A Wave, Suspended: Follow-on Biologics

By Angelo De Palma, Ph.D., Contributing Editor, and Paul Thomas, Managing Editor Regardless of process, product can equal product, Sensabaugh argued. In other words, products that are slightly different analytically can behave essentially the same in patients, despite the fact that they were manufactured by different companies, through different processes, at different locations. Sensabaugh noted that six structurally identical and equivalent HGH products — from Eli Lilly’s Humatrope to Teva’s Tev-Tropin—are on the market today, having been approved in an earlier era under regulations for small-molecule drugs (see "Product Equals Product," below). In fact, HGH will probably serve as the classic case study for follow-on protein product approval. FDA considers the six products “similar” chemically and therapeutically equivalent despite their diverse manufacturing pedigrees. The critical regulatory issues for biosimilars, Fenton said, will be ensuring patient safety through expanded human clinical testing, and protecting innovators’ intellectual property. While FDA expects to offer a guidance document on follow-on biologics some time in 2006, manufacturers should not expect blanket guidance for all biosimilar candidates. “Demonstrating ‘generic’ interchangeability for follow-on proteins may be impossible,” Clouse said. “They will have to be considered on a case-by-case basis.” As occurred with small-molecule generics after enactment of the Hatch-Waxman Act of 1984, which essentially established the generics industry, original patent-holders will not meekly relinquish control over franchises they developed over many years. Originator firms will attack biogenerics from every angle: legal, intellectual property, medical and scientific. Through established lifecycle-management strategies, large biotech companies will create versions of their products incorporating chemical modifications (such as PEGylation), or changes in dosage form or delivery vehicle. At the same time, they will try to raise scientific questions, for example on the similarity — or lack thereof — between their proteins and follow-on products. Typically, these battles will be fought over higher-order