IDE Basics

November 4, 2014

Soma Kalb

Director (Acting)

Investigational Device Exemption (IDE) Program

Office of Device Evaluation

Center for Devices and Radiological Health

U.S. Food and Drug Administration
Learning Objectives

• To understand the regulatory context of device clinical 

investigations

• To understand when an IDE is required

• To understand the IDE application process and FDA 

decisions on those applications

• To understand the roles of key players in IDE studies

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Overview

• Regulatory authority and framework for device 

clinical investigations

• Discussion of studies requiring an IDE 

• The IDE application and FDA decisions

• Office-level review of IDE application-specific issues

• Roles of sponsors, investigators, and IRBs
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Section 520(g) of the FD&C Act

Exemption for Devices for Investigational Use

“It is the purpose of this subsection to encourage, to the 

extent consistent with the protection of the public 

health and safety and with ethical standards, the 

discovery and development of useful devices

intended for human use and to that end to maintain 

optimum freedom for scientific investigators in their 

pursuit of that purpose.”
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Law (FD&C Act) Þ Regulation

Several parts of the Code of Federal Regulations (CFR) pertain to 

IDEs:

• 21 CFR 812 Investigational Device Exemptions

• 21 CFR 50 Protection for Human Subjects, 

Informed Consent (IC) Regulation

• 21 CFR 54 Financial Disclosure of Investigators

• 21 CFR 56 Institutional Review Boards (IRBs) 

As of July 9, 2012 - Section 601 of FDASIA - FDA Safety and 

Innovation Act
Investigational Device Exemption

• 21 CFR 812.1:

“An approved investigational device exemption 

(IDE) permits a device that otherwise would be required 

to comply with a performance standard or to have 

premarket approval to be shipped lawfully for the 

purpose of conducting investigations of that device.”

• An IDE is a regulatory submission that permits clinical 

investigation of devices.

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Approved IDEs are Exempt from 

Regulations Pertaining to:

Good Manufacturing 

Practices (GMPs) except 

Design Controls

Color Additive requirements

• Banned Devices 

• Restricted Device 

requirements

• Misbranding 

• Registration

• Performance Standards

• 510(k)

• PMA

• HDE

•

•
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Provisions of the IDE Regulation

• Describes applicability of the IDE regulations

• Provides administrative information

• Outlines the contents of the IDE application

• Describes FDA actions on IDE applications

• Assigns responsibilities to participants
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Overview

• Regulatory authority and framework for device clinical 

investigations

• Discussion of studies requiring an IDE 

• The IDE application and FDA decisions

• Office-level review of IDE application-specific issues

• Roles of sponsors, investigators, and IRBs
Types of Studies

• Pivotal Study

– Designed to collect definitive evidence on safety and 

effectiveness for a specified intended use, typically in a 

statistically justified number of subjects

• Feasibility Study

– Capture preliminary safety and effectiveness data typically in a 

small number of subjects (typically to inform pivotal study)

• Sponsor-investigator Studies

– Not intended to support a marketing application

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Types of Studies

• Early Feasibility Study

– Small number of subjects

– Device may be early in development, before final device design

– Approval may be based on less nonclinical data than would be 

needed to support the initiation of a larger clinical study on a more 

final device design

– Guidance “Investigational Device Exemptions (IDEs) for Early 

Feasibility Medical Device Clinical Studies, Including Certain 

First in Human (FIH) Studies”

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When is an IDE needed?

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Device 

Study

Exempt

Not 

Exempt NonSignificant 

Risk (NSR)

Significant 

Risk (SR) Full requirements

Abbreviated

requirements
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Exempt Studies (21 CFR 812.2(c))

No IDE Needed

• Commercial devices used in accordance with labeling 

• Many diagnostic devices

• Testing of consumer preference, of a modification, or of 

a combination of devices, when not determining safety 

or effectiveness and not putting subjects at risk

• Veterinary devices or research on/with laboratory 

animals

• Custom devices as defined in 812.3(b)
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“Practice of Medicine”

“Nothing in this Act shall be construed to limit or 

interfere with the authority of a health care practitioner to 

prescribe or administer any legally marketed device to a 

patient for any condition or disease within a legitimate 

health care practitioner-patient relationship....” 

From Section 1006 of the FD&C Act
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“Practice of Medicine”

• Physician should:

– Be well informed about the product

– Use firm scientific rationale and sound medical 

evidence

– Maintain records on use and effects

• IDE not required; institution may require IRB 

review/approval and informed consent

• Other prohibitions still apply 
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“Basic Physiological Research”

• Investigating a physiological principle

• No intent to develop the device for marketing

• Only using the device to address the research question

• No IDE needed; IRB approval and informed consent 

should be obtained
When is an IDE needed?

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Device 

Study

Exempt

Not 

Exempt NonSignificant 

Risk (NSR)

Significant 

Risk (SR) Full requirements

Abbreviated

requirements
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Significant Risk (SR) Study

• Presents a potential for serious risk to the health, 

safety, and welfare of a subject and is: 

– an implant; or

– used in supporting or sustaining human life; or

– of substantial importance in diagnosing, curing, 

mitigating, or treating disease or preventing 

impairment of human health

– otherwise poses a risk

See 21 CFR 812.3(m)
Risk Determination

• Sponsor makes initial determination 

• IRB reviews the sponsor’s determination 

– Information provided by the sponsor includes device description, 

prior investigations, investigational plan, subject selection, risk 

assessment and rationale used in making its SR or NSR 

determination

• If the IRB disagrees with a sponsor’s NSR assessment, 

the IRB must inform the clinical investigator, and where 

appropriate, the sponsor. (21 CFR 812.66)

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Non-Exempt Studies

• Non-Significant Risk – no IDE submission to FDA 

needed

– abbreviated requirements (labeling, IRB, consent, monitoring, 

reporting, prohibition on promotion) 

– IRB serves as the FDA’s surrogate for review, approval, and 

continuing review of the NSR device studies. 

– An NSR device study may start at the institution as soon as the 

IRB reviews and approves the study

• Significant Risk – Study can not begin until IDE is 

approved by FDA

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Study Risk Determination Inquiries to 

FDA

• FDA is available to help in making the risk determination

• Sponsor submits “Study Risk Determination” Q-Submission

• FDA issues letter indicating if study is

– Basic physiological research

– Exempt

– Not exempt: SR or NSR

• FDA is final arbiter

“The Pre-submission Program 

and Meetings with FDA Staff”

http://www.fda.gov/downloads/

MedicalDevices/DeviceRegulati

onandGuidance/GuidanceDocu

ments/UCM311176.pdf

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Overview

• Regulatory authority and framework for device clinical 

investigations

• Discussion of studies requiring an IDE 

• The IDE application and FDA decisions

• Office-level review of IDE application-specific issues

• Roles of sponsors, investigators, and IRBs
The IDE Application (812.20)

• Name and address of sponsor

• Report of prior investigations and 

investigational plan

• Manufacturing, processing, 

packing, and storage of device

• Investigator agreement 

• List of the name, address, and 

chairperson of each IRB 

• Participating institutions 

• Charge for device

• Environmental assessment

• Labeling

• Subject materials including 

informed consent

• Additional information requested 

by FDA

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FDA Review of the Application

• FDA sends acknowledgement with IDE number: 

GYYxxxxx (e.g. G140001)

• IDE sent to appropriate review division based on 

intended use

• Lead reviewer assembles team of experts to review the 

application and make decision with management 

concurrence within 30 days

• FDA issues a decision letter to the sponsor

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FDA Submissions after Approval

• Supplements (812.35)

– Change in protocol

– Change in device

• Reports (812.150)

– Annual progress

– Unanticipated adverse device effects

– Follow-up completion

– Current list of investigators

– Final report

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FDA Decisions and Letters

• Approval

– Approves the trial for specified number of sites and subjects

– Enrollment can begin once IRB approval is obtained

• Approval with conditions

– Approves the trial for specified number of sites and subjects 

provided conditions (deficiencies) are addressed within 45 days

– Enrollment can begin once IRB approval is obtained

• Disapproval

– Study may not begin; sponsor must address deficiencies and 

obtain FDA approval to start study

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Regulatory Basis for Disapproval

• There has been a failure to comply with regulatory requirements 

• The application contains an untrue statement of material fact, or 

omits material information 

• The sponsor fails to respond to a request for additional information 

• There is reason to believe that the 

– risks are not outweighed by the anticipated benefits to the 

subjects and the knowledge to be gained, 

– informed consent is inadequate, 

– investigation is scientifically unsound, or

– device as used is ineffective

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Regulatory Basis for Disapproval

• It is otherwise unreasonable to begin due to the way the device is 

used or the inadequacy of:

– the report of prior investigations or the investigational plan;

– the manufacturing, processing, packaging, storage, and/or 

installation of the device; or

– monitoring and review of the investigation. 

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Revision to FD&C Act, July 2012

FDA shall not disapprove an IDE because:

• The investigation may not support a substantial equivalence or de 

novo classification determination or approval of a device

• The investigation may not meet a requirement, including a data 

requirement, relating to the approval or clearance of a device; or an 

additional or different investigation may be necessary to support 

clearance or approval of the device

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Revision to FD&C Act

• This means that an IDE cannot be disapproved on the 

basis of FDA’s belief that the study design is inadequate 

to support a future PMA, 510(k), humanitarian device 

exemption (HDE), or de novo classification. 

– Disapproval is based on concerns related to subject 

safety and protections

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Other Elements of FDA Decision Letters

• Study design considerations

– Recommendations (but not requirements) regarding 

study design to help study achieve its goals

• Future considerations

– Issues relevant for future submissions (e.g. future 

marketing application)

• Sponsors are not required to respond to these elements

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Summary: FDA Letter

• Decisions: can you start the study?

þ Approval

þ Approval with conditions

ý Disapproval

• Study design considerations and future considerations do NOT 

require a response. They have no bearing on the IDE decision.

• Guidance: “FDA Decisions for IDE Clinical Investigations”

http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidance

documents/ucm279107.pdf

Require deficiencies to 

be addressed

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Overview

• Regulatory authority and framework for device clinical 

investigations

• Discussion of studies requiring an IDE 

• The IDE application and FDA decisions

• Office-level review of IDE application-specific issues

• Roles of sponsors, investigators, and IRBs
SOP for Review of IDE ApplicationSpecific Issues

• Goal of CDRH Clinical Trials Enterprise: To conduct device trials 

in the U.S. in a timely, efficient, and cost-effective manner, while 

maintaining appropriate patient protections

• Standard Operating Procedure (SOP) in place to improve 

efficiency, consistency, and predictability of the IDE process

• http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidanc

e/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/uc

m384135.htm

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SOP Policy and Scope

• IDE approvability decisions typically made at Division level.

• With SOP, Office-level Clinical Trials Director (CTD) is 

involved in selected submissions

– Provides objective review of outstanding issues to help 

resolve specific challenges 

• Applies to original IDEs, new study supplements, and 

expansions of studies from feasibility to pivotal for which a 

decision other than full approval is made

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SOP Provisions

• Teleconference with sponsors

– FDA offers a teleconference to occur within 10 days of a 1st

round disapproval (DSAP) or 2nd (or later) round DSAP or 

approval with conditions (APCN)

• CTD review of DSAP and APCN decisions

– CTD and review team meet prior to 10-day t-con to discuss IDE 

and remaining issues

• CTD interaction during review of 3rd (and subsequent) round 

response to DSAP or APCN 

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SOP Goals

• To help ensure consistency in decision-making

• To facilitate sharing of best practices across divisions

• To encourage higher levels of interaction

• To help prepare sponsor to respond

– 10-day meeting

– “Outside” perspective on letter

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Overview

• Regulatory authority and framework for device clinical 

investigations

• Discussion of studies requiring an IDE 

• The IDE application and FDA decisions

• Office-level review of IDE application-specific issues

• Roles of sponsors, investigators, and IRBs
Key Players

• Sponsor: initiates, but does not actually conduct, the 

investigation

• Investigator: actually conducts a clinical investigation, 

i.e., under whose immediate direction the test article is 

administered or dispensed to, or used involving, a 

subject

• Institutional Review Board (IRB): reviews, approves 

(initially and continuing) biomedical research at a given 

institution

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Sponsor Responsibilities

• Select qualified investigators and provide them with information 

they need

– Obtain investigator agreements

• Ensure proper monitoring

– Select appropriate monitors

– Secure compliance, evaluate and handle unanticipated adverse device 

effects

• Obtain IRB and FDA review and approval

– For study initiation and for resumption of terminated studies

– IDE application and supplements

– Keep IRB and FDA informed of significant new information

• Control devices

• Comply with Subpart A (labeling, promotion, import/export)
Sponsor Responsibilities Cont’d

21 CFR 812 Supbart G

• Maintain adequate records

• Grant inspections to FDA (establishments and records)

• Prepare and submit reports

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- Correspondence

- Investigator Agreements

- Device Disposition

- Adverse effects and complaints

- Unanticipated adverse 

device effects

- Withdrawal of IRB Approval

- Current Investigator list

- Progress reports

- Recall and device disposition

- Final report

- Failure to obtain informed consent

- Significant risk device 

determinations
Investigator Responsibilities

21 CFR 812 Subpart E

• Conduct investigation per signed agreement, investigational plan, 

FDA regulations and conditions of approval

• Protect rights, safety, and welfare of subjects under care

• Control of investigational devices

– Supervise device use, appropriate disposal

• Obtain appropriate informed consent

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Investigator Responsibilities Cont’d

21 CFR 812 Supbart G

• Maintain adequate records

• Grant inspections to FDA (establishments and records)

• Prepare and submit reports (to sponsor, IRB)

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- Correspondence

- Subject case history

- Case report forms, 

consent, medical records

- Device Disposition

- Adverse effects and complaints

- Protocol

- Unanticipated adverse 

device effects

- Withdrawal of IRB Approval

- Progress reports

- Final report

- Failure to obtain informed consent

- Protocol deviations
Institutional Review Boards - 21 CFR 56

• Purpose: to protect the rights and welfare of human subjects 

involved in FDA-regulated investigations and investigations that 

support applications for research (e.g. IDEs) or marketing permits

– Risk determination, Review of protocols and informed consent, 

Review of changes to protocols, Continuing review 

• An IRB must comply with the IRB (Part 56) and IDE (Part 812) 

regulations

• FDA does periodic inspections of the IRB’s records and procedures 

to determine compliance with the regulations

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Learning Objectives

• To understand the regulatory context of device clinical 

investigations

• To understand when an IDE is required

• To understand the IDE application process and FDA 

decisions on those applications

• To understand the roles of key players in IDE studies

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Thank you

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