The world of biosimilar manufacturing seems laden with sugar and spice. While these “generic” biologicals have been deemed to have the potential to create competition and result in healthcare savings—although not to the extent of generic products—technical issues with manufacturing these products have troubled drug manufacturers. At the annual meeting of the National Comprehensive Cancer Network (NCCN) in Hollywood, Florida, a physician expert took to the podium to present NCCN’s position on biosimilars. Andrew D. Zelenetz, MD, PhD, is a medical oncologist and vice chair of medical informatics, Department of Medicine Memorial Sloan Kettering Cancer Center.
Zelenetz began by saying that the NCCN has been thinking about biosimilars for quite a while and they even published a white paper
on the topic back in 2011. “Many of the recommendations from the paper found their way into the FDA guidelines on biosimilars,” said Zelenetz. He went on to share the FDA’s definition of a biosimilar. According to the FDA, biosimilars are a type of biological product that are licensed by the FDA because they are highly similar to an already FDA-approved biological product, known as the biological reference product, and have been shown to have no clinically meaningful differences from the reference product.
“Biologics are expensive and the therapeutic spending in oncology dominates all of medicine’s spending,” said Zelenetz. It has been estimated that the annual spending on oncology biologicals in 2014 touched $28 billion. The 10 most-used drugs in 2012 were biologics, Zelenetz said, many of which used in cancer management.
Explaining the economics associated with the use of biological products, he said that with several biologicals moving towards patent expiration, the industry and other stakeholders are paying increased attention to understanding how biological biosimilars can replace these expensive biologicals. “The extremely high prices of most biological products has forced us to look for options,” Zelenetz said.
The biological manufacturing process is extremely complex…much more than that of a small molecule, Zelenetz continued. Studies have confirmed there could exist a lot to lot variation with the innovator products themselves. Analytical evaluation of biological products, including rituximab have shown differences based following slight changes in the manufacturing process. “Is this difference acceptable?” Zelenetz asked. Additionally, immunogenicity risks could be heightened with these variations, which ultimately translate into clinical efficacy and could also raise questions about interchangeability with the reference product, although the United States does not yet have any interchangeable biosimilars
At the preclinical stage, the structure and function of the biosimilar is important to ensure minimal lot to lot variation. Manufacturers also have to be wary of the fingerprint-like identity of biosimilars, including their amino acid sequence and post-translational modifications, higher-order structure, bioactivity, glycoforms, and impurity profile.
Zelenetz told the audience that educating stakeholders, particularly the prescribing physicians, about biosimilars is critical. Physicians need to be educated on safety and efficacy of these products. “Biosimilars need not necessarily be cost-effective, but may yield 20%-40% discount compared with the reference,” he added.
What are the implications of biosimilars for the NCCN? Although only 1 has been approved so far by the FDA, biosimilars should be added as an alternative to the originator product, Zelenetz said.