Differences in Regulatory Requirements Between Western Countries and Japan

The author consistently observes that Japanese regulatory requirements follow a reactive approach.

In other words, the Ministry of Health, Labour and Welfare (MHLW) typically revises ministerial ordinances only after pharmaceutical and medical device companies have already achieved compliance.

In contrast, regulatory requirements in Western countries incorporate the expectations and guidance of regulatory authorities when issued.

Therefore, even if companies cannot comply immediately upon issuance, authorities expect them to achieve compliance within several years.

For example, 21 CFR Part 11 was published in March 1997 and became effective in August 1997, but full-scale inspections did not begin until around 1999-2000. First, regulatory authorities codify their expectations into regulatory requirements, then wait for an appropriate period for companies to achieve compliance before conducting inspections and issuing observations for non-compliance.

Which approach represents the proper way?

Excessive Time Lag from Global Regulatory Requirements

Furthermore, the time lag from global regulatory requirements is excessively long.

The GMP ministerial ordinance and QMS ministerial ordinance revised last year serve as good examples.

The GMP ministerial ordinance underwent its first major revision in 16 years. The ordinance was published on April 28, 2021, and became effective on August 1, 2021. This represented only approximately three months of transition period despite being a major revision.

The QMS ministerial ordinance was revised to align with ISO 13485:2016, but there was still a five-year gap. ISO 13485:2016 was published in March 2016, while the QMS ministerial ordinance revision was published on March 26, 2021, with a three-year grace period until March 2024.

Comparison Table: Regulatory Revision Timeline

Regulation	International Standard/Reference	Publication Date	Japan Revision	Time Gap	Transition Period
21 CFR Part 11	US FDA Rule	March 1997 (effective August 1997)	N/A (not applicable in Japan)	N/A	Full inspections began 1999-2000
GMP Ordinance	PIC/S GMP Guidelines	Ongoing updates	April 28, 2021 (effective August 1, 2021)	16 years from previous revision	Approximately 3 months
QMS Ordinance	ISO 13485:2016	March 2016	March 26, 2021 (effective immediately)	5 years	3-year grace period (until March 2024)

Companies exporting products overseas face double standards. They must learn and implement Western standards on their own initiative.

Inadequate Response to Public Comments

In addition to slow revisions, Japanese ordinances provide extremely unhelpful responses to public comments. The author has submitted public comments in the past, but received responses simply stating “We believe there are no problems with the current situation” without any reasoning.

In the United States, federal law requires responses to public comments to be documented in what is called a “Preamble” and published in the Federal Register.

At that time, authorities must carefully describe how they modified the draft in response to public comments, or if they did not make changes, provide detailed reasoning (FDA’s rationale).

Public comments are carefully considered, and for lengthy ones, creating the Preamble (i.e., responses to public comments) often takes two to three years.

However, in Japan, the typical practice is to solicit public comments as a formality, provide perfunctory responses, and promptly issue the ordinance with virtually no revisions to the draft.

Furthermore, despite slow revisions, the transition period until revised enforcement is short. For example, in the case of the recent GMP ordinance, despite it being a major revision, the transition period was only approximately three months.

Complexity of Japanese Regulatory Requirements

Additionally, Japanese regulatory requirements are complicated. In addition to ministerial ordinances, enforcement notices (article-by-article explanations), division director notices, and administrative communications (Q&A) are issued. Items that cannot be understood simply by reading the ordinance, or requirements that must be complied with, are often described in article-by-article explanations and Q&A documents.

Moreover, article-by-article explanations frequently reference PIC/S Guidelines.

Originally, PIC/S, unlike ICH, is an assembly of regulatory authorities. Regulatory authorities in each country are supposed to create their own national regulatory requirements based on PIC/S Guidelines.

However, important global requirements that the MHLW has not issued, such as data integrity guidelines, exist, and pharmaceutical companies are directed to refer to PIC/S Guidelines.

Can domestic data integrity inspections truly be conducted under such circumstances?

The MHLW has not issued its own comprehensive data integrity guideline. Instead, the 2021 GMP ordinance revision incorporated data integrity requirements and references PIC/S guideline PI 041 “Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments” in the article-by-article explanations. While this approach provides guidance, it places the burden on companies to interpret international guidelines without formal domestic guidance documents.

Lack of Original Japanese Regulatory Innovation

Advanced concepts such as data integrity and risk-based approaches have all been developed by overseas regulatory authorities, and unfortunately, Japan has originated almost none of these.

As one of the three major pharmaceutical consumer nations and a member of the trilateral regulatory framework, questions must be raised about the state of Japan’s regulatory approach.

Understanding the International Regulatory Landscape

To provide context for beginners while maintaining professional accuracy, it is important to understand the global regulatory environment:

PIC/S (Pharmaceutical Inspection Co-operation Scheme): An international organization established to harmonize GMP inspection systems worldwide. Japan joined PIC/S in 2014, committing to align its GMP requirements with international standards. As of 2026, PIC/S has over 50 member authorities from more than 40 countries.

ICH (International Council for Harmonisation): A project that brings together regulatory authorities and pharmaceutical industry representatives from Europe, Japan, and the United States to discuss scientific and technical aspects of pharmaceutical product registration. Unlike PIC/S, ICH focuses on harmonizing technical requirements for pharmaceuticals for human use.

Key International Standards Referenced:

• ICH Q9: Quality Risk Management
• ICH Q10: Pharmaceutical Quality System
• ISO 13485: Medical devices – Quality management systems
• GAMP 5: Good Automated Manufacturing Practice for pharmaceutical computerized systems

Regulatory Reform Considerations

The challenges identified in this column reflect systemic issues that require attention:

1. Proactive vs. Reactive Approach: Regulatory requirements should provide forward-looking guidance that drives industry improvement, not merely codify existing practices.

2. Meaningful Public Consultation: Public comment processes should genuinely influence regulatory development, with transparent documentation of how stakeholder input shaped final requirements.

3. Adequate Transition Periods: Companies need sufficient time to implement major regulatory changes, particularly when requirements involve significant system modifications or cultural changes.

4. Clear Domestic Guidance: While referencing international standards is appropriate, domestic regulatory authorities should provide clear guidance documents tailored to the national context, not simply refer companies to external sources.

5. Innovation in Regulatory Science: Japan’s position as a major pharmaceutical nation should be reflected in leadership on regulatory innovation, not just adoption of concepts developed elsewhere.

These considerations are not criticisms of individuals but rather opportunities for systematic improvement in Japan’s pharmaceutical regulatory framework to better serve patient safety while maintaining industrial competitiveness.

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Note: This article represents the author’s professional observations and is intended to stimulate constructive discussion about regulatory approaches. Specific implementation details should always be confirmed with current regulatory guidance and appropriate authorities.