NMPA issued the "MAH Quality Subject Responsibility Management Regulations", which will come into force on March 1, 2023!

Drug MAHs shall implement the provisions on the supervision and administration of the main responsibility for drug quality and safety

Chapter I General Provisions

Article 1 These Provisions
are formulated in accordance with the Drug Administration Law of the People's Republic of China, the Vaccine Administration Law of the People's Republic of China, the Measures for the Administration of Drug Registration, the Measures for the Supervision and Administration of Drug Production, as well as good manufacturing practices, good management practices for drug sales, and quality management practices for pharmacovigilance, in order to implement the main responsibility for quality and safety of drug marketing authorization holders (hereinafter referred to as "holders").

Article 2 Within the territory of the People's Republic of China, these Provisions
shall apply to the holder's lawful implementation of the main responsibility for drug quality and safety and its supervision and management.

Article 3 The holder shall comply with the "Drug Administration Law of the People's Republic of China" and other relevant laws and regulations, establish and improve the drug quality management system in accordance with the requirements of the quality management practice for non-clinical research of drugs, the management practice of drug clinical trials, the good management practice of drug production, the good management practice of drug sales, and the quality management practice of pharmacovigilance, and be responsible for
the safety, effectiveness and quality controllability of drugs in the whole process of drug development, production, operation and use in accordance with law.

Chapter II: Responsibilities and Requirements for Key Positions of Holders

Article 4 The holder shall establish a management department with clear responsibilities, allocate management personnel appropriate to the scale of drug production and operation, clarify the responsibilities of non-clinical research, clinical trials, production and sales, post-marketing research, adverse reaction monitoring and reporting, etc.
, and comply with the requirements of
relevant quality management practices.
The holder shall independently set up a quality management department, perform the quality management responsibilities of the whole process, participate in all quality-related activities, and be responsible for reviewing all documents
related to quality management.

Article 5 The person in charge of the enterprise (main responsible person), the person in charge of production management (hereinafter referred to as the person in charge of production), the person in charge of quality management (hereinafter referred to as the person in charge of quality), the person authorized for quality and other key positions of the holder (including pharmaceutical production enterprises) shall be full-time personnel of the enterprise and meet the relevant requirements
of relevant quality management specifications.
The person in charge of quality management and the person in charge of production management shall not concurrently serve
each other.

For the production and quality management of specific drug varieties, the holder shall specify the person in charge and other responsible personnel
directly responsible for it.

Article 6: The legal representative and the responsible person (main responsible person) of the enterprise are fully responsible for
the quality of drugs.
The person in charge of the enterprise is fully responsible for the daily management of the enterprise and implements the main responsibility of quality management in the whole process; Responsible for assigning a special quality manager, providing necessary conditions and resources, and ensuring that the quality management department performs its duties independently; Responsible for the allocation of special quality authorized personnel to ensure the independent performance of drug marketing release responsibilities; Responsible for handling major safety incidents related to drug quality to ensure that risks are controlled in a timely manner; Responsible for establishing a training and assessment system for production management and quality management; Responsible for appointing or designating a person in charge of
pharmacovigilance.

The person in charge of the enterprise shall have working experience in pharmaceutical-related fields and be familiar with relevant laws, regulations, rules and regulations
of drug supervision and administration.

Article 7 The person in charge of production is mainly responsible for the management of drug production, ensuring that the production and storage of drugs are organized in accordance with the approved process regulations; Ensure the good operation of the plant and facilities and equipment, complete the necessary verification work, and ensure the quality of drug production; Ensure the effective operation of the production management training system, and carry out training and assessment
for all personnel of drug production management.

The person in charge of production shall have: pharmacy or related professional background, bachelor degree or above or intermediate or above professional and technical title or licensed pharmacist qualification, more than three years of practical experience in drug production and quality management, including at least one year of drug production management experience, familiar with relevant laws, regulations and rules and regulations
of drug production management.

Article 8 The person in charge of quality is responsible for drug quality management, establishing quality control and quality assurance systems, supervising the implementation of relevant quality management standards, and ensuring the effective operation of the quality management system; Ensure that the production process control and drug quality control meet the requirements of relevant regulations and standards; Ensure the truthfulness, accuracy, completeness and traceability of data and records of drug production, inspection and so on; Ensure the effective operation of the quality management training system, and carry out training and assessment
for all personnel of drug quality management.

The person in charge of quality shall have: pharmacy or related professional background, bachelor degree or above or intermediate or above professional and technical title or licensed pharmacist qualification, more than five years of practical experience in drug production and quality management, including at least one year of drug quality management experience, familiar with relevant laws, regulations and rules and regulations
of drug quality management.

Article 9: Quality authorized persons independently perform their duties for drug release, ensuring that the production and inspection of each batch of released drugs comply with relevant laws and regulations, drug registration management requirements, and quality standards
.
Without the signature and consent of the quality licensee, the product shall not be released
.

The quality authorized person shall have: a pharmaceutical or related professional background, a bachelor's degree or above or a professional and technical title of intermediate level or above, or a licensed pharmacist qualification, more than five years of practical experience in drug production and quality management, engaged in drug production process control and quality inspection, and familiar with relevant laws, regulations, and rules and regulations
of drug supervision and administration.

The holder can set up multiple quality licensees according to the size of the enterprise, covering the release responsibilities
of all products of the enterprise.
Each quality authorized person shall have a clear division of labor and must not overlap.

When the quality authorized person is absent for any reason, after approval by the legal representative of the enterprise or the person in charge of the enterprise, he may temporarily transfer his duties to other quality authorized persons or personnel with relevant qualifications, and stipulate in writing the scope, matters and time limit
of the subauthorization.
During the period of sub-authorization, the original quality licensee must still bear the corresponding responsibility
.

Article 10: The person in charge of pharmacovigilance is responsible for the establishment, operation, and continuous improvement of the pharmacovigilance system, ensuring that the pharmacovigilance system meets the requirements of
relevant laws and regulations and pharmacovigilance quality management practices.

The person in charge of pharmacovigilance shall be a manager with a certain position, shall have: medical, pharmacy, epidemiology or related professional background, bachelor degree or above or intermediate or above professional and technical titles, more than three years of work experience in pharmacovigilance, familiar with China's pharmacovigilance-related laws, regulations and technical guidelines, and have the knowledge and skills
of pharmacovigilance management.

Chapter III: Holder Quality Management Requirements

Article 11 The holder shall establish a quality management system covering the entire process of drug production, and produce in accordance with national drug standards, quality standards and production processes approved by the drug regulatory department to ensure that the entire process of drug production continues to meet the requirements of
good manufacturing practices.

Article 12 The holder shall establish and improve the drug quality management system, covering the whole life cycle process of non-clinical research, clinical trials, production and operation, post-marketing research, adverse reaction monitoring and reporting, etc.
; Quality objectives that meet the requirements of drug quality management should be established, and the quality management system should be continuously improved to ensure that the drugs produced meet the intended use and registration requirements
.

Article 13: The holder shall conduct audits of suppliers of raw materials, excipients, packaging materials and containers that come into direct contact with drugs, and ensure that the raw materials, excipients, packaging materials and containers that come into direct contact with drugs purchased and used meet the requirements for medicinal use, and comply with the quality management specifications formulated by the drug regulatory department under the State Council and the relevant requirements of relevant review and approval, as well as the requirements
of laws and regulations.

Article 14 The holder shall establish a post-marketing change control system for drugs in accordance with the relevant provisions on drug supervision and the requirements of good manufacturing practices, and formulate and implement internal change classification principles, change items, work procedures and risk management requirements; The change management category shall be determined after full research, evaluation and necessary verification in combination with the characteristics of the product, and shall be implemented after approval and filing, or specified in the annual report
.

Where production is commissioned, relevant research, evaluation and necessary verification
shall be carried out jointly with the entrusted production enterprise.

Article 15: Pharmaceutical manufacturers shall establish procedures for the release of drugs from the factory, clarify the standards and conditions for the release of drugs from the factory, review the results of drug quality inspections, key production records, and deviation control, and conduct quality inspections
of drugs.
If it meets the relevant standards and conditions, it can be released from the factory only after being signed by the quality authorized person
.

The holder shall perform the responsibility of drug market release, formulate drug release procedures, review the factory release procedures formulated by the entrusted manufacturer, clarify the market release standards of drugs, review the drug test results and release documents released by the pharmaceutical manufacturer, and if it meets the relevant provisions, it can only be released for marketing
after being signed by the quality authorized person.
When necessary, the holder may audit
the consignee's drug production records, inspection records, deviation investigations, etc.

Article 16 Where the production of drugs is entrusted, the holder shall evaluate the quality assurance capabilities and risk management capabilities of the entrusted party, and sign a quality agreement and a commissioned production agreement with the entrusted party in accordance with regulations; shall perform the obligations of material supplier assessment and approval, change management review, product listing release and annual report; It shall supervise the entrusted party's performance of the obligations stipulated in the agreement, conduct regular on-site audits of the entrusted party's quality management system, and ensure that the quality management systems of both parties are effectively connected and that the production process continues to meet the statutory requirements
.

The Holder shall not transfer through the quality agreement the obligations and liabilities
that should be performed by the Holder according to law.

Pharmaceutical manufacturers that accept commissioned production shall strictly implement the quality agreement, organize the production of commissioned drugs in accordance with good manufacturing practices, actively cooperate with the audit of the holder, and take corrective and preventive measures to implement rectification in accordance with all defects found in the audit
.

Article 17: The holder shall ensure that drug storage and transportation activities comply with requirements such as the Good Management Standards for Drug Trading
.
Where the storage, transportation or sale of drugs is entrusted, the holder shall assess the quality assurance ability and risk management ability of the entrusted party, sign an entrustment agreement and quality agreement with the entrusted party in accordance with relevant provisions, and periodically review the storage and transportation management of the entrusted enterprise to ensure that the storage and transportation process meets the requirements of the quality management practice for drug business and the storage conditions of drugs
.

Enterprises entrusted with storage and transportation shall carry out storage and transportation activities in accordance with the requirements of the Good Management Standards for Drug Trading, perform their obligations under the agreement, and bear corresponding legal responsibilities
.

Article 18: Holders shall establish and implement a drug traceability system in accordance with law, establish their own or entrust a third party to establish an information traceability system as required, assign traceability labels to drugs in sales and packaging units at all levels of drugs, provide traceability information to downstream pharmaceutical trading enterprises and drug use, promptly and accurately record and preserve information on the entire process of drugs, realize drug traceability, and provide traceability data
to the drug regulatory departments in accordance with provisions.

Article 19: The holder shall establish and improve the drug recall system in accordance with the relevant provisions on drug recall, and if it is discovered that the drug has quality problems or other potential safety hazards, initiate the recall in accordance with the relevant provisions, promptly notify the relevant enterprise or use, and at the same time submit the investigation and assessment report, recall plan and recall notice to the local provincial drug regulatory department for the record
.
Where the recalled drugs need to be destroyed, they shall be destroyed
in accordance with relevant provisions.

After the recall is completed, the recall and handling of the drug shall be promptly reported
to the local provincial drug regulatory department and the competent health department in accordance with relevant provisions.

Article 20: Holders shall establish a pharmacovigilance system, establish specialized pharmacovigilance departments, carry out pharmacovigilance work in accordance with requirements such as pharmacovigilance quality management practices, and carry out activities such as monitoring, identification, assessment and control of adverse drug reactions and other harmful reactions related to medication, to minimize drug safety risks
.

Article 21 The holder shall formulate a post-market risk management plan, actively carry out post-market research, and periodically carry out post-market evaluations based on post-market research on the safety, efficacy and quality controllability of drugs, and conduct comprehensive analysis and assessment
of the benefits and risks of drugs.
According to the evaluation results, quality improvement or risk prevention and control measures
such as revising drug instructions, improving quality standards, improving process prescriptions, suspending production and sales, recalling drugs, and applying for cancellation of drug approval documents are taken in accordance with the law.

For drugs with conditional approval, the holder shall take corresponding risk management measures and complete relevant research
as required within the specified period.

Article 22: The holder shall formulate a plan for handling drug safety incidents, and periodically organize and carry out training and emergency drills
.
In the event of a major safety incident related to drug quality, the holder shall immediately take effective measures to dispose of the relevant drug and its raw materials, excipients, packaging materials and containers directly in contact with drugs, relevant production lines, etc.
, to prevent the harm from expanding
.

Article 23: The holder shall establish a reporting system for the suspension of production of
drugs in short supply.
Where the production of drugs included in the list of shortage drugs included in the national implementation suspension report is stopped, it shall be reported to the local provincial drug administration department six months before the planned suspension of production; In the event of an unexpected suspension of production, it shall be reported to the local provincial drug administration department
within three days.
If necessary, report
to the State Drug Administration.

Article 24: Holders shall have the capacity for liability compensation required by law, establish relevant management procedures and systems for liability compensation, and implement a system
of primary responsibility for compensation.
The liability compensation capacity should match
factors such as the risk degree of the product, the market size and the personal injury compensation standard.
The holder shall have relevant certificates of liability compensation capacity or corresponding commercial insurance purchase contracts
.

Chapter IV Holder Quality Management Mechanism

Article 25: Quality management personnel shall supervise the implementation of requirements such as good manufacturing practices in the production and inspection of each batch of drugs, organize investigations into deviations that occur, and promptly employ control measures for potential quality risks; The person in charge of quality shall ensure that the review of production records and inspection records is completed before the release of each batch of drugs, that quality-related changes are reviewed and approved in accordance with regulations, and that all major deviations and inspection over-standards have been investigated and dealt with in a timely manner
.

Article 26 The person in charge of quality shall periodically organize a review and analysis of production management and quality management in combination with product risks, and in principle, study and judge repetitive risks and emerging risks at least once a quarter, formulate corrective and preventive measures, and continuously improve the quality management system
。 The person in charge of the enterprise shall regularly listen to the quality management work report of the quality responsible person, fully listen to the opinions and suggestions of the quality person in charge on the prevention and control of drug quality risks, and provide necessary conditions and resources for the implementation of quality risk prevention and control
.

Article 27 The holder shall establish an annual reporting system
.
The person in charge of the enterprise shall designate a specialized agency or personnel to be responsible for the annual report work, to ensure that the information in the annual drug report is true, accurate, complete and traceable, and complies with the requirements
of laws, regulations and relevant provisions.
The report writer shall summarize the production and sales, post-marketing research, risk management, etc.
of the drug in the previous natural year, form an annual report in accordance with the annual report template formulated by the State Medical Products Administration, and report
to the local provincial drug administration department after approval by the legal representative of the enterprise or the person in charge of the enterprise (or his written authorization).

Article 28: Holders shall periodically conduct self-inspections or internal audits to monitor the implementation of
good manufacturing practices, good management practices for drug trading, and pharmacovigilance quality management practices.
Self-inspection or internal audit shall have a plan and records, and a self-inspection report shall be formed after the completion of the self-inspection, including at least the basic situation of the self-inspection, the conclusions of the evaluation, and suggestions for
corrective and preventive measures.

Article 29: The holder shall establish a training management system, formulate training programs or plans, and carry out pre-job training and continuing training
for all personnel engaged in drug research and development management, production management, quality management, sales management, pharmacovigilance, and post-marketing research.
The training content includes at least relevant regulations, corresponding job responsibilities and skills, etc
.
The holder shall keep training records and periodically evaluate the effectiveness of
training.

Chapter V: Supervision and Management

Article 30: Provincial-level drug regulatory departments shall, in accordance with their duties, strengthen supervision and inspection of holders within their administrative regions, taking the holder's implementation of the main responsibility for drug quality and safety as the content of supervision and inspection, focusing on inspecting the performance of duties by key personnel and quality management related personnel, and the operation of the quality management system
.

Article 31: The provincial-level drug regulatory departments shall, on the basis of the actual needs of drug supervision, formulate a drug quality spot check inspection plan, clarifying the objectives and key points of spot check and inspection; Spot checks and inspections can be organized on the quality of APIs, related excipients, packaging materials and containers that directly contact drugs
.

Article 32: The holder shall cooperate with the drug regulatory department's supervision and inspection and spot check inspection, and cooperate with the extended inspection of relevant parties, and shall not refuse or evade supervision and inspection, shall not interfere with, obstruct or refuse random inspection and inspection, shall not forge, destroy or conceal relevant evidence materials, and shall not use sealed or seized items
without authorization.

Where supervision and inspection or random inspection find non-compliance, the drug regulatory department shall take measures such as suspending production, sales, use, and import to control risks; Where violations or crimes are suspected, they shall be promptly investigated and handled in accordance with law or transferred to the judicial organs
.

Article 33: Provincial-level drug regulatory departments shall lawfully establish drug safety credit archives for holders (pharmaceutical manufacturing enterprises) within that administrative region, and follow provisions to publicize and disclose relevant information, strengthen the analysis and use of credit file data, and periodically carry out risk research and judgment
.

Chapter VI Supplementary Provisions

Article 34: Where there are special provisions for narcotic drugs, psychotropic substances, toxic drugs for medical use, precursor chemicals for pharmaceuticals, radioactive drugs, vaccines and other biological products, Chinese medicine tablets, Chinese medicine formula granules, etc.
, follow those provisions
.

Article 35: These Provisions shall take effect
on March 1, 2023.