[Federal Register Volume 89, Number 179 (Monday, September 16, 2024)]
[Rules and Regulations]
[Pages 75493-75497]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-20999]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. FDA-2024-N-4082]


Medical Devices; Therapeutic Devices; Classification of the 
Pediatric Continuous Renal Replacement Therapy System

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is

[[Page 75494]]

classifying the pediatric continuous renal replacement therapy system 
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 pediatric continuous renal replacement 
therapy system'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.

DATES: This order is effective September 16, 2024. The classification 
was applicable on April 29, 2020.

FOR FURTHER INFORMATION CONTACT: Gema Gonzalez, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 2530, Silver Spring, MD 20993-0002, 301-796-6519, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the pediatric continuous renal 
replacement therapy system as class II (special controls), which we 
have determined will provide a reasonable assurance of safety and 
effectiveness.
    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 (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 (see 21 U.S.C. 360c(i)) to a predicate device 
that does not require premarket approval. We determine whether a new 
device is substantially equivalent to a predicate device by means of 
the procedures for premarket notification under section 510(k) of the 
FD&C Act (21 U.S.C. 360(k)) and part 807 (21 CFR part 807).
    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 (see also part 860, subpart D (21 CFR part 860, subpart D)). 
Section 207 of the Food and Drug Administration Modernization Act of 
1997 (Pub. L. 105-115) established the first procedure for De Novo 
classification. Section 607 of the Food and Drug Administration Safety 
and Innovation Act (Pub. L. 112-144) modified the De Novo application 
process by adding a second procedure. 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 is required 
to 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 placed 
within class III, the De Novo classification is considered to be the 
initial classification of the device.
    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 section 513(f)(2)(B)(i) of the FD&C 
Act). As a result, other device sponsors do not have to submit a De 
Novo request or premarket approval application to market a 
substantially equivalent device (see section 513(i) of the FD&C Act, 
defining ``substantial equivalence''). Instead, sponsors can use the 
510(k) process, when necessary, to market their device.

II. De Novo Classification

    On October 9, 2018, FDA received Medtronic, Inc.'s request for De 
Novo classification of the CARPEDIEM System. 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 the 
general controls, will provide reasonable assurance of the safety and 
effectiveness of the device.
    Therefore, on April 29, 2020, FDA issued an order to the requester 
classifying the device into class II. In this final order, FDA is 
codifying the classification of the device by adding 21 CFR 
876.5861.\1\ We have named the generic type of device pediatric 
continuous renal replacement therapy system, and it is identified as a 
device intended for use as an artificial kidney system for the 
management of pediatric patients with acute kidney injury and/or fluid 
overload by performing such therapies as hemodialysis, hemofiltration, 
hemodiafiltration, and isolated ultrafiltration. Using a hemodialyzer 
with a semipermeable membrane, the hemodialysis system removes toxins 
or excess fluid from the patient's blood using the principles of 
convection (via ultrafiltration) and/or diffusion (via a concentration 
gradient in dialysate). The hemodialysis delivery machine, with an 
automated ultrafiltration controller, controls and monitors the 
parameters related to this processing, including the rate at which 
blood and dialysate are pumped through the system, and the rate at 
which fluid is removed from the patient. During treatment, a patient's 
blood is circulated through the blood tubing set connected to the 
hemodialyzer's blood compartment. Blood access devices and accessories 
for hemodialysis required for the prescribed treatment are regulated 
under 21 CFR 876.5540.
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    \1\ FDA notes that the ACTION caption for this final order is 
styled as ``Final amendment; final order,'' rather than ``Final 
order.'' Beginning in December 2019, this editorial change was made 
to indicate that the document ``amends'' the Code of Federal 
Regulations. The change was made in accordance with the Office of 
Federal Register's (OFR) interpretations of the Federal Register Act 
(44 U.S.C. chapter 15), its implementing regulations (1 CFR 5.9 and 
parts 21 and 22), and the Document Drafting Handbook.
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    FDA has identified the following risks to health associated 
specifically with this type of device and the measures

[[Page 75495]]

required to mitigate these risks in table 1.

Table 1--Pediatric Continuous Renal Replacement Therapy System Risks and
                           Mitigation Measures
------------------------------------------------------------------------
       Identified risks to health              Mitigation measures
------------------------------------------------------------------------
Adverse tissue reaction................  Biocompatibility evaluation,
                                         Pyrogenicity testing, and
                                         Non-clinical performance
                                          testing.
Death..................................  Labeling,
                                         Clinical performance testing,
                                          and
                                         Usability testing.
Infection..............................  Labeling,
                                         Reprocessing validation,
                                         Pyrogenicity testing,
                                         Shelf life testing, and
                                         Usability testing.
Inadequate or incomplete treatment.....  Non-clinical performance
                                          testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing;
                                         Usability testing; and
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Clearance of essential blood substances  Non-clinical performance
 or medications.                          testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing;
                                         Usability testing; and
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Blood loss or blood cell destruction...  Non-clinical performance
                                          testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing; and
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Thermal injury.........................  Non-clinical performance
                                          testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing;
                                         Usability testing; and
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Blood leak into the dialysis fluid.....  Non-clinical performance
                                          testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing; and
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Fluid imbalance........................  Non-clinical performance
                                          testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing; and
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Air embolism...........................  Non-clinical performance
                                          testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing;
                                         Usability testing; and
                                         Software verification,
                                          validation, and hazard
                                          analysis.
Fluid pump(s) reversal resulting in air  Non-clinical performance
 infusion via the arterial bloodline.     testing;
                                         Clinical performance testing;
                                         Labeling;
                                         Shelf-life testing;
                                         Usability testing; and
                                         Software, verification,
                                          validation, and hazard
                                          analysis.
Electrical shock.......................  Electrical safety testing.
Electromagnetic interference with other  Electromagnetic compatibility
 devices/equipment.                       (EMC) testing.
------------------------------------------------------------------------

    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. 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 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) of the FD&C Act.

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,

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neither an environmental assessment nor an environmental impact 
statement is required.

IV. Paperwork Reduction Act of 1995

    This final order establishes special controls that refer to 
previously approved collections of information found in other FDA 
regulations and guidance. 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. 3501-3521). The collections 
of information in part 860, subpart D, regarding De Novo classification 
have been approved under OMB control number 0910-0844; the collections 
of information in 21 part 814, subparts A through E, regarding 
premarket approval, have been approved under OMB control number 0910-
0231; the collections of information in part 807, subpart E, regarding 
premarket notification submissions, have been approved under OMB 
control number 0910-0120; the collections of information in 21 CFR part 
820, regarding quality system regulation, have been approved under OMB 
control number 0910-0073; and the collections of information in 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.  876.5861 to subpart F to read as follows:


Sec.  876.5861  Pediatric continuous renal replacement therapy system.

    (a) Identification. A pediatric continuous renal replacement 
therapy hemodialysis system is a device intended for use as an 
artificial kidney system for the management of pediatric patients with 
acute kidney injury and/or fluid overload by performing such therapies 
as hemodialysis, hemofiltration, hemodiafiltration, and isolated 
ultrafiltration. Using a hemodialyzer with a semipermeable membrane, 
the hemodialysis system removes toxins or excess fluid from the 
patient's blood using the principles of convection (via 
ultrafiltration) and/or diffusion (via a concentration gradient in 
dialysate). The hemodialysis delivery machine, with an automated 
ultrafiltration controller, controls and monitors the parameters 
related to this processing, including the rate at which blood and 
dialysate are pumped through the system, and the rate at which fluid is 
removed from the patient. During treatment, a patient's blood is 
circulated through the blood tubing set connected to the hemodialyzer's 
blood compartment. Blood access devices and accessories for 
hemodialysis required for the prescribed treatment are regulated under 
Sec.  876.5540.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Clinical performance testing must confirm the safety and the 
accuracy, precision, and reproducibility of the non-clinical 
performance data under anticipated conditions of use.
    (2) Usability testing must demonstrate that a user can correctly 
use the hemodialysis delivery device based solely on reading the 
instructions for use.
    (3) Non-clinical performance testing data must demonstrate that the 
device performs as intended under anticipated conditions of use. The 
following performance characteristics must be tested:
    (i) Hemodialysis delivery system performance testing must include:
    (A) Fluid flow accuracy testing; and
    (B) Functional testing of system components including sensors, 
pumps, and scales to acceptance criteria.
    (ii) Hemodialyzer performance testing must include:
    (A) Ultrafiltration;
    (B) Blood and dialysate pressure drop;
    (C) Clearance rates;
    (D) Sieving coefficients;
    (E) Mechanical hemolysis;
    (F) Structural integrity;
    (G) Blood compartment integrity;
    (H) Volume of the blood compartment; and
    (I) Chemical analysis of the dialyzer membrane.
    (iii) Blood tubing set performance testing must include:
    (A) Pressure leak testing;
    (B) Worst-case endurance testing;
    (C) Priming volume assessment;
    (D) Tensile testing of joints and materials of all tubing segments;
    (E) Pressure transducer leak testing;
    (F) Clamp occlusion;
    (G) Mechanical hemolysis; and
    (H) Kink testing.
    (4) Software verification, validation, and hazard analysis must be 
performed.
    (5) Performance data must demonstrate the electromagnetic 
compatibility (EMC), electrical safety, and wireless compatibility of 
the device.
    (6) The tissue-contacting components of the device must be 
demonstrated to be biocompatible.
    (7) Performance data must demonstrate the sterility of the patient-
contacting components of the device.
    (8) Performance data must validate the reprocessing instructions 
for the reusable components of the device.
    (9) The patient-contacting components of the device must be 
demonstrated to be non-pyrogenic.
    (10) Performance data must support the shelf life of the device by 
demonstrating continued sterility, package integrity, and device 
functionality over the identified shelf life.
    (11) Device labeling must include:
    (i) Hemodialysis delivery system labeling must provide detailed 
information regarding the safe use of the dialysis machine, including:
    (A) Overall description of the device and individual components or 
accessories labeled for use with the delivery system;
    (B) Description of the safety-related components included in the 
system;
    (C) Identification of operational parameters;
    (D) Alarms and troubleshooting information;
    (E) Cleaning, disinfection, and preventative maintenance 
procedures; and
    (F) A statement that the device is intended for use by operators 
trained in the administration of continuous renal replacement therapy 
and in the management of its complications.
    (ii) Hemodialyzer labeling must include:
    (A) Description of compatibility;
    (B) Shelf life;
    (C) Storage conditions;
    (D) Instructions for the preparation of the hemodialyzer, 
initiation of dialysis, troubleshooting, and discontinuance of 
dialysis;
    (E) Membrane surface area, priming (blood) volume, maximum 
transmembrane pressure, maximum blood flow and maximum dialysate rate 
for each model;
    (F) Summary of the in vitro performance data; and
    (G) A non-pyrogenic statement.
    (iii) Blood tubing set labeling must provide detailed information 
regarding the safe use of the device, including:
    (A) Description of compatibility;
    (B) Shelf life;
    (C) Storage conditions;
    (D) Identification of the components in the package;

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    (E) Total length of the arterial and venous tubing sets;
    (F) Outer diameter (OD) of the pump segment;
    (G) Priming volume;
    (H) Identification of the hemodialysis delivery systems which are 
compatible with the blood tubing set;
    (I) Identification of the largest gauge needle that can be used 
with the injection port, if applicable; and
    (J) Identification of the maximum operating pressures for the 
transducer protectors.

    Dated: September 11, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-20999 Filed 9-13-24; 8:45 am]
BILLING CODE 4164-01-P