Measures for the Supervision and Administration of Pharmaceutical Production

Published:

2021-11-26


Measures for the Supervision and Administration of Pharmaceutical Production
(Promulgated by Decree No. 28 of the State Administration of Market Supervision and Administration on January 22, 2020)

 

Chapter I General Provisions

Article 1 In order to strengthen the supervision and administration of drug production and regulate drug production activities, in accordance with the Drug Administration Law of the People's Republic of China (hereinafter referred to as the Drug Administration Law), the 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 Regulations for the Implementation of the Drug Administration Law of the People's Republic of China and other laws These Measures are formulated for administrative regulations.
Article 2 The production, supervision and administration of drugs listed within the territory of the People's Republic of China shall comply with these Measures.
Article 3 Pharmaceutical production activities shall comply with laws, regulations, rules, standards and norms, and ensure the authenticity, accuracy, integrity and traceability of information throughout the process.
To engage in drug production activities, the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government where the enterprise is located should approve it, obtain a drug production license according to law, strictly abide by the drug production quality control standards, and ensure that the production process continues to meet legal requirements.
The holder of a drug marketing license shall establish a drug quality assurance system, perform the responsibility of drug marketing release, and be responsible for the quality of the drug for which the drug registration certificate has been obtained.
The manufacturer of prepared slices of traditional Chinese medicine shall perform the relevant obligations of the holder of the drug marketing license to ensure that the production process of prepared slices of traditional Chinese medicine continues to meet the statutory requirements.
API manufacturing enterprises shall organize production according to the approved production process, strictly abide by the pharmaceutical production quality management standards, and ensure that the production process continues to meet the statutory requirements.
The manufacturing enterprises of the auxiliary materials, packaging materials and containers that are directly in contact with drugs and other units and individuals engaged in drug related production activities shall bear corresponding responsibilities according to law.
Article 4 The holders of drug marketing licenses and drug manufacturing enterprises shall establish and implement a drug traceability system, assign traceability marks to drug sales packaging units at all levels according to regulations, implement drug traceability by means of information technology, timely and accurately record and preserve drug traceability data, and provide traceability information to the drug traceability collaborative service platform.
Article 5 The SDA shall be responsible for the supervision and administration of drug production throughout the country, and shall supervise and guide the drug production supervision and administration of the drug regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government.
The pharmaceutical supervisory and administrative departments of provinces, autonomous regions and municipalities directly under the Central Government are responsible for the supervision and administration of pharmaceutical production within their respective administrative areas, and are responsible for the licensing, inspection and punishment of pharmaceutical production.
The Food and Drug Audit and Inspection Center of the State Drug Administration (hereinafter referred to as the Inspection Center) organizes the formulation of technical specifications and documents for drug inspection, undertakes overseas inspections and organizes vaccine inspections, analyzes and evaluates the risks found in inspections, makes inspection conclusions and puts forward disposal suggestions, and is responsible for the guidance and evaluation of the quality management system of drug inspection institutions in all provinces, autonomous regions and municipalities directly under the Central Government.
The Information Center of the State Drug Administration is responsible for the construction and management of the drug traceability collaborative service platform, drug safety credit archives, and the unified coding of drug production sites.
The specialized technical institutions for drug review, inspection, verification, monitoring and evaluation set up or designated by the drug regulatory department according to law shall undertake relevant technical work and issue technical conclusions in accordance with their duties, so as to provide technical support for drug production supervision and management.

 

Chapter II Production License

Article 6 Pharmaceutical production shall meet the following requirements:
(1) There are legally qualified pharmaceutical technicians, engineering technicians and corresponding technical workers, the legal representative, the person in charge of the enterprise, the person in charge of production management (hereinafter referred to as the person in charge of production), the person in charge of quality management (hereinafter referred to as the person in charge of quality), the quality authorized person and other relevant personnel who meet the conditions specified in the Drug Administration Law and the Vaccine Administration Law;
(2) There are factory buildings, facilities, equipment and a hygienic environment suitable for drug production;
(3) There are institutions and personnel capable of quality control and quality inspection of the drugs produced;
(4) Having necessary instruments and equipment capable of conducting quality management and quality inspection on the drugs produced;
(5) There are rules and regulations to ensure the quality of drugs and meet the requirements of drug production quality management specifications.
Those engaged in vaccine production shall also meet the following conditions:
(1) Have moderate scale and sufficient capacity reserves;
(2) Have systems, facilities and equipment to ensure biological safety;
(3) Meet the needs of disease prevention and control.
Article 7 To engage in the production of pharmaceutical preparations, raw materials and prepared slices of traditional Chinese medicine, the applicant shall apply to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where it is located in accordance with these Measures and the requirements for application materials prescribed by the SDA.
The holder of a drug marketing license who entrusts others to produce preparations shall meet the conditions specified in Items 1, 3 and 5 of Paragraph 1 of Article 6 of these Measures, sign an entrustment agreement and a quality agreement with eligible drug producing enterprises, and submit the relevant agreement and the application materials of the actual production site to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where the holder of the drug marketing license is located, To apply for a drug production license in accordance with these Measures.
The applicant shall be responsible for the authenticity of all the contents of his application materials.
Article 8 After receiving an application, the drug regulatory department of a province, autonomous region or municipality directly under the Central Government shall handle it according to the following circumstances:
(1) If the application matters do not fall within the scope of the authority of the department according to law, the department shall immediately make a decision not to accept the application and inform the applicant to apply to the relevant administrative organ;
(2) If the application item does not need to obtain an administrative license according to law, the applicant shall be informed immediately that it is not 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 on the spot;
(4) If the application materials are incomplete or do not meet the requirements of formal examination, the applicant shall be given a notice to supplement and correct the materials on the spot or within five days, informing the applicant of all the contents that need to be supplemented and corrected at one time. If the applicant fails to do so within the time limit, the application shall be accepted as of the date of receiving the application materials;
(5) If the application materials are complete and meet the requirements of formal examination, or the applicant submits all the supplementary materials as required, it shall be accepted.
If the drug regulatory department of a province, autonomous region or municipality directly under the Central Government accepts or rejects the application for a drug production license, it shall issue a notice of acceptance or rejection with its own special seal and date.
Article 9 The drug regulatory department of the province, autonomous region or municipality directly under the Central Government shall make a decision within 30 days from the date of acceptance.
If it meets the requirements after examination, it shall be approved, and a drug production license shall be issued within 10 days from the date of making the written approval decision; If the requirements are not met, a written decision on disapproval shall be made, and reasons shall be given.
The pharmaceutical supervisory and administrative departments of provinces, autonomous regions and municipalities directly under the Central Government shall, in accordance with the relevant provisions of the Good Manufacturing Practice for Drugs, organize the technical examination, evaluation and on-site inspection of the application materials.
Article 10 The drug regulatory department of a province, autonomous region or municipality directly under the Central Government shall publicize the conditions, procedures, time limit, catalogue of all materials to be submitted and the model text of the application on the website and office of the administrative organ.
The information about the drug production license issued by the drug regulatory department of a province, autonomous region or municipality directly under the Central Government shall be made public, and the public shall have the right to consult it.
Article 11 When examining the application for a drug production license, the drug regulatory department of a province, autonomous region or municipality directly under the Central Government shall publicize the results of the examination and approval, and provide conditions to facilitate the applicant's inquiry and approval process.
Without the consent of the applicant, the drug regulatory department, professional and technical institutions and their staff shall not disclose the trade secrets, undisclosed information or confidential business information submitted by the applicant, unless otherwise stipulated by law or involving national security and major social and public interests.
Article 12 Where an application for a drug production license directly involves a significant interest relationship between the applicant and others, the applicant and the interested party shall have the right to apply for a hearing in accordance with the provisions of laws and regulations.
When examining the application of a drug producing enterprise, the drug regulatory department of a province, autonomous region or municipality directly under the Central Government shall make a public announcement and hold a hearing if it considers that the application involves public interests.
Article 13 The term of validity of the drug production license is five years, which is divided into the original and the duplicate. The form of drug production license shall be uniformly formulated by the SDA. The electronic certificate of the drug production license has the same legal effect as the paper certificate.
Article 14 The pharmaceutical production license shall clearly state the license number, classification code, enterprise name, unified social credit code, domicile (business site), legal representative, enterprise responsible person, production responsible person, quality responsible person, quality authorized person, production address and production scope, license issuing authority, license issuing date, validity period and other items.
The enterprise name, unified social credit code, domicile (business site), legal representative and other items shall be consistent with the relevant contents specified in the business license issued by the market supervision and administration department.
Article 15 The items specified in a drug production license are divided into licensing items and registration items.
The licensing matters refer to the production address and production scope.
The registered items refer to the enterprise name, domicile (business site), legal representative, person in charge of the enterprise, person in charge of production, person in charge of quality, quality authorized person, etc.
Article 16 In case of any change to the items of the drug production license, an application for the change of the drug production license shall be submitted to the original license issuing authority. Without approval, the license items shall not be changed.
The original issuing authority shall decide whether to approve the change within 15 days from the date of receiving the enterprise's application for change. If no change is made, the applicant shall explain the reasons in writing and inform the applicant of the right to apply for administrative reconsideration or bring an administrative lawsuit according to law.
If the production address or scope of production is changed, the drug producing enterprise shall submit the relevant materials related to the changed contents in accordance with the provisions of Article 6 of these Measures and the relevant technical requirements for change, and submit them to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where they are located for examination and decision.
If a workshop or production line is to be built, rebuilt or expanded in its original location or in a different place, it shall comply with the relevant regulations and technical requirements, submit the relevant materials involving the changes, and report to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where it is located for inspection of the compliance of drug production quality management regulations. The enterprise shall be notified of the inspection results. If the inspection results meet the requirements and the products meet the release requirements, they can be marketed. The relevant changes shall be stated in the duplicate of the drug production license.
If the above changes involve the contents of the drug registration certificate and its annexes, they shall be submitted to the Drug Evaluation Center of the SDA for updating the drug registration certificate and its annexes after being approved by the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government.
Article 17 Any change in the registered items of the drug production license shall be applied to the original license issuing authority for change registration of the drug production license within 30 days after the market supervision and administration department approves the change or the enterprise completes the change. The original issuing authority shall go through the change procedures within ten days from the date of receiving the enterprise's application for change.
Article 18 After the change of the drug production license, the original issuing authority shall record the content and time of the change on the copy of the drug production license, re issue the original drug production license according to the changed content, and take back the original drug production license. The termination period of the changed drug production license shall remain unchanged.
Article 19 Where it is necessary to continue the production of drugs at the expiration of the validity period of a drug production license, an application for a new drug production license shall be submitted to the original license issuing authority six months before the expiration of the validity period.
The original license issuing authority shall, in combination with the enterprise's compliance with the laws and regulations on drug administration, the drug production quality management standards and the operation of the quality system, review according to the principle of risk management, and decide whether to grant a new license before the expiry of the drug production license. If a new certificate is granted in accordance with the provisions, the original certificate shall be withdrawn and a new certificate shall be issued; If it does not conform to the provisions, it shall make a written decision not to re issue the certificate, explain the reasons, and inform the applicant of the right to apply for administrative reconsideration or bring an administrative lawsuit according to law; If no decision is made within the time limit, it shall be deemed that it agrees to re issue the certificate and go through the corresponding formalities.
Article 20 Under any of the following circumstances, the drug production license shall be cancelled by the original license issuing authority and announced:
(1) Active application for cancellation of drug production license;
(2) The drug production license has not been reissued at the expiration of its validity period;
(3) The business license is revoked or cancelled according to law;
(4) The drug production license is revoked or revoked according to law;
(5) Other circumstances under which the administrative license shall be cancelled according to laws and regulations.
Article 21 If a drug production license is lost, the holder of the drug marketing license and the drug production enterprise shall apply to the original license issuing authority for reissue, and the original license issuing authority shall reissue the drug production license within 10 days according to the original approval items. The license number and validity are consistent with the original license.
Article 22 No unit or individual may forge, alter, lease, lend, buy or sell a pharmaceutical production license.
Article 23 The drug regulatory department of a province, autonomous region or municipality directly under the Central Government shall update the handling of the issue, reissue, change, reissue, revocation, cancellation and cancellation of the drug production license in the drug safety credit file within 10 days after the completion of the handling.

Chapter III Production Management

Article 24 Anyone engaged in pharmaceutical production activities shall abide by the quality control norms for pharmaceutical production, conduct production in accordance with the national pharmaceutical standards, the pharmaceutical registration standards and production processes approved by the pharmaceutical supervisory and administrative departments, submit and continuously update site management documents in accordance with regulations, conduct risk assessment and continuous improvement in the operation process of the quality system, and ensure that the entire pharmaceutical production process continues to meet the statutory requirements. Production and inspection records shall be complete and accurate and shall not be fabricated or tampered with.
Article 25 The holder of the vaccine marketing license shall have the factory facilities and equipment necessary for vaccine production and inspection, be equipped with qualified management personnel, establish and improve the quality management system, and have the ability to produce vaccines that meet the registration requirements. If it is necessary to entrust production beyond the vaccine production capacity, it shall be approved by the SDA.
Article 26 Anyone engaged in pharmaceutical production activities shall abide by the quality control standards for pharmaceutical production, establish and improve the quality control system for pharmaceutical production, cover all factors affecting pharmaceutical quality, and ensure that the whole process of pharmaceutical production continues to meet the statutory requirements.
Article 27 A holder of a drug marketing license shall establish a drug quality assurance system, assign special personnel to be independently responsible for drug quality management, conduct regular audits of the quality management system of entrusted drug producing enterprises and drug handling enterprises, and supervise their continued ability to ensure and control quality.
Article 28 The legal representative and principal responsible person of the holder of the drug marketing license shall be fully responsible for the drug quality and perform the following duties:
(1) A special quality director shall be assigned to take charge of drug quality management independently;
(2) Assign a special quality authorized person to independently perform the responsibility of drug marketing release;
(3) Supervise the normal operation of the quality management system;
(4) Regularly carry out quality system audits of drug production related activities of drug manufacturers, suppliers and other interested parties to ensure continuous compliance;
(5) Perform change management responsibilities according to change technical requirements;
(6) Evaluate the quality of the entrusted enterprises, and communicate with the users;
(7) Cooperate with the drug regulatory authorities in the extended inspection of drug marketing license holders and related parties;
(8) In case of any major safety incident related to drug quality, it shall timely report and handle the risk according to the risk management plan formulated by the holder to ensure that the risk is controlled in a timely manner;
(9) Other responsibilities stipulated by laws and regulations.
Article 29 The legal representative and principal person in charge of a drug producing enterprise shall be fully responsible for its drug production activities and perform the following duties:
(1) A special person in charge of quality shall be assigned to independently take charge of drug quality management, supervise the implementation of quality management specifications, ensure proper production process control and quality control, and ensure that drugs meet the national drug standards and drug registration standards;
(2) Assign a special quality authorized person to perform the responsibility of drug delivery release;
(3) Supervise the normal operation of the quality management system, and ensure the authenticity of drug production process control, quality control, records and data;
(4) In case of any major safety incident related to drug quality, it shall be reported in a timely manner and risk disposal shall be carried out according to the risk management plan formulated by the enterprise to ensure that the risk is controlled in a timely manner;
(5) Other responsibilities stipulated by laws and regulations.
Article 30 The holder of the drug marketing license and the drug manufacturing enterprise shall conduct a health examination every year for the staff members who have direct contact with drugs and establish health records, so as to avoid those who suffer from infectious diseases or other diseases that may contaminate drugs from engaging in production activities that have direct contact with drugs.
Article 31 In the course of drug production, drug marketing license holders and drug manufacturing enterprises shall carry out quality management activities such as risk assessment, control, verification, communication and examination, and take effective risk control measures against identified risks in a timely manner to ensure product quality.
Article 32 To engage in drug production activities, the suppliers or production enterprises of the raw materials, excipients, packaging materials and containers directly in contact with drugs and other related materials used shall be examined to ensure that the purchase and use meet the requirements of laws and regulations.
The raw materials and excipients needed for the production of drugs shall meet the pharmaceutical requirements and the relevant requirements of the corresponding production quality management standards. Packaging materials and containers in direct contact with drugs shall meet the pharmaceutical requirements and meet the standards for safeguarding human health and safety.
Article 33 The manufacturers of APIs, excipients, packaging materials and containers directly in contact with drugs that have been approved or have passed the related review and approval shall comply with the quality management specifications formulated by the SDA and the related review and approval requirements, ensure the continuous compliance of the quality assurance system, and accept the quality audit of the drug marketing license holders, Accept the supervision and inspection or extended inspection of the drug regulatory department.
Article 34 Pharmaceutical producing enterprises shall determine the confirmation and verification to be carried out according to the confirmation and verification plan. Regularly evaluate facilities, equipment, production process and cleaning methods, and confirm that they continue to maintain validation status.
Article 35 Pharmaceutical producing enterprises shall take control measures to prevent pollution, cross contamination, confusion and errors, regularly check and evaluate the applicability and effectiveness of the control measures, so as to ensure that pharmaceuticals meet the prescribed national pharmaceutical standards and pharmaceutical registration standards, and meet the requirements of pharmaceutical production quality control norms.
The holder of the drug marketing license and the drug manufacturing enterprise shall not produce other products in the drug manufacturing plant that will adversely affect the drug quality.
Article 36 Measures shall be taken to reduce the risk of confusion and error in the operation of drug packaging, and drug packaging shall ensure that drugs within the validity period are not contaminated during storage and transportation.
The statements in the drug directions and labels shall be scientific, standardized and accurate, the words shall be clear and legible, and shall not be modified or supplemented by pasting, cutting, or altering.
Article 37 Pharmaceutical producing enterprises shall establish procedures for the release of pharmaceuticals from the factory, specify the standards and conditions for the release from the factory, review the results of pharmaceutical quality inspection, key production records and deviation control, and conduct quality inspection of pharmaceuticals. Those meeting the standards and conditions can be released from the factory only after being signed by the quality authorized person.
The holder of the drug marketing license shall establish the drug marketing release procedures, review the drug inspection results and release documents released from the factory by the drug manufacturer, and release the drug to the market only after being signed by the quality authorized person.
Only when the prepared slices of traditional Chinese medicine meet the national drug standards or the processing specifications formulated by the drug regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government can they be delivered and sold.
Article 38 The holder of the drug marketing license and the drug manufacturing enterprise shall conduct self inspection every year, monitor the implementation of the drug production quality management standards, evaluate whether the enterprise meets the requirements of relevant laws and regulations, and propose necessary corrective and preventive measures.
Article 39 Holders of drug marketing licenses shall establish an annual reporting system and report to the drug regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government on drug production and sales, post marketing research, risk management, etc. every year in accordance with the provisions of the SDA.
The holder of the vaccine marketing license shall submit an annual report to the SDA in accordance with the relevant provisions.
Article 40 Holders of drug marketing licenses shall continue to evaluate and control the risks and benefits of drugs, formulate post marketing drug risk management plans, actively carry out post marketing research, further verify the safety, effectiveness and quality controllability of drugs, and strengthen the continuous management of drugs already on the market.
Article 41 Holders of drug marketing licenses shall establish a pharmacovigilance system and carry out pharmacovigilance work in accordance with the pharmacovigilance quality control standards formulated by the SDA.
The holder of the drug marketing license and the drug producing enterprise shall regularly inspect the drug quality, efficacy and adverse reactions of their own units. If any suspected adverse reaction is found, it shall be reported in a timely manner as required.
Article 42 Where a holder of a drug marketing license entrusts the production of drugs, it shall comply with the relevant provisions on drug administration.
Where a holder of a drug marketing license entrusts a qualified drug manufacturing enterprise to produce drugs, it shall evaluate the quality assurance ability and risk management ability of the entrusted party, sign a quality agreement and an entrustment agreement with the entrusted party in accordance with the requirements of the Guidelines for Drug Entrusted Production Quality Agreements formulated by the SDA, and supervise the entrusted party to perform its obligations under the relevant agreements.
The entrusted party shall not entrust the entrusted drugs to a third party for production again.
The API that has been approved or passed the related review and approval shall be produced by itself, and may not be commissioned to produce by others.
Article 43 The holder of the drug marketing license shall manage and control the changes in the production process in accordance with the requirements of the Good Manufacturing Practice for Drugs, and formulate the process procedures according to the approved production process. Production process changes shall be studied, approved, filed or reported according to law, and subject to the supervision and inspection of the drug regulatory department.
Article 44 The holder of the drug marketing license and the drug manufacturing enterprise shall annually review, analyze and record the product quality of the drugs produced according to their varieties, so as to confirm the stability and reliability of the process and the applicability of the current quality standards for raw materials, auxiliary materials and finished products.
Article 45 In case of any change in the organization, the person in charge of the enterprise, the person in charge of production, the person in charge of quality and the person authorized for quality, the registration shall be completed within 30 days from the date of the change.
The holder of the vaccine marketing license shall, within 15 days from the date of change, report to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where it is located the change of the person in charge of production, the person in charge of quality, the person authorized for quality and other key positions.
Article 46 If the holder of the drug marketing license stops the production of the drugs listed in the list of drugs in short supply for which the production suspension report is implemented by the State, he shall report to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where he is located six months before the planned production suspension is implemented; If unexpected production stoppage occurs, it shall be reported to the drug regulatory department of the province, autonomous region or municipality directly under the Central Government within three days. If necessary, report to the SDA.
After receiving the report, the drug regulatory department shall promptly notify the leading unit of the linkage mechanism for the consultation of the drug supply assurance work in shortage at the same level.
Article 47 If the holder of the drug marketing license is an overseas enterprise, it shall designate an enterprise legal person within the territory of China to perform the obligations of the holder of the drug marketing license as stipulated in the Drug Administration Law and these Measures, and be responsible for coordinating and cooperating with the overseas inspection work.
Article 48 Where the production site of a holder of a drug marketing license is located abroad, it shall organize production in accordance with the provisions of the Drug Administration Law and these Measures, and cooperate with the overseas inspection work.

Chapter IV Supervision and Inspection

Article 49 The pharmaceutical supervisory and administrative departments of provinces, autonomous regions and municipalities directly under the Central Government shall be responsible for the supervision and administration of the holders of drug marketing licenses and the manufacturers of pharmaceutical preparations, chemical raw materials and prepared slices of traditional Chinese medicine within their respective administrative regions.
The pharmaceutical supervisory and administrative departments of provinces, autonomous regions and municipalities directly under the Central Government shall conduct daily supervision and inspection of suppliers and manufacturers of raw materials, auxiliary materials, packaging materials and containers that directly contact drugs, and carry out extended inspections when necessary.
Article 50 If the holder of the drug marketing license and the entrusted production enterprise are not in the same province, autonomous region or municipality directly under the Central Government, the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where the holder of the drug marketing license is located shall be responsible for the supervision and administration of the holder of the drug marketing license, and the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where the entrusted production enterprise is located shall be responsible for the supervision and administration of the entrusted production enterprise. The drug regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government shall strengthen the mutual notification of supervision and inspection information, update the supervision and inspection information to the drug safety credit archives in a timely manner, carry out investigation according to the notification and the update of the regulatory information in the drug safety credit archives, and make administrative treatment to the drug marketing license holders or entrusted manufacturing enterprises according to law, and conduct joint inspection when necessary.
Article 51 Pharmaceutical supervisory and administrative departments shall establish and improve the system of professional and specialized inspectors, define the qualification standards, inspection responsibilities, hierarchical management, ability training, code of conduct, performance evaluation and exit procedures of inspectors, and improve the professional quality and work level of inspectors. Inspectors shall be familiar with drug laws and regulations and have professional knowledge of drugs.
The pharmaceutical supervisory and administrative department shall, in accordance with the regulatory authority, the scale of the pharmaceutical industry and the inspection tasks, provide an adequate team of inspectors to meet the needs of the inspection work. In areas where there are manufacturers of high-risk drugs such as vaccines, a corresponding number of drug inspectors with inspection skills and experience of high-risk drugs such as vaccines should also be assigned.
Article 52 The pharmaceutical supervisory and administrative departments of provinces, autonomous regions and municipalities directly under the Central Government shall, according to the needs of supervision, conduct pre marketing inspection on the conformity of pharmaceutical production quality control specifications for applicants for drug marketing licenses and their entrusted manufacturing enterprises who hold pharmaceutical production licenses according to the following requirements:
(1) For varieties that fail to pass the inspection on the conformity of the drug production quality control standards that are suitable for the production conditions of the drug, the pre marketing inspection on the conformity of the drug production quality control standards shall be carried out. Where on-site verification of drug registration is required for drugs to be produced, the Drug Evaluation Center of the State Drug Administration shall notify the verification center and inform the drug regulatory departments and applicants of relevant provinces, autonomous regions and municipalities directly under the Central Government. The Inspection Center shall coordinate with the drug regulatory departments of relevant provinces, autonomous regions and municipalities directly under the Central Government to carry out the on-site inspection of drug registration and the compliance inspection of drug production quality management specifications before marketing at the same time;
(2) If it is not necessary to conduct on-site verification of drug registration for the proposed drugs, the Drug Evaluation Center of the SDA shall inform the drug regulatory departments and applicants of the provinces, autonomous regions, and municipalities where the production sites are located, and the drug regulatory departments of the relevant provinces, autonomous regions, and municipalities directly under the Central Government shall conduct their own pre marketing inspection on the compliance of drug production quality management specifications;
(3) For the varieties that have passed the compliance inspection of the drug production quality control specifications that are suitable for the production conditions of the drug, the drug regulatory department of the relevant province, autonomous region, or municipality directly under the Central Government shall decide whether to carry out the pre marketing compliance inspection of the drug production quality control specifications according to the risk management principle.
Where a pre marketing inspection on the conformity of drug production quality management specifications is carried out, a written report on the inspection results shall be prepared after the inspection, which shall serve as an important basis for the supervision of drug marketing. If the pre marketing inspection of the compliance of the drug production quality control specifications involves the change of the drug production license, the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government that originally issued the license shall make a decision in accordance with the change procedure.
The commercial batch that has passed the corresponding pre marketing compliance inspection of drug production quality management specifications can be marketed after obtaining the drug registration certificate and meeting the product release requirements. The holder of the drug marketing license shall focus on strengthening the production, sales, risk management and other measures of the above batches of drugs.
Article 53 The main contents of drug production supervision and inspection include:
(1) The implementation of relevant laws and regulations, the implementation of drug production quality management specifications, pharmacovigilance quality management specifications and relevant technical specifications by drug marketing license holders and drug manufacturers;
(2) Whether the drug production activities are consistent with the relevant contents specified in the drug variety archives;
(3) Implementation of vaccine storage and transportation management specifications;
(4) Pharmaceutical consignment production quality agreement and consignment agreement;
(5) Implementation of risk management plan;
(6) Change management.
Supervision and inspection include permission inspection, routine inspection, cause inspection and other inspections.
Article 54 The drug regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government shall adhere to the principle of risk management and full process control, formulate annual inspection plans and carry out supervision and inspection according to the risk study and judgment. The annual inspection plan shall at least include the inspection scope, content, method, focus, requirements, time limit, and the organization undertaking the inspection.
Article 55 The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the Central Government shall determine the inspection frequency according to the characteristics of drug varieties, dosage forms, and control categories, in combination 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 previous inspections, inspections, adverse reaction monitoring, complaints and reports, etc.:
(1) The production enterprises of narcotic drugs, Category I psychotropic drugs and pharmaceutical precursor chemicals shall be inspected at least once a quarter;
(2) For manufacturers of high-risk drugs such as vaccines, blood products, radioactive drugs, toxic drugs for medical use, sterile drugs, etc., the compliance of drug production quality management specifications shall be checked at least once a year;
(3) For pharmaceutical manufacturers other than the above products, a certain proportion of them shall be selected each year for supervision and inspection, but all enterprises within their respective administrative regions shall be inspected within three years;
(4) Suppliers and manufacturers of raw materials, auxiliary materials, packaging materials and containers that directly contact drugs shall be subject to supervision and inspection at a certain proportion every year, and all enterprises in their own administrative areas shall be inspected within five years.
The drug regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government may adjust the frequency of inspection in light of the actual situation of drug production supervision within their respective administrative regions.
Article 56 When the SDA and the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the Central Government organize supervision and inspection, they shall formulate inspection plans, specify inspection standards, and truthfully record the on-site inspection. If sampling inspection or research is needed, the relevant provisions shall apply. The inspection conclusion shall be clear and definite, and the inspected unit shall be informed of the problems found in the inspection in writing. If rectification is required, the rectification content and rectification period shall be proposed, and the situation after rectification shall be checked if necessary.
When conducting supervision and inspection, the drug regulatory department shall assign more than two inspectors to conduct supervision and inspection, and the inspectors shall show the law enforcement certificates to the inspected unit. The staff of the drug regulatory department shall keep confidential the trade secrets they know.
Article 57 During the supervision and inspection, the holder of the drug marketing license and the drug manufacturing enterprise shall explain the situation and provide relevant materials according to the needs of the inspection:
(1) Drug production site management documents and change materials;
(2) The implementation of supervision, inspection and rectification by drug manufacturers;
(3) Handling of unqualified drugs;
(4) Pharmacovigilance institutions, personnel, system formulation and monitoring, identification, evaluation and control of suspected adverse drug reactions;
(5) Materials on the implementation of conditional approval of varieties and post marketing research;
(6) Other necessary materials to be reviewed.
Article 58 After the on-site inspection is completed, the on-site inspection shall be analyzed and summarized, and the defects found in the inspection shall be objectively, fairly and impartially assessed for risk, and the on-site inspection conclusion shall be drawn.
The dispatched unit shall be responsible for the comprehensive study and judgment of the on-site inspection conclusions.
Article 59 Where the SDA and the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the Central Government, through supervision and inspection, find defects in the management of drug production or vaccine storage and transportation, and there is evidence to prove that there may be potential safety hazards, they shall take corresponding measures according to law:
(1) If it basically meets the requirements of drug production quality management specifications and needs to be rectified, a warning letter shall be issued and corresponding measures such as warning, interview and rectification within a time limit shall be taken according to risks;
(2) If there are quality problems or other potential safety hazards in drugs, the drug regulatory department shall issue a warning letter according to the supervision and inspection, and take control measures such as suspension of production, sales, use and import according to the risk.
Where a drug has quality problems or other potential safety hazards, if the holder of the drug marketing license should recall the drug according to law but fails to recall it, the drug regulatory department of the province, autonomous region or municipality directly under the Central Government shall order it to recall.
After the risk is eliminated, the drug regulatory department that takes control measures shall remove the control measures.
Article 60 In the course of drug production supervision and inspection, if any risk of drug quality and safety is found, it shall be reported to the sending unit in a timely manner. If the drug regulatory department determines that the risk is a major drug quality and safety risk, it shall promptly report to the drug regulatory department at the next higher level and the local people's government at the same level.
Article 61 In the process of drug production supervision and inspection, if any suspected violation of drug laws, regulations and rules is found, on-site control measures shall be taken in a timely manner, and evidence collection shall be carried out in accordance with regulations. The drug regulatory department shall investigate and deal with according to its duties and powers, and transfer the suspected crimes to the public security organ for handling.
Article 62 The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the Central Government shall, according to law, incorporate the regulatory information of the holders of drug marketing licenses and drug manufacturing enterprises within their respective administrative areas into the drug safety credit archives for management, and keep the relevant data updated dynamically. Regulatory information includes drug production license, daily supervision and inspection results, investigation and handling of illegal acts, random inspection of drug quality, records of bad behaviors, complaints and reports, etc.
Article 63 The SDA and the pharmaceutical supervisory and administrative departments of provinces, autonomous regions, and municipalities directly under the Central Government shall not interfere with the normal production activities of the holders of drug marketing licenses and pharmaceutical producing enterprises, ask for or accept money or property, or seek other benefits in the course of production supervision and administration.
Article 64 Individuals and organizations who find that drug marketing license holders or drug producing enterprises are engaged in illegal production activities have the right to report to the drug regulatory department, which shall verify and deal with them in a timely manner in accordance with relevant provisions.
Article 65 In the event of a major safety incident related to drug quality, the holder of the drug marketing license shall immediately take control measures such as sealing up the relevant drugs and their raw materials, excipients, packaging materials and containers that directly contact the drugs, and relevant production lines, and immediately report to the drug regulatory department and relevant departments of the province, autonomous region, or municipality directly under the Central Government where they are located The drug regulatory department of the municipality directly under the Central Government shall report to the people's government at the provincial level within 24 hours and to the SDA at the same time.
Article 66 The drug regulatory departments of provinces, autonomous regions, and municipalities directly under the Central Government shall increase the frequency of supervision and inspection on drug marketing license holders and drug producing enterprises with bad credit records, and may impose joint punishments in accordance with State regulations.
Article 67 If the drug regulatory department of a province, autonomous region, or municipality directly under the Central Government fails to timely discover the systemic risks of drug safety in the production link, or to timely eliminate the hidden dangers of drug safety in the area under supervision and administration, or if the people's government at the provincial level fails to perform its drug safety duties, or to timely eliminate the major regional hidden dangers of drug safety, the SDA shall interview its principal responsible persons.
The drug regulatory department of the province, autonomous region or municipality directly under the Central Government and the local people's government interviewed shall immediately take measures to rectify the drug regulatory work.
The interview and rectification shall be included in the review and assessment records of the drug supervision and administration of the provinces, autonomous regions and municipalities directly under the Central Government and the local people's governments.

Chapter V Legal Liabilities

Article 68 Under any of the following circumstances, a penalty shall be imposed in accordance with Article 115 of the Drug Administration Law:
(1) The holder of the drug marketing license and the drug manufacturing enterprise shall obtain approval for changing the production address and scope of production without obtaining approval;
(2) The drug production license is still in production after the expiry date.
Article 69 If the holder of the drug marketing license and the drug manufacturing enterprise fail to produce in accordance with the requirements of the quality control standards for drug production, and have any of the following circumstances, which are serious as stipulated in Article 126 of the Drug Administration Law, they shall be punished according to law:
(1) No special person in charge of quality is assigned to independently take charge of drug quality management and supervise the implementation of quality management specifications;
(2) The holder of the drug marketing license is not equipped with a special quality authorized person to perform the drug marketing release responsibility;
(3) The drug manufacturing enterprise is not equipped with a special quality authorized person to perform the responsibility of drug ex factory release;
(4) The quality management system cannot operate normally, and the records and data of drug production process control and quality control are untrue;
(5) Failure to take effective risk control measures for identified risks in a timely manner, and failure to ensure product quality;
(6) Other serious violations of drug production quality management standards.
Article 70 If the manufacturing enterprises and suppliers of auxiliary materials, packaging materials and containers that directly contact drugs fail to comply with the relevant requirements of the quality management standards formulated by the SDA, and cannot ensure the continuous compliance of the quality assurance system, the drug regulatory departments of the provinces, autonomous regions and municipalities directly under the Central Government where they are located shall punish them in accordance with the provisions of Article 126 of the Drug Administration Law.
Article 71 In any of the following circumstances, the drug regulatory department of the province, autonomous region or municipality directly under the Central Government where the holder of the drug marketing license or the drug producing enterprise is located shall impose a fine of not less than 10000 yuan but not more than 30000 yuan:
(1) The name, domicile (business site) and legal representative of the enterprise fail to change the registered items as required;
(2) Failing to conduct annual health examination and establish health records for staff directly exposed to drugs as required;
(3) Failing to make a production suspension report on the drugs listed in the list of drugs in short supply for which the production suspension report is implemented by the State in accordance with the provisions.
Article 72 If a pharmaceutical supervisory and administrative department commits any of the following acts, the directly responsible person in charge and other directly responsible persons shall be punished in accordance with Article 149 of the Pharmaceutical Administration Law:
(1) Concealed, false, delayed or omitted drug safety incidents;
(2) Failing to promptly investigate and deal with the drug safety violations found;
(3) Failing to discover the systemic risks of drug safety in a timely manner, or failing to eliminate the hidden dangers of drug safety in the supervision and management area in a timely manner, causing serious impact;
(4) Other persons who fail to perform their duties of drug supervision and administration, causing serious adverse effects or heavy losses.

Chapter VI Supplementary Provisions

Article 73 The time limit stipulated in these Measures shall be calculated in working days. The time required for technical review and assessment, on-site inspection and enterprise rectification in drug production license shall not be included in the period.
Article 74 Site management documents refer to the summary documents of pharmaceutical production activities prepared by pharmaceutical manufacturers, which are part of the quality management document system of pharmaceutical manufacturers. Relevant requirements of site management documents shall be formulated separately.
The APIs, excipients and packaging materials directly in contact with drugs, container production sites and overseas production sites that have been approved or reviewed through related review and approval shall be given a unified code.
Article 75 A warning letter refers to a letter issued by a drug regulatory department according to law in the course of drug regulatory activities, where there is evidence to prove that there may be potential safety hazards. The warning letter shall specify the existing defects, problems and rectification requirements.
Article 76 The number format of the drug production license is "province abbreviation+four digit year number+four digit serial number". The number of the original drug production license will remain unchanged if the enterprise changes its name or issues a new license.
When an enterprise is divided, a new number shall be added while the original drug production license number is retained. In case of business merger, one original drug production license number shall be retained.
Article 77 The classification code is an English letter string for statistical classification of the production scope within the license. Capital letters are used to classify the drug marketing license holders and product types, including: A represents the drug marketing license holders of self production, B represents the drug marketing license holders of entrusted production, C represents the entrusted drug manufacturers, and D represents the API manufacturers; The lowercase letters are used to distinguish the properties of preparations. h stands for chemical drugs, z stands for Chinese patent drugs, s stands for biological products, d stands for in vitro diagnostic reagents managed by drugs, y stands for herbal pieces, q stands for medical gases, t stands for special drugs, and x stands for others.
Article 78 The scope of production of the drug production license shall be filled in accordance with the requirements of the General Principles of Preparations in the Pharmacopoeia of the People's Republic of China and other national drug standards.
Article 79 Where the relevant laws and regulations of the State provide otherwise for the production of vaccines, blood products, narcotic drugs, psychotropic substances, toxic drugs for medical use, radioactive drugs, pharmaceutical precursor chemicals, etc., such provisions shall prevail.
Article 80 Vaccines exported shall meet the standards or contractual requirements of the importing country (region).
Article 81 The Measures shall come into force as of July 1, 2020. On August 5, 2004, the Measures for the Supervision and Administration of Drug Production promulgated by Order No. 14 of the former State Food and Drug Administration shall be repealed at the same time.

 

 

 

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