1Seminar 6-11-2012 Agenda1. Drug Development – General Overview2. Biopharmaceutics Definitions Types of products Development Production Quality Assurance Market and future developments3. Biosimilars Definitions Products Regulatory aspects Challenges Market and Future Developments
2Jacques Schipper- 1974 Master Chemistry and Molecular Pharmacology- 1979 PhD Neuropharmacology- 1983 Scientist University of Amsterdam- 1992 Discovery Project Manager AntidepressantsSolvay 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
Drug DevelopmentGeneral OverviewFrom Molecule to MarketJacques Schipper, PUMLima, 6 November 2012
4From Molecule to Market (small molecules)Knowledge & Medical needIdea for New TherapyChemical Synthesis and Biological TestingSelection of Development CandidatePreclinical Safety EvaluationPhase I - Clinical trials (Safety & Tolerance)Phase II - Clinical Trials (Efficacy)Phase III - Large Scale Clinical TrialsFirst Registration SubmissionApproval and launched to marketDiscoveryDevelopmentProducttimeestimatein years>4>8> 1
5Drug Discovery Phase 1Clinical TrialsPhase 2Clinical TrialsPhase 3Clinical TrialsPriority Substance50%40%60%70%Drug Candidate Survival RatesProduct RegistrationOverall only 8% SurviveProbability of success in each phaseFFFNOON. maleate
6Global R&D expenditure has grown significantlyConfidential Slide No. 12CMR International 2006/2007 Pharmaceutical R&D FactbookPerspectiveInsightOpinionGlobal pharmaceutical R&D expenditure 1996–2009p010203040506070801996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006p 2007p 2008p 2009pGlobalR&Dexpenditure(US$bn).YearP - Projected figures have been calculated based on an average annual growth in R&D expenditure between 2000 and 2005.
7Yet, the number of new approved drugs tend to decreaseConfidential Slide No. 54CMR International 2006/2007 Pharmaceutical R&D FactbookPerspectiveInsightOpinionNumber of new molecular entities and new active substances firstlaunched onto the world market 1996-2005051015202530354045501996 1997 1998 1999 2000 2001 2002 2003 2004 2005Year of first launchNumberofNMEs/NASsNumber of NMEs first launched onto the world marketNumber of NASs first launched onto the World Market
8Development time is long and has not decreased (in spite ofefforts)Confidential Slide No. 55CMR International 2006/2007 Pharmaceutical R&D FactbookPerspectiveInsightOpinionDevelopment time for medicines first launched onto the world market1998-200546810121416181998 1999 2000 2001 2002 2003 2004 2005*Year of first launchDevelopmenttime(3yearmovingaverage/years).All Companies Major Companies* The development time data point for 2005 includes data from 2004 and 2005 onlyMajor companies are defined as those spending =US$ 1.8 billion in 2005 on ethical pharmaceutical R&D.
9Research Strategy: How to select R&D projectsMedical needCommercialOpportunityScientificFeasibility Viable Projects
10Lead-FindingTeamsLO Teams ED TeamsLife CycleTeamsProjectTeamsProject Teams to facilitate development processTarget-focusDisease-focusTarget selectionfor LFTarget Engagement POC Lite POCPushfrom Target toClinical DiseasePullto Clinical Diseasefrom TargetLO nomination Approval
11If you leave it to the departments, this happens in projects
12Preclinical Developmentsafety pharmacologyacute toxicologysubacute toxicology(2-4 weeks)genotoxicityClinicalCandidateStart clinicalpharmacologyKg -production (GMP)early dose formClinical Development PlanBiomarker strategyProof of Concept StrategyDevelopmentCandidate
13Phase 1 : Bridging from animals into humans: translationalmedicine and question based drug development• Translational approach: alignment between animal andclinical 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 thetherapeutic indicationGo/no-go decisioninto PoC / Phase 2Combined with safety and first clinical data
14Early DevelopmentTeamResearch and Early DevelopmentPoCStudyresultsFull Developmentin-houseDevelop witha PartnerOut-licenceStopKey decision points after Proof of Concept study
15Full 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• EtcTypically takes more than 3 years at the expense of >200 M$ and>3000 patients are included in clinical studies