Japan Aims to Cut Antibiotics Reliance on China by Resuming API Production

Antibiotics are essential for treating and preventing infections. In Japan, efforts to reduce dependence on China for the raw materials and ingredients needed to produce these drugs are intensifying.

Without a stable supply of these materials, proper medical treatments and surgeries would be impossible, making antimicrobial drugs a lifeline for the Japanese people.

To address this risk, the government has designated these drugs as critical goods for economic security. With Japan's heavy reliance on China, the urgency to address this issue is growing. Pharmaceutical companies are scrambling to ramp up domestic production.

Reviving Domestic Production

A towering fermentation tank stands out at Meiji Seika Pharma's Gifu Factory, a subsidiary of Meiji Holdings located in Kitagata Town, Gifu Prefecture.

Once the largest in Asia, this 11-meter-high tank holds 165 kiloliters. It is used to produce raw materials and active ingredients for penicillin-based antibiotics.

Factory manager Koichi Mitomo proudly states, "No other facility in Japan can produce penicillin on this scale. We offer fast, efficient, and cost-effective production."

With government support aimed at achieving self-sufficiency in antibiotic production, the company has resumed production of penicillin active ingredients after nearly 30 years.

The company plans to produce 200 tons of raw materials annually, with full-scale production starting in 2025. The goal is to establish a mass production system for penicillin active ingredients by 2030.

Leveraging Technology

The Gifu Factory was originally established in 1971 for penicillin production but halted operations in 1994 due to profitability issues.

Now, with a team of about 140 employees, including some of the original staff, the factory is preparing to resume production. Achieving domestic production of active ingredients would strengthen Japan's pharmaceutical supply chain.

Mitomo notes, "The employees are highly motivated because they feel they're contributing to an important social cause."

The Gifu Factory has preserved its production strains and operates one of the country's largest fermentation and wastewater treatment systems.

With government subsidies, the factory is integrating cutting-edge technology while utilizing its existing infrastructure. Labor-intensive tasks, such as manually loading raw materials into tanks, have been automated. Production records have been digitized. These innovations have made the factory a more attractive workplace for younger generations and women.

The Challenge of Drug Pricing

Penicillin, discovered by British bacteriologist Sir Alexander Fleming from mold, is often hailed as the greatest medical breakthrough of the 20th century. It remains vital for treating infections and is commonly prescribed in internal medicine and ENT clinics. It also plays a key role in preventing infections during surgeries.

However, despite its importance to public health, almost all raw materials and active ingredients for beta-lactam antibiotics, including penicillin, are imported from China.

About five years ago, production issues in China led to a prolonged supply disruption. This resulted in a shortage of cefazolin, an antibiotic produced by Japan's Nichi-Iko Pharmaceutical. The shortage severely impacted Japanese medical facilities, even forcing the postponement of some surgeries.

Dr Chikara Nakahama, who conducted a national survey of clinical physicians during the crisis, noted, "Supply shortages are directly linked to patients' lives. That period brought a significant surge in awareness of the crisis in Japan."

Although the crisis raised awareness of the issue, Japan's development of antimicrobial drugs has since remained stagnant.

Dr Hiroshi Kakeya, director of the Osaka International Research Center for Infectious Diseases, explains, "In Japan, generic drugs are promoted to lower medical costs, but the low price of antimicrobial drugs makes them less appealing to manufacturers."

The recent depreciation of the yen has further exacerbated the issue. As production costs rise, more manufacturers are ceasing production due to profitability concerns.

Dr Kakeya warns, "If China were to restrict the export of active ingredients, domestic supplies would deplete, leading to serious disruptions in infection treatment."

Government Initiatives

In response to the ongoing crisis, the Japanese government designated four beta-lactam antibiotics as specified critical goods in 2022 under the Economic Security Promotion Act.

To support this initiative, they allocated approximately ¥55 billion JPY (about $384 million USD) for essential investments, including facility upgrades.

In 2023, Meiji Seika Pharma and Shionogi Pharma, the production arm of Shionogi & Co, were chosen as key partners to enhance domestic antibiotic production.

Shionogi Pharma will begin trial production of active ingredients at its Kanegasaki Factory in Iwate Prefecture starting in FY 2025 and onwards.

Transferring Critical Skills

Professor Hideaki Hanaki of the Kitasato Institute, which provides bacterial strains to Shionogi Pharma, emphasizes, "While equipment is important, the most crucial factor is training skilled personnel. It's a significant advantage that experts with the necessary knowledge have remained in Japan. We were on the brink of losing our capability for domestic production."

Shionogi Pharma had no prior production experience, so it sought the expertise of two experienced technicians in their 60s to acquire their skills.

At Meiji Seika Pharma's Gifu Factory, only about ten employees who were originally involved in production remain at the company.

Mitomo reflects, "If we had started five years later, passing down these skills would have been a real challenge."

Antibiotics like penicillin are produced through microbial fermentation. This requires continuous monitoring and adjustment of fermentation conditions, including nutrient and oxygen levels in the tanks.

This level of precision is often compared to the craftsmanship of sake brewing and demands expert knowledge and skill.

Mitomo says, "In the future, I'd like to see artificial intelligence learn and replicate fermentation patterns."

While Japan is making strides toward a stable supply of antibiotics, low drug prices remain a challenge. Continued government support is essential for long-term sustainability.

Dr Kakeya suggests, "To maintain sustainable domestic production, it may be necessary to reassess drug prices or for the government to purchase certain active ingredients."

(Read the article in Japanese.)

Author: Sarasa Shimizu, The Sankei Shimbun