IDE Application for an Investigational Device: - The Johns Hopkins ...

IDE Application for an Investigational Device: 

Investigational Device Exemption Application Guidance and Template for 

Significant Risk Devices 

ICTR Navigators 

March 20, 2013 

Version 2.0 

ACKNOWLEDGEMENT: 

We are grateful to the Office for Investigator-Sponsored IND and IDE Support at the University of Pittsburgh for the use of selected 

materials which have been modified and incorporated into this document for use by the Johns Hopkins research community.

ICTR DDRS: IDE Application Guidance & Template for Significant Risk Devices Version 2.0 

1.0 Table of Contents 

Section 

Page 

1.0 Table of Contents 2 

2.0 Abbreviations 2 

3.0 FDA Websites 2 

3.1 Definitions 3 

4.0 Introduction 6 

5.0 Guidance and Instructions 7 

5.1 Template Comments 7 

5.2 Regulations and Guidance Documents 7 

5.3 Number of Copies to be Submitted 8 

5.4 Application Header and Footer 8 

5.5 Binding 8 

5.6 FDA Mailing Addresses 10 

5.7 Website Hyperlinks 11 

5.8 Questions and Additional Information 11 

5.9 Application Template Guidance 11 

2.0 Abbreviations 

CFR Code of Federal Regulations 

FDA U.S. Food and Drug Administration 

CDER Center for Drug Evaluation and Research 

CBER Center for Biologics Evaluation and Research 

CDRH Center for Devices and Radiological Health 

CMC Chemistry, Manufacturing, and Controls 

GCP Good Clinical Practices 

GLP Good Laboratory Practices 

GMP Good Manufacturing Practices 

BLA Biologic License Application 

NDA New Drug Application 

PMA Pre-Market Application 

IDE Investigational Device Exemption 

3.0 FDA Websites 

A list of several FDA websites containing useful information for investigators using an 

investigational device is provided below. It is strongly suggested that these websites be reviewed 

before submitting an IDE application to the FDA. 

FDA Forms website: 

http://www.fda.gov/aboutfda/reportsmanualsforms/forms/default.htm 

FDA Title 21 Regulations Search Engine (e.g., IDE regulations 21CRF812) website: 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=812&showFR=1 

FDA Device Advice: Comprehensive Regulatory Assistance 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm 

FDA Original IDE Application Administrative Checklist 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/Investig 

ationalDeviceExemptionIDE/ucm046706.htm 

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Running Clinical Trials website: 

http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm 

FDA – CDRH Investigational Device Exemption (IDE) Application website: 



FDA – Sponsor-Investigator Responsibilities (IDE) website 



FDA – CDRH Device Guidance Documents: 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm 

FDA- Formal Meetings between the FDA and Sponsors or Applicants (pre-IDE): 


ationalDeviceExemptionIDE/ucm046164.htm#pre_ide 

FDA - CDER PRE-IND Consultation Contacts 

http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm134493.htm 

FDA CDRH Overview of Device Regulation 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/default.htm 

FDA CDRH Learn (Educational tool) 

http://www.fda.gov/Training/CDRHLearn/default.htm 

3.1 Definitions 

Term 

Component 

Custom device 

Design history file 

(DHF ) 

Design input 

Design output 

Definition 

Component means any raw material, substance, piece, part, software, 

firmware, labeling, or assembly which is intended to be included as part of the 

finished, packaged, and labeled device. 

Custom device means a device that: (1)Necessarily deviates from devices 

generally available or from an applicable performance standard or premarket 

approval requirement in order to comply with the order of an individual 

physician or dentist; (2) Is not generally available to, or generally used by, 

other physicians or dentists; (3) Is not generally available in finished form for 

purchase or for dispensing upon prescription; (4) Is not offered for commercial 

distribution through labeling or advertising; and (5) Is intended for use by an 

individual patient named in the order of a physician or dentist, and is to be 

made in a specific form for that patient, or is intended to meet the special 

needs of the physician or dentist in the course of professional practice 

Design history file (DHF) means a compilation of records which describes the 

design history of a finished device. 

Design input means the physical and performance requirements of a device 

that are used as a basis for device design. 

Design output means the results of a design effort at each design phase and 

at the end of the total design effort. The finished design output is the basis for 

the device master record. The total finished design output consists of the 

device, its packaging and labeling, and the device master record. 

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Design review 

Design 

Validation 

Device history 

record (DHR) 

Device master 

record (DMR) 

Feasibility Study 

Finished device 

Implant 

Investigation 

Investigational 

device 

Investigational 

device 

exemption (IDE) 

Investigator 

Lot (or batch) 

Noninvasive 

Pivotal 

Design review means a documented, comprehensive, systematic examination 

of a design to evaluate the adequacy of the design requirements, to evaluate 

the capability of the design to meet these requirements, and to identify 

problems. 

Design validation means establishing by objective evidence that device 

specifications conform with user needs and intended use(s). 

Device history record (DHR) means a compilation of records containing the 

production history of a finished device. 

Device master record (DMR) means a compilation of records containing the 

procedures and specifications for a finished device 

Feasibility studies are preliminary studies done with prototypes of the device 

that may require additional modification once it is used in a clinical setting. 

The device in these trials is not in its final state (as it will be marketed) and 

data from these studies is not sufficient to support a marketing application. 

Finished device means any device or accessory to any device that is suitable 

for use or capable of functioning, whether or not it is packaged, labeled, or 

sterilized. 

Implant is a device that is placed into a surgically or naturally formed cavity of 

the human body and is intended to remain there for a period of 30 days or 

more. In order to protect public health, FDA may determine that devices 

placed in subjects for shorter periods are also implants. 

Investigation is a clinical investigation or research involving one or more 

subjects to determine the safety and/or effectiveness of a device. 

Investigational device is a device, including a transitional device, which is the 

object of an investigation. 

IDE refers to the regulations under 21 CFR 812. An approved IDE means that 

the IRB (and FDA for significant risk devices) has approved the sponsor‟s 

study application and all the requirements under 21 CFR 812 are met. 

Investigator is an individual who actually conducts a clinical investigation, i.e., 

under whose immediate direction the investigational device is administered, 

dispensed to, or used involving a subject. In the event of an investigation 

being conducted by a team of individuals, "investigator" refers to the 

responsible leader of that team. 

Lot or batch means one or more components or finished devices that consist 

of a single type, model, class, size, composition, or software version that are 

manufactured under essentially the same conditions and that are intended to 

have uniform characteristics and quality within specified limits 

Noninvasive, when applied to a diagnostic device or procedure, means one 

that does not by design or intention: (1) Penetrate or pierce the skin or 

mucous membranes of the body, the ocular cavity, or the urethra, or (2) enter 

the ear beyond the external auditory canal, the nose beyond the nares, the 

mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina 

beyond the cervical os. For purposes of this part, blood sampling that involves 

simple venipuncture is considered noninvasive, and the use of surplus 

samples of body fluids or tissues that are left over from samples taken for 

non-investigational purposes is also considered noninvasive. 

Pivotal studies are done with the device as it will be in its final state. The 

purpose of the pivotal clinical study is to collect the primary evidence of safety 

and effectiveness to support a marketing submission or application. 

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Premarket 

Approval 

(PMA) 

Premarket 

Notification 

[PMN or 510(k)] 

Remanufacturer 

Rework 

Significant risk 

device 

(SR device) 

Sponsor 

Sponsorinvestigator 

Transitional 

device 

Unanticipated 

adverse device 

effect 

Validation 

A premarket approval means any premarket approval application for a Class 

III medical device, including all information submitted with or incorporated by 

reference therein. (21 CFR 814.3) 

510(k) refers to the type of submission to FDA described under 21 CFR 807 

Subpart E in which the applicant must establish that their device is 

substantially equivalent to a legally marketed device. This type of submission 

is used for most Class II devices and some Class I devices. 

Remanufacturer means any person who processes, conditions, renovates, 

repackages, restores, or does any other act to a finished device that 

significantly changes the finished device's performance or safety 

specifications, or intended use. 

Rework means action taken on a nonconforming product so that it will fulfill 

the specified DMR requirements before it is released for distribution. 

Significant risk device is an investigational device that: (1) is intended as an 

implant and presents a potential for serious risk to the health, safety, or 

welfare of a subject; (2) is for use in supporting or sustaining human life and 

represents a potential for serious risk to the health, safety, or welfare of a 

subject; (3) is for a use of substantial importance in diagnosing, curing, 

mitigating, or treating disease or otherwise preventing impairment of human 

health and presents a potential for serious risk to the health, safety, or welfare 

of a subject; or (4) otherwise presents a potential for serious risk to a subject. 

Sponsor is a person or other entity that initiates but does not actually conduct 

the investigation. An entity other than an individual (e.g., a corporation or an 

agency) which uses one or more of its own employees to conduct an 

investigation that it has initiated is considered to be a sponsor, not a sponsorinvestigator, 

and the employees are considered to be investigators. The 

sponsor of an IDE must be located in the United States (see 21 CFR 812.18). 

Sponsor-investigator is an individual who both initiates and actually conducts, 

alone or with others, a clinical investigation, i.e., under whose immediate 

direction the investigational device is administered, dispensed, or used. The 

term does not, for example, include a corporation or agency. The obligations 

of a sponsor-investigator include those of an investigator and those of a 

sponsor. 

Transitional device is a device subject to section 520(l) of the FD&C Act and 

which FDA previously regulated as a new drug or an antibiotic drug before 

May 28, 1976. 

Unanticipated adverse device effect is any serious adverse effect on health or 

safety, any life-threatening problem or death caused by, or associated with a 

device, if that effect, problem, or death was not previously identified in nature, 

severity, or degree of incidence in the application; or any other unanticipated 

serious problem associated with a device that relates to the rights, safety, or 

welfare of subjects. 

Validation means confirmation by examination and provision of objective 

evidence that the particular requirements for a specific intended use can be 

consistently fulfilled. 

Reference: FDA IDE Definitions and Acronyms webpage 

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4.0 Introduction 

4.1. Introduction: 

The information provided in this document is intended to provide a general process overview and a 

template for an Investigational Device Exemption (IDE) application submission for significant risk 

devices reviewed by the FDA Center for Devices and Radiological Health (CDRH). The document 

is written from the perspective that the person submitting the IDE application is a Sponsor- 

Investigator. A Sponsor-Investigator is someone who is both 1) responsible for initiating the 

studies conducted with the investigational device and 2) who conducts the studies. 

The contents of this document are based on the FDA regulations governing investigational 

devices, 21CFR812 and FDA guidance documents. However, each device and associated clinical 

trials may have unique features or circumstances that are not addressed by this document or the 

reference guidance documents cited herein. In such cases, the Sponsor-Investigator should 

consult with the ICTR-DDRS. 

4.2 IDE Application Submission: 

The necessity to submit IDE applications depends on the purpose, design, and nature of the 

clinical investigations involving the use of a FDA-approved or unapproved device. If the research 

is not being conducted for the purpose of determining the safety and effectiveness of the 

device for a specific clinical indication and the research use of the device does not place 

the participants at significant risk, then it is generally exempt from the requirement of 

submission of an IDE application. 

The submission of an IDE application is required if the reviewing institutional review board 

(IRB) determines that the device, or its proposed use in the research study, constitutes a 

“significant risk” to the research participants. 

A “significant risk device study” is defined by FDA regulations as “a study of a device that 

presents a potential for serious risk to the health, safety, or welfare of a subject and (1) is an 

implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in 

diagnosing, curing, mitigating or treating disease, or otherwise prevents impairment of human 

health; or (4) otherwise presents a potential for serious risk to the health, safety, or welfare of a 

subject.” 

A “non-significant risk device study” is a study of a device that does not meet the FDA‟s 

definition for a “significant risk device study.” 

An FDA Guidance document entitled, “Information Sheet Guidance for IRBs, Clinical 

Investigators, and Sponsors: Significant Risk and Non-significant Risk Medical Device 

Studies” is available for more information on making this risk determination. 

The clinical investigation of the safety and/or effectiveness of an unapproved device is typically 

divided into two phases, Feasibility studies and Pivotal studies. A FDA-mandated, clinical 

investigation of a device following its FDA approval is a Post-Marketing study. 

4.3 Feasibility studies 

Feasibility (pilot or proof-of-concept) studies of an unapproved device represent the initial human 

experience with the device and typically involve one investigator at one site with a limited number 

of subjects (e.g., 10 or less). Data from the feasibility study will not be considered as pivotal 

evidence of safety and effectiveness but rather as a basis to finalize and confirm the device design 

and determine its potential for further development. 

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4.4 Pivotal studies 

The conduct of Pivotal (multi-center) studies of an unapproved device may be for the purpose of 

obtaining the FDA‟s approval to market the device as a 510(k) device or to obtain FDA‟s approval 

of a Pre-Market Application (PMA) for the device. 

510(k) device studies 

The primary purpose of Pivotal studies directed at obtaining the FDA‟s approval to market 

an unapproved device as a 510(k) device is to validate that the product performs in an 

equivalent manner to another legally marketed (i.e., predicate) device. Substantial 

equivalence between the devices may be demonstrated through side-by-side comparisons 

of the device or pilot studies with the unapproved device alone. 

PMA device studies 

The primary purpose of Pivotal studies directed at obtaining the FDA‟s approval of a PMA 

for a device is to demonstrate, based on valid scientific evidence, reasonable assurance of 

the safety and effectiveness of the device for its proposed labeling indication. 

While there are numerous regulations, guidance documents and other references pertaining to 

significant risk IDE applications, those provided in this document are those most commonly used 

and/or most widely applicable. The following references will give the Sponsor-Investigator a 

general overview of the basic IDE application content and format. 

[FDA Regulation - 21CRF812 Subpart B--Investigational Device Application (IDE): 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=812&showFR=1&subpa 

rtNode=21:8.0.1.1.9.2 ] 

5.0 Guidance and Instructions 

5.1 Template Comments 

The enclosed template guidance is a suggested format based on federal regulations and guidance 

documents. Within each section of the application template are references to applicable FDA 

regulations, web addresses to FDA guidance documents, comments/instructions, web addresses 

to FDA forms, and suggested formatting and/or language. These instructions outline what should 

be included or inserted into a particular section and may also address special considerations. As 

this is a basic template and each significant risk device IDE application is unique, best judgment 

should be used concerning the information to be included in the submission. The Sponsor- 

Investigator may use this format or adapt it as appropriate for the particular investigational device 

being evaluated. Each section of the application should begin on new page and index tabs should 

be used to mark each section of the application. Thus, each section in this document should start 

on a new page. A blank template with just the cover letter, title page, and suggested section 

headings and subheadings is available for download at the DDRS website. 

5.2 Regulations and Guidance documents 

Throughout this document are a number references to regulations and guidance documents. 

These references have been included to provide the Sponsor-Investigator with direction and 

guidance when completing a significant risk IDE application. The references will not address every 

situation that may be encountered. If the applicant has questions after reviewing the references 

provided, they should contact the ICTR Research Navigators for assistance by submitting a 

Connection Request to the DDRS. 

Page 7 of 78


5.3 Number of Copies to be submitted 

Three signed copies of the IDE application are required. One original copy and two photocopies of 

the IDE application must be sent with the initial submission. Of note: Once the FDA receives the 

application and begins the review process, they may ask for additional desk copies. 

5.4 Application Header and Footer 

The following is the suggested format of document headers and footers to be used with the initial 

IDE submission. Note: Headers and footers are not included in the template and must be inserted 

manually and may be modified as appropriate. 

Header: 

[Left Hand Side] 

IDE Application Date: [INSERT DATE] 

[INSERT Device Name] 

[Right Hand Side] 

IDE Number: pending 

Footer: 

[Left Hand Side] 

[Right Hand Side] 

John Hopkins University Page [##] 

[INSERT: Sponsor-Investigator Name] 

Confidential and Proprietary 

5.5 Binding for Paper Submissions 

If a project manager has been assigned to the IDE application being prepared for submission or if 

contact information is available for a project manager within the Office/Division that will review the 

application, it is suggested that the Sponsor-Investigator contact the project manager to review 

how the IDE materials should be bound. 

If a project manager has not yet been assigned to the IDE, general guidelines for binding a paper 

IDE application are provided below. Neither CDER nor CDRH specify a color of binders for IDE 

submissions under their purview, but they do request uniformity in the manner in which the 

information is bound. CDRH does however provide recommendations concerning the format for 

paper submissions, which are listed below in under number 3. 

The following binding guidance information presented is from CBER and may be found at the 

FDA‟s website in a document entitled “SOPP 8007: DCC Binding Procedures for Regulatory 

Documents” located at following web address: 

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Procedures 

SOPPs/ucm109596.htm 

IDE submissions that are received loose or which are inadequately bound may be returned 

to the Sponsor-Investigator for rebinding and resubmission which can significantly delay 

the FDA review process. 

1. FDA Binding Recommendations: 

NOTE: While the following binders have a 3” capacity, CDRH prefers that each binder not 

exceed 2”. Neither CBER nor CDER have expressed this preference. 

a. Archive - ACCO Gray Stock Number 25974 or Smead Stock Number 81552 or 

Oxford Stock Number ESS-129005 or similar type 

b. Duplicate (or First Review Copy) - ACCO Executive Red Stock Number 25079 or 

Smead Red Stock Number 81752 or similar type 

Page 8 of 78


c. Second and additional review copies - Any color pressboard report binder except 

Gray or Red. 

2. Information about Binders/Folders: 

Note: The vendor information listed below is provided as an example of where these items 

may be purchased and is not intended as an endorsement of the vendor or a mandatory 

vendor to be used for purchase. 

a. Archive (original copy)- Gray (ACCO Gray Stock Number 25974 or Smead Stock 

Number 81552 or Oxford Stock Number ESS-129005 or similar type) 

i. Example Vendor 

1. GovGroup.com: 

http://www.govgroup.com/pressguard-binder-cover-smd81552-2183502- 

prd1.htm 

b. Duplicate (or First Review Copy) – Red (ACCO Executive Red Stock Number 25079 

or Smead Red Stock Number 81752 or similar type) 


1. Office Depot: 

http://www.officedepot.com/a/products/934380/ACCO-60percent-Recycled- 

Pressboard-Binder-With/ 

c. Second and additional review copies - Any color pressboard report binder except 

Gray or Red. 


1. Office Depot: 

http://www.officedepot.com/a/products/193664/ACCO-Presstex-60percent- 

Recycled-Binder-Side/ 

3. In order to facilitate FDA's handling of IDE applications, the following recommendations are 

offered: 

a. Use paper with nominal dimensions of 8 1/2" by 11" 

b. Use at least a 1 1/2" wide left margin to allow for binding into jackets 

c. Use 3-hole punched paper to allow for binding into jackets 

d. If the submission exceeds 2" in thickness, separate into volumes and identify 

volume number 

e. Clearly and prominently identify submission as original IDE application or, for 

additional submissions to an IDE application, clearly identify the FDA assigned 

document number (e.g., G960000) and the reason for the submission (e.g., 

amendment or supplement) and the type of submission (e.g., Response to FDA 

letter; Addition of New Institution, etc.) 

f. All copies of each submission must be identical 

g. Do not combine IDEs, PMAs and 510(k)s together; each is a separate submission 

h. Unless the IDE sponsor has provided authorization in writing for another person to 

submit information on the sponsor's behalf, only the IDE sponsor may amend, 

supplement, or submit reports to the IDE 

i. Sequentially number the pages, providing a detailed table of contents, and use tabs 

to identify each section. This will help to facilitate the review of the submission. 

j. The outside wrapper of each submission should identify the contents, for example, 

"IDE Application," "Supplemental IDE," "Waiver," etc. 

Page 9 of 78


4. Identification of binders: 

Required on front folder in a clear, sharp, permanent-type print in BLACK ink - Permanent 

adhesive labels may be used in a clear, sharp print - Printing must withstand a "Scotch 

Tape Test" which consists of pressing a strip of "Scotch" tape firmly on the printed area and 

removing - There should be NO transfer of the printed area on the tape. NOTE: This is 

suggested based upon CDER guidance for IND applications. 

a. All binders being submitted are to identified with the following labels: 

APPLICATION FOR INVESTIGATIONAL DEVICE EXEMPTION 

ORIGINAL SUBMISSION 

IDE NO._____ (For the initial submission of the new application leave 

blank) 

NAME OF DEVICE 

SPONSOR NAME 

This submission: VOL.___OF___VOLS. 

5.6 FDA Mailing Addresses 

Sponsors of a significant risk device investigation must submit a signed "Application for 

Investigational Device Exemption" in triplicate. 

1) For devices regulated by the Center for Devices and Radiological Health, send to: 

Food and Drug Administration 

Center for Devices and Radiological Health 

Document Mail Center - WO66-G609 

10903 New Hampshire Avenue 

Silver Spring, Maryland 20993-0002 

2) For devices regulated by the Center for Biologics Evaluation and Research (CBER), send to: 


Center for Biologics Evaluation and Research 

Document Control Center (HFM-99), 

1401 Rockville Pike, Suite 200N, 

Rockville, MD 20852-1448 

3) For devices regulated by the Center for Drug Evaluation and Research (CDER), send to: 


Center for Drug Evaluation and Research 

Central Document Control Room, 

5901-B Ammendale Rd., 

Beltsville, MD 20705-1266. 

You must state on the outside wrapper what the submission is (e.g. "original IDE application"). 

[See: 21 CFR Sec. 812.19 Address for IDE correspondence] 

[See FDA Device Advice: IDE Application-Address for IDE Applications] 

Page 10 of 78


5.7 Website Address Hyperlinks 

All hyperlinks to websites included in this document are operational as of the date of this version. 

If any non-functional hyperlinks are identified in this document, please contact the ICTR Research 

Navigators via the contact information below so that the links may be updated. 

5.8 Questions and Additional Information Contact 

For questions regarding any of the information presented or use of the template, please contact the 

ICTR Research Navigators at ICTR_Navigators@jhmi.edu or via telephone at 410-955-8120 or 

410-614-5383. 

5.9 Application Template Guidance 

Application Section 

Page 

Cover Letter 12 

Cover Page 15 

Form FDA 3415 (optional) 16 

Table of Contents 17 

Section 1: Sponsor-Investigator Information 20 

Section 2: Brief Overview of Clinical Plan 21 

Section 3: Report of Prior Investigations 23 

Section 4: Investigational Plan 28 

Section 5: Methods, Facilities and Controls Information 45 

Section 6: Example of Investigator Agreements, Certification of Investigators 51 

and Financial Interest 

Section 7: Reviewing Institutional Review Boards 54 

Section 8: Other Involved Institutions 56 

Section 9: Device Charges 58 

Section 10: Labeling 60 

Section 11: Consent Materials 62 

Section 12: Other Relevant Information 64 

Section 13: Reference List 66 

Section 14: Appendices 68 

Page 11 of 78


Cover Letter 

[INSTRUCTIONS: The suggested format for the cover letter that accompanies the IDE application 

may be found below.] 

[INSERT: Sponsor-Investigator letterhead or address] 

[INSERT: Date of letter] 


Center for Devices and Radiological Health 

Document Mail Center - WO66-G609 

10903 New Hampshire Avenue 

Silver Spring, Maryland 20993-0002 

OR 


Center for Biologics Evaluation and Research 

Document Control Center (HFM-99) 

1401 Rockville Pike, Suite 200N 

Rockville, MD 20852-1448 

OR 


Center for Drug Evaluation and Research 

Central Document Control Room 

5901-B Ammendale Rd. 

Beltsville, MD 20705-1266 

Re: 

Original IDE Application for [INSERT: Name of Device], [If applicable, reference the IDE 

number or Pre-IDE number here] 

Dear Madam/Sir: 

Pursuant to 21 CFR 812, I am submitting an original, Sponsor-Investigator IDE application for 

[INSERT: Name of Device]. Enclosed are one original [INSERT: color of original copy binder here 

(e.g. (Grey)] and two [INSERT: binder color of copies here (e.g. (Blue)] copies for your review. 

Device Information: 

Device name: 

Specify the name of the device under investigation here. 

Intended use of device: 

Specify the intended use of the investigational device; i.e., as per the objective(s) of the 

planned clinical investigation. 

Page 12 of 78


Sponsor-Investigator Contact Information: 

Sponsor-investigator name and degree(s) 

Academic department or division affiliation 

Full campus address 

Telephone number 

FAX number 

Manufacturer Information: 

Name of device manufacturer 

Full address 

Contact person 

Telephone number 

FAX number 

Additional Information: 

Pre-IDE/Pre-IDE meetings: 

[INSTRUCTIONS: Describe any discussions with the FDA reviewing division regarding this 

device. If a Pre-IDE document was submitted, indicate the Pre-IDE number assigned and 

the name of the FDA reviewer, if known. If a Pre-IDE meeting occurred, provide the name 

of the FDA contact person and a copy of the meeting minutes. If there was no Pre-IDE 

document submitted or Pre-IDE meeting, indicate such here.] 

Waiver requests: 

[INSTRUCTIONS: Identify any requests for waivers and include a justification for the 

waiver. If no waivers are being requested, indicate such here.] 

Referenced files: 

[INSTRUCTIONS: Identify any files that are referenced in the IDE application, such as an 

existing Premarket Approval, Premarket Notification 510(k), IDE, or device master file. If 

such files were not submitted by the sponsor-investigator, include a letter (e.g. Letter of 

Authorization or Letter of Cross Reference) from the owner of the files that grants FDA 

permission to reference the file in its review of this IDE application. If there are no 

referenced files, indicate such here.] 

If you have any questions about the material included in this IDE, please do not hesitate to contact 

me as per above. [COMMENT: If there is another person designated to interact with the FDA on 

behalf of the Sponsor-Investigator, then state “[INSERT: name] is authorized to interact with the 

FDA on my behalf and [INSERT: name‟s] contact information is [INSERT: phone, email, and fax].” 

Thank you in advance for your consideration. 

Sincerely, 

[INSERT: Sponsor-Investigator Name] 

[INSERT: Title] 

[INSERT: Affiliation] 

Page 13 of 78


Enclosure: 

Attachment: 

[INSERT: designation for any attachment cited in cover letter] 

[INSERT: description for any attachment cited in cover letter] 

Page 14 of 78


Cover Page 

[COMMENT: A suggested format for the cover page of the IDE application is provided below.] 

Original 

Investigational Device Exemption 

Application 

[INSERT: DATE] 

IDE Application Title: [Insert title] 

Device Name: 

IDE Number: 

[Insert name] 

[Insert “Pending” if not yet assigned] 

Sponsor-Investigator: [Insert typed name and contact information] 

Page 15 of 78


Form FDA 3415 

[REGULATORY REFERENCE: Agency Information Collection Activities; Submission for 

OMB Review; Comment Request; Premarket Notification 510(k) Submissions (FDA; HHS)] 

“FDA form 3514 was developed to assist respondents in organizing 510(k) data for submission to 

FDA. This form also assists respondents in organizing and submitting data for other FDA medical 

device programs such as premarket approval applications, investigational device exemptions, and 

humanitarian device exemptions.” 

[INSTRUCTIONS: Completion and inclusion of Form FDA 3415 is optional, however, it is strongly 

encouraged for device trials under the review of CBER as per the guidance below.] 

[REGULATORY REFERENCE: CBER Standard Operating Procedures and Policies: 

Submission of Paper Regulatory Applications to CBER [SOPP 8110 Version #2 April 

5, 2010] 

“CDRH Submission Cover Sheet (Form FDA-3514) is a form used voluntarily by those 

making submissions to CDRH. Use of this form for device submissions being made to 

CBER is strongly encouraged since it will facilitate timely processing of submissions by 

DCC (Document Control Center).‟ 

Page 16 of 78


Table Of Contents 

[SECTION INTRODUCTION: Any requirements for this section of the IDE application will be 

provided below. Some of the information included may not be applicable to all IDE applications.] 

[INSTRUCTIONS: An IDE Table of Contents is strongly recommended, but is not specifically 

required by the regulations. 

Changes may be made to the Table of Contents provided below based on the needs of individual 

IDE applications.] 

Page 17 of 78


Table of Contents 

Volume 1 

Section Title Page 

1.0 Sponsor-Investigator Information 

2.0 Brief Overview of Clinical Plan 

3.0 Report of Prior Investigations 

4.0 Investigational Plan 

4.1 Purpose of the Investigation 

4.2 Clinical Protocol 

4.2.1 Title of clinical protocol 

4.2.2 Study design 

4.2.3 Subject selection 

4.2.4 Study procedures 

4.2.5 Study outcome evaluations 

4.2.6 Sample Case Report Form 

4.3 Risk Analysis 

4.4 Description of investigational device 

4.5 Monitoring procedures 

4.6 Additional Records and Reports 

Volume 2 


5.0 Methods, Facilities and Control Information 

6.0 Example and Certification of Investigator Agreements and 

Financial Interest 

7.0 Reviewing Institutional Review Boards 

8.0 Other Involved Institutions 

9.0 Device Charges 

10.0 Labeling 

11.0 Consent materials 

12.0 Other Relevant Information 

13.0 Reference List 

14.0 Appendices 

LIST OF TABLES 

Volume 1 


Table 1 

Table 2 

Volume 2 


Table 3 

Table 4 

Table 5 

Page 18 of 78


LIST OF FIGURES 

Volume 1 


Figure 1 

Figure 2 

Volume 2 


Figure 3 

Figure 4 

LIST OF ATTACHMENTS 

Volume 1 


Attachment 1 

Attachment 2 

Volume 2 


Attachment 3 

Attachment 4 

Page 19 of 78


Section 1.0: Sponsor-Investigator Information 

[SECTION INTRODUCTION: The requirements for this section of the IDE application are provided 

below. Some of the information included may not be applicable to all IDE applications. 

General instructions and comments on the format and content of this section of the IDE 

application, along with a list of guidance documents and additional regulatory references, are 

provided. Within each subheading of this section are additional instructions, comments, suggested 

text, web addresses for forms, web addresses for specific guidance documents, and/or 

regulations.] 

[REGULATORY REFERENCE: 21CFR812.20(b)(1)] 

An IDE application shall include: 

(1) The name and address of the sponsor. 

[REGULATORY REFERENCE: 21CFR812.20(a)(3)] 

(a)(3) A sponsor shall submit three copies of a signed "Application for an Investigational Device 

Exemption" (IDE application), together with accompanying materials, by registered mail or by hand 

to the address in 812.19. 

1.0 Name, Address and Signature of Sponsor Investigator 

[INSTRUCTIONS: Specify the name, address, and contact information of the Sponsor-Investigator 

of the IDE application here.] 

Name and degree(s) 

Title 

Address 

[INSERT: Full title and academic department here.] 

[INSERT: Full campus address here.] 

Phone number 

[INSERT: Full office telephone number here.] 

FAX number 

[INSERT: Fax number here.] 

Email Address 

[INSERT: Email address here.] 

Signature of Sponsor-Investigator:___________________ Date: ____________ 

[IMPORTANT: All three copies of the IDE application (the original and the two copies) submitted 

to the FDA MUST BE SIGNED AND DATED BY THE SPONSOR-INVESTIGATOR.] 

Page 20 of 78


Section 2.0: Brief Overview of Clinical Plan(s) 

[SECTION INTRODUCTION: There is no regulatory requirement for this section of the IDE 

application, however, it is suggested that the applicant provide the following in an attempt to make 

the job of the FDA reviewer easier. General instructions and comments on the format and content 

of this section of the IDE application are provided.] 

Page 21 of 78


2.0 Brief Overview of Clinical Plan(s) 

[ INSTRUCTIONS: Incorporate a very brief description (i.e., not a complete protocol) of each of the 

clinical studies (e.g., feasibility, pilot, pivotal/comparative) of the device currently planned. 

This section should briefly summarize (no more than a paragraph), for each planned clinical study, 

the title, design, sample size, primary outcome measures and expected principal results.] 

2.1 Descriptive title 

A. Study design 

B. Sample size 

C. Primary outcome measures 

D. Principal results (expected) 

[INSTRUCTIONS: Delete 2.2 if no additional studies are proposed or add 2.3, etc. as required.] 

2.2 Descriptive title 

A. Study design 

B. Sample size 

C. Primary outcome measures 

D. Principal results (expected) 

Page 22 of 78


Section 3.0: Report of Prior Investigations 




application, along with a list of guidance documents and additional regulation references, are 



regulations.] 


(2) A complete report of prior investigations of the device 

[REGULATORY REFERENCE: Sec. 812.27 Report of prior investigations] 

Sec. 812.27 Report of prior investigations. 

(a)General: The report of prior investigations shall include reports of all prior clinical, animal, and 

laboratory testing of the device and shall be comprehensive and adequate to justify the proposed 

investigation. 

(b)Specific contents: The report also shall include: 

(1) A bibliography of all publications, whether adverse or supportive, that are relevant to an 

evaluation of the safety or effectiveness of the device, copies of all published and 

unpublished adverse information, and, if requested by an IRB or FDA, copies of other 

significant publications. 

(2) A summary of all other unpublished information (whether adverse or supportive) in the 

possession of, or reasonably obtainable by, the sponsor that is relevant to an evaluation 

of the safety or effectiveness of the device. 

(3) If information on nonclinical laboratory studies is provided, a statement that all such 

studies have been conducted in compliance with applicable requirements in the good 

laboratory practice regulations in part 58, or if any such study was not conducted in 

compliance with such regulations, a brief statement of the reason for the 

noncompliance. Failure or inability to comply with this requirement does not justify 

failure to provide information on a relevant nonclinical test study. [45 FR 3751, Jan. 18, 

1980, as amended at 50 FR 7518, Feb. 22, 1985] 

[REGULATORY REFERENCE: GUIDANCE ON THE REVIEW OF INVESTIGATIONAL DEVICE 

EXEMPTIONS (IDE) APPLICATIONS FOR FEASIBILITY STUDIES (May 17, 1989)] 

Per this guidance, it is the Sponsor-Investigator‟s “responsibility to define and conduct adequate 

tests to establish the lack of unreasonable risk and the expected performance of a device prior to 

clinical use. A limited trial may represent the initial introduction of a device into a human 

population; therefore, FDA must be assured that sufficient batteries of tests have been completed. 

It is the prerogative of the Sponsor-Investigator to indicate whether some preclinical tests (e.g., 

chronic toxicity) are not essential to early clinical studies and will be initiated only if the device will 

undergo further clinical study.”] 

[COMMENT: The report of prior investigations of the device must include reports of all prior 

clinical, animal testing, and laboratory testing of the investigational device. The report must be 

suitably comprehensive and inclusive of adequate data and information so as to justify that the 

proposed clinical investigation of the device possesses an appropriate benefit-to-risk ratio.] 

Page 23 of 78


3.0 Report of Prior Investigations 

[INSTRUCTIONS: Insert the following language and delete Sections 3.1 through 3.3 ONLY if the 

device(s) under study is/are already cleared or approved by the FDA for commercial distribution. 

Modify as appropriate: 

“Please refer to Appendix X for permission from the manufacturer authorizing FDA to access the 

manufacturer‟s [Insert: PMA, 510K application, or Device Master Record]. 

No additional 21 CFR 58 compliant studies have been conducted by the Sponsor-investigator in 

support of this application.”] 

3.1 Prior Non-Clinical Investigations of the Device 

A. Non-clinical investigations conducted under the direction or request of the 

sponsor-investigator 

a. Laboratory studies 

i. Unpublished laboratory studies: 

[INSTRUCTIONS: List, by name or purpose of the study, each 

previously conducted, unpublished laboratory study of the device that is 

relevant (i.e., whether adverse or supportive) to the proposed clinical 

evaluation of the safety and/or effectiveness of the device. For each of 

these listed laboratory studies, provide a summary of the study that 

includes an adequate 1) description of the study methods; 2) outcome 

data; and 3) relevant (i.e., safety and/or effectiveness) conclusion(s) of 

the study. If there are no unpublished laboratory studies that are 

relevant to the proposed clinical evaluation of the safety and/or 

effectiveness of the device, specify “None”. 

Incorporate under this section (or by reference to an Appendix) copies of 

any adverse information derived from unpublished laboratory studies of 

the device (if applicable). If the unpublished laboratory studies did not 

reveal any adverse information, specify this.] 

ii. 

Published laboratory studies: 

[INSTRUCTIONS: Provide a bibliography of all published laboratory 

studies of the device that are relevant (i.e., whether adverse or 

supportive) to the proposed clinical evaluation of the safety and/or 

effectiveness of the device. For each of the listed publications, provide a 

brief summary of the relevant (i.e., safety and/or effectiveness) 

information or conclusion(s) of the respective study (studies). If there are 

no published laboratory studies that are relevant to the proposed clinical 

evaluation of the safety and/or effectiveness of the device, specify 

“None”. 

If applicable, incorporate under this section (or a referenced an 

Appendix) copies of all respective publications that contain adverse 

information regarding the device. If the published laboratory studies did 

not reveal any adverse information, specify this.] 

Page 24 of 78


b. Animal studies 

i. Unpublished animal studies 

[INSTRUCTIONS: List, by name or nature of the study, each 

unpublished animal study of the device that is relevant (i.e., whether 

adverse or supportive) to the proposed clinical evaluation of the safety 

and/or effectiveness of the device. For each of these listed animal 

studies, provide a summary of the study that includes an adequate 1) 

rationale for animal selection; 2) statistical justification for the number of 

animals studied; 3) description of the study methods; 4) outcome data; 

and 5) relevant (i.e., safety and/or effectiveness) conclusion(s) of the 

study. If there are no unpublished animal studies that are relevant to the 

proposed clinical evaluation of the safety and/or effectiveness of the 

device, specify “None”. 

If applicable, incorporate under this section (or by reference to an 

Appendix) copies of any adverse information derived from unpublished 

animal studies of the device. If the unpublished animal studies did not 

reveal any adverse information, specify this.] 

ii. 

Published animal studies 

[INSTRUCTIONS: Provide a bibliography of all published animal studies 

of the device that are relevant (i.e., whether adverse or supportive) to the 

proposed clinical evaluation of the safety and/or effectiveness of the 

device. For each of the listed publications, provide a brief summary of 

the relevant (i.e., safety and/or effectiveness) information or 

conclusion(s) of the respective study (studies). If there are no published 

animal studies that are relevant to the proposed clinical evaluation of the 

safety and/or effectiveness of the device, specify “None”. 

Incorporate under this section (or by reference to an Appendix) copies of 

all respective publications that contain adverse information regarding the 

device (if applicable). If the published animal studies did not reveal any 

adverse information, specify this.] 

c. Compliance with Good Laboratory Practice for Nonclinical Laboratory 

Studies regulations (21 CFR Part 58) 

[INSTRUCTIONS: Specify whether or not the unpublished and/or published 

laboratory and animal studies of the device, described above, were conducted in 

a laboratory or facility that is certified as operating in full compliance with the 

FDA‟s GLP regulations. If the studies were not conducted in compliance with 

the FDA‟s GLP regulations, provide a brief statement of the reason for noncompliance.] 

B. Relevant non-clinical investigations conducted by other investigators 

a. Laboratory studies 

Page 25 of 78


[INSTRUCTIONS: Provide a bibliography of all published laboratory studies of 

the device conducted by other investigators that are relevant (i.e., whether 

adverse or supportive) to the proposed clinical evaluation of the safety and/or 

effectiveness of the device. For each of the listed publications, provide a brief 

summary of the relevant (i.e., safety and/or effectiveness) information or 

conclusion(s) of the respective study (studies). If there are no other published 

laboratory studies that are relevant to the proposed clinical evaluation of the 

safety and/or effectiveness of the device, specify “None”. 

Incorporate under this section (or by reference to an Appendix) copies of all 

respective publications that contain adverse information regarding the device (if 

applicable). If the published laboratory studies did not reveal any adverse 

information, specify this.] 

b. Animal studies 

[INSTRUCTIONS: Provide a bibliography of all published animal studies of the 

device conducted by other investigators that are relevant (i.e., whether adverse 

or supportive) to the proposed clinical evaluation of the safety and/or 

effectiveness of the device. For each of the listed publications, provide a brief 

summary of the relevant (i.e., safety and/or effectiveness) information or 

conclusion(s) of the respective study (studies). If there are no other published 

animal studies that are relevant to the proposed clinical evaluation of the safety 

and/or effectiveness of the device, specify “None”. 



applicable). If the published animal studies did not reveal any adverse 


3.2 Prior Clinical Investigations of the Device 

A. Prior clinical investigations conducted by the sponsor-investigator 

a. Unpublished clinical investigations 

[INSTRUCTIONS: List, by name or nature of the investigation, each prior 

clinical investigation of the device that is relevant (i.e. whether adverse or 

supportive) to the proposed clinical evaluation of the safety and/or effectiveness 

of the device For each of these listed clinical investigations, provide a summary 

of the investigation that includes an adequate 1) rationale for subject selection; 

2) statistical justification for the number of subjects studied; 3) description of the 

study methods; 4) outcome data; and 5) relevant (i.e., safety and/or 

effectiveness) conclusion(s) of the investigation. If there are no unpublished, 

prior clinical investigations that are relevant to the proposed clinical evaluation of 

the safety and/or effectiveness of the device, specify “None”. 

Incorporate under this section (or by reference to an Appendix) copies of any 

adverse information derived from prior, unpublished clinical investigations of the 

device (if applicable). If the prior, unpublished clinical investigations of the 

device did not reveal any adverse information, specify this.] 

Page 26 of 78


b. Published clinical investigations 

[INSTRUCTIONS: Provide a bibliography of all publications regarding prior 

clinical investigations of the device that are relevant (i.e., whether adverse or 

supportive) to the proposed clinical evaluation of the safety and/or effectiveness 

of the device. For each of the listed publications, provide a brief summary of the 

relevant (i.e., safety and/or effectiveness) information or conclusion(s) of the 

respective clinical study (studies). If there are no publications of prior clinical 

investigations that are relevant to the proposed clinical evaluation of the safety 

and/or effectiveness of the device, specify “None”. 



applicable). If the publications of prior clinical investigations did not reveal any 

adverse information, specify this.] 

c. Authorization to access other IDE applications under which prior clinical 

investigations of the device were conducted 

[INSTRUCTIONS: As applicable, incorporate into this section (or a reference 

Appendix) a letter, signed by the Sponsor-Investigator, that authorizes the FDA 

to access (each of) the prior IDE application(s) under which the above-cited, 

prior clinical investigations of the device were conducted.] 

B. Other published clinical investigations 

[INSTRUCTIONS: Provide a bibliography of all publications of prior clinical 

investigations of the device conducted by other investigators that are relevant (i.e., 

whether adverse or supportive) to the proposed clinical evaluation of the safety 

and/or effectiveness of the device. For each of the listed publications, provide a 

brief summary of the relevant (i.e., safety and/or effectiveness) information or 

conclusion(s) of the respective clinical study (studies). If there are no other 

publications of prior clinical investigations that are relevant to the proposed clinical 

evaluation of the safety and/or effectiveness of the device, specify “None”. 

Incorporate under this section (or a referenced an Appendix) copies of all respective 

publications that contain adverse information regarding the device (if applicable). If 

the publications of prior clinical investigations did not reveal any adverse 


3.3 Clinical, Animal and Laboratory Studies Supporting Prior FDA-Approval to Market 

the Device 

[INSTRUCTIONS: Incorporate this section only if the device being evaluated is already 

approved by the FDA for marketing; (i.e., for an indication that is different than that being 

evaluated in the proposed clinical investigation.) 

If the device is marketed commercially, incorporate under this section (or by reference to an 

Appendix) written correspondence from the device manufacturer that permits the FDA to 

access the manufacturer‟s Pre-Market Approval (PMA) or 510k application for the device.] 

Page 27 of 78


Section 4.0: Investigational Plan 







regulations.] 

[REGULATORY REFERENCE: 21CFR812.25] 

Sec. 812.25 Investigational plan. 

The investigational plan shall include, in the following order: 

(a)Purpose. The name and intended use of the device and the objectives and duration of 

the investigation. 

(b)Protocol. A written protocol describing the methodology to be used and an analysis of 

the protocol demonstrating that the investigation is scientifically sound. 

(c)Risk analysis. A description and analysis of all increased risks to which subjects will be 

exposed by the investigation; the manner in which these risks will be minimized; a 

justification for the investigation; and a description of the patient population, including the 

number, age, sex, and condition. 

(d)Description of device. A description of each important component, ingredient, property, 

and principle of operation of the device and of each anticipated change in the device during 

the course of the investigation. 

(e)Monitoring procedures. The sponsor's written procedures for monitoring the investigation 

and the name and address of any monitor. 

(f)Labeling. Copies of all labeling for the device. 

(g)Consent materials. Copies of all forms and informational materials to be provided to 

subjects to obtain informed consent. 

*(h)IRB information A list of the names, locations, and chairpersons of all IRB's that have 

been or will be asked to review the investigation, and a certification of any action taken by 

any of those IRB's with respect to the investigation. 

*(i)Other institutions The name and address of each institution at which a part of the 

investigation may be conducted that has not been identified in paragraph (h) of this section. 

(j)Additional records and reports. A description of records and reports that will be 

maintained on the investigation in addition to those prescribed in subpart G. 

*[NOTE: Items (h) and (i) are addressed in Sections 7.0 and 8.0] 

Page 28 of 78


[NOTE: The clinical protocol for a limited Feasibility (or pilot) study of a device is, in general, less 

ambitious than the clinical protocol(s) for Pivotal studies; the latter being directed at 

demonstrating reasonable assurance of safety and effectiveness the device. (E.g., the 

protocol for a Feasibility study may not include comparison of the use of the device with a 

control, as is required for Pivotal studies of the device.) The clinical protocol for a 

Feasibility study should, however, have an objective and be reasonably defined; and, 

where applicable, should address and account for critical safety concerns.] 

[REGULATORY REFERENCE: GUIDANCE ON THE REVIEW OF INVESTIGATIONAL DEVICE 

EXEMPTIONS (IDE) APPLICATIONS FOR FEASIBILITY STUDIES (May 17, 1989)] 

With regard to feasibility studies, per this guidance, the Sponsor-Investigator must “include a 

thorough risk analysis which describes the risks to the subject, how they will be minimized and a 

justification that they are reasonable in relation to the expected benefits. The scope and duration 

of limited studies will vary, but in general, are less ambitious than full clinical studies which provide 

the pivotal evidence of safety and effectiveness. The investigational plan should have a valid 

scientific objective and reasonable study protocol.” Per this guidance, “disapprovals” are “limited to 

situations where there are critical safety-related concerns.” Additionally per the guidance, 

“deficiencies (other than critical safety-related concerns) can be corrected or clarified under a 

conditional approval decision.”] 

The FDA relies upon only valid scientific evidence to determine whether there is reasonable 

assurance that the device is safe and effective for its proposed labeling indication. Valid scientific 

evidence used to determine the effectiveness of a device shall consist of one or more wellcontrolled 

investigation(s) of the device unless the FDA has determined that the requirement for a 

well-controlled investigation is not reasonably applicable to the device. In the latter situation, the 

FDA may authorize reliance upon other valid scientific evidence which the FDA has determined is 

sufficient evidence from which to determine the effectiveness of the device (i.e., in the absence of 

well-controlled investigation). The clinical protocol for, and the report of the results of, a wellcontrolled 

investigation shall include the following: 

(i) 

(ii) 

A clear statement of the objectives of the study. 

A method of selection of the subjects that: 

 

 

 

 

 

Provides adequate assurance that the subjects are suitable for the purpose of the 

study; 

Provides diagnostic criteria of the condition to be treated or diagnosed and, where 

appropriate, confirmatory laboratory tests; 

Provides (i.e., in the case of a device intended to prevent a disease or condition) 

evidence of susceptibility and exposure to the condition against which prophylaxis is 

desired; 

Assigns the subjects to test groups, if used , in such as a way as to minimize any 

potential bias; and 

Assures comparability between test groups and any control groups of pertinent 

variables such as sex, severity or duration of the disease, and use of therapy other than 

the test device. 

(iii) 

An explanation of the methods of observation and recording of results utilized, including the 

variables measured, quantitation, assessment of any subject‟s response, and steps taken 

to minimize any possible bias of subjects and observers. 

Page 29 of 78


(iv) 

A comparison of the results of treatment or diagnosis with a control in such a fashion as to 

permit quantitative evaluation. The precise nature of the control must be specified and an 

explanation provided of the methods employed to minimize any possible bias of the 

observers and analysts of the data. Level and methods of “blinding”, if appropriate and 

used, are to be documented. Generally, four types of comparisons are recognized: 

No treatments: Where objective measurements of effectiveness are available and 

placebo effect is negligible, comparison of the objective results in comparable groups of 

treated and untreated patients. 

 

Placebo controlled: Where there may be a placebo effect with the use of a device, 

comparison of the results of the use of the device with an ineffective device used under 

conditions designed to resemble the conditions of use under investigation as far as 

possible. 

Active treatment control: Where an effective regimen of therapy may be used for 

comparison; e.g., the condition being treated is such that the use of a placebo or the 

withholding of treatment would be inappropriate or contrary to the interest of the patientsubject. 

 

Historical control: In certain circumstances, such as those involving diseases with high 

and predictable mortality or signs and symptoms of predictable duration or severity, or 

in the case of prophylaxis where morbidity is predictable, the results of use of the device 

may be compared quantitatively with prior experience historically derived from the 

adequately documented natural history or the disease or condition in comparable 

patients or populations who received no treatment or who followed an established 

effective regimen (i.e., therapeutic, diagnostic, prophylactic). 

[GUIDANCE DOCUMENTS FOR STATISTICAL CONSIDERATIONS OF DEVICE TRIALS: 

 

 

 

 

Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials 

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

m071072.htm 

Statistical Guidance: How many subjects and sites do I have to include in the study? 

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

e/InvestigationalDeviceExemptionIDE/ucm051480.htm#statistics 

Statistical Guidance for Clinical Trials of Non Diagnostic Medical Devices 

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

m106757.htm 

Perspectives on Clinical Studies for Medical Device Submissions (Statistical) 

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

cuments/UCM106755.pdf 

Page 30 of 78


4.0 Investigational Plan 

4.1 Purpose of the Investigation 

A. Name of investigational device 

[INSTRUCTIONS: Specify the name of the investigational device.] 

B. Intended use of the investigational device 

[INSTRUCTIONS: Summarize the intended use of the investigational device.] 

C. Objectives of the clinical investigation 

a. Primary objective(s) 

[INSTRUCTIONS: Describe the primary objective(s) of the proposed clinical 

investigation of the device. Additionally, indicate that the proposed clinical 

investigation constitutes a: 

Feasibility study directed at or involving a(n): 

o 

o 

o 

o 

Initial evaluation of the device in humans or a certain clinical 

population 

Evaluation of potential safety issues associated with the use of the 

device 

Evaluation of device design; 

Assessing certain human factors (e.g., patient or operator) 

associated with the use of the device; or 

o Other specified device characteristic or device application 

consideration. 

Pilot study to obtain preliminary data upon which to base a subsequent pivotal 

study of the device 

OR 

Pivotal clinical study to collect the primary evidence of safety and effectiveness 

to support a marketing submission or application] 

b. Secondary objective(s) 

[INSTRUCTIONS: If a feasibility study, describe any secondary objective(s) of 

the proposed clinical investigation of the device. If a pivotal study, provide a best 

estimate of the number of months or years it will take to complete (1) the clinical 

study addressed under section 2.0, Clinical Protocol; and (2) the overall clinical 

investigation of the device to determine safety and efficacy.] 

Page 31 of 78


D. Anticipated duration of the clinical investigation: 

4.2 Clinical Protocol 

[INSTRUCTIONS: Provide a best estimate of the number of months or years it will 

take to complete the proposed study of the device.] 

The full clinical protocol is included for FDA review in Appendix___. [INSERT: Provide 

full version of the clinical protocol in the referenced appendix.] 

A. Title of clinical protocol 

[INSTRUCTIONS: Specify the title of the clinical study.] 

a. Protocol Number 

[INSTRUCTIONS: Incorporate only if applicable.] 

b. Version number and date 

[INSTRUCTIONS: Number supplemental applications consecutively and include 

the date of the current application.] 

B. Study design 

a. General study design 

[INSTRUCTIONS: If a feasibility trial, describe the type/design (e.g., open-label, 

observational) of the proposed clinical study. 

Note that for Pivotal Studies of investigational devices, the results of treatment 

or diagnosis with the investigational device must be compared with a control in 

such a fashion as to permit a quantitative evaluation. The precise nature of the 

comparison (control) group must be specified in the general description of the 

study design; i.e.: No treatment control, Placebo control, active treatment 

control, or historical control.] 

i. Minimization of potential bias. 

[INSTRUCTIONS: If a feasibility trial, delete. For pivotal trials only, 

describe the specific measures (e.g., randomization, blinding) that will be 

taken to minimize/avoid bias on the part of the subjects, investigators, 

and analysts.] 

b. Study design schematic 

[INSTRUCTIONS: Provide a schematic diagram of the study design, 

procedures, and stages as applicable.] 

Page 32 of 78


C. Detailed description of conduct of the trial and all methodologies to be used 

[SPECIAL NOTE: Applicant must be certain that the language used in the following 

section of the IDE application is consistent with language contained in the clinical 

protocol.] 

a. General characteristics of the proposed subject population(s) 

[INSTRUCTIONS: Provide a general description of the characteristics of the 

proposed subject population(s). Provide a justification for the suitability of this 

(these) population(s) for the purpose of the investigation.] 

i. Women and Minorities 

[INSTRUCTIONS: Provide a brief description and/or justification of how 

these populations will be incorporated or excluded into the investigation.] 

b. Anticipated number of research subjects 

[INSTRUCTIONS: Define „enrollment‟. Specify the estimated total number of 

subjects to be enrolled into the clinical study and the anticipated number of 

subjects expected to complete the study.] 

c. Inclusion criteria 

[INSTRUCTIONS: List the specific criteria for including subjects for participation 

in the clinical study. Note that these criteria should be inclusive of diagnostic 

criteria and, where appropriate, confirmatory laboratory tests applicable to the 

specific disease or condition to be treated or diagnosed by the investigational 

device. In the case of an investigational device intended to prevent a disease or 

condition, the criteria for subject inclusion should provide for evidence of 

susceptibility and exposure to the condition against which prophylaxis is 

desired]. 

d. Exclusion criteria 

[INSTRUCTIONS: List the specific criteria for excluding subjects from 

participation in the clinical study.] 

D. Study procedures 



protocol.] 

a. Screening procedures 

[INSTRUCTIONS: Describe or list the procedures that will be performed to verify 

a subject‟s eligibility for participation in the clinical study.] 

Page 33 of 78


b. Study treatment and/or diagnostic product procedures 

[INSTRUCTIONS: Describe, in detail, the study treatment or diagnostic products 

(e.g., the investigational device and, if applicable, comparative devices or 

products) that will be administered to each study group or arm of the proposed 

clinical investigation; to include, for each study treatment or diagnostic product, 

the product name and FDA-approval status, dose or dose range (if applicable), 

route/mode of administration, dosing or exposure schedule, and treatment or 

exposure duration. Describe, if applicable, any plans for dose or exposure 

reductions or increases based on the data accrued with study progression.] 

i. Allocation to treatment 

[INSTRUCTIONS: Incorporate only if the proposed clinical study 

involves multiple treatment arms. Describe the plan and procedures 

for allocating subjects to the various treatment or diagnostic arms of the 

study so as to ensure comparability between test groups and any control 

groups with regard to pertinent variables such as gender, severity or 

duration of disease, and use of therapy other than the investigational 

device.] 

ii. Breaking the blind 

[INSTRUCTIONS: Incorporate only if the proposed clinical study is 

blinded. Describe the procedures for breaking the blind should a given 

subject suffer a serious adverse event wherein knowledge of the identity 

of the study treatment or diagnostic product received by the subject is 

necessary for effective emergency treatment of the event.] 

iii. Treatment adherence/Study compliance 

[INSTRUCTIONS: If applicable, describe the procedures that will be 

used to assess subject compliance/adherence with the assigned study 

treatment or diagnostic product regimen. 

Specify the criteria and procedures for withdrawing subjects from study 

participation due to non-compliance with the study treatment or 

diagnostic product regimen, if applicable, and/or the study procedures or 

investigators instructions. 

Specify if subjects withdrawn from study participation due to 

noncompliance will be replaced and, if so, the corresponding procedures 

for their replacement.] 

c. Follow-up procedures 

i. Procedures to assess efficacy 

[INSTRUCTIONS: If applicable, specify the parameters (i.e., 

observations and/or measurements) that will be used to evaluate the 

efficacy of the study treatment or diagnostic product(s); to include the 

methods and timing for assessing, recording, and analyzing these 

parameters. 

Page 34 of 78


If the proposed clinical study does not involve evaluation(s) of the 

efficacy of the investigational device, state this.] 

ii. 

Procedures to assess safety 

[INSTRUCTIONS: Specify the parameters (i.e., procedures, laboratory 

tests, or other measures) that will be used to evaluate the safety of the 

study treatment or diagnostic product(s); to include the methods and 

timing for assessing, recording, and analyzing these parameters.] 

iii. 

Supportive care 

[INSTRUCTIONS: Describe any supportive care (i.e., procedures, 

laboratory tests, or other measures) that will be administered in the 

course of trial follow-up.] 

d. Schedule of activities (Study Table) 

[INSTRUCTIONS: Incorporate, as a referenced attachment (i.e., Appendix ___), 

a table that summarizes the protocol procedures that will be performed at 

screening, for treatment or diagnosis, and at follow-up (if applicable).] 

E. Statistical Considerations and Study outcome evaluations 



protocol.] 

a. Study endpoints 

[INSTRUCTIONS: Summarize the primary and, if applicable, secondary 

endpoints or outcomes that will be evaluated in the clinical study. 

Primary endpoint(s): 

Secondary endpoints: 

b. Sample size determination 

[INSTRUCTIONS: Specify the number of subjects planned to be enrolled into 

the clinical study (i.e., to complete the clinical study) and the reason(s) for the 

choice of this sample size. Include, if applicable, calculations of the power of the 

study or provide an alternate explanation for the proposed sample size. For 

example, if the purpose of the proposed clinical study is to obtain pilot data upon 

which to base a subsequent pivotal study of the investigation device, state this 

and provide a clinical justification for the sample size selected.] 

Page 35 of 78


c. Outcome data and data analysis 

[INSTRUCTIONS: Use this header for feasibility trials. Delete „Data analysis, 

efficacy analysis, safety analysis, and interim analysis headers below. 

Describe the specific observations and/or measurements that will form the basis 

for evaluating the primary and, if applicable, secondary endpoints or outcomes 

of the clinical study. 

Describe how these data will be evaluated in addressing the feasibility 

objective(s) of the clinical study and/or in making a decision to proceed with 

further clinical investigation of the investigational device.] 

Data analysis 

[INSTRUCTIONS: Use “Data Analysis” header for pivotal trials. 

Outcome data and data analysis‟ above.] 

Delete „c. 

i. Efficacy analysis 

[INSTRUCTIONS: Describe the analysis population(s) and statistical 

methods that will be employed in the analysis (analyses) of primary and 

secondary (if any) endpoints related to evaluation(s) of the efficacy of the 

study treatment or diagnostic product(s). Include the level(s) of significance 

to be used.] 

ii. Safety analysis 

[INSTRUCTIONS: Describe the analysis population(s) and statistical 

methods that will be employed in the analysis of the safety of the study 

treatment or diagnostic product(s). Include the level of significance to be 

used.] 

iii. Interim analysis 

[INSTRUCTIONS: Incorporate only if an interim analysis is planned. 

Describe the timing and nature of the planned interim analysis. Address 

corresponding procedures; such as who will perform the interim analysis and 

to whom the results of the analysis will be provided. 

Describe the procedures for reporting, to the FDA, any deviation(s) from the 

original statistical plan based on the results of the interim analysis (i.e., any 

deviation(s) from the original statistical plan should be described and justified 

in a supplemental IDE application).] 

d. Data and Safety Monitoring (DSM) Plan/Committee 

[INSTRUCTIONS: Describe the Data and Safety Monitoring Plan. If a Data 

Safety Monitoring Committee will provide oversight, describe the composition 

and operations or include DSM Charter as a referenced attachment (i.e., 

Appendix ___).] 

Page 36 of 78


[For additional information about DSM plans, see “Guidance for Data and Safety 

Monitoring Plans: Sponsor-Investigator Initiated Clinical Trials”] 

e. Early stopping rules 

[INSTRUCTIONS: Describe the early stopping rules of the trial.] 

f. Study Interruption or withdrawal 

[INSTRUCTIONS: Include here any potential reasons for interruption or 

discontinuation of the protocol.] 

4.3 Risk Analysis 


section of the IDE application is consistent with language contained in the clinical protocol.] 

A. Anticipated risks 

[INSTRUCTIONS: Describe all increased risks to which the subjects (patientssubjects 

and normal controls, if applicable) will be exposed as a result of their 

participation in the clinical study. 

Address the steps that will be taken to minimize these risks. 

Provide an analysis of the benefit-to-risk ratio of study participation (i.e., for each of 

the study populations, as applicable) and a corresponding justification for 

conducting the clinical study.] 

B. Adverse event recording/reporting 

a. Adverse event definitions 

[INSTRUCTIONS: The following is an EXAMPLE of suggested text used by the 

University of Pittsburgh. Prior to submission for FDA review, the applicant 

should confirm that the clinical protocol definitions and definitions used here are 

consistent.] 

Adverse effect: Any untoward medical occurrence in a clinical study of an 

investigational device; regardless of the causal relationship of the problem with 

the device or, if applicable, other study treatment or diagnostic product(s). 

Associated with the investigational device or, if applicable, other study 

treatment or diagnostic product(s): There is a reasonable possibility that 

the adverse effect may have been caused by the investigational device or, if 

applicable, the other study treatment or diagnostic product(s). 

Disability: A substantial disruption of a person‟s ability to conduct normal life 

functions. 

Page 37 of 78


Life-threatening adverse effect: Any adverse effect that places the 

subject, in the view of the Sponsor-Investigator, at immediate risk of death from 

the effect as it occurred (i.e., does not include an adverse effect that had it 

actually occurred in a more severe form, might have caused death). 

Serious adverse effect: Any adverse effect that results in any of the following 

outcomes: death, a life-threatening adverse effect, inpatient hospitalization or 

prolongation of existing hospitalization, a persistent or significant 

disability/incapacity, or a congenital anomaly/birth defect. 

Hospitalization: Hospitalization shall include any initial admission (even if less 

than 24 hours) to a healthcare facility as a result of a precipitating clinical 

adverse effect; to include transfer within the hospital to an intensive care unit. 

Hospitalization or prolongation of hospitalization in the absence of a 

precipitating, clinical adverse effect (e.g., for a preexisting condition not 

associated with a new adverse effect or with a worsening of the preexisting 

condition; admission for a protocol-specified procedure) is not, in itself, a serious 

adverse effect. 

Unexpected adverse effect: Any adverse effect, the frequency, specificity or 

severity of which is not consistent with the risk information described in the 

clinical study protocol(s) or elsewhere in the current IDE application, as 

amended. 

Unanticipated adverse device effect (UADE): Any serious adverse effect on 

health or safety or any life-threatening problem or death caused by, or 

associated with, a device, if that effect, problem, or death was not previously 

identified in nature, severity, or degree of incidence in the investigational plan or 

IDE application (including a supplementary plan or application), or any other 

unanticipated serious problem associated with a device that relates to the rights, 

safety, or welfare of subjects (21 CFR 812.3(s)). 

b. Eliciting adverse effect information 



should confirm that the clinical protocol description of how adverse effect 

information will be elicited from subjects and text used here are consistent.] 

Clinical study participants will be routinely questioned about adverse effects at 

study visits. 

c. Recording and assessment of adverse effects 



should confirm that the clinical protocol description of how adverse effects will 

be recorded and assessed and the text used here are consistent.] 

All observed or volunteered adverse effects (serious or non-serious) and 

abnormal test findings, regardless of treatment group, if applicable, or suspected 

causal relationship to the investigational device or, if applicable, other study 

treatment or diagnostic product(s) will be recorded in the subjects‟ case 

Page 38 of 78


histories. For all adverse effects, sufficient information will be pursued and/or 

obtained so as to permit 1) an adequate determination of the outcome of the 

effect (i.e., whether the effect should be classified as a serious adverse effect) 

and; 2) an assessment of the casual relationship between the adverse effect 

and the investigational device or, if applicable, the other study treatment or 

diagnostic product(s). 

Adverse effects or abnormal test findings felt to be associated with the 

investigational device or, if applicable, other study treatment or diagnostic 

product(s) will be followed until the effect (or its sequelae) or the abnormal test 

finding resolves or stabilizes at a level acceptable to the Sponsor-Investigator. 

i. Abnormal test findings: 

[INSTRUCTIONS: The following is an EXAMPLE of suggested text 

used by the University of Pittsburgh. Prior to submission for FDA review, 

the applicant should confirm that the clinical protocol and text used here 

regarding abnormal test findings are consistent.] 

An abnormal test finding will be classified as an adverse effect if one or 

more of the following criteria are met: 

• The test finding is accompanied by clinical symptoms. 

• The test finding necessitates additional diagnostic evaluation(s) or 

medical/surgical intervention; including significant additional 

concomitant drug or other therapy. (Note: simply repeating a test 

finding, in the absence of any of the other listed criteria, does not 

constitute an adverse effect.) 

• The test finding leads to a change in study dosing or exposure or 

discontinuation of subject participation in the clinical study. 

• The test finding is considered an adverse effect by the Sponsor- 

Investigator. 

ii. 

iii. 

Causality and severity assessment 

[INSTRUCTIONS: The following is an EXAMPLE of suggested text 

used by the University of Pittsburgh. Prior to submission for FDA review, 

the applicant should confirm that the clinical protocol and text used here 

regarding causality and severity assessment are consistent.] 

The Sponsor-Investigator will promptly review documented adverse 

effects and abnormal test findings to determine 1) if the abnormal test 

finding should be classified as an adverse effect; 2) if there is a 

reasonable possibility that the adverse effect was caused by the 

investigational device or, if applicable, other study treatment or 

diagnostic product(s); and 3) if the adverse effect meets the criteria for a 

serious adverse effect. 

If the Sponsor-Investigator‟s final determination of causality is “unknown 

and of questionable relationship to the investigational device or, if 

applicable, other study treatment or diagnostic product(s)”, the adverse 

effect will be classified as associated with the use of the investigational 

device or study treatment or diagnostic drug product(s) for reporting 

Page 39 of 78


purposes. If the Sponsor-Investigator‟s final determination of causality is 

“unknown but not related to the investigational device or, if applicable, 

other study treatment or diagnostic product(s)”, this determination and 

the rationale for the determination will be documented in the respective 

subject‟s case history. 

d. Reporting of adverse effects to the FDA 



should confirm that the clinical protocol description of adverse effect reporting to 

FDA and the text used here are consistent. 

NOTE: An example Form FDA 3500A has been included in the Appendices for 

the applicant‟s reference only. Instructions for form completion are also 

provided. Neither the example form nor the instructions for completion should 

be included in the IDE submission for FDA review. 

NOTE: In the case of Sponsor-Investigator, the reports should be reported to 

FDA and the IRB at the same time.] 

The Sponsor-Investigator will submit a completed FDA Form 3500A to the 

FDA‟s Center for Devices and Radiological Health for any observed or 

volunteered adverse effect that is determined to be an unanticipated adverse 

device effect. A copy of this completed form will be provided to all participating 

sub-investigators. 

The completed FDA Form 3500A will be submitted to the FDA as soon as 

possible and, in no event, later than 10 working days after the Sponsor- 

Investigator first receives notice of the adverse effect. 

If the results of the Sponsor-Investigator‟s follow-up evaluation show that an 

adverse effect that was initially determined to not constitute an unanticipated 

adverse device effect does, in fact, meet the requirements for reporting; the 

Sponsor-Investigator will submit a completed FDA Form 3500A as soon as 

possible, but in no event later than 10 working days, after the determination was 

made. 

For each submitted FDA Form 3500A, the Sponsor-Investigator will identify all 

previously submitted reports that that addressed a similar adverse effect 

experience and will provide an analysis of the significance of newly reported 

adverse effect in light of the previous, similar report(s). 

Subsequent to the initial submission of a completed FDA Form 3500A, the 

Sponsor-Investigator will submit additional information concerning the reported 

adverse effect as requested by the FDA. 

e. Reporting of adverse effects to the responsible IRB 

[INSERT: Suggested text is provided below. If used, the applicant should 

confirm that the clinical protocol description of adverse effect reporting to the 

IRB and the text used here are consistent prior to submission for FDA review.] 

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As per the Johns Hopkins Medicine Institutional Review Board Guideline entitled 

„Research Using FDA Test Articles (August 2010),” the IDE Sponsor- 

Investigator will submit to all reviewing IRBs and participating investigators any 

evaluation of an unanticipated device effect within ten (10) working days of first 

receiving notice of the effect (21 CFR 812.150 (b)(1)). 

Follow-up information to reported adverse effects will be submitted to the IRB as 

soon as the relevant information is available. If the results of the Sponsor- 

Investigator‟s follow-up investigation show that an adverse effect that was 

initially determined to not require reporting to the IRB does, in fact, meet the 

requirements for reporting; the Sponsor-Investigator will report the adverse 

effect to the IRB as soon as possible, but in no event later than 10 calendar 

days, after the determination was made. 

C. Withdrawal of subjects due to adverse effects 

[INSTRUCTIONS: Specify the criteria and procedures for withdrawing subjects from 

continued exposure to the investigational device or, if applicable, other study 

treatment or diagnostic product(s) due to an observed or volunteered adverse effect; 

to include the type and timing of data to be collected from withdrawn subjects. 

Specify if subjects withdrawn from study participation due to an adverse effect will 

be replaced and, if so, the corresponding procedures for their replacement.] 

4.4 Description of the Investigational Device 

[INSTRUCTIONS: Provide a description of each important component, ingredient or 

element, property, and principle of operation of the investigational device. 

Describe any anticipated change(s) in the investigational device during the course of the 

clinical study, if applicable. If no changes to the device are anticipated, state this.] 

4.5 Monitoring Procedures 

[INSERT: Incorporate the text provided below as written, then add the information 

addressed in the „instructions‟ below.] 

Johns Hopkins University policy requires a monitoring process for receipt, dispensing, and 

record keeping concerning all devices that are studied using an IDE granted by FDA. The 

monitoring process shall be performed by the Compliance Monitoring Specialists of the 

Johns Hopkins Office of Human Subjects Research (OHSR). The address of the Johns 

Hopkins Office of Human Subjects Research is: 

Johns Hopkins Office of Human Subjects Research 

1620 M c Elderry Street 

Reed Hall - B130 

Baltimore, MD 21205-1911 

Researchers who serve as a Sponsor-Investigator for an IDE research study are required 

by the Johns Hopkins University to follow FDA regulations 21 CFR 812 Subpart C 

applicable to Sponsor responsibilities. 

Page 41 of 78


Compliance Monitoring Specialists of the Johns Hopkins OHSR will conduct a monitoring 

visit for investigators holding an IDE to determine compliance with FDA Sponsor 

requirements in 21 CFR 812 before initiation of the research. 

[INSTRUCTIONS: Describe the nature and timing of any quality control/quality assurance 

reviews (i.e., independent of the previously described monitoring activities) that will be 

undertaken by the Sponsor-Investigator to ensure appropriate conduct of the clinical study 

and quality and completeness of the accrued study data. I.e., describe the data and safety 

monitoring plan for the clinical study as outlined in the IRB application or include DSM 

plan/charter in the appendices and reference same here. 

As 21CFR 812.43(d) does not give specific criteria for selection of monitors, as Sponsor- 

Investigator, the applicant is responsible for choosing appropriate monitors based on 

identified risk. Therefore, if one or both (internal and external) monitors are required they 

must be identified here. The investigator running the trial is technically responsible for 

overall „internal monitoring‟, but may delegate this responsible to another project team 

member. If a Sponsor-Investigator is running trial, then she/he is technically responsible for 

all trial monitoring, whether internal or external. Include names and contact information for 

internal and external monitors.] 

Internal Monitor: 

Name 

Title 

Address 

Phone number 

FAX number 

Email Address 

External Monitor: 

Name 

Title 

Address 

Phone number 

FAX number 

Email Address 

4.6 Additional Records and Reports 

A. Data handling and record-keeping 

[INSTRUCTIONS: Describe the procedures for management and retention of study 

data including accounting for any missed, unused, and/or spurious data. In 

appendices, include a copy of Case Report Forms (CRF) and reference “See 

Appendix__.” 

Page 42 of 78


Identify, if applicable, any clinical study data that will be recorded directly on the 

CRF, whereupon the CRF data is to be considered the Source Data. It is strongly 

suggested that CRFs NOT be used to collect source data. However, if any CRFs 

are to be used to collect source data, then there must be an SOP describing the 

CRFs and the procedures for documenting the source data on the CRFs. 

Additionally, the CRFs must be signed and dated at the time the data is collected by 

the person collecting the data. 

If an electronic system will be used as the sole instrument for the recording and 

analysis of clinical and laboratory data related to the safety and/or efficacy of the 

investigational device, address compliance with the FDA‟s electronic records and 

electronic signatures regulations at 21 CFR Part 11.] 

B. Record maintenance and retention 

[INSTRUCTIONS: Insert the following text provided, then add information discussed 

in instructions below. Prior to submission for FDA review, the applicant should 

confirm that the clinical protocol and provided text used here are consistent.] 

The Sponsor-Investigator will retain the specified records and reports for up to 2 

years after the marketing application is approved for the investigational device; or, if 

a marketing application is not submitted or approved for the investigational drug, 

until 2 years after investigations under the IDE have been discontinued and the FDA 

so notified. 

[INSTRUCTIONS: Describe how the subject-specific data and Case Report Forms 

will be coded and how these materials, and the subject identification code list, will 

be stored so as to protect the subjects‟ confidentiality. Specify that subject names 

or other directly identifiable information will not appear on any reports, publications, 

or other disclosures of clinical study outcomes.] 

C. Clinical Trial Registration 

[COMMENTS: Per Title VIII of the Food and Drug Administration Amendments Act 

of 2007 or FDAAA (U.S. Public Law 110-85) clinical trial registration and reporting 

requirements, all applicable trials must be registered at clinicaltrials.gov, and results 

reported as required. As part of this requirement, the FDA created the Form FDA 

3674 to certify compliance with registration of trials. 

To follow are a number of resources that provide additional guidance and 

information concerning this requirement. If the Sponsor-Investigator needs 

additional guidance, please contact the ICTR Research Navigators. Even if the 

protocol being submitted is not required to be registered at ClinicalTrials.gov, the 

Sponsor-Investigator must check the appropriate box in section 9 of the form and 

submit the Form FDA 3674, entitled „Certification of Compliance, under 42 U.S.C § 

282(j)(5)(B), with Requirements of ClinicalTrials.gov Data Bank (42 U.S.C § 282(j))‟, 

with the IND application.] 

Page 43 of 78


[GUIDANCE INFORMATION RESOURCES FOR TRIAL REGISTRATION] 

FDA Guidance Document on registering trials on ClinicalTrials.gov 

Clinicaltrials.gov Protocol Registration System Information Website 

NIH Grantees Clinicaltrials.gov and FDAAA Policy Site 

Elaboration of Definitions of Responsible Party and Applicable Clinical Trial 

JHM IRB Organizational Policy 

JHM IRB Organizational Guideline 

Form FDA 3674 website to download PDF fillable form 

Form FDA 3674 instructions website 

[INSTRUCTIONS: An “applicable device” clinical trial is a prospective clinical study 

of health outcomes comparing an intervention with a device against a control in 

human subjects (other than a small clinical trial to determine the feasibility of a 

device, or a clinical trial to test prototype devices where the primary outcome 

measure relates to feasibility and not to health outcomes). If the applicant‟s clinical 

trial meets the definition of “applicable device” trial, include the following text and 

provide a completed FDA Form 3674 in appendices. If it does not meet the 

definition of applicable trial, state so here.] 

Please see the signed and dated Form FDA 3674 in Appendix ____. 

Page 44 of 78


Section 5.0: Methods, Facilities and Controls Information 







regulations.] 


A description of the methods, facilities, and controls used for the manufacture, processing, 

packing, storage, and, where appropriate, installation of the device, in sufficient detail so that a 

person generally familiar with good manufacturing practices can make a knowledgeable judgment 

about the quality control used in the manufacture of the device. 

[REGULATORY REFERENCE: 21CFR820.30 Design Controls] 

(a)General: 

(1) Each manufacturer of any class III or class II device, and the class I devices listed in paragraph 

(a)(2) of this section, shall establish and maintain procedures to control the design of the device in 

order to ensure that specified design requirements are met. 

(2) The following class I devices are subject to design controls: 

(i) Devices automated with computer software; and 

(ii) The devices listed in the following chart: 

Section 

Device 

868.6810 Catheter, Tracheobronchial Suction. 

878.4460 Glove, Surgeon's. 

880.6760 Restraint, Protective. 

892.5650 System, Applicator, Radionuclide, Manual 

892.5740 Source, Radionuclide Teletherapy 

(b)Design and development planning; Each manufacturer shall establish and maintain plans that 

describe or reference the design and development activities and define responsibility for 

implementation. The plans shall identify and describe the interfaces with different groups or 

activities that provide, or result in, input to the design and development process. The plans shall 

be reviewed, updated, and approved as design and development evolves. 

(c)Design input: Each manufacturer shall establish and maintain procedures to ensure that the 

design requirements relating to a device are appropriate and address the intended use of the 

device, including the needs of the user and patient. The procedures shall include a mechanism for 

addressing incomplete, ambiguous, or conflicting requirements. The design input requirements 

shall be documented and shall be reviewed and approved by a designated individual(s). The 

approval, including the date and signature of the individual(s) approving the requirements, shall be 

documented. 

Page 45 of 78


(d)Design output: Each manufacturer shall establish and maintain procedures for defining and 

documenting design output in terms that allow an adequate evaluation of conformance to design 

input requirements. Design output procedures shall contain or make reference to acceptance 

criteria and shall ensure that those design outputs that are essential for the proper functioning of 

the device are identified. Design output shall be documented, reviewed, and approved before 

release. The approval, including the date and signature of the individual(s) approving the output, 

shall be documented. 

(e)Design review: Each manufacturer shall establish and maintain procedures to ensure that 

formal documented reviews of the design results are planned and conducted at appropriate stages 

of the device's design development. The procedures shall ensure that participants at each design 

review include representatives of all functions concerned with the design stage being reviewed and 

an individual(s) who does not have direct responsibility for the design stage being reviewed, as 

well as any specialists needed. The results of a design review, including identification of the 

design, the date, and the individual(s) performing the review, shall be documented in the design 

history file (the DHF). 

(f)Design verification: Each manufacturer shall establish and maintain procedures for verifying the 

device design. Design verification shall confirm that the design output meets the design input 

requirements. The results of the design verification, including identification of the design, 

method(s), the date, and the individual(s) performing the verification, shall be documented in the 

DHF. 

(g)Design validation: Each manufacturer shall establish and maintain procedures for validating the 

device design. Design validation shall be performed under defined operating conditions on initial 

production units, lots, or batches, or their equivalents. Design validation shall ensure that devices 

conform to defined user needs and intended uses and shall include testing of production units 

under actual or simulated use conditions. Design validation shall include software validation and 

risk analysis, where appropriate. The results of the design validation, including identification of the 

design, method(s), the date, and the individual(s) performing the validation, shall be documented in 

the DHF. 

(h)Design transfer: Each manufacturer shall establish and maintain procedures to ensure that the 

device design is correctly translated into production specifications. 

(i)Design changes: Each manufacturer shall establish and maintain procedures for the 

identification, documentation, validation or where appropriate verification, review, and approval of 

design changes before their implementation. 

(j)Design history file: Each manufacturer shall establish and maintain a DHF for each type of 

device. The DHF shall contain or reference the records necessary to demonstrate that the design 

was developed in accordance with the approved design plan and the requirements of this part. 

Page 46 of 78


5.0 Methods, Facilities and Control Information 

[COMMENT: This section of the IDE application should incorporate or reference a 

description of the methods, facilities, and controls used for the manufacturing, processing, 

packaging, and (if applicable) installation of the device.] 

5.1 Device Manufacturer 

A. Manufacturer name, address, and contact information 

[INSTRUCTIONS: Incorporate the following information.] 

Name of device manufacturer: 

Address: 

Contact person: 

Telephone number: 

FAX number: 

B. Manufacturer compliance with Subpart C, Design Controls (section 820.30), of 

the Quality System Regulations (21 CFR Part 820): 

[INSTRUCTIONS: Specify whether or not the manufacturer of the device is a 

commercial or contract manufacturer with a history of operating in full compliance 

with the FDA‟s Quality System Regulations; in particular the Design Controls section 

(i.e., Section 820.30) of these regulations. If the manufacturer of the device does 

not operate, or does not have a history of operating, in full compliance with these 

regulations, provide a reason for such non-compliance (e.g., INSERT: “The 

manufacturer of the device does not have a history of operating in full compliance 

with 21 CFR 820 because Johns Hopkins University is an academic institution and 

the proposed clinical investigation of the device is limited to a 

study.”) 

If the device being evaluated in the proposed clinical investigation is currently a 

commercially marketed device (i.e., labeled for a different clinical indication), specify 

this and incorporate under this section (or in a referenced Appendix), a letter or 

other written notification from the commercial manufacturer authorizing the FDA to 

access the manufacturer‟s respective PMA or 510K application or, if applicable, the 

manufacturer‟s Device Master Record. (E.g. INSERT: “The device under study is 

commercially available and is under investigation for a new indication. A Letter of 

Authorization to the manufacturer‟s is included in this application as 

Appendix X.”) 

If the device being evaluated in the proposed clinical investigation is currently being 

evaluated (e.g., for a different clinical indication) under a separate industrysponsored 

IDE, specify this and incorporate under this section (or in a referenced 

Appendix), a letter or other written notification from the manufacturer authorizing the 

FDA to access the manufacturer‟s respective IDE or Device Master Record (i.e., the 

compilation of records containing the procedures and specifications for a finished 

device). (E.g. INSERT: “The device under study is currently being evaluated for a 

different clinical indication under an industry sponsored IDE. A Letter of 

Authorization to the manufacturer‟s Device Master Record is included in this 

application as Appendix X.”)] 

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C. Device Design and Manufacturing Information 

[INSTRUCTIONS: Incorporate these sections if the device (or other 

components of the device system) is/are being manufactured by or under the 

direction of the Sponsor-Investigator for the specific purpose of its evaluation 

under this IDE application. If this is not the case, so state here and delete 

Section C.a through and including Section E.] 

Note: The extent of the manufacturing information to be provided under this section 

must be adequate so as to permit a judgment that the manufacturing, processing 

and quality control testing procedures will result routinely in a device that meets the 

intended specifications. It is recommended that the manufacturing information be 

presented in the following format and address, at a minimum, the following 

information: 

a. Device design: 

[INSTRUCTIONS: Provide an adequate characterization or description of the 

device and its operation to include the (a): 

• Design/engineering drawing of the device 

• Rationale for the device design 

• Device and device performance specifications 

• Description of the device materials (including biocompatibility information) 

• Description of device function (e.g., how does the device and/or other 

components/subsystems work together to achieve the desired function) 

• Validation testing for the subsystems and main system 

Note: the manufacture of devices for evaluation under Sponsor-Investigator IDE 

applications is subject to compliance with the Design Controls section (Section 

820.30) of the FDA‟s Quality System Regulations (21 CFR Part 820). While it is 

not necessary to address compliance with each of the Design Control 

requirements in the IDE application, the Sponsor-Investigator and/or 

manufacturer should be able to provide certain documentation that the following 

activities have occurred and/or that applicable processes and procedures are in 

place: 

i. Design input 

[INSTRUCTIONS: Design input refers to the process for ensuring that 

design requirements relating to a device are appropriate and address the 

intended use of the device, including the needs of the user and patient. 

Design input establishes the desired physical and performance 

requirements of device that are used as a basis for device design. The 

design input discussions and requirements should be documented and 

should be reviewed and approved by the Sponsor-Investigator. The 

approval, including the date and signature of the Sponsor-Investigator, 

should also be documented. 

Page 48 of 78


ii. 

Design output 

[INSTRUCTIONS: Design output refers to the process for defining and 

documenting that the output of the device will be in conformance with the 

design input requirements. Design output procedures shall contain or 

make reference to acceptance criteria and shall ensure that those design 

outputs that are essential for the proper functioning of the device are 

identified. Design output discussions (i.e., which are anticipated to occur 

at each design phase and at the end of the total design effort) should be 

documented, reviewed, and approved by the Sponsor-Investigator before 

the next design phase or release of the device. The approval, including 

the date and signature of the Sponsor-Investigator, should be 

documented. Note that the design output process forms the basis for the 

acceptance criteria of the final device that appear in a Device Master 

Record; i.e., the compilation of the records containing the procedures 

and specifications for a finished device.] 

iii. 

Design verification 

[INSTRUCTIONS: Design verification involves confirmation by 

examination/testing and the provision of objective evidence that the 

design output meets the design input requirements. The results of the 

design verification, including identification of the design stage, 

method(s), the date, and the individual(s) performing the verification 

should be documented in a Design History File; i.e., the compilation of 

records which describes the design history of a finished device.] 

iv. 

Design review 

[INSTRUCTIONS: Design review refers to formal, systematic (i.e., 

conducted at planned intervals) reviews of the design verification results 

conducted at appropriate stages of the device‟s design development for 

the purpose of evaluating the adequacy of the design requirements, 

evaluating the capability of the design to meet these requirements, and 

identifying problems. The outcome of the design reviews, including 

identification of the design stage, the date, and the individuals involved in 

the review should be documented in the Design History File.] 

v. Design validation 

[INSTRUCTIONS: Design validation refers to the process and 

procedures for confirming, by the collection of objective evidence, that 

the device specifications conform to the user‟s needs and intended 

use(s). Design validation should be performed under defined operating 

conditions on initial production units, lots, or batches, or their 

equivalents. Design validation should include testing of production units 

under actual or simulated use conditions; and should, where appropriate, 

include software validation and risk analysis. The results of the design 

validation evaluation(s), including identification of the design, method(s), 

the date, and the individual(s) performing the validation should be 

documented in the Device History File.] 

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vi. 

Design transfer 

[INSTRUCTIONS: There should be an established (i.e., written) process 

and corresponding procedures for ensuring that the acceptance criteria 

associated with the final device design acceptance are correctly 

translated into production specifications.] 

vii. 

Design changes 

D. Manufacturing controls 

[INSTRUCTIONS: There should be an established (i.e., written) process 

and corresponding procedures for the identification, documentation, 

validation or where appropriate verification, review, and approval of 

design changes before their implementation.] 

[INSTRUCTIONS: Provide a description of the process validation and the 

manufacturing controls (i.e., quality control testing) that will be used to ensure that 

the device(s) is (are) produced in accordance with the device design and 

performance specifications. 

Note that process validation refers to objective evidence that a process consistently 

produces a product that meets its predetermined specifications. Appropriate 

process validation is particularly important if the manufacturing process results in 

the production of multiple units of the device wherein only a sample of the total 

batch or lot will actually undergo defined quality control testing to ensure that the 

devices meet or exceed defined specifications prior to their release for human use. 

Emphasis on appropriate process validation may be lessened if the manufacturing 

process is directed at producing a lot or batch comprised of only one or a very 

limited number of devices and the quality control testing is performed on each 

device in the lot or batch prior to its release for human use. It is thus important to 

specify under this section if the manufacturing process will be directed at producing 

only one or a limited number of devices per given lot or batch.] 

E. Processing, Packaging, Storage and Installation 

[INSTRUCTIONS: Provide a description of any processing, package, storage and/or 

installation of the device (as applicable.)] 

Page 50 of 78


Section 6.0: Example of Investigator Agreements, Certification of Investigators 

and Financial Interest 







regulations.] 

[REGULATORY REFERENCE: 21CFR812.20(b)(4&5)] 

(b)Contents: An IDE application shall include: 

(4) An example of the agreements to be entered into by all investigators to comply with 

investigator obligations under this part, and a list of the names and addresses of all 

investigators who have signed the agreement. 

(5) A certification that all investigators who will participate in the investigation have signed 

the agreement, that the list of investigators includes all the investigators participating in 

the investigation, and that no investigators will be added to the investigation until they 

have signed the agreement. 

[REGULATORY REFERENCE: 21 CFR 54 Financial Disclosures By Clinical Investigators 

21 CFR 54.4 Certification and disclosure requirements 

For purposes of this part, an applicant must submit a list of all clinical investigators who conducted 

covered clinical studies to determine whether the applicant's product meets FDA's marketing 

requirements, identifying those clinical investigators who are full-time or part-time employees of the 

sponsor of each covered study. The applicant must also completely and accurately disclose or 

certify information concerning the financial interests of a clinical investigator who is not a full-time 

or part-time employee of the sponsor for each covered clinical study. Clinical investigators subject 

to investigational new drug or investigational device exemption regulations must provide the 

sponsor of the study with sufficient accurate information needed to allow subsequent disclosure or 

certification. The applicant is required to submit for each clinical investigator who participates in a 

covered study, either a certification that none of the financial arrangements described in 54.2 exist, 

or disclose the nature of those arrangements to the agency. Where the applicant acts with due 

diligence to obtain the information required in this section but is unable to do so, the applicant shall 

certify that despite the applicant's due diligence in attempting to obtain the information, the 

applicant was unable to obtain the information and shall include the reason. 

(a) The applicant (of an application submitted under sections 505, 506, 510(k), 513, or 515 of the 

Federal Food, Drug, and Cosmetic Act, or section 351 of the Public Health Service Act) that relies 

in whole or in part on clinical studies shall submit, for each clinical investigator who participated in 

a covered clinical study, either a certification described in paragraph (a)(1) of this section or a 

disclosure statement described in paragraph (a)(3) of this section. 

(1) Certification: The applicant covered by this section shall submit for all clinical investigators (as 

defined in 54.2(d)), to whom the certification applies, a completed Form FDA 3454 attesting to 

the absence of financial interests and arrangements described in paragraph (a)(3) of this 

section. The form shall be dated and signed by the chief financial officer or other responsible 

corporate official or representative. 

Page 51 of 78


(2) If the certification covers less than all covered clinical data in the application, the applicant shall 

include in the certification a list of the studies covered by this certification. 

(3) Disclosure Statement: For any clinical investigator defined in 54.2(d) for whom the applicant 

does not submit the certification described in paragraph (a)(1) of this section, the applicant 

shall submit a completed Form FDA 3455 disclosing completely and accurately the following: 

(i) Any financial arrangement entered into between the sponsor of the covered study and the 

clinical investigator involved in the conduct of a covered clinical trial, whereby the value of 

the compensation to the clinical investigator for conducting the study could be influenced by 

the outcome of the study; 

(ii) Any significant payments of other sorts from the sponsor of the covered study, such as a 

grant to fund ongoing research, compensation in the form of equipment, retainer for 

ongoing consultation, or honoraria; 

(iii) Any proprietary interest in the tested product held by any clinical investigator involved in a 

study; 

(iv) Any significant equity interest in the sponsor of the covered study held by any clinical 

investigator involved in any clinical study; and 

(v) Any steps taken to minimize the potential for bias resulting from any of the disclosed 

arrangements, interests, or payments. 

(b) The clinical investigator shall provide to the sponsor of the covered study sufficient accurate 

financial information to allow the sponsor to submit complete and accurate certification or 

disclosure statements as required in paragraph (a) of this section. The investigator shall promptly 

update this information if any relevant changes occur in the course of the investigation or for 1 year 

following completion of the study. 

(c) Refusal to file application. FDA may refuse to file any marketing application described in 

paragraph (a) of this section that does not contain the information required by this section or a 

certification by the applicant that the applicant has acted with due diligence to obtain the 

information but was unable to do so and stating the reason. 

[NOTE: Examples of an Investigator Agreement, Form FDA 3454 (Financial Interest Certification) 

and Form FDA 3455 (Financial Interest Disclosure) are provided in the Appendices for applicant 

reference] 

Page 52 of 78


6.0 Example of Investigator Agreements, Certification of Investigators and Financial 

Interest 

6.1 Investigator‟s Agreement 

A. As an example of the investigator‟s agreement used in this study, the document as 

completed by supply name of Sponsor Investigator, the Principal Investigator of this 

study, is shown in Appendix_____ [INSERT: Include correct Appendix number] 

B. The investigator's curriculum vitae is provided in Appendix_____ 

[INSERT: Include correct Appendix number] 

C. A statement of the investigator's relevant experience (including the dates, location, 

extent and type of experience) is provided in Appendix_____ 


D. An explanation of the circumstances that led to the termination of any investigation 

or research endeavor in which the investigator was involved has been provided in 

Appendix_____ [INSERT: Include correct Appendix number] 

E. A statement of the investigator's commitment to: conduct the investigation in 

accordance with the agreement, the investigational plan, Part 812 and other 

applicable FDA regulations, and conditions of approval imposed by the reviewing 

IRB and FDA; supervise all testing of the device involving human subjects; and 

ensure that the requirements for obtaining informed consent are met is provided in 

Appendix ____ [INSERT: Include correct Appendix number] 

F. A statement of the investigator‟s commitment to provide sufficient and accurate 

financial disclosure information and update information if any relevant changes 

occur during the investigation and for one year following the completion of the study 

is provided in Appendix _____ [INSERT: Include correct Appendix number] 

G. Certification that all participating investigators have signed the agreement and that 

no investigator will be added until the agreement is signed is provided in Appendix 

_____ [INSERT: Include correct Appendix number] 

H. Name and address of investigators who have signed the agreement. The list 

containing the names and respective address of investigators who have signed the 

investigator‟s agreement for this study is shown in Appendix _____ 


Page 53 of 78


Section 7.0: Reviewing Institutional Review Boards 







regulations.] 



A list of the name, address, and chairperson of each IRB that has been or will be asked to review 

the investigation and a certification of the action concerning the investigation taken by each such 

IRB should be included here. If the IRB application has not yet been submitted and no designation 

has been made as to which JHM IRB will be reviewing the application, list all JHM IRB 

chairpersons here.] 

Page 54 of 78


7.0 Reviewing Institutional Review Boards 

7.1 Name, address, and chairperson of each reviewing IRB 

A. This study will be reviewed by a single IRB [INSTRUCTIONS: Include if applicable, 

otherwise delete this statement] 

Name: 

Address: 

Chairperson(s): 

B. Certification of action taken by IRB 

Delete non- 

[INSTRUCTIONS: Complete and include the applicable statement. 

applicable statement.] 

a. This investigation has already been approved by the following IRB‟s (The 

respective approval letters are shown in Appendix number(s) (Supply correct 

designation(s): [INSERT: List all applicable IRB‟s] 

b. This investigation is currently awaiting or is under review by the following IRB‟s: 

[INSERT: List all applicable IRB‟s] 

C. Names and addresses of additional institutions, not previously identified, where a part of 

the investigation may be conducted 

[INSERT: List all applicable IRB‟s. If none, indicate so here.] 

Name: 

Address: 


Page 55 of 78


Section 8.0: Other Involved Institutions 







regulations.] 



(7) The name and address of any institution at which a part of the investigation may be conducted 

that has not been identified in accordance with paragraph (b)(6) of this section. 

Page 56 of 78


8.0 Other Involved Institutions 

[INSTRUCTIONS: If applicable, list the name(s) and address(es) of any institution(s) at which a 

part of the clinical investigation of the device may be conducted and that has (have) not already 

been identified under the previous section (Reviewing Institutional Review Boards). If no 

institutions, other than those already listed above will be involved in conducting part of the clinical 

investigation, specify “None”.] 

Name: 

Address: 


Page 57 of 78


Section 9.0: Device Charges 







regulations.] 



(8) If the device is to be sold, the amount to be charged and an explanation of why sale does not 

constitute commercialization of the device. 


Promotion of Investigational Devices 

Under §812.7, a sponsor, investigator, or any person acting for or on behalf of a sponsor or 

investigator cannot: 

Promote or test market an investigational device, until after FDA has approved the device 

for commercial distribution. 

Commercialize an investigational device by charging the subjects or investigators a higher 

price than that necessary to recover costs of manufacture, research, development, and 

handling. 

Unduly prolong an investigation. If data developed by the investigation indicate that 

premarket approval (PMA) cannot be justified, the sponsor must promptly terminate the 

investigation. 

Represent that an investigational device is safe or effective. 

However, the sponsor may advertise for research subjects to solicit their participation in a study. 

Appropriate advertising methods include but are not necessarily limited to: newspaper, radio, TV, 

bulletin boards, posters, and flyers that are intended for prospective subjects. 

Advertisements should be reviewed and approved by the IRB to assure that it is not unduly 

coercive and does not promise a certainty of cure beyond what is outlined in the consent and the 

protocol. No claims should be made, either explicitly or implicitly, that the device is safe or effective 

for the purposes under investigation, or that the test article is known to be equivalent or superior to 

any other device. 

FDA considers direct advertising for study subjects to be the start of the informed consent and 

subject selection process. 

Additional guidance is available in the following guidance documents: 

"Information Sheets: Guidance for Institutional Review Boards and Clinical Investigators, 1998 - 

Recruiting for Study Subjects 

Preparing Notices of Availability of Investigational Medical Devices and for Recruiting Study 

Subjects 

Page 58 of 78


9.0 Device Charges 

[INSTRUCTIONS: Specify whether or not any of the investigators or the research subjects or their 

insurance providers will be charged for the device. 

If there will be a charge for the device, indicate the amount that will be charged and provide an 

explanation as to why charging this amount does not involve commercialization of the device (i.e., 

justify that the amount charged for the device represents only the actual costs associated with 

research and development, manufacture and distribution of the device.)] 

Page 59 of 78


Section 10.0: Device Labeling 







regulations.] 



(10) Copies of all labeling for the device 


Sec. 812.5 Labeling of investigational devices. 

(a)Contents. An investigational device or its immediate package shall bear a label with the 

following information: the name and place of business of the manufacturer, packer, or distributor (in 

accordance with 801.1), the quantity of contents, if appropriate, and the following statement: 

"CAUTION--Investigational device. Limited by Federal (or United States) law to investigational 

use." The label or other labeling shall describe all relevant contraindications, hazards, adverse 

effects, interfering substances or devices, warnings, and precautions. 

(b)Prohibitions. The labeling of an investigational device shall not bear any statement that is false 

or misleading in any particular and shall not represent that the device is safe or effective for the 

purposes for which it is being investigated. 

(c)Animal research. An investigational device shipped solely for research on or with laboratory 

animals shall bear on its label the following statement: "CAUTION--Device for investigational use in 

laboratory animals or other tests that do not involve human subjects." 

(d) The appropriate FDA Center Director, according to the procedures set forth in 801.128 or 

809.11 of this chapter, may grant an exception or alternative to the provisions in paragraphs (a) 

and (c) of this section, to the extent that these provisions are not explicitly required by statute, for 

specified lots, batches, or other units of a device that are or will be included in the Strategic 

National Stockpile. 

Page 60 of 78


10.0 Device Labeling 

[INSTRUCTIONS: Incorporate under this section (or by reference to an Appendix) a copy 

of the label that will be attached to the device or its immediate package and any other 

product labeling that will be provided to investigators. 

Note that the FDA‟s investigational device regulations (21 CFR Sec. 809.10(c)(2)(i)) specify 

that the investigational device or its immediate package shall bear a label with the following 

information: 

• Name and place of business of the manufacturer, packager, or distributor of the 

device; 

• Quantity of contents, if appropriate; 

• The statement, “CAUTION – Investigational device. Limited by Federal law to 

investigational use” 

• A description (i.e., on the immediate label or other product labeling) of all currently 

known and relevant contraindications, hazards, adverse effects, interfering 

substances or devices, warnings, and precautions] 

Page 61 of 78


Section 11.0: Consent Materials 







regulations.] 



(11) Copies of all forms and informational materials to be provided to subjects to obtain informed 

consent. 

Page 62 of 78


11.0 Consent Materials 

[INSTRUCTIONS: Incorporate under this section (or by reference to an Appendix) the 

proposed informed consent form(s) that will be used for the clinical investigation(s) of the 

device included as part of this IDE application. 

If applicable, incorporate under this section (or by reference to an Appendix) any other 

informational materials that will be provided to potential research subjects in obtaining their 

informed consent for study participation.] 

11.1 Patient Consent Forms 

A. A copy of the proposed Informed Consent document for this trial is provided in 

Appendix____. [INSERT: Provide correct appendix number.] 

B. A copy of _________________ [INSERT: Include other patient educational or 

informational documents that are to be presented to the subject which are being 

provided for FDA review] materials have been provided in Appendix ______. 

[INSERT: Provide correct appendix number.] 

Page 63 of 78


Section 12.0: Other Relevant Information 







regulations.] 



(12) Any other relevant information FDA requests for review of the application. 

Page 64 of 78


12.0 Other Relevant Information 

[INSTRUCTIONS: Incorporate under this section, any other relevant information that the FDA has 

requested for review of the application; e.g., information requested subsequent to a pre-IDE 

discussion of the proposed application.] 

Page 65 of 78


Section 13.0: Reference List 

[SECTION INTRODUCTION: Provide a list of references cited in the IDE application here. 

NOTE: The bibliographical information may instead be provided after each of the IDE application 

sections. If the Sponsor-Investigator chooses to do this, delete this section here and from the table 

of contents.] 

Page 66 of 78


13. Reference List 

[INSTRUCTIONS: Insert bibliographical information/literature cited.] 

Page 67 of 78


Section 14.0: Appendices 

[SECTION INTRODUCTION: Provide a list of the appendices in order of appearance in the 

sections of the IDE application. Before each new appendix, include a cover page describing the 

document(s) that will be found in that appendix. 

[ADDITIONAL INSTRUCTIONS: Copies of selected papers referenced in the IDE application: 

While not required, it is strongly suggested that the Sponsor-Investigator provide copies of key 

papers that are referenced in the body of the IDE application. Providing copies of any significant 

papers will make it easier for the FDA reviewers should they want additional information. As with 

the other appendices, include a cover page with this appendix, listing in order of appearance the 

citations for the papers being submitted with the IDE application.] 

Page 68 of 78


14.0 Appendices 

[INSTRUCTIONS: Insert and number appendix cover pages and materials in the order of 

appearance within the IDE ] 

Page 69 of 78


(EXAMPLE) 

APPENDIX ______ 

INVESTIGATOR AGREEMENT FOR CLINICAL INVESTIGATION OF THE 

___________________________ 

(Specify Investigational Device(s)) 

I, __________________________, agree to participate as the Principal Investigator in the clinical 

investigation of the ______________________________ [INSERT: Specify investigational device.] 

I have reviewed the following Food and Drug Administration (FDA) regulations: 21 CFR Part 812, 

Investigational Device Exemptions; 21 CFR Part 50, Protection of Human Subjects; and 21 CFR 

Part 54, Financial Disclosure by Clinical Investigators. 

I agree and/or certify that: 

1. I will conduct the clinical investigation in accordance with this agreement, all requirements of the 

investigational plan, IDE regulations, other applicable regulations of the FDA, and any conditions of 

approval imposed by my reviewing Institutional Review Board (IRB) or FDA. I agree to abide by all 

of the responsibilities of Investigators addressed under 21 CFR Part 812, Subpart E and Subpart 

G, including but not limited to the following: 

a. I will obtain written approval from the authorized IRB for the institution at which this 

investigation will be conducted. If I am not also the sponsor-investigator of the corresponding 

IDE application, I will submit the certification of IRB approval and any conditions of this 

approval to the Sponsor (Sponsor-Investigator). 

b. I will ensure that Informed Consent is obtained from each subject participating in this clinical 

investigation in accordance with the informed consent regulation found in 21 CFR Part 50, and 

that a signed copy of the informed consent is available to the Sponsor (Sponsor-Investigator) 

and the Sponsor‟s (Sponsor-Investigator‟s) designated monitor. 

c. I will supervise all testing of the [INSERT: Specify investigational device] on human subjects 

and will allow only those physician co-investigators listed on the last page of this agreement to 

administer this devices and/or perform follow-up medical evaluations on the device. 

d. I will be responsible for accountability of the [INSERT: Specify investigational device] at the 

study site and, if I am not also the Sponsor-Investigator of the corresponding IDE application, I 

will return all unused [INSERT: Specify investigational device] to the Sponsor (Sponsor- 

Investigator) or otherwise follow the instructions of the Sponsor (Sponsor-Investigator) for 

disposal of the unused devices. 

e. I will ensure the accurate completion of protocol case report forms and, if I am not also the 

Sponsor-Investigator of the corresponding IDE application, I will submit completed protocol 

case report forms, progress reports, and a final report to the Sponsor (Sponsor-Investigator) at 

the time frames specified in the Protocol and/or FDA regulations. 

f. I will direct the retention of required records and documents related to the investigation. 

Page 70 of 78


2. I have the appropriate, relevant qualifications to conduct and to oversee the conduct of the clinical 

investigation as documented by the following: [Check applicable statement] 

____ 

____ 

My relevant qualifications, including dates, location, extent, and type of experience, are 

listed in my most recent curriculum vitae (CV), which is attached to this Agreement and 

which will be maintained by the sponsor (sponsor-investigator) of the corresponding IDE 

application. 

My curriculum vitae (CV) does not reflect my relevant qualifications, therefore attached to 

this Agreement is a statement of my relevant experience (including dates, location(s), 

extent, and type of experience) which will be maintained by the sponsor (sponsorinvestigator) 

of the corresponding IDE application. 

3. There are no reasons to question my ability to oversee the appropriate conduct of this clinical 

investigation. [Check applicable statement] 

____ I have never participated in an investigation or other research activity which was terminated 

(disqualified) by FDA, the IRB (or equivalent), or sponsor of a study due to a noncompliance 

issue. 

____ I have participated in an investigation or other research activity which was terminated 

(disqualified) by FDA, the IRB (or equivalent), or sponsor of a study due to a noncompliance 

issue. The specific circumstances leading to this termination and my role in the 

respective problems or issues and the resolution of these problems or issues are 

summarized in an attachment to this Agreement. 

5. As required by 21 CFR Part 54, Financial Disclosure by Clinical Investigators, I will disclose 

sufficient and accurate financial information to the sponsor (sponsor-investigator) by completing 

the Certification of Financial Interest form (attached) and if applicable, the Disclosure of Financial 

Interest form (attached). I will also notify the sponsor (sponsor-investigator) if my disclosed 

financial information changes at any time during the clinical investigation or up to one year 

following the closure of the study. 

Investigator‟s Signature___________________________________ 

Date_______ 

Page 71 of 78



CERTIFICATION OF ALL PARTICIPATING INVESTIGATORS 

PRINCIPAL INVESTIGATOR 

____________________________________________ 

Name of Principal Investigator (please print or type) 

____________________________________________ 

Office (Mailing Address) 

____________________________________________ 

______________________________ ______________________________ 

City/State/Zip 

E-mail 

______________________________ ______________________________ 

Telephone 

FAX 

____________________________________________ __________________ 

Signature of Principal Investigator 

Date 

PHYSICIAN CO-INVESTIGATORS 

[INSTRUCTIONS: A current CV or statement of relevant experience and a completed Certification 

of Financial Interest statement and, if applicable, Financial Interest Disclosure statement is 

required to be submitted to the Sponsor (Sponsor-Investigator) for each physician co-investigator 

listed below.] 

As a physician co-investigator for this investigation, I have read the foregoing and agree to be 

bound by its terms. 

____________________________________________ 

Name of Physician Co-Investigator (please print or type) 

____________________________________________ 

Signature 

____________ 

Date 

____________________________________________ 


____________________________________________ 

Signature 

____________ 

Date 

____________________________________________ 


____________________________________________ 

Signature 

____________ 

Date 

Page 72 of 78


NON-PHYSICIAN CO-INVESTIGATORS 

[INSTRUCTIONS: A current CV or statement of relevant experience and a completed Form FDA 

3454 (Certification of Financial Interest) and, if applicable, a completed Form FDA 3455 (Financial 

Interest Disclosure) is required to be submitted to the Sponsor (Sponsor-Investigator) for each nonphysician 

co-investigator listed below.] 

As a non-physician co-investigator for this investigation, I have read the foregoing and agree to be 

bound by its applicable terms. 

_____________________________________________ 

Name of Co-Investigator (please print or type) 

_____________________________________________ 

Signature 

____________ 

Date 

_____________________________________________ 


_____________________________________________ 

Signature 

____________ 

Date 

_____________________________________________ 


_____________________________________________ 

Signature 

____________ 

Date 

_____________________________________________ 


_____________________________________________ 

Signature 

____________ 

Date 

_____________________________________________ 


_____________________________________________ 

Signature 

____________ 

Date 

Page 73 of 78



CVs OF ALL PARTICIPATING INVESTIGATORS 

Page 74 of 78


APPENDIX ______ CERTIFICATION: FINANCIAL INTERESTS AND ARRANGEMENTS OF 

CLINICAL INVESTIGATORS 

Form FDA -3454 

Page 75 of 78



DISCLOSURE: FINANCIAL INTERESTS AND ARRANGEMENTS OF 

CLINICAL INVESTIGATORS 

Form FDA 3455 

Page 76 of 78



FDA FORM 3500A MEDWATCH FDA MEDICAL PRODUCTS REPORTING 

FDA FORM 3500A Forms Link 

Instructions for Completing Form FDA 3500A 

Page 77 of 78


Page 78 of 78

IDE Application for an Investigational Device: - The Johns Hopkins ...

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