1 drug developmentv1
- 1. 1 Seminar 6-11-2012 Agenda 1. Drug Development – General Overview 2. Biopharmaceutics Definitions Types of products Development Production Quality Assurance Market and future developments 3. Biosimilars Definitions Products Regulatory aspects Challenges Market and Future Developments
- 2. 2 Jacques Schipper - 1974 Master Chemistry and Molecular Pharmacology - 1979 PhD Neuropharmacology - 1983 Scientist University of Amsterdam - 1992 Discovery Project Manager Antidepressants Solvay Pharma - 1999 International Development Manager Solvay Pharma - 2007 Senior Project Director Organon - 2009 Senior Project Director Schering Plough - 2012 Senior Project Director MSD - Senior expert PUM
- 3. Drug Development General Overview From Molecule to Market Jacques Schipper, PUM Lima, 6 November 2012
- 4. 4 From Molecule to Market (small molecules) Knowledge & Medical need Idea for New Therapy Chemical Synthesis and Biological Testing Selection of Development Candidate Preclinical Safety Evaluation Phase I - Clinical trials (Safety & Tolerance) Phase II - Clinical Trials (Efficacy) Phase III - Large Scale Clinical Trials First Registration Submission Approval and launched to market Discovery Development Product time estimate in years >4 >8 > 1
- 5. 5 Drug Discovery Phase 1 Clinical Trials Phase 2 Clinical Trials Phase 3 Clinical Trials Priority Substance 50%40% 60% 70% Drug Candidate Survival Rates Product Registration Overall only 8% Survive Probability of success in each phase F F F N O O N . maleate
- 6. 6 Global R&D expenditure has grown significantly Confidential Slide No. 12 CMR International 2006/2007 Pharmaceutical R&D Factbook PerspectiveInsightOpinion Global pharmaceutical R&D expenditure 1996–2009p 0 10 20 30 40 50 60 70 80 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006p 2007p 2008p 2009p GlobalR&Dexpenditure(US$bn). Year P - Projected figures have been calculated based on an average annual growth in R&D expenditure between 2000 and 2005.
- 7. 7 Yet, the number of new approved drugs tend to decrease Confidential Slide No. 54 CMR International 2006/2007 Pharmaceutical R&D Factbook PerspectiveInsightOpinion Number of new molecular entities and new active substances first launched onto the world market 1996-2005 0 5 10 15 20 25 30 35 40 45 50 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 Year of first launch NumberofNMEs/NASs Number of NMEs first launched onto the world market Number of NASs first launched onto the World Market
- 8. 8 Development time is long and has not decreased (in spite of efforts) Confidential Slide No. 55 CMR International 2006/2007 Pharmaceutical R&D Factbook PerspectiveInsightOpinion Development time for medicines first launched onto the world market 1998-2005 4 6 8 10 12 14 16 18 1998 1999 2000 2001 2002 2003 2004 2005* Year of first launch Developmenttime(3yearmovingaverage/years). All Companies Major Companies * The development time data point for 2005 includes data from 2004 and 2005 only Major companies are defined as those spending =US$ 1.8 billion in 2005 on ethical pharmaceutical R&D.
- 9. 9 Research Strategy: How to select R&D projects Medical need Commercial Opportunity Scientific Feasibility Viable Projects
- 10. 10 Lead-Finding Teams LO Teams ED Teams Life Cycle Teams Project Teams Project Teams to facilitate development process Target-focus Disease-focus Target selection for LF Target Engagement POC Lite POC Push from Target to Clinical Disease Pull to Clinical Disease from Target LO nomination Approval
- 11. 11 If you leave it to the departments, this happens in projects
- 12. 12 Preclinical Development safety pharmacology acute toxicology subacute toxicology (2-4 weeks) genotoxicity Clinical Candidate Start clinical pharmacology Kg -production (GMP) early dose form Clinical Development Plan Biomarker strategy Proof of Concept Strategy Development Candidate
- 13. 13 Phase 1 : Bridging from animals into humans: translational medicine and question based drug development • Translational approach: alignment between animal and clinical pharmacology • Use of biomarkers • Use of human models for disease state • Proof of Concept definition and study design • Question based drug development – Presence / absence of the compound in the target organ – Presence or absence of pharmacodynamic activity at well tolerated doses – Appropriate or inappropriate pharmacodynamic characteristics according to the therapeutic indication Go/no-go decision into PoC / Phase 2 Combined with safety and first clinical data
- 14. 14 Early Development Team Research and Early Development PoC Study results Full Development in-house Develop with a Partner Out-licence Stop Key decision points after Proof of Concept study
- 15. 15 Full Development Clinical Program • Pivotal studies for proof of efficacy • Pivotal studies for proof of safety • Long term safety data (>100 patients for 1 year, >300 for 6months) • Long term efficacy data (EU) • Special populations • Drug – drug interactions • Etc Typically takes more than 3 years at the expense of >200 M$ and >3000 patients are included in clinical studies