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Many hurdles lie between a biosimilar and success on the market. In particular, there are three main questions that companies will be asking themselves.
Many hurdles lie between a biosimilar and success on the market. In particular, there are three main questions that companies will be asking themselves when entering the biosimilars arena:
• Can highly comparable biological products be manufactured to exacting quality standards? Given the depth of knowledge involved in the creation of the originator product and advances in both analytical techniques and protein manufacturing this is highly complex, but it is achievable.
• Can the requirements of the European regulators be satisfied? The guidance from the European Medicines Agency (EMA) on Chemistry, Manufacturing and Controls (CMC), nonclinical and clinical aspects is very clear, and several biosimilar products have already been approved — including human growth hormones, erythropoietins and granulocyte colonystimulating factors. The stringent requirements of regulators are highly complex and significant expertise is also required to complete the necessary extensive clinical programmes. However, all of this is achievable.
• Can products be commercialised once they reach the market? This question often receives less attention compared with the previous two questions, even though successful commercialisation is vital for the longterm viability of each product, as well as the biosimilars market as a whole. There is little documented evidence about effective commercialisation strategies. The main obstacle to overcome initially is the restrictions placed on pharmacy substitution of an originator drug with a biosimilar — either for legal or clinical reasons. Therefore, successful commercialisation will depend on winning the acceptance of clinicians to interchange their prescribing of originator products for biosimilars. This will require investment in clinical detailing infrastructure.
To make the situation more difficult, biosimilar manufacturers are also faced with the actions of the originator companies who are desperately fighting the introduction of biosimilars. This is usually done through communication to key influencers and decision makers, with much of their efforts directed at raising doubts over the safety of biosimilars. The evidence against biosimilars that has been cited by innovators often presents a distorted picture. For example:
• Comparison of isoforms shows a major difference between biosimilar and originator products. The evidence came from different biosimilar products sourced from Asia and did not address the very high quality requirements for biosimilars in the EU.1 None of the biosimilar products were registered in Europe.
• Biosimilars may cause serious safety issues. It is possible that small changes in the manufacture of a biological product could lead to immunogenicity problems, an example being Johnson & Johnson's Eprex in the late 1990s/early 2000s, when the drug was linked to cases of pure red cell aplasia. However, immunogenicity is an issue related to all biopharmaceuticals — whether they are originator or biosimilar products.
The main benefit of a biosimilar product is its ability to help reduce the cost of care for patients, while at the same time maintaining the level of quality, safety and efficacy experienced with the originator medicines. This should enable more patients to be treated or may help to fund the use of a newer, highcost therapeutics. Biosimilars may also provide improvements over the originator product for example by incorporating improved safety devices, tamper evident packaging and improved data in the package information.
Despite the potential advantages offered by biosimilars, healthcare professionals have generally been cautious about introducing them into their practice — mainly based on anti-biosimilar communication both before and since their introduction. Many clinicians have waited until experience from other countries or hospitals proves the quality, safety and efficacy of biosimilars, and we are starting to see increasingly strong adoption over time.
Biosimilars will continue to be developed and approved. However, the high cost of entry means that only those companies that are willing to absorb the costs and risks of development, registration and commercialisation will emerge as real competitors. In each therapeutic market I would expect to see only a handful of different biosimilar products, although several brands may be registered from each development programme.
Eventually, the biosimilar market will evolve as a sizeable part of the pharmaceutical market that differs from both the originator and generic market. Generally, biosimilars are expected to capture less market share from the originators compared with standard generics, but at prices that are more moderately discounted than generics. The commercialisation strategies for biosimilar manufacturers will probably develop as a hybrid of generic and originator approaches. In the early years, companies will use commercialisation tactics reminiscent of those for originator products including medical communication activities, clinical detailing to prescribers and product branding. These tactics will move eventually towards a more generic approach based on lowering the cost of sales as acceptance of quality, safety and efficacy increases.
Paul Greenland is Biosimilars Marketing Director for Europe, Middle East and Africa at Hospira.
1. Presentation given by Stephan Fischer on behalf of the European Biopharmaceutical Enterprise (EBE) at the 3rd PDMA Meeting on Biologics (Tokyo, Japan, 17 February 2009).