Masterstudiengang "Drug Regulatory Affairs"


Evaluation of the legal basis of biological and biotechnological product applications in Europe and US and discussion of consequences for similar biological medicinal product applications

Florian Strohmaier (Abschlußjahr: 2008)

Language: English

In this master thesis two main focuses are set. Firstly, the evaluation of the historic development of the legal basis of biologic and biotechnology derived medicinal product application procedures. Secondly, the consequences and hurdles for biosimilar applications effected by the different authorisation procedures for biologics either due to the historic development or based on the regulation of distinct product classes.

This evaluation will be limited to the legislative development in the European Union and the United States as these two regions stand for the most relevant economic areas with the highest turnover of biological drugs. Consequently, the regulatory bodies, i.e. EMEA and FDA, have the most comprehensive experience and scientific knowledge in the field of biologic and biotechnology derived drugs and thus have a leading role in scientific discussions that significantly influence the establishment of the legislative basis for approval of these medicines.

In the evaluation of the legal basis for the first part the broad spectrum of biologic products is covered, starting with blood products continuing with vaccines and biotechnology derived products and ending up with the latest developments in the jurisdiction of advanced therapies. However, for the generic industry currently only a minor number of product classes is of interest which are topically biotechnology derived products and some biologic products that have blockbuster status and thus are in the focus of the generic industry. Therefore, the approval pathways for similar biological medicinal products and its hurdles are discussed in the second part of this thesis on the basis of some exemplary products that represent these product classes.

For biotechnology derived products two different types should be evaluated. Firstly, a non-glycosylated relatively simple well-characterisable protein. For this category human growth hormone also called somatropin (INN) was chosen which has already been approved as biosimilar and which accounts for the product class that includes among others products like insulin, hyaluronidase or recombinant salmon calcitonin. Secondly, a glycosylated protein with its variable glycosylated side chains should be evaluated that is much more complex in its molecular structure and heterogeneity. As an example erythropoietin was selected that is representative for many cytokines and also antibodies.

Finally to include also a biologic product low-molecular-weight heparin that is obtained mainly from porcine intestine or bovine lung was included in the evaluation as this would be an example for a biologic product being of interest for the generic industry.
The evaluation shows that the regulation of biologics in Europe an the United States is heavily influenced by the point of departure and the different approaches in the regulation of medicinal products. Meanwhile the legislative basis for most biologic medicines is consistent and clear, however new product classes like advanced therapies or even biosimilars trigger regulatory uncertainties that require new laws and support of regulatory authorities in form of guidelines.

Concerning biosimilars the European Union together with the EMEA currently plays the leading role and embosses the regulatory landscape for these products, but there are still some major gaps, e.g. interchangeability, that have to be filled.

In the United States the situation is much more complicated due to the split up of the approval of biologics as drugs via FD&C Act or biologics via PHS Act. However, it can be expected that a law regulating biosimilars independent from the approval pathway of their reference products will be passed at least in 2009. Then the FDA can regain the lost time and set up guidance for the approval and interchangeability of biosimilar products.

Pages: 55