[Federal Register Volume 78, Number 95 (Thursday, May 16, 2013)]
[Rules and Regulations]
[Pages 28733-28735]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-11628]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 880

[Docket No. FDA-2013-M-0042]


Medical Devices; General Hospital and Personal Use Monitoring 
Devices; Classification of the Ingestible Event Marker

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) is classifying the 
ingestible event marker into class II (special controls). 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 17, 2013. The classification was 
applicable beginning July 10, 2012.

FOR FURTHER INFORMATION CONTACT: James Cheng, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 1326, Silver Spring, MD 20993-0002, 301-796-6306.

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, 126 Statute 1054), 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) 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. Within 
30 days after the issuance of an order classifying the device, FDA must 
publish a notice in the Federal Register announcing this 
classification.
    In accordance with section 513(f)(1) of the FD&C Act, FDA issued an 
order on May 7, 2012, classifying the Proteus Personal Monitor 
including ingestible event marker 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 May 14, 2012, Proteus Biomedical, Inc., 
submitted a petition requesting classification of the Proteus Personal 
Monitor including ingestible event marker 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 petition 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 petition and the medical literature, FDA 
determined that the device can be classified into class II with the 
establishment of special controls. FDA believes these special controls 
will provide reasonable assurance of the safety and effectiveness of 
the device.
    The device is assigned the generic name ingestible event marker, 
and it is identified as a prescription device used to record time-
stamped, patient-logged events. The ingestible component links 
wirelessly through intrabody communication to an external recorder 
which records the date and time of ingestion as well as the unique 
serial number of the ingestible device.
    FDA has identified the following risks to health associated with 
this type of

[[Page 28734]]

device and the measures required to mitigate these risks:

     Table 1--Ingestible Event Marker Risks and Mitigation Measures
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            Identified risks                   Mitigation measures
------------------------------------------------------------------------
Adverse tissue reaction................  Biocompatibility Testing.
                                         Labeling (dose limits).
Systemic toxicity......................  Toxicology Testing.
                                         Labeling (dose limits).
Electromagnetic incompatibility........  Electromagnetic Compatibility
                                          Testing.
                                         Wireless Testing.
                                         Labeling.
Electrical safety issues...............  Electrical Safety Testing.
                                         Labeling.
Electrical/Mechanical failure..........  Nonclinical Performance
                                          Testing.
Failure to mark event..................  Nonclinical Performance
                                          Testing.
                                         Clinical Evaluation.
Failure to excrete.....................  Animal Testing.
Usability..............................  Human Factors Testing.
                                         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:
    1. The device must be demonstrated to be biocompatible and non-
toxic;
    2. Nonclinical, animal, and clinical testing must provide a 
reasonable assurance of safety and effectiveness, including device 
performance, durability, compatibility, usability (human factors 
testing), event recording, and proper excretion of the device;
    3. Appropriate analysis and nonclinical testing must validate 
electromagnetic compatibility performance, wireless performance, and 
electrical safety; and
    4. Labeling must include a detailed summary of the nonclinical and 
clinical testing pertinent to use of the device and the maximum number 
of daily device ingestions.
    Ingestible event markers 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.  880.6305(a) (21 
CFR 880.6305(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 authorized 
under section 520(e) and defined as a general control in section 
513(a)(1)(A)(i) of the FD&C Act.
    Therefore, on July 10, 2012, FDA issued an order to the petitioner 
classifying the device into class II. FDA is codifying the 
classification of the device by adding Sec.  880.6305.
    Following the effective date of this final classification 
administrative order, any firm submitting a 510(k) premarket 
notification for an ingestible event marker will need to comply with 
the special controls named in the final administrative order.
    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 ingestible event marker 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. Petition: Request for Evaluation of Automatic Class III 
Designation Under Section 513(f)(2) of the Federal Food, Drug, and 
Cosmetic Act From Proteus Biomedical, Inc., dated May 9, 2012.

List of Subjects in 21 CFR Part 880

    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 
880 is amended as follows:

PART 880--GENERAL HOSPITAL AND PERSONAL USE DEVICES

0
1. The authority citation for 21 CFR part 880 continues to read as 
follows:

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


0
2. Add Sec.  880.6305 to subpart G to read as follows:

[[Page 28735]]

Sec.  880.6305  Ingestible event marker.

    (a) Identification. An ingestible event marker is a prescription 
device used to record time-stamped, patient-logged events. The 
ingestible component links wirelessly through intrabody communication 
to an external recorder which records the date and time of ingestion as 
well as the unique serial number of the ingestible device.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The device must be demonstrated to be biocompatible and non-
toxic;
    (2) Nonclinical, animal, and clinical testing must provide a 
reasonable assurance of safety and effectiveness, including device 
performance, durability, compatibility, usability (human factors 
testing), event recording, and proper excretion of the device;
    (3) Appropriate analysis and nonclinical testing must validate 
electromagnetic compatibility performance, wireless performance, and 
electrical safety; and
    (4) Labeling must include a detailed summary of the nonclinical and 
clinical testing pertinent to use of the device and the maximum number 
of daily device ingestions.

    Dated: May 10, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-11628 Filed 5-15-13; 8:45 am]
BILLING CODE 4160-01-P