Blockbuster Release! The General Administration of China issued MAH regulations on the supervision and management of the main responsibility of drug quality, and obligations and responsibilities must not be transferred through quality agreements! !

In order to urge drug MAHs to implement the main responsibility for drug quality and further strengthen the quality supervision and management of the whole life cycle of drugs, the State Food and Drug Administration organized and drafted the "Provisions on the Implementation of Drug Quality Subject Responsibility Supervision and Administration by Drug Marketing Authorization Holders (Draft for Comments)", which is now open to the public for comments. Please send relevant feedback to the email yaopinjianguan-2@nmpa.gov.cn before December 9, 2022, and the subject of the email should indicate "Feedback on the Implementation of the Provisions on the Management of Holders' Entity Responsibilities".

Annex: Provisions on the Supervision and Administration of Drug Quality Subject Responsibility by Drug Marketing Authorization Holders (Draft for Comments)

General Department of the State Food and Drug Administration

November 29, 2022

annex

Drug MAHs implement drug quality

Provisions on the Supervision and Administration of Subject Responsibility (Draft for Solicitation of Comments)

Article 1 [Purpose] 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 Supervision and Administration of Drug Production, as well as good manufacturing practices, good management practices for drug sales, and pharmacovigilance quality management practices, in order to supervise drug marketing authorization holders (hereinafter referred to as holders) to implement the main responsibility for drug quality and further standardize drug production and trading activities.

Article 2 [Scope of Application] Within the territory of the People's Republic of China, these Provisions apply to the holder's lawful implementation of the main responsibility for drug quality, pharmaceutical production and trading activities, and their supervision and management.

Article 3 [General Requirements] 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 drug manufacturing quality management practices, drug trading quality management practices, pharmacovigilance quality management practices, etc., and be responsible for the safety, effectiveness and quality controllability of the entire process of drug development, production, operation and use in accordance with law.

Article 4 [Requirements for Institutional Establishment] 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 drug research and development management, production management, quality management, sales management, pharmacovigilance, post-marketing research, etc., and meet the requirements of relevant quality management specifications. Among them, the quality management department shall be set up independently, perform quality management duties, participate in all quality-related activities, and be responsible for reviewing all documents related to the quality management of drug production and operation.

Article 5 [Requirements for Key Personnel] Holders (including pharmaceutical production enterprises) shall be equipped with personnel in key positions such as the person in charge of the enterprise, 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 the person in charge of pharmacovigilance. The above key positions should be full-time personnel of the enterprise and meet the relevant requirements of relevant quality management specifications.

Article 6 [Responsibilities and Requirements of the Person in Charge of the Enterprise] The person in charge of the enterprise is the main person responsible for the quality of drugs, fully responsible for the daily management of the enterprise, and implements the main responsibility for quality 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 assigning special quality authorized persons to independently perform the responsibility of drug market release; Responsible for handling major safety incidents related to drug quality to ensure that risks are controlled in a timely manner; Responsible for organizing and establishing a training and assessment system for enterprise personnel, carrying out training and assessment for all personnel in drug production management and quality management, and improving the quality awareness and compliance awareness of enterprise personnel.

The person in charge of the enterprise shall have a university (bachelor's degree) or above and work experience in pharmaceutical-related professional fields, and understand the relevant laws and regulations of drug supervision and administration.

Article 7 [Responsibilities and Requirements of the Person in Charge of Production] The person in charge of production is mainly responsible for ensuring that production is organized in accordance with the approved process regulations, ensuring the good operation of plants and facilities, completing the necessary verification work, and ensuring the quality of drugs.

The person in charge of production shall have a pharmaceutical 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 pharmaceutical production management experience, and have received professional knowledge training related to the products produced.

Article 8 [Responsibilities and Requirements of the Quality Manager] The quality person in charge is responsible for the quality management of the whole process of drugs, establishes a quality control and quality assurance system, supervises the implementation of relevant quality management specifications, and ensures 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 that data and records of drug production, inspection and other products are true, accurate, complete and traceable.

The person in charge of quality shall have a pharmaceutical 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 pharmaceutical production and quality management, including at least one year of drug quality management experience, and have received professional knowledge training related to the products produced.

Article 9 [Duties and Requirements of Quality Authorized Persons] 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 an intermediate or above professional and technical title or a licensed pharmacist qualification, more than five years of practical experience in drug production and quality management, have been engaged in drug production process control and quality inspection, and have undergone relevant business training.

Article 10: [Duties and Requirements of the Person in charge of pharmacovigilance] The person in charge of pharmacovigilance is responsible for the operation and continuous improvement of the pharmacovigilance system, ensuring that the pharmacovigilance system meets the requirements of relevant laws, regulations and technical specifications.

The person in charge of pharmacovigilance shall be a manager with a certain position, shall have a 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 and regulations and technical guidelines, and have the knowledge and skills of pharmacovigilance management.

Article 11 [Production Management Requirements] 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 departments, to ensure that the entire process of drug production continues to meet the requirements of good manufacturing practices.

Article 12 [Quality Management Requirements] 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, reporting and treatment of drugs; 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 [Requirements for the Administration of Raw and Auxiliary Packaging] The holder shall audit suppliers such as raw materials, excipients, packaging materials and containers that come into direct contact with drugs, and ensure that the raw materials, auxiliary materials, packaging materials and containers 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 such as corresponding related review and approval, as well as the requirements of laws and regulations.

Article 14 [Change Management Requirements] 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, formulate and implement internal change classification principles, change items, work procedures, and risk management requirements, and determine the change management category after full research, evaluation, and necessary verification in combination with product characteristics, and implement it after approval, filing, or indicate it 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 [Requirements for Release Management] The holder shall perform the responsibility for the release of drugs on the market, formulate procedures for the release of drugs on the market, review the procedures for the release of drugs formulated by the entrusted manufacturer, clarify the standards for the release of drugs, and review the drugs released by the entrusted party from the factory, as well as drug production records, inspection records, deviation investigations, etc., and if they meet the relevant provisions, they may only be released for listing after being signed by the quality authorized person.

Pharmaceutical manufacturers shall establish procedures for the release of drugs from the factory, clarify the standards and conditions for factory release, and review the results of drug quality inspection, key production records and deviation control, and conduct quality inspection 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.

Article 16 [Requirements for the Administration of Entrusted Production] Where the production of drugs is entrusted, the holder shall evaluate the quality assurance ability and risk management ability of the entrusted party, and sign a quality agreement and a commissioned production agreement with the entrusted party in accordance with regulations; It shall perform the obligations of raw and auxiliary material supplier review, 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 by means of a quality agreement the obligations and liabilities that are legally required by the Holder.

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: [Requirements for the Administration of Storage and Transportation] Holders shall ensure that drug storage and transportation activities comply with requirements such as quality management practices 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: [Requirements for Traceability Management] Holders shall establish and implement a drug traceability system in accordance with law, establish an information-based traceability system, provide traceability information to downstream pharmaceutical trading enterprises and drug-using units, and promptly and accurately record and preserve information on the entire process of drug production and circulation, so as to realize drug traceability.

Article 19: [Annual Report Management Requirements] Holders shall establish an annual report system, collect information on the production and sales, post-marketing research, risk management, and other such aspects of the drugs they hold annually, and report to the drug regulatory departments of the province, autonomous region, municipality directly under the Central Government, and the Xinjiang Production and Construction Corps (hereinafter referred to as the "provincial-level drug regulatory departments").

Article 20 [Requirements for the Administration of Drug Recalls] The holder shall establish and improve a drug recall system, and if it is discovered that the drug has quality problems or other potential safety hazards, initiate the recall in accordance with relevant provisions, promptly notify the relevant pharmaceutical trading enterprises and user units, 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. The recalled drugs shall be disposed of in accordance with regulations, and if they need to be destroyed, they shall be destroyed under the supervision of the drug regulatory department at or above the county level or notary institution.

After the recall is completed, the drug recall and handling shall be promptly reported to the local provincial drug regulatory department and the competent health department.

Article 21: [Pharmacovigilance Requirements] Holders shall establish specialized pharmacovigilance departments, establish pharmacovigilance systems, 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 drug-related harmful reactions, to minimize drug safety risks.

Article 22 [Post-marketing Research Requirements] The holder shall formulate a post-market risk management plan, actively carry out post-market research, and periodically carry out post-market evaluation based on post-market research on the safety, efficacy, and quality controllability of drugs, and conduct comprehensive analysis and assessment of the risks and benefits of drugs. According to the assessment 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 23: [Requirements for Drug Safety Incidents] Holders shall formulate a drug safety incident handling plan, and organize and carry out training and emergency drills. In the event of a 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 24: [Requirements for the Management of Production Suspension Reports] The holder shall establish a reporting system for the suspension of production of shortage drugs. Where the production of drugs or vaccines included in the list of shortage drugs listed in the national implementation suspension report is stopped, it shall be reported to the local provincial drug regulatory 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 25: [Claims for Liability Compensation] 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 shall match factors such as the degree of risk of the product, the market size, and the compensation standards for tort damages. The holder shall have relevant certificates of liability compensation capacity or corresponding insurance purchase intentions, commercial insurance purchase contracts, etc.

Article 26: [Approval Review Mechanism] Quality management personnel shall supervise the implementation of requirements such as good manufacturing practices in the production and inspection of each batch of drugs, investigate the organization where deviations occur, and promptly employ control measures for potential quality risks; The person in charge of quality shall ensure that in each batch of drugs to urge the drug marketing authorization holder to implement the main responsibility for drug quality, further strengthen the quality supervision and management of the whole life cycle of drugs, complete the review of production records and inspection records before release, ensure that quality-related changes are reviewed and approved in accordance with regulations, and ensure that all major deviations and inspection exceeding standards have been investigated and dealt with in a timely manner.

Article 27 [Monthly Analysis Mechanism] The person in charge of quality shall organize a review and analysis of production management and quality management every month, study and judge repetitive risks and emerging risks, 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 28: [Annual Reporting Mechanism] The responsible persons of enterprises shall designate specialized agencies or personnel to be responsible for annual report work, ensuring 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 29: [Requirements for Self-Inspection Management] Holders shall conduct annual self-inspections to monitor the implementation of good manufacturing practices, good management practices for drug trading, and quality management practices for pharmacovigilance. The self-inspection 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 30 [Training Management Requirements] 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 production and quality management. The training content includes at least relevant regulations, corresponding job responsibilities and skills, etc. The holder shall keep training records on file and periodically evaluate the effectiveness of training.

Article 31: [Requirements for Supervision and Management] Provincial-level drug regulatory departments shall, in accordance with their duties, strengthen supervision and inspection of holders in their jurisdictions in accordance with their duties, taking the holders' implementation of the main responsibility for drug quality as the content of key supervision and inspection, and focusing on inspecting key personnel and quality management related personnel performing their duties and performing their duties, and the operation of the quality management system. Where it is discovered that there may be risks to the quality and safety of drugs, a risk control decision shall be made after assessment, and where violations and crimes are suspected, they shall be promptly investigated and handled in accordance with law or transferred to the judicial organs.

The holder shall accept the supervision and inspection of the unit by the drug regulatory department, and cooperate with the extended inspection of relevant parties, and shall not refuse or evade supervision and inspection, shall not forge, destroy or conceal relevant evidence materials, and shall not use sealed or seized items without authorization.

Article 32: [Requirements for Special Categories of Drugs] Where there are special provisions for narcotic drugs, psychotropic substances, toxic drugs for medical use, pharmaceutical precursor chemicals, radioactive drugs, vaccines, and other biological products, follow those provisions.

Article 33 [Chinese Medicine Pieces and Formula Granule Enterprises] Chinese medicine pieces manufacturers and Chinese medicine formula granule manufacturers shall refer to these Provisions.

Article 34 [Definition of Responsible Persons of Enterprises] The responsible persons of enterprises in these Provisions include the legal representative and principal responsible persons of enterprises.

Article 35 [Implementation Date] These Provisions shall take effect on XX, 2022.