Regulation of biopharmaceuticals, tissue engineering and biogenerics : key issues for the developer

The objective of the present study is to examine the effect of regulation on development of new biopharmaceuticals, tissue engineering and biogenerics. This includes defining key issues, which may influence the outcome of receiving marketing authorization. Most of the results are based on interviews conducted with experts with different backgrounds: regulators, representatives of biocompanies, investors, researchers and representatives of trade associations. Product information retrievable from the homepages of the EMEA and FDA has also been used as a data source. A review article is also included as it highlights central issues of the thesis and contains new information in addition to the review data. Integration of regulation from the very early stages of product development and a sound understanding of regulatory requirements will have a positive impact on product development. However, detailed regulation is not necessarily available as new technologies push forth. This often leads to case-by-case evaluation, which is demanding and time consuming for both product developer and regulator. Tissue engineering is an example of such emerging technologies for which the regulation is still immature or lacking. According to the present study, a centralised evaluation seems the only possible route for ensuring uniform assessment of tissue engineering products. Currently product developers should develop products according to the medicinal products legislation, which also applies to biopharmaceuticals. Risk assessment and management is essential for Tissue engineering as the risks of these technologies are generally regarded as being substantial. Biogenerics, called similar biological medicinal products in the EU legislation, are and have been in the focus of heated debate in the EU and USA although generics may be regarded as an inevitable step of the technological cycle. The pivotal regulatory issue is the question of comparability, for which the present study reflected no agreement. Control of post-translational modifications, immunogenicity and the extent of clinical trials required by the regulators pose major challenges for the biogenerics manufacturers. Thus, at the present time, biogenerics should be regulated on a case-by-case basis. Data from this thesis shows that intensified monitoring of the safety prof11e is called for. It is evident that risks of biotechnology-derived products are different from small chemical entities. This should lead to focused risk management programs. The main risk is the transmission of infectious agents. From the regulatory point of view, the risk management of biologicals is currently far from optimal as the appropriate legislation lags behind. The SPCs (Summary of Product Characteristics) of the EMEA and the PIs (Package Inserts) of the FDA of 32 approved biopharmaceuticals were compared. A general observation was that the EU SPC is more detailed in its instructions and the approach to safety information was clearly stricter. This difference may reflect the approaches to risk management of new medicinal products by the two agencies. Consequently, in spite of increasing harmonisation of the regulatory requirements, there are significant differences between the regulatory approaches that should be taken into consideration in drafting clinical development plans for biopharmaceuticals for global market.reviewe