Biosimilars - Evolution or Revolution?

BIOSIMILARS
(SIMILAR BIOLOGICAL MEDICINAL PRODUCTS / FOLLOW-ON BIOLOGICS)
Contents
Chapter 1
Strategy Options for Entering the Biosimilar Market
Tim Oldham PhD, BSc (Hons), LLB (Hons)
Acting Head, EMEA Region
Vice-President, Business Planning and Operations Effectiveness, Mayne Pharma plc, UK
Chair, Biosimilars and Biotechnology Committee, European Generic Medicines Association
1 The opportunity: why consider biosimilars at all?
1.1 Overview
1.2 Biologics and biosimilars defined
1.3 Contribution of biologics to modern healthcare: the market potential
1.4 Public policy issues: healthcare economics and innovation
1.5 Biosimilars: what’s all the fuss?
2 Development: What does it actually take to bring a biosimilar to market?
2.1 Overview
2.2 Experience of the market leaders
2.3 Product development
2.4 Clinical development
2.5 Manufacturing capacity
2.6 Regulatory strategy
2.7 Pharmacovigilance
2.8 Making the trade-offs: cost, time and risk
2.9 Proving comparability: is it strictly necessary?
3 Working out the profit potential: what are the conditions to make an economic return and how can they be maximised?
3.1 Overview
3.2 Minimum efficient market size
3.3 Target market drivers
3.4 Market share drivers
3.5 Sales and marketing cost drivers
3.6 Price drivers
3.7 Legal costs
3.8 Has risk reduction won over healthcare economics?
4 Market structure: players and issues
4.1 Overview
4.2 Regulatory frameworks and their evolution
4.3 Post-authorisation issues
4.4 Big biotech positions and strategies
4.5 Biosimilar developers
Chapter 2
Product Similarity for Biosimilars
Meena Subramanyam PhD
Senior Director, Clinical Science and Technology, Biogen Idec Inc., USA
1 Impact of manufacturing process on the biosimilar product
1.1 Demonstration of pharmaceutical equivalence
1.2 Requirements for demonstrating “similarity”
1.3 Impact of changes to cell culture process
1.4 The “tool kit”
2 Preparation of a comparability package to the regulators
2.1 Quality data –The EMEA guidance
2.2 The Reference Standard
2.3 Non-clinical data
2.4 Clinical data
3 Approved biosimilars - Similarity considerations for specific products
4 How similar is “SIMILAR”
5 The future
6 Acknowledgement
Chapter 3
Clinical Trials for Biosimilars
Peter H Kalinka PhD
CEO and Managing Director, Accelsiors Group International
Instructor for Clinical Development of Pharmaceuticals and Biologics, Advanced Biotechnology Studies, Johns Hopkins University
1 Requirements for a robust clinical protocol
1.1 Introduction
1.2 Clinical protocol design
1.3 Clinical case studies
1.4 Summary and Conclusion
2 Factors affecting size of clinical study
2.1 Literature Data
2.2 Valuable Information
3 Clinical demonstration of bioequivalence
4 Determination of clinical and surrogate end-points
5 Summary and Conclusion
Chapter 4
Regulatory Issues – European Perspective
Gabriele Schaeffner PhD
Principal Consultant, Parexel International GmbH, Germany
1 Regulatory considerations for clinical trials
1.1 How the clinical programme forms part of a risk-based comparability assessment
1.2 ICH recommended design, scope and scale to provide sufficient safety and efficacy
1.3 Selection of comparators for various products
1.4 Where to carry out the clinical trial
1.5 Clinical Risk Management
1.6 Impact of clinical testing on timelines and cost
1.7 To what extent can ‘abbreviated use’ be applied?
1.8 Is it necessary to conduct a clinical trial for every indication?
1.9 Conclusion
2 EU current guidance and draft guidance explained
2.1 EU directives to date
2.2 Guidance documents, adopted guidelines, drafts for consultation and concept papers
2.3 CHMP guidance on quality issues and non-clinical and clinical issues
2.4 Implications of ICH Q5E for the industry
2.5 Concepts of biosimilarity and essential similarity explained: which is most appropriate and why?
2.6 Focus on products: recombinant human insulin, somatotropin, human granulocyte colony stimulating factor and recombinant human erythropoietin
2.7 Update from EMEA/DIA meeting in Paris in December 2005
2.8 Future outlook for marketing authorisation applications: will this remain a barrier to success?
2.9 Predictions for future regulatory guidance and directives
2.10 Conclusion
3 Practical considerations when dealing with the European regulators
3.1 How the case-by-case approach works in practice
3.2 Experiences with essential similarity issues
3.3 How the Centralised Procedure is working in practice
3.4 How the generics manufacturer can benefit from the Centralised Procedure
3.5 Where applicants go wrong / Lessons that can be learnt with hindsight
3.6 Recommended strategies for success
3.7 When advice from the regulators should be sought
3.8 Content of a Scientific Advice Package
3.9 Without an ‘abridged’ application, what short cuts are possible?
3.10 Features of Omnitrope that counted in its favour with the EMEA
3.11 Risk management strategy
3.12 Conclusion
4 Role of the European Commission in the route to Marketing Authorisation
4.1 Current and future legal framework for biosimilars
4.2 Consequences of the ‘Pharma Review’ for the industry
4.3 Application of the Bolar provision to biosimilars – details of the clause
4.4 Required studies and trials
4.5 Implications of the Commission’s ruling on Omnitrope for the industry
4.6 To what extent does the use of published data and ‘well established use’ render an application susceptible to challenge?
4.7 Proof-of-principle: Does this work in practice? Will it be necessary to conduct trials for every indication?
4.8 Conclusion
5 Regulatory case studies and precedents in the EU
5.1 Introduction
5.2 Analysis of the data submitted for successful approval of rhGH containing similar products (Omnitrope, Valtropin)
5.3 Analysis of the data submitted for Alpheon
5.4 Conclusion
6 Routes to regulatory approval in the EU
6.1 The principle routes
6.2 Routes for generic medicinal products and similar biological medicinal products
Chapter 5
Regulatory Issues – US Perspective
Alan Liss PhD
Formerly Senior Director, Biotechnology, DRI, USA
1 FDA’s stand in the absence of formal regulatory guidance
2 Anticipated FDA draft guidance
3 REGULATORY CASE STUDIES AND PRECEDENTS IN THE US
3.1 Comparability Protocols
3.2 The FDA's approval of Avonex, a Biogen/Idec product
3.3 Insulins
4 Routes to regulatory approval in the US and the rest of the world
4.1 A path forward
Chapter 6
Legal Issues
Antonio Maschio, PhD
Partner, D Young & Co, UK
Isla Furlong, PhD
D Young & Co, UK
1 Determination of the patent environment / freedom to operate
1.1 Introduction
1.2 What is patentable?
1.3 How to conduct freedom-to-operate determinations
1.4 What can you do before a patent expires?
2 The law as defined by legal precedent: case studies
2.1 Sandoz GmbH v Roche Diagnostics GmbH (EWHC Ch 1313; http://www.bailii.org/ew/cases/EWHC/Ch/2004/1313.html) (Inventive Step)
2.2 Kirin Amgen Inc. & Others v Hoechst Marion Roussel Limited & Others (UKHL 46; http://www.bailii.org/uk/cases/UKHL/2004/46.html)
3 Strategy for overcoming the legal obstacles and 'clearing the way' for development
3.1 Introduction
3.2 Strategies for early development of biosimilars - what can be done before the patent has expired?
3.3 Summary
Chapter 7
Opportunities and Barriers in the Biosimilars Market: Evolution or Revolution for Generics Companies
Jo Pisani, Yann Bonduelle
PricewaterhouseCoopers
1 Introduction
2 Commercial Drivers for Biosimilars
2.1 Erythropoietin
2.2 Granulocyte-colony stimulating factor (G-CSF)
2.3 Interferon alpha
2.4 Interferon beta
2.5 Human growth hormone
2.6 Recombinant human insulin
3 Country Market Opportunities
3.1 Germany
3.2 United Kingdom
3.3 France
3.4 Italy
3.5 Spain
3.6 United States
4 Required Skill Sets
5 Pricing Strategy
6 Summary