IND Regulatory Requirements and Recommendations

1
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

2
Biologic Oncology Products Reviewed in CDER

• Monoclonal Antibodies
• Therapeutic Proteins
• Immunomodulators
• Enzymes
• Fusion Proteins

3
Getting StartedIND 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

4
OODP Website

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

5
OODP Website (Cont.)

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

6
Pre-IND Meetings

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

7
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/guid
  ance/2125fnl.htm)
• Propose Realistic Dates
• Submit Briefing Packages Using Assigned Pre-IND
  Numbers

8
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)

9
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

10
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)

11
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

12
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

13
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

14
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

15
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!

16
Questions?

• FDA/CDER/OND/OODP/DBOP Contact Information
• Main Line 301-796-2320
• Fax [phone]
• Initial Contact-CPMS
• Email karen.jones_at_fda.hhs.gov
• IND Specific Contact
• Assigned Regulatory Project Manager