Research

In the US, the Biologics Price Competition and Innovation (BPCI) Act was signed into law on 23 March 2010, giving FDA the authority to approve biosimilars. FDA then issued guidelines for biosimilar applications in February 2012 in the form of three draft guidance documents [1]. Despite this, there remain scientific issues regarding the assessment biosimilars and the criteria for establishing biosimilarity and interchangeability of biosimilars [2].

US-based Epirus Biopharmaceuticals (Epirus) announced on 4 January 2013 that its biosimilar infliximab candidate had ‘achieved bioequivalence’ to Remicade (infliximab) in a single dose comparator trial.

Period: January to August 2012 

Biologicals are large, complex and heterogeneous proteins with variable molecular weights, typically ranging from 18,000 to 45,000 Da. The active substance of a biological is a collection of large protein isoforms and not a single molecular entity. This fact makes manufacturing of biosimilars much more of a challenge than when producing traditional small molecule generics. It also makes it highly unlikely that the active substances between two products are identical and makes it extremely difficult to establish biopharmaceutical equivalence using analytical techniques.

European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use adopted the final guideline on biosimilar monoclonal antibody (mAb) and it came into effect in December 2012. The agency is also currently reviewing two marketing authorization applications (MAAs) for the biosimilar mAb infliximab.

Biopharmaceuticals, drugs produced by live cell culture, have a fast growing market for the treatment of a range of conditions. Despite their clinical importance, however, their cost could impose an increasing burden on either national healthcare systems or patients’ out-of-pocket expenses. The potential for reducing the costs of biopharmaceuticals is therefore attracting the attention of policymakers in the health sector.

Monoclonal antibodies (mAbs) are high molecular weight proteins (~150 kDa), with highly complex secondary and tertiary structures, subject to post-translational modifications, such as glycosylation.

Period: January to August 2012 

Manufacturing of biosimilars is much more challenging than producing traditional small molecule generics. Reasons for this include, in the first place, the huge costs associated with manufacturing of biosimilars, along with the fact that the risk of failure for biosimilars is significantly higher than that for small molecule generics. Secondly, biosimilars are larger and more complex molecules to manufacture. Finally, minor changes in the manufacturing process can cause significant changes in efficacy or immunogenicity.

EMA approved its first biosimilar granulocyte colony-stimulating factor (G-CSF, filgrastim) for use in Europe back in 2008, since then, several biosimilar G-CSFs have been approved, including Biograstim, Filgrastim ratiopharm, Ratiograstim, Tevagrastim, Filgrastim Hexal, Zarzio and Nivestim. All biosimilar G-CSFs were approved using Amgen’s Neupogen as the reference product. Filgrastim ratiopharm was withdrawn on 20 April 2011.

Period: January to August 2012 

In the area of regulation of biosimilars Europe has by far the best-established framework for approval and EMA has already issued both general and product specific guidelines for biosimilar applications to the EU [1]. The first biosimilar was approved in the EU in 2006 for Omnitrope (somatropin). There are now 14 biosimilars approved for use in Europe for three reference products: erythropoietin, granulocyte-colony stimulating factor and somatropin [2].

Period: January to August 2012 

The US is somewhat behind Europe in the biosimilars race, but has issued draft guidance and is expected to have a practical biosimilar approval pathway in place in the near future.