When attending lectures by the Ministry of Health, Labour and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA), one frequently encounters presentations emphasizing “compliance with approved matters.” Companies that have committed violations in the past have had their names repeatedly cited in lectures and conferences over extended periods, serving as cautionary examples.
Compliance with approved matters is, of course, fundamental. Violations should never occur. However, one must question whether misconduct is truly so commonplace among pharmaceutical companies in Japan that such emphasis is warranted.
In recent years, the pharmaceutical industry has indeed experienced significant quality issues. For instance, in the early 2020s, several generic drug manufacturers were found to have manufactured products using methods different from those described in their approval documents and to have created false data records, resulting in business suspension orders. Additionally, in 2023, an organized data falsification incident involving a Site Management Organization (SMO) came to light, sending shockwaves throughout the industry. These misconduct cases are serious matters that threaten patient safety and undoubtedly require stringent responses.
However, such serious misconduct cases are limited to specific companies, and many pharmaceutical companies are genuinely committed to quality assurance. Excessive emphasis on examples from particular companies may foster unwarranted distrust of the entire industry.
Furthermore, does merely adhering to approved matters ensure the manufacture of high-quality pharmaceuticals? The answer is no. Compliance with approved matters represents only the minimum requirement and is insufficient by itself. True quality assurance demands a more comprehensive and preventive approach, including risk management, continuous improvement, and periodic product quality reviews.
Regarding the revision of the GMP Ministerial Ordinance, there was indeed a delay from the initially planned timeline. On April 28, 2021, the “Partial Revision of the Ministerial Ordinance on Standards for Manufacturing Control and Quality Control of Drugs and Quasi-drugs” (Ministry of Health, Labour and Welfare Ordinance No. 90 of 2021) was promulgated and came into effect on August 1 of the same year. This revision was implemented following Japan’s accession to the Pharmaceutical Inspection Co-operation Scheme (PIC/S) in July 2014, with the objective of achieving international harmonization.
The revised GMP Ministerial Ordinance introduced the concept of the Pharmaceutical Quality System (PQS) and codified requirements for quality risk management, product quality review, retention of reference samples, stability monitoring, and supplier management of raw materials. This revision signals a shift from the passive stance of “compliance with approved matters” to an active approach of “continuous quality improvement.”
There have certainly been differences between Japan’s GMP Ministerial Ordinance and the PIC/S GMP Guidelines. The PIC/S GMP Guidelines undergo continuous revision; for example, Annex 1 (Manufacture of Sterile Medicinal Products) underwent major revision in 2022, with more specific requirements for Contamination Control Strategy (CCS) and application of quality risk management. While Japan codified the essential requirements of PIC/S GMP through the 2021 revision, continued attention to international developments and ongoing harmonization remain necessary.
While it is important to hold specific companies accountable for misconduct, is it not more urgent to elevate the quality assurance level of the entire industry? Systematic approaches to quality improvement are required, including ensuring data integrity (DI), effective operation of pharmaceutical quality systems, and fostering a quality culture.
The Ministry of Health, Labour and Welfare issued the “GMP Case Studies (2022 Edition)” in 2022, with a supplementary edition published in 2024. Additionally, the “GMP Inspection Guidelines” were established in March 2024, with partial revisions made in September 2024, demonstrating the regulatory authorities’ commitment to providing continuous guidance. Utilizing these guidelines and sharing knowledge and experiences across the industry will lead to genuine quality improvement.
Moving forward, alongside responding to individual misconduct cases, it is essential to focus on building preventive quality assurance systems, continuing harmonization with international standards, and improving the quality culture across the entire industry. If patient safety is to be prioritized, the industry should learn from past failures while constructing forward-looking quality assurance systems.
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