On Nov. 29, 2022, China National Medical Products Administration (NMPA) released the draft of Administrative Rules on Supervising Marketing Authorization Holder (MAH) as the Main Entity to Fulfill Responsibilities for Drug Quality (hereafter referred to as the Administrative Rules).
China’s drug MAH system has been implemented nationwide since the revised Drug Administration Law came into force in 2019. The obligations for MAHs are mentioned in Drug Administration Law, and is now detailed in the Administrative Rules.
The Administrative Rules applies to MAHs in China, requiring them to establish drug quality management system and be responsible for the safety, effectiveness, and quality controllability during drug development, manufacture, supply, and use according to the Drug Administration Law, Good Manufacturing Practices (GMP), Good Supply Practices (GSP), Good Pharmacovigilance Practices (GVP), and relevant regulations.1
The below are some highlights:
MAH shall establish departments with clear and concrete responsibilities of administrating drug development, manufacture, quality, sales, pharmacovigilance, and post-marketing study. The departments shall be assigned with enough administrative staff tailored to the manufacture and supply scales.
The quality management department shall be set independently. It shall fulfill the quality management responsibilities, engage in all activities related to drug quality, and review all the documents related to drug quality during manufacture and supply.
MAHs, including drug manufacturers, shall assign full-time staff members to work as the key personnel. The key personnel shall meet corresponding requirements in terms of educational background, work experience, professional accreditation, and regulatory knowledge.
1) Responsible person for the corporate
¨ Taking full charge of the routine management of the corporate and fulfilling entity responsibility for the whole-process quality;
¨ Designating the responsible person for drug quality and providing necessary conditions and resources to ensure the quality management department function independently;
¨ Designating the qualified person for independently fulfilling the responsibility of releasing products to the market;
¨ Handling major safety events related to drug quality, to ensure immediate control of the risks;
¨ Establishing the corporate training & examination system for all manufacture management and quality management staffs to improve their awareness of quality and compliance.
2) Responsible person for manufacture management
¨ Ensuring manufacturing activities obey the approved manufacturing process;
¨ Ensuring the factory and facility function well;
¨ Completing necessary validation to ensure drug quality.
3) Responsible person for quality management
¨ Managing drug quality during the whole process;
¨ Establishing quality control and quality assurance systems;
¨ Supervising the compliance of relevant quality management rules, to ensure the quality management system function effectively;
¨ Ensuring the manufacturing process control and drug quality control comply with relevant regulations and standards;
¨ Ensuring the data and records of drug manufacture and testing are authentic, accurate, complete, and traceable.
4) Qualified person (QP)
¨ Independently responsible for releasing products to the market;
¨ Ensuring the manufacture and testing of each released batch of products comply with drug registration requirements, quality standards, and relevant regulation.
*Products shall never be released to the market without the QP’s signature.
5) Responsible person for pharmacovigilance
¨ Responsible for operating and continuously improving the pharmacovigilance system, to ensure the system complies with relevant laws, regulations, and technical rules.
Quality Management System
MAH shall establish and improve the drug quality management system (QMS), which should cover the drug’s whole life cycle, including:
¨ Non-clinical study;
¨ Clinical trial;
¨ Manufacture & supply;
¨ Post-marketing study;
¨ Monitoring and handling adverse reactions, etc.
MAH shall also make quality goals and improve the QMS to ensure the manufactured drugs comply with intended use and registration requirements.
Management of APIs, Excipients and Packaging Materials
MAH shall audit the suppliers of active pharmaceutical ingredients (APIs), excipients, and packaging materials & containers (altogether abbreviated as AEPs). MAH shall ensure the purchased AEPs comply with the requirements for medicinal use, quality management rules of NMPA, and requirements for associated review of AEPs and finished dosage forms.
Management of Post-approval Changes
MAH shall establish a post-approval change control system, including:
¨ Making rules for classifying the changes;
¨ Making a list of changes;
¨ Formulating work procedures and risk management requirements;
¨ Confirming the classification of the change after sufficient research, evaluation, and necessary validation based on the product’s properties;
¨ If the MAH entrusts manufacture to another company, the MAH shall do the above research, evaluation, and validation together with the entrusted manufacturer.
Management of Entrusted Manufacture
In the case of entrusting manufacture, MAH shall fulfil the following obligations:
¨ Evaluating the quality assurance and risk management capabilities of the entrusted manufacturer;
¨ Signing the quality agreement and manufacturing entrustment agreement with the entrustee,
¨ Auditing the AEP suppliers, reviewing the changes, releasing products to the market, and compiling the annual report,
¨ Supervising the entrustee to fulfill its obligations stipulated in the agreements;
¨ Conducting on-site audit of the entrustee’s QMS;
¨ Ensuring the entruster’s QMS connects to the entrustee’s QMS effectively;
¨ Ensuring the manufacturing process comply with regulations.
* MAH shall never transfer its obligations and responsibilities to the entrustee via quality agreement.
Contact BaiPharm to learn about MAH’s other responsibilities.
¨ Key Points for Manufacturing Entrustment Under China's MAH System
¨ China Implements New Rules on Drug MAH's Annual Reports
¨ Drug Recall in China: MAHs Shall Shoulder the Main Responsibility