Investigator Responsibilities under IND and IDE

As a consequence of  increased volume  of investigator-initiated clinical research involving drugs and/or devices, there are numerous institutional considerations to ensure that investigators and their research staffs are appropriately equipped to manage all aspects of the regulatory responsibilities and obligations associated with initiating and conducting such research.

PLEASE READ:

1.   Sponsor and Investigator Responsibility checklist with supporting documents (Partners Human Research Quality Improvement (QI) Program)

2. Understanding FDA Regulatory Requirements for Investigational New Drug Applications for Sponsor-Investigators (M. E. Blair Holbein, PhD, J Inv Medicine (2009), v. 57, n. 6, p. 689-695).

1. Contact CTSC for assistance with IND applications, if needed

2. Create the study protocol using one of the accepted industry templates. Language and format used for grants is not acceptable

3. Prepare IND package using templates and examples below. Allow  at least 4-6 weeks for IND preparation, collation, pagination, copying etc.   

  • Cover Letter (Example)
  • IND (TemplateExample). Sometimes  the  manufacturing information (CMC Section) can be abbreviated if:  a) a letter of authorization to cross-reference the original IND is available, or b) if the drug is approved and product insert is available
  • Fill out Form 1571, Investigational New Drug Application (Example). When downloading this form from the FDA website, note the OMB expiration date in the upper right corner. You form will not be accepted if it is past the expiration date. Instructions for filling out the Form1571 can be found here 
  • Fill out Form 1572, Statement of the Investigator (Example). Please read Frequently Asked Questions about Form 1572.
  • Fill out Certification Form 3674 (Clinicaltrials.gov attestation). Typically, you must submit the form 3674 with a new IND. Protocol amendments will require resubmission of this form (Example). If you plan to upload your trial to Clinicaltrials.gov, but have not done it yet, mark box  b. For instructions on how to fill out, click here
  • Assemble and bind volumes into plastic binders. Each binder must be labeled using the FDA format (Template)

4. Each Submission should contain: a signed cover letter, signed Form 1571, and the IND document. Create 3 copies of the entire submission. 

5. Send to:

Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
5901-B Ammendale Rd. Beltville, MD 20705-1266

Start with the FDA Website "Device Advice: Investigational Device Exemptions"

Download the  

comprehensive summary of device classification, regulations, IDE submissions, Humanitarian use designation etc.

Definitions

A medical device is:
"an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

  • intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals,
    OR
  • intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of it's primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes."

IMPORTANT: the clinical study of a new indication for an already marketed device falls under the IDE regulation.

Exemptions

Some studies may be exempt from the IDE regulations (21 CFR 812.2(c)), if: 

1. a legally marketed device when used in accordance with its labeling,
2. a diagnostic device if it is:
         • noninvasive;
         • does not require an invasive sampling procedure that presents significant risk;
         • does not by design or intention introduce energy into a subject;
          • and is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure;
3.  consumer preference testing…of legally marketed device(s)
4. a device intended solely for veterinary use;
5. a device shipped solely for research with laboratory animals

IDE requirements

• Study approved by an institutional review board (IRB). If the study involves a significant risk device, the IDE must also be approved by FDA;
• Informed consent from all patients obtained and documented;
• The device is labeled “CAUTION- Investigational Device. Limited to investigational use only”
• Sponsor-investigator complies with monitoring requirements
• Records and reports are maintained

How to file an IDE with the FDA


The IDE submission includes:
• Cover Letter
• Application

Content of the Cover Letter:

1. A statement that this is an original IDE application
2. Device information: a brief overview of the device
3. Sponsor-investigator contact information;
4. Device manufacturer information;
5. Applicant information (who submits this application);
6. Other relevant information (e.g. prior discussions with the FDA)

Example of a Cover Letter


 Content of an IDE Application: 

1. Table of Contents
2. Report of prior investigations (including animal work)
3. Investigational plan
4. Risk analysis (in table format)
5. Description of the device
6. Monitoring procedures
7. Manufacturing information
8. Sponsor-investigator information, including CV;
9. IRB information;
10. Sales information;
11. Environmental impact statement
12. Labeling
13. Informed Consent materials
14. Other information as pertinent

Use this IDE Template to generate IDE Application. The template expands each section in greater details.

Suggested format for IDE submissions

  • 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.).
  • Make 3 identical copies of each submission
  • In addition, the sponsors mush provide an eCopy per Guidance "eCopy Program for Medical Device Submissions."

Ready to submit? Use a helpful checklist for IDE Application

UCSF’s Clinical and Translational Science Institute has assessed and pre-selected a number of Contract Research Organizations (CROs) that offer a broad range of key research services. The CROs have been chosen on the basis of their proven technical expertise, flexibility, past experience in working with academic investigators, and price. UCSF offers a referral service to UC Davis investigators.

Currently pre-selected CROs offer a broad spectrum of expertise and services, including (but not limited to):

  • High-throughput screening
  • ADME (in vitro and in vivo)
  • Pharmacokinetics and pharmacodynamics
  • Toxicology (including GLP tox)
  • Bio/analytical services
  • Medicinal Chemistry and custom synthesis
  • GMP manufacturing
  • Preclinical disease models
  • Biocompatibility (for device development)

Additional CROs with device development expertise are currently being identified.

To get connected to a CRO, see UCSF website or contact Irina Gitlin (irina.gitlin@ucsf.edu or 415-514-8510).

Expanded Access or compassionate use is the use of investigational drug outside of a clinical trial for the sole purpose of treating a patient or patients with serious or life-threatening disease who have no acceptable medical option. Serious diseases or conditions are those associated with morbidity that has a substantial impact on day-to-day functioning. Whether a disease is serious is a matter of clinical judgement. Examples cited by FDA include epilepsy and in situ breast cancer.

Expanded Access includes three options:
• Treatment IND
• Group C treatment IND
• Emergency Use IND

Download the comprehensive summary here

NEW! 2013 Draft Guidance
Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers:

  • Who can make a submission? 
  • What are the roles of the patient’s physician and FDA ?
  • When should individual patient access be requested?
  • When can emergency use access begin?
  • And more....