1. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH Working with FDA: Biological Products and Clinical Development 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. Working with FDA: Biological Products and Clinical Development Karen Jones Biologic Oncology Products Reviewed in CDER  Monoclonal Antibodies  Therapeutic Proteins  Immunomodulators  Enzymes  Fusion Proteins

3. Working with FDA: Biological Products and Clinical Development Karen Jones 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/def ault.htm  Guidance Documents http://www.fda.gov/cder/regulatory/default. htm

4. Working with FDA: Biological Products and Clinical Development Karen Jones OODP Website  Oncology Tools Approved Oncology Drugs Regulatory Tools Oncology Reference Tools Patient Liaison Program Additional Resources FDA Centers and Divisions

5. Working with FDA: Biological Products and Clinical Development Karen Jones OODP Website (Cont.)  Access to Unapproved Drugs Single Patient or Emergency Use Treatment IND

6. Working with FDA: Biological Products and Clinical Development Karen Jones Pre-IND Meetings  Determine necessity Experience Novel Product Novel Clinical Trial Design

7. Working with FDA: Biological Products and Clinical Development Karen Jones 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

8. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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. Working with FDA: Biological Products and Clinical Development Karen Jones 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