[Federal Register Volume 87, Number 30 (Monday, February 14, 2022)]
[Rules and Regulations]
[Pages 8190-8192]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-03096]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 870

[Docket No. FDA-2021-N-0999]


Medical Devices; Cardiovascular Devices; Classification of the 
Adjunctive Predictive Cardiovascular Indicator

AGENCY: Food and Drug Administration, Department of Health and Human 
Services (HHS).

ACTION: Final amendment; final order.

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SUMMARY: The Food and Drug Administration (FDA or we) is classifying 
the adjunctive predictive cardiovascular indicator 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 predictive cardiovascular indicator'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 February 14, 2022. The classification 
was applicable on March 16, 2018.

FOR FURTHER INFORMATION CONTACT: Aneesh Deoras, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 2564, Silver Spring, MD 20993-0002, 240-402-4363, 
<a href="/cdn-cgi/l/email-protection#f0b19e95958398deb4959f829183b0969491de989883de979f86"><span class="__cf_email__" data-cfemail="90d1fef5f5e3f8bed4f5ffe2f1e3d0f6f4f1bef8f8e3bef7ffe6">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the adjunctive predictive 
cardiovascular indicator as class II (special controls), which we have 
determined will provide a reasonable assurance of safety and 
effectiveness. In addition, we believe this action will enhance 
patients' access to beneficial innovation, 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 (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. 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.
    We believe this De Novo classification will enhance patients' 
access to beneficial innovation. When FDA classifies a device into 
class I or II via the De Novo process, the device can

[[Page 8191]]

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 less-burdensome 510(k) 
process, when necessary, to market their device.

II. De Novo Classification

    On September 26, 2016, FDA received Edwards Lifesciences, LLC's 
request for De Novo classification of the Acumen Hypotension Prediction 
Index (HPI) Feature Software. 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 March 16, 2018, 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 
870.2210.\1\ We have named the generic type of device adjunctive 
predictive cardiovascular indicator, and it is identified as a 
prescription device that uses software algorithms to analyze 
cardiovascular vital signs and predict future cardiovascular status or 
events. This 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 Predictive Cardiovascular Indicator Risks and
                           Mitigation Measures
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             Identified risks                    Mitigation measures
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Delayed or incorrect treatment due to       Software verification,
 erroneous device output resulting from      validation, and hazard
 software malfunction or algorithm error.    analysis;
                                            Non-clinical performance
                                             testing;
                                            Clinical performance
                                             testing; and Labeling.
Delayed or incorrect treatment due to user  Usability assessment, and
 misinterpretation or overreliance on        Labeling.
 indicator.
------------------------------------------------------------------------

    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.
    At the time of classification, adjunctive predictive cardiovascular 
indicators 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 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 the guidance document ``De Novo Classification 
Process (Evaluation of Automatic Class III Designation)'' 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.  870.2210 to subpart C to read as follows:


Sec.  870.2210  Adjunctive predictive cardiovascular indicator.

    (a) Identification. The adjunctive predictive cardiovascular 
indicator is a prescription device that uses software algorithms to 
analyze cardiovascular

[[Page 8192]]

vital signs and predict future cardiovascular status or events. This 
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) 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 impact of all applicable sensor 
acquisition hardware characteristics and associated hardware 
specifications;
    (iii) A description of sensor data quality control measures;
    (iv) A description of all mitigations for user error or failure of 
any subsystem components (including signal detection, signal analysis, 
data display, and storage) on output accuracy;
    (v) A description of the expected time to patient status or 
clinical event for all expected outputs, accounting for differences in 
patient condition and environment; and
    (vi) The sensitivity, specificity, positive predictive value, and 
negative predictive value in both percentage and number form.
    (2) A scientific justification for the validity of the predictive 
cardiovascular indicator algorithm(s) must be provided. This 
justification must include verification of the algorithm calculations 
and validation using an independent data set.
    (3) A human factors and usability engineering assessment must be 
provided that evaluates the risk of misinterpretation of device output.
    (4) A clinical data assessment must be provided. This assessment 
must fulfill the following:
    (i) The assessment must include a summary of the clinical data 
used, including source, patient demographics, and any techniques used 
for annotating and separating the data.
    (ii) The clinical data must be representative of the intended use 
population for the device. Any selection criteria or sample limitations 
must be fully described and justified.
    (iii) The assessment must demonstrate output consistency using the 
expected range of data sources and data quality encountered in the 
intended use population and environment.
    (iv) The assessment must evaluate how the device output correlates 
with the predicted event or status.
    (5) Labeling must include:
    (i) A description of what the device measures and outputs to the 
user;
    (ii) Warnings identifying sensor acquisition factors that may 
impact measurement results;
    (iii) Guidance for interpretation of the measurements, including a 
statement that the output is adjunctive to other physical vital sign 
parameters and patient information;
    (iv) A specific time or a range of times before the predicted 
patient status or clinical event occurs, accounting for differences in 
patient condition and environment;
    (v) Key assumptions made during calculation of the output;
    (vi) The type(s) of sensor data used, including specification of 
compatible sensors for data acquisition;
    (vii) The expected performance of the device for all intended use 
populations and environments; and
    (viii) Relevant characteristics of the patients studied in the 
clinical validation (including age, gender, race or ethnicity, and 
patient condition) and a summary of validation results.

    Dated: February 7, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-03096 Filed 2-11-22; 8:45 am]
BILLING CODE 4164-01-P


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