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Webinar Topics

Early Feasibility Study (EFS) Investigational 

Device Exemptions

A Valuable Regulatory Tool for Medical Device 

Development

New FDA Draft Guidance

“FDA Categorization of Investigational Device 

Exemption (IDE) Devices to Assist the Centers 

for Medicare and Medicaid Services (CMS) 

with Coverage Decisions”

2 
Carla M. Wiese

Policy Analyst for the Early Feasibility Program

Office of Device Evaluation

Center for Devices and Radiological Health

Early Feasibility Study (EFS) 

Investigational Device 

Exemptions

 

A Valuable Regulatory Tool for 

Medical Device Development

3 
Agenda

• What an Early Feasibility Study is 

How it can benefit sponsors

• Key Elements of the EFS Guidance Document 

What does doing the “right testing at the right time” mean? 

• What a successful pathway to an EFS IDE approval looks 

like

• Common questions/tips

• Helpful links

4 
What an EFS IDE is

IDE - Investigational Device Exemption

• An IDE submission allows an investigational device to be used in a 

clinical study in order to collect safety and effectiveness data. 

EFS IDE - A standard IDE except...

• There are significant unknowns about how the device will perform

 Device is generally early in development or 

 Device has a new intended use

• Small number of subjects in the clinical investigation

 Initial evaluation of safety and/or effectiveness

 Proof of concept

* EFS is an 

informal 

designation 5 
How Conducting an EFS in 

the US Benefit Sponsors

Permits A More Efficient Pathway to US Commercialization

• FDA feedback early in product development may...

 Help the sponsor improve their development strategy and 

reduce the chances that unnecessary testing is completed.

 Increase the predictability of data requirements for a 

future study or commercialization needs. 

• Data collection in the US patient population may be easier to 

leverage to support later studies.

6 
How Conducting an EFS in the 

US Benefit Sponsors

Additional Benefits

• Assurance of patient protection under the IDE 

regulations 

• Have better access to technical experts and Key 

Opinion Leaders in the US

• Logistical advantage and proximity to US innovation 

centers 

• Allows for device iteration, including during the EFS 

study, which may result in high quality products

7 
Some Types of IDE studies

EFS Feasibility Pivotal

Small number of patients, < 15 

(approximate)

More patients than EFS Number of patients 

determined by statistical 

needs

 There are fundamental questions 

about device performance & safety 

 Device design may change.

 There may be limited nonclinical 

data available

Enough is known about 

the design, procedure or 

indication to justify 

clinical studies with more 

patients than EFS

Device is the final design 

and there is significant 

information known about 

the design, procedure and 

indication.

Purpose of study can be...

 to demonstrate a proof of concept

 determine what design or procedure 

changes could optimize the therapy

 And more...

Purpose of study can be...

 capture preliminary 

safety and 

effectiveness 

information and to 

adequately plan an 

appropriate pivotal 

study

Purpose of study can be...

 Demonstrate safety and 

effectiveness to support 

a marketing application

*note: not all of these phases are required for market approval

8 
Key Elements of the EFS 

Guidance

• Doing the “Right Testing at the Right Time”

 Comprehensive testing during early phases of device 

development may add cost without significant return (some 

testing may be deferred) 

 EFS is not to take the place of informative nonclinical testing 

• Unknowns and risk can be addressed by...

 Using clinical mitigations to provide patients with extra 

protection 

 The use of more frequent/detailed reporting

 Informed consent recommendations

9 
Key Elements of the EFS 

Guidance continued...

• Allows for timely device and clinical protocol 

changes 

 More changes can be made during the study through 5-day 

notification rather than FDA approval

 Contingent approval: approval of anticipated or proposed 

device changes can be obtained contingent on the completion 

of an agreed upon test plan and acceptance criteria

• Recommendations on pre-submission contents is 

provided

 An example risk assessment method is provided 10
What Does Doing the 

“Right Testing at the 

Right Time” Mean?

11
• Different test methods for small batches

 E.g. – Single lot Ethylene Oxide sterilization versus full Ethylene Oxide 

sterility validation

• Some test data could be leveraged. Examples...

 Some biocompatibility endpoints could be leveraged from an animal 

study if one is conducted.

 Some test data could be leveraged from a previous version of the 

device. 

FDA Recognizes the Value of 

Alternative Nonclinical Test 

Methods and Leveraging Data

12
Risk presented to patient (after clinical mitigations are 

considered) versus potential benefit.

• Is the probability of failure or patient harm understood and can this 

be mitigated? 

(e.g. risk of irritation to a material, possible mitigation = timely 

clinical assessments/interventions)

• Can a potential failure/harm be detected and mitigated? (e.g. risk of 

patient pain, possible mitigation = titrating therapy, ability to revert to 

standard of care)

FDA Recognizes That Some 

Nonclinical Testing Could be 

Deferred

13
• Can the clinical study be controlled to further protect 

patients? 

(e.g. limiting use of a device to the hospital instead of the 

home, where it may eventually be used, may change EMC 

testing needs)

• Is the clinical situation emergent and/or are there are no 

alternatives available? 

(e.g. long term durability testing deferred due to the 

criticality of short term benefit) 

Considerations for Deferral of 

Nonclinical Testing Continued...

14
Considerations for Deferral of 

Nonclinical Testing Continued...

• Will the nonclinical test data provide valuable information on how 

the device will perform in the proposed clinical study? 

(E.g. If test data will not inform the clinical study today but will 

characterize the device and will be important for developing 

specifications prior to a marketing approval, data could be gathered in 

parallel with the clinical study and submission of this data to FDA 

could be deferred.)

Note: If the clinical situation is non-emergent and there are therapeutic 

alternatives, the amount of nonclinical testing may need to be comparable 

to other available therapies.

15
Understanding and Explaining 

the Utility of the Nonclinical 

Tests is Important

• If it is an animal study, which device performance data will inform 

the human clinical study?

• Is the test conservative or not?

• Is the test validated? 

• Does the test have historical value?

• Will the data be used for quality control in the future?

 What will the data tell us? Are there options to protect patients 

when nonclinical testing has limited utility? 16
What a Successful Pathway 

to an EFS IDE Approval 

Looks Like

17
Recommendation #1

Sponsor is Well Prepared

• Sponsor knows what information they want to learn 

from the EFS

• Sponsor uses their resources: FDA guidance 

documents and recognized standards, CDRH Learn 

Modules, external experts

• Sponsor has reached out to an EFS representative to 

discuss their submission strategy

18
Recommendation #2

Submissions are well planned

• Informational meeting may be useful, for novel ideas in 

particular

• Initial pre-sub includes all the information described in the 

guidance (Goal: agree upon the risks and test plan)

• Additional pre-subs as needed (ex: if test requirements are 

uncertain/discuss clinical protocol)

• IDE submission contains all required information

19
Note: 

The use of pre-submissions to discuss the test plan and the 

clinical protocol... 

• Can be useful when the nonclinical testing needed is unclear, 

can be used to agree upon the test plan that will support an IDE 

submission with FDA

• May avoid the need to re-do expensive and time consuming 

testing

• May help determine appropriate clinical mitigations, reporting 

requirements and the patient population for whom the benefitrisk profile supports inclusion into the EFS

Highly Recommended 20
Submissions are high quality

• Contain enough information for FDA to provide 

valuable feedback.

 Reference the EFS Guidance and IDE required elements (links are 

located at the end of this presentation)

• Contents are well organized and navigable.

• High quality scientific discussion and evidence is 

provided. 

Recommendation #3

21
Recommendation #4

The sponsor is able to describe why additional nonclinical 

testing will not be informative and that a human clinical study 

is appropriate.

• There is a clear identification of potential risks & how they will 

be addressed

 Nonclinical testing, clinical mitigations, reporting

• Explanation is provided for why the plan is sufficient: 

 Explain what can/cannot be learned from bench tests/animal models and 

why any information to be leveraged is directly applicable to the study

• List which tests will be done to support the EFS versus which 

will be done to support a later study if applicable

22
Common Questions

23
Question #1

Is EFS for Novel Technology Only?

NO: EFS are just small studies used to gather information when 

there are significant unknowns.

EFS May be Used for a Variety of Reasons

• To study a novel device

• To study an expanded access (e.g. for devices used for compassionate 

use or emergency use cases) 

• To support new indications for a marketed device

24
When is a good time to talk to 

FDA about an EFS?

After...

• You have established your general device design, intended use 

and what information you would like to gather from the EFS

Before...

• Expensive and time consuming nonclinical testing has been 

started

 It is recommended to communicate with FDA informally 

throughout the development process to optimize submission 

efficiency 

25
The guidance document contains an 

optional risk assessment template. 

When/How is this used?

Called a “Device Evaluation Strategy (DES) Table”

• Can be helpful if you do not currently use another 

method for assessing risk (e.g. ISO standard).

• Should contain a high level description of risks, not as 

detailed as an FMEA. More from a clinician’s perspective.

• Intent is to link primary risks together with risk 

mitigations.

26
Tips

27
1. If you are iterating your device, keep samples of previous 

generations.

• They may be useful in the future for establishing 

biocompatibility equivalence, for example.

2. Keep clear and detailed records of the testing completed 

with each device iteration.

• Ensure that a detailed description of the device iteration is 

included in protocols.

• This may help leverage information in future submissions.

Tips

28
3. If you would like to use test results that were not obtained per 

standard FDA recommendations, we recommend that you 

provide an explanation for why the data is sufficient.

• E.g. If your animal study is intended to support device safety and 

deviates from 21 CFR 58 (Good Laboratory Practices) we 

recommend that you tabulate each part of the regulations, list how 

the study deviates and how you will ensure data integrity and 

minimize bias.

Tips

29

Note: Only animal studies intended to support device safety need to address 21 CFR 58. 

Reference FDA guidance “The Applicability of Good Laboratory Practice in Premarket Device 

Submissions: Questions & Answers” for further information.
Tips

If your animal study is intended to support device safety and 

deviates from GLP, FDA recommends that it include...

• Protocol signed/dated by all key parties prior to initiation of the study

Including objectives, acceptance criteria, and detailed procedures

Include IACUC protocol with amendments 

Clear description of the animals enrolled in the study and their 

final designation

• Quality measures and an explanation of how data integrity is ensured. 

QA personnel to monitor the study - may be in the same company but 

organizationally separate and independent of those engaged in the 

study. 

• Animal facility licenses, accreditations, and assurances

30 Note: Reference FDA guidance on EFS and the draft guidance “General Considerations for 

Animal Studies for Medical Devices” for further information.
4. Understand that FDA feedback is not a directive. It is 

information for your consideration and to assist with 

further discussion.

Tips

31
Helpful Links

• Early Feasibility Study Guidance

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceD

ocuments/UCM279103.pdf2 

• EFS CDRH Learn Modules

http://www.accessdata.fda.gov/cdrh_docs/presentations/EFS/story.html 

• Pre-Submission Guidance 

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDo

cuments/UCM311176.pdf 

• IDE Submission Information

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevi

ce/InvestigationalDeviceExemptionIDE/ucm046706.htm#reqele

• Design Controls Guidance

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/u

cm070627.htm

• Electronic Submissions Guidance

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceD

ocuments/UCM313794.pdf 

 

32
Carla Wiese Carla.Wiese@fda.hhs.gov

Andrew Farb, M.D. Andrew.Farb@fda.hhs.gov

Joel Anderson, Ph.D. Joel.Anderson@fda.hhs.gov

Joy Samuels-Reid, M.D. (pediatric 

specialist) Joy.Sameuls-Reid@fda.hhs.gov

Hiren Mistry (ICDB, PIDB, VSDB) Hiren.Mistry@fda.hhs.gov

Rob Kazmierski (CDDB, CEDB, IEDB) Robert.Kazmierski@fda.hhs.gov

Katie Wallon (CSDB, SHDB) Katherine.Wallon@fda.hhs.gov

Erin Keegan Erin.Keegan@fda.hhs.gov

Devjani Saha, Ph.D. Devjani.Saha@fda.hhs.gov

Jemin Dedania Jemin.Dedania@fda.hhs.gov

Charles Warner Charles.Warner@fda.hhs.gov

Krutanjali Shah Krutanjali.Shah@fda.hhs.gov

Tieuvi Nguyen, Ph.D. Tieuvi.Nguyen@fda.hhs.gov

Angelo Green, Ph.D., DABT Angelo.Green@fda.hhs.gov

Andrew Fu, Ph.D. Andrew.Fu@fda.hhs.gov

David Birsen David.Birsen@fda.hhs.gov

Thomas Claiborne, Ph.D. (Ted) Thomas.Claiborne@fda.hhs.gov

Maureen Dreher, Ph.D. Maureen.Dreher@fda.hhs.gov

Christopher Scully, Ph.D. Christopher.Scully@fda.hhs.gov

EFS Representatives

33
Questions? 

Want to share your EFS experience & thoughts for 

Improvement? Contact Carla Wiese, Policy Analyst for the 

Early Feasibility Program - 301-796-0627 or 

Carla.wiese@fda.hhs.gov

General questions about early feasibility studies? Contact 

CDRH's Division of Industry and Consumer Education (DICE) 

at dice@fda.hhs.gov, 1-800-638-2041, or 301-796-7100 

Slide Presentation, Transcript and Webinar Recording will be 

available at:

http://www.fda.gov/training/cdrhlearn

Under “How to Study and Market Your Device” Heading

34
“FDA Categorization of Investigational Device Exemption 

(IDE) Devices to Assist the Centers for Medicare and Medicaid 

Services (CMS) with Coverage Decisions”

Carla M. Wiese

Policy Analyst for the Early Feasibility Program

Office of Device Evaluation

Center for Devices and Radiological Health 35

New FDA Draft Guidance
Agenda

• Why IDEs are conducted and why they are 

categorized

• Why there is new guidance related to CMS 

categorization

• What the changes are between the old policy and 

the new policy

• Considerations when changing from Category A 

to B

• How a category designation may affect coverage 

in a study

• Other factors that may impact coverage 36
Why Are IDE Studies Conducted?

An investigational device exemption (IDE) allows an 

investigational device to be used in a clinical study in 

order to collect safety and effectiveness data. 

• FDA approval of an IDE submission indicates FDA has 

determined: 

 The sponsor has provided adequate data to support initiation of 

the study.

 There are no subject protection concerns to preclude initiation of 

the study after IRB approval.

 Benefit-risk profile for the study is favorable.

37 Reference: 21 CFR 812
Generally, an IDE study is conducted to answer 

outstanding questions about safety and effectiveness.

However, the extent to which initial questions of 

safety and effectiveness are already addressed depends 

on many factors.

38

Why Are IDE studies Conducted?

Continued...
Why IDEs Are Categorized

 An Interagency Agreement (IA) between CMS 

and the FDA was made in 1995 to support CMS’ 

decision making for coverage. As part of this 

agreement, FDA assigns a device with an FDA 

approved IDE to one of two categories: 

– Experimental/Investigational (Category A) 

– Non-experimental/Investigational (Category B)

 This agreement allowed for expanded coverage 

to include some investigational devices.

39
Why IDEs Are Categorized

The category designation was to be based on the 

extent to which “initial questions of safety and 

effectiveness” have been answered.

Specific criteria were defined in the 1995 IA for 

how FDA would determine the appropriate 

category. 

The categorization has been used by CMS as part 

of its determination of whether or not items and 

services meet the requirements for Medicare 

coverage. 40
Why There is New Guidance 

Related to CMS Categorization

1) The previous FDA policy regarding 

categorization did not adequately articulate 

criteria that are relevant to certain studies 

such as feasibility studies.

2) The previous policy did not contain sufficient 

guidance regarding how a category designation 

may change from A to B.

3) The previous criteria did not consider all 

regulatory pathways. (e.g. de novo submission)

41
Additional Factors

CMS changed from local Medicare Administrative 

Contractor review and approval of IDE studies to a 

centralized review and approval of IDE studies 

effective January 1, 2015. 

Interactions between FDA and CMS since that time 

have highlighted a need for changes to 

categorization in order to improve consistency. 

42
1995 Interagency Agreement Draft Guidance

Detailed criteria were used to designate

an IDE device category.

Criteria have been simplified to ensure that 

devices fall into the correct category.

Limited or no visibility to how a 

category change may occur as 

knowledge is gained.

Draft guidance provides an explanation of 

how a category change may occur.

No examples provided. Examples provided.

FDA review team makes the category 

designation.

Unchanged

Category designation is to be based on 

the degree to which initial questions of 

safety and effectiveness are resolved.

Unchanged

The categorization will then be used by 

CMS as part of its determination of 

whether or not items and services will 

be covered. 

Unchanged

43

Changes The same
Draft Guidance

Draft guidance is proposed documentation not yet 

ready for implementation.

Issuance Date: June 1, 2016

Comment period closes: August 1, 2016

www.regulations.gov 

docket # FDA-2016-D-1159 

44
Regulatory Context: 

Category A

Category A: Experimental 

42 CFR 405.201(b): 

“...a device for which ‘absolute risk’ of the device types has not 

been established (that is, initial questions of safety and 

effectiveness have not been resolved) and the FDA is unsure 

whether the device type can be safe and effective.”

45
Proposed Criteria:

Category A

FDA intends to consider a device to be in Category A if 

one or more of the following criteria are met:

1. No PMA approval, 510(k) clearance or de novo 

request has been granted for the proposed device 

or similar devices, and non-clinical and/or clinical 

data on the proposed device do not resolve initial 

questions of safety and effectiveness. 

46
2. The proposed device has different 

characteristics compared to a legally 

marketed device; and information related to 

the marketed device does not resolve initial 

questions of safety and effectiveness for the 

proposed device. Available non-clinical 

and/or clinical data on the proposed device 

also do not resolve these questions. 

47

Proposed Criteria:

Category A
3. The proposed device is being studied for a 

new indication or new intended use for 

which information from the proposed or 

similar device related to the previous 

indication does not resolve initial questions 

of safety and effectiveness. Available nonclinical and/or clinical data on the proposed 

device relative to the new indication or 

intended use also do not resolve these 

questions. 48

Proposed Criteria: 

Category A
A device is completely novel and has no, or 

limited, previous human use and there are 

initial questions of safety and effectiveness. 

There is adequate non-clinical information to 

support initiation of an early feasibility study 

that will provide data to inform potential 

device design or procedural improvements. 

49

Category A Example
An already approved or cleared device is being 

evaluated for a new intended use or indication wherein 

the device will be placed in a different anatomical 

location. 

The device’s technology is unchanged from what was 

initially approved; however, it is uncertain as to 

whether the device can be safely placed in the new 

anatomical location and whether the device can also be 

effective in the new anatomical location. Therefore, 

there are inadequate data to resolve the initial 

questions of safety and effectiveness relative to the 

new intended use or indication. 50

Category A Example
Category B: Nonexperimental/Investigational 

42 CFR 405.201(b)

“...a device for which the incremental risk is the 

primary risk in question (that is, initial questions of 

safety and effectiveness of that device type have 

been resolved), or it is known that the device type 

can be safe and effective because, for example, 

other manufacturers have obtained FDA premarket 

approval or clearance for that device type.” 

51

Regulatory Context:

Category B
Proposed Criteria: 

Category B

FDA intends to consider a device to be in Category B if one 

or more of the following criteria are met:

1. No PMA approval, 510(k) clearance or de novo request 

has been granted for the proposed device or similar 

devices; however, available clinical data (e.g., 

feasibility study data) and/or non-clinical data for the 

proposed device or a similar device resolve the initial 

questions of safety and effectiveness. 

52
2. The proposed device has similar 

characteristics compared to a legally 

marketed device, and information related to 

the marketed device resolves the initial 

questions of safety and effectiveness for the 

proposed device. Additional non-clinical 

and/or clinical data on the proposed device 

may have been used in conjunction with the 

leveraged information to resolve these 

questions. 53

Proposed Criteria:

Category B
3. The proposed device is being studied for a 

new indication or new intended use; 

however, information from the proposed or 

similar device related to the previous 

indication resolves the initial questions of 

safety and effectiveness. Additional nonclinical and/or clinical data on the proposed 

device may have been used in conjunction 

with the leveraged information to resolve 

these questions. 54

Proposed Criteria:

Category B
Adequate data have been gathered from nonclinical testing and the clinical results of a 

feasibility study such that initial questions of 

safety and effectiveness have been resolved. A 

pivotal study will be initiated to provide the 

primary clinical evidence for the safety and 

effectiveness of the device in support of a 

future marketing application. 

55

Category B Example
An approved device will be evaluated for a new 

indication. 

Data exist on the approved device for another 

similar indication, and non-clinical data have 

also been supplied such that the initial 

questions of safety and effectiveness related to 

the new indication have been resolved. The 

new study to be conducted will provide further 

data regarding device performance for this new 

indication. 

56

Category B Example
When Are IDEs Categorized?

The FDA review team will make a categorization 

decision at the time of the first approval (full or 

conditional) of an IDE study. 

A categorization change will be considered for study 

expansion or upon a request for re-designation.

The category is included in FDA’s approval letter for 

the IDE.

57
Information That May Support 

a Category Change

• Nonclinical test data

• External data on the technology (e.g. data from other 

similar devices)

• Preliminary clinical data on the device

58
Example of a Change From 

Category A to B

Adequate data have been gathered on a device from 

non-clinical testing, the completion of an early 

feasibility study within the United States (US), as well 

as a small non-US clinical study such that initial 

questions of safety and effectiveness have been 

resolved. Additional data are needed to help inform a 

pivotal study design; therefore, a traditional feasibility 

study will be initiated. 

Although the early feasibility study was originally 

designated as Category A, adequate data as described 

above have since been gathered to support a change to 

Category B for the traditional feasibility study. 59
How a Categorization Designation 

May Affect Coverage in a Study

• If the study is designated Category A: the 

device may not be covered but routine care 

and services may be covered.

• If the study is designated Category B: then 

the device and routine care and services may 

be covered.

60
Other Factors That May Affect 

Coverage in a Study

• Has a previous national coverage decision been 

made for the device type and/or procedure?

 A coverage decision may supersede the category designation.

• Will the device be adjunctive to a procedure in 

which a coverage decision has been made?

 A coverage decision may supersede the category designation.

• Is the device relevant to the Medicare population?

• Have other CMS criteria been met (reference the 

CMS website link at the end of this presentation)?

• Others... 61
Links

Link to the FDA Draft Guidance

“FDA Categorization of Investigational Device Exemption (IDE) 

Devices to Assist the Centers for Medicare and Medicaid Services 

(CMS) with Coverage Decisions” 

• http://www.fda.gov/downloads/MedicalDevices/DeviceRegulatio

nandGuidance/GuidanceDocuments/ucm504091.pdf

Link to a CMS website 

“Medicare Coverage Related to Investigational Device Exemption 

(IDE) Studies”

• https://www.cms.gov/medicare/coverage/IDE/index.html

62
Questions? 

Contact CDRH's Division of Industry and Consumer Education 

(DICE) at dice@fda.hhs.gov, 1-800-638-2041, or 301-796-

7100 

Slide Presentation, Transcript and Webinar Recording will be 

available at:

http://www.fda.gov/training/cdrhlearn

Under “How to Study and Market Your Device” Heading

63