Pharmaceutical Technologist - January 2008 - (Page 15)

Morioka 32 drugs that were approved in the US and Europe, only 11 were then approved in Japan — 29 months after Europe. This indicates that clinical development in Japan takes longer and the rate of approval failure is considerably higher, even though the same drugs have been approved abroad. Managing clinical development in Japan seems to be ineffective and inefficient. Research shows that it takes approximately 11.5 years and ¥3.5 billion to move a drug from preclinical studies to approval.4,5 Clinical development During 1995 to 2005, Takeda initiated Phase I studies in Japan for eight compounds, and Phase I studies abroad for 19 compounds. Three of these underwent clinical trials simultaneously abroad and in Japan. However, Takeda is more likely to opt for Phase I clinical trials abroad rather than domestically as they are statistically faster and very safe as a result of the strong support they receive from participating physicians and clinical research organizations (CROs). Even though foreign clinical trials cost more than domestic trials, the fairness and reliability of foreign regulatory agencies is a deciding factor for the Japanese pharmaceutical industry as it is essential to get the results as soon as possible. Why the delay? One possible reason for the delay is the low productivity of R&D activities in Japan. For example, Takeda’s R&D budget for 2006 was ¥200 billion, which was 20% higher than the previous year. This figure is the largest among Japanese pharmaceutical companies — Daiichi-Sankyo’s R&D budget was ¥158 billion (up 8.8%) and Astellas Pharma’s was ¥135 billion (up 5.8%). The rapid increase of Takeda’s R&D budget is a result of the approaching patent expiries in 2009 of its blockbuster drugs. However, the amount is still considerably lower than the 2005 R&D expenditure of Pfizer (approximately ¥820 billion) and Sanofi-Aventis (approximately ¥570 billion). Takeda’s R&D expense shows that the company has spent a significant amount in acquiring promising drug candidates from US start-up companies, which suggests poor R&D performance within the company. The company has, therefore, reorganized its research institutes and plans to build a new research facility in 2010 in Fujisawa (Japan). It hopes that this facility will create new drug candidates from 2011 onwards. There is an increasing trend for small- and medium-sized Japanese companies (as well as the large ones) to conduct clinical trials abroad despite costs. However, there are several reasons why these companies have opted for this move. ● The systems — such as current good clinical practice (cGCP) and Institutional Review Board data collection and storage — and management of Japanese clinical research institutions, are often insufficient — both in number and quality — and do not support effective or efficient clinical trials. For example, there is a shortage of skilled research nurses in hospitals, and it is difficult to find nurses to aid in clinical trials as few hospitals have specific research nurses, and many nurses have double or triple assignments to attend to other than clinical trials. ● Collaboration between physicians and pharmaceutical companies is ineffective in large, late-stage trials, and only very enthusiastic doctors will participate in trials that have little support from their institutions. ● Investigators’ meetings are frequently held by sponsor companies to discuss case studies, but the outcomes are usually poor because of strong instruction by sponsors and principal investigators. ● There are few physicians in Japan who have sufficient knowledge and experience of clinical trials; they often lack the relevant education and training concerning pharmaceutical regulatory affairs and cGCP. ● Protocols and the case report form are determined by the pharmacologists of sponsor companies, which frequently results in delays and the poor performance of clinical trials, as corrections and additions are often required. However, the tide seems to be on the turn as some foreign pharmaceutical companies are hiring more experienced Japanese physicians with higher salaries, but some foreign pharmaceutical companies have also begun to bring in American and European physicians for specific research. For example, Banyu Pharmaceuticals, a Japanese subsidiary of Merck and Co., has There is an increasing trend for small- and medium-sized Japanese companies (as well as the large ones) to conduct clinical trials abroad despite costs. hired 19 physicians; Pfizer (Japan), 18; and Novartis (Japan), 12. This trend may influence domestic pharmaceutical companies to also hire experienced physicians to improve clinical trials. Additionally, if clinical development managers from companies were also physicians, then the attitudes of physicians towards clinical trials may change for the better. There is little corporate, physician or patient participation in Japanese clinical trials compared with overseas trials. Patients have little knowledge regarding clinical trials, and lack voluntary spirit when it comes to medical advancement. It should also be noted that, where as patients who participate in US clinical trials receive free medication, the Japanese all participate in a national health insurance system, meaning that they do not have to consider the cost of medication. Regulatory agencies have little incentive for clinical development. Because of the lack of scientific experience, regulatory officers are uninterested in improving clinical trial design, and make no effort to participate. They only advise sponsors regarding regulations ● ● www.ptemagazine.com 15 http://www.ptemagazine.com

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Pharmaceutical Technologist - January 2008 Contents Editor's Comment News Morpheus Market Watch Lagging Japanese Drug R&D Croatia’s Innovation Integrating PAT with Biopharmaceutical Development and Manufacture Q&A

Pharmaceutical Technologist - January 2008

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