GMP for Excipients and GMP Guidelines for Packaging Materials in China have been published in draft format for industry comment by China’s National Medical Products Administration (NMPA).
The new draft regulations entitled “Good Manufacturing Practice for Pharmaceutical Excipients” and “Good Manufacturing Practice for Pharmaceutical Packaging Materials” are set to take effect in 2025 and aim to standardize and enhance the quality management systems of manufacturers of pharmaceutical excipients and packaging materials. Before formal implementation, these manufacturers should promptly improve their facilities and equipment, and perfect their quality management systems to ensure compliance with the requirements of the GMP for pharmaceutical excipients and drug packaging materials.
The new guidelines align with the Drug Administration Law, the Measures for the Administration of Drug Registration, and the Measures for the Supervision and Administration of Drug Production. In this article, we highlight the significant changes from the previous 2006 version of GMP for excipients and the impact on pharmaceutical drug marketing authorization holders, excipient manufacturers, and packaging material manufacturers. If you wish to submit comments, the deadline to do so is August 20, 2024, and you can find details on how to do so at the end of this article.
Enhanced Quality Management Systems
Impact on Manufacturers:
- Excipients and Packaging Manufacturers: Must establish and enhance their quality management systems with detailed management documents, operating procedures, and records tailored to their production scale. Regular quality assessments and thorough inspection of each production batch before release are mandatory. For exported products, compliance with the quality standards of the importing country is required.
- Drug Marketing Authorization Holders: Need to ensure that their suppliers meet the new stringent quality management requirements. This includes evaluating and approving suppliers and conducting rigorous incoming inspections.
Change Management
Impact on Manufacturers:
- Excipients and Packaging Manufacturers: Required to implement a robust change management system to handle changes in production processes or raw materials. Changes must be categorized based on risk, thoroughly researched, and approved by both the quality management and product registration departments before implementation. Depending on the type of change, the Regulatory Registration Manager needs to report, file or supplement an application with the NMPA. Only after the NMPA grants approval can manufacturers implement changes.
- Drug Marketing Authorization Holders: Must be promptly informed of any changes in production processes or raw material sources that could impact product quality. They are responsible for evaluating these changes and ensuring they do not compromise drug safety and efficacy.
Supplier Management and Audits
Impact on Authorization Holders and Suppliers:
- Excipients and Packaging Manufacturers: Subject to stringent evaluation and approval processes. Regular quality assessments and on-site audits of their quality management systems are mandatory.
- Drug Marketing Authorization Holders: Responsible for conducting regular quality assessments and on-site audits of major suppliers’ quality management systems. They must review suppliers’ quality control and inspection capabilities, especially when inspections are outsourced. A quality agreement with suppliers is required, and any changes in excipients must be thoroughly evaluated for their impact on drug quality and stability.
External Communication and Cooperation
Impact on Manufacturers:
- Excipients and Packaging Manufacturers: Must cooperate closely with marketing authorization holders, providing access to relevant documents, records, and facilities. Prompt communication of any changes in production processes or raw material sources that could impact product quality is required.
- Drug Marketing Authorization Holders: Need to ensure open lines of communication with suppliers to promptly address any changes that could affect the quality and stability of the drug.
Entrusted Production Management
Impact on Manufacturers:
- Excipients and Packaging Manufacturers: Intending to outsource production must declare and clarify the production entity as per review procedures and organize production according to stipulated requirements.
- Drug Marketing Authorization Holders: Must ensure that any outsourced production complies with the new GMP for excipients standards and is thoroughly vetted.
Responsibilities of Drug Marketing Authorization Holders Quality Management
- Authorization holders are responsible for establishing and maintaining a quality management system for pharmaceutical excipients and packaging materials. This includes evaluating and approving all suppliers and conducting rigorous incoming inspections. Regular quality reviews and audits of suppliers are required to ensure compliance with medicinal standards.
Supplier Audits
- Authorization holders must conduct regular quality assessments and on-site audits of major suppliers’ quality management systems. This ensures that the pharmaceutical excipients and packaging materials used in drug production meet safety and quality standards.
Quality Control
- Authorization holders need to review the quality control and inspection capabilities of manufacturers. A quality agreement with suppliers is essential, and any changes in excipients must be thoroughly evaluated for their impact on drug quality and stability.
Role of Drug Regulatory Authorities
Supervision and Inspection: Provincial drug regulatory departments will strengthen policy enforcement, ensuring that manufacturers conduct self-inspections and improve their quality management levels. Regular inspections and quality sampling of excipients and packaging materials will be conducted to maintain oversight.
Risk Handling and Legal Enforcement: Regulatory authorities will investigate and penalize non-compliance with the new GMP standards. Notifications to cease using non-compliant products and updates to the registration status of products based on inspection outcomes will be enforced. Information Sharing: The NMPA will facilitate information sharing through an information registration platform, enabling better supervision and unified manufacturer and product data management.
Implementation Timeline and Transition
A clear timeline for implementation is set for January 2025, giving manufacturers time to upgrade facilities and quality management systems to ensure compliance. The previous guidelines from 2006 will be repealed upon the new regulations’ implementation.
Conclusion
The new GMP for excipients represents a substantial upgrade over the 2006 version, the new GMP guidelines for packaging materials in contact with pharmaceuticals represent new requirements for manufacturers.
Overall, there is a stronger emphasis on comprehensive quality management systems, stringent change management, enhanced supplier audits, and rigorous regulatory supervision.
For regulatory affairs managers of pharmaceutical drug marketing authorization holders, this means heightened responsibility in ensuring compliance and maintaining robust quality systems. Excipients and packaging manufacturers will face increased scrutiny and will need to demonstrate adherence to stringent standards to maintain their business relationships.
The collaborative effort between manufacturers, authorization holders, and regulatory authorities will be crucial in achieving the overarching goal of ensuring drug safety and efficacy.
How to submit your comments
You can submit comments using the feedback form found in Annex 2 to yaopinjianguan-2@nmpa.gov.cn with the subject “Feedback on GMP of Pharmaceutical Excipients, Pharmaceutical Packaging Materials and Related Announcements”.
Further information
For assistance in setting up a GMP for Excipients or a GMP for Pharmaceutical Packaging that are compliant to these new requirements, please contact Cisema.
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