[Federal Register Volume 79, Number 95 (Friday, May 16, 2014)]
[Rules and Regulations]
[Pages 28401-28404]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-11173]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. FDA-2014-N-0431]


Medical Devices; Gastroenterology-Urology Devices; Classification 
of the Colon Capsule Imaging System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
colon capsule imaging 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 colon capsule 
imaging 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 June 16, 2014. The classification was 
effective beginning January 29, 2014.

FOR FURTHER INFORMATION CONTACT: Irene Bacalocostantis, Center for 
Devices and Radiological Health, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 66, Rm. G244, Silver Spring, MD 20993-0002, 
301-796-6814.

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, July 9, 2012), 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 (21 U.S.C. 
360) 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) 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

[[Page 28402]]

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.
    Given Imaging Ltd. submitted a request on November 21, 2012, for 
classification of the PillCam[supreg] COLON 2 capsule endoscopy 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 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 January 29, 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.  876.1330 (21 CFR 
876.1330).
    Following the effective date of this final classification 
administrative order, any firm submitting a premarket notification 
(510(k)) for a colon capsule imaging system will need to comply with 
the special controls named in the final administrative order.
    The device is assigned the generic name colon capsule imaging 
system, and it is identified as a prescription, single-use ingestible 
capsule designed to acquire video images during natural propulsion 
through the digestive system. It is specifically designed to visualize 
the colon for the detection of polyps. It is intended for use only in 
patients who had an incomplete optical colonoscopy with adequate 
preparation, and a complete evaluation of the colon was not technically 
possible.
    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--Colon Capsule Imaging System Risks and Mitigation Measures
----------------------------------------------------------------------------------------------------------------
         Identified risk                                        Mitigation measure
----------------------------------------------------------------------------------------------------------------
Adverse tissue reaction.........  Biocompatibility.
Equipment, malfunction leading    Electrical safety, thermal and mechanical safety.
 to injury.                       Software validation, verification, and hazard analysis.
                                  Non-clinical testing.
                                  Labeling.
Interference with other devices   Electromagnetic compatibility testing.
 and with this device (e.g.,      Software validation, verification, and hazard analysis.
 interference with image          Non-clinical testing.
 acquisition, patient
 information compromised).
Poor image acquisitions.........  Optical imaging performance testing
                                  Non-clinical testing.
                                  Labeling.
Failure to excrete..............  Labeling.
Misinterpretation of the          Clinical performance data.
 captured images.                 Non-clinical testing.
                                  Labeling.
Possibility of missing a polyp,   Clinical performance data.
 or falsely identifying a polyp.  Software validation, verification, and hazard analysis.
                                  Labeling.
Abdominal pain, nausea,           Clinical performance data.
 vomiting, choking.               Labeling.
----------------------------------------------------------------------------------------------------------------

    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:
     The capsule must be demonstrated to be biocompatible.
     Non-clinical testing data must demonstrate the mechanical 
and functional integrity of the device under physically stressed 
conditions. The following performance characteristics must be tested 
and detailed protocols must be provided for each test:
    [cir] Bite test to ensure that the capsule can withstand extreme 
cases of biting.
    [cir] pH resistance test to evaluate integrity of the capsule when 
exposed to a range of pH values.
    [cir] Battery life test to demonstrate that the capsule's operating 
time is not constrained by the battery capacity.
    [squ] Shelf-life testing to demonstrate that the device performs as 
intended at the proposed shelf-life date.
    [cir] Optical testing to evaluate fundamental image quality 
characteristics such as resolution, field of view, depth of field, 
distortion, signal-to-noise ratio, uniformity, and image artifacts. A 
test must be performed to evaluate the potential of scratches, caused 
by travelling through the gastrointestinal tract, on the transparent 
window of the capsule and their impact on the optical and color 
performance.
    [cir] An optical safety analysis must be performed based on maximum 
(worst-case) light exposure to internal gastrointestinal mucosa, and 
covering ultraviolet, visible, and near-infrared ranges, as 
appropriate. A mitigation analysis must be provided.
    [cir] A color performance test must be provided to compare the 
color differences between the input scene and output image.

[[Page 28403]]

    [cir] The video viewer must clearly present the temporal or spatial 
relationship between any two frames as a real-time lapse or a travel 
distance. The video viewer must alert the user when the specific video 
interval is captured at a frame rate lower than the nominal one due to 
communication errors.
    [cir] A performance test evaluating the latency caused by any 
adaptive algorithm such as adjustable frame rate must be provided.
    [cir] If the capsule includes a localization module, a localization 
performance test must be performed to verify the accuracy and precision 
of locating the capsule position within the colon.
    [cir] A data transmission test must be performed to verify the 
robustness of the data transmission between the capsule and the 
recorder. Controlled signal attenuation should be included for 
simulating a non-ideal environment.
    [cir] Software validation, verification, and hazards analysis must 
be provided.
    [cir] Electrical equipment safety, including thermal and mechanical 
safety and electromagnetic compatibility (EMC) testing must be 
performed. If the environments of intended use include locations 
outside of hospitals and clinics, appropriate higher immunity test 
levels must be used. Labeling must include appropriate EMC information.
    [cir] Information demonstrating immunity from wireless hazards.
     The clinical performance characteristics of the device for 
the detection of colon polyps must be established. Demonstration of the 
performance characteristics must include assessment of positive percent 
agreement and negative percent agreement compared to a clinically-
acceptable alternative structural imaging method.
     Clinician labeling must include:
    [cir] Specific instructions and the clinical and technical 
expertise needed for the safe use of the device.
    [cir] A detailed summary of the clinical testing pertinent to use 
of the device, including the percentage of patients in which a polyp 
was correctly identified by capsule endoscopy, but also the percent of 
patients in which the capsule either missed or falsely identified a 
polyp with respect to the clinically acceptable alternative structural 
imaging method.
    [cir] The colon cleansing procedure.
    [cir] A detailed summary of the device technical parameters.
    [cir] A detailed summary of the device- and procedure-related 
complications pertinent to use of the device.
    [cir] An expiration date/shelf life.
     Patient labeling must include:
    [cir] An explanation of the device and the mechanism of operation.
    [cir] Patient preparation procedure.
    [cir] A brief summary of the clinical study. The summary should not 
only include the percentage of patients in which a polyp was correctly 
identified by capsule endoscopy, but also the percent of patients in 
which the capsule either missed or falsely identified a polyp with 
respect to the clinically acceptable alternative structural imaging 
method.
    [cir] A summary of the device- and procedure-related complications 
pertinent to use of the device.
    Colon capsule imaging systems are prescription devices restricted 
to patient use only upon the authorization of a practitioner licensed 
by law to administer or use the device. (Proposed Sec.  876.1330(a); 
see section 520(e) of the FD&C Act (21 U.S.C. 360j(e)) and Sec.  
801.109 (21 CFR 801.109) (Prescription devices).) Prescription-use 
restrictions are a type of general controls 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 prostate lesion documentation 
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, 
and is available electronically at http://www.regulations.gov.

1. K123666: De Novo Request per 513(f)(2) of the Federal Food, Drug, 
and Cosmetic Act from Given Imaging Ltd., dated November 21, 2012.

List of Subjects in 21 CFR Part 876

    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 
876 is amended as follows:

PART 876--GASTROENTEROLOGY-UROLOGY DEVICES

0
1. The authority citation for 21 CFR part 876 continues to read as 
follows:

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


0
2. Add Sec.  876.1330 to subpart B to read as follows:


Sec.  876.1330  Colon capsule endoscopy system.

    (a) Identification. A prescription, single-use ingestible capsule 
designed to acquire video images during natural propulsion through the 
digestive system. It is specifically designed to visualize the colon 
for the detection of polyps. It is intended for use only in patients 
who had an incomplete optical colonoscopy with adequate preparation, 
and a complete evaluation of the colon was not technically possible.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The capsule must be demonstrated to be biocompatible.
    (2) Non-clinical testing data must demonstrate the mechanical and 
functional integrity of the device under physically stressed 
conditions. The following performance characteristics

[[Page 28404]]

must be tested and detailed protocols must be provided for each test:
    (i) Bite test to ensure that the capsule can withstand extreme 
cases of biting.
    (ii) pH resistance test to evaluate integrity of the capsule when 
exposed to a range of pH values.
    (iii) Battery life test to demonstrate that the capsule's operating 
time is not constrained by the battery capacity.
    (iv) Shelf-life testing to demonstrate that the device performs as 
intended at the proposed shelf-life date.
    (v) Optical testing to evaluate fundamental image quality 
characteristics such as resolution, field of view, depth of field, 
distortion, signal-to-noise ratio, uniformity, and image artifacts. A 
test must be performed to evaluate the potential of scratches, caused 
by travelling through the gastrointestinal tract, on the transparent 
window of the capsule and their impact on the optical and color 
performance.
    (vi) An optical safety analysis must be performed based on maximum 
(worst-case) light exposure to internal gastrointestinal mucosa, and 
covering ultraviolet, visible, and near-infrared ranges, as 
appropriate. A mitigation analysis must be provided.
    (vii) A color performance test must be provided to compare the 
color differences between the input scene and output image.
    (viii) The video viewer must clearly present the temporal or 
spatial relationship between any two frames as a real-time lapse or a 
travel distance. The video viewer must alert the user when the specific 
video interval is captured at a frame rate lower than the nominal one 
due to communication errors.
    (ix) A performance test evaluating the latency caused by any 
adaptive algorithm such as adjustable frame rate must be provided.
    (x) If the capsule includes a localization module, a localization 
performance test must be performed to verify the accuracy and precision 
of locating the capsule position within the colon.
    (xi) A data transmission test must be performed to verify the 
robustness of the data transmission between the capsule and the 
recorder. Controlled signal attenuation should be included for 
simulating a non-ideal environment.
    (xii) Software validation, verification, and hazards analysis must 
be provided.
    (xiii) Electrical equipment safety, including thermal and 
mechanical safety and electromagnetic compatibility (EMC) testing must 
be performed. If the environments of intended use include locations 
outside of hospitals and clinics, appropriate higher immunity test 
levels must be used. Labeling must include appropriate EMC information.
    (xiv) Information demonstrating immunity from wireless hazards.
    (3) The clinical performance characteristics of the device for the 
detection of colon polyps must be established. Demonstration of the 
performance characteristics must include assessment of positive percent 
agreement and negative percent agreement compared to a clinically 
acceptable alternative structural imaging method.
    (4) Clinician labeling must include:
    (i) Specific instructions and the clinical and technical expertise 
needed for the safe use of the device.
    (ii) A detailed summary of the clinical testing pertinent to use of 
the device, including the percentage of patients in which a polyp was 
correctly identified by capsule endoscopy, but also the percent of 
patients in which the capsule either missed or falsely identified a 
polyp with respect to the clinically acceptable alternative structural 
imaging method.
    (iii) The colon cleansing procedure.
    (iv) A detailed summary of the device technical parameters.
    (v) A detailed summary of the device- and procedure-related 
complications pertinent to use of the device.
    (vi) An expiration date/shelf life.
    (5) Patient labeling must include:
    (i) An explanation of the device and the mechanism of operation.
    (ii) Patient preparation procedure.
    (iii) A brief summary of the clinical study. The summary should not 
only include the percentage of patients in which a polyp was correctly 
identified by capsule endoscopy, but also the percent of patients in 
which the capsule either missed or falsely identified a polyp with 
respect to the clinically acceptable alternative structural imaging 
method.
    (iv) A summary of the device- and procedure-related complications 
pertinent to use of the device.

    Dated: May 9, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-11173 Filed 5-15-14; 8:45 am]
BILLING CODE 4160-01-P