[Federal Register Volume 82, Number 198 (Monday, October 16, 2017)]
[Rules and Regulations]
[Pages 47969-47971]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-22286]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. FDA-2017-N-5224]


Medical Devices; Gastroenterology-Urology Devices; Classification 
of the Enzyme Packed Cartridge

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the enzyme packed cartridge into class II (special controls). The 
special controls that apply to the device type are identified in this 
order and will be part of the codified language for the enzyme packed 
cartridge's classification. We are taking this action because we have 
determined that classifying the device into class II (special controls) 
will provide a reasonable assurance of safety and effectiveness of the 
device. We believe this action will also enhance patients' access to 
beneficial innovative devices, in part by reducing regulatory burdens.

DATES: This order is effective October 16, 2017. The classification was 
applicable on November 20, 2015.

FOR FURTHER INFORMATION CONTACT: Joshua Silverstein, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 1615, Silver Spring, MD, 20993-0002, 301-
796-5155, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the enzyme packed cartridge as 
class II (special controls), which we have determined will provide a 
reasonable assurance of safety and effectiveness. In

[[Page 47970]]

addition, we believe this action will enhance patients' access to 
beneficial innovation, in part by reducing regulatory burdens by 
placing the device into a lower device class than the automatic class 
III assignment.
    The automatic assignment of class III occurs by operation of law 
and without any action by FDA, regardless of the level of risk posed by 
the new device. Any device that was not in commercial distribution 
before May 28, 1976, is automatically classified as, and remains 
within, class III and requires premarket approval unless and until FDA 
takes an action to classify or reclassify the device (see 21 U.S.C. 
360c(f)(1)). We refer to these devices as ``postamendments devices'' 
because they were not in commercial distribution prior to the date of 
enactment of the Medical Device Amendments of 1976, which amended the 
Federal Food, Drug, and Cosmetic Act (the FD&C Act).
    FDA may take a variety of actions in appropriate circumstances to 
classify or reclassify a device into class I or II. We may issue an 
order finding a new device to be substantially equivalent under section 
513(i) of the FD&C Act to a predicate device that does not require 
premarket approval (see 21 U.S.C. 360c(i)). We determine whether a new 
device is substantially equivalent to a predicate by means of the 
procedures for premarket notification under section 510(k) of the FD&C 
Act and part 807 (21 U.S.C. 360(k) and 21 CFR part 807, respectively).
    FDA may also classify a device through ``De Novo'' classification, 
a common name for the process authorized under section 513(f)(2) of the 
FD&C Act. Section 207 of the Food and Drug Administration Modernization 
Act of 1997 established the first procedure for De Novo classification 
(Pub. L. 105-115). Section 607 of the Food and Drug Administration 
Safety and Innovation Act modified the De Novo application process by 
adding a second procedure (Pub. L. 112-144). A device sponsor may 
utilize either procedure for De Novo classification.
    Under the first procedure, the person submits a 510(k) for a device 
that has not previously been classified. After receiving an order from 
FDA classifying the device into class III under section 513(f)(1) of 
the FD&C Act, the person then requests a classification under section 
513(f)(2).
    Under the second procedure, rather than first submitting a 510(k) 
and then a request for classification, if the person determines that 
there is no legally marketed device upon which to base a determination 
of substantial equivalence, that person requests a classification under 
section 513(f)(2) of the FD&C Act.
    Under either procedure for De Novo classification, FDA shall 
classify the device by written order within 120 days. The 
classification will be according to the criteria under section 
513(a)(1) of the FD&C Act. Although the device was automatically within 
class III, the De Novo classification is considered to be the initial 
classification of the device.
    We believe this De Novo classification will enhance patients' 
access to beneficial innovation, in part by reducing regulatory 
burdens. When FDA classifies a device into class I or II via the De 
Novo process, the device can serve as a predicate for future devices of 
that type, including for 510(k)s (see 21 U.S.C. 360c(f)(2)(B)(i)). As a 
result, other device sponsors do not have to submit a De Novo request 
or premarket approval application in order to market a substantially 
equivalent device (see 21 U.S.C. 360c(i), defining ``substantial 
equivalence''). Instead, sponsors can use the less burdensome 510(k) 
process, when necessary, to market their device.

II. De Novo Classification

    On January 2, 2015, Alcresta, Inc. submitted a request for De Novo 
classification of the RELIZORBTM. 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. We classify 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 that, in 
combination with the general controls, provide reasonable assurance of 
the safety and effectiveness of the device for its intended use (see 21 
U.S.C. 360c(a)(1)(B)). After review of the information submitted in the 
request, we determined that the device can be classified into class II 
with the establishment of special controls. FDA has determined that 
these special controls, in addition to general controls, will provide 
reasonable assurance of the safety and effectiveness of the device.
    Therefore, on November 20, 2015, FDA issued an order to the 
requestor classifying the device into class II. FDA is codifying the 
classification of the device by adding 21 CFR 876.5985. We have named 
the generic type of device enzyme packed cartridge, and it is 
identified as an ex vivo prescription device that is used in enzymatic 
hydrolysis of macronutrients into their essential nutrient forms at the 
time of delivery. The device consists of an outer casing containing an 
inert polymer with a covalently bound enzyme through which nutritional 
formula is directed. The device fits in line with enteral feeding 
systems.
    FDA has identified the following risks to health associated 
specifically with this type of device and the measures required to 
mitigate these risks in table 1.

     Table 1--Enzyme Packed Cartridge Risks and Mitigation Measures
------------------------------------------------------------------------
            Identified risks                   Mitigation measures
------------------------------------------------------------------------
Adverse tissue reaction................  Biocompatibility testing, Non-
                                          clinical testing, In vivo
                                          testing, and Labeling.
Mechanical failure.....................  Non-clinical testing, Shelf
                                          life testing, and Labeling.
     Deprivation of care.......
     Device clogging...........
     Filter becomes dislodged
     and releases beads into enteral
     formula.
Reduced enzymatic effect...............  Non-clinical testing, In vivo
                                          testing, Shelf life testing,
                                          and Labeling.
Use error..............................  Human factors testing and
                                          Labeling.
Infection..............................  Shelf life testing and
                                          Labeling.
------------------------------------------------------------------------

    FDA has determined that special controls, in combination with the 
general controls, address these risks to health and provide reasonable 
assurance of safety and effectiveness. In order for a device to fall 
within this classification, and thus avoid automatic classification in 
class III, it would have to comply with the special controls named in 
this

[[Page 47971]]

final order. The necessary special controls appear in the regulation 
codified by this order. This device is subject to premarket 
notification requirements under section 510(k).
    At the time of classification, enzyme packed cartridges are for 
prescription use only. Prescription devices are exempt from the 
requirement for adequate directions for use for the layperson under 
section 502(f)(1) of the FD&C Act (21 U.S.C. 352(f)(1)) and 21 CFR 
801.5, as long as the conditions of 21 CFR 801.109 are met.

III. Analysis of 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.

IV. 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.

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 part 876 continues to read as follows:

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


0
2. Add Sec.  876.5985 to subpart F to read as follows:


Sec.  876.5985   Enzyme packed cartridge.

    (a) Identification. An enzyme packed cartridge is an ex vivo 
prescription device that is used in enzymatic hydrolysis of 
macronutrients into their essential nutrient forms at the time of 
delivery. The device consists of an outer casing containing an inert 
polymer with a covalently bound enzyme through which nutritional 
formula is directed. The device fits in line with enteral feeding 
systems.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The patient contacting components of the device must be 
demonstrated to be biocompatible.
    (2) In vivo testing must be performed and must demonstrate that the 
device causes neither an adverse tissue response nor adverse 
performance.
    (3) Non-clinical testing must demonstrate that the device performs 
as intended under anticipated conditions of use. The following 
performance characteristics must be demonstrated:
    (i) Mechanical testing to demonstrate that the device can withstand 
clinical forces;
    (ii) Flow rate and leakage testing to demonstrate that the device 
does not impede the flow of enteral formula;
    (iii) Demonstration of enzymatic effect on intended macronutrient;
    (iv) The amount of enzyme that exits the cartridge must be 
characterized;
    (v) Validation that the device does not adversely impact the 
nutritional composition of enteral formula; and
    (vi) Validation that the device does not impede flow alarms on 
enteral feeding pumps.
    (4) Human factors testing must be performed to characterize use 
error risks.
    (5) Performance data must support shelf life by demonstrating 
package integrity and device functionality over the identified shelf 
life.
    (6) Labeling must include the following:
    (i) A detailed summary of in vivo testing pertinent to use of the 
device, including device-related adverse events;
    (ii) A detailed summary of compatible formulas that is supported by 
non-clinical testing, including the expected enzymatic conversion as a 
percentage;
    (iii) Detailed instructions on how to place the device into an 
enteral feeding circuit;
    (iv) A warning regarding the possibility for misconnections; and
    (v) Expiration date or shelf life.
    (7) Patient labeling must be provided and must include:
    (i) Relevant warnings, precautions, adverse effects, and 
complications;
    (ii) A description of the device and how it operates;
    (iii) Instructions on how to correctly use the device; and
    (iv) The benefits and risks associated with the use of the device.

    Dated: October 10, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-22286 Filed 10-13-17; 8:45 am]
 BILLING CODE 4164-01-P