The vast majority of therapeutic drugs are small molecules – that is, produced via medicinal chemistry. But there are also a number of important biologics on the market. In contrast to small molecule therapies, biologics are produced from living cells and are often large, heterogeneous proteins that are very sensitive to the production environment. They are therefore generally more complicated and difficult to manufacture than small molecules.
By current count, there are over 250 biologic products and vaccines on the market, and two of the top ten therapies on the market, Remicade and Enbrel, are among them. Several oft-prescribed biologics are nearing the end of their patent protection, raising the question of how and when less expensive “generic” biologics might be made available.
Generic small molecule drugs are chemically identical to the original. To gain marketing approval, the primary hurdle is showing bioequivalence in man. The nature of biologics, however, means that the generic versions can be made to be quite similar, but probably not identical, to the original. For this reason they’re known as biosimilars. Approval of biosimilars is likely to require a combination of complex bioanalytic, pharmacodynamic and clinical tests, since small differences in process, cell lines or formulation may significantly influence the composition, bioactivity and patient safety.
The European Union Drug Regulation agency has been the first to issue guidelines on the use and development of biosimilars, and the FDA is slated to release guidelines in the near future. In the recent Health Care Reform bill, a framework for biosimilars was outlined, and includes a 12-year exclusivity period to encourage development of innovative biologics. However, the predominant issues are in the area of patient efficacy and safety. Several notable adverse effects have been documented when process was changed for biologics, raising additional concerns that any biosimilar product must be proven both safe and effective. In terms of overall cost, the savings from biosimilars are likely to be modest, since the processes used to produce biologics are both time and labor intensive.
Biotechnology helped develop several new classes of drugs that have permanently improved the treatments of inflammatory disease, diabetes and oncology. It is crucial that new biotechnology innovations are encouraged by whatever framework is developed, and that new research avenues are commercialized. To paraphrase the philanthropist Mary Lasker: “If you think research is expensive, try disease.”
For more information, please check out the FDA website and the website for Bio, the Biotechnology Industry Organization.
