Researchers tested whether the assumption that it is not required to demonstrate therapeutic equivalence with the branded product because therapeutic equivalence is assumed from pharmaceutical equivalence. This has far-reaching implications, since many regulations rely on this assumption for the approval of biosimilar products.

In this study biosimilar and branded vancomycin were compared. Vancomycin is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by gram-positive bacteria.

The biosimilar products were similar with respect to their pharmacokinetic characteristics, protein binding and antibacterial activity to the original Eli Lilly vancomycin (VAN-Lilly).

However, in a staphylococcus aureus infection model, the antibacterial activity of the biosimilar vancomycin preparations proved to be significantly inferior to that of VAN-Lilly. One generic could not even achieve bacteriostasis, and others showed a pronounced Eagle effect, with paradoxical bacterial growth at high antibiotic concentrations, whereas VAN-Lilly exhibited bactericidal activity over a broad concentration range.

There is a caveat to the story, however. The above results were for products marketed between 2002 and November 2004 (when Eli Lilly sold its brand name and production secrets to several manufacturers worldwide). After November 2004, the production process of some biosimilar vancomycin preparations was therefore changed. Those produced according to the original Eli Lilly protocol showed in vivo antibacterial potency similar to that of VAN-Lilly.

The authors noted that high concentrations of fermentation impurities in the biosimilar products probably explain their impaired antibacterial activity and the Eagle effect.

This research further highlights the difficulties with demonstrating the ‘comparability’ of biosimilar products and the fact that the manufacturing process is critical in producing biosimilars. Despite these challenges, biosimilars have the potential to provide both cost savings and greater accessibility to biopharmaceuticals.

Related article

Regulatory recommendations for biosimilars in the EU

The biosimilars challenge

Reference

Glück T. Is Generic Vancomycin Inferior to Branded Vancomycin? Medscape. 29 September 2010