Order of the State Administration for Market Regulation

　　No. 28

　　The “Measures for the Supervision and Administration of Pharmaceutical Production” were reviewed and approved at the 1st Bureau Meeting of the State Administration for Market Regulation held on January 15, 2020. They are now promulgated and shall take effect as of July 1, 2020.

　　Director Xiao Yaqing

　　January 22, 2020

　　Measures for the Supervision and Administration of Pharmaceutical Production

　　(Promulgated by Order No. 28 of the State Administration for Market Regulation on January 22, 2020)

　　Chapter 1 General Provisions

　　Article 1: In order to strengthen the supervision and management of pharmaceutical production and standardize pharmaceutical manufacturing activities, these Measures are formulated in accordance with the "Drug Administration Law of the People's Republic of China" (hereinafter referred to as the "Drug Administration Law"), the "Law of the People's Republic of China on Traditional Chinese Medicine," the "Law of the People's Republic of China on Vaccine Administration" (hereinafter referred to as the "Vaccine Administration Law"), the "Administrative Licensing Law of the People's Republic of China," and the "Regulations for the Implementation of the Drug Administration Law of the People's Republic of China," as well as other relevant laws and administrative regulations.

　　Article 2: Production and supervisory management activities for pharmaceutical products listed in the territory of the People’s Republic of China shall comply with these Measures.

　　Article 3: Any entity engaged in pharmaceutical production activities shall comply with laws, regulations, rules, standards, and guidelines, and ensure that information throughout the entire process is authentic, accurate, complete, and traceable.

　　To engage in pharmaceutical manufacturing activities, one must obtain approval from the drug regulatory authority of the province, autonomous region, or municipality where the business is located and legally acquire a pharmaceutical manufacturing license. Furthermore, one must strictly comply with Good Manufacturing Practice (GMP) guidelines to ensure that the manufacturing process continuously meets statutory requirements.

　　The marketing authorization holder of a drug shall establish a drug quality assurance system, fulfill the responsibility for drug release upon market launch, and be accountable for the quality of drugs for which it has obtained drug registration certificates.

　　Chinese medicinal herb slice manufacturers shall fulfill the relevant obligations of the marketing authorization holder and ensure that the production process of Chinese medicinal herb slices continuously complies with statutory requirements.

　　Active pharmaceutical ingredient manufacturers shall organize production in accordance with the approved manufacturing processes, strictly comply with the Good Manufacturing Practice for Pharmaceuticals, and ensure that the production process continuously meets statutory requirements.

　　Manufacturing enterprises of excipients, packaging materials and containers that directly contact drugs, as well as other entities and individuals engaged in drug-related production activities, shall assume their corresponding responsibilities in accordance with the law.

　　Article 4: The marketing authorization holder and the pharmaceutical manufacturer shall establish and implement a drug traceability system, assign traceability identifiers to each level of sales packaging units in accordance with applicable regulations, use information technology to carry out drug traceability, promptly and accurately record and store drug traceability data, and provide traceability information to the drug traceability collaborative service platform.

　　Article 5: The National Medical Products Administration is responsible for the nationwide supervision and management of pharmaceutical production and shall supervise and guide the pharmaceutical production supervision and management work carried out by the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government.

　　The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government are responsible for the supervision and management of drug production within their respective administrative areas, and undertake tasks such as licensing, inspection, and enforcement actions related to the drug production stage.

　　The National Medical Products Administration’s Center for Drug and Food Inspection and Verification (hereinafter referred to as the Verification Center) is responsible for developing technical specifications and documents for drug inspections, conducting overseas inspections, and organizing vaccine surveillance activities. It also analyzes and assesses risks identified during inspections, draws inspection conclusions, and provides recommendations for corrective actions. Additionally, the Center provides guidance and evaluation of the quality management systems of drug inspection agencies in all provinces, autonomous regions, and municipalities directly under the central government.

　　The Information Center of the National Medical Products Administration is responsible for the construction and management of the pharmaceutical traceability collaboration service platform and the pharmaceutical safety credit archive, and it assigns unified codes to pharmaceutical manufacturing sites.

　　The professional technical institutions for drug review, inspection, verification, monitoring, and evaluation, established or designated by the drug regulatory authorities in accordance with the law, shall, within their respective responsibilities, undertake relevant technical work and issue technical conclusions to provide technical support for the supervision and management of drug production.

　　Chapter 2: Production Licensing

　　Article 6: To engage in pharmaceutical production, the following conditions must be met:

　　(1) There shall be qualified pharmaceutical technicians, engineering technicians, and corresponding skilled workers who have been legally certified; the legal representative, enterprise head, production management head (hereinafter referred to as the “production head”), quality management head (hereinafter referred to as the “quality head”), quality authorization person, and other relevant personnel shall meet the requirements stipulated in the "Drug Administration Law" and the "Vaccine Administration Law."

　　(2) Possess facilities, equipment, and sanitary conditions that are suitable for pharmaceutical production;

　　(3) An organization and personnel capable of conducting quality management and quality inspection for the pharmaceutical products being manufactured;

　　(4) Possess the necessary instruments and equipment for quality management and quality inspection of the drugs produced;

　　(5) There are established rules and regulations to ensure drug quality, and these comply with the requirements of Good Manufacturing Practice for pharmaceuticals.

　　Those engaged in vaccine production activities shall also meet the following conditions:

　　(1) Possess an appropriate scale and sufficient production capacity reserves;

　　(2) Possess systems, facilities, and equipment that ensure biosafety;

　　(3) Meets the needs of disease prevention and control.

　　Article 7: Applicants engaging in the manufacture of preparations, active pharmaceutical ingredients, and traditional Chinese medicine granules shall submit their applications to the drug regulatory authorities of the province, autonomous region, or municipality where they are located, in accordance with these Measures and the requirements for submission materials stipulated by the National Medical Products Administration.

　　The marketing authorization holder who entrusts another party with the manufacture of pharmaceutical preparations shall meet the conditions stipulated in Article 6, Paragraph 1, Items 1, 3, and 5 of these Measures, and shall sign a consignment agreement and a quality agreement with a qualified pharmaceutical manufacturer. The relevant agreements and documentation pertaining to the actual production site shall be submitted together to the drug regulatory authority of the province, autonomous region, or municipality where the marketing authorization holder is located, and an application for a pharmaceutical production license shall be filed in accordance with the provisions of these Measures.

　　The applicant shall be responsible for the authenticity of all contents of the application materials.

　　Article 8: After receiving an application, the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall handle it accordingly based on the following circumstances:

　　(1) If the application does not fall within the purview of this department’s authority according to law, a decision rejecting the application shall be made immediately, and the applicant shall be informed to submit the application to the relevant administrative authority.

　　(2) If the application does not require administrative licensing according to law, the applicant shall be immediately informed that the application will not be accepted.

　　(3) If the application materials contain errors that can be corrected on the spot, the applicant should be allowed to correct them on the spot.

　　(4) If the application materials are incomplete or do not meet the requirements of the formal review, the applicant shall be issued a notice requiring supplementary materials on the spot or within five days, clearly informing the applicant of all the items that need to be corrected in one go. If the applicant is not notified within the specified period, the application shall be deemed to have been accepted as of the date on which the application materials were received.

　　(5) If the application materials are complete and meet the requirements of the formal review, or if the applicant submits all the supplementary materials as required, the application shall be accepted.

　　The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall issue a notice of acceptance or a notice of non-acceptance, stamped with the official seal of their department and dated, when they accept or reject an application for a drug production license.

　　Article 9: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall make a decision within thirty days from the date of acceptance.

　　If the application meets the prescribed requirements, it shall be approved, and a drug production license shall be issued within ten days from the date of the written approval decision. If the application does not meet the prescribed requirements, a written decision of non-approval shall be made, stating the reasons therefor.

　　The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall organize technical reviews and assessments of submitted documentation, as well as on-site inspections, in accordance with relevant regulations such as the Good Manufacturing Practice for Pharmaceuticals.

　　Article 10: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall publicly display on their administrative agencies’ websites and in their office premises the requirements, procedures, time limits, a list of all materials to be submitted, and sample application forms necessary for applying for a drug production license.

　　Information regarding drug production licenses issued by the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall be made publicly available, and the public has the right to access such information.

　　Article 11: When reviewing applications for drug production licenses, the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall publicly disclose the approval results and provide convenient conditions for applicants to inquire about the progress of their applications.

　　Without the applicant’s consent, the drug regulatory authorities, specialized technical institutions, and their staff members shall not disclose any trade secrets, undisclosed information, or confidential business information submitted by the applicant, except as otherwise provided by law or where such disclosure is necessary to protect national security or major public interests.

　　Article 12: If the application for a drug production license directly involves significant interests between the applicant and other parties, the applicant and any interested parties shall, in accordance with laws and regulations, enjoy the right to request a hearing.

　　When reviewing applications from pharmaceutical manufacturers, the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall, if they deem that public interests are involved, publicly announce such cases and hold hearings.

　　Article 13: The validity period of a pharmaceutical production license is five years, and it consists of an original copy and a duplicate copy. The format of the pharmaceutical production license shall be uniformly prescribed by the National Medical Products Administration. The electronic certificate of a pharmaceutical production license has the same legal effect as the paper certificate.

　　Article 14: A pharmaceutical production license shall specify the following items: license number, classification code, enterprise name, unified social credit code, registered address (business premises), legal representative, person in charge of the enterprise, person in charge of production, quality manager, authorized quality representative, production address and scope of production, issuing authority, date of issuance, and validity period.

　　The enterprise name, unified social credit code, registered address (business premises), legal representative, and other such items shall be consistent with the relevant information stated on the business license issued by the market supervision and administration department.

　　Article 15: The items specified on the Pharmaceutical Production License are divided into licensing items and registration items.

　　Permitted items refer to the production address and production scope, among other things.

　　The registered items refer to the enterprise name, domicile (business premises), legal representative, person in charge of the enterprise, person in charge of production, person in charge of quality, and authorized quality personnel, among others.

　　Article 16: Any changes to the licensed items of a pharmaceutical production license shall be submitted to the original licensing authority for an application for amendment to the pharmaceutical production license. No unauthorized changes to the licensed items shall be made without prior approval.

　　The original issuing authority shall, within fifteen days from the date of receipt of the enterprise’s application for amendment, make a decision on whether to approve the amendment. If the amendment is not approved, the authority shall provide a written explanation of the reasons and inform the applicant of their right to file an administrative reconsideration or bring an administrative lawsuit in accordance with the law.

　　If a pharmaceutical manufacturer changes its production address or production scope, it shall, in accordance with Article 6 of these Measures and relevant technical requirements for such changes, submit the pertinent documentation pertaining to the changes and obtain approval from the drug regulatory authority of the province, autonomous region, or municipality where it is located.

　　For the construction, reconstruction, or expansion of workshops or production lines at the original site or at a new location, the project must comply with relevant regulations and technical requirements. Relevant documentation pertaining to the changes must be submitted and approved by the drug regulatory authority of the province, autonomous region, or municipality where the facility is located, which will conduct a compliance inspection against the Good Manufacturing Practice (GMP) standards for pharmaceutical products. The inspection results shall be notified to the enterprise. If the inspection results meet the required standards and the product satisfies the release criteria, it may be marketed and sold. Details of any such changes shall be recorded in the duplicate copy of the pharmaceutical manufacturing license.

　　If the aforementioned changes involve the contents stated in the drug registration certificate and its appendices, after being approved by the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government, they shall be reported to the Drug Review Center of the National Medical Products Administration for updating the relevant contents of the drug registration certificate and its appendices.

　　Article 17: If any changes are made to the registered items of a drug production license, the enterprise shall, within thirty days after the change has been approved by the market supervision and administration department or after the enterprise has completed the change itself, apply to the original licensing authority for an amendment to the drug production license registration. The original licensing authority shall complete the amendment procedures within ten days from the date of receipt of the enterprise’s amendment application.

　　Article 18: After a change is made to the pharmaceutical production license, the original issuing authority shall record the content and date of the change on the duplicate copy of the pharmaceutical production license. The authority shall then reissue the original copy of the pharmaceutical production license according to the revised content, and retrieve the original copy of the pharmaceutical production license. The expiration date of the amended pharmaceutical production license remains unchanged.

　　Article 19: If the validity period of a pharmaceutical production license is about to expire and the manufacturer intends to continue producing pharmaceuticals, it shall apply to the original issuing authority for reissuance of the pharmaceutical production license six months prior to the expiration date.

　　The original issuing authority, taking into account the enterprise’s compliance with pharmaceutical management laws and regulations, Good Manufacturing Practice for Pharmaceuticals, and the operation of its quality system, shall conduct a review based on risk-management principles and make a decision on whether to reissue the pharmaceutical production license before the expiration date of the current license. If the enterprise meets the prescribed requirements, the original license will be revoked and a new license will be issued. If the enterprise does not meet the requirements, the authority shall issue a written decision denying the reissuance, stating the reasons therefor and informing the applicant of their right to file an administrative reconsideration or bring an administrative lawsuit in accordance with the law. If no decision is made within the prescribed time limit, it shall be deemed that the authority has approved the reissuance, and the relevant procedures will be completed retroactively.

　　Article 20: If any of the following circumstances exist, the drug production license shall be revoked by the original issuing authority and publicly announced:

　　(1) Those who voluntarily apply to cancel their drug production license;

　　(2) The drug production license has expired and has not been reissued;

　　(3) The business license has been revoked or canceled in accordance with the law;

　　(4) The drug production license has been revoked or canceled in accordance with the law;

　　(5) Other circumstances where administrative licenses shall be revoked as stipulated by laws and regulations.

　　Article 21: In the event that a drug manufacturing license is lost, the marketing authorization holder and the drug manufacturer shall apply to the original issuing authority for a replacement. The original issuing authority shall reissue the drug manufacturing license within ten days, based on the originally approved details. The license number, validity period, and other relevant information shall be consistent with those of the original license.

　　Article 22: No entity or individual may forge, alter, lease, lend, or trade pharmaceutical production licenses.

　　Article 23: The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government shall update the information on the issuance, re-issuance, modification, re-issuance upon loss, revocation, cancellation, and deregistration of drug production licenses in the drug safety credit files within ten days after completing the relevant procedures.

　　Chapter 3: Production Management

　　Article 24: Those engaged in pharmaceutical manufacturing activities shall comply with the Good Manufacturing Practice for Pharmaceuticals, produce in accordance with national pharmaceutical standards, drug registration standards approved by the drug regulatory authorities, and established manufacturing processes. They shall submit and continuously update site management documentation as required, conduct risk assessments and continuous improvements throughout the operation of the quality system, and ensure that the entire pharmaceutical manufacturing process consistently meets statutory requirements. Records related to production, inspection, and other activities shall be complete and accurate, and no falsification or alteration shall be permitted.

　　Article 25: The marketing authorization holder of a vaccine shall possess the necessary facilities, equipment, and infrastructure for vaccine production and testing, be equipped with qualified management personnel, establish a comprehensive quality management system, and have the capability to produce vaccines that meet the registered requirements. If the holder’s own production capacity is insufficient and it becomes necessary to outsource production, such outsourcing must be approved by the National Medical Products Administration.

　　Article 26: Those engaged in pharmaceutical manufacturing activities shall comply with the Good Manufacturing Practice for Pharmaceuticals, establish and improve a pharmaceutical manufacturing quality management system that covers all factors affecting drug quality, and ensure that the entire pharmaceutical manufacturing process continuously meets statutory requirements.

　　Article 27: The marketing authorization holder of a pharmaceutical product shall establish a pharmaceutical quality assurance system and assign dedicated personnel to independently oversee pharmaceutical quality management. They shall conduct regular audits of the quality management systems of contracted pharmaceutical manufacturers and pharmaceutical distributors, and ensure that these entities continuously maintain their capacity for quality assurance and control.

　　Article 28: The legal representative and principal person in charge of the marketing authorization holder of a pharmaceutical product shall bear full responsibility for the quality of the drug and shall perform the following duties:

　　(1) Appoint a dedicated quality manager who is independently responsible for pharmaceutical quality management;

　　(2) Appoint a dedicated quality authorization person to independently assume responsibility for the release of pharmaceutical products for market launch.

　　(3) Supervise the normal operation of the quality management system;

　　(4) Conduct regular quality system audits of activities related to drug production involving pharmaceutical manufacturers, suppliers, and other relevant parties to ensure ongoing compliance.

　　(5) Fulfill change management responsibilities in accordance with the requirements of the change technical specifications.

　　(6) Conduct quality assessments of entrusted operating enterprises and communicate information with user units and other relevant parties.

　　(7) Cooperate with the drug regulatory authorities in conducting extended inspections of marketing authorization holders and related parties;

　　(8) In the event of a major safety incident involving drug quality, it shall be reported promptly and risk management measures shall be implemented in accordance with the risk management plan developed by the marketing authorization holder, ensuring that the risk is brought under control in a timely manner.

　　(9) Responsibilities stipulated by other laws and regulations.

　　Article 29: The legal representative and principal person in charge of a pharmaceutical manufacturing enterprise shall bear full responsibility for the enterprise’s pharmaceutical production activities and shall perform the following duties:

　　(1) Appoint a dedicated quality manager who shall be independently responsible for pharmaceutical quality management, supervise the implementation of quality management standards, ensure appropriate control over the production process and quality control measures, and guarantee that pharmaceutical products comply with national pharmaceutical standards and drug registration standards.

　　(2) Appoint a dedicated quality authorization person to fulfill the responsibility of releasing drugs for shipment from the factory;

　　(3) Supervise the normal operation of the quality management system and ensure the authenticity of pharmaceutical production process controls, quality controls, as well as records and data.

　　(4) In the event of a major safety incident related to drug quality, it shall be reported promptly and risk management measures specified in the company’s risk management plan shall be implemented without delay to ensure that the risk is brought under control in a timely manner.

　　(5) Responsibilities stipulated by other laws and regulations.

　　Article 30: The marketing authorization holder and the pharmaceutical manufacturer shall conduct annual health examinations for personnel directly handling drugs and establish health records, ensuring that individuals suffering from infectious diseases or other conditions that could contaminate drugs are not engaged in production activities involving direct contact with drugs.

　　Article 31: The marketing authorization holder and the pharmaceutical manufacturer, in the course of pharmaceutical production, shall carry out quality management activities such as risk assessment, risk control, validation, communication, and auditing. They shall promptly adopt effective risk control measures for identified risks to ensure product quality.

　　Article 32: In engaging in pharmaceutical manufacturing activities, enterprises shall conduct audits of suppliers or manufacturers of relevant materials—including active pharmaceutical ingredients, excipients, and packaging materials and containers that come into direct contact with drugs—to ensure that the procurement and use of such materials comply with regulatory requirements.

　　The raw materials and excipients required for pharmaceutical production shall meet pharmacopoeial requirements as well as the relevant requirements of the corresponding Good Manufacturing Practice (GMP) guidelines. Packaging materials and containers that come into direct contact with drugs shall also meet pharmacopoeial requirements and comply with standards that ensure human health and safety.

　　Article 33: Manufacturing enterprises of active pharmaceutical ingredients, excipients, and packaging materials and containers that directly contact drugs, which have been approved or passed the associated review and approval process, shall comply with the quality management standards established by the National Medical Products Administration as well as the relevant requirements for associated review and approval. They shall ensure that their quality assurance systems remain continuously compliant, undergo quality audits conducted by the marketing authorization holder, and accept supervision and inspection—or extended inspections—by the drug regulatory authorities.

　　Article 34: Pharmaceutical manufacturers shall identify the necessary confirmations and validations to be conducted and implement them in accordance with the confirmation and validation plan. They shall periodically evaluate facilities, equipment, manufacturing processes, and cleaning methods to ensure that these remain consistently in a validated state.

　　Article 35: Pharmaceutical manufacturers shall implement control measures to prevent contamination, cross-contamination, confusion, and errors. They shall regularly inspect and evaluate the suitability and effectiveness of these control measures to ensure that pharmaceutical products meet the prescribed national pharmaceutical standards and drug registration standards, as well as comply with the requirements of Good Manufacturing Practice for Pharmaceuticals.

　　The marketing authorization holder and the pharmaceutical manufacturer shall not produce other products in the pharmaceutical production facility that could adversely affect the quality of the drug.

　　Article 36: Pharmaceutical packaging operations shall adopt measures to reduce the risk of confusion and errors. Pharmaceutical packaging must ensure that drugs within their expiration date remain free from contamination during storage and transportation.

　　The wording on drug instructions and labels shall be scientific, standardized, and accurate. The text must be clear and easily legible, and no modifications or additions may be made by means of pasting, cutting, or altering.

　　Article 37: Pharmaceutical manufacturers shall establish procedures for the release of drugs from the factory, clearly defining the standards and conditions for such release. They shall also review the results of drug quality inspections, key production records, and deviation control measures, and conduct quality inspections on the drugs themselves. Only those drugs that meet the specified standards and conditions may be released from the factory after being signed off by the person authorized for quality assurance.

　　The marketing authorization holder of a drug shall establish a drug release procedure, review the inspection results and release documents for drugs released by the drug manufacturer, and only after being signed off by the person authorized for quality can the drugs be released for marketing.

　　Chinese medicinal herbs in decoction pieces may be released for sale only if they comply with the national pharmaceutical standards or the processing specifications formulated by the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government.

　　Article 38: The marketing authorization holder and the pharmaceutical manufacturer shall conduct annual self-inspections to monitor the implementation of Good Manufacturing Practices for pharmaceuticals, assess whether the enterprise complies with relevant regulatory requirements, and propose necessary corrective and preventive measures.

　　Article 39: The marketing authorization holder of a pharmaceutical product shall establish an annual reporting system and, in accordance with the regulations of the National Medical Products Administration, submit annually to the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government reports on such matters as pharmaceutical production and sales, post-marketing studies, and risk management.

　　The marketing authorization holder of a vaccine shall submit an annual report to the National Medical Products Administration as required.

　　Article 40: The marketing authorization holder of a pharmaceutical product shall continuously conduct risk-benefit assessments and risk management, develop a post-marketing risk management plan, proactively carry out post-marketing studies to further confirm the safety, efficacy, and controllability of quality of the drug, and strengthen ongoing management of drugs already on the market.

　　Article 41: The marketing authorization holder of a pharmaceutical product shall establish a pharmacovigilance system and carry out pharmacovigilance activities in accordance with the Pharmacovigilance Quality Management Standards formulated by the National Medical Products Administration.

　　The marketing authorization holder and the pharmaceutical manufacturer shall regularly monitor the quality, efficacy, and adverse reactions of their pharmaceutical products. If any suspected adverse reactions are identified, they shall promptly report them as required.

　　Article 42: If the marketing authorization holder of a drug entrusts another party with the manufacturing of the drug, such entrustment shall comply with relevant regulations on drug management.

　　If the marketing authorization holder of a drug entrusts a qualified pharmaceutical manufacturer to produce the drug, it shall assess the entrusted party’s capability in quality assurance and risk management. In accordance with the Guidelines on Quality Agreements for Contract Manufacturing of Drugs formulated by the National Medical Products Administration, the holder shall sign a quality agreement and a contract manufacturing agreement with the entrusted party, and shall supervise the entrusted party’s fulfillment of its obligations as stipulated in these agreements.

　　The entrusted party shall not re-entrust the pharmaceutical products produced under the commission to a third party for further production.

　　Active pharmaceutical ingredients that have been approved or approved through associated review and approval shall be produced by the applicant itself and may not be further entrusted to others for production.

　　Article 43: The marketing authorization holder of a drug shall manage and control any changes to the manufacturing process in accordance with the requirements of the Good Manufacturing Practice for Pharmaceuticals, and shall develop process specifications based on the approved manufacturing process. Any changes to the manufacturing process shall be subject to thorough research and, in accordance with the law, shall obtain approval, file a record, or submit a report, and shall be subject to supervision and inspection by the drug regulatory authorities.

　　Article 44: The marketing authorization holder and the pharmaceutical manufacturer shall conduct annual product quality review and analysis for each drug variety they produce, and maintain corresponding records, to confirm the stability and reliability of the manufacturing process as well as the suitability of the current quality standards for raw materials, excipients, and finished products.

　　Article 45: If there are changes to the organizational structure related to the quality management system of the marketing authorization holder of a drug or the drug manufacturer, as well as to the enterprise’s principal, production manager, quality manager, and quality authorized person, the relevant registration procedures shall be completed within thirty days from the date of such change.

　　The marketing authorization holder of a vaccine shall, within fifteen days from the date of any change, report to the drug regulatory authority of the province, autonomous region, or municipality where it is located the changes in key personnel such as the production manager, quality manager, and quality authorized representative.

　　Article 46: For drugs listed on the National Shortage Drug List requiring a production suspension report, the marketing authorization holder who ceases production shall report to the drug regulatory authority of the province, autonomous region, or municipality directly under the central government where it is located six months prior to the planned suspension. In the event of an unexpected production suspension, the holder shall report to the drug regulatory authority of the province, autonomous region, or municipality directly under the central government within three days. If necessary, the holder shall also report to the National Medical Products Administration.

　　After receiving a report, the drug regulatory authority shall promptly notify the leading unit of the inter-agency coordination mechanism for ensuring the supply of scarce drugs at the same level.

　　Article 47: If the marketing authorization holder of a pharmaceutical product is an overseas enterprise, it shall designate a corporate legal entity based in China to fulfill the obligations of the marketing authorization holder as stipulated in the Drug Administration Law and these Measures, and shall be responsible for coordinating and cooperating with inspections conducted overseas.

　　Article 48: If the manufacturing site of the marketing authorization holder for a drug is located overseas, the holder shall organize production in accordance with the Drug Administration Law and the provisions of these Measures, and shall cooperate with overseas inspection activities.

　　Chapter 4: Supervision and Inspection

　　Article 49: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government are responsible for the supervision and management of marketing authorization holders, pharmaceutical preparation manufacturers, chemical raw material drug manufacturers, and traditional Chinese medicine decoction piece manufacturers within their respective administrative jurisdictions.

　　The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall conduct routine supervision and inspection of suppliers and manufacturers of raw materials, excipients, packaging materials, and containers that come into direct contact with drugs, and shall carry out extended inspections when necessary.

　　Article 50: If the marketing authorization holder of a drug and the contract manufacturing enterprise are located in different provinces, autonomous regions, or municipalities directly under the central government, the drug regulatory authority of the province, autonomous region, or municipality where the marketing authorization holder is located shall be responsible for the supervision and management of the marketing authorization holder, while the drug regulatory authority of the province, autonomous region, or municipality where the contract manufacturing enterprise is located shall be responsible for the supervision and management of the contract manufacturing enterprise. The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall strengthen mutual exchange of inspection and supervision information, promptly update such information into the drug safety credit files, and, based on the information exchanged and the status of updates in the drug safety credit files, conduct investigations and impose administrative penalties on the marketing authorization holder or the contract manufacturing enterprise in accordance with the law. Where necessary, joint inspections may be carried out.

　　Article 51: The drug regulatory authorities shall establish and improve a system of professional and specialized inspectors, clearly defining the qualification standards for inspectors, their inspection duties, hierarchical management, competency training, codes of conduct, performance evaluation, and exit procedures, thereby enhancing inspectors’ professional competence and work standards. Inspectors shall be familiar with pharmaceutical laws and regulations and possess specialized knowledge in the pharmaceutical field.

　　The drug regulatory authorities shall, based on their regulatory responsibilities, the scale of the pharmaceutical industry, and inspection tasks, allocate an adequate team of inspectors to ensure that inspection work is adequately supported. In regions with pharmaceutical enterprises producing high-risk drugs such as vaccines, there shall also be a corresponding number of drug inspectors who possess the skills and experience necessary for inspecting high-risk drugs like vaccines.

　　Article 52: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall, based on regulatory needs, conduct pre-market compliance inspections against applicants for drug marketing authorization who hold drug production licenses, as well as their contract manufacturing enterprises, in accordance with the following requirements:

　　(1) For drug products that have not passed the compliance inspection under the Good Manufacturing Practice (GMP) standards appropriate to the manufacturing conditions for such drugs, a pre-marketing GMP compliance inspection shall be conducted. Specifically, if the drug to be manufactured requires an on-site inspection as part of the drug registration process, the Drug Review Center of the National Medical Products Administration shall notify the Inspection Center and inform the drug regulatory authorities of the relevant provinces, autonomous regions, and municipalities directly under the central government, as well as the applicant. The Inspection Center will coordinate with the drug regulatory authorities of the relevant provinces, autonomous regions, and municipalities directly under the central government to simultaneously carry out both the on-site inspection for drug registration and the pre-marketing GMP compliance inspection.

　　(2) If the pharmaceutical product proposed for manufacturing does not require on-site verification of drug registration, the Center for Drug Evaluation of the National Medical Products Administration shall notify the drug regulatory authorities of the provinces, autonomous regions, and municipalities where the manufacturing site is located, as well as the applicant. The relevant provincial, autonomous region, and municipal drug regulatory authorities shall independently conduct compliance inspections against the Good Manufacturing Practice (GMP) standards prior to market launch.

　　(3) For products that have already passed the compliance inspection under the Pharmaceutical Production Quality Management Regulations appropriate to the production conditions of the drug, the drug regulatory authorities of the relevant provinces, autonomous regions, and municipalities directly under the central government shall, based on risk management principles, decide whether to conduct a pre-marketing compliance inspection under the Pharmaceutical Production Quality Management Regulations.

　　For pre-market compliance inspections of Good Manufacturing Practice for pharmaceutical products, a written report detailing the inspection findings and results shall be prepared upon completion of the inspection and submitted as an important basis for post-market regulatory oversight of the pharmaceutical product. If the pre-market compliance inspection of Good Manufacturing Practice involves changes to matters related to the pharmaceutical production license, the drug regulatory authorities of the province, autonomous region, or municipality that originally issued the license shall make a decision in accordance with the prescribed amendment procedures.

　　Commercial-scale batches that have successfully passed the pre-market compliance inspection under the Good Manufacturing Practice for Pharmaceuticals may be released for sale after obtaining the drug registration certificate, provided they meet the product release requirements. The marketing authorization holder of the drug shall place particular emphasis on strengthening measures related to the production, sales, and risk management of the aforementioned batches.

　　Article 53: The main contents of the supervision and inspection of pharmaceutical production include:

　　(1) The status of the marketing authorization holder and the pharmaceutical manufacturer in complying with relevant laws and regulations, implementing Good Manufacturing Practice for Pharmaceuticals, Good Pharmacovigilance Practice, and related technical specifications;

　　(2) Whether the pharmaceutical production activities are consistent with the relevant information specified in the drug product dossier;

　　(3) Implementation of the standardized management procedures for vaccine storage and transportation;

　　(4) Pharmaceutical Contract Manufacturing Quality Agreement and Commissioning Agreement;

　　(5) Implementation status of the risk management plan;

　　(6) Status of change management.

　　Supervisory inspections include licensing inspections, routine inspections, cause-based inspections, and other types of inspections.

　　Article 54: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall adhere to the principles of risk management and full-process control. Based on risk assessments, they shall formulate annual inspection plans and carry out supervisory inspections. The annual inspection plan shall include at least the scope, content, methods, key areas, requirements, time limits, and institutions responsible for conducting the inspections.

　　Article 55: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall determine the frequency of inspections based on such factors as the type of drug, dosage form, control category, and other relevant characteristics, as well as the overall national drug safety situation, drug safety risk alert information, major drug safety incidents and their investigation and handling information, and previous inspection results, testing findings, adverse reaction monitoring data, and complaint and report records.

　　(1) Pharmaceutical manufacturers of narcotic drugs, Class I psychotropic substances, and drug-related precursors shall be inspected at least once per quarter.

　　(2) For manufacturers of high-risk drugs such as vaccines, blood products, radiopharmaceuticals, toxic drugs for medical use, and sterile drugs, compliance inspections with the Good Manufacturing Practice for Pharmaceuticals shall be conducted at least once per year.

　　(3) For pharmaceutical manufacturers other than those producing the aforementioned products, a certain proportion shall be selected annually for supervisory inspections; however, all enterprises within this administrative region must be inspected within three years.

　　(4) Each year, a certain proportion of suppliers and manufacturers of raw materials, excipients, packaging materials and containers that come into direct contact with pharmaceutical products will be selected for spot checks and supervision. Within five years, all enterprises within this administrative region will have been inspected.

　　The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government may adjust the frequency of inspections based on the actual conditions of drug production supervision within their respective administrative regions.

　　Article 56: When the National Medical Products Administration and the medical product supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government organize supervisory inspections, they shall develop an inspection plan, specify inspection standards, and accurately record the on-site inspection conditions. If sampling inspections or further studies are required, they shall be conducted in accordance with relevant regulations. The inspection conclusions shall be clear and unambiguous, and any issues identified during the inspection shall be communicated to the inspected entity in writing. For those requiring rectification, specific rectification measures and deadlines shall be proposed, and, if necessary, follow-up inspections shall be conducted to verify the effectiveness of the rectification efforts.

　　When conducting supervision and inspection, the drug regulatory authority shall assign two or more inspectors to carry out the inspection. The inspectors shall present their law enforcement credentials to the inspected entity. Staff members of the drug regulatory authority shall maintain the confidentiality of any commercial secrets they become aware of.

　　Article 57: During inspections and supervisory checks, the marketing authorization holder of a drug and the drug manufacturer shall, as required by the inspection, explain the relevant circumstances and provide the necessary materials.

　　(1) Documentation on the management of pharmaceutical manufacturing sites, as well as change-related materials;

　　(2) The pharmaceutical manufacturer’s compliance with supervisory inspections and the implementation of corrective measures;

　　(3) Handling of cases involving substandard drug quality;

　　(4) The establishment of pharmacovigilance institutions, personnel, and systems, as well as the monitoring, identification, assessment, and control of suspected adverse drug reactions;

　　(5) Materials for conducting post-marketing studies on varieties approved under conditional approval;

　　(6) Other necessary materials requiring review.

　　Article 58: Upon completion of the on-site inspection, the inspection findings shall be analyzed and summarized. The defects identified during the inspection shall be assessed for risk in an objective, fair, and impartial manner, and a conclusion on the on-site inspection shall be issued.

　　The sending organization is responsible for conducting a comprehensive assessment of the on-site inspection findings.

　　Article 59: If the National Medical Products Administration and the medical product regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government identify defects in pharmaceutical production management or in the storage and transportation management of vaccines through supervision and inspection, and there is evidence suggesting potential safety hazards, they shall take appropriate measures in accordance with the law.

　　(1) For those that basically meet the requirements of the Good Manufacturing Practice for Pharmaceuticals but require rectification, a warning letter shall be issued, and corresponding measures—such as warnings, interviews, or deadlines for rectification—shall be taken based on the level of risk.

　　(2) If a drug is found to have quality issues or other safety hazards, the drug regulatory authority shall, based on the results of supervision and inspection, issue a warning letter and, according to the level of risk, take corresponding control measures such as suspending production, sales, use, and import.

　　If a drug has quality issues or other safety hazards, and the marketing authorization holder fails to recall the drug in accordance with the law, the drug regulatory authorities of the province, autonomous region, or municipality directly under the central government shall order it to carry out the recall.

　　After the risk has been eliminated, the drug regulatory authority that imposed control measures shall lift those measures.

　　Article 60: During the course of conducting supervisory inspections of pharmaceutical production, if any risks to the quality and safety of pharmaceuticals are identified, such risks shall be promptly reported to the sending authority. If the drug regulatory authority determines that a risk is a serious one affecting the quality and safety of pharmaceuticals, it shall promptly report it to the next higher-level drug regulatory authority and the local people's government at the same level.

　　Article 61: During the course of conducting supervisory inspections of pharmaceutical production, if any behavior suspected of violating pharmaceutical laws, regulations, or rules is discovered, on-site control measures shall be promptly implemented, and evidence collection shall be carried out in accordance with applicable provisions. The pharmaceutical regulatory authority shall, in accordance with its duties and powers, take lawful enforcement actions; cases suspected of constituting criminal offenses shall be referred to public security organs for handling.

　　Article 62: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall, in accordance with the law, incorporate regulatory information on marketing authorization holders and pharmaceutical manufacturers within their administrative jurisdictions into the drug safety credit档案 management system and ensure that the relevant data are dynamically updated. Such regulatory information includes pharmaceutical manufacturing licenses, results of routine supervision and inspection, enforcement actions against illegal activities, random quality inspections of pharmaceutical products, records of adverse behaviors, and complaints and reports.

　　Article 63: In their supervisory and administrative work related to pharmaceutical production, the National Medical Products Administration and the medical product regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall not impede the normal production activities of marketing authorization holders or pharmaceutical manufacturers; they shall not solicit or accept any property or benefits, nor shall they seek any other form of gain.

　　Article 64: Individuals and organizations who discover that the marketing authorization holder or the pharmaceutical manufacturer is engaged in illegal production activities have the right to report such activities to the drug regulatory authority. The drug regulatory authority shall, in accordance with relevant regulations, promptly verify and handle these reports.

　　Article 65: In the event of a major safety incident involving the quality of pharmaceutical products, the marketing authorization holder shall immediately take control measures such as sealing off the relevant pharmaceutical products, their raw materials, excipients, packaging materials and containers that come into direct contact with the drugs, as well as related production lines. The holder shall also immediately report the incident to the drug regulatory authorities and relevant departments of the province, autonomous region, or municipality directly under the central government where it is located. The drug regulatory authorities of the province, autonomous region, or municipality directly under the central government shall, within twenty-four hours, report the incident to the people's government at the provincial level and simultaneously notify the National Medical Products Administration.

　　Article 66: The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall increase the frequency of supervision and inspection for marketing authorization holders and pharmaceutical manufacturers with adverse credit records, and may implement joint punitive measures in accordance with national regulations.

　　Article 67: If the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government fail to promptly identify systemic risks in drug safety during the manufacturing process, fail to promptly eliminate drug safety hazards within their jurisdictions, or if the provincial-level people's governments fail to fulfill their responsibilities for drug safety and fail to promptly eliminate major regional drug safety hazards, the National Medical Products Administration shall hold a talk with their principal officials.

　　The drug regulatory authorities and local people's governments of provinces, autonomous regions, and municipalities that have been summoned shall immediately take measures to rectify their drug regulatory work.

　　The results of the interviews and the status of corrective actions shall be included in the evaluation and assessment records of the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government, as well as in the drug regulatory work assessment records of local people's governments.

　　Chapter 5: Legal Liability

　　Article 68: Any of the following circumstances shall be subject to penalties in accordance with Article 115 of the Drug Administration Law:

　　(1) The marketing authorization holder and the pharmaceutical manufacturer, when changing their production address or scope of production, shall obtain approval but have failed to do so;

　　(2) Continuing production despite the expiration of the drug manufacturing license.

　　Article 69: If the marketing authorization holder and the pharmaceutical manufacturer fail to produce drugs in accordance with the requirements of the Good Manufacturing Practice for Pharmaceuticals, and one of the following circumstances applies, such cases shall be deemed as serious violations under Article 126 of the Drug Administration Law and shall be subject to penalties in accordance with the law:

　　(1) No dedicated quality manager has been appointed to independently oversee pharmaceutical quality management and ensure compliance with quality management standards.

　　(2) The marketing authorization holder of the drug has failed to appoint a dedicated quality authorizer to fulfill the responsibility of releasing the drug for market.

　　(3) The pharmaceutical manufacturer has failed to appoint a dedicated quality authorization person to fulfill the responsibility of releasing drugs for shipment.

　　(4) The quality management system is not functioning properly, and the records and data related to process control and quality control in pharmaceutical production are inaccurate.

　　(5) Failure to promptly implement effective risk control measures for identified risks, thereby failing to ensure product quality;

　　(6) Other circumstances involving serious violations of the Good Manufacturing Practice for Pharmaceuticals.

　　Article 70: If manufacturers and suppliers of excipients, packaging materials, and containers that come into direct contact with drugs fail to comply with the quality management standards and other relevant requirements established by the National Medical Products Administration, and thus cannot ensure the ongoing compliance of their quality assurance systems, the drug regulatory authorities of the respective provinces, autonomous regions, and municipalities directly under the central government shall impose penalties in accordance with Article 126 of the Drug Administration Law.

　　Article 71: If the marketing authorization holder of a drug and the drug manufacturer fall into any of the following circumstances, they shall be fined between 10,000 yuan and 30,000 yuan by the drug supervision and administration department of the province, autonomous region, or municipality where they are located:

　　(1) The enterprise name, registered address (business premises), and legal representative have failed to register the required changes as stipulated.

　　(2) Failing to conduct annual health examinations and establish health records for personnel who directly handle pharmaceutical products as required;

　　(3) Failure to submit production suspension reports as required for drugs listed on the National Shortage Drug List subject to production suspension reporting.

　　Article 72: If the drug regulatory authority engages in any of the following acts, the directly responsible principal and other persons directly liable shall be penalized in accordance with the provisions of Article 149 of the Drug Administration Law:

　　(1) Concealing, falsely reporting, delaying the reporting of, or failing to report drug safety incidents;

　　(2) Failure to promptly investigate and address identified violations of drug safety laws and regulations;

　　(3) Failure to promptly identify systemic risks in the drug safety system or failure to promptly eliminate potential safety hazards within the supervised and regulated area, resulting in serious consequences;

　　(4) Other instances of failing to fulfill drug supervision and management duties, resulting in serious adverse effects or significant losses.

　　Chapter VI Supplementary Provisions

　　Article 73: The time limits stipulated in these Measures shall be calculated in working days. The time required for technical review and assessment, on-site inspections, and enterprise rectifications in the pharmaceutical production license process shall not be included in these time limits.

　　Article 74: Site management documents refer to summary documents on pharmaceutical production activities prepared by pharmaceutical manufacturers; they are part of the pharmaceutical manufacturer’s quality management documentation system. Specific requirements for site management documents shall be formulated separately.

　　Active pharmaceutical ingredients, excipients, and packaging materials and containers that directly contact drugs—along with their approved or associated review-and-approval sites, as well as overseas production sites—will all be assigned a unified code.

　　Article 75: A warning letter refers to a letter issued by the drug regulatory authority, in accordance with the law, during drug regulatory activities, when there is evidence indicating potential safety risks. The warning letter shall specify the defects, issues, and requirements for corrective actions.

　　Article 76: The format of the drug production license number is “Abbreviated provincial name + four-digit year code + four-digit sequential number.” If a company changes its name or other license details, or if the license is reissued, the original drug production license number remains unchanged.

　　In the case of corporate spin-offs, while retaining the original drug manufacturing license number, a new number is added. In the case of corporate mergers, only one original drug manufacturing license number is retained.

　　Article 77: The classification code is an alphanumeric string used to statistically categorize the scope of production covered by a license. Uppercase letters are used to classify the marketing authorization holder and product type, as follows: A stands for a marketing authorization holder who manufactures drugs independently; B stands for a marketing authorization holder who commissions others to manufacture drugs; C stands for a drug manufacturer that accepts commissioned production; D stands for an active pharmaceutical ingredient (API) manufacturer. Lowercase letters are used to distinguish the attributes of dosage forms: h represents chemical drugs, z represents traditional Chinese medicine preparations, s represents biological products, d represents in vitro diagnostic reagents managed as drugs, y represents processed Chinese medicinal herbs, q represents medical gases, t represents special drugs, and x represents other categories.

　　Article 78: The scope of production indicated on the pharmaceutical production license shall be filled in accordance with the General Rules for Preparations in the Pharmacopoeia of the People’s Republic of China and other national pharmaceutical standards.

　　Article 79: Where other provisions are stipulated by relevant national laws and regulations concerning the production of vaccines, blood products, narcotic drugs, psychotropic drugs, toxic medicinal products for medical use, radioactive drugs, and drug-related precursors that are easily used for the manufacture of illicit drugs, such provisions shall prevail.

　　Article 80: Vaccines exported shall comply with the standards of the importing country (or region) or the requirements stipulated in the contract.

　　Article 81: These Measures shall take effect as of July 1, 2020. The “Measures for the Supervision and Administration of Pharmaceutical Production,” promulgated by Order No. 14 of the former State Food and Drug Administration on August 5, 2004, shall be repealed concurrently.