Biosimilars

1. Anurag Rathore

+ Author Affiliations

1. Department of Chemical Engineering, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi, 110016, India

Biosimilars, also referred to as the follow-on protein products in the U.S., can be defined as biotech drugs that have been shown to have comparable quality, safety and efficacy to the original product. Discussion and resolution of the various scientific and regulatory factors behind approval of biosimilars is perhaps one of the most significant events in the last decade for biotechnology.

There is a strong push for laying out a regulatory path for approval of biosimilars. Healthcare is already one of the largest expenses for developed societies (U.S., Europe and Japan) and is slowly becoming a concern for emerging economies as well. As per one published estimate, the cost of biotech therapies is expected to steadily grow about 30 percent (an approximately 20 fold increase in 10 years) by 2016. Another published study puts the financial savings by the European health care providers from approval of the first wave of biosimilar products at $2 billion. The financial case for biosimilars will continue to serve as the engine for laying down the regulatory framework that facilitates approval of biosimilars in the U.S.

There are some key aspects that make the task of approval of biosimilars more challenging than the traditional small molecule generics, for which the regulatory path is clear and accepted:

• Capital investments (including the operating costs) associated with manufacturing of biosimilars along with the risk of failure for biosimilars are significantly higher than that for small molecule generics. The result is a relatively smaller discount for biosimilars compared to the small molecule generics.
• Seemingly minor changes in manufacturing process have been known to cause significant change in efficacy or immunogenicity of the drug in the clinic.
• Biosimilars are larger and more complex molecules with associated structural heterogeneities when compared to their small molecule counterparts. This is the reason that biosimilars cannot be completely characterized analytically.
• The exact manner in which the numerous product quality attributes of a biosimilar impact the safety and efficacy of the product in the clinic is generally not known completely. In particular, immunogenicity assessments of novel and biosimilar products still heavily depend on clinical studies.

In view of the above discussion, it is clear that the regulators have the daunting task of keeping the balance between the financial benefit from allowing approval of biosimilars and the safety of the patients. The European Medicines Agency (EMA) has done a commendable job of successfully creating the regulatory framework that allows for review and approval of biosimilars. This has led to approval of recombinant somatropin, recombinant human epoetin alfa and recombinant filgrastim in Europe. Now that the U.S. Congress has passed a law allowing biosimilars, we look forward to a timely but responsible creation of a regulatory process that can bring them to the U.S. market.