[Federal Register Volume 81, Number 3 (Wednesday, January 6, 2016)]
[Rules and Regulations]
[Pages 378-380]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-33264]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 884

[Docket No. FDA-2015-N-4408]


Medical Devices; Obstetrical and Gynecological Devices; 
Classification of the Intravaginal Culture System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
intravaginal culture 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 intravaginal 
culture system'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 January 6, 2015. The classification was 
applicable on November 2, 2015.

FOR FURTHER INFORMATION CONTACT: Jason Roberts, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. G218, Silver Spring, MD 20993-0002, 240-402-6400, 
[email protected].

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 (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&CAct, 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.
    On February 23, 2015, INVO Bioscience, submitted a request for 
classification of the INVOcellTM Intravaginal Culture 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 for de novo classification 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 November 2, 2015, FDA issued an order to the 
requestor classifying the device into class II. FDA is codifying the 
classification of the device by adding Sec.  884.6165 (21 CFR 
884.6165).
    Following the effective date of this final classification order, 
any firm submitting a premarket notification (510(k)) for an 
intravaginal culture system will need to comply with the special 
controls named in this final order. The device is assigned the generic 
name intravaginal culture system, and it is identified as a 
prescription device intended for preparing, holding, and transferring 
human gametes or embryos during intravaginal in vitro fertilization 
(IVF) or intravaginal culture procedures.
    FDA has identified the following risks to health associated 
specifically with this type of device, as well as the measures required 
to mitigate these risks in table 1:

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   Table 1--Intravaginal Culture System Risks and Mitigation Measures
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       Identified risks                   Mitigation measures
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Damage to gametes and/or       Nonclinical performance testing.
 embryos or disruption of the  Shelf life testing.
 IVF process.                  Clinical testing.
                               Sterilization validation.
                               Labeling.
Patient injury (e.g.,          Nonclinical performance testing.
 hypersensitivity, toxicity,   Shelf life testing.
 abrasion, discomfort).        Biocompatibility.
                               Clinical testing.
                               Sterilization validation.
                               Labeling.
Infection....................  Sterilization validation.
                               Reprocessing validation.
                               Nonclinical performance testing.
                               Shelf life testing.
                               Clinical testing.
                               Labeling.
Transfer of incorrect embryos  Labeling.
 to patient.
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    FDA believes that special controls, in combination with the general 
controls, address these risks to health and provide reasonable 
assurance of the safety and effectiveness.
    Intravaginal culture system devices are prescription devices 
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), 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 
intravaginal culture system they intend to market.

II. Environmental Impact, No Significant 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 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 is on display in the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, and is available for viewing by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday; it 
is also available electronically at http://www.regulations.gov.

1. DEN150008: De novo Request per 513(f)(2) from INVO Bioscience, 
dated February 23, 2015.

List of Subjects in 21 CFR Part 884

    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 
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. Add Sec.  884.6165 to subpart G to read as follows:


Sec.  884.6165  Intravaginal culture system.

    (a) Identification. An intravaginal culture system is a 
prescription device intended for preparing, holding, and transferring 
human gametes or embryos during intravaginal in vitro fertilization or 
intravaginal culture procedures.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Clinical performance testing must demonstrate the following:
    (i) Comfort and retention of the intravaginal culture device;
    (ii) Adverse vaginal tissue reactions associated with intravaginal 
culture;
    (iii) Maximum number of gametes and/or embryos that can be placed 
in a device; and
    (iv) Rates of embryo development to the designated stage, 
implantation rates, clinical pregnancy rates, live birth rates, and any 
adverse events or outcomes.
    (2) Nonclinical performance testing must demonstrate that the 
device performs as intended under anticipated conditions of use. The 
following performance characteristics must be demonstrated:
    (i) Mouse embryo assay testing to assess embryotoxicity by 
evaluating the gamete and embryo-contacting device components effect on 
the growth and development of mouse embryos to the blastocyst stage;
    (ii) Endotoxin testing on gamete and embryo-contacting components 
of the device;
    (iii) Cleaning and disinfection validation of reusable device 
components;
    (iv) Sterility maintenance of the culture media within the device 
throughout the vaginal incubation

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period and subsequent embryo extraction; and
    (v) Ability of the device to permit oxygen and carbon dioxide 
exchange between the media contained within the device and the external 
environment throughout the vaginal incubation period.
    (3) The patient-contacting components of the device must be 
demonstrated to be biocompatible.
    (4) Performance data must demonstrate the sterility of the device 
components intended to be provided sterile.
    (5) Shelf life testing must demonstrate that the device maintains 
its performance characteristics and the packaging of device components 
labeled as sterile maintain integrity and sterility for the duration of 
the shelf life.
    (6) Labeling for the device must include:
    (i) A detailed summary of the clinical testing, including device 
effectiveness, device-related complications, and adverse events;
    (ii) Validated methods and instructions for reprocessing of 
reusable components;
    (iii) The maximum number of gametes or embryos that can be loaded 
into the device;
    (iv) A warning that informs users that the embryo development is 
first evaluated following intravaginal culture; and
    (v) A statement that instructs the user to use legally marketed 
assisted reproductive technology media that contain elements to 
mitigate the contamination risk (e.g., antibiotics) and to support 
continued embryonic development over the intravaginal culture period.
    (7) Patient labeling must be provided and must include:
    (i) Relevant warnings, precautions, and adverse effects and 
complications;
    (ii) Information on how to use the device;
    (iii) The risks and benefits associated with the use of the device; 
and
    (iv) A summary of the principal clinical device effectiveness 
results.

    Dated: December 30, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-33264 Filed 1-5-16; 8:45 am]
 BILLING CODE 4164-01-P