# Presentation: 463191

## IND Regulatory Requirements and Recommendations

**Karen D. Jones**
- Chief, Project Management Staff
- Division of Biologic Oncology Products
- Office of Oncology Drug Products
- Office of New Drugs
- Center for Drug Evaluation and Research
- FDA

## Biologic Oncology Products Reviewed in CDER 

- Monoclonal Antibodies
- Therapeutic Proteins
- Immunomodulators
- Enzymes
- Fusion Proteins

## Getting StartedIND Recommended Reading

- Regulations:  Title 21 of the Code of Federal Regulations (CFR)
- Parts 50, 56, 312
- The OODP Website
- _http://www.fda.gov/cder/Offices/OODP/default.htm_
- Guidance Documents
- _http://www.fda.gov/cder/regulatory/default.htm_

## OODP Website 

- Oncology Tools
- Approved Oncology Drugs
- Regulatory Tools
- Oncology Reference Tools
- Patient Liaison Program
- Additional Resources
- FDA Centers and Divisions

## OODP Website (Cont.)

- Access to Unapproved Drugs
- Single Patient or Emergency Use
- Treatment IND

## Pre-IND Meetings

- Determine necessity
- Experience
- Novel Product
- Novel Clinical Trial Design

## Pre-IND Meetings (Cont.)

- Submit Complete Request: as per Guidance for Industry:  Formal Meetings with Sponsors and Applicants for PDUFA Products, Feb. 2000 (via fax, email or paper) (_http://www.fda.gov/cder/guidance/2125fnl.htm_)
- Propose Realistic Dates
- Submit Briefing Packages Using Assigned Pre-IND Numbers

## IND Exemptions 

- Applicable Regulation:  21 CFR 312.2
- Guidance for Industry: IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer, January 2004 (_http://www.fda.gov/cder/guidance/6036fnl.pdf_)

## Submit a Complete IND Application 

- Cover Letter
- Completed FDA Form 1571
- Information Specified by 21 CFR 312.23
- Appropriate Letters of Cross-reference
- Format:  CTD preferred
- Paper Submissions:
- Three Copies, Bound as per CDER Requirements
- Desk Copies Permitted/Contact Assigned Project Manager

## Complete IND Application (Cont.) 

- Electronic Submissions:  eCTD
- Guidance for Industry:  Providing Regulatory Submissions in Electronic Format-Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, April 2006 (http://www.fda.gov/cder/guidance/7087rev.htm)
- Submit to Correct Center/Office/Division
- Be Available or Designate Contact (in cover letter)

## Initial IND Submission:  What to Expect from FDA/CDER/OODP/DBOP 

- Acknowledgment Letter (or Exemption letter, if appropriate)
- Telephone Contacts
- Request for Clarification of Submitted Information
- Request for Additional Information
- Request for Revisions of Submitted Information, e.g. Protocols
- Written Notification that IND May Proceed; or,
- Verbal Notification of clinical hold by Day 30, Followed by Written Notification within 7 Days

## Clinical Holds on Phase 1 Trials: 21 CFR 312.42(b)(1)(i-iv)

- Subjects Exposed to Unreasonable and Significant Risk of Illness or Injury
- Clinical Investigators *not* Qualified to Conduct Study
- Investigator Brochure Misleading, Erroneous or Materially Incomplete
- Insufficient Information Submitted to Assess Risks to Subjects

## Clinical Holds on Phase 2 or 3 Trials 21 CFR 312.42(b)(2)(i and ii) 

- Any of the Conditions Listed for Phase 1 Trials
- Study Plan or Protocol Deficient in Design to Meet Stated Objectives

## Interactions with FDA/CDER During Product Development (Phase 1, 2 and 3) 

- Review Letters
- Telephone Contacts
- FDA Initiated Teleconferences and/or Meetings
- Sponsor Initiated Teleconferences and/or Meetings

## Helpful Tips

- Clearly Indicate Assigned IND Number on All Submissions
- Notify the RPM when Time-sensitive Documents are Submitted
- File Timely/Complete submissions, e.g., Safety Reports, Annual Reports
- When in Doubt, Communicate, Communicate, Communicate!

## Questions?

- FDA/CDER/OND/OODP/DBOP Contact Information:
- Main Line:  301-796-2320
- Fax:  301-796-9849
- Initial Contact-CPMS
- Email:  karen.jones@fda.hhs.gov
- IND Specific Contact
- Assigned Regulatory Project Manager