One of the biggest challenges in developing and manufacturing antibodies is proving the equivalence or similarity to the reference product. Antibodies are highly complex molecules with secondary and tertiary structures subject to post-translational modifications such as glycosylation. Many times they may be heterogeneous and contain a small population of antibody variants (microheterogeneity). Small alterations in process development can lead to unacceptable changes in safety and efficacy. It is also quite possible that the subtle differences encountered in a biosimilar antibody in terms of molecular structure cannot be detected by current methods.

It could be a challenge to demonstrate that such differences have no impact on clinical efficacy and safety. This complexity is reflected in the amount of documentation required to be submitted for the marketing authorisation application, for example, on structure, physicochemical characteristics, biological activity (potency), manufacturing approach, and quality control. Moreover, a biosimilar antibody company usually has no data on critical in-process controls and intermediates in the manufacturing process of the innovator (it being proprietary and confidential information). The fact that they have to purify the drug substance from commercially available sources adds further complexity to the situation.

Despite the challenges associated with the development of biosimilar drugs, many drug manufacturers are entering the race to develop biosimilars, especially for blockbuster monoclonal antibodies (mAbs). According to Citeline's Pipeline database, there are currently 49 biosimilar mAbs in the pipeline. The vast majority of these mAbs (43) are in preclinical development. Geographically, the majority of development is taking place equally in Europe and Asia. Very little is happening in the Americas, as only six of the 49 mAbs in the pipeline are being developed by companies in these areas. Most notably absent in the development of biosimilar mAbs are the US companies. This may be a consequence of the lack of guidance in the US. Considering this new crop of mAbs to come and that a number of mAbs, previously developed by pharmaceutical companies, will be losing patent protection over the next few years, a stiff competition is expected. Speed-to-market would be a critical factor in deciding the survival for many of the companies engaged in mAb development. Faster development is possible by partnerships and licensing deals and collaboration will be an important strategy for overcoming some of the difficulties associated with the development of biosimilars.

The Asian challenge is therefore to comply with the EU or the US regulatory requirements and still produce the drugs at a price that will be acceptable locally. This may not be easy, despite the cost advantage of producing the drugs in south-east Asia. The price differential between originator and follow-on biologicals is only about 30 percent in Europe at the moment.

On the other hand, original drug makers are pushing for high benchmarks to scare off competition, but governments and regulators are aware that biosimilars are key to keep healthcare costs down. Whether European and US manufacturers of biosimilars will be able to enter the local markets more easily or find themselves bogged down by local competition is a matter of debate.