The Current Situation of Japanese Medicinal Plants Industry and its Significance on the Pharmaceutical Industry 2-1b - 農業知識入口網

2. Current situation of crude drug products

2-1. Kampo medicines

During the early approval stage of Kampo extract formulations, lack of regulation details led to products with less content of constituents than decoctions. In 1986, the government re-established the regulations for quality control and this became known
as Marukan. The revised standards8) required extract content products to contain homogenous amount of dried extract that was equivalent to the amount generated from standard decoctions prepared via traditional methods (note that each company devised its own standard decoctions). The amount of two or more indicator ingredients of extracts had to be comparable to the standard decoction also, and the accepted range for these ingredients was defined at ±50% mid-range. In contrast to the Traditional Chinese medicinal products that incorporate whole extracts in every production, and consequently vary in amount among the batches, Kampo extract formulations contain very stable and consistent amount of ingredients across all batches.

After 2006, the JP created a regulation list for Kampo extracts based on each company’s standards. The following eight formulations were added and listed in the pharmacopoeia4): Kakkonto (Ge-Gen-Tang), Daiokanzoto (Da-Huang-Gan-Cao-Tang), Kamishoyosan (Jia-Wei-Xiao-Yao-San), Ryokeijutsukanto (Ling-Gui-Shu-Gan-Tang), Hochuekkito (Bu-Zhong-Yi-Qi-Tang), Saireito (Chai-Ling-Tang), Hangekobokuto (Ban-Xia-Hou-Pu-Tang), Keishibukuryogan (Gui-Zhi-Fu-Ling-Wan). For each extract, the following sets of standards were defined:

(1) Contents of indicator ingredients, (2) Method of preparation, (3) Description, (4) Identification, (5) Purity (heavy metals, arsenic, etc.), (6) Loss of drying, (7) Total ash, (8) Assay, (9) Container and Storage.

Each company devised their own regulations and standards in their approval documents for formulations and crude drugs. Even though these standards were independently implemented, they all fell within the wider range of JP standards.

In addition to the official GMP for medicine, JKMA established a self-imposed standard called “GMP for Kampo products” in 1988 for the manufacturing of Kampo extract formulations. They also established a crude drug control manager who oversaw the quality assurance of crude drugs, and included additional testing of aristolochic acid and residual pesticides in the 2007 revision 9). Regulations such as GAP, GFCP, GACP had not been established in Japan yet.