Sponsoring an IND? Ignorance is Not Always Blissful

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1 Translational Science 2013 Navigating The FDA Regulatory Landscape April 19, 2013 Washington D.C. Sponsoring an IND? Ignorance is Not Always Blissful Lisa A. Speicher, Ph.D Director, Clinical Trials Office Director, Office of IND/IDE Support The Children's Hospital of Philadelphia

2 Disclosure Information Sponsoring an IND Lisa Speicher I have no conflicts to disclose

3 Yeah, Yeah, I know. I don t mind signing that Form 7115, I mean 1751, I mean 15 whatever I can sign it.

4 So, what exactly did you sign and what does it mean??? FDA Form 1571

5 What else did you promise to do when you signed the Form 1572?

6 Data Analyses SAE REPORTS FEASIBILITY SCIENTIFIC REVIEW F D A G CRFs P IRB AUDITS CTRC PATIENT BILLS C B U D G E C T A Enter at your own Risk Training FUNDING Grants CITI CMC Drug Accountability BIOINFORMATICS

7 Barriers to Efficient Clinical/Translational Research Starring YOU, the Sponsor Investigator al & Clinical Research Regulations IND/IDE Regulatory Burden S-I : Inadequate experience/training Insufficient Institutional Support Funding/Resources Understanding of Responsibility Well trained staff

8 What Degree of Support Do You Need? Depends on complexity of program Do I even need an IND? Approved drug? Different formulation? Population? Expanded Access Single patient IND Emergency use NCE? Laboratory experiments? CMC? FDA Liaison? Monitoring? Well trained Study Coordinator? Translational research: Crossing the valley of death Nature 453, (2008) Belle Mellor

9 You can delegate but consider this Your CRC is navigating for: Your Subjects Your projects You The Institution

10 Ultimately, the PI are responsible even though Your CRC is navigating for: Your Subjects Your projects You The Institution Now multiply this by the number of studies you delegate to your team

11 Clinical Investigator Common Deficiencies: Failure to follow the investigational plan Inadequate subject protection including informed consent issues Protocol deviations Inadequate recordkeeping Inadequate accountability for the investigational product

12 Who (where) is the weakest link? Human Subject Protection Proper Informed consent Protocol Adherence Regulatory Binders Adverse Event Reporting Drug Studies Clinical Samples Documentation processed, stored, shipped properly, collected at proper time w/ proper labels Proper storage/destruction/return Drug Accountability Proper dose given Appropriate person administering drug IND Annual reports External IND Safety reports Know submission requirements Proper SAE reporting Understand AE and SAE Definition Lab certs, normal ranges +.. IRB approval letters & correspondence Signed protocol & amendments 1572, CV, Investigators brochure Proper documentation of missed tests Labs outside protocol specified window Any missed tests, labs, visits Confirm all eligibility requirements are met Current IRB approved protocol Verbal consent Title 45 Part & 406 Properly signed, dated, documented Current IRB approved ICF/assent

13 So where do you start? True understanding of your responsibilities A well trained staff Full understanding of the informed consent process A well written, well designed protocol A protocol is not a grant Be clear, no ambiguity Use institutional template (if available) Assure feasibility Thorough understanding of eligibility criteria Document! If it isn t documented, it didn t happen Institutional guidance

14 CTSA IND/IDE Taskforce Recommendations Critical for AHCs to have programs that: Ensure adequate training of their sponsor investigators Provide assistance with IND exemption determinations Provide support for IND/IDE application submissions and maintenance Provide oversight for sponsor investigator activities. Provide assistance with GLP and GMP regulations Support for Investigator-Initiated Clinical Research Involving Investigational Drugs or Devices: The Clinical and Translational Science Award Experience Academic Medicine, Vol. 86, No. 2 / February 2011

15 3 Potential Institutional Models for Sponsor-Investigator Oversight & Support

16 3 Potential Institutional Models for Sponsor-Investigator Oversight & Support

17 3 Potential Institutional Models for Sponsor-Investigator Oversight & Support

18 CTSA IND/IDE Taskforce Recommendation Human participant protection in research conducted by sponsor investigators is best served by an institution investigator partnership designed to adequately support and provide oversight of the IND/IDE regulatory responsibilities with either a central consultative or full-service office. To ensure robust protection of human participants and to mitigate regulatory risks, AHCs are encouraged to develop programs appropriate to their institutional structures and their portfolios of investigator-initiated drug and device research.

19 Should Academic Health Centers Consider Risked Base Compliance? AHC Insurance Policy for Sponsor-Investigators Manage regulatory documents Real time Monitoring IND Exemption determination Manage SAE reporting over the last 5 years, only 9 warning letters were issued to AHC. That is less than 2 per year and does not present a compelling case for why training is needed the scale and scope of the problem sounds weak to me

20 Weather prediction sunny and clear

21 Weather Prediction: chance of light rain, drizzle

22 Photo: EDDIE MULHOLLAND Weather prediction: Heavy Rain

23 Photo: EDDIE MULHOLLAND Weather prediction: Heavy winds and rain

24 Photo: EDDIE MULHOLLAND Weather prediction: Dangerous winds, rain, hurricane

25 Should AHCs Consider Risked Base Compliance? No! We re not very good at predicting the weather

26 You are responsible Train your staff Follow your protocol Action, not intent matters If it isn t documented, it didn t happen Learn who at your institution can help