The Comprehensive Affairs Department of NMPA Solicits Public Comments on “Key Points for Inspection of Drug Product MAHs (Draft for Comments)”

In order to strengthen the supervision and management of drug marketing authorization holders (hereinafter referred to as holders), supervise the holders to fulfill the quality management responsibilities of the entire life cycle of drugs in accordance with the law, and further standardize the supervision and inspection work of holders, this inspection point is formulated in accordance with the "Drug Administration Law", "Vaccine Administration Law", "Drug Production Supervision and Management Measures", "Drug Production Quality Management Standards", etc.

I. Scope of application

This inspection point is applicable to the supervision and inspection of domestic holders who entrust the production of drugs. For holders who produce drugs on their own in China, supervision and inspection shall be carried out in accordance with the requirements of laws, regulations, rules and regulations, and at the same time refer to the relevant requirements of this inspection point.

II. Inspection content

(I) General requirements

1. (General requirements for holders) Holders shall establish a quality assurance system covering the entire process of drug development, production, sales and use, continuously strengthen quality control and quality assurance capabilities, and be responsible for the safety, effectiveness and quality controllability of the entire process of drug development, production, sales and use in accordance with the law.

2. (Marketing release requirements) The holder is responsible for the marketing release of drugs and shall establish drug marketing release management procedures, review the product release procedures formulated by the entrusted manufacturer, clarify the product marketing release standards, and review the drugs released by the entrusted manufacturer as well as the drug production records, inspection records, deviation investigations, etc. If they meet the relevant regulations, they can be released for marketing only after being signed by the quality authorized person.

3. (Management requirements for entrusted production) The holder shall sign a commission contract and quality agreement with the entrusted manufacturer to implement the legal obligations stipulated in the "Drug Administration Law" and various quality management requirements stipulated in the drug production quality management regulations.

4. (Traceability management requirements) The holder shall establish a drug traceability system, implement the drug traceability system, and provide traceability information in accordance with regulations; when selling drugs, provide relevant traceability information to downstream companies or medical institutions to achieve traceability of the entire drug process.

5. (Pharmacovigilance requirements) The holder shall establish and improve the pharmacovigilance system and standardize pharmacovigilance activities. If the holder entrusts a third-party institution to carry out drug vigilance activities, the pharmacovigilance capability of the entrustee shall be reviewed to ensure the implementation of the drug vigilance quality management standards and relevant regulatory requirements.

(II) Institutions and personnel

6. (Organizational setup) The holder shall establish a management department with clear responsibilities and be equipped with management personnel that match the scale of the entrusted drug production. There shall be an organizational chart, and the established management department shall clearly define the responsibilities of drug research and development management, production management, quality management, sales management, storage and transportation management, drug vigilance, post-marketing research, etc., and comply with the requirements of relevant technical specifications. Among them, the quality management department shall be set up independently and perform the responsibilities of quality management. The quality management department shall participate in all quality-related activities and be responsible for reviewing all documents related to the drug production and operation quality management standards. The quality management department shall not entrust its responsibilities to other departments.

7. (Key personnel) The person in charge of the enterprise, the person in charge of quality, the person authorized by quality, the person in charge of production, and the person in charge of drug vigilance of the holder shall be full-time employees of the enterprise, and their qualifications and responsibilities shall comply with the requirements of the drug production quality management standards and the drug vigilance quality management standards.

The person in charge of quality shall be fully responsible for the quality management of the entire process of drugs, establish a quality management department and a quality assurance system, independently perform duties, and ensure the effective operation of the quality management department. The person authorized to quality is mainly responsible for the release of drugs and shall independently perform duties to ensure that the production and inspection of each batch of released drugs comply with relevant laws and regulations and drug registration management requirements.

8. (Job responsibilities) The responsibilities of each position in the organizational structure shall cover all obligations and responsibilities that the holder shall perform as stipulated by drug laws and regulations, without omissions, and ensure that the responsibilities are effectively implemented; departments and personnel shall accurately understand job responsibilities and receive necessary training, including pre-job training and continuing training.

(III) Production management

9. (Confirmation of facilities and equipment) The holder shall confirm that the production conditions and capabilities of the entrusted production enterprise, such as the factory facilities and equipment, meet the requirements of the production process and quality standards of the entrusted production varieties.

10. (Supervision of the production process) The holder shall provide guidance and necessary supervision on the production process of entrusted production drugs to ensure that the entrusted production enterprise can stably produce drugs that meet the intended use and registration requirements in accordance with the registered process.

11. (Process Validation) The holder shall audit the entrusted production enterprise's drug process validation, continuous process confirmation and other activities to ensure that the product's production process and quality are under control.

12. (On-site Audit) The holder shall formulate the entrusted production enterprise's on-site audit cycle based on risk, audit the entrusted production enterprise regularly, increase the frequency of on-site audits for high-risk varieties such as sterile drugs, and continuously ensure the document system of drug quality and safety.

13. (Auditing process procedures, etc.) The holder shall review the production process procedures, product key quality attributes, key process control parameters, intermediate product and finished product quality standards and other quality documents established by the entrusted production enterprise to ensure compliance with the requirements.

14. (Product Information Rules) The holder shall formulate or confirm the entrusted production enterprise's preparation and management rules for the product batch number, production date, and expiration date of the production of drugs, which shall be consistent with the quality agreement or the quality management system document requirements of the entrusted production enterprise.

15. (Co-production assessment) The holder shall regularly review the effectiveness of the co-production risk control measures of the entrusted manufacturer. If the co-production varieties change, the risk assessment shall be re-conducted.

16. (Rework and Recycling) The holder shall confirm the management procedures for the rework and recycling of the production drugs of the entrusted manufacturer, and approve the rework and recycling of the entrusted products in writing. The entrusted manufacturer shall record the relevant activities truthfully and in detail and make them part of the batch record.

17. (Instructions and Labels) The holder shall specify the printing, acceptance, use and processing procedures of drug instructions and labels. If the entrusted manufacturer purchases or prints the drug instructions and labels by itself, the holder shall confirm the relevant operating procedures established by the entrusted manufacturer, and regularly review the implementation of the requirements of the documents by the entrusted manufacturer to ensure that the source, printing and use of drug instructions and labels are accurate, formal and legal.

18. (Storage Conditions) The holder shall review whether the storage of the entrusted production drugs complies with the requirements of the product storage conditions, and shall regularly review the storage management of the entrusted production enterprise to ensure that the measures to prevent confusion, errors, contamination and cross-contamination during the storage process are safe and effective.

Specific news link: The General Department of the National Medical Products Administration publicly solicits opinions on the "Key Points for Inspection of Drug Marketing Authorization Holders (Draft for Comments)"