Digital Health Regulation

Online Course

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 Class II
Introduction to FDA Pre-Market Digital
Health Regulation (Part II)

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FDAs Functional Approach for Regulating Sw
• Function: A distinct purpose of a product. Could be the intended use or a subset of the
intended use of the product.
• Examples:
➢ A product with an intended use to analyze data has one function: analysis.
➢ A product with an intended use to store, transfer, and analyze data has three functions: (1)
storage, (2) transfer, and (3) analysis.

• Device function - A function that meets the definition of a device under section 201(h)
of the FD&C Act.
• Device Function Under Review
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FDAs Policy for Regulating Sw

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21st Century Cures Changes FDA ‘s Policy
• Section 3060(a) of the 21st Century Cures Act amended section 520 of the Federal
Food, Drug, and Cosmetic Act (FD&C Act) removing certain software functions
from the definition of device in section 201(h) of the FD&C Act

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Shaping FDAs’ Policy

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FDA Aligns Its Guidance's with 3060
• Mobile Medical Applications (MMA)
• General Wellness: Policy for Low Risk Devices
• Medical Device Data Systems, Medical Image Storage Devices, and Medical
Image Communications Devices (MDDS)
• Off-the-Shelf Software Use in Medical Devices
• Guidance for the Submission of Premarket Notifications for Medical Image
Management Devices

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 Guidance amended with MMA
with software functions that
were excluded shifted to
Appendix A

Proprietary and Confidential 2020 Physio-Logic Ltd. 8

Section 3060 Deregulation Criteria (Non-device CDS)
• NOT intended to acquire, process, or analyze a medical image or a signal from an in vitro diagnostic device

or a pattern or signal from a signal acquisition system (EEG, ECG, CT, medical devices)

• Intended for the purpose of displaying, analyzing, or printing medical information about a patient or other

medical information (symptoms, test results, clinical practice guidelines)

• Intended for the purpose of supporting or providing recommendations to a health care professional about

prevention, diagnosis, or treatment of a disease or condition

• Intended for the purpose of enabling a health care professional to independently review the basis for such

recommendations that such software presents so that it is not the intent that such health care professional

rely primarily on any of such recommendations to make a clinical diagnosis or treatment decision regarding

an individual patient.
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FDA Draft Guidance - Exclusion Criteria 3 & 4

; ;

Proprietary and Confidential

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#1 Example of Non-Device CDS Function
Software that compares patient signs, symptoms, or results with available
practice guidelines (clinical society-based) to recommend condition-specific
diagnostic tests, investigations, or therapy. The practice guidelines are described
as the basis for the recommendation and provided for the HCP to review, such
that the HCP does not rely primarily on the software’s recommendation.

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#1st Example - Does it Meet All 4 Criteria?
Criteria Met?
not intended to acquire, process, or analyze a medical image or a signal from Yes
an in-vitro diagnostic device or a pattern or signal from a signal acquisition
system (1)

Intended for the purpose of displaying, analyzing, or printing medical Yes

information about a patient or other medical information (2)

Intended for the purpose of supporting or providing recommendations (3) Yes

Is the Intended User an HCP? (3,4) Yes

Can the User Independently Review the Basis? (4) Yes

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#2nd Example of Device CDS – Enforcement Discretion
Machine-learning algorithm, for which the logic and inputs are not explained,
that trends and classifies patient-specific data (e.g., blood test results, weight)
to alert HCPs to potential triggers that may be indicative of cholesterol
management issues. At this time, FDA does not intend to enforce compliance
with applicable requirements of the FD&C 559 Act for this Device CDS,
because it is an aggregation of data intended to provide clinical information for
a non-serious situation or condition (i.e., “inform x non-serious”).

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2nd Example - Does it Meet all 4 Criteria?
Criteria Met?
not intended to acquire, process, or analyze a medical Yes
image or a signal from an in-vitro diagnostic device or a
pattern or signal from a signal acquisition system (1)
Intended for the purpose of displaying, analyzing, or Yes
printing medical information about a patient or other
medical information (2)
Intended for the purpose of supporting or providing Yes
recommendations (3)
Is the Intended User an HCP? (3,4) Yes
Can the User Independently Review the Basis? (4) No

Machine-learning algorithm, for which the logic

and inputs are not explained

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3rd Example - Device CDS - Enforcement Discretion
Software that provides information to a patient about the use of a prescription drug that is consistent
with the FDA-required labeling and the patient’s prescription, such as reminding the patient how or when
to take a prescribed drug. Such software does not recommend changes in dose or drug discontinuation
that HCPs do not oversee (unless drug labeling includes such recommendations). This software is
Device CDS, because it is intended for a patient. At this time, FDA does not intend to enforce
compliance with applicable requirements of the FD&C Act for this software function, because it is an
aggregation of data intended to provide clinical information for a non-serious situation or condition (i.e.,
“inform x non-serious”) and because the basis for the recommendation (FDA-required labeling) is
described to the user, so that the software is intended for the patient to be able to independently
evaluate the basis for the software’s recommendations.
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#3rd Example - Does it Meet All 4 Criteria?
Criteria Met?
not intended to acquire, process, or analyze a medical Yes
image or a signal from an in-vitro diagnostic device or a
pattern or signal from a signal acquisition system (1)
Intended for the purpose of displaying, analyzing, or Yes
printing medical information about a patient or other
medical information (2)
Intended for the purpose of supporting or providing Yes
recommendations (3)
Is the Intended User an HCP? (3,4) No
Can the User Independently Review the Basis? (4) Yes

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#4th Example - Device CDS – Oversight Focus
Machine-learning algorithm, for which the logic and inputs are not explained, that categorizes likely
symptoms of seasonal influenza for each flu season based on location and current electronic health
records of patients diagnosed or suspected to have influenza to assist HCPs in differentiating between
common flu symptoms and other illnesses (e.g., common cold) in a particular season. This software is a
Device CDS function, because the HCP is not expected to be able to independently evaluate the basis
for the software’s recommendations. FDA intends to focus its regulatory oversight on this software,
because it is intended to inform clinical management for a serious situation or condition.
Note: If the HCP could evaluate the basis for the software’s recommendations, because the logic and
inputs for the machine-learning algorithm and data inputs used for the algorithm were explained and
available to the HCP, then this software would be considered Non-Device CDS (Section VII.A).
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Does it meet all the Four Criteria?
Criteria Met?
not intended to acquire, process, or analyze a medical Yes
image or a signal from an in-vitro diagnostic device or a
pattern or signal from a signal acquisition system (1)
Intended for the purpose of displaying, analyzing, or Yes
printing medical information about a patient or other
medical information (2)
Intended for the purpose of supporting or providing Yes
recommendations (3)
Is the Intended User an HCP? (3,4) Yes
Can the User Independently Review the Basis? (4) No

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November 2020 Report on Non-Device Sw
• Section 3060(b) requires that HHS publish a report every two years
• Examine the risks and benefits to health associated with the software
functions described in section 520(o)(1) of the FD&C Act

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FDA’s Policy - Multiple Software Functions
• Applies to the regulation of products containing at least one device
function and at least one non-device software function

“In the case of a product with multiple functions that contains:

• (A) at least one software function that meets the criteria under paragraph (1) or that otherwise does not meet the definition of
device under section 201(h); and
• (B) at least one function that does not meet the criteria under paragraph (1) and that otherwise meets the definition of a device
under section 201(h), the Secretary shall not regulate the software function of such product described in subparagraph (A) as a
device.
Notwithstanding the preceding sentence, when assessing the safety and effectiveness of the device
function or functions of such product described in subparagraph (B), the Secretary may assess the
impact that the software function or functions described in subparagraph (A) have on such device
function or functions” (Section 520(o)(2) of the FD&C Act (21 U.S.C. 360j(o)(2))

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FDA’s Premarket Review Policy of Multiple Function Product
• “Other functions” are not the subject of the FDA’s review simply because they are
part of a multiple function device product.
• However, the FDA may assess the impact of “other functions” when assessing
the safety and effectiveness of the device functions-under-review of a multiple
function device product

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tTitle

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tTitle

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The Decision-Making Process
• Medical device?
• Search existing classification
• Determine applicable pre-market regulatory requirements
tTitle

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Product Classification Database

tTitle

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tTitle

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General Controls
• Apply to all three classes of medical devices; however, they are the only level of controls that
apply to Class I devices.

1.Adulteration;
2.Misbranding; tTitle
3.Device registration and listing;
4.Premarket notification;
5.Banned devices;
6.Notification and repair, replacement, and refund;
7.Records and reports;
8.Restricted devices; and
9.Good Manufacturing Practices

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Special Controls
• Apply to Class II devices to assure the safety and effectiveness of the device
• Vary from product to product can include:
➢ Performance standards
➢ Post-market surveillance
tTitle
➢ Special labelling requirements
➢ Premarket data requirements
➢ Guidelines

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Premarket Notification - Section 510(k) of Federal FD&C Act
• 510(k) submitted before marketing a device, the submitter must receive an order, in the form of a
letter, from FDA which finds the device to be substantially equivalent (SE) and states that the device
can be marketed in the U.S. This order "clears" the device for commercial distribution.

tTitle
• A 510(k) will demonstrate that the device to be marketed is at least as safe and effective, that is,
substantially equivalent, to a legally marketed device, Predicate device, that is not subject to PMA.
• It is a marketing clearance application - 510(k)s are “cleared”

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When is a 510(k) Required?
• Introducing a device into commercial distribution (marketing) for the first time.
• A change or modification of a legally marketed device and that change could significantly affect its
safety or effectiveness.

tTitle

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Substantial Equivalence
• Device is substantially equivalent if, in comparison to a predicate it:
• has the same intended use as the predicate; and has the same technological characteristics
as the predicate; or

tTitle
• has the same intended use as the predicate; and has different technological characteristics
and the information submitted to FDA: does not raise new questions of safety and
effectiveness; and demonstrates that the device is at least as safe and effective as the
predicate-legally marketed device

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Impact of Functionality on 510(k) Strategy

tTitle

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 SE Decision Making Process
• Is the predicate device legally marketed?
• Do the devices have the same intended use?
• Do the devices have the same technological characteristics?
tTitle
• Do the different technological characteristics of the devices raise different questions of safety and
effectiveness?
• Two Parts:
a) Are the methods acceptable?
b) Do the data demonstrate substantial equivalence?

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510(k) Performance Testing
• Bench, Animal, or Clinical
• Necessary performance tests depend on the complexity of
• the device and its intended use and indications
• Consider FDA Guidance Documents tTitle
• Consider comparative testing to demonstrate substantial equivalence
• Include: test methods, acceptance criteria and test results for review

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tTitle
Informal

Clock stops
180 days

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Pre-sub
• A formal written request from an applicant for feedback from FDA provided in the form of:
➢ a formal written response or
➢ a meeting or teleconference in which the feedback is documented in meeting minutes
tTitle
• When FDA’s feedback on specific questions is necessary to guide product development and/or
application preparation (i.e., prior to intended submission of an IDE or marketing
application)
• Request must include specific questions regarding review issues relevant to a planned IDE or
marketing application (e.g., questions regarding pre-clinical and clinical testing protocols or data
requirements).

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CONTACT
Gadi Ginot
+972 50 8317449

GADI@PHYSIO-LOGIC.CO.IL
WWW.PHYSIO-LOGIC.CO.IL

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