Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Biosimilars in the EU and in the US

Dr. Karin Markgraf (Abschlußjahr: 2008)

Language: English

Biopharmaceuticals represent one of the fastest-growing segments of the pharmaceutical industry [Biophoenix 2007]. A generation of biological / biotechnology-derived medicinal products are reaching the end of their patent protection time [Wiecek et al 2006]. As with medicinal products containing small molecules as the active substance, this situation creates an opportunity for generic biologicals to enter the market.
Special regulatory requirements for biosimilars are needed, since biological substances are complex, often heterogeneous and slight deviations in the manufacturing process can cause molecular or structural differences which may have influence on safety and efficacy.

Biosimilars regulatory legislation is considerably more advanced in Europe, since a number of biosimilar guidances exist. The overarching guideline on similar biological medicinal products CHMP/437/04 defines the philosophy and principles of biosimilar approval. In addition, a set of biosimilar guidelines has been introduced in the EU, which can be mainly categorized according to their focus on nonclinical and clinical or quality issues, or on specific product-classes. Furthermore, it is likely that more EMEA guidances will be provided in the future.
The centralised procedure is the mandatory marketing authorisation process for biosimilar medicinal products in the EU. The submitted information should not be limited to CTD Modules 1 to 3 like for classical generic products. Additional non-clinical and clinical data of Modules 4 and 5, determined on a case-by-case basis in accordance with relevant scientific guidelines and taking into account the specific characteristic of each individual biological product, have to be submitted, which shows the comparability between biosimilar and reference product [2001/83/EC as amended]. Comparability is defined as the exercise that will demonstrate that two products have similar profiles in terms of quality, safety and efficacy [EMEA/CPMP/BWP/3207/00/Rev1]. A close contact to the EMEA will help the applicant to demonstrate comparability.

In contrast to the EU, the biosimilar regulatory pathway is still under discussion in the US. In the past, the FDA has classified some recombinant proteins as drugs while others are classified as biological products. Abbreviated approvals were given only for proteins classified as drugs. Until now (March 2008), there is no abbreviated approval pathway for biological products. But several bills, which are currently introduced in the House and the Senate, will provide a biosimilar approval pathway for the US.
All current bills would amend the PHS Act and establish an abbreviated process for a biological product that contains a similar active substance as an already approved biological product. These bills are strongly discussed by many parties, such as generic, innovator and patient associations.
The current bills vary on how comparability / similarity must be shown, though they generally require biosimilarity, identical routes of administration, strengths, dosage forms, and the same mechanism of action for the same therapeutic indication. All the bills concentrate mainly on recombinant proteins, but also mention the need for further guidances by the FDA. As one of the most discussed points varied is the market exclusivity periods for the innovator product and for the first biosimilar product provided by the bills.

This master thesis represents the current status (until March 2008) of regulatory requirements for biosimilar biological medicinal products in the European Union, describes the less regulated situation in the United States of America, and provides a comparison between these two major global pharmaceutical markets.

Pages: 48