[Federal Register Volume 89, Number 173 (Friday, September 6, 2024)]
[Rules and Regulations]
[Pages 72715-72717]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-20081]



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 Rules and Regulations
                                                 Federal Register
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 This section of the FEDERAL REGISTER contains regulatory documents 
 having general applicability and legal effect, most of which are keyed 
 to and codified in the Code of Federal Regulations, which is published 
 under 50 titles pursuant to 44 U.S.C. 1510.
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  Federal Register / Vol. 89, No. 173 / Friday, September 6, 2024 / 
Rules and Regulations  

[[Page 72715]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 876

[Docket No. FDA-2024-N-3972]


Medical Devices; Gastroenterology-Urology Devices; Classification 
of the Hemodialyzer With Expanded Solute Removal Profile

AGENCY: Food and Drug Administration, HHS.

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the hemodialyzer with expanded solute removal profile 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 hemodialyzer with expanded solute removal profile'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 6, 2024. The classification 
was applicable on August 28, 2020.

FOR FURTHER INFORMATION CONTACT: Jade Noble, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 2684, Silver Spring, MD 20993-0002, 240-402-5077, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Upon request, FDA has classified the hemodialyzer with expanded 
solute removal profile 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 September 16, 2019, FDA received Baxter Healthcare Corporation's 
request for De Novo classification of the Theranova Dialyzers 
(Theranova 400, Theranova 500). 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 August 28, 2020, FDA issued an order to the requester

[[Page 72716]]

classifying the device into class II. In this final order, FDA is 
codifying the classification of the device by adding 21 CFR 
876.5862.\1\ We have named the generic type of device hemodialyzer with 
expanded solute removal profile, and it is identified as a device 
intended for use as part of an artificial kidney system for the 
treatment of patient with renal failure by performing such therapies as 
hemodialysis, hemofiltration, and hemodiafiltration. A hemodialyzer 
with expanded solute removal profile includes modifications to the 
semipermeable membrane that allows for increased removal or uremic 
retention solutes compared with standard high-flux hemodialyzers of the 
high permeability hemodialysis system classification (Sec.  876.5860 
(21 CFR 876.5860)) including solutes at the upper end of the ``middle'' 
molecular weight range (0.5 kDa to 60 kDa). This device is intended to 
be used with the extracorporeal hemodialysis delivery systems, blood 
tubing sets, blood access devices, and accessories regulated under 21 
CFR 876.5820, 876.5860, 876.5540, and/or 876.5600.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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--Hemodialyzer With Expanded Solute Removal Profile Risks and
                           Mitigation Measures
------------------------------------------------------------------------
    Identified risks to health               Mitigation measures
------------------------------------------------------------------------
Adverse tissue reaction...........  Biocompatibility evaluation,
                                     Pyrogenicity testing, and Non-
                                     clinical performance testing.
Infection or pyrogen reaction.....  Labeling, Pyrogenicity testing,
                                     Sterilization validation, Non-
                                     clinical performance testing, and
                                     Shelf-life testing.
Inadequate or incomplete treatment  Non-clinical performance testing,
                                     Labeling, and Shelf-life testing.
Clearance of essential blood        Non-clinical performance testing,
 substances or medications.          Clinical performance testing,
                                     Labeling, and Shelf-life testing.
Blood loss or blood cell            Non-clinical performance testing,
 destruction.                        Labeling, and Shelf-life testing.
Blood leak into the dialysis fluid  Non-clinical performance testing,
                                     Labeling, and Shelf-life testing.
Air or particle embolism..........  Non-clinical performance testing,
                                     Labeling, and Shelf-life testing.
Fluid imbalance...................  Non-clinical performance testing and
                                     Labeling.
Acid-base imbalance...............  Non-clinical performance 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. 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, 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 CFR 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 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.  876.5862 to read as follows:


Sec.  876.5862  Hemodialyzer with expanded solute removal profile.

    (a) Identification. A hemodialyzer with expanded solute removal 
profile is a device intended for use a part of an artificial kidney 
system for the treatment of patients with renal failure by performing 
such therapies as hemodialysis, hemofiltration, and hemodiafiltration. 
A hemodialyzer with expanded solute removal profile includes 
modifications to the semipermeable membrane that allows for increased 
removal of uremic retention solutes compared with standard high-flux 
hemodialyzers of the high permeability hemodialysis system 
classification (Sec.  876.5860), including solutes at the upper end of 
the ``middle'' molecular weight range (0.5 kDa to 60 kDa). This device 
is intended to be used with the extracorporeal hemodialysis delivery 
systems, blood tubing sets, blood access devices, and accessories 
regulated under Sec. Sec.  876.5820, 876.5860, 876.5540, and/or 
876.5600.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Clinical performance testing under anticipated conditions of 
use must

[[Page 72717]]

evaluate the solute removal profile and document all adverse events.
    (2) 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) Ultrafiltration;
    (ii) Blood and dialysate pressure drop;
    (iii) Clearance rates;
    (iv) Sieving coefficients;
    (v) Mechanical hemolysis;
    (vi) Structural integrity;
    (vii) Blood compartment integrity;
    (viii) Volume of the blood compartment; and
    (ix) Endotoxin retention of the dialyzer membrane.
    (3) The tissue-contacting components of the device must be 
demonstrated to be biocompatible. Biocompatibility evaluation must 
include a chemical analysis of the dialyzer membrane.
    (4) Performance data must demonstrate the sterility of the patient-
contacting components of the device.
    (5) The patient-contacting components of the device must be 
demonstrated to be non-pyrogenic.
    (6) Performance data must support the shelf life of the device by 
demonstrating continued sterility, package integrity, and device 
functionality over the identified shelf life.
    (7) Device labeling must include:
    (i) Shelf life;
    (ii) Storage conditions;
    (iii) Instructions for the preparation of the hemodialyzer, 
initiation of dialysis, troubleshooting, and discontinuance of 
dialysis;
    (iv) Membrane surface area, priming (blood) volume, maximum 
transmembrane pressure, maximum blood flow and maximum dialysate rate 
for each model;
    (v) A non-pyrogenic statement;
    (vi) A summary of the in vitro performance data, provided in 
tabular form; and
    (vii) A summary of the clinical performance data.

    Dated: August 30, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-20081 Filed 9-5-24; 8:45 am]
BILLING CODE 4164-01-P