Products & Services
Drug Manufacturing Supervision and Administration Measures
2023-04-27
The Measures for the Supervision and Administration of Pharmaceutical Production was considered and adopted at the 1st Bureau Meeting of 2020 of the State Administration of Market Supervision and Administration (SAMSA) on 15 January 2020, and is hereby promulgated and shall come into force from 1 July 2020 onwards.
Xiao Yaqing, Director General
22nd January 2020
Measures for the Supervision and Administration of Pharmaceutical Production
(Published on 22 January 2020 by Order No. 28 of the State Administration for Market Supervision and Administration)
Chapter I General Provisions
Article 1 In order to strengthen the supervision and management of drug production and regulate drug production activities, according to 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 and administrative regulations, the formulation of these measures.
Article 2 The production and supervision and management activities of medicines listed in the territory of the People's Republic of China shall comply with these Measures.
Article 3 engaged in pharmaceutical production activities, shall comply with laws, regulations, rules, standards and norms to ensure that the whole process of information is true, accurate, complete and traceable.
Engaged in drug production activities, should be approved by the local provincial, autonomous regions and municipalities directly under the Central Drug Administration, according to the law to obtain a drug production licence, strict compliance with the quality management standards for drug production, to ensure that the production process continues to meet the statutory requirements.
The holder of a listed drug licence shall establish a drug quality assurance system, fulfil the responsibility of releasing drugs to the market, and be responsible for the quality of the drugs for which it has obtained a certificate of drug registration.
Manufacturers of Chinese medicine tablets shall fulfil the relevant obligations of the holder of the listed drug licence to ensure that the production process of Chinese medicine tablets continues to meet the statutory requirements.
API manufacturers shall organise production in accordance with the approved production process, strictly comply with the Good Manufacturing Practice, and ensure that the production process continues to meet the statutory requirements.
The manufacturers of excipients, packaging materials and containers in direct contact with medicines, as well as other units and individuals engaged in production activities related to medicines, which have been reviewed by association, shall bear the corresponding responsibilities in accordance with the law.
Article IV drug marketing licence holders, drug manufacturers should establish and implement a drug traceability system, in accordance with the provisions of the drug sales at all levels of packaging unit traceability marking, the implementation of drug traceability through information technology, timely and accurate records, preservation of drug traceability data, and drug traceability to the collaborative service platform to provide traceability information.
Article 5 The State Drug Administration in charge of national drug production supervision and management work, the provinces, autonomous regions and municipalities directly under the Central Drug Administration supervision and management of drug production supervision and management work to supervise and guide.
Provinces, autonomous regions, municipalities directly under the Central Drug Administration is responsible for the supervision and management of drug production in the administrative region, bear the production of drugs in the process of licensing, inspection and punishment.
State Drug Administration Food and Drug Audit and Inspection Center (hereinafter referred to as the Verification Center) organization to formulate technical specifications and documents for drug inspections, undertake inspections outside the country as well as the organization of vaccine inspections, etc., analysis and assessment of the risks found in the inspection, make inspection conclusions and put forward proposals for the disposal of provinces, autonomous regions and municipalities directly under the central government is responsible for drug inspection agencies quality management system guidance and assessment.
The Information Centre of the State Drug Administration is responsible for the collaborative service platform for drug traceability, the construction and management of drug safety credit files, and the unified coding of drug production sites.
Drug supervision and management departments set up or designated by law, such as drug evaluation, inspection, verification, monitoring and evaluation of professional and technical institutions, in accordance with their duties to undertake the relevant technical work and issue technical conclusions for the supervision and management of drug production to provide technical support.
Chapter II Production Licensing
Article VI engaged in the production of drugs, shall meet the following conditions:
(a) there are qualified according to law, pharmacy technicians, engineers and corresponding skilled 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 of the authorised person and other relevant personnel in line with the "Drug Administration Law" "Vaccine Administration Law" stipulates the conditions;
(ii) There are plants, facilities, equipment and hygienic environments suitable for drug production;
(C) There are organisations and personnel who can carry out quality management and quality inspection of the drugs produced;
(D) Have the necessary instruments and equipment for quality management and quality inspection of the drugs produced;
(E) have regulations to ensure the quality of drugs, and in line with the requirements of the Good Manufacturing Practice.
Engaged in vaccine production activities, should also have the following conditions:
(A) have a moderate scale and sufficient capacity reserves;
(ii) Have systems and facilities and equipment to ensure biological safety;
(C) in line with disease prevention and control needs.
Article VII engaged in the preparation, raw materials, traditional Chinese medicine production activities, the applicant shall, in accordance with these measures and the State Drug Administration of the information required to declare the location of the provincial, autonomous regions, municipalities directly under the central drug supervision and management department to submit an application.
Commissioned the production of preparations of pharmaceutical products listed on the licence holder, should have the first paragraph of Article 6, paragraph 1, paragraph 1, paragraph 3, paragraph 5 of the conditions set out in these measures, and qualified drug manufacturers to sign a commissioning agreement and quality agreement, the relevant agreement and the actual production site application information submitted to the pharmaceutical products listed on the licence holder of the province, autonomous region, municipality directly under the central government drug supervision and management department, in accordance with the provisions of these measures Provisions of the application for drug production licence.
The applicant shall be responsible for the authenticity of all the application materials.
Article 8 Provinces, autonomous regions, municipalities directly under the Central Drug Administration received the application, shall be dealt with in accordance with the following circumstances:
(A) the application does not belong to the department's terms of reference, shall immediately make a decision of inadmissibility, and inform the applicant to the relevant administrative organs;
(B) the application does not need to obtain administrative licences according to law, the applicant shall be immediately informed of inadmissibility;
(C) application materials there can be corrected on the spot error, the applicant should be allowed to correct on the spot;
(D) application materials are incomplete or do not meet the formal review requirements, shall be issued on the spot or within five days to the applicant to correct the material notice, a one-time notification to the applicant needs to make corrections to all the contents of the late notification, since the date of receipt of the application materials shall be accepted;
(E) application materials are complete, meet the formal review requirements, or the applicant in accordance with the requirements to submit all corrective materials, be accepted.
Provinces, autonomous regions, municipalities directly under the Central Drug Administration to accept or reject the application for a drug production licence, shall issue the department stamped and dated notice of acceptance or notification of inadmissibility.
Article IX provinces, autonomous regions and municipalities directly under the Central Drug Administration shall, within thirty days from the date of acceptance, make a decision.
After reviewing the regulations, be approved, and from the date of written approval of the decision within ten days from the date of issuance of the drug production licence; does not meet the requirements of the written decision of disapproval, and the reasons.
Provinces, autonomous regions, municipalities directly under the Central Drug Administration in accordance with the relevant provisions of the Good Manufacturing Practice and other organisations to carry out the declaration of technical review and evaluation of information, on-site inspection.
Article 10 The drug administration department of the province, autonomous region or municipality directly under the central government shall make public on the website and office premises of the administrative organ the conditions, procedures and deadlines required for applying for a drug manufacturing licence, the catalogue of all the materials to be submitted and the model text of the application form.
Provinces, autonomous regions and municipalities directly under the Central Drug Administration issued by the drug manufacturing licence information shall be made public, the public has the right to access.
Article XI provinces, autonomous regions and municipalities directly under the Central Drug Administration for the application for drug production licence review, shall make public the results of the approval, and provide conditions to facilitate the applicant to query the approval process.
Without the consent of the applicant, the drug supervision and management departments, professional and technical institutions and their staff shall not disclose the applicant submitted commercial secrets, undisclosed information or confidential business information, except as otherwise provided by law or involving national security, major social and public interests.
Article 12 Where the application for a drug manufacturing licence directly involves a significant interest relationship between the applicant and others, the applicant and the interested party shall enjoy the right to apply for a hearing in accordance with the provisions of laws and regulations.
In reviewing the application of a drug manufacturer, the drug administration department of a province, autonomous region or municipality directly under the central government shall make a public announcement and hold a hearing if it believes that public interest is involved.
Article XIII of the drug production licence is valid for five years, divided into the original and copies. Drug production licence style by the State Drug Administration unified development. Drug production licence electronic certificate and paper certificate has the same legal effect.
Article 14 The drug production license shall contain the license number, classification code, enterprise name, unified social credit code, residence (place of business), legal representative, responsible person for the enterprise, the person in charge of production, the person in charge of quality, the quality of the authorized person, production address and production range, the issuing authority, the date of issuance of the license, the expiry date of validity and other items.
Enterprise name, unified social credit code, residence (place of business), legal representative and other items should be consistent with the market supervision and management department issued business licence contained in the relevant content.
Article XV of the drug production licence is divided into licensing matters and registration matters.
Licensing matters refers to the production address and production scope.
Registration matters refers to the enterprise name, residence (business premises), legal representative, the person in charge of the enterprise, the person in charge of production, the person in charge of quality, quality authorised person.
Article XVI of the drug production licence to change the licensing matters, to the original licensing authority to apply for a change in the drug production licence. Without approval, shall not change the licence matters.
The original licensing authority shall receive a change in the enterprise within fifteen days from the date of application to make a decision on whether to grant the change. Do not change, shall state the reasons in writing, and inform the applicant of the right to apply for administrative reconsideration or administrative litigation according to law.
Change of production address or production scope, drug manufacturers should be in accordance with the provisions of Article 6 of these Measures and related changes in the technical requirements, submitted to the content of the change involves the relevant materials, and reported to the seat of the provinces, autonomous regions and municipalities directly under the Central Drug Administration to review the decision.
The original location or off-site new construction, alteration, expansion of the workshop or production line, should be in line with the relevant provisions and technical requirements, submitted to the content of the change involves the relevant materials, and reported by the local provinces, autonomous regions and municipalities directly under the Central Drug Administration for drug production quality management specification compliance inspection, the results of the inspection shall be notified to the enterprise. Inspection results in line with the provisions of the product in line with the release requirements can be marketed and sold. The relevant changes should be set out in the copy of the drug production licence.
The above changes relate to the certificate of registration of drugs and its annexes to the content, by the provinces, autonomous regions and municipalities directly under the Central Drug Administration for approval, reported to the State Drug Administration Drug Evaluation Centre to update the certificate of registration of drugs and its annexes to the relevant content.
Article XVII changes in the registration of drug production license, should be approved by the market supervision and management departments to change or change after the completion of the enterprise within thirty days, to the original licensing authority to apply for a change in the registration of drug production license. The original licensing authority shall, within ten days from the date of receipt of the enterprise change application for change.
Article 18 After the change of the drug production license, the original licensing authority shall record the content and time of the change in the copy of the drug production licence, and in accordance with the changed content of the original drug production licence reissued, the original drug production licence is withdrawn, after the change of the termination of the termination of the drug production licence remains unchanged.
Article 19 The expiry of the validity of the drug production licence, the need to continue to produce drugs, should be six months before the expiry of the validity of the original licensing authority to apply for re-issuance of the drug production licence.
The original licensing authority in conjunction with the enterprise to comply with drug laws and regulations, drug production quality management standards and quality system operation, based on the principle of risk management review, the expiry of the validity of the drug production licence to make a decision on whether to grant its re-issuance. In accordance with the provisions of the re-issuance of the permit, the original permit is withdrawn, re-issuance; does not comply with the provisions of the written decision not to re-issue the permit, and explain the reasons, and inform the applicant of the right to apply for administrative reconsideration or administrative litigation in accordance with the law; overdue decision is deemed to agree to re-issue of the permit, and to make up for the corresponding formalities.
Article 20 In one of the following cases, the drug production licence shall be cancelled by the original issuing authority and shall be announced:
(A) the initiative to apply for cancellation of the drug production licence;
(B) the expiry of the validity of the drug production licence has not been reissued;
(C) business licence has been revoked or cancelled according to law;
(D) The drug production licence has been suspended or revoked according to law;
(E) laws and regulations shall be cancelled administrative licensing of other circumstances.
Article 21 of the drug production license is lost, the holder of the listed drug license, drug manufacturers shall apply to the original licensing authority to reissue, the original licensing authority in accordance with the original approved matters within ten days to reissue the drug production licence. The licence number and validity period shall be the same as the original licence.
Article 22 No unit or individual shall not forge, alter, rent, lend, buy or sell drug production licences.
Article 23 The provinces, autonomous regions and municipalities directly under the Central Drug Administration shall issue, re-issue, change, reissue, revocation, cancellation, cancellation of drug production licences, etc., within ten days after the completion of the processing work in the drug safety credit file updated.
Chapter III Production Management
Article 24 Engaged in pharmaceutical production activities, shall comply with the quality management standards for drug production, in accordance with national drug standards, drug registration standards approved by the drug regulatory authorities and production processes, in accordance with the provisions of the submission and continuous updating of site management documents, risk assessment and continuous improvement of the quality system operation process, to ensure that the entire process of drug production continues to meet the statutory requirements. Production, inspection and other records shall be complete and accurate, and shall not be fabricated or tampered with.
Article 25 The holder of a listed vaccine license shall have vaccine production, inspection of necessary plant facilities and equipment, with qualified management personnel, the establishment of a sound quality management system, with the production of vaccines in line with the requirements of the registration of the ability to exceed the vaccine production capacity of the commissioned production, shall be approved by the State Drug Administration.
Article 26 engaged in pharmaceutical production activities, shall comply with the Good Manufacturing Practice, the establishment of a sound quality management system for drug production, covering all factors affecting the quality of medicines, to ensure that the entire process of drug production continues to meet the statutory requirements.
Article 27 The holder of the marketing authorisation for pharmaceutical products shall establish a pharmaceutical quality assurance system, with special personnel independently responsible for the quality management of pharmaceutical products, the entrusted pharmaceutical production enterprises, pharmaceutical business enterprises quality management system for regular audit, supervision of its continued quality assurance and control capabilities.
Article 28 The legal representative and principal person in charge of the holder of the listed drug licence shall be fully responsible for the quality of the drug, and shall perform the following duties:
(a) To have a special quality person independently responsible for the quality management of medicines;
(B) equipped with special quality authorised person independently performs the responsibility of drug listing and release;
(C) Supervise the normal operation of the quality management system;
(d) Conducting regular quality system audits of the activities of drug manufacturers, suppliers and other relevant parties related to drug production to ensure continuous compliance;
(E) In accordance with the technical requirements for change, to fulfil the responsibility of change management;
(vi) Conducting quality assessment of commissioned enterprises and communicating information with users and other units;
(vii) Cooperate with the drug regulatory authorities in the extended inspection of the listed drug licence holders and related parties;
(viii) In the event of a major safety incident related to the quality of medicines, it shall promptly report and carry out risk management according to the risk management plan formulated by the holder to ensure that the risk is controlled in a timely manner;
(IX) other laws and regulations of the responsibility.
Article 29 The legal representative and main person in charge of the pharmaceutical production enterprise shall be fully responsible for the enterprise's pharmaceutical production activities, and perform the following duties:
(a) To equip special quality person in charge independently responsible for the quality management of drugs, supervise the implementation of quality management standards, ensure proper production process control and quality control, and ensure that the drugs comply with the national drug standards and drug registration standards;
(ii) Equipped with special quality authorised person to perform the responsibility of drug factory release;
(iii) Supervise the normal operation of the quality management system to ensure proper production process control and quality control as well as the authenticity of records and data of the pharmaceutical products;
(D) Occurrence of major safety incidents related to drug quality, should be promptly reported and risk management plan developed by the enterprise to carry out risk disposal, to ensure that the risk is controlled in a timely manner;
(E) Other responsibilities stipulated by laws and regulations.
Article 30 The holder of the listed drug licence and the drug manufacturer shall conduct annual health checks and establish health records for the staff in direct contact with the drugs, and avoid personnel suffering from infectious diseases or other diseases that may contaminate the drugs from engaging in production activities in direct contact with the drugs.
Article 31 In the production of medicines, the holder of the marketing authorisation for medicines and the pharmaceutical manufacturer shall carry out quality management activities such as risk assessment, control, validation, communication and audit, and take timely and effective risk control measures for the identified risks in order to ensure the quality of the products.
Article 32 Engaged in drug production activities, should be used for raw materials, excipients, packaging materials and containers in direct contact with the drug and other related materials suppliers or manufacturers to audit, to ensure that the purchase and use in accordance with regulatory requirements.
The raw materials and excipients required for the production of drugs should meet the requirements for medicinal use and the relevant requirements of the corresponding production quality management standard. Packaging materials and containers that are in direct contact with drugs shall comply with the requirements for medicinal use and the standards for safeguarding human health and safety.
Article 33 The approval or through the associated review and approval of raw materials, excipients, direct contact with pharmaceutical packaging materials and containers of the manufacturer, shall comply with the State Drug Administration to develop quality management standards and associated review and approval of the relevant requirements to ensure that the quality assurance system continues to be compliant with the quality audit of the holder of the marketing authorisation of the drug to accept the quality of the audit, acceptance of drug supervision and management supervision and management of the department of supervision and inspection or extension of the inspection. Inspection.
Article 34 The drug manufacturer shall determine the confirmation and verification to be carried out, and implement them in accordance with the confirmation and verification plan. Regularly evaluate the facilities, equipment, production processes and cleaning methods to confirm that they continue to maintain the validation status.
Article 35 The drug manufacturing enterprise shall adopt control measures to prevent contamination, cross-contamination, confusion and errors, and regularly check and assess the applicability and effectiveness of the control measures to ensure that the drugs meet the prescribed national drug standards and drug registration standards, and comply with the requirements of the Good Manufacturing Practice.
The holder of the listed drug licence and the drug manufacturer shall not produce other products in the drug production plant that adversely affect the quality of the drug.
Article 36 Drug packaging operations shall take measures to reduce the risk of confusion and error, and drug packaging shall ensure that drugs within the validity period are not contaminated during storage and transport.
The expressions in the instructions and labels of medicines shall be scientific, standardised and accurate, and the text shall be clear and legible, and shall not be modified or supplemented by means of pasting, cutting, or alteration.
Article 37 Drug manufacturers shall establish drug factory release procedures, specify the standards and conditions for factory release, and review the results of drug quality inspection, key production records and deviation control. If it meets the standards and conditions, it can be released from the factory only after signed by the quality authorised person.
The holder of the listed drug licence shall establish a procedure for the release of drugs on the market, and audit the test results and release documents of the drugs released from the factory of the drug manufacturer, and the drugs shall be released on the market only after the signature of the person authorised by the quality.
Chinese medicine tablets in line with national drug standards or provinces, autonomous regions and municipalities directly under the Central Drug Administration formulated concoction norms, before the factory, sales.
Article 38 The holder of the listed drug licence and the drug manufacturer shall carry out self-inspection every year to monitor the implementation of the quality management standard for drug production, assess whether the enterprise complies with the requirements of the relevant laws and regulations, and put forward the necessary corrective and preventive measures.
Article 39 The holder of a listed drug license shall establish an annual report system, in accordance with the provisions of the State Drug Administration to the provinces, autonomous regions and municipalities directly under the Central Drug Administration to report annually on the production and sale of drugs, post-marketing research, risk management and other situations.
Vaccine marketing licence holder shall, in accordance with the provisions of the State Drug Administration for annual reports.
Article 40 The holder of a listed drug license shall continue to carry out drug risk assessment and control, the development of post-marketing drug risk management plan, take the initiative to carry out post-marketing research on the safety, efficacy and quality of the drug can be controlled to further confirm, and strengthen the continuous management of listed drugs.
Article 41 The holder of a listed drug license shall establish a pharmacovigilance system, in accordance with the State Drug Administration developed pharmacovigilance quality management standards for pharmacovigilance work.
The holder of the listed drug licence, drug manufacturers should always examine the quality, efficacy and adverse reactions of the unit of the drug. If any suspected adverse reaction is found, it shall be promptly reported in accordance with the requirements.
Article 42 Where the holder of a listed drug licence commissions the production of a drug, it shall comply with the relevant provisions of drug administration.
The holder of a listed drug license entrusted to qualified drug manufacturers to produce drugs, should be entrusted to the quality assurance capabilities and risk management capabilities of the assessment, according to the State Drug Administration to develop the quality of the commissioned production of drugs and the requirements of the quality of the agreement with the commissioning of the agreement signed with the quality agreement and commissioning agreement to supervise the commissioned party to perform the obligations agreed upon in the relevant agreements.
The entrusted party shall not re-commission the production of the commissioned drugs to a third party.
APIs approved or approved through associated review and approval shall be produced by themselves and shall not be entrusted again.
Article 43 The holder of the listed drug licence shall manage and control the change of production process in accordance with the requirements of the Good Manufacturing Practice for Drugs and formulate the process protocols according to the approved production process. Changes in the production process shall carry out research and obtain approval, record or report in accordance with the law, and accept the supervision and inspection of the drug supervision and management department.
Article 44 The holder of the listed drug license, drug manufacturers shall annually review and analyse the quality of the products produced according to the varieties of the drugs produced, record, in order to confirm the stability and reliability of the process, as well as the applicability of raw materials, excipients, finished products of the current quality standards.
Article 45 The holder of a marketing authorisation for drugs, drug manufacturers of quality management system related to the organisational structure, the person in charge of the enterprise, the person in charge of production, the person in charge of quality, the quality of the person authorised to change, shall, within thirty days from the date of the change, complete the registration formalities.
The holder of a listed vaccine licence shall, within fifteen days from the date of change, report to the drug administration 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 in charge of quality, the person authorised by the quality and other key positions.
Article 46 Included in the national implementation of the shortage of drugs to report the list of drugs, drugs listed on the licence holder to stop production, should be six months before the implementation of the planned suspension of production to the seat of the provincial, autonomous regions, municipalities directly under the Central Drug Administration to report; unanticipated shutdown of the occurrence of three days to report to the seat of the provincial, autonomous regions, municipalities directly under the Central Drug Administration. If necessary, report to the State Drug Administration.
Upon receipt of the report, the drug supervision and administration department shall promptly notify the lead unit of the consultative joint mechanism for the supply and security of drugs in short supply at the same level.
Article 47 Where the holder of a listed drug licence is an overseas enterprise, it shall designate an enterprise corporation in China to perform the obligations of the holder of a listed drug licence as stipulated in the Drug Administration Law and these Measures, and shall be responsible for coordinating and cooperating with the overseas inspection work.
Article 48 Where the production site of the holder of the listed drug licence is outside China, the holder shall organise the 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 drug supervision and management departments of provinces, autonomous regions and municipalities directly under the Central Government shall be responsible for the supervision and management of the holders of marketing authorisations for pharmaceutical products, preparations, chemical raw materials, and traditional Chinese medicines and tablets manufacturers in the administrative region.
Provinces, autonomous regions, municipalities directly under the Central Drug Administration shall raw materials, excipients, packaging materials and containers in direct contact with the drugs and other suppliers, manufacturers to carry out routine supervision and inspection, and when necessary, to carry out extended inspection.
Article 50 Where the holder of the marketing authorisation for the medicine and the commissioned manufacturer are not in the same province, autonomous region or municipality directly under the central government, the drug supervision and management department of the province, autonomous region or municipality directly under the central government where the holder of the marketing authorisation for the medicine is located shall be responsible for the supervision and management of the holder of the listing authorisation for the medicine and the drug supervision and management department of the province, autonomous region or municipality directly under the central government where the commissioned manufacturer is located shall be responsible for the supervision and management of the commissioned manufacturer. Provinces, autonomous regions, municipalities directly under the Central Drug Administration shall strengthen supervision and inspection information mutual notification, timely supervision and inspection information updated to the drug safety credit file, can be based on the notification situation and drug safety credit file in the supervision and management of information updates to carry out investigations, the holder of the marketing authorisation of the drug or the commissioned production enterprise in accordance with the law to make administrative treatment, if necessary, can carry out joint inspections.
Article 51 The drug supervision and management department shall establish and improve the system of professional and specialised inspectors, clarify the qualification standards, inspection duties, grading and management, competence training, code of conduct, performance evaluation and exit procedures and other provisions of the inspectors, and improve the professional quality and working level of the inspectors. Inspectors should be familiar with drug laws and regulations and possess professional knowledge of drugs.
The drug supervision and management department shall, according to the supervisory authority, the scale of the drug industry and inspection tasks, equip an adequate team of inspectors to guarantee the needs of inspection work. Areas where there are vaccines and other high-risk drug manufacturers shall also be equipped with a corresponding number of drug inspectors with skills and experience in the inspection of vaccines and other high-risk drugs.
Article 52 The drug supervision and management departments of provinces, autonomous regions and municipalities directly under the Central Government shall, in accordance with the regulatory needs, carry out pre-market inspections of compliance with the Good Manufacturing Practice for pharmaceutical products in accordance with the following requirements for applicants for marketing authorisation of pharmaceutical products holding a pharmaceutical production licence and their commissioned manufacturing enterprises:
(a) not through the production of the drug with the production conditions of the drug production quality management standard compliance inspection of varieties, should be carried out before the listing of the drug production quality management standard compliance inspection. Among them, the proposed production of drugs need to carry out on-site verification of drug registration, the State Drug Administration Drug Evaluation Centre notified the Verification Centre to inform the relevant provinces, autonomous regions and municipalities directly under the Central Drug Administration and the applicant. Verification Centre to coordinate the relevant provinces, autonomous regions, municipalities directly under the Central Drug Administration, simultaneous on-site verification of drug registration and pre-market drug production quality management standard compliance checks;
(B) the proposed production of drugs do not need to carry out on-site verification of drug registration, the State Drug Administration Drug Evaluation Centre informed the production site where the province, autonomous region, municipality directly under the Central Drug Administration and the applicant, the relevant provinces, autonomous regions, municipalities directly under the Central Drug Administration to carry out their own pre-launch drug production quality management norms compliance checks;
(C) has passed with the production of the drug production quality management standard compliance inspection of varieties, the relevant provinces, autonomous regions and municipalities directly under the Central Drug Administration in accordance with the principle of risk management to decide whether to carry out pre-market drug production quality management standard compliance inspection.
To carry out pre-market drug production quality management standard compliance inspection, at the end of the inspection, the inspection situation, inspection results should be formed into a written report, as an important basis for the supervision of the listing of drugs. Pre-market drug production quality management standard compliance inspection involves changes in drug production licence matters, by the original license issued by the provincial, autonomous regions and municipalities directly under the Central Drug Administration in accordance with the change procedures to make a decision.
Commercial-scale batches that have passed the corresponding pre-market drug production quality management standard compliance inspection may be listed for sale after obtaining the drug registration certificate and meeting the product release requirements. The holder of the listed drug licence shall focus on strengthening the production and sales, risk management and other measures of the said batches of drugs.
Article 53 The main contents of drug production supervision and inspection include:
(1) The implementation of relevant laws and regulations and the implementation of the Good Manufacturing Practice for Drugs, the Good Manufacturing Practice for Pharmacovigilance and relevant technical specifications by the holders of the listed drug licences and the drug manufacturing enterprises;
(ii) Whether the drug production activities are consistent with the relevant contents contained in the drug variety files;
(C) the implementation of vaccine storage, transport management standards;
(iv) The quality agreement for commissioned production of drugs and the commissioning agreement;
(v) Implementation of risk management plan;
(vi) Change management.
Supervision and inspection include licensing inspection, routine inspection, inspection for cause and other inspections.
Article 54 Provinces, autonomous regions and municipalities directly under the Central Drug Administration shall adhere to the principle of risk management, control, according to the risk assessment, formulate annual inspection plans and carry out supervision and inspection. The annual inspection plan at least includes the scope of inspection, content, mode, focus, requirements, time limit, the institution undertaking the inspection.
Article 55 Provinces, autonomous regions and municipalities directly under the Central Drug Administration shall, according to the characteristics of drug varieties, dosage forms, control categories, etc., combined with the overall situation of national drug safety, drug safety risk warning information, major drug safety incidents and their investigation and handling of information, etc., as well as previous inspections, inspections, monitoring of adverse reactions, complaints and reports, etc., to determine the frequency of inspection:
(i) The inspection of enterprises manufacturing narcotic drugs, Class I psychotropic drugs and drug-type perishable chemicals shall be conducted not less than once per quarter;
(ii) For high-risk drug manufacturers of vaccines, blood products, radiopharmaceuticals, toxic drugs for medical use, sterile drugs and other high-risk drugs, no less than one inspection per year for compliance with the Good Manufacturing Practice;
(C) for drug manufacturers other than the above products, a certain percentage of the annual sampling to carry out supervision and inspection, but should be within three years of the administrative region of all enterprises to carry out inspections;
(D) of raw materials, excipients, packaging materials and containers in direct contact with drugs, such as suppliers, manufacturers to take a certain percentage each year to carry out supervision and inspection, within five years of the administrative region of all enterprises to carry out inspections.
Provinces, autonomous regions and municipalities directly under the Central Drug Administration can combine the actual situation of drug production supervision in the administrative region, adjust the frequency of inspection.
Article 56 The State Drug Administration and the provinces, autonomous regions, municipalities directly under the Central Drug Administration supervision and management departments to organize supervision and inspection, should develop inspection programs, clear inspection standards, truthful records of on-site inspection, the need for sample testing or research, in accordance with relevant regulations. Inspection conclusions should be clear, the problems found in the inspection should be informed in writing to the inspected unit. The need for rectification, should be proposed to rectify the content and rectification period, if necessary, the rectification of the situation after the implementation of the inspection.
Supervision and inspection, drug supervision and management departments should be assigned more than two inspectors to implement supervision and inspection, inspectors should be inspected units to show law enforcement documents. Drug supervision and management department staff of the known commercial secrets shall be kept confidential.
Article 57 During the supervision and inspection, the holder of the listed drug licence and the drug manufacturer shall explain the situation and provide relevant materials according to the inspection needs:
(A) drug production site management documents and change materials;
(B) Drug manufacturers to accept the supervision and inspection and rectification and implementation;
(iii) The handling of unqualified drug quality;
(D) Pharmacovigilance institutions, personnel, system development, as well as suspected adverse drug reactions monitoring, identification, assessment and control;
(E) implementation of conditional approval of varieties, to carry out post-marketing research materials;
(F) need to review other necessary materials.
Article 58 After the end of the on-site inspection, the on-site inspection shall be analysed and summarized, and objectively, fairly and impartially assess the risk of defects found in the inspection and make on-site inspection conclusions.
The sending unit is responsible for the on-site inspection conclusions for a comprehensive study.
Article 59 The State Drug Administration and the provinces, autonomous regions and municipalities directly under the Central Drug Administration through supervision and inspection found that there are defects in the management of drug production or vaccine storage, transport management, there is evidence that there may be a potential safety hazard, it should be taken in accordance with the corresponding measures:
(A) basically meet the requirements of the drug production quality management standards, the need for rectification, should be issued a letter of caution and based on the risk of corresponding to take caution, interview, deadline for rectification and other measures;
(B) the existence of quality problems or other safety hazards of drugs, drug supervision and management departments in accordance with the supervision and inspection, should be issued a letter of caution, and according to the risk of taking the appropriate suspension of production, sales, use, import and other control measures.
Drugs with quality problems or other hidden safety risks, the holder of the listed drug licence should be recalled in accordance with the law and not recalled, the provincial, autonomous regions and municipalities directly under the Central Drug Administration shall order its recall.
After the risk is eliminated, the drug supervision and management department taking control measures shall lift the control measures.
Article 60 In the process of drug production supervision and inspection, found that there is a risk of drug quality and safety, shall promptly report to the sending unit. Drug supervision and management department after research and judgement is a major drug quality and safety risks, should be promptly reported to the next level of drug supervision and management departments and local people's governments at the same level.
Article 61 To carry out drug production supervision and inspection process, found that there are suspected violations of drug laws, rules and regulations, shall promptly take on-site control measures, in accordance with the provisions of the evidence collection work. Drug supervision and management departments shall investigate and deal with in accordance with their duties and authority, suspected of committing a crime is transferred to the public security organs.
Article 62 Provinces, autonomous regions and municipalities directly under the Central Drug Administration shall, in accordance with the law, the administrative region of the holder of the marketing authorisation of drugs and drug manufacturers of regulatory information into the drug safety credit file management, and to maintain the dynamic update of the relevant data. Regulatory information including drug production permit, daily supervision and inspection results, investigation and handling of violations, drug quality sampling and testing, records of malpractice and complaints and reports.
Article 63 The State Drug Administration and the drug supervision and management departments of provinces, autonomous regions and municipalities directly under the Central Government in the production supervision and management work, shall not impede the normal production activities of the holder of the marketing authorisation of drugs, drug manufacturers, shall not solicit or accept property, and shall not seek other benefits.
Article 64 Individuals and organisations who find that a holder of a listed drug permit or a drug manufacturer is engaged in illegal production activities shall have the right to report to the drug supervision and administration department, which shall promptly verify and deal with the matter in accordance with the relevant provisions.
Article 65 In the event of a major safety incident related to the quality of drugs, the holder of a listed drug licence shall immediately take control measures such as sealing and storage of the drugs concerned, their raw materials, auxiliary materials, as well as packaging materials and containers in direct contact with the drugs and the relevant production lines, and immediately report to the drug supervision and management department of the province, autonomous region or municipality directly under the central government and the relevant departments, and the drug supervision and management department of the province, autonomous region or municipality directly under the central government shall Provinces, autonomous regions, municipalities directly under the Central Drug Administration shall report within twenty-four hours to the provincial people's government, and at the same time report to the State Drug Administration.
Article 66 Provinces, autonomous regions, municipalities directly under the central drug supervision and management departments of the adverse credit record of drug listing permit holders, drug manufacturers, shall increase the frequency of supervision and inspection, and can be in accordance with national regulations to implement joint disciplinary action.
Article 67 Provinces, autonomous regions, municipalities directly under the Central Drug Administration failed to timely discover the production of drug safety systematic risk, failed to timely eliminate the supervision and management of the region of drug safety risks, or provincial people's government failed to fulfil its responsibilities for drug safety, and failed to timely eliminate the regional major drug safety risks, the State Drug Administration shall be the principal person in charge of the interview.
Interviewed provinces, autonomous regions, municipalities directly under the Central Drug Administration and local people's governments should immediately take measures to rectify the supervision and management of drugs.
Interview and rectification should be included in the provinces, autonomous regions and municipalities directly under the Central Drug Administration and local people's government drug supervision and management work evaluation, assessment records.
Chapter V Legal Liability
Article 68 Any of the following circumstances, in accordance with Article 115 of the Drug Administration Law shall be punished:
(A) the holder of the listed drug licence and drug manufacturers to change the production address, the scope of production should be approved but not approved;
(ii) Where a drug production licence exceeds its validity period and still carries out production.
Article 69 If the holder of a listed drug licence and a drug manufacturing enterprise fails to produce in accordance with the requirements of the Good Manufacturing Practice for Drugs, and one of the following circumstances falls within the serious circumstances stipulated in Article 126 of the Drug Administration Law, it shall be punished in accordance with the law:
(A) Failure to have a special quality officer independently responsible for drug quality management, supervision of the implementation of quality management standards;
(B) The holder of the marketing licence of the drug is not equipped with a special quality authorised person to carry out the responsibility of drug listing and release;
(C) drug manufacturers are not equipped with special quality authorised person to carry out the responsibility of drug factory release;
(D) The quality management system cannot operate normally, and the records and data of drug production process control and quality control are not true;
(E) the identified risks are not timely and effective risk control measures, unable to ensure product quality;
(F) Other serious violations of the quality management standards for drug production.
Article 70 The manufacturers and suppliers of excipients, packaging materials and containers in direct contact with drugs do not comply with the quality management standards formulated by the State Drug Administration and other relevant requirements, and fail to ensure that the quality assurance system continues to be compliant, by the location of the provincial, autonomous regions and municipalities directly under the Central Drug Administration in accordance with the provisions of Article 126 of the Drug Administration Law shall be punished.
Article 71 Where the holder of a marketing authorisation for pharmaceutical products and a pharmaceutical manufacturing enterprise has any of the following circumstances, the drug supervision and management department of the province, autonomous region or municipality directly under the central government where it is located shall impose a fine of not less than ten thousand yuan and not more than thirty thousand yuan:
(A) the enterprise name, residence (place of business), the legal representative does not apply for changes in registration matters in accordance with the provisions;
(B) not in accordance with the provisions of the annual direct contact with the drug staff health checks and establish health records;
(C) Failure to follow the provisions of the drugs included in the national implementation of the list of drugs in short supply discontinued report discontinued report.
Article 72 Where a drug administration department commits any of the following acts, the person in charge and other persons directly responsible shall be punished in accordance with the provisions of Article 149 of the Drug Administration Law:
(a) Concealing, falsely reporting, delaying or omitting to report drug safety incidents;
(ii) Failure to promptly investigate and deal with drug safety offences discovered;
(iii) Failure to timely detect systemic risks in drug safety, or failure to timely eliminate hidden dangers in drug safety in the supervision and management area, resulting in serious impacts;
(D) Other non-performance of drug supervision and management responsibilities, resulting in serious adverse effects or significant losses.
Chapter VI Supplementary Provisions
Article 73 The period of time prescribed in these Measures shall be calculated in working days. The time required for technical review and assessment, on-site inspection, and enterprise rectification in the drug production licence shall not be counted as a period.
Article 74 The site management document refers to the document outlining the drug production activities prepared by the drug manufacturer, which is a part of the quality management document system of the drug manufacturer. The requirements related to site management documents are separately formulated.
Approved or associated review and approval of APIs, excipients and packaging materials and containers in direct contact with the drug production sites, overseas production sites are given a unified code together.
Article 75 The letter of caution, refers to the drug supervision and management department in the drug supervision and management activities, there is evidence that there may be a potential safety hazard, according to the law issued a letter. Cautions letter should contain the existence of defects, problems and rectification requirements.
Article 76 The format of the drug production licence number is "province abbreviation + four years + four sequential number". Enterprises to change the name and other licensing items and re-issuance, the original drug production licence number remains unchanged.
When an enterprise splits up, the original number of the drug production licence will be retained and a new number will be added at the same time. Enterprise merger, the original drug production licence number to retain one.
Article 77 The classification code is the scope of production within the licence for statistical classification of the English alphabet string. Upper-case letters are used to categorise the holder of the marketing licence for drugs and product types, including: A for the holder of the marketing licence for self-produced drugs, B for the holder of the marketing licence for commissioned production of drugs, C for the commissioned drug manufacturers, D for the production of raw materials; lower-case letters are used to differentiate between the attributes of the preparations, h for chemical drugs, z for pCms, s for biological products, d for in vitro diagnostic reagents managed by the drug in vitro diagnostic reagents under the management of pharmaceutical products, y for traditional Chinese medicine tablets, q for medical gases, t for special pharmaceutical products, x for others.
Article 78 The production scope of the drug production licence shall be completed in accordance with the General Principles of Preparations of the Pharmacopoeia of the People's Republic of China and other national drug standards.
Article 79 The relevant state laws and regulations on the production of vaccines, blood products, narcotic drugs, psychotropic substances, toxic drugs for medical use, radioactive drugs, drugs and other chemicals, in accordance with its provisions.
Article 80 The exported vaccines shall meet the standards or contractual requirements of the importing country (region).
Article 81 These Measures shall come into force on 1 July 2020, and the Measures for Supervision and Administration of Pharmaceutical Production promulgated by the former State Food and Drug Administration Order No. 14 of 5 August 2004 shall be repealed at the same time.
