As mentioned on the Fisher Clinical Services blog, in July 2015, the U.S. Court of Appeals allowed Sandoz to launch the first US biosimilar. In the European Union, almost 20 biosimilars are already approved by the European Medicines Agency. The stakes are high with biosimilars as their path to the market requires them to fully compare the biosimilar to the originator. Each of those comparative trials cannot begin until the biosimilar sponsor successfully sources the reference drug.
The clinical trial approval pathway for biosimilars differs fundamentally from what’s required of a generic market approval. This is based on the fact that, unlike biosimilar companies, generic manufacturers do not have to prove the safety and efficacy of their drugs through clinical trials because these trials have already been conducted by the brand name company. Hence generic applicants only have to scientifically demonstrate that their product is bioequivalent and, therefore, need comparator drugs for only 24-36 healthy patients.
In contrast, biosimilars do have to go through Phase I and Phase III clinical trials. This fundamental difference in the regulatory pathway is the main reason why the failure rate of generic drugs only is around 10%, whereas it is as high as 50% for biosimilars. For the development of biosimilars, the reference drugs are already needed at the preclinical stage.
During this preclinical work, analytical testing and characterization of the reference drug is performed. The goal is to guarantee that the biological characteristics are as close as possible to the originator drug. As part of this process, the reference library is built up during a period that can extend from several months up to one year, which includes as many different lots as possible. The rationale for this approach is each lot might have slightly different characteristics that make it easier to do a “bio-similar” and not a “bio-worse” or “bio-better.” The latter would have to go through a completely new approval process.
Phase III trials for biosimilars often include thousands of vials or syringes of the reference drug. This often causes the costs for comparators to hit the multi-million dollar mark. As a result, your sourcing approach in these cases takes on increased importance. One point to consider is sourcing the reference drug for a Phase III trial might only be done once the characteristic batch analysis has been performed and the reference drug is guaranteed to be within the characteristic range during the preclinical analyses. During this short time period, the supplier should reserve the required quantities until it is confirmed that this specific batch is a suitable reference drug for the biosimilar in development.
Another key consideration is the short shelf life of biologics. Oftentimes, a 12 months shelf life is not sufficient for covering a complex Phase III study. Needless to say, an early and expert definition of the sourcing strategy for reference drugs in biosimilar trials is crucial to saving thousands in the long run (or perhaps even more).
As recently published by the business intelligence provider GBI Research, the global biosimilar market value could hit $55 billion by 2020. We will continue to publish more blogs on this topic as it’s sure to affect many of us in the industry over the next five years.