Biopharmaceuticals: Approval Trends in 2007

More than 70% of the products were produced in mammalian cells.
Oct 01, 2008
Volume 21, Issue 10

Gary Walsh, PhD
The year 2007 witnessed the approval of 15 biopharmaceuticals in the United States and/or European Union (EU). The 15 approvals included six erythropoietin (EPO)-based products, three antibodies, and two hormones, as well as a one therapeutic enzyme, one recombinant vaccine, one growth factor, and a fusion product (Table 1).

The target indications included anemia (six products) hereditary genetic conditions (four products), cancer prevention or treatment (two products), and neovascular macular degeneration, rheumatoid arthritis, and infertility (one product each).

Table 1. Biopharmaceuticals (defined as recombinant protein, monoclonal antibody, and nucleic acid-based products) approved in the United States or European Union in 2007. Biosimilars are in shaded rows.
Only nine of the 15 products were genuinely new to the market in 2007. The other six, although approved in one region last year, had gained approval before 2007 in another world region (Table 1).

In terms of expression systems used, 11 of the 15 approved biopharmaceuticals are produced using mammalian cell lines; two in E. coli, one in Saccharomyces cerevisiae; and notably, one in a baculovirus/insect cell-based system. Overall, this trend confirms the prominence of mammalian-based expression systems in the biopharmaceutical sector. On the other hand, Cervarix's approval is particularly noteworthy as it is the first biopharmaceutical approved for human use that is produced using an insect-cell–based expression system.

A wide range of therapeutic proteins (e.g., tPA, interferon γ, and hepatitis B surface antigen) have been produced at laboratory scale using such systems. A small number of approved veterinary medicines (e.g., Intervet's porcilis pesti subunit vaccine) are commercially manufactured using such systems. The advantages of recombinant insect-cell–based production include high levels of intracellular expression and rapid cell growth on relatively inexpensive media. However, issues including low extracellular expression levels and the exact nature of post-translational modifications achieved have been cited as disadvantages of this system.

Perhaps the single most notable feature of the 2007 approvals is the number of biosimilar products that entered the market in the EU. Of the 14 products approved for the first time last year in Europe, five are biosimilars (Abseamed, Binocrit, Epoetin alfa Hexal, Retacrit, and Silapo; Table 1). This clearly illustrates that the biosimilar legislative framework developed by the EU works in practice. Another notable fact is that all five products are EPO-based. This is not surprising given that EPO is the single most lucrative biopharmaceutical on the market. EPO-based products represent three of the top 10 blockbuster biopharmaceuticals (Aranesp, Procrit/Eprex, and Epogen)1 , and relevant company annual reports show a cumulative annual market value in excess of $10 billion for these three products. The approval of biosimilar EPOs also confirms the practical feasibility of illustrating comparability of a glycosylated biosimilar to its reference medicine.

Quick Recap
Further analysis of the nine products entering the market for the first time last year provides additional insights. The five biosimilar products contain only two different active ingredients: The active ingredient in Abseamed, Binocrit, and Epoetin alfa Hexal (recombinant human erythropoietin alfa) is identical in each case, while Retacrit and Silapo also share an identical active substance (epoetin zeta). Furthermore, Mircera is a PEGylated version of a product already on the market (Neorecormon) and the twin active substances in Pergoveris are already marketed as individual products (Gonal F and Luveris).

The remainder of this article focuses on individual products approved for the first time in 2007, with product information detailed in a monograph format. The information was drawn from regulatory sources and the web sites of sponsoring companies.2,3 Monographs detailing the products listed in Table 1 that had gained prior approval in some world region were included in previous articles.4–6 Therefore, they are not considered below.

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