[Federal Register Volume 80, Number 38 (Thursday, February 26, 2015)]
[Rules and Regulations]
[Pages 10330-10333]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-03934]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 884

[Docket No. FDA-2014-M-1957]


Medical Devices; Obstetrical and Gynecological Devices; 
Classification of the Assisted Reproduction Embryo Image Assessment 
System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is classifying the 
Assisted Reproduction Embryo Image Assessment System 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 Assisted Reproduction Embryo Image Assessment System 
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 February 26, 2015. The classification 
was applicable June 6, 2014.

FOR FURTHER INFORMATION CONTACT: Michael Bailey, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. G120, Silver Spring, MD 20993-0002, 301-796-6530.

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), 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.

[[Page 10331]]

    Section 513(f)(2) of the FD&C Act, 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), 
the person requests a classification under section 513(f)(2) of the 
FD&C Act. 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.
    On August 3, 2012, FDA issued an order classifying the EEVA System 
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 August 
23, 2012, Auxogyn, Inc., submitted a de novo request for classification 
of the EEVA System under section 513(f)(2) of the FD&C Act. The 
manufacturer recommended that the device be classified into class II 
(Ref. 1).
    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 June 6, 2014, FDA issued an order to the requestor 
classifying the device into class II. FDA is codifying the 
classification of the device by adding Sec.  884.6195 (21 CFR 
884.6195).
    Following the effective date of this final classification 
administrative order, any firm submitting a premarket notification 
(510(k)) for an Assisted Reproduction Embryo Image Assessment System 
will need to comply with the special controls named in the final 
administrative order.
    The device is assigned the generic name Assisted Reproduction 
Embryo Image Assessment System, and it is identified as a prescription 
device that is designed to obtain and analyze light microscopy images 
of developing embryos. This device provides information to aid in the 
selection of embryo(s) for transfer when there are multiple embryos 
deemed suitable for transfer or freezing.
    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:

 Table 1--Assisted Reproduction Embryo Image Assessment System Risks and
                           Mitigation Measures
------------------------------------------------------------------------
            Identified risk                    Mitigation measures
------------------------------------------------------------------------
Damage or Destruction of the Embryo....  Non-Clinical Performance
                                          Testing.
                                         Software Verification,
                                          Validation & Hazard Analysis.
                                         Clinical Testing.
                                         Electromagnetic Compatibility
                                          Testing.
                                         Electrical Safety Testing.
                                         Labeling.
                                         Training.
Infection (Contamination of Device,      Cleaning and Disinfection
 Labware, and Incubator).                 Validation.
                                         Labeling.
                                         Training.
Incorrect Embryo Development Prediction  Non-Clinical Performance
                                          Testing.
                                         Software Verification,
                                          Validation & Hazard Analysis.
                                         Clinical Testing.
                                         Labeling.
                                         Training.
Electromagnetic Interference/Electrical  Electromagnetic Compatibility
 Safety Issues.                           Testing.
                                         Electrical Safety Testing.
                                         Labeling.
Use Error..............................  Labeling.
                                         Training.
------------------------------------------------------------------------

    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:

 Clinical performance testing must demonstrate a reasonable 
assurance of the safety and effectiveness of the device to predict 
embryo development. Classification performance (sensitivity and 
specificity) and predictive accuracy (Positive Predictive Value and 
Negative Predictive Value) must be

[[Page 10332]]

assessed at the subject and embryo levels.
 Software validation, verification, and hazard analysis must be 
provided.
 Non-clinical performance testing data must demonstrate the 
performance characteristics of the device. Testing must include the 
following:
    [cir] Total light exposure and output testing;
    [cir] a safety analysis must be performed based on maximum (worst-
case) light exposure to embryos, which also includes the safety of the 
light wavelength(s) emitted by the device;
    [cir] simulated-use testing;
    [cir] Mouse Embryo Assay testing to assess whether device operation 
impacts growth and development of mouse embryos to the blastocyst 
stage;
    [cir] cleaning and disinfection validation of reusable components;
    [cir] package integrity and transit testing;
    [cir] hardware fail-safe validation;
    [cir] electrical equipment safety and electromagnetic compatibility 
testing; and
    [cir] prediction algorithm reproducibility.
 Labeling must include the following:
    [cir] A detailed summary of clinical performance testing, including 
any adverse events;
    [cir] specific instructions, warnings, precautions, and training 
needed for safe use of the device;
    [cir] appropriate electromagnetic compatibility information;
    [cir] validated methods and instructions for cleaning and 
disinfection of reusable components; and
    [cir] information identifying compatible cultureware and explain 
how they are used with the device.

    An Assisted Reproduction Embryo Image Assessment System is a 
prescription device restricted to patient use only upon the 
authorization of a practitioner licensed by law to administer or use 
the device. (See 21 CFR 801.109 (Prescription devices).)
    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 Assisted Reproduction Embryo Image 
Assessment System 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 part 801, regarding labeling, 
have been approved under OMB control number 0910-0485.

IV. Reference

    The following reference has been placed on display in the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.

1. K120427: De Novo Request from Auxogyn, Inc., dated August 23, 
2012.

List of Subjects in 21 CFR Part 884

    Medical devices, Obstetrical and Gynecological devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
884 is amended as follows:

PART 884--OBSTETRICAL AND GYNECOLOGICAL DEVICES

0
1. The authority citation for 21 CFR part 884 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.


0
2. Section 884.6195 is added to subpart G to read as follows:


Sec.  884.6195  Assisted Reproduction Embryo Image Assessment System.

    (a) Identification. An Assisted Reproduction Embryo Image 
Assessment System is a prescription device that is designed to obtain 
and analyze light microscopy images of developing embryos. This device 
provides information to aid in the selection of embryo(s) for transfer 
when there are multiple embryos deemed suitable for transfer or 
freezing.
    (b) Classification. Class II (special controls). The special 
control(s) for this device are:
    (1) Clinical performance testing must demonstrate a reasonable 
assurance of safety and effectiveness of the device to predict embryo 
development. Classification performance (sensitivity and specificity) 
and predictive accuracy (Positive Predictive Value and Negative 
Predictive Value) must be assessed at the subject and embryo levels.
    (2) Software validation, verification, and hazard analysis must be 
provided.
    (3) Non-clinical performance testing data must demonstrate the 
performance characteristics of the device. Testing must include the 
following:
    (i) Total light exposure and output testing;
    (ii) A safety analysis must be performed based on maximum (worst-
case) light exposure to embryos, which also includes the safety of the 
light wavelength(s) emitted by the device;
    (iii) Simulated-use testing;
    (iv) Mouse Embryo Assay testing to assess whether device operation 
impacts growth and development of mouse embryos to the blastocyst 
stage;
    (v) Cleaning and disinfection validation of reusable components;
    (vi) Package integrity and transit testing;
    (vii) Hardware fail-safe validation;
    (viii) Electrical equipment safety and electromagnetic 
compatibility testing; and
    (ix) Prediction algorithm reproducibility.
    (4) Labeling must include the following:
    (i) A detailed summary of clinical performance testing, including 
any adverse events;
    (ii) Specific instructions, warnings, precautions, and training 
needed for safe use of the device
    (iii) Appropriate electromagnetic compatibility information;
    (iv) Validated methods and instructions for cleaning and 
disinfection of reusable components; and
    (v) Information identifying compatible cultureware and explain how 
they are used with the device.


[[Page 10333]]


    Dated: February 20, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-03934 Filed 2-25-15; 8:45 am]
BILLING CODE 4164-01-P