[Federal Register Volume 87, Number 24 (Friday, February 4, 2022)]
[Rules and Regulations]
[Pages 6422-6425]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-02369]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 880

[Docket No. FDA-2021-N-0998]


Medical Devices; General Hospital and Personal Use Devices; 
Classification of the Alternate Controller Enabled Infusion Pump

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 alternate controller enabled infusion pump 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 alternate controller enabled infusion pump'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: 
    Effective date: This order is effective February 4, 2022.
    Applicability date: The classification was applicable on February 
14, 2019.

FOR FURTHER INFORMATION CONTACT: Ryan Lubert, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3574, Silver Spring, MD 20993-0002, 240-402-6357, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Upon request, FDA has classified the alternate controller enabled 
infusion pump 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 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 October 29, 2018, FDA received Tandem Diabetes Care, Inc.'s 
request for De Novo classification of the t:slim X2

[[Page 6423]]

insulin pump with interoperable technology. 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 generals 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 February 14, 2019, 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 
880.5730.\1\ We have named the generic type of device ``alternate 
controller enabled infusion pump,'' and it is identified as an 
alternate controller enabled infusion pump (ACE pump). The ACE pump is 
a device intended for the infusion of drugs into a patient. The ACE 
pump may include basal and bolus drug delivery at set or variable 
rates. ACE pumps are designed to reliably and securely communicate with 
external devices, such as automated drug dosing systems, to allow drug 
delivery commands to be received, executed, and confirmed. ACE pumps 
are intended to be used both alone and in conjunction with digitally 
connected devices for the purpose of drug delivery.
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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--Alternate Controller Enabled Infusion Pump Risks and Mitigation
                                Measures
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            Identified risk                    Mitigation measures
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Patient harm due to inadequate drug      Basal and bolus drug delivery
 delivery accuracy that leads to over     accuracy validation testing,
 infusion or under infusion of drug.      Device use life reliability
                                          testing, Design mitigations to
                                          prevent cross-channeling.
                                         Validated and traceable risk
                                          control measures for
                                          identified hazards.
Patient harm due to undetected pump      Hazard detection (e.g., drug
 occlusions that pose risk of under       occlusion) validation testing.
 infusion of drug.
Patient harm due to incompatibility      Drug compatibility testing.
 between the drug and the pump that may
 lead to over infusion or under
 infusion of drug, or exposure to
 harmful substances leached from pump
 materials into the infused drug
 solution.
Inability to provide appropriate         Validated communication
 treatment due to loss of communication   specifications, processes, and
 with digitally connected alternate       procedures with digitally
 pump controller devices.                 connected devices.
Commands from the digitally connected    Validated communication
 alternate pump controller devices that   specifications, processes, and
 conflict with existing pump commands     procedures with digitally
 may lead to unintended over or under     connected devices, Validated
 infusion of drug.                        failsafe design features.
Conflicting interfaces resulting in      Validated communication
 over or under delivery.                  specifications, processes, and
                                          procedures with digitally
                                          connected devices, Validated
                                          failsafe design features.
Patient harm due to insecure             Validated communication
 transmission of data.                    specifications, processes, and
                                          procedures with digitally
                                          connected devices.
Patient harm due to inability to         Validated data logging
 determine source of dosing error when    capability.
 used in an integrated system.
Patient harm due to exposure to          Biocompatibility testing,
 hazardous and non-biocompatible          Validation of reprocessing
 materials or pathogens.                  procedures.
Patient harm due to data transmission    Electrical safety,
 interference/electromagnetic             electromagnetic compatibility,
 disturbance.                             and radio frequency wireless
                                          safety testing.
Patient harm due to incorrect use of     Human Factors testing,
 pump, operational, and/or use-related    Transparent pump performance
 errors.                                  descriptions in 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 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

[[Page 6424]]

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 the 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 880

    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 
880 is amended as follows:

PART 880--GENERAL HOSPITAL AND PERSONAL USE DEVICES

0
1. The authority citation for part 880 continues to read as follows:

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

0
2. Add Sec.  880.5730 to subpart F to read as follows:


Sec.  880.5730   Alternate controller enabled infusion pump.

    (a) Identification. An alternate controller enabled infusion pump 
(ACE pump) is a device intended for the infusion of drugs into a 
patient. The ACE pump may include basal and bolus drug delivery at set 
or variable rates. ACE pumps are designed to reliably and securely 
communicate with external devices, such as automated drug dosing 
systems, to allow drug delivery commands to be received, executed, and 
confirmed. ACE pumps are intended to be used both alone and in 
conjunction with digitally connected medical devices for the purpose of 
drug delivery.
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) Design verification and validation must include the following:
    (i) Evidence demonstrating that device infusion delivery accuracy 
conforms to defined user needs and intended uses and is validated to 
support safe use under actual use conditions.
    (A) Design input requirements must include delivery accuracy 
specifications under reasonably foreseeable use conditions, including 
ambient temperature changes, pressure changes (e.g., head-height, 
backpressure, atmospheric), and, as appropriate, different drug fluidic 
properties.
    (B) Test results must demonstrate that the device meets the design 
input requirements for delivery accuracy under use conditions for the 
programmable range of delivery rates and volumes. Testing shall be 
conducted with a statistically valid number of devices to account for 
variation between devices.
    (ii) Validation testing results demonstrating the ability of the 
pump to detect relevant hazards associated with drug delivery and the 
route of administration (e.g., occlusions, air in line, etc.) within a 
clinically relevant timeframe across the range of programmable drug 
delivery rates and volumes. Hazard detection must be appropriate for 
the intended use of the device and testing must validate appropriate 
performance under the conditions of use for the device.
    (iii) Validation testing results demonstrating compatibility with 
drugs that may be used with the pump based on its labeling. Testing 
must include assessment of drug stability under reasonably foreseeable 
use conditions that may affect drug stability (e.g., temperature, light 
exposure, or other factors as needed).
    (iv) The device parts that directly or indirectly contact the 
patient must be demonstrated to be biocompatible. This shall include 
chemical and particulate characterization on the final, finished, fluid 
contacting device components demonstrating that risk of harm from 
device-related residues is reasonably low.
    (v) Evidence verifying and validating that the device is reliable 
over the ACE pump use life, as specified in the design file, in terms 
of all device functions and in terms of pump performance.
    (vi) The device must be designed and tested for electrical safety, 
electromagnetic compatibility, and radio frequency wireless safety and 
availability consistent with patient safety requirements in the 
intended use environment.
    (vii) For any device that is capable of delivering more than one 
drug, the risk of cross-channeling drugs must be adequately mitigated.
    (viii) For any devices intended for multiple patient use, testing 
must demonstrate validation of reprocessing procedures and include 
verification that the device meets all functional and performance 
requirements after reprocessing.
    (2) Design verification and validation activities must include 
appropriate design inputs and design outputs that are essential for the 
proper functioning of the device that have been documented and include 
the following:
    (i) Risk control measures shall be implemented to address device 
system hazards and the design decisions related to how the risk control 
measures impact essential performance shall be documented.
    (ii) A traceability analysis demonstrating that all hazards are 
adequately controlled and that all controls have been validated in the 
final device design.
    (3) The device shall include validated interface specifications for 
digitally connected devices. These interface specifications shall, at a 
minimum, provide for the following:
    (i) Secure authentication (pairing) to external devices.
    (ii) Secure, accurate, and reliable means of data transmission 
between the pump and connected devices.
    (iii) Sharing of necessary state information between the pump and 
any digitally connected alternate controllers (e.g., battery level, 
reservoir level, pump status, error conditions).
    (iv) Ensuring that the pump continues to operate safely when data 
is received in a manner outside the bounds of the parameters specified.
    (v) A detailed process and procedure for sharing the pump interface 
specification with digitally connected devices and for validating the 
correct implementation of that protocol.
    (4) The device must include appropriate measures to ensure that 
safe therapy is maintained when communications with digitally connected 
alternate controller devices is interrupted, lost, or re-established 
after an interruption (e.g., reverting to a pre-programmed, safe drug 
delivery rate). Validation testing results must demonstrate that 
critical events that occur during a loss of communications (e.g., 
commands, device malfunctions, occlusions, etc.) are handled 
appropriately during and after the interruption.
    (5) The device design must ensure that a record of critical events 
is stored and accessible for an adequate period to allow for auditing 
of communications between digitally connected devices and to facilitate 
the sharing of pertinent information with the responsible parties for 
those connected devices. Critical events to be stored by the system 
must, at a minimum, include:
    (i) A record of all drug delivery
    (ii) Commands issued to the pump and pump confirmations
    (iii) Device malfunctions
    (iv) Alarms and alerts and associated acknowledgements
    (v) Connectivity events (e.g., establishment or loss of 
communications)
    (6) Design verification and validation must include results 
obtained through a

[[Page 6425]]

human factors study that demonstrates that an intended user can safely 
use the device for its intended use.
    (7) Device labeling must include the following:
    (i) A prominent statement identifying the drugs that are compatible 
with the device, including the identity and concentration of those 
drugs as appropriate.
    (ii) A description of the minimum and maximum basal rates, minimum 
and maximum bolus volumes, and the increment size for basal and bolus 
delivery, or other similarly applicable information about drug delivery 
parameters.
    (iii) A description of the pump accuracy at minimum, intermediate, 
and maximum bolus delivery volumes and the method(s) used to establish 
bolus delivery accuracy. For each bolus volume, pump accuracy shall be 
described in terms of the number of bolus doses measured to be within a 
given range as compared to the commanded volume. An acceptable accuracy 
description (depending on the drug delivered and bolus volume) may be 
provided as follows for each bolus volume tested, as applicable: Number 
of bolus doses with volume that is <25 percent, 25 percent to <75 
percent, 75 percent to <95 percent, 95 percent to <105 percent, 105 
percent to <125 percent, 125 percent to <175 percent, 175 to 250 
percent, and >250 percent of the commanded amount.
    (iv) A description of the pump accuracy at minimum, intermediate, 
and maximum basal delivery rates and the method(s) used to establish 
basal delivery accuracy. For each basal rate, pump accuracy shall be 
described in terms of the amount of drug delivered after the basal 
delivery was first commanded, without a warmup period, up to various 
time points. The information provided must include typical pump 
performance, as well as worst-case pump performance observed during 
testing in terms of both over-delivery and under-delivery. An 
acceptable accuracy description (depending on the drug delivered) may 
be provided as follows, as applicable: The total volume delivered 1 
hour, 6 hours, and 12 hours after starting delivery for a typical pump 
tested, as well as for the pump that delivered the least and the pump 
that delivered the most at each time point.
    (v) A description of delivery hazard alarm performance, as 
applicable. For occlusion alarms, performance shall be reported at 
minimum, intermediate, and maximum delivery rates and volumes. This 
description must include the specification for the longest time period 
that may elapse before an occlusion alarm is triggered under each 
delivery condition, as well as the typical results observed during 
performance testing of the pumps.
    (vi) For wireless connection enabled devices, a description of the 
wireless quality of service required for proper use of the device.
    (vii) For any infusion pumps intended for multiple patient reuse, 
instructions for safely reprocessing the device between uses.

    Dated: January 26, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-02369 Filed 2-3-22; 8:45 am]
BILLING CODE 4164-01-P