For new drugs to be included as prescription drugs, applications with specified data on safety, stability, clinical test results etc. are required. New Kampo drugs are regulated in essentially the same way as Western drugs in Japan. They are regarded as a form of combined drug, and the same data required for new western drugs are required for new Kampo drugs in the Pharmaceuticals and Medical Devices Agency (PMDA). All the mandatory toxicity study results including special toxicity tests such as for mutagenicity, carcinogenicity and teratogenicity are required as also are the results of three-phase clinical trials.

The high value of Chinese medicines in modern medical practice is indicated by its remarkable growth as prescription drugs in the Japanese market. While 19% physicians recorded having prescribed Chinese medicines in 1979, the percentage increased to 79% in 1989. According to another survey, at least 65% physicians administered both Chinese and modern medicine. Physicians generally recognize Chinese medicine as a complement to modern medicine and it is common knowledge in Japanese society that traditional drugs are safe. As per an in-hospital side-effect monitoring report in 1989, Chinese medicines accounted for a low 1.3% of all cases.

Quality standards of folk and Kampo medicines are based on different evaluation methods, with the effect of the former being assessed on the sum of pharmacological actions of the effective ingredients contained in the raw herb similar to chemical substances. With respect to evaluation and safety, those raw herbs, components of an industrial product with long-established use as folk medicine, are listed in the corresponding monograph and are freely usable within the range of the monograph.

For the evaluation of Chinese medicines on the other hand, importance is given to the ‘empirical facts or experience’ such as reference data, clinical test reports etc. Safety and efficacy is estimated based on general methods employed by modern medical science.

Since the policy of requiring scientific evidence for safety and efficacy was instituted by the Japanese Government in the year 1967, the MHLW has been running a programme for the re-evaluation of all drugs marketed before this. Results of the first re-evaluation of ethical drugs approved prior to 1967 have been made public since 1973 and those of second re-evaluation of ethical drugs approved from October 1967 to March 1980 since 1988. These two re-evaluations completed 99% and 58% respectively of the total number of products. In addition a new system to re-evaluate the efficacy and safety of all ethical drugs every five years was launched in 1988. The methods of re-evaluation of Chinese medicines not being clearly established, an official notification has been issued on 1 February 1991 and a first selection was made of eight prescriptions, with the manufacturers being requested to furnish necessary data to prove their effectiveness and safety.

All these measures resulted in the improvement of the quality control of Kampo drugs in the mid-1980s. An Advisory Committee for Kampo Drugs was established in 1982 in close association with the Pharmaceuticals Affairs Bureau of the MHLW. A working group on the quality of Kampo drugs was established and three years later, a new regulation was issued by the Pharmaceutical Affairs Bureau setting standards for the manufacture and quality control of Kampo drugs. The regulation calls for quality monitoring of specific ingredients, using at least two different chemical or physical methods to test them. Also since 1986, GMP, a standard required of pharmaceutical drugs issued by MHLW in 1976 applies to Kampo drugs too. In addition, in 1988, the Japan Kampo Medicine Manufacturers’ Association drew up self-imposed guidelines that take into consideration the unique nature of Kampo drugs. In 1985 guidelines for extract-based ethical drugs in oriental medicine formulations were developed, according to which data from a comparative study of the extract and a standard decoction have to be provided by the manufacturer of an ethical extract product. Besides data on the crude drug and on the standard decoction prepared in accordance with the TCM prescription, a comparative study has to describe the content of an indicator ingredient in the finished product, which is required to be more than 70% of the content of the indicator ingredient in the standard decoction. For collection of data on adverse drug reactions in Japan there are three major systems of the MHLW:

1. The Adverse Drug Reaction Monitoring System monitors 2,915 designated monitoring hospitals, which have been requested to report cases of adverse reactions to MHLW. This is a voluntary monitoring system, and 1,158 cases of adverse reaction were reported in 1990, of which 15 cases pertained to Kampo drugs.
2. The Pharmacy Monitoring System formed by 2,733 pharmacies mainly collects data on cases of adverse reactions to OTC drugs; 400 cases have been reported annually in the recent years, among which common adverse reactions caused by Kampo drugs are minor, involving symptoms such as gastric discomfort and skin problems.
3. Manufacturers’ Adverse Reaction Reporting involves reporting by the concerned companies, wherein recently several severe cases of ‘Shosikoto’, including drug-induced hepatitis and pneumonitis documented at medical conferences and journals have been reported to MHLW.

In addition, since 1988 the newly drafted Good Post-Marketing Surveillance Practice (GPMSP) has been used on a pilot scale for western drugs dispensed in Japan. When new Kampo drugs are approved and appear on the market, these guidelines will also apply to them.