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Biosimilars Safe, Effective Alternatives to Originator Biologics
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As the first biosimilars are being introduced and becoming more common in the United States, it is worthwhile to understand how the approval process works. With fewer clinical studies required than are usual for new biological drugs, biosimilar drugs can come to market and be accessible to patients more quickly — with no negative impact on safety or effectiveness.
The information required by the FDA to approve a biosimilar focuses on proving that there are no clinically meaningful differences between the biosimilar and the corresponding reference product, and that the structures of the two products are highly similar. To prove this point, extremely sensitive comparisons are conducted of the structure and function of both the biosimilar and reference product. The emphasis is placed on these technical methods because they are commonly more sensitive than clinical studies for detecting differences that may exist.
As a follow-up to the analytical methods used to confirm that there are no clinically relevant differences, an additional pharmacokinetic study (or studies) is conducted directly comparing the biosimilar and reference product. Pharmacokinetic studies evaluate what happens to drug levels within the body after it is administered, including how much of the drug remains in circulation in the hours and days following administration.
The FDA also focuses on potential immunogenicity. Before a biosimilar can be approved, comparative human clinical studies must establish that the biosimilar is not more immunogenic — does not provoke a greater immune system response that might lead to major clinical consequences — than the reference product, although lower levels of immunogenicity with a biosimilar are acceptable.
Although the exact analytical and clinical study designs are not predefined by the FDA and can vary from one biosimilar to another, in the final analysis, all must provide compelling evidence of highly similar quality, safety and efficacy compared with the reference product — otherwise known as the “totality of evidence.” The totality of evidence provided to support approval of a biosimilar differs from that provided for approval of standard new biological drugs. In the case of new biological drugs, the goal is to prove that the drug is safe and effective to treat a particular disease, whereas in the case of a biosimilar, the focus is to ensure that the biosimilar is highly similar to an already approved reference product, and that any differences that may exist are proven to have no impact on safety or effectiveness.
It is important for anyone prescribing or using a biological drug to know that the FDA has a single standard for safety and efficacy. The FDA will not approve any biological drug — whether it is an original biological getting approved for the first time or a biosimilar to an already licensed reference product — unless it is convinced that the biological drug is safe and effective for its intended use. As a result, health care providers and patients can be reassured that biosimilars provide similar efficacy benefits with the same safe outcomes as provided by the biological reference product.
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Hillel P. Cohen, PhD, and Dorothy McCabe, PhD, FCP, are co-chairs of the education committee of the Biosimilar Forum, a nonprofit organization intended to advance biosimilars in the United States with the intent of expanding access and availability of biological medicines, and improving health care.
Disclosure: Hillel reports an employment relationship with Sandoz and owns stock in Novartis. McCabe reports an employment relationship with Boehringer-Ingelheim.