What are biosimilars?
Biosimilars are similar, but not identical, versions of approved biological medicines no longer protected by patents.
How do biosimilars differ from “generic” pharmaceuticals?
Generic pharmaceuticals are usually relatively simple, small-molecule drug products that can be manufactured via chemical synthesis to create an exact replica of the original product. By comparison, biosimilars are not required to be identical copies of the original products because most biological medicines are far more complex and it is therefore virtually impossible to create exact replicas.
Although an exact copy of the original product is not required, it is essential to create a biosimilar that has no significant differences to the original product and is highly similar in terms of safety, purity and efficacy.
How are biosimilars regulated?
Many countries have established a legal framework to allow approval of biosimilars via an abbreviated registration process. As with all biological medicines, biosimilars are assessed prior to approval by regulatory authorities, for example the European Medicines Agency (EMA). A key component of the regulatory submission for biosimilars is the comparability data derived from thorough analysis of both the biosimilar and the original product to demonstrate that there are no significant differences.
What products have been approved as biosimilars?
Fourteen biosimilars have been approved so far in Europe within the product classes of human growth hormone, granulocyte stimulating factor and erythropoietin. Biosimilars have also been approved in Japan, Canada, Australia and numerous other countries throughout the world.
Biosimilars are not marketed in the United States because until recently there was not a legal pathway that allowed their regulatory approval. The required legislation was enacted in March 2010 and FDA is currently writing the associated guidelines.
How are biosimilars manufactured?
Biosimilar and biological medicines are usually produced using living systems through recombinant DNA technology. Each company developing biosimilars typically develops and maintains its own proprietary cell line and manufacturing process, which often includes multiple stages to ensure that the target product is sufficiently separated from residual cell line contaminants.
How do we ensure biosimilars are sufficiently similar to the original products?
It is challenging to create biosimilars that have no significant differences to the original products because biological products are generally complex and require complicated manufacturing processes involving the use of living cells. Significant advances in process and analytical science, however, allow this goal to be achieved.
At all stages during process development there are strategies that can be employed to help create a biosimilar product, from selecting the correct cell line to modifying a manufacturing process so that only the correct product is purified. Supporting this are current analytical methods that are extremely sensitive and precise and provide detailed evaluation of any differences between the original product and biosimilar.
This process and analytical science is the foundation of creating biosimilars that have no significant differences to the original product. Testing in animals or humans may also be required to further investigate any differences; however, as it is unethical and unnecessary to perform these studies without reason, animal and human studies are only conducted after careful consideration.
Are biosimilars of high quality?
All biological medicines, including biosimilars, manufactured in Europe are made according to current Good Manufacturing Practice (cGMP), which dictates that they are produced consistently and to a high quality standard. Manufacturing facilities are subject to routine cGMP and Pre-Approval Inspections (PAI) for cGMP compliance, therefore ensuring that high standards are in place.
As with all biological medicines, manufacturers of biosimilars must monitor the effects of their products once approved and supplied for medical use. This is known as “pharmacovigilance” and includes mechanisms to detect and assess any adverse reactions, any of which need to be appropriately communicated.
Why are biosimilars important?
Biological medicines are often more expensive than small molecule pharmaceuticals as they are difficult to develop and manufacture. Although many biological drugs are very important in the treatment of conditions such as cancer and diabetes, their expensive nature means that not all patients who could benefit from these medicines have the necessary access.
Biosimilars represent one way in which patients can gain greater access to affordable, high quality medicines. When biological medicines are no longer protected by patents, they become available for development and commercialisation by other companies, which introduces competition in the market.
Also, because the initial research is not required and development timelines are shortened, biosimilars cost less to develop than original products, ultimately resulting in price reductions for patients. Although this price decrease is generally less than that seen for small molecule generics even a 30 to 50% price reduction provides significant savings in overall healthcare costs.