China Marketing Authorization Holder (MAH): Responsibilities for Drug Quality
After consulting on the draft in Nov. 2022, China National Medical Products Administration (NMPA) released the Administrative Rules on Supervising Drug Marketing Authorization Holder as the Main Entity to Fulfill Responsibilities Drug Quality (hereafter referred to as the Rules) on Dec. 29, 2022. The Rules will take effect on March 1, 2023.
The Rules apply to MAHs in China, requiring them to
- obey the Drug Administration Law and relevant laws & regulations;
- comply with Good Manufacturing Practices (GMP), Good Supply Practices (GSP), Good Pharmacovigilance Practices (GVP);
- establish and improve the drug quality management system;
- be responsible for the safety, effectiveness, and quality controllability during drug development, manufacture, supply, and use.
The Rules detail the drug quality responsibilities in the following aspects:
Main Aspects of Drug Quality Responsibilities in China
|MAH Organization and Departments||Key persons:|
|– Legal representative, responsible person of the corporate|
|– Responsible person for manufacture|
|– Responsible person for quality|
|– Qualified Person (QP)|
|– Responsible person for pharmacovigilance|
|MAH Quality Management Requirements||Managing active pharmaceutical ingredients (APIs), excipients, and packaging materials|
|Managing post-marketing changes|
|Managing market release|
|Managing entrusted manufacture|
|Managing storage and transportation|
|Managing drug traceability|
|Managing drug recall|
|Establishing pharmacovigilance system|
|Conducting post-marketing study|
|Handling drug safety events|
|Reporting halted production|
|Fulfilling legal liability|
|MAH Quality Management Mechanism||Reviewing batch records|
|Management analysis and review of drug manufacture and quality at least once every quarter|
|Writing annual report|
|Conducting internal review/audit|
The detailed responsibilities are as follows:
Organization and Department
MAH shall establish departments with clear responsibilities for
– non-clinical study;
– clinical trial;
– manufacture & supply;
– post-marketing study;
– monitoring and handling adverse reactions, etc.
The quality management department should be independent from other departments. It is responsible for fulfilling the whole-process quality management responsibilities, engaging in all quality-related activities, and reviewing all the documents related to quality management.
Responsibilities of Key Persons
All the key persons shall be full-time employees of the MAH.
|Legal Representative, Responsible Person of the Corporate||Taking full responsibilities for drug quality:
1) Taking full charge of the routine management of the corporate, and fulfilling the entity responsibility for the whole-process quality;
2) Designating the responsible person for drug quality, and providing necessary conditions and resources to ensure the quality management department function independently;
3) Designating the qualified person for independently fulfilling the responsibility of releasing products to the market;
4) Handling major safety events related to drug quality, to ensure immediate control of the risks;
5) Establishing the training & examination system for manufacture management and quality management;
6) Appointing the person responsible for pharmacovigilance.
|Responsible Person for Manufacture||Managing drug manufacture:
1) Ensuring drugs are manufactured and stored according to the approved process;
2) Ensuring the factory and facility function well, and completing necessary validation to ensure drug quality;
3) Ensuring the manufacture management training system function effectively; conducting trainings and exams for all the persons involved in drug manufacture management.;
|Responsible Person for Quality||Managing drug quality:
1) Establishing quality control and quality assurance systems, supervising the implementation of GMP, GSP, and GVP, as well as ensuring the quality management system function effectively;
2) Ensuring the manufacturing process control and drug quality control comply with relevant regulations and standards;
3) Ensuring the data and records of drug manufacturing and testing are authentic, accurate, complete, and traceable;
4) Ensuring the quality management training system function effectively; conducting trainings and exams for all staff members engaged in drug quality management.
|Qualified Person (QP)||1) Independently responsible for releasing products to the market;
2) 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.
|Responsible Person for Pharmacovigilance||Establishing, operating, and continuously improving the pharmacovigilance system, to ensure the system complies with relevant laws, regulations, and GVP.|
Auditing AEP Suppliers
MAHs shall audit the suppliers of APIs, excipients, and packaging materials & containers (altogether abbreviated as AEPs). To be more specific, 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.
Managing Post-marketing Changes
MAHs shall establish the system for controlling post-marketing changes, including
– formulating the classification principles for internal changes, change lists, change procedures, and risk management requirements;
– determining the change classification only after sufficient research, evaluation, and necessary validation. If entrusting manufacture to another company, the MAH shall conduct the research, evaluation, and validation together with the entrustee.
– carrying out the change after approval/filing, or recording the change in the annual report.
Managing Market Release
MAHs as manufacturers shall
– establish procedures for releasing products to the market;
– clarify standards and conditions for market release;
– review the quality testing result, critical manufacturing record, and deviation control situation;
– conduct quality testing.
If the MAH entrusts manufacture to another company, the MAH shall still make market release procedures, review the entrustee’s market release procedures, clarify release standards, and review the drug testing result and market release documents. When necessary, the MAH can review the entrustee’s manufacturing record, testing record, and deviation investigation.
If the products are qualified, they can be released with the QP’s signature.
Managing Entrusted Manufacture
In case of manufacture entrusted to another company, the MAH shall first evaluate the entrustee’s quality assurance and risk management capabilities, and then sign quality agreement and entrustment agreement with the entrustee. View the detailed requirements at BaiPharm’s report “Key Points for Manufacturing Entrustment Under China’s MAH System”
The MAH shall never transfer the obligations and responsibilities that shall be taken by itself to the entrustee.
Managing Storage and Transportation
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