Regulations on the Supervision and Administration of Drug Production

Measures for the Supervision and Administration of Drug Production

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

 

Chapter One   General   Provisions

　　Article 1 To strengthen the supervision and administration of drug production and regulate drug production 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 "Traditional Chinese Medicine Law of the People's Republic of China", the "Vaccine Administration Law of the People's Republic of China" (hereinafter referred to as the "Vaccine Administration Law"), the "Administrative Licensing Law of the People's Republic of China", the "Implementation Regulations of the Drug Administration Law of the People's Republic of China" and other laws and administrative regulations.

　　Article 2 The production and supervision management activities of drugs marketed within the territory of the People's Republic of China shall comply with these measures.

　　Article 3 Those engaged in drug production activities shall comply with laws, regulations, rules, standards, and norms, ensuring that the entire process information is true, accurate, complete, and traceable.

　　Those engaged in drug production activities shall obtain approval from the drug supervision and administration department of the province, autonomous region, or municipality where they are located, legally obtain a drug production license, strictly comply with the Good Manufacturing Practice for Drugs, and ensure that the production process continuously meets legal requirements.

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

　　Traditional Chinese medicine decoction piece production enterprises shall fulfill the relevant obligations of the drug marketing authorization holder and ensure that the production process of traditional Chinese medicine decoction pieces continuously meets legal requirements.

　　Active pharmaceutical ingredient production enterprises shall organize production according to the approved production process, strictly comply with the Good Manufacturing Practice for Drugs, and ensure that the production process continuously meets legal requirements.

　　Enterprises producing excipients, packaging materials, and containers directly contacting drugs that are subject to related evaluations, as well as other units and individuals engaged in drug-related production activities, shall bear corresponding responsibilities according to law.

　　Article 4 Drug marketing authorization holders and drug production enterprises shall establish and implement a drug traceability system, assign traceability identifiers to each level of drug sales packaging units as prescribed, implement drug traceability through information technology means, timely and accurately record and preserve 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 national supervision and administration of drug production and supervises and guides the drug production supervision and administration work of the drug supervision and administration departments 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 drug production supervision and administration within their administrative regions, undertaking licensing, inspection, and punishment work related to drug production.

　　The Food and Drug Inspection and Verification Center of the National Medical Products Administration (hereinafter referred to as the Verification Center) organizes the formulation of drug inspection technical specifications and documents, undertakes overseas inspections and vaccine inspections, analyzes and evaluates risks found during inspections, makes inspection conclusions and proposes disposal suggestions, and is responsible for guiding and evaluating the quality management systems of drug inspection agencies in provinces, autonomous regions, and municipalities directly under the central government.

　　The Information Center of the National Medical Products Administration is responsible for the drug traceability collaborative service platform, the construction and management of drug safety credit files, and the unified coding of drug production sites.

　　Professional technical institutions for drug evaluation, inspection, verification, monitoring, and evaluation set up or designated by the drug supervision and administration departments according to law shall undertake relevant technical work according to their duties and issue technical conclusions to provide technical support for drug production supervision and administration.

 

Chapter Two   Production Licensing

　　Article 6 Those engaged in drug production shall meet the following conditions:

　　(1) Have pharmaceutical technical personnel, engineering technical personnel, and corresponding technical workers who have been qualified according to law; the legal representative, enterprise leader, production management leader (hereinafter referred to as production leader), quality management leader (hereinafter referred to as quality leader), quality authorized person, and other related personnel meet the conditions stipulated in the "Drug Administration Law" and "Vaccine Administration Law";

　　(2) Have factories, facilities, equipment, and sanitary environments suitable for drug production;

　　(3) Have institutions and personnel capable of quality management and quality inspection of the drugs produced;

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

　　(5) Have rules and regulations to ensure drug quality and comply with the requirements of Good Manufacturing Practice for Drugs.

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

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

　　(2) Have systems, facilities, and equipment to ensure biosafety;

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

　　Article 7 Applicants engaged in the production of preparations, active pharmaceutical ingredients, and traditional Chinese medicine decoction pieces shall submit applications to the drug supervision and administration departments of the provinces, autonomous regions, or municipalities where they are located in accordance with these measures and the application material requirements prescribed by the National Medical Products Administration.

　　Drug marketing authorization holders who entrust others to produce preparations shall meet the conditions stipulated in items (1), (3), and (5) of the first paragraph of Article 6 of these measures, sign entrustment and quality agreements with qualified drug production enterprises, and submit the relevant agreements and actual production site application materials together to the drug supervision and administration departments of the provinces, autonomous regions, or municipalities where the drug marketing authorization holder is located, applying for a drug production license in accordance with these measures.

　　Applicants shall be responsible for the authenticity of all content in their application materials.

　　Article 8 Upon receiving an application, the drug supervision and administration departments of provinces, autonomous regions, or municipalities shall handle it according to the following situations:

　　(1) If the application matter is not within the department's authority according to law, a decision of non-acceptance shall be made immediately and the applicant shall be informed to apply to the relevant administrative agency;

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

　　(3) If there are errors in the application materials that can be corrected on the spot, the applicant shall be allowed to correct them immediately;

　　(4) If the application materials are incomplete or do not meet the formal review requirements, a notice to supplement materials shall be issued on the spot or within five days, informing the applicant of all the content that needs to be supplemented at one time. If the notice is not given within the time limit, the application shall be deemed accepted from the date of receipt of the application materials;

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

　　The drug supervision and administration departments of provinces, autonomous regions, or municipalities shall issue an acceptance notice or a non-acceptance notice stamped with the department's official seal and dated when accepting or not accepting the drug production license application.

　　Article 9: The drug supervision and administration departments 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 review meets the regulations, approval shall be granted, and the drug production license shall be issued within ten days from the date of the written approval decision; if it does not meet the regulations, a written decision of disapproval shall be made with reasons explained.

　　The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the Central Government shall organize the technical review and evaluation of application materials and on-site inspections in accordance with the Good Manufacturing Practice for Drugs and other relevant regulations.

　　Article 10: The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the Central Government shall publicize on the administrative agency's website and office premises the conditions, procedures, time limits, the full list of materials to be submitted, and sample application forms required for applying for a drug production license.

　　The relevant information on the issuance of drug production licenses by the drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the Central Government shall be made public, and the public has the right to access it.

　　Article 11: When reviewing applications for drug production licenses, the drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the Central Government shall disclose the approval results and provide conditions to facilitate applicants in checking the approval process.

　　Without the applicant's consent, the drug supervision and administration departments, professional technical institutions, and their staff shall not disclose the applicant's submitted trade secrets, undisclosed information, or confidential business information, except as otherwise provided by law or involving national security or major social public interests.

　　Article 12: If the application for a drug production license directly involves significant interest relations between the applicant and others, the applicant and interested parties shall have the right to request a hearing in accordance with laws and regulations.

　　When reviewing the application of a drug production enterprise, if the drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the Central Government consider it involves public interest, they shall announce it to the public and hold a hearing.

　　Article 13: The validity period of a drug production license is five years, divided into an original and a duplicate. The format of the drug production license is uniformly formulated by the National Medical Products Administration. The electronic certificate of the drug production license has the same legal effect as the paper certificate.

　　Article 14: The drug production license shall specify items such as license number, classification code, enterprise name, unified social credit code, domicile (business premises), legal representative, enterprise head, production head, quality head, quality authorized person, production address and production scope, issuing authority, date of issuance, and validity period.

　　Items such as enterprise name, unified social credit code, domicile (business premises), and legal representative shall be consistent with the relevant content stated in the business license issued by the market supervision department.

　　Article 15: The items specified in the drug production license are divided into licensing items and registration items.

　　Licensing items refer to production address and production scope, etc.

　　Registration items refer to enterprise name, domicile (business premises), legal representative, enterprise head, production head, quality head, quality authorized person, etc.

　　Article 16: To change the licensing items of the drug production license, an application for change shall be submitted to the original issuing authority. Without approval, licensing items shall not be changed arbitrarily.

　　The original issuing authority shall make a decision on whether to approve the change within fifteen days from the date of receiving the enterprise's change application. If the change is not approved, the reasons shall be explained in writing, and the applicant shall be informed of the right to apply for administrative reconsideration or initiate administrative litigation according to law.

　　When changing the production address or production scope, the drug production enterprise shall submit relevant materials involving the change in accordance with the provisions of Article 6 of these Measures and related change technical requirements, and submit them to the drug supervision and administration department of the province, autonomous region, or municipality where it is located for review and decision.

　　For workshops or production lines that are rebuilt, expanded, or newly built at the original site or a different location, they shall comply with relevant regulations and technical requirements, submit relevant materials involving the change, and be subject to Good Manufacturing Practice conformity inspection by the drug supervision and administration department of the province, autonomous region, or municipality where it is located. The inspection results shall be notified to the enterprise. If the inspection results comply with regulations and the products meet release requirements, they may be marketed. Relevant changes shall be recorded in the duplicate of the drug production license.

　　If the above changes involve the content specified in the drug registration certificate and its attachments, after approval by the drug supervision and administration department of the province, autonomous region, or municipality, the National Medical Products Administration Drug Evaluation Center shall be reported to update the relevant content of the drug registration certificate and its attachments.

　　Article 17: For changes to the registration items of the drug production license, an application for change registration of the drug production license shall be submitted to the original issuing authority within thirty days after the market supervision department approves the change or the enterprise completes the change. The original issuing authority shall handle the change procedures within ten days from the date of receiving the enterprise's change application.

　　Article 18: After the drug production license is changed, the original issuing authority shall record the content and time of the change on the duplicate of the drug production license, reissue the original drug production license according to the changed content, recover the original drug production license, and the expiration date of the changed drug production license shall remain unchanged.

　　Article 19: When the validity period of the drug production license expires and continued drug production is needed, an application for reissuance of the drug production license shall be submitted to the original issuing authority six months before the expiration.

　　The original issuing authority shall review based on the enterprise's compliance with drug management laws and regulations, Good Manufacturing Practice, and quality system operation, and make a decision on whether to approve reissuance before the expiration of the drug production license according to risk management principles. If approved, the original certificate shall be recovered and reissued; if not approved, a written decision of disapproval shall be made with reasons explained, and the applicant shall be informed of the right to apply for administrative reconsideration or initiate administrative litigation according to law; if no decision is made within the time limit, it shall be deemed as consent to reissuance, and the corresponding procedures shall be completed.

　　Article 20: The drug production license shall be canceled by the original issuing authority and announced in the following circumstances:

　　(1) Voluntary application for cancellation of the drug production license;

　　(2) The validity period of the drug production license has expired without reissuance;

　　(3) The business license has been legally revoked or canceled;

　　(4) The drug production license has been legally revoked or withdrawn;

　　(5) Other circumstances where administrative licenses shall be canceled according to laws and regulations.

　　Article 21: If the drug production license is lost, the drug marketing authorization holder or drug production enterprise shall apply to the original issuing authority for reissuance. The original issuing authority shall reissue the drug production license within ten days according to the original approved items. The license number, validity period, etc., shall be consistent with the original license.

　　Article 22: No unit or individual shall forge, alter, rent, lend, or sell drug production licenses.

　　Article 23: The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government shall update the status of drug production license issuance, reissuance, changes, reissuance of lost licenses, revocation, cancellation, and deregistration in the drug safety credit file within ten days after the completion of the processing work.

Chapter 3   Production Management

　　Article 24: Engaging in drug production activities shall comply with the Good Manufacturing Practice for Drugs, produce according to national drug standards, drug registration standards approved by the drug supervision and administration department, and production processes, submit and continuously update site management documents as required, conduct risk assessments and continuous improvements on the quality system operation process, ensuring the entire drug production process continuously meets legal requirements. Production and inspection records shall be complete and accurate, and fabrication or alteration is prohibited.

　　Article 25: Vaccine marketing authorization holders shall have the necessary plant facilities and equipment for vaccine production and inspection, equip qualified management personnel, establish a sound quality management system, and have the capability to produce vaccines that meet registration requirements. If production capacity is exceeded and outsourcing is necessary, approval from the National Medical Products Administration is required.

　　Article 26: Engaging in drug production activities shall comply with the Good Manufacturing Practice for Drugs, establish and improve the drug production quality management system covering all factors affecting drug quality, ensuring the entire drug production process continuously meets legal requirements.

　　Article 27: Drug marketing authorization holders shall establish a drug quality assurance system, assign dedicated personnel independently responsible for drug quality management, regularly audit the quality management systems of entrusted drug production enterprises and drug distribution enterprises, and supervise their continuous capability for quality assurance and control.

　　Article 28: The legal representative and principal responsible person of the drug marketing authorization holder shall be fully responsible for drug quality and perform the following duties:

　　(1) Assign a dedicated quality manager independently responsible for drug quality management;

　　(2) Assign a dedicated quality authorized person independently performing drug marketing release responsibilities;

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

　　(4) Regularly conduct quality system audits on drug production enterprises, suppliers, and other related parties involved in drug production activities to ensure continuous compliance;

　　(5) Fulfill change management responsibilities according to changes in technical requirements;

　　(6) Conduct quality assessments of entrusted business enterprises and communicate information with users and others;

　　(7) Cooperate with drug supervision and administration departments in extended inspections of the drug marketing authorization holder and related parties;

　　(8) In the event of major safety incidents related to drug quality, promptly report and carry out risk handling according to the risk management plan formulated by the holder to ensure timely risk control;

　　(9) Other responsibilities prescribed by laws and regulations.

　　Article 29: The legal representative and principal responsible person of the drug production enterprise shall be fully responsible for the drug production activities of their enterprise and perform the following duties:

　　(1) Assign a dedicated quality manager independently responsible for drug quality management, supervise the implementation of quality management standards, ensure appropriate production process control and quality control, and guarantee that drugs meet national drug standards and drug registration standards;

　　(2) Assign a dedicated quality authorized person to perform drug release responsibilities;

　　(3) Supervise the normal operation of the quality management system, ensuring drug production process control, quality control, and the authenticity of records and data;

　　(4) In the event of major safety incidents related to drug quality, promptly report and carry out risk handling according to the risk management plan formulated by the enterprise to ensure timely risk control;

　　(5) Other responsibilities prescribed by laws and regulations.

　　Article 30: Drug marketing authorization holders and drug production enterprises shall conduct annual health checks for personnel directly in contact with drugs and establish health records to prevent individuals with infectious diseases or other diseases that may contaminate drugs from engaging in drug production activities involving direct contact with drugs.

　　Article 31: Drug marketing authorization holders and drug production enterprises shall carry out quality management activities such as risk assessment, control, validation, communication, and audit during drug production, and take effective risk control measures promptly for identified risks to ensure product quality.

　　Article 32: Engaging in drug production activities shall include auditing suppliers or manufacturers of active pharmaceutical ingredients, excipients, packaging materials, and containers directly contacting drugs to ensure purchased and used materials comply with regulatory requirements.

　　Raw materials and excipients required for drug production shall meet pharmaceutical requirements and relevant Good Manufacturing Practice requirements. Packaging materials and containers directly contacting drugs shall meet pharmaceutical requirements and standards ensuring human health and safety.

　　Article 33: Manufacturers of approved or jointly reviewed active pharmaceutical ingredients, excipients, packaging materials, and containers directly contacting drugs shall comply with the quality management standards formulated by the National Medical Products Administration and related joint review requirements, ensure continuous compliance of the quality assurance system, accept quality audits by drug marketing authorization holders, and accept supervision or extended inspections by drug supervision and administration departments.

　　Article 34: Drug production enterprises shall determine necessary qualifications and validations and implement them according to the qualification and validation plan. Facilities, equipment, production processes, and cleaning methods shall be regularly evaluated to confirm continuous validation status.

　　Article 35: Drug production enterprises shall take control measures to prevent contamination, cross-contamination, confusion, and errors, regularly inspect and evaluate the applicability and effectiveness of control measures to ensure drugs meet prescribed national drug standards and drug registration standards and comply with Good Manufacturing Practice requirements.

　　Drug marketing authorization holders and drug production enterprises shall not produce other products in drug production plants that adversely affect drug quality.

　　Article 36: Drug packaging operations shall take measures to reduce the risk of confusion and errors, and drug packaging shall ensure that drugs are not contaminated during storage and transportation within the validity period.

Statements in drug instructions and labels shall be scientific, standardized, and accurate, with clear and easily distinguishable text, and shall not be modified or supplemented by pasting, cutting, or altering.

　　Article 37: Drug production enterprises shall establish drug release procedures, clarify release standards and conditions, review drug quality inspection results, key production records, and deviation control status, and conduct drug quality inspections. Drugs meeting standards and conditions may be released after signing by the quality authorized person.

　　Drug marketing authorization holders shall establish drug marketing release procedures, review drug inspection results and release documents from drug production enterprises, and drugs may be marketed after signing by the quality authorized person.

　　Chinese herbal pieces may only be released and sold if they meet the national drug standards or the processing specifications formulated by the drug regulatory authorities of provinces, autonomous regions, or municipalities directly under the central government.

　　Article 38: The drug marketing authorization holders and drug manufacturing enterprises shall conduct annual self-inspections to monitor the implementation of Good Manufacturing Practice (GMP) for drugs, assess whether the enterprise complies with relevant regulatory requirements, and propose necessary corrective and preventive measures.

　　Article 39: Drug marketing authorization holders shall establish an annual reporting system and report annually to the drug regulatory authorities of provinces, autonomous regions, or municipalities directly under the central government on drug production and sales, post-marketing research, risk management, and other related matters in accordance with the regulations of the National Medical Products Administration.

　　Vaccine marketing authorization holders shall submit annual reports to the National Medical Products Administration as required.

　　Article 40: Drug marketing authorization holders shall continuously conduct drug risk-benefit assessments and controls, develop post-marketing drug risk management plans, proactively carry out post-marketing studies, further confirm the safety, efficacy, and quality controllability of drugs, and strengthen continuous management of marketed drugs.

　　Article 41: Drug marketing authorization holders shall establish a pharmacovigilance system and carry out pharmacovigilance work in accordance with the pharmacovigilance quality management standards formulated by the National Medical Products Administration.

　　Drug marketing authorization holders and drug manufacturing enterprises shall regularly investigate the quality, efficacy, and adverse reactions of their drugs. Suspected adverse reactions should be reported promptly as required.

　　Article 42: Drug marketing authorization holders who entrust drug production shall comply with relevant drug management regulations.

　　Drug marketing authorization holders who entrust qualified drug manufacturing enterprises to produce drugs shall evaluate the quality assurance capability and risk management capability of the entrusted party, sign quality agreements and entrustment agreements with them according to the guidelines for drug contract manufacturing quality agreements formulated by the National Medical Products Administration, and supervise the entrusted party to fulfill the obligations stipulated in the agreements.

　　The entrusted party shall not subcontract the entrusted drug production to a third party.

　　Approved or related-reviewed active pharmaceutical ingredients (APIs) shall be produced by the holder themselves and shall not be subcontracted to others.

　　Article 43: Drug marketing authorization holders shall manage and control changes in production processes according to the requirements of Good Manufacturing Practice, formulate process procedures based on the approved production process, conduct studies on production process changes, and obtain approval, filing, or reporting as required by law, subject to supervision and inspection by drug regulatory authorities.

　　Article 44: Drug marketing authorization holders and drug manufacturing enterprises shall annually conduct product quality review and analysis by product type for the drugs they produce, and keep records to confirm process stability and reliability, as well as the applicability of current quality standards for raw materials, excipients, and finished products.

　　Article 45: When there are changes in the organizational structure related to the quality management system of drug marketing authorization holders and drug manufacturing enterprises, including changes in enterprise leaders, production leaders, quality leaders, and quality authorized persons, registration procedures shall be completed within thirty days from the date of change.

　　Vaccine marketing authorization holders shall report changes in key personnel such as production leaders, quality leaders, and quality authorized persons to the drug regulatory authorities of the province, autonomous region, or municipality directly under the central government where they are located within fifteen days from the date of change.

　　Article 46: For drugs listed in the national shortage drug list requiring production suspension reporting, if the drug marketing authorization holder plans to stop production, they shall report to the drug regulatory authorities of the province, autonomous region, or municipality directly under the central government where they are located six months before the planned suspension; in case of unexpected suspension, they shall report within three days. If necessary, report to the National Medical Products Administration.

　　After receiving the report, the drug regulatory authorities shall promptly notify the leading unit of the same-level shortage drug supply guarantee work consultation and coordination mechanism.

　　Article 47: If the drug marketing authorization holder is a foreign enterprise, it shall designate a corporate legal person within China to fulfill the obligations of the drug marketing authorization holder stipulated in the Drug Administration Law and these measures, and be responsible for coordinating and cooperating with overseas inspections.

　　Article 48: If the production site of the drug marketing authorization holder is overseas, production shall be organized in accordance with the Drug Administration Law and these measures, and cooperate with overseas inspections.

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 drug marketing authorization holders and manufacturers of preparations, chemical APIs, and Chinese herbal pieces within their administrative regions.

　　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 directly contact drugs, and carry out extended inspections when necessary.

　　Article 50: If the drug marketing authorization holder and the entrusted manufacturing enterprise are not in the same province, autonomous region, or municipality directly under the central government, the drug regulatory authority where the drug marketing authorization holder is located shall be responsible for supervising the holder, and the drug regulatory authority where the entrusted manufacturing enterprise is located shall be responsible for supervising the entrusted manufacturer. The drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall strengthen mutual notification of supervision and inspection information, promptly update supervision and inspection information in the drug safety credit file, and may conduct investigations based on notifications and updates in the drug safety credit file, take administrative actions against the drug marketing authorization holder or entrusted manufacturer according to law, and conduct joint inspections if necessary.

　　Article 51: Drug regulatory authorities shall establish and improve a professional inspector system, clarify inspector qualification standards, inspection responsibilities, hierarchical management, capacity training, code of conduct, performance evaluation, and exit procedures, to improve inspectors' professional quality and work level. Inspectors shall be familiar with drug laws and regulations and possess professional drug knowledge.

Drug regulatory authorities shall allocate sufficient inspectors according to regulatory authority, scale of the pharmaceutical industry, and inspection tasks to meet inspection needs. Regions with high-risk drug manufacturers such as vaccine producers shall also allocate a corresponding number of inspectors with skills and experience in inspecting high-risk drugs like vaccines.

　　Article 52: According to regulatory needs, the drug regulatory authorities of provinces, autonomous regions, and municipalities directly under the central government shall conduct pre-market GMP compliance inspections on applicants holding drug production licenses and their entrusted manufacturers according to the following requirements:

　　(1) Varieties that have not passed GMP compliance inspections suitable for the production conditions of the drug shall undergo pre-market GMP compliance inspections. For drugs requiring on-site registration inspections, the National Medical Products Administration Drug Evaluation Center shall notify the inspection center and inform the relevant provincial, autonomous region, or municipal drug regulatory authorities and applicants. The inspection center shall coordinate with the relevant provincial, autonomous region, or municipal drug regulatory authorities to conduct drug registration on-site inspections and pre-market GMP compliance inspections simultaneously;

　　(2) For drugs planned for production that do not require on-site drug registration inspection, the Drug Evaluation Center of the National Medical Products Administration shall notify the drug supervision departments of the provinces, autonomous regions, and municipalities where the production sites are located, as well as the applicants. The relevant provincial, autonomous region, and municipal drug supervision departments shall conduct pre-market drug production quality management compliance inspections on their own.

　　(3) For varieties that have passed the drug production quality management compliance inspection suitable for the production conditions of the drug, the relevant provincial, autonomous region, and municipal drug supervision departments shall decide whether to conduct pre-market drug production quality management compliance inspections based on risk management principles.

When conducting pre-market drug production quality management compliance inspections, a written report on the inspection situation and results shall be prepared after the inspection, serving as an important basis for drug market supervision. If the pre-market drug production quality management compliance inspection involves changes to the drug production license matters, the original issuing provincial, autonomous region, or municipal drug supervision department shall make decisions according to the change procedures.

　　Commercial scale batches that pass the corresponding pre-market drug production quality management compliance inspection may be marketed after obtaining the drug registration certificate and meeting product release requirements. The drug marketing authorization holder shall focus on strengthening production, sales, and risk management measures for the above batches of drugs.

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

　　(1) The implementation by the drug marketing authorization holder and drug production enterprises of relevant laws, regulations, and the implementation of drug production quality management standards, pharmacovigilance quality management standards, and related technical specifications;

　　(2) Whether drug production activities are consistent with the relevant contents recorded in the drug variety files;

　　(3) Implementation of vaccine storage and transportation management standards;

　　(4) Drug entrusted production quality agreements and entrusted agreements;

　　(5) Implementation of risk management plans;

　　(6) Change management.

　　Supervision and inspection include licensing inspection, routine inspection, cause-based inspection, and other inspections.

　　Article 54 The drug supervision departments of provinces, autonomous regions, and municipalities shall adhere to the principles of risk management and full-process control, formulate annual inspection plans based on risk assessment, and carry out supervision and inspection. The annual inspection plan shall at least include the scope, content, methods, focus, requirements, time limits, and institutions responsible for the inspection.

　　Article 55 The drug supervision departments of provinces, autonomous regions, and municipalities shall determine the inspection frequency based on drug varieties, dosage forms, control categories, combined with the overall national drug safety situation, drug safety risk warning information, major drug safety incidents and their investigation and handling information, as well as past inspections, testing, adverse reaction monitoring, complaints, and reports:

　　(1) For manufacturers of narcotic drugs, first-class psychotropic drugs, and precursor chemicals for drug production, inspections shall be conducted at least once per quarter;

　　(2) For manufacturers of high-risk drugs such as vaccines, blood products, radioactive drugs, toxic medical drugs, and sterile drugs, drug production quality management compliance inspections shall be conducted at least once a year;

　　(3) For drug manufacturers other than the above products, a certain proportion shall be randomly inspected annually, but all enterprises within the administrative region shall be inspected within three years;

　　(4) For suppliers and manufacturers of raw materials, excipients, packaging materials, and containers directly contacting drugs, a certain proportion shall be randomly inspected annually, and all enterprises within the administrative region shall be inspected within five years.

　　The drug supervision departments of provinces, autonomous regions, and municipalities may adjust the inspection frequency based on the actual drug production supervision work within their administrative regions.

　　Article 56 When the National Medical Products Administration and the drug supervision departments of provinces, autonomous regions, and municipalities organize supervision and inspection, they shall formulate inspection plans, clarify inspection standards, truthfully record on-site inspection situations, and conduct sampling inspection or research as required according to relevant regulations. Inspection conclusions shall be clear and definite, and problems found during the inspection shall be notified in writing to the inspected units. If rectification is needed, the rectification content and deadline shall be proposed, and if necessary, follow-up inspections shall be conducted after rectification.

　　During supervision and inspection, the drug supervision department shall assign two or more inspectors to carry out the inspection. Inspectors shall present law enforcement credentials to the inspected units. Staff of the drug supervision department shall keep confidential any business secrets they become aware of.

　　Article 57 During supervision and inspection, the drug marketing authorization holders and drug production enterprises shall explain situations and provide relevant materials as needed for the inspection:

　　(1) Drug production site management documents and change materials;

　　(2) Acceptance of supervision and inspection and rectification implementation by drug production enterprises;

　　(3) Handling of drug quality nonconformities;

　　(4) Establishment of pharmacovigilance institutions, personnel, systems, and monitoring, identification, evaluation, and control of suspected adverse drug reactions;

　　(5) Materials for post-marketing studies of conditionally approved varieties;

　　(6) Other necessary materials for review.

　　Article 58 After the on-site inspection ends, the on-site inspection situation shall be analyzed and summarized, and defects found during the inspection shall be objectively, fairly, and impartially risk-assessed, and an on-site inspection conclusion shall be made.

　　The dispatching unit is responsible for comprehensive judgment of the on-site inspection conclusion.

　　Article 59 If the National Medical Products Administration and the drug supervision departments of provinces, autonomous regions, and municipalities find defects in drug production management or vaccine storage and transportation management through supervision and inspection, and there is evidence of potential safety hazards, they shall take corresponding measures according to law:

　　(1) If basically compliant with drug production quality management standards but requiring rectification, a warning letter shall be issued and corresponding measures such as warnings, interviews, and time-limited rectifications shall be taken based on risk;

　　(2) If there are drug quality problems or other safety hazards, the drug supervision department shall issue a warning letter based on the supervision and inspection situation and take control measures such as suspension of production, sales, use, or import according to risk.

　　If the drug has quality problems or other safety hazards and the drug marketing authorization holder fails to recall the drug as required by law, the drug supervision department of the province, autonomous region, or municipality shall order the recall.

　　After risk elimination, the drug supervision department that took control measures shall lift the control measures.

　　Article 60 During the drug production supervision and inspection process, if drug quality safety risks are found, they shall be reported to the dispatching unit in a timely manner. If the drug supervision department judges it to be a major drug quality safety risk, it shall promptly report to the higher-level drug supervision department and the local people's government at the same level.

　　Article 61 During the process of drug production supervision and inspection, if suspected violations of drug laws, regulations, or rules are found, on-site control measures shall be promptly taken, and evidence collection shall be properly conducted according to regulations. The drug supervision and administration department shall investigate and handle according to its duties and authority, and transfer suspected criminal cases to the public security authorities for processing.

　　Article 62 The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government shall, in accordance with the law, incorporate the regulatory information of drug marketing authorization holders and drug manufacturing enterprises within their administrative regions into the drug safety credit file management, and maintain dynamic updates of relevant data. Regulatory information includes drug manufacturing licenses, routine supervision and inspection results, handling of illegal acts, drug quality sampling inspections, records of adverse behaviors, and complaints and reports.

　　Article 63 The National Medical Products Administration and the drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government shall not obstruct the normal production activities of drug marketing authorization holders and drug manufacturing enterprises during production supervision and management, shall not solicit or accept property, nor seek other benefits.

　　Article 64 Individuals and organizations who discover illegal production activities by drug marketing authorization holders or drug manufacturing enterprises have the right to report to the drug supervision and administration departments, which shall verify and handle the reports promptly in accordance with relevant regulations.

　　Article 65 In the event of a major safety incident related to drug quality, the drug marketing authorization holder shall immediately take control measures such as sealing the relevant drugs and their raw materials, excipients, packaging materials and containers directly contacting the drugs, and related production lines, and immediately report to the drug supervision and administration departments of the province, autonomous region, or municipality directly under the central government where they are located and relevant departments. The drug supervision and administration departments of the province, autonomous region, or municipality directly under the central government shall report to the provincial people's government within 24 hours and simultaneously report to the National Medical Products Administration.

　　Article 66 The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government shall increase the frequency of supervision and inspection for drug marketing authorization holders and drug manufacturing enterprises with poor credit records, and may implement joint disciplinary actions in accordance with national regulations.

　　Article 67 If the drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government fail to timely identify systemic drug safety risks in the production process or fail to promptly eliminate drug safety hazards within their supervision areas, or if the provincial people's government fails to fulfill drug safety responsibilities and fails to promptly eliminate regional major drug safety hazards, the National Medical Products Administration shall conduct interviews with their main responsible persons.

　　The drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government and local people's governments that are interviewed shall immediately take measures to rectify the drug supervision and administration work.

　　The interview and rectification situations shall be included in the evaluation and assessment records of the drug supervision and administration work of the drug supervision and administration departments of provinces, autonomous regions, and municipalities directly under the central government and local people's governments.

Chapter Five   Legal Liability

　　Article 68 In any of the following circumstances, penalties shall be imposed in accordance with Article 115 of the Drug Administration Law:

　　(1) The drug marketing authorization holder and drug manufacturing enterprise change the production address or production scope without approval when approval is required;

　　(2) Continuing production after the drug manufacturing license has expired.

　　Article 69 If the drug marketing authorization holder and drug manufacturing enterprise fail to produce in accordance with the requirements of the drug production quality management standards and have any of the following circumstances, which constitute serious violations as stipulated in Article 126 of the Drug Administration Law, penalties shall be imposed according to law:

　　(1) Failure to appoint a dedicated quality responsible person independently responsible for drug quality management and supervision of quality management standard implementation;

　　(2) The drug marketing authorization holder fails to appoint a dedicated quality authorized person to fulfill the drug marketing release responsibility;

　　(3) The drug manufacturing enterprise fails to appoint a dedicated quality authorized person to fulfill the drug release responsibility;

　　(4) The quality management system cannot operate normally, and records and data of drug production process control and quality control are not authentic;

　　(5) Failure to take effective risk control measures in a timely manner for identified risks, unable to ensure product quality;

　　(6) Other serious violations of drug production quality management standards.

　　Article 70 If excipient manufacturers and suppliers of packaging materials and containers directly contacting drugs fail to comply with the quality management standards and other related requirements formulated by the National Medical Products Administration and cannot ensure the continuous compliance of the quality assurance system, the drug supervision and administration departments of the province, autonomous region, or municipality directly under the central government where they are located shall impose penalties in accordance with Article 126 of the Drug Administration Law.

　　Article 71 If the drug marketing authorization holder and drug manufacturing enterprise have any of the following circumstances, the drug supervision and administration departments of the province, autonomous region, or municipality directly under the central government where they are located shall impose a fine of not less than 10,000 yuan and not more than 30,000 yuan:

　　(1) Failure to handle registration changes for enterprise name, domicile (business premises), or legal representative as required;

　　(2) Failure to conduct annual health checks and establish health records for personnel directly contacting drugs as required;

　　(3) Failure to report production suspension for drugs listed in the national shortage drug list requiring production suspension reports as required.

　　Article 72 If the drug supervision and administration department has any of the following behaviors, penalties shall be imposed on the directly responsible supervisors and other directly responsible personnel in accordance with Article 149 of the Drug Administration Law:

　　(1) Concealing, falsely reporting, delaying reporting, or omitting reporting drug safety incidents;

　　(2) Failure to promptly investigate and handle discovered drug safety violations;

　　(3) Failure to timely identify systemic drug safety risks or to promptly eliminate drug safety hazards within the supervision area, causing serious impact;

　　(4) Other failures to perform drug supervision and administration duties, causing serious adverse effects or major losses.

Chapter Six   Appendix   Provisions

　　Article 73 The time limits stipulated in these measures are calculated in working days. The time required for technical review and evaluation, on-site inspection, and enterprise rectification in drug manufacturing licensing is not included in the time limits.

　　Article 74 Site management documents refer to overview documents of drug production activities prepared by drug manufacturing enterprises and are part of the quality management document system of drug manufacturing enterprises. Relevant requirements for site management documents shall be formulated separately.

　　Approved or related reviewed and approved production sites for active pharmaceutical ingredients, excipients, and packaging materials and containers directly contacting drugs, including overseas production sites, shall be assigned a unified code.

Article 75 A warning letter refers to a letter issued by the drug supervision and administration department during drug supervision and administration activities when there is evidence indicating possible safety hazards. The warning letter shall specify the defects, problems, and rectification requirements.

　　Article 76 The format of the drug production license number is "province abbreviation + four-digit year + four-digit serial number." When a company changes its name or other license items and reissues the license, the original drug production license number remains unchanged.

　　When a company splits, a new number is added while retaining the original drug production license number. When companies merge, only one original drug production license number is retained.

　　Article 77 The classification code is a string of English letters used to statistically categorize the production scope within the license. Uppercase letters classify drug marketing authorization holders and product types, including: A represents self-produced drug marketing authorization holders, B represents entrusted production drug marketing authorization holders, C represents entrusted drug production enterprises, D represents raw material drug production enterprises; lowercase letters distinguish formulation attributes, h represents chemical drugs, z represents traditional Chinese patent medicines, s represents biological products, d represents in vitro diagnostic reagents managed as drugs, y represents Chinese herbal pieces, q represents medical gases, t represents special drugs, x represents others.

　　Article 78 The production scope of the drug production license shall be filled in accordance with the General Rules for Preparations of the "Pharmacopoeia of the People's Republic of China" and other national drug standards.

　　Article 79 If national laws and regulations have special provisions for the production of vaccines, blood products, narcotic drugs, psychotropic drugs, toxic medical drugs, radioactive drugs, and precursor chemicals for drugs, those provisions shall apply.

　　Article 80 Exported vaccines shall comply with the standards or contractual requirements of the importing country (region).

　　Article 81 These measures shall come into effect on July 1, 2020. The "Drug Production Supervision Measures" promulgated by the former State Food and Drug Administration Order No. 14 on August 5, 2004, shall be repealed simultaneously.