DCAT Week 2014 BioPharmaceutical Forum: Biosimilars—Development, Regulatory, and Marketing Experiences
Although the United States still has yet to work out the regulatory details to obtain approval for biosimilars, Europe and other countries, particularly growth markets, offer market potential for biosimilars. DCAT’s 2014 BioPharmaceutical Forum: Biosimilars—Development, Regulatory, and Marketing Experiences, held March 13, 2014, examined both the opportunities and challenges in biosimilar development and commercialization.
Assessing the opportunity
Biosimilars are a small, but growing segment of the global biopharmaceutical market accounting for 0.4% of the $137-billion biologics market in the so-called “mature eight” markets of the United States, EU5 (France, Germany, Italy, Spain, and United Kingdom), Canada, and Japan in 2012, according to IMS (1). In growth markets, biosimilars accounted for 10.7% of a $15-billion biologics market in 2012. By 2017, biosimilars are expected to represent 3–5% of an estimated $205-235 billon global biologics market(1).
For biosimilars in general and particularly with the opportunity of more complex molecules, such as monoclonal antibodies to become biosimilars, developers face the challenge of developing a manufacturing process that can achieve comparability to the reference product. Development activities center on replicating the process conditions of the reference product to drive the process toward producing a “highly similar product”. Because innovators do not typically publically disclose their manufacturing processes, biosimilar developers have to ascertain the process conditions that will allow them to achieve comparability, or “biosimilarity”. An added complication facing biosimilar developers is whether to take advantage of advances in cell line development and bioprocessing innovations to develop a more efficient manufacturing process to produce a biosimilar. The industry has seen titers increase from less than 1 g/L in 2000 to titers of 10 g/L or more in 2014. A fundamental issue for a biosimilar developer in evaluating the cost and time for biosimilar development is deciding whether to take advantage of innovative manufacturing processes that may result in better yields and more efficient manufacturing processes, but may generate a product sufficiently different from the reference standard that it would not be considered a “biosimilar.”
Biosimilar developers also face quandaries in cell-line development. In terms of conventional host cells systems, mammalian cell culture systems (primarily Chinese hamster ovary (CHO) cells) account for the majority of host cells or 56% of the systems used and E. coli comprise 29% of the host cells used in biopharmaceutical production. (2). An important issue in biosimilar development is determining whether a host cell system that is different from what was used by the innovator can be used for biosimilar development and commercialization.
Applying highly sophisticated analytical techniques to characterize these molecules and the potential to take advantage of a more advanced host cell and expression technology in the development of biosimilars is likely possible. However, regulatory authorities may be cautious and maintain a high bar regarding meeting the “biosimilar” criteria when a technology different from the innovatory process is used. In the U.S., we won’t know how the FDA will view the use of different technologies until they issue their long awaited guidance documents on development of biosimilars.
Blog article by: Patti Seymour
1. G. Lewis, “Pharma Transformation in Turbulent Times,” presented at DCAT Week 2014 (New York, 2014).
2. T. Fritz, C. Lightcap, and K. Shah, “Manufacturing Strategies for Biosimilars,” Pharma Manufacturing, June 12, 2012.