When Patients Become Plaintiffs

Summary

The first generation of biopharmaceuticals manufactured using recombinant technologies was launched in the 1980s, and patents protecting them are now nearing expiration. As with small molecule drugs, the expiration of patents creates an opportunity for generic biologicals to enter the market.

Due to the complexity of biological drugs, such products are usually referred to as 'biosimilars' or 'follow-on biologics', although the term 'biogenerics' may be applied to simple peptides.

Despite delays by the US FDA, and opposition from originator companies, biosimilars now represent one of the most rapidly evolving areas of product development in the pharmaceutical industry. The EU already has legislation in place for the approval of biosimilars, and the US is set to follow suit following the passing of landmark legislation by the US Senate Health Committee in June 2007. In the same month another significant milestone in the development of biosimilars was reached when the EMEA recommended three biosimilar versions of recombinant erythropoietin (EPO), a complex glycoprotein, for approval.

As discussed in this Report, companies active in the biosimilars sector are currently targeting products which are now off-patent in Europe: in particular human growth hormone (hGH), EPO and granulocyte colonystimulating factor (G-CSF). However, there are many more potential targets for development in areas, which have so far attracted fewer developers in the Western markets.

This Report focuses on 59 protein and 14 peptide therapeutics, which achieved high-volume global sales in 2006. Half of the protein products generated sales in excess of $500 million. We analyse these potential targets in the context of other commercial products based on the same active ingredient which are on the market or in development worldwide.

This information, derived from the Pharmaprojects database, will provide the reader with a snapshot of the commercial landscape relevant to each target product, and highlight related or improved products which may themselves become targets for biosimilar development.

We next examine the scientific issues involved in assessing the equivalence of biosimilar products and review the more important analytical procedures available for this purpose, including techniques with an established role in protein analysis, as well as emerging techniques like nuclear magnetic resonance spectroscopy and mass spectrometry. Regulatory requirements are likely to be more demanding for products bearing post-translational modifications, since relatively minor structural changes can alter therapeutically-relevant characteristics. Case studies focus on specific biosimilar products, which have recently undergone analytical and immunological evaluation.

The EU has been the initial target of most companies developing biosimilars for the regulated markets. Most development work in the biosimilars field is being conducted by large generic or speciality pharmaceutical companies.

These firms have been busy setting up subsidiaries or spin-offs focused on biosimilars and linking up with smaller companies, which have enabling technologies for the production of biosimilars. We profile 15 selected companies based in India, Europe, the US, Canada and Israel, which are poised for competition in the (regulated) biosimilars market.

We forecast in detail the top five protein therapeutics categories open to biosimilar competition, worth over 50% of the total protein market in 2006.

We estimate that total sales of follow-on proteins and biosimilars will rise from $30 million in 2006 to $3.2 billion in 2011, which represents a market penetration of 2.7% across the board. We appreciate that this figure, which is low by the standards of conventional generics, may disappoint some. It is partly due to the fact that certain important product groups, most notably the epoetins, cannot be sold in the important US market during the forecast period owing to patent restrictions. Also, widespread physician dispensing in Japan creates a bias against generics in that country. Thus, Europe will lead the way in biosimilar sales, with 45% of the world market. Apart from a few niche proteins and peptides, there is currently no available full-year sales history for any approved biosimilar.

Contents

• Chapter 1 The Product Liability Headache: Why IT's Worse for Medical Products
  • 1.1 The Cost of Torts
  • 1.2 What's Unique about Medical Products
  • 1.3 Risky Products and Vulnerable Customers
  • 1.4 High Expectations
  • 1.5 The Industries' Image Problem
  • 1.6 The Possibility of Criminal Liability
  • 1.7 The Double Whammy
  • 1.8 Today's Tort Targets
  • 1.9 The Learned Intermediary Doctrine
  • 1.10 Clinical Trials
• Chapter 2 A Case Study: What Industry Can Learn from The Vioxx Episode
  • 2.1 The Impact on Merck & Co
  • 2.2 The Impact on The Industry
  • 2.3 The Science behind The Drug
  • 2.4 Success and Suspicions
  • 2.5 Reaction to The Recall
  • 2.6 The Lesson: Heed The Auguries
  • 2.6.1 Notice Hints in The Data
  • 2.6.2 Gather More Data
  • 2.6.3 Don't Oversell
• Chapter 3 Global Concepts of Liability: Uniform Goals, Diverse Methods
  • 3.1 Expanding Liability
  • 3.2 Common Law and Civil Law
  • 3.3 Finding A Middle Way
  • 3.4 Implementing The Middle Way
  • 3.5 National Autonomy
  • 3.5.1 Germany
  • 3.5.2 Spain
  • 3.5.3 England
• Chapter 4 Drug and Device Product Liability in The US
  • 4.1 Why US Litigation Processes Matter
  • 4.2 The Foundation Cases
  • 4.3 The Legal Devices That Help Claimants
  • 4.3.1 Discovery
  • 4.3.2 Contingent Fees
  • 4.3.3 Class Actions
  • 4.3.4 Punitive Damages
  • 4.4 A Big Complication: 50 Sets of Rules
  • 4.4.1 California's All-Share-Liability Doctrine
  • 4.4.2 Michigan's Unique Pharma Suit Limit
  • 4.5 The Standards for Tort Cases
  • 4.6 Congressional Relief for Manufacturers
• Chapter 5 What Manufacturers Can Do to Minimise Exposure
  • 5.1 Improving Industry Image and Lowering Expectations
  • 5.2 Resisting Speeding Products to Market
  • 5.3 Handling Recalls Properly
  • 5.4 Labelling and Warnings
  • 5.5 Vetting Advertising and Promotion More Carefully
  • 5.6 Clear and Comprehensive Records Policies
  • 5.7 Ensuring Financial Protection
• Chapter 6 What The Future May Hold
  • 6.1 Upswing in Prescribing: Adverse Interactions Multiply
  • 6.2 The Impact of Advances in Genetics
  • 6.2.1 Tailoring Therapy to Patients
  • 6.2.2 Improving Clinical Trial Design
  • 6.2.3 Protection against Privacy Violation Suits
  • 6.3 Better Understanding of Mechanisms of Action
  • 6.4 The Impact of Direct-to-Consumer Promotion
  • 6.5 Closer US-Eu Cooperation
  • 6.6 Europe's New Emphasis on Managing Risk
  • 6.7 The Speed of Drug Approvals
  • 6.8 New Fda Training Priorities
  • 6.9 Fda Efforts to Pre-Empt State Law Claims
  • 6.10 Congressional Interest in Limiting Lawsuits
• Chapter 7 Conclusion
• List of Tables
  • Table 1.1: Medical Devices That Could Be Subject to Liability Suits
  • Table 1.2: Drugs That Could Be Subject to Liability Suits