2022-28131. Medical Devices; Cardiovascular Devices; Classification of the Adjunctive Hemodynamic Indicator With Decision Point

AGENCY:

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

ACTION:

Final amendment; final order.

SUMMARY:

The Food and Drug Administration (FDA, Agency, or we) is classifying the adjunctive hemodynamic indicator with decision point 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 hemodynamic indicator with decision point'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 December 27, 2022. The classification was applicable on March 1, 2021.

FOR FURTHER INFORMATION CONTACT:

Shawn Forrest, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 2224, Silver Spring, MD 20993-0002, 301-796-5554, [e-mail].

SUPPLEMENTARY INFORMATION:

I. Background

Upon request, FDA has classified the adjunctive hemodynamic indicator with decision point 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, in part 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.

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

II. De Novo Classification

On April 3, 2020, FDA received Fifth Eye Inc.'s request for De Novo classification of the Analytic for Hemodynamic Instability. 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 1, 2021, 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 870.2220.^[1] We have named the generic type of device adjunctive hemodynamic indicator with decision point, and it is identified as a device that identifies and monitors hemodynamic condition(s) of interest and provides notifications at a clinically meaningful decision point. This device is intended to be used adjunctively along with other monitoring and patient information.

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 Hemodynamic Indicator With Decision Point Risks and Mitigation Measures

Identified risks	Mitigation measures
Delayed or incorrect treatment due to erroneous output as a result of software malfunction or algorithm error	Software verification, validation, and hazard analysis; Non-clinical performance testing; Clinical data; and Labeling.
Delayed or incorrect treatment due to user misinterpretation	Usability assessment, 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 21 CFR 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 parts 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

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

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

2. Add § 870.2220 to subpart C to read as follows:

§ 870.2220

Adjunctive hemodynamic indicator with decision point.

(a) Identification. An adjunctive hemodynamic indicator with decision point is a device that identifies and monitors hemodynamic condition(s) of interest and provides notifications at a clinically meaningful decision point. This device is intended to be used adjunctively along with other monitoring and patient information.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) Software description, verification, and validation based on comprehensive hazard analysis and risk assessment must be provided, including:

(i) Full characterization of technical parameters of the software, including algorithm(s);

(ii) Description of the expected impact of all applicable sensor acquisition hardware characteristics on performance and any associated hardware specifications;

(iii) Specification of acceptable incoming sensor data quality control measures;

(iv) Mitigation of impact of user error or failure of any subsystem components (signal detection and analysis, data display, and storage) on output accuracy; and

(v) The sensitivity, specificity, positive predictive value, and negative predictive value in both percentage and number form for clinically meaningful pre-specified time windows consistent with the device output.

(2) Scientific justification for the validity of the hemodynamic indicator algorithm(s) must be provided. Verification of algorithm calculations and validation testing of the algorithm must use an independent data set.

(3) Usability assessment must be provided to demonstrate that risk of misinterpretation of the status indicator is appropriately mitigated.

(4) Clinical data must support the intended use and include 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) Output measure(s) must be compared to an acceptable reference method to demonstrate that the output represents the measure(s) that the device provides in an accurate and reproducible manner;

(iii) The data set must be representative of the intended use population for the device. Any selection criteria or limitations of the samples must be fully described and justified;

(iv) Where continuous measurement variables are displayed, agreement of the output with the reference measure(s) must be assessed across the full measurement range; and

(v) Data must be provided within the clinical validation study or using equivalent datasets to demonstrate the consistency of the output and be representative of the range of data sources and data quality likely to be encountered in the intended use population and relevant use conditions in the intended use environment.

(5) Labeling must include the following:

(i) The type of sensor data used, including specification of compatible sensors for data acquisition, and a clear description of what the device measures and outputs to the user;

(ii) Warnings identifying factors that may impact output results;

(iii) Guidance for interpretation of the outputs, including warning(s) specifying adjunctive use of the measurements;

(iv) Key assumptions made in the calculation and determination of measurements; and

(v) A summary of the clinical validation data, including details of the patient population studied ( e.g., age, gender, race/ethnicity), clinical study protocols, and device performance with confidence intervals for all intended use populations.

Dated: December 21, 2022.

Lauren K. Roth,

Associate Commissioner for Policy.

Footnotes

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.