[Federal Register Volume 89, Number 172 (Thursday, September 5, 2024)]
[Rules and Regulations]
[Pages 72317-72319]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-19736]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 870

[Docket No. FDA-2024-N-3947]


Medical Devices; Cardiovascular Devices; Classification of the 
Adjunctive Open Loop Fluid Therapy Recommender

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 
classifying the adjunctive open loop fluid therapy recommender 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 adjunctive open loop fluid therapy 
recommender'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 5, 2024. The classification 
was applicable on November 13, 2020.

FOR FURTHER INFORMATION CONTACT: Biniyam Taddese, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 2544, Silver Spring, MD 20993-0002, 240-
402-6570, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the adjunctive open loop fluid 
therapy recommender 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

[[Page 72318]]

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 June 4, 2019, FDA received Edwards Lifesciences' request for De 
Novo classification of the Acumen Assisted Fluid Management (AFM) 
Software Feature. 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 November 13, 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 
870.5600.\1\ We have named the generic type of device adjunctive open 
loop fluid therapy recommender, and it is identified as a prescription 
device that uses software algorithms to analyze cardiovascular vital 
signs and predict a patient's estimated response to fluid therapy. The 
device is intended for adjunctive use with other physical vital sign 
parameters and patient information and is not intended to independently 
direct therapy.
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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 required to 
mitigate these risks in table 1.

    Table 1--Adjunctive Open Loop Fluid Therapy Recommender Risks and
                           Mitigation Measures
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       Identified risks to health              Mitigation measures
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Delay in monitoring or treatment.......  Software verification,
                                          validation, and hazard
                                          analysis; Usability
                                          assessment; and Labeling.
Inappropriate or missed treatment due    Software verification,
 to over-reliance on software             validation, and hazard
 recommendation, which is affected by     analysis; Non-clinical
 algorithm or software error, or          performance testing; Usability
 inaccurate input from sensors or users.  assessment; Clinical
                                          performance testing; and
                                          Labeling.
Fluid overload due to over-reliance on   Software verification,
 software recommendations, which are      validation, and hazard
 affected by algorithm or software        analysis; Non-clinical
 error, or inaccurate input from          performance testing; Usability
 sensors or users.                        assessment; Clinical
                                          performance testing; and
                                          Labeling.
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    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

[[Page 72319]]

premarket notification requirements under section 510(k) of the FD&C 
Act.
    At the time of classification, the adjunctive open loop fluid 
therapy recommender is 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 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 870

    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 
870 is amended as follows:

PART 870--CARDIOVASCULAR DEVICES

0
1. The authority citation for part 870 continues to read as follows:

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


0
2. Add Sec.  870.5600 to subpart F to read as follows:


Sec.  870.5600  Adjunctive open loop fluid therapy recommender

    (a) Identification. The adjunctive open loop fluid therapy 
recommender is a prescription device that uses software algorithms to 
analyze cardiovascular vital signs and predict a patient's estimated 
response to fluid therapy. The device is intended for adjunctive use 
with other physical vital sign parameters and patient information and 
is not intended to independently direct therapy.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Clinical performance testing under anticipated conditions of 
use must fulfill the following:
    (i) A summary of the clinical performance testing must include the 
relevant patient demographics, and any statistical techniques used for 
analyzing the data;
    (ii) Subjects must be representative of the intended use population 
for the device. Any selection criteria or sample limitations must be 
fully described and justified;
    (iii) Testing must demonstrate the recommendation consistency using 
the expected range of data sources and data quality encountered in the 
intended patients, users, and environments; and
    (iv) Testing must evaluate the relationship between algorithm 
recommendations, therapeutic actions, and predicted physiological event 
or status.
    (2) A software description and the results of verification and 
validation testing based on a comprehensive hazard analysis and risk 
assessment must be provided, including:
    (i) A full characterization of the software technical parameters, 
including algorithms;
    (ii) A description of the expected recommendation, accounting for 
differences in patient condition and environment;
    (iii) A description of all mitigations for user error or failure of 
any subsystem components (including signal detection, signal analysis, 
data display, and storage) that affect the device's recommendations;
    (iv) A characterization of algorithm sensitivity to variations in 
user inputs;
    (v) A characterization of sensor accuracy and performance;
    (vi) A description of sensor data quality control measures; and
    (vii) Safeguards to reduce the possibility of fluid overload.
    (3) A scientific justification for the validity of the algorithm(s) 
must be provided. This justification must include non-clinical 
verification and validation of the algorithm calculations and clinical 
validation using an independent data set.
    (4) A human factors and usability engineering assessment must be 
provided.
    (5) Labeling must include:
    (i) A description of what the device measures, how the device 
decides to issue recommendations, and the expected range of frequency 
of recommendations, while accounting for differences in patient 
condition and environment;
    (ii) Detailed information regarding limitations of the device's 
algorithm, and key assumptions made when the device issues a 
recommendation;
    (iii) Warnings identifying sensor acquisition factors that may 
impact measurement results;
    (iv) Warnings identifying user errors that affect the device's 
recommendations;
    (v) Detailed information regarding the expected impact of user 
input errors on the device recommendations;
    (vi) Guidance for interpretation of the device's recommendations, 
including a description that the recommendation is adjunctive to other 
physical vital sign parameters and patient information;
    (vii) Description of the impact of the compatible sensor(s) on the 
device's performance;
    (viii) The expected performance of the device for all intended 
patients, users, and environments;
    (ix) Relevant characteristics of the patients studied in the 
clinical validation (such as age, gender, race or ethnicity, and 
patient condition) and a summary of validation results; and
    (x) Description of the software safeguards that are in place to 
prevent fluid overload, and description of any limitation of the 
software safeguards.

    Dated: August 28, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-19736 Filed 9-4-24; 8:45 am]
BILLING CODE 4164-01-P