International Journal of Risk & Safety in Medicine - Volume 21, issue 1-2

Authors: van Boxtel, Chris J.

Article Type: Other

DOI: 10.3233/JRS-2009-0453

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 1-3, 2009

Authors: Rägo, Lembit

Article Type: Research Article

Abstract: Regulatory experience of approving and monitoring safety of biosimilar medicines varies across the World. Recently the European Union has taken lead in establishing a transparent regulatory process for approving biosimilars. The EU to date has approved a number of biosimilars, such as several formulations of somatotropin, epoetin and most recently, filgrastim. The prevailing view among regulators is that as proteins are much more complex than small molecule medicines, it may not be possible to demonstrate the identical nature of two biological products originating from different manufacturing sources solely based on quality information. This leads to the thinking that follow-on biological …products manufactured after expiry of patent and other exclusivity rights by “generic” manufacturers can not be approved using the same simplified regulatory procedures as applied for small molecule based generic drugs. Generating additional nonclinical and clinical data to demonstrate that these medicines have an equivalent, or similar, safety and efficacy profile to the originator product is needed. However, several parties have raised concerns that these regulatory measures may not be enough to ensure the safety and efficacy of these products. In this article a short review of regulatory experience, main principles and issues concerning quality, safety and efficacy (as often inseparable) of these products is given. Show more

Keywords: Biosimilar, pharmacovigilance, drug safety, drug regulation

DOI: 10.3233/JRS-2009-0456

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 5-11, 2009

Authors: Barnes, Henry J. | Ragnarsson, Gert | Alván, Gunnar

Article Type: Research Article

Abstract: Biological medicines have introduced a new set of quality and safety issues because these medicinal products are large molecules synthesized in complex biological processes and may have pharmacodynamic properties that need extra consideration and study for safe administration to humans. A complex manufacturing process and molecular structure means that the exact identity of the material cannot be guaranteed by analytical technology alone but requires a well understood and reproducible manufacturing process. Furthermore, the production systems utilizing recombinant DNA technology in living cell systems are influenced by a multitude of factors that are not easily controlled. The result is that identity …between manufactured lots of one product or between similar products (i.e., biosimilars) is difficult to confirm. Purification and analytical methods such as HPLC, CE, UPLC, SEC, ELISA, ELISpot, SPR and the transgenic mouse immunogenicity model are briefly reviewed as means of achieving the highest possible degree of safety for patients using biological medicines. Show more

Keywords: Biologics, quality, drug safety, regulation

DOI: 10.3233/JRS-2009-0454

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 13-22, 2009

Authors: Gogtay, N.J. | Dhingra, M.S. | Yadav, A. | Chandwani, H.

Article Type: Research Article

Abstract: Vaccine development in India, though slow to start, has progressed by leaps and bounds in the past 60 years transforming it from a nation completely dependent on imported vaccines to one not only self-sufficient in the production of vaccines conforming to international standards, but also a major supplier of the same to UNICEF. Vaccine development is tightly regulated by a hierarchy of regulatory bodies. Guidelines provided by the Indian Council of Medical Research (ICMR) set the rules of conduct for clinical trials from Phase I to IV studies as well as studies on combination vaccines. These guidelines address ethical issues …that arise during a vaccine study. A network of Adverse Drug Reaction (ADR) monitoring centers along with the Adverse Events Following Immunization (AEFI) monitoring program provide the machinery for vaccine pharmacovigilance. Show more

DOI: 10.3233/JRS-2009-0457

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 23-30, 2009

Authors: Löfgren, Hans

Article Type: Research Article

Abstract: This article provides a synopsis of the new dynamics of the global biopharma industry. The emergence of global generics companies with capabilities approximating those of ‘big pharma’ has accelerated the blurring of boundaries between the innovator and generics sectors. Biotechnology-based products form a large and growing segment of prescription drug markets and regulatory pathways for biogenerics are imminent. Indian biopharma multinationals with large-scale efficient manufacturing plants and growing R&D capabilities are now major suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across both developed and developing countries. In response to generic competition, innovator companies employ a range of life …cycle management techniques, including the launch of ‘authorised generics’. The generics segment in Australia will see high growth rates in coming years but the prospect for local manufacturing is bleak. The availability of cheap generics in international markets has put pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new policy direction was announced in November 2006. Lower generics prices will have a negative impact on some incumbent suppliers but industrial renewal policies for the medicines industry in Australia are better focused on higher value R&D activities and niche manufacturing of sophisticated products. Show more

Keywords: Pharmaceutical industry, India, generics, biogeneric, biopharma industry, Australia

DOI: 10.3233/JRS-2009-0459

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 31-40, 2009

Authors: Schück, Stéphane | Texier, Nathalie

Article Type: Research Article

Abstract: The future of the pharmaceutical industry lies with biotechnology. Biological drugs are complicated, expensive products used to treat complex conditions but their contributions to public health are important. A number of biopharmaceuticals on the market have seen their patent protection expired which led to the development of biosimilars. Biosimilars are embedded in the field of biotechnology and their use in therapeutics raise some questions with respect to their safety because of complex production methodologies. This paper summarizes the French law regarding the safety and the development of such drugs.

Keywords: Biosimilars, safety, pharmacovigilance, French law

DOI: 10.3233/JRS-2009-0458

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 41-45, 2009

Authors: Lekkerkerker, Frits

Article Type: Research Article

DOI: 10.3233/JRS-2009-0455

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 47-52, 2009

Authors: Giezen, Thijs J. | Straus, Sabine M.J.M. | Mantel-Teeuwisse, Aukje K.

Article Type: Research Article

DOI: 10.3233/JRS-2009-0465

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 53-58, 2009

Authors: Hama, Rokuro

Article Type: Research Article

Abstract: In Japan not only pharmaceutical companies but also authorities have finally acknowledged their responsibility for class-action suits concerning biologicals including non-heated concentrates contaminated with Human Immunodeficiency Virus (HIV), dried dura mater inducing Creutzfeldt–Jakob disease (CJD) and fibrinogen contaminated with hepatitis C virus (HCV). Japan's yearly consumption of albumin in 1985 was 3.84 million l (800 kg/million person year). That is almost one quarter to one third of the world consumption and this was heavily criticized by other countries. Anti-HCV antibody was introduced for screening of blood as soon as it became available commercially in the late 1989s. The …incidence of Post Transfusion Hepatitis (PTH) fell dramatically from about 10% to about 3% and to less than 1% after the second generation anti-HCV antibody was introduced for screening. After the out-of-court settlement of the suit concerning concentrates-induced HIV, two victims participated as members of a committee for the amendment of the Pharmaceutical Affairs Law, especially those paragraphs dealing with biologicals, which passed and was made known in 2002. According to the new Law, pharmaceutical companies have to discard, recall and stop selling a product when they know that it could induce harmful health problems. In the new Law bio-derived products are clearly defined and a pharmaceutical company is obliged to keep records of bio-derived products for at least 30 years after shipping them. Medical institutions are obliged to keep records of bio-derived products for at least 20 years after they used them. Blood is now strictly screened by 20 mini-pool Nucleic acid amplification technique (20MP NAT). However, there are still several problems regarding biologicals including: 1. A steady increase of newly approved biologicals. 2. Too easy approval of not only biopharmaceuticals but also devices. 3. A lack of strict regulation of clinical trials done by academia. 4. Questions of dosing of biologicals in the future. Show more

Keywords: Biologicals, blood product, safety, vaccination

DOI: 10.3233/JRS-2009-0466

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 59-68, 2009

Authors: Chen, Yixin | Wu, Zhi Ang | Zhang, Chengxu | Wu, Zhonghao

Article Type: Research Article

DOI: 10.3233/JRS-2008-0443A

Citation: International Journal of Risk and Safety in Medicine, vol. 21, no. 1-2, pp. 69-74, 2009