1. Working group on Pharmacokinetics and Population Pharmacokinetics of factor concentrates Alfonso Iorio, on behalf of the working group

2. DISCLOSURES Financial conflicts of interests – McMaster University has received funds for research and service agreements from Bayer, Baxalta, Biogen, NovoNordisk, Octapharma, and Pfizer. Non-financial (intellectual) conflicts – PI for the WAPPS project (www.wapps-hemo.org) No mention of unlicensed products

3. WORKING GROUP Core members – A Iorio, V Blanchette, P Collins, K Fischer, J Blatny, E Neufeld Additional members – D Lillicrap, D Hart, M Makris PK and PopPK consultants – A Edginton, S Ito

4. Previous SSC Communications The design and analysis of half-life and recovery studies for factor VIII and factor IX. Factor VIII/Factor IX Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis. Morfini M, Lee M, Messori A. Thromb Haemost. 1991 Sep 2;66(3):384-6.

5. Previous SSC Communications Scientific and Standardization Committee Communication The Design and Analysis of Pharmacokinetic Studies of Coagulation Factors On behalf of the Subcommittee on Factor VIII and Factor IX of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis M. Lee, M. Morfini, S. Schulman, J. Ingerslev and the Factor VIII/Factor IX Scientific and Standardization Committee of the ISTH Posted on the ISTH SSC on March 21, 2001

6. Previous SSC Communications … the approaches recommended here are primarily intended for clinical trials of factor concentrates that are being compared to other, similar preparations. … studies on individual patients for diagnostic or therapeutic purposes may not necessarily be relevant to what is discussed here.

7. Previous SSC Communications

8. AIMS: Primary PK and PopPK estimates of factor concentrates: – Reporting – Interpretation – Assessment in clinical practice – Study design for “real world/PM” PopPK assessment

9. AIMS: Secondary PK and PopPK estimation: – During registration phase – To compare different molecules – Choice of time points – ….

10. PROCESS How (and whether) to best involve: – Pharmaceutical companies PK/PopPK experts – FDA / EMA PK/PopPK experts – Authors of PK/PopPK published papers – Patient representatives

11. PROGRESS 2 conference calls 1 panel survey Bi-monthly conference calls Review of the existing literature Review of regulators guidance Draft recommendations on primary goals

12. Questions time Thank you for attention Slides posted on: http://hemophilia.mcmaster.ca/resources