical specificity data;
o. Device reference limit data;
p. Device precision/reproducibility data;
q. Device stability data to include:
i. Real-time stability;
ii. Freeze-thaw stability;
iii. Transport and temperature stability;
iv. Post-hybridization signal stability;
v. Photostability of probe; and
r. Documentation that demonstrates the clinical validity of the
device. The documentation must include data from clinical studies, a
minimum of two peer-reviewed published literature references using the
specific device seeking marketing clearance, or both. Documentation for
the clinical studies and peer-reviewed published literature references
cited must include the following elements:
i. Documentation that the sponsor's probe was used in the
literature reference,
ii. Number and type of specimens,
iii. Target population studied,
iv. Upper reference limit, and
v. Range of positive probe results.
2. Your Sec. 809.10(b)(12) (21 CFR 809.10(b)(12)) compliant
labeling must include a statement summarizing the data identified in
Sec. 864.1870(b)(1)(xiii) through (b)(1)(xviii) and a description of
the studies supporting the information, including the pre-specified
acceptance criteria for these performance studies, justification for
the pre-specified acceptance criteria, and whether the pre-specified
acceptance criteria were met.
3. Your Sec. 809.10 compliant labeling must include:
a. A warning that reads ``The assay results are intended to be
interpreted only by a qualified pathologist or cytogeneticist.''
b. A warning that reads ``This device is not for high-risk uses
such as selecting therapy, predicting therapeutic response or disease
screening.''
c. A warning that reads ``The use of this device for diagnosis,
monitoring or risk assessment has not been established.''
Early growth response 1 (EGR1) gene fluorescence in-situ
hybridization (FISH) test system for specimen characterization are
prescription devices restricted to patient use only upon the
authorization of a practitioner licensed by law to administer or use
the device. (See section 520(e) of the FD&C Act (21 U.S.C. 360j(e)) and
21 CFR 801.109 (Prescription devices).). Prescription-use restrictions
are a type of general control as defined in section 513(a)(1)(A)(i) of
the FD&C Act.
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) of the FD&C Act 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 has
determined that premarket notification is necessary to provide
reasonable assurance of the safety and effectiveness of the device.
Therefore, this device type is not exempt from premarket notification
requirements. Persons who intend to market this type of device must
submit to FDA a premarket notification, prior to marketing the device,
which contains information about the early growth response 1 (EGR1)
gene fluorescence in-situ hybridization (FISH) test system for specimen
characterization they intend to market.
II. 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.
III. Paperwork Reduction Act of 1995
This final administrative 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 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 21 CFR part 864 continues to read as
follows:
Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.
0
2. Add Sec. 864.1870 to subpart B to read as follows:
Sec. 864.1870 Early growth response 1 (EGR1) gene fluorescence in-
situ hybridization (FISH) test system for specimen characterization.
(a) Identification. An early growth response 1 (EGR1) gene
fluorescence in-situ hybridization (FISH) test system for specimen
characterization is a device intended to detect the EGR1 probe target
on chromosome 5q in bone marrow specimens from patients with acute
myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The assay
results are intended to be interpreted only by a qualified pathologist
or cytogeneticist. These devices do not include automated systems that
directly report results without review and interpretation by a
qualified pathologist or cytogeneticist.
[[Page 52197]]
These devices also do not include any device intended for use to select
patient therapy, predict patient response to therapy, or to screen for
disease as well as any device with a claim for a particular diagnosis,
prognosis, monitoring, or risk assessment.
(b) Classification. Class II (special controls). The special
controls for this device are:
(1) Premarket notification submissions must also include the
following information:
(i) A detailed description of all probes included in the kit;
(ii) Purpose of each probe;
(iii) Probe molecular specificity;
(iv) Probe specificity;
(v) Probe limits;
(vi) Probe sensitivity;
(vii) Specification of required ancillary reagents,
instrumentation, and equipment;
(viii) Specification of the specimen collection, processing,
storage and slide preparation methods;
(ix) Specification of the assay procedure;
(x) Specification of control elements that are incorporated into
the recommended testing procedures;
(xi) Specification of risk mitigation elements: Description of all
additional procedures, methods, and practices incorporated into the
directions for use that mitigate risks associated with testing;
(xii) Specification of the criteria for test result interpretation
and reporting;
(xiii) Device analytical sensitivity data;
(xiv) Device analytical specificity data;
(xv) Device reference limit data;
(xvi) Device precision/reproducibility data;
(xvii) Device stability data to include:
(A) Real-time stability,
(B) Freeze-thaw stability,
(C) Transport and temperature stability,
(D) Post-hybridization signal stability,
(E) Photostability of probe, and
(xviii) Documentation that demonstrates the clinical validity of
the device. The documentation must include data from clinical studies,
a minimum of two peer-reviewed published literature references using
the specific device seeking marketing clearance, or both. Documentation
for the clinical studies and peer-reviewed published literature
references cited must include the following elements:
(A) Documentation that the sponsor's probe was used in the
literature reference,
(B) Number and type of specimens,
(C) Target population studied,
(D) Upper reference limit, and
(E) Range of positive probe results.
(2) Your Sec. 809.10(b)(12) of this chapter compliant labeling
must include a statement summarizing the data identified in paragraphs
(b)(1)(xiii) through (xviii) of this section and a description of the
studies supporting the information, including the pre-specified
acceptance criteria for these performance studies, justification for
the pre-specified acceptance criteria, and whether the pre-specified
acceptance criteria were met.
(3) Your Sec. 809.10 of this chapter compliant labeling must
include:
(i) A warning that reads ``The assay results are intended to be
interpreted only by a qualified pathologist or cytogeneticist.''
(ii) A warning that reads ``This device is not for high-risk uses
such as selecting therapy, predicting therapeutic response or disease
screening.''
(iii) A warning that reads ``The use of this device for diagnosis,
monitoring or risk assessment has not been established.''
Dated: August 27, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-20882 Filed 9-2-14; 8:45 am]
BILLING CODE 4164-01-P