Outi Nieminen

Risk management for biological products

The risks of biotechnology-derived products and other biologicals are different from the risks of small chemical entities and, thus, their risk management will have special features. For many biological products, the safety is mainly dependent on the starting materials and the manufacturing process. Therefore, their risk management must be focused accordingly. In certain issues, such as immunogenicity of recombinant DNA products, a proper risk management plan can only be built during the pre-licensing studies. Application of special epidemiological methods for investigation of very rare safety signals is crucial for some biologicals, e.g. vaccines. Genetically modified viruses used as vaccines and vectors for gene transfer, as well as xenogeneic cells, carry major public health risks. Therefore, the use of such products is possible only with extensive risk management programmes. Some elements of these programmes may be difficult to enforce because of legal, ethical and practical obstacles.The main special risk of biologicals is the transmission of infectious agents. The mitigation of this risk is complicated by the ever-changing epidemiological situation and the long latency of some infections. The impact of any measure for risk reduction of essential products, such as vaccines and plasma-derived medicinal products, must be considered carefully from the overall benefit/risk point of view. The risk must be reduced to the lowest level that is reasonably achievable without unduly putting the availability of essential products at risk. Adequate expertise and consultations with special experts are important in the risk management of the new advanced therapies in order to ensure the full understanding of the risks and to avoid creating unnecessary barriers for innovation.Due to the sensitive issues linked with biotechnology-derived products and other biologicals, risk communication is of critical importance. From the regulatory point of view, the risk management of biologicals is far from optimal, especially in the EU where legislation lags behind the progress in the field, and where the concerted actions of the national regulatory agencies need improvement. From the industry point of view, the risk management plans for biologicals should be designed in multidisciplinary teams.

Regulation of biogenerics: a survey of viewpoints.

Background and objectives‘Biogenerics’ regulation has brought about a heated debate within the EU as the first biopharmaceuticals are going off patent. This study aims to examine the opportunities and challenges offered by biogenerics by surveying the viewpoints of experts in regulatory agencies and in companies developing novel biopharmaceuticals and biogenerics.MethodsOral interviews were conducted in 2002 and 2003 with experts including representatives of the European Generic Medicines Association (EGA) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in Brussels, three innovator biotech companies, and five other experts in Finland. Additionally, four biogenerics companies and one innovator company abroad answered a structured, written questionnaire.Results and conclusionAccording to this study, biogenerics should be regulated on a case-by-case basis. The interviewees were not unanimous as to whether comparability can be addressed and which are the most challenging areas for proving comparability. Immunogenicity was considered to be a major problem for biogenerics. Therefore, a requirement for an intensified monitoring of the safety profile during post-marketing was thought to be justified in many cases.

Biotechnology Regulation: Views of the Authorities, Investors, and Product Developers in Finland

This study addresses regulatory issues and problems associated with product development of biotechnological medical products and devices. Data were collected from interviews with Finnish companies, including: (1) recent startup companies and more established companies that develop biopharmaceuticals and devices; (2) primary public and private investors in Finland, including venture and corporate capitalists; (3) private Finnish insurance companies; and (4) representatives of the Finnish national authorities. Two United States biotechnology companies, and European Agency for the Evaluation of Medicinal Products and U.S. Food and Drug Administration representatives were also interviewed. Results show that, in Finland, developers, regulators, and investors have strong confidence in the success of Finnish biotechnology. However, according to this study, the regulatory definition of product categories of new biotechnological products is still evolving. This may lead to difficulties in achieving a definitive understanding of the exact regulatory procedures required to gain authorization to market these products and, thus, determining the information required to adequately describe early product development. Key issues are: scale-up of manufacture, product purification, safety aspects, and maintaining comparability with reference to possible changes in the manufacturing process. Improvements in dialogue in the development phases in terms of scientific advice should be promoted.