[Benikoji Incident Research Report Vol. 2] Ethical Issues Logically Concluded from the Use of Industrial Mutant Strains — Insights from Comparison with Antibiotic Manufacturing: Ingesting Unknown Substances with No Dietary History, Whole, at High Concentrations, and Long-Term

Kunsei Club Co., Ltd. (Hayashima-cho, Tsukubo-gun, Okayama Prefecture) continues to disseminate the "Benikoji Incident Research Report" series with the aim of presenting the scientific and legal issues of the Kobayashi Pharmaceutical benikoji incident to society at large. The second report addresses the manufacturing characteristics of the BP-412 strain used by Kobayashi Pharmaceutical in its product — that it is an industrial mutant strain and that no purification process existed — and what problems these characteristics entailed in terms of safety evaluation.

[Summary] The NITE BP-412 strain was created using the same method as industrial mutant strains used in the production of antibiotics such as penicillin and tetracycline. In pharmaceutical manufacturing, a purification process follows fermentation, and byproducts are discarded. However, because Benikoji Colestehelp was a food product, no purification process existed, and the fermented material was directly formulated into a product. The product design inherently allowed for the long-term, high-concentration ingestion of unknown byproducts with no dietary history. This is a critical consideration for safety evaluation.

1. Industrial mutant strains are a method also used in antibiotic manufacturing

Many of today's major antibiotics, such as penicillin, tetracycline, cephalosporin, and erythromycin, are produced through microbial fermentation. To increase production efficiency, "industrial breeding strains" created by subjecting wild-type strains to mutagenesis (e.g., UV irradiation, chemical mutagens) are often used.

The BP-412 strain was also created using similar methods in this context. In other words, the use of industrial mutant strains itself is an established manufacturing technique.

2. However, in pharmaceuticals, byproducts are "purified and discarded"

What is critically important in antibiotic manufacturing is the post-fermentation process — the purification and extraction process.

Fermentation using mutant strains produces numerous byproducts in addition to the target main component. In pharmaceutical manufacturing, these byproducts are removed and discarded through the purification process. The final product contains only the main component at a controlled purity.

This is one of the key mechanisms for ensuring safety in pharmaceuticals.

3. Benikoji Colestehelp had no purification process

Because Benikoji Colestehelp was sold as a food product (a Food with Function Claims), it did not have the purification and refinement processes required for pharmaceutical manufacturing.

The fermented material of the benikoji mold produced by solid-state fermentation — the entire fermented material including monacolin K and other byproducts — was directly formulated and encapsulated.

It is confirmed that consumers ingested not just the purified active ingredient, but the entire fermented material.

4. The byproducts are "unknown substances with no dietary history"

Traditional benikoji foods have a dietary history spanning over a thousand years, and their safety is supported by historical and academic knowledge.

However, with the BP-412 strain, the composition of metabolites produced by mutagenesis may differ from that of traditional benikoji mold. The formulation was carried out without sufficient identification and evaluation of what those byproducts are — both in terms of type and quantity.

5. The structure of the problem: "Ingesting something unknown, whole, at high concentrations, and long-term"

Summarizing the above, the design of Benikoji Colestehelp had the following structure:

- Use of an industrial mutant strain (BP-412) with no dietary history - No purification process — byproducts directly mixed into the product - Composition of byproducts unidentified and unevaluated - General consumers self-administering high-concentration, long-term, continuous intake

If this were a pharmaceutical, this structure would be evaluated and addressed during the approval review process. How this structure was evaluated within the framework of food products — this is a critical issue that should be scientifically and administratively verified as the starting point of this incident.

[Reference Comparison] Antibiotic Manufacturing Process vs. Benikoji Colestehelp Manufacturing Process

① Fermentation

Fermentation with industrial mutant strain: Produces main component + numerous byproducts

Solid-state fermentation with BP-412 strain: Produces monacolin K + unknown byproducts

② Purification

Purification/extraction process exists: Only main component isolated → byproducts discarded

No purification process: Solid fermented material directly formulated

③ Product

Purified main component: Composition known and quality-controlled

Whole fermented material: Type and quantity of byproducts unknown

④ Intake

Taken under doctor's supervision: Dosage and duration strictly controlled

Self-administered by general consumers: High-concentration, long-term, continuous intake

Conclusion

Safety ensured: Purification + approval review + prescription management

Becomes a critical consideration for safety evaluation: Structure of long-term intake of byproducts with no dietary history

[Next Issue Preview] Vol. 3

Vol. 3 will compare with EU Novel Food regulations. It will examine the regulatory treatment of mutant strains like BP-412 in Europe and clarify the institutional differences with Japan's food safety administration. The framework of prior evaluation required by Europe for products containing novel ingredients without traditional dietary history will serve as an important axis of comparison to illuminate the structural problems of this incident.

Reference Documents

1. Gunze Limited, Published Patent JP2009095304A (specifies creation of BP-412 strain through mutagenesis)

2. Kobayashi Pharmaceutical Co., Ltd., Official News Release (July 17, 2018) (officially announced use of BP-412 strain)

3. Various published literature on antibiotic manufacturing (purification processes for penicillin, tetracycline, etc.)

[Published by]

Kunsei Club Co., Ltd. Representative Director & Pharmacist Masaaki Mori

〒701-0303 611-1 Maegata, Hayashima-cho, Tsukubo-gun, Okayama Prefecture

TEL: 086-483-0602　　E-mail: sales@kunsei.co.jp

https://kunsei.com/archives/category/benikoji (Benikoji issue verification site)