Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

What are the prospects for a global "biosimilar"development? Comparison of the regulatory requirements for the marketing authorisation of biosimilar products using the example of implemented or proposed legislation in the EU, Canada, Japan and the proposed WHO guidance ***

Dr. Uwe Goßlar (Abschlußjahr: 2010)

Summary
Language: English
Biopharmaceutical drugs which are defined as medicines made by or derived from living organisms by applying biotechnological methods, are one of the fasted growing segments of the pharmaceutical industry.
Development of new drugs and biologic drugs in particular is a lengthy and cost intensive process. Although one of the most challenging aspects of drug discovery is identifying candidate compounds, the most expensive part is the process of taking the candidate through all the required stages of pre-clinical and clinical research and the regulatory process. The overall costs for the development of a biological drug range from 1.24 1.33 billion USD and exceed the development costs for new chemical entities (e.g. 802 million USD) by far.
Whereas in developed countries, the rapidly rising costs of health care, including supplies of medicines, are a matter of intense public concern (costs per year for biotherapeutic drug treatment is on average 16425 USD), the cost of medicines in developing countries can be matter of life and death. Measures to stimulate price competition with innovator drugs and to keep the balance between the continuous development of better innovative medicines and the reduction of public health care costs, include the establishment of a legislation for abbreviated regulatory application pathways for follow-on versions of innovator drugs, thereby facilitating their market entry after expiry of patent protection and data exclusivity.
Follow-on versions of biotechnological medicines are commonly known as biosimilar medicines. The concept of biosimilar medicines is the approval for marketing authorization of a biosimilar product with a reduced non-clinical and clinical data package based on a thorough demonstration of comparability of the biosimilar product to an existing approved product in terms of quality, safety and efficacy. The costs to develop biosimilar medicines are consequentially less compared to the development costs for the innovator product, thereby allowing biosimilar products to enter the market at reduced prices. Biosimilar medicines are therefore considered a major opportunity to provide better access to affordable life-saving medicines. The significance of the introduction of biosimilar medicines may be equal to the emergence of generic medicines.
An important factor for the success of a biosimilar development program, set up by a global acting pharmaceutical company is the ability to access global markets. The European Union (EU) created a policy and legal framework for the marketing approval of biosimilar products with the introduction of the concept of biosimilar products into the EU legislation in 2003 and the biosimilar concept and legislation is evolving rapidly in other countries since. At the global level divergent approaches exist with regards to the regulatory oversight of this type of product for which a variety of terms such as biosimilars, follow-on biologics, follow-on proteins and subsequent entry biologics are used. Legislation for regulatory oversight is either implemented or currently under discussion in an increasing number of countries worldwide.
In March 2009 for example the Japan Minister of Health issued a biosimilar guidance providing instructions on the development and registration of biosimilar products. A regulatory framework for biosimilars is currently in preparation in Canada. The World Health Organization (WHO) has also started to establish a guideline on the evaluation of similar biotherapeutic products in 2008. Countries, mainly less developed countries, which dont have the knowledge and resources to develop their own guidelines, may implement and employ the principles provided by the WHO for the evaluation and licensing of biosimilar products.
Global acting pharmaceutical companies which intend to set up global biosimilar development programs and marketing strategies need therefore to take the regional differences in the regulatory requirements for the abbreviated licensing application early in development into account. Regulatory differences in these regions may dictate the need for replicate programs resulting in increased effort and expenditure and longer time to market.
In order to investigate the prospects of a global biosimilar development program, this master thesis compares the principles and regulatory requirements for abbreviated marketing authorization procedures for similar biological medicinal products in the EU, Canada, Japan and as proposed by the WHO. Differences, in particular in the scope of the respective regulatory frameworks, the intellectual property rights, the reference product requirements, the comparability program requirements, the possibility to extrapolate clinical data, and their impact on a global biosimilar registration strategy by means of a globally acceptable data package suitable for the said jurisdictions are presented.
In conclusion, the regulatory requirements for biosimilar products appear to be very similar in the high regulated markets of the EU, Canada and Japan. Also the proposed WHO guideline, demonstrates a high scientific level which is comparable to other high regulated markets. All regulatory pathways share the same scientific and regulatory principles. Never the less, early consultation with the regulatory authorities in the regions concerned is recommended in order to determine whether the data are compliant with the requirements of the specific regions. The impact of ethnic differences on the required clinical data package should be evaluated on a case by case basis. However, the requirement that the reference product, which should be used during the whole development, should be approved in the individual territory has been identified as a major obstacle to a global biosimilar development. Whereas the Canadian and the WHO guideline do not strictly require or propose the use of a reference product approved in the individual territory, it is required in the EU and Japan.
Pages 98