The Ministry of Health & Welfare of Japan (MHW) has a number of missions, and these are reflected in its structure, which covers health planning, environmental health, social welfare, health insurance, and pensions. The Pharmaceutical Affairs Bureau (PAB) is the competent agency for drug regulation within the Ministry and technical support is provided by the National Institute of Health.

Japan's market in prescription drugs constitutes approximately 22% of the world market. However, like many other countries, Japan is having a hard time controlling medical expenditure: more than 5% of its GNP is spent on health care, and as much as 30% of this amount is spent on pharmaceutical products. In view of the market size, government policies in the regulation of these products have a significant impact.

The primary mission of the Pharmaceutical Affairs Bureau is to ensure the efficacy and safety of drugs. At the present time, this includes regulatory activities such as reviewing new drug applications or managing postmarketing surveillance. The second mission is to promote Japan's pharmaceutical industry, to foster the development of orphan drugs, and encourage basic research. The MHW is responsible for managing Japan's health insurance system and monitoring expenditure and the price of drugs that are reimbursed by the system is set by the Health Insurance Bureau in collaboration with the Pharmaceutical Affairs Bureau. The PAB employs 180 staff, including 80 pharmacists and 8 medical doctors.

Discussion is ongoing among drug regulatory authorities worldwide as to what is the best drug review system to employ. A number of alternatives are available, but the number one question is whether to perform the review within the agency, or to seek expertise outside. In fact, the reason why some agencies have so many employees and Japan has so few, is that Japan uses outside expertise. Another option would be to make the agency independent by charging user fees. In this way, the agency can hire the necessary staff in line with available resources. Although this is the method employed in some countries, it would be difficult for the PAB to adopt this kind of administrative independence.

The MHW is linked to a semi-governmental Drug Organization which supplements and channels resources and the Ministry uses this intensively to carry out research and development promotion, drug review, and GLP inspection. Another outside body which provides support is the Central Pharmaceutical Affairs Council (CPAC), which is made up of almost 200 members - mostly university professors, physicians, lawyers and other experts, and is in charge of drug review. This body gives advice to the Ministry on the advisability of approving a product.

Future mission of the Ministry of Health & Welfare

The MHW has recently been jolted by two incidents. In 1993, reports of 15 deaths were received concerning an antiviral, sorivudine, within one month of marketing. It was later found that this adverse event had been observed during the drug development stage, but had not been reported nor reflected as a warning in the package insert. This incident raised serious concerns on the quality of the conduct of clinical trials in Japan, the MHW's supervision of drug development, and post-marketing safety measures.

The second incident concerned blood products and this matter is still under investigation. Allegedly there was an unnecessary delay in approving safer blood products and in recalling the older ones. This incident has cast doubt on whether it is appropriate to seek outside expertise when formulating policies, since this procedure dilutes responsibility. Further criticism has also been levelled on the desirability of allowing one bureau to deal with both governmental and industry affairs, leading to difficult and incompatible situations when the needs for safety contradict the interests of industry.

In order to improve this situation, two measures have been adopted. A revision of the Pharmaceutical Affairs Law will come into force in April 1997, and a restructuring of the MHW is under way. The new law will reform clinical trial conduct, improve new drug approval review, and upgrade post-marketing safety measures. At the same time, the Drug Organization has been given more resources to participate in the drug review. Those divisions within the PAB dealing with industry interests will be moved to the Health Policy Bureau. The Pharmaceutical Affairs Bureau will be renamed the Pharmaceutical Safety Bureau which will reflect its primary objective of protecting public safety.

The MHW is reinforcing internal review of new drug approvals and a Review Centre will be established in the National Institute of Hygienic Sciences where officials will perform drug review and prepare evaluation reports in consultation with the CPAC.

Restructuring of Ministry of Health & Welfare

On concluding, I should like to stress the importance for a drug regulatory authority to accept change when this is needed. The MHW has been faced with this challenge and has made sizable adjustments in its efforts to respond to the real and immediate needs of the Japanese people.

* * *