Responsibilities of Validation Personnel

Background and Legal Framework

On April 28, 2021, the Ministry of Health, Labour and Welfare (MHLW) promulgated the “Ministerial Ordinance Partially Amending the Ministerial Ordinance on Standards for Manufacturing Control and Quality Control of Pharmaceuticals and Quasi-drugs” (MHLW Ordinance No. 90 of 2021, hereinafter referred to as the “Revised GMP Ordinance”).

The Revised GMP Ordinance came into force on August 1, 2021, marking a significant update to Japan’s pharmaceutical manufacturing regulatory framework.

Additionally, on April 28, 2021, the MHLW issued a notification titled “Regarding Partial Revision of the Ministerial Ordinance on Standards for Manufacturing Control and Quality Control of Pharmaceuticals and Quasi-drugs” (issued by the Director of the Supervisory Guidance and Narcotics Control Division, Pharmaceutical Safety and Environmental Health Bureau, MHLW; hereinafter referred to as the “Implementation Notice”). This notification contains article-by-article explanations of the Revised GMP Ordinance, providing essential guidance for manufacturers on compliance requirements.

Validation Personnel Requirements

Regulatory Requirements under Article 13

The Revised GMP Ordinance, Article 13 (Validation), establishes the following requirements:

Manufacturers must ensure that persons designated in advance perform the following duties based on procedures and other documentation:

1. Validation shall be conducted in the following cases:
   1. (a) When manufacturing of pharmaceuticals is newly initiated at the manufacturing site
   1. (b) When there are changes to manufacturing procedures or other aspects that significantly affect product quality
   1. (c) In other cases deemed necessary for appropriately conducting manufacturing control and quality control of products
2. The plan and results of validation as specified in item (1) shall be reported in writing to the organization responsible for quality assurance operations.

Furthermore, based on the results of validation specified in paragraph 1, item 1, when improvements are necessary for manufacturing control or quality control, manufacturers must take required measures and create and retain records of such measures.

Definition and Qualifications of Validation Personnel

The phrase “persons designated in advance” refers to validation personnel. The requirements for validation personnel are explained in Section 3, Article-by-Article Explanations (hereinafter referred to as “Article-by-Article Explanations”) of the Implementation Notice as follows:

Article 13 (Validation) Related Provisions:

This provision stipulates the validation operations to be performed by persons designated in advance by pharmaceutical manufacturers. For persons designated in advance, it is required that staff members who are thoroughly familiar with the facilities, procedures, processes, and other aspects subject to validation be designated in advance as persons responsible for such validation. Their duties and authority should be appropriately defined in documentation pursuant to Article 6, paragraph 4 of the GMP Ordinance.

This requirement emphasizes the importance of technical competence and comprehensive knowledge of the specific systems and processes being validated. The validation personnel must possess both theoretical understanding and practical experience relevant to their assigned validation responsibilities.

Responsibilities of Validation Personnel

Distinction Between Requirements and Guidelines

While the requirements for validation personnel are specified in the Revised GMP Ordinance and Article-by-Article Explanations, the specific responsibilities of validation personnel are not detailed in these documents. Instead, they are described in Section 4, Validation Guidelines (hereinafter referred to as “Validation Guidelines”) of the Implementation Notice as follows:

Implementation Notice, Section 4: Validation Guidelines

(4) Duties of Validation Personnel

The duties performed by validation personnel shall include the following applicable tasks:

1. Supervise and manage the preparation and revision of validation protocols.
2. Supervise and manage that validation is appropriately conducted in accordance with validation protocols, and provide necessary instructions to relevant staff members.
3. Supervise and manage the appropriate recording and storage of data collected during validation, and provide necessary instructions to relevant staff members.
4. When deviations from validation protocols occur, supervise and manage the recording of such deviations, consideration and evaluation of their impact on verification results, and provide necessary instructions to relevant staff members.
5. Supervise and manage the preparation of documents regarding validation results pursuant to Article 13, paragraph 1, item 2 or Article 41, paragraph 1, item 2 of the GMP Ordinance (hereinafter referred to as “validation reports”), and provide necessary instructions to relevant staff members.
6. For manufacturing sites of pharmaceutical manufacturers, report validation reports to the organization responsible for quality assurance operations; for manufacturing sites of quasi-drug manufacturers, report to the quality department.

Key Distinction: Supervision vs. Approval

According to the Validation Guidelines, validation personnel are assigned “supervisory and management” responsibilities. This is a critical distinction that has important practical implications for pharmaceutical manufacturing organizations.

Specifically, validation personnel are not required to assume responsibility for the preparation or approval of validation reports themselves. Their role is to oversee and manage the validation process, ensuring that appropriately qualified staff members carry out the necessary work under proper guidance and supervision.

This supervisory model allows for flexibility in organizational structure and enables validation personnel to focus on ensuring the quality and integrity of the validation process rather than being directly involved in all documentation tasks.

Flexibility in Organizational Structure

Furthermore, neither the Revised GMP Ordinance nor the Implementation Notice stipulates that only one validation person may be designated. This provides significant flexibility for manufacturers in structuring their validation programs.

It is considered desirable that validation personnel be appointed for each product or process, with individuals who are thoroughly familiar with the relevant operations and facilities assuming these roles. This approach ensures that validation activities are overseen by personnel with the most appropriate technical expertise and practical knowledge for the specific systems or processes being validated.

This flexibility recognizes that modern pharmaceutical manufacturing operations are often complex and diverse, requiring specialized knowledge across different product types, manufacturing technologies, and facility systems. By allowing multiple validation personnel with specific areas of expertise, the regulations enable manufacturers to build more effective and technically robust validation programs.

Responsibilities of the Quality Assurance Department

Limited Regulatory Requirements

The responsibilities of the quality assurance department regarding validation are similarly not detailed in the Revised GMP Ordinance or Article-by-Article Explanations. The only specific requirement is found in item 5 of section (4) of the Validation Guidelines mentioned above.

The requirement specifies only that the quality assurance department must receive validation reports in writing. Importantly, it does not mandate that the quality assurance department must be the approver of validation reports.

Approval Authority Flexibility

Under the Revised GMP Ordinance, there is no specification regarding who must approve validation reports. The regulations allow for flexible approaches to approval authority:

• Validation personnel assigned to each product or process may approve the relevant validation reports
• The quality assurance department may approve validation reports
• A combination approach may be adopted based on the specific organizational structure and product complexity

This flexibility in approval authority enables manufacturers to design validation programs that align with their organizational structure, the complexity of their products and processes, and their overall quality management system architecture.

Practical Considerations and Best Practices

Integration with Quality Systems

While the regulations provide flexibility, manufacturers should ensure that their validation programs are fully integrated with their overall quality management system. The relationship between validation personnel and the quality assurance department should be clearly defined in organizational documentation, including:

• Clear delineation of responsibilities and authorities
• Communication protocols for validation planning and reporting
• Escalation procedures for validation failures or significant deviations
• Document approval workflows that ensure appropriate oversight

Documentation and Traceability

Regardless of the chosen organizational structure, manufacturers must maintain comprehensive documentation that demonstrates:

• The qualifications and training of designated validation personnel
• The specific scope of responsibility assigned to each validation person
• Clear procedures for validation planning, execution, and reporting
• Records of all validation activities and their outcomes

Continuous Improvement

The regulatory framework emphasizes that validation is not a one-time activity but an ongoing process. Manufacturers should establish systems for:

• Periodic review of validation status
• Revalidation when significant changes occur
• Ongoing verification of continued process control
• Learning from validation results to improve processes and procedures

Conclusion

The Revised GMP Ordinance provides a flexible yet rigorous framework for validation activities in pharmaceutical manufacturing. By distinguishing between supervisory responsibilities and approval authority, the regulations enable manufacturers to structure their validation programs in ways that best suit their organizational needs while ensuring appropriate oversight and quality assurance.

The key principles that emerge from this regulatory framework are:

• Validation personnel must be technically competent and thoroughly familiar with the systems and processes they oversee
• Multiple validation personnel may be designated, allowing for specialized expertise
• The role of validation personnel is primarily supervisory and managerial rather than executory
• The quality assurance department must receive validation reports but is not necessarily required to approve them
• Manufacturers have flexibility in determining approval authority for validation reports

Understanding these principles enables pharmaceutical manufacturers to develop effective, compliant validation programs that support product quality while maintaining operational efficiency. The emphasis on supervision and management rather than direct execution of all validation tasks reflects a mature regulatory approach that recognizes the complexity of modern pharmaceutical manufacturing and the need for specialized technical expertise at various organizational levels.