Biosimilar products

European Medicines Agency (2005), Guidance documents on biosimilar products. Available at http //www.emea.eu.int/htms/human/biosimilar/biosimilarfin.htm (accessed October 2005). 

WHO Informal Consultation on INN Pohcy for Biosimilar products http //www.who.int/medicines/serv-ices/inn/inn bio/en/index. html... 

This may create a barrier of entry for manufacturers of biosimilar products, and is why these firms are taking calculated risks to enter the market with very limited guidance from the regulatory bodies. The question that must be asked is, Is it worth... 

With regard to the FDA, it is believed that biosimilar products are inevitable. The major pharma industry, once again, is fighting this in order that it may protect its monopoly position. The Food and Drug Administration has indicated that within the very near future, they aim to develop an abbreviated process for limited types of biologies, and will provide guidance on the types of tests needed to demonstrate struc-... 

In the US, the Hatch-Waxman legislation has started the wheels turning with regard to biosimilar acceptance. The legislation that the FDA utilizes as its reference point is provision 505 (b) (2), which allows for the approval of different biological therapies when compared to the originator s product. Both the EU and the US are under increased pressure to approve biosimilar products as soon as possible. The basis of this reality cannot be understated. 

The development path for small-molecule generics has been clear for many years. In contrast, the path for biosimilar products or follow-on biologies has only recently been clarified in Europe (October 2005), and regulatory uncertainty remains in the United States. The new European guideline 2004/27/EC clearly... 

TABLE 1.3-12. Regulatory Criteria for Biosimilar Products or Follow-Ou Biologies... 

Terminology Generics Biosimilar products or Follow-on biologies ... 

The biotechnology industry had its share of major R D and clinical trial success. The big gains for biotech products are mainly in anemia cancer TNF alpha inhibitors human insulin with short, mixed, and long duration of action interferon for multiple sclerosis and hepatitis C monoclonal antibodies for cancer RSV and immuno-inflammatory diseases. This success has resulted in attracting top pharmaceutical companies and R D funds for biosimilar products with improved properties. It is easier for start-up companies in the above areas to attract capital and angel investors or to conclude licensing deals and find marketing partners. 

The active substance of the biosimilar product must be similar in molecular and biological terms to the active substance of the reference medicinal product e. IFN alpha 2a is not similar to IFN alpha 2b... 

In another application, UHPLC-MS technology was developed for rapid comparison of a candidate biosimilar to an innovator monoclonal antibody (mAb) (37). In this study, UHPLC-MS was developed for rapid verification of identity and characterization of sequence variants and posttranslational modifications (PTMs) for mAb products. Although the biosimilar product is expected to have the same amino acid sequence and modifications as the innovator s product, the observed intact mass by UHPLC-MS was different for the biosimilar compared to the innovator protein. Peptide mapping using UHPLC-MS/MS (38) revealed that the mass difference between the biosimilar and the innovator s product was due to a two amino acid residue variance in the heavy chain sequence of the biosimilar (Figure 8.6). 

---