Provisions for the Supervision and Administration of Drug Production

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

 

Chapter 1 General Provisions

 

Article 1 The Provisions for the Supervision and Administration of Drug Production is hereby enacted to strengthen drug production supervision and management, and regulate the manufacturing of drugs in accordance with the Drug Administration Law of the People’s Republic of China (hereinafter referred to as the Drug Administration Law), Law of the People's Republic of China on Traditional Chinese Medicine, Law of the People’s Republic of China on Vaccine Administration (hereinafter referred to as the Vaccine Administration Law), Administrative License Law of the People’s Republic of China and the Regulations for Implementation of the Drug Administration Law of the People’s Republic of China.

 

Article 2 These Provisions apply to the production, supervision and management of drugs marketed within the territory of the People's Republic of China.

 

Article 3 Any enterprise engaging in pharmaceutical manufacturing should comply with laws, regulations, rules, standards and specifications, and ensure that all the information is true, accurate, complete and traceable.

 

Any enterprise engaging in pharmaceutical manufacturing should be approved by the drug administration at the level of province, autonomous region, and municipality directly under the Central Government, obtain a drug production license and strictly comply with the drug manufacturing quality management specifications, thus ensuring that the productive process meets the legal requirements continuously.

 

The marketing authorization holder should establish a drug quality assurance system, fulfill the responsibility of releasing drugs on the market, and should be responsible for the quality of drugs with the Drug Registration Certificate.

 

The manufacturer of TCM decoction pieces should fulfill the relevant obligations of the marketing authorization holder, and ensure that the productive process of TCM decoction pieces could continuously meet the legal requirements.

 

The manufacturer of active pharmaceutical ingredients should organize production according to the approved process while strictly complying with the drug manufacturing quality management specifications, and ensure that the productive process could continuously meet the legal requirements.

 

The manufacturer of associated review expedient, package material and vessel directly contacting the drug and other individual and institution engaged in drug manufacturing should assume the corresponding responsibility by law.

 

Article 4 Marketing authorization holder and drug manufacturer should establish and implement the drug traceability system, and give drug trace identity according to the provisions of the sales package unit. The marketing authorization holder and drug manufacturer use information means to trace the drug, timely and precisely record and keep drug trace data, and provide trace information to the drug trace service platform.

 

Article 5 The NMPA is responsible for supervision and management of drug production nationwide, and supervises and guides the drug production supervision and management conducted by the competent drug administration of province, autonomous region and municipality.

 

The competent drug administration of province, autonomous region and municipality is responsible for drug production supervision and management within its administrative area, and assumes work such as drug production approval, inspection and punishment.

 

The Center for Food and Drug Inspection of NMPA (the Inspection Center) organizes the formulation of drug inspection specification and document, conducts overseas check and organizes vaccine inspection. The Inspection Center analyzes, assesses, checks and discovers risks, provides inspection conclusion and disposal comment, and is responsible for the guidance and assessment of quality management system of drug inspection organ of province, autonomous region and municipality.

 

The Information Center, NMPA is responsible for building and managing drug traceability service platform and drug safety credit archive, and providing uniform code of drug production venue. 

 

The professional technology organ for drug review, test, inspection, monitoring and evaluation established or specified by drug administration by law assumes the relevant technology work and issues conclusion according to due responsibilities, and provides technical support for drug production supervision and management.

Chapter II Production License

 

Article 6 Conditions below should be met before engagement in drug production:

 

(i) Certified medicine technician, engineering technician, corresponding technical worker, legal representative, enterprise leader, production management leader (production leader), quality management leader (quality leader), qualified person and other personnel complying with the Drug Administration Law and Vaccine Administration Law;

 

(ii) Plant, facility, equipment and sanitary environment suitable for drug production;

 

(iii) Facility and personnel capable of quality management and test of drug production;

 

(iv) Necessary device to conduct quality management and test of drug production;

 

(v) Drug quality assurance rules and procedures; compliance with good manufacturing practices.

 

During vaccine production, conditions below should be met:

 

(i)Appropriate size and adequate productivity reserve;

 

(ii)System, facilities and equipment to guarantee biological safety;

 

(iii) Compliance with disease prevention and control need.

 

Article 7 For production of preparation, active pharmaceutical ingredient and TCM decoction piece, the applicant should follow the Provisions and NMPA document application requirements, and lodge application to the competent drug administration of province, autonomous region and municipality.

 

The marketing authorization holder entrusting others to produce preparation should have the condition as set forth by article 6.1.1, 6.1.3., 6.1.5, sign the commission agreement and quality agreement with the compliance drug manufacturer, submit the consolidated documents of relevant agreements and actual production venue application documents to the competent drug administration of province, autonomous region and municipality of the place of marketing authorization holder, and apply for processing of the drug manufacturing license according to the Provisions.

 

The applicant should be responsible for authenticity of all application documents.

 

Article 8 Upon request, the competent drug administration of province, autonomous region and municipality should respectively process according to scenarios below:

 

(i) When the application item doesn’t belong to the scope of authority of the administration by law, immediately make decision to refuse processing the application, and inform the applicant to make application to the competent authority;

 

(ii) When the application item doesn’t need administrative license by law, immediately inform the applicant of no processing;

 

(iii) When the application document has error that can be corrected onsite, allow the application to make onsite correction;

 

(iv) When application documents are not complete or don’t conform to formal inspection requirements, send it onsite or within five days to the applicant to make up the document notification, and inform on one time the applicant all contents to be made up. In case of failure to inform within the specified period, it’s deemed as accepted since date of receipt of application documents;

 

(v) When application documents are complete and conform to formal inspection requirements, or the applicant submit all required makeup documents, it’s accepted.

 

When the competent drug administration of province, autonomous region and municipality accepts or refuses the application for drug manufacturing license, issue the acceptance notification or refusal notification with the special department seal and date.

 

Article 9 The competent drug administration of province, autonomous region and municipality should make decision within thirty days since the date of acceptance.

 

In case of compliance with provisions through review, approval is granted, and the drug manufacturing license is issued within ten days since the written approval decision is made; in case of incompliance with provisions, make the written decision on refusal, and explain reasons.

 

The competent drug administration of province, autonomous region and municipality will follow provisions such as Good Manufacturing Practices to conduct technical review, evaluation and onsite check on the application documents.

 

Article 10 The competent drug administration of province, autonomous region and municipality should showcase in the website of the administrative organ and office venue the condition, procedure, term for application for the drug manufacturing license, catalog of all submissions and the template application form, etc.

 

The competent drug administration of province, autonomous region and municipality should release relevant information for issuing the drug manufacturing license, and the general public has the right for reference.

 

Article 11 When the competent drug administration of province, autonomous region and municipality reviews the application for processing the drug manufacturing license, fairly review and approve the results, and provide the condition to facilitate the applicant to enquire the approval progress.

 

Without the applicant’s permission, the competent drug administration, professional technical organ and work staff thereof should not disclose the business secret, undisclosed information or confidential business information, unless otherwise provided by law or involving national security and major social public interests. 

 

Article 12 When the application for processing the drug manufacturing license directly involves the relation of major interest between the applicant and others, the applicant and stakeholder have the right to apply for hearing according to the laws and regulations.

 

During review on the application by the drug manufacturer, when the competent drug administration of province, autonomous region and municipality thinks the public interest is involved, make a public announcement and hold the hearing.

 

Article 13 The drug manufacturing license has a validity period of five years, and is composed of the original and counterpart. The type of drug manufacturing license is uniformly formulated by NMPA. The electronic and written drug manufacturing license has the same and equal legal effect.

 

Article 14 The drug manufacturing license should carry items such as the license number, classification code, name of company, unified social credit code, venue (business place), legal representative, company leader, production leader, quality leader, qualified person, production address and scope, issuance organ, issuance date, and validity term. 

 

Items such as name of company, unified social credit code, venue (business place) and legal representative should be consistent with the relevant information on the business license issued by the market regulatory authority.

 

Article 15 Items carried by the drug manufacturing license are composed of the license item and registration item.

 

The license item refers to the production address and scope, etc.

 

The registration item refers to name of company, venue (business place), legal representative, company leader, production leader, quality leader, qualified person, etc. 

 

Article 16 In case of change of license items in the drug manufacturing license, make the change application to the original issuance organ.

 

The original issuance organ should make decision on whether to allow the change within fifteen days upon receipt of the change application. In case of refusal, explain reasons in writing, and inform the applicant of the right to apply for administrative reconsideration or bring an administrative suit by law.

 

In case of change of production address or scope, the drug manufacturer should follow Article 6 and relevant technical requirements for change, submit relevant documents on the change content and report to the corresponding competent drug administration of province, autonomous region and municipality for review and decision.

 

In case of building, remodeling, expanding the workshop or production line in the original or different place, follow relevant provisions and technical requirements, and submit relevant documents on the change content and report to the corresponding competent drug administration of province, autonomous region and municipality for inspection on compliance with GMP, and inform the manufacturer of the inspection result. When the inspection result complies, and the product conforms to the release requirements, marketing is allowed. Relevant change status should be carried in the counterpart of the drug manufacturer license.

 

When the above change item involves the content carried by the drug registration certificate and its attachment, upon approval by the competent drug administration of province, autonomous region and municipality, report to the Center for Drug Evaluation, NMPA to refresh relevant content of the drug registration certificate and its attachment.

 

Article 17 In case of change of registration item in the drug manufacturing license, within thirty days when the market regulatory authority verifies the change or the company finishes the change, apply for registration of change in the drug manufacturing license to the original issuance organ. Within ten days after receipt of the company’s change request, the original issuance organ should process the change procedure.

 

Article 18 After change of drug manufacturing license, the original issuance organ should record the change content and time in the counterpart of the drug manufacturing license. According to the changed content, re-issue the original of the drug manufacturing license, and take back the former original of the drug manufacturing license. The expiration term of the new drug manufacturing license remains unchanged.

 

Article 19 When the drug manufacturing continues at the expiration of the validity term of drug manufacturing license, apply for a new drug manufacturing license to the original issuance organ six months before the expiration of validity term.

 

Based on the company's compliance with the drug administration laws and regulations, GMP and quality system operation, and according to the risk management principle, the original issuance organ conducts review, and makes decision on whether allowing to issue the new certificate before the expiration of the validity period of drug manufacturing license. In case of compliance and allowing issuance of new certificate, take back the original certificate and issue a new one; in case of incompliance, make a written decision of declining issuance of the new certificate, and explain reasons. Inform the applicant of the right to apply for administrative reconsideration or bring an administrative suit by law. Failure to make decision within the specified period is deemed as consent to issuance of a new certificate, and the corresponding procedure will be processed.

 

Article 20 In case of one of scenarios below, the drug manufacturing license is canceled by the original issuance organ, and an announcement is made:

 

(i) Actively apply for cancellation of the drug manufacturing license;

 

(ii) A new certificate is not issued at the expiration of validity period of the drug manufacturing license;

 

(iii) The business license is revoked or canceled by law;

 

(iv) The drug manufacturing license is revoked or removed by law;

 

(v) Other scenarios to cancel the administrative license by law and regulation.

 

Article 21 In case of drug manufacturing license missing, the marketing authorization holder and drug manufacturer should apply for a new one from the original issuance organ. The original issuance organ issues a new drug manufacturing license within ten days according to the original verification items. The license number, validity period, etc. are consistent with the original one.

 

Article 22 Any institution or individual should not fabricate, alter, lease, lend, buy or sell the drug manufacturing license.

 

Article 23 Within ten days after processing of the drug manufacturing license such as issuance, reissuance, change, makeup, revoking, removal and cancellation, the competent drug administration of province, autonomous region and municipality should refresh the information in the drug safety credit file within ten days after processing. 

 

Chapter III Production Management

 

Article 24 The drug manufacturing should follow the GMP, national pharmaceutical standard and conduct production according to the drug registration standard and production process verified by the competent drug administration. The drug manufacturing should submit and continuously refresh the venue management document, conduct risk assessment and continuous improvement on quality system operation, and ensure compliance of drug production process with the statutory requirements. The production and test record should be complete and precise, without fabrication and alteration.   

 

Article 25 The vaccine marketing authorization holder should have the plant necessary for vaccine production and test, provide qualified management staff, establish the all-round quality management system, and have the capability to produce the vaccine compliance with registration requirements. In case of beyond the vaccine productivity and necessity for entrusted production, NMPA approval is required. 

 

Article 26 In case of engagement in drug production, observe GMP, establish and improve the drug production quality system covering all factors influencing the drug quality, and ensure compliance of the drug production process with the statutory requirements. 

 

Article 27 The marketing authorization holder should establish the drug quality assurance system, provide special personnel responsible for drug quality management, periodically review the quality management system of the entrusted drug manufacturer and operator, and supervise its ongoing capacity for quality assurance and control.

 

Article 28 The legal representative and main leader of marketing authorization holder should be fully responsible for drug quality, and perform responsibilities below:

 

(i) Provide special quality leader responsible for drug quality management;

 

(ii) Provide special qualified person responsible for performing responsibility for drug marketing release;

 

(iii) Supervise normal operation of quality management system;

 

(iv) Periodically conduct quality system review on the drug manufacturer, supplier and relevant drug manufacturing activity, and ensure ongoing compliance;

 

(v) Perform change management responsibility according to the change technology requirements;

 

(vi) Conduct quality assessment on the entrusted operator, and information communication with the user;

 

(vii) Cooperate with the competent drug administration’s extended inspection on the marketing authorization holder and relevant party;

 

(viii) In case of serious safety event with drug quality, timely report, handle risk according to the holder’s formulated risk management plan, and ensure that the risk is timely controlled;

 

(ix) Other responsibilities as provided by law and regulation

 

Article 29 The legal representative and main leader of the drug manufacturer should be fully responsible for the company’s drug manufacturing, and perform responsibilities below:

 

(i) Provide the special quality leader responsible for drug quality management, supervising implementation of drug management specification, ensuring proper manufacturing process control and quality control, and drug’s compliance with national drug standard and registration standard;

 

(ii) Provide the special qualified person responsible for drug release;

 

(iii) Supervise normal operation of quality management system, and ensure authenticity of drug production process control, quality control and record and data;

 

(iv) In case of serious safety event associated with drug quality, timely report, and handle risk according to the company’s formulated risk management plan and ensure that the risk is timely controlled;

 

(v) Other responsibilities as provided by law and regulation.

 

Article 30 The marketing authorization holder, and drug manufacturer should conduct the yearly health examination on the work staff directly contacting the drug and set up the health archive, and prevent the personnel with contagious disease or other disease possibly contaminating the drug from directly contacting the drug production.

 

Article 31 The marketing authorization holder, and drug manufacturer should conduct quality management such as risk assessment, control, validation, communication and review during drug production, and timely take effective risk control measure for identified risks to secure product quality. 

 

Article 32 In case of engagement in drug production, conduct review on supplier or manufacturer of active pharmaceutical ingredient, expedient, package material and vessel directly contacting the drug, and ensure compliance of procurement and use.

 

The active pharmaceutical ingredient, expedient for drug production should conform to drug use requirement and the corresponding GMP. The package material and vessel directly contacting the drug should conform to the drug use requirement, and meet the standard to secure human health and safety.

 

Article 33 The manufacturer of active pharmaceutical ingredient, expedient package material and vessel directly contacting the drug with approval or passing the associated review and approval should abide by the quality management specification of NMPA and relevant associated review and approval requirements, ensure ongoing compliance of quality assurance system, accept quality review of market authorization holder and accept supervision or extended inspection of the competent drug administration.

 

Article 34 The drug manufacturer should make sure that the verification and validation is conducted as scheduled. Periodically assess the facility, equipment, production process and cleaning method, and ensure the ongoing validation status.

 

Article 35 The drug manufacturer should take the control measures to prevent contamination, cross contamination, confusion and error, periodically inspect the applicability and effectiveness of control measures, and ensure that the drug reaches the prevailing national drug standard and drug registration standard, and conforms to the GMP.

 

The marketing authorization holder and drug manufacturer should not produce other product with adverse influence on drug quality in the drug production plant.

 

Article 36 The drug package operation should have measures to mitigate confusion and error risk, and ensure that the drug within the validity period is not contaminated during storage and transportation.

 

The expression in drug instruction and label should be scientific, standard, accurate, and the wording should be clear and legible. It’s prohibited to make alteration or supplement by adhesion, cutting or alteration.

 

Article 37 The drug manufacturer should establish the drug release procedure, clarify release standard, condition, review the drug quality test result, important production record and deviation control, and conduct drug quality test. When meeting the standard and condition, the release is allowed after signature by the qualified person.  

 

The marketing authorization holder should establish the drug marketing release procedure, and review the test results for drugs released by drug manufacturers and release documents, and allows marketing release after signature by the qualified person. 

 

The TCM decoction piece should meet national drug standard or specifications formulated by the competent drug administration of province, autonomous region and municipality before release and sales.

 

Article 38 The marketing authorization holder and drug manufacturer should conduct yearly self-inspection, and monitor implementation of GMP, assess whether the company conforms to the prevailing regulatory requirements, and put forward necessary corrective and preventive measure.

 

Article 39 The marketing authorization holder should establish the yearly reporting system, and report information such as the drug production, sales, post-marketing research and risk management to the competent drug administration of province, autonomous region and municipality every year according to NMPA requirements.

 

The vaccine marketing authorization holder should yearly report to the NMPA.

 

Article 40 The marketing authorization holder should continuously conduct drug risk benefit assessment and control, formulate post-marketing drug risk management plan, actively conduct post-marketing research, further validate the drug safety, effectiveness and quality controllability, and enhance continuous management on the marketing drug.

 

Article 41 The marketing authorization holder should establish the pharmacovigilance system, and conduct pharmacovigilance work according to pharmacovigilance quality management specification formulated by NMPA.

 

The marketing authorization holder and drug manufacturer should often examine the company’s drug quality, efficacy and adverse reaction. In case of the suspected adverse reaction, timely produce the required report.

 

Article 42 The marketing authorization holder’s entrusted production drug should conform to relevant drug administration provisions.

 

When the marketing authorization holder entrusts the eligible drug manufacturer to produce the drug, conduct assessment on the contractor’s quality assurance and risk management capacity, sign the quality agreement and commission agreement with the contractor according to the guideline for quality agreement on drug entrusted production of NMPA, and supervise the contractor’s performance of the agreed obligation. 

 

The contractor should not assign the entrusted drug to the third party for production.

 

The active pharmaceutical ingredient with approval or passing associated review and approval should be self produced rather than entrusted production by others.

 

Article 43 The marketing authorization holder should manage and control the production process change according to GMP, and formulate the process procedure according to the verified production process. Conduct research on the production process change, obtain approval, archiving or conduct reporting by law, and accept supervision and inspection by the competent drug administration.

 

Article 44 The marketing authorization holder and drug manufacturer should conduct retrospective analysis and recording of the produced drug quality according to variety, confirm process stability and liability, and suitability of prevailing quality standard for the active pharmaceutical ingredient, expedient and finished product.

 

Article 45 In case of change of the architecture, company leader, production leader, quality leader, and qualified person related to the quality management system of marketing authorization holder and drug manufacturer, complete the registration procedure within thirty days since the date of change.

 

Within fifteen days after the date of change, the vaccine marketing authorization holder report change of important work personnel such as the production leader, quality leader and qualified person to the competent drug administration of province, autonomous region and municipality.

 

Article 46 For the drug in the shortage drug list of the national decommissioning report, and the marketing authorization holder stops production, report to the competent drug administration of province, autonomous region and municipality six months before the scheduled decommissioning. In case of unexpected decommissioning, report to the competent drug administration of province, autonomous region and municipality within three days. If necessary, report to the NMPA.

 

Upon receipt of report, the competent drug administration should timely report to the leading entity of chamber of shortage drug supply security at the same level.

 

Article 47 When the marketing authorization holder is an overseas company, specify a Chinese domestic enterprise legal person to perform the obligation of the marketing authorization holder as set forth by the Drug Administration Law and the Provisions, and cooperate with the overseas inspection.

 

Article 48 When the production venue of marketing authorization holder is overseas, organize production according to the Drug Administration Law and the Provisions, and cooperate with the overseas inspection.

 

Chapter IV Regulatory Inspection

 

Article 49 The competent drug administration of province, autonomous region and municipality is responsible for supervision and management of the marketing authorization holder, and manufacturer of preparation, chemical active pharmaceutical ingredient and TCM decoction piece within the administration.  

 

The competent drug administration of province, autonomous region and municipality should conduct daily supervision and inspection on the supplier and manufacturer of active pharmaceutical ingredient, expedient, package material and vessel directly contacting drug, and conduct extended inspection if necessary. 

 

Article 50 When the marketing authorization holder and entrusted manufacturer are not within the same province, autonomous region, municipality, the competent drug administration of province, autonomous region and municipality of the marketing authorization holder's place is responsible for supervision and management on the marketing authorization holder. The competent drug administration of province, autonomous region and municipality of the entrusted manufacturer's place is responsible for supervision and management on the entrusted manufacturer. The competent drug administration of province, autonomous region and municipality should intensify reciprocal reporting of supervision and inspection information, and timely refresh the supervision and inspection information into the drug safety credit archive. Conduct investigation according to the refreshed regulation information of the announcement and drug safety credit archive, impose administrative treatment on the marketing authorization holder or entrusted manufacturer by law, and conduct joint inspection if necessary. 

 

Article 51 The competent drug administration should establish and improve the occupational and professional inspector system, make clear provisions on qualification, inspection responsibility, hierarchy management, capacity training, code of conduct, performance evaluation and exit procedure, and lift the professional quality and work level of the inspector. The inspector should be familiar with the pharmaceutical laws and regulation, and have the professional medical knowledge.

 

According to the regulatory authority, drug production scale and inspection task, etc. The competent drug administration should be adequately staffed to secure the inspection work need. For the place with the manufacturer of high-risk drug such as vaccine, also provide the corresponding number of inspectors with competency and experience for inspecting high-risk drugs such as vaccine.

 

Article 52 Upon the regulatory need, the competent drug administration of province, autonomous region and municipality will conduct the pre-marketing GMP conformance inspection on the marketing authorization applicant with drug manufacturing license and its entrusted manufacturer according to requirements below:

 

(i) For the drug variety failing to pass the GMP conformance inspection corresponding to the drug production condition, the pre-marketing GMP conformance inspection should be conducted. When the proposed production drug needs to undergo the onsite drug inspection, the Center for Drug Evaluation, NMPA notifies the inspection center, and informs the competent drug administration of province, autonomous region and municipality and applicant. The inspection center coordinates the competent drug administration of province, autonomous region and municipality to simultaneously conduct the onsite drug inspection and pre-marketing GMP conformance inspection;

 

(ii) When the proposed production drug doesn’t need to undergo the onsite drug inspection, the Center for Drug Evaluation, NMPA informs the competent drug administration of province, autonomous region and municipality of the workplace and applicant. The competent drug administration of province, autonomous region and municipality will solely conduct the pre-marketing GMP conformance inspection;

 

(iii) For the drug variety passing the GMP conformance inspection corresponding to the drug production condition, the competent drug administration of province, autonomous region and municipality determines whether to conduct the pre-marketing GMP conformance inspection based on the risk management principle.

 

In case of pre-marketing GMP conformance inspection, after inspection, form the written report on the inspection status and result, and take it as the important basis for drug marketing regulation. When the pre-marketing GMP conformance inspection involves the change of drug manufacturing license item, the competent drug administration of province, autonomous region and municipality of the original issuance place makes decision according to the change procedure.

 

For the business scale batch passing the corresponding pre-marketing GMP conformance inspection, obtain the drug registration certificate and meet the product release requirements before marketing sales. The marketing authorization holder should reinforce measures concerning production, sales, and risk management on the above batch of drugs.  

 

Article 53 Regulatory inspection on drug production mainly includes:

 

(i) The marketing authorization holder and drug manufacturer should implement the prevailing laws and regulations, GMP, and technology specifications such as quality management standard for pharmacovigilance

 

(ii) Is the drug production consistent with those contents carried by the drug variety archive;

 

(iii) Implementation of vaccine storage and transportation management;

 

(iv) Quality agreement and commission agreement for drug entrusted production;

 

(v) Implementation of risk management plan;

 

(vi) Change management.

 

The regulatory inspection includes authorized inspection, regular inspection, causal inspection and other inspection.

 

Article 54 The competent drug administration of province, autonomous region and municipality should follow the principle of risk management and whole-process control, and formulate the yearly inspection plan and conduct regulatory inspection according to the risk judgement. The yearly inspection plan should at least include the inspection range, content, method, focus, requirement, time limit and inspection-conducting organ, etc. 

 

Article 55 The competent drug administration of province, autonomous region and municipality should determine the inspection frequency according to the drug variety, dosage form, regulatory type, and based on overall status of national drug safety, drug safety risk warning, serious drug safety event, investigation and processing information, as well as previous check, test, adverse reaction monitoring and complaint and reporting:

 

(i) The manufacturer of anesthesia drug, class I psychotropic drug, pharmaceutical precursor chemical should not be inspected no less than once every quarter;

 

(ii) The manufacturer of high-risk drug such as vaccine, blood product, radioactive drug, medical toxic drug, sterile drug should undergo the GMP conformance inspection no less than once a year;

 

(iii) For the manufacturer of drug beyond the product above, conduct the regulatory inspection at a certain ratio every year; however, all manufacturers within the administrative region should be inspected within three years;

 

(iv) For the supplier and manufacturer of active pharmaceutical ingredient, expedient, package material and vessel directing contacting the drug, conduct the regulatory inspection at a certain ratio every year; however, all manufacturers within the administrative region should be inspected within five years;

 

The competent drug administration of province, autonomous region and municipality may regulate the inspection frequency according to the actual regulatory status of drug production within its administrative region.

 

Article 56 When organizing the regulatory inspection, NMPA and the competent drug administration of province, autonomous region and municipality should formulate the inspection plan, clarify inspection criteria and truthfully record onsite inspection. The sampling test or research, if any, should be performed according to relevant provisions. The inspection conclusion should be clear-cut. The issues discovered during inspection should be reported to the inspected entity in writing. If rectification is required, put forward the rectification content and deadline, and inspect the modified status if necessary. 

 

During regulatory inspection, the competent drug administration should assign more than two inspectors to implement regulatory inspection. The inspector should present to the inspected entity the work permit. The work staff of competent drug administration should keep confidential the known business secret. 

 

Article 57 During regulatory inspection, the marketing authorization holder and drug manufacturer should explain status and provide relevant documents according to the inspection need:

 

(i) Drug production venue management document and change information;

 

(ii) Drug manufacturer’s acceptance of regulatory inspection and rectification implementation;

 

(iii) Disposal of drug quality incompliance;

 

(iv) Pharmacovigilance facility, staff and system formulation and suspected adverse drug reaction monitoring, identification, assessment and control;

 

(v) Documents on the variety with approval with condition, and conduct of post-marketing research;

 

(vi) Other necessary documents to be inspected.

 

Article 58 After onsite inspection, analyze and summarize onsite inspection, conduct risk judgment on discovered deficiency in an objective, fair and just manner, and produce onsite inspection conclusion.

 

The assigned entity should conduct comprehensive judgement on the onsite inspection conclusion.

 

Article 59 When NMPA and the competent drug administration of province, autonomous region and municipality conducts regulatory inspection and discovers deficiency with drug production management or vaccine storage, and transportation management, or evidence shows safety hazard, the countermeasures should be taken by law:

 

(i) Basically conform to GMP. When rectification is required, issue the warning letter, and take measures such as warning, admonition and rectification within the specified period should be taken according to the risk; 

 

(ii) When the drug has quality issue or other safety hazard, the competent drug administration should issue the warning letter according to the regulatory inspection result, and take measures such as suspending production, sales, use, and import according to the risk.

 

When the drug has quality issue or other safety hazard or the marketing authorization holder fails to recall the drug to be recalled by law, the competent drug administration of province, autonomous region and municipality should instruct the recall.

 

When the risk is removed, the measure taken by the competent drug administration should be lifted.

 

Article 60 The drug quality safety risk discovered during drug production regulatory inspection should be timely reported to the assigned entity. When the competent drug administration judges that it belongs to the serious drug quality safety risk, timely report to the superior drug administration and the local people’s government of the same level.

 

Article 61 When suspected violation of drug law, regulation and rules is discovered during drug production regulatory inspection, onsite control measures should be timely taken, and attach importance to the specified evidence collection. The competent drug administration should conduct legitimate inspection according to responsibility and authority, and the suspected crime should be transferred to the public security organ.

 

Article 62 The competent drug administration of province, autonomous region and municipality should incorporate the regulatory information of marketing authorization holder and drug manufacturer within the administrative region into the drug safety credit archive, and sustain dynamic update of relevant data. The regulatory information includes drug manufacturing license, daily regulatory inspection result, illegal behavior handling, drug quality random test, adverse behavior record, complaint and reporting, etc.

 

Article 63 During production inspection management, NMPA and the competent drug administration of province, autonomous region and municipality should not interfere with normal production of marketing authorization holder and drug manufacturer, seek or receive treasure, or pursue other interests.

 

Article 64 When the individual and institution discover the marketing authorization holder or drug manufacturer has illegal production, reserve the right to report to the competent drug administration. The drug administration should timely conduct verification and processing according to relevant provisions.

 

Article 65 In case of serious safety event associated with drug quality, the marketing authorization holder should immediately take measures such as sealing of relevant drug and its active pharmaceutical ingredient and expedient and package material and vessel directly conducting the drug and relevant production line, and inform the competent drug administration of province, autonomous region and municipality and other relevant authority. The competent drug administration of province, autonomous region and municipality should report to the provincial people’s government within twenty-four hours and concurrently the NMPA. 

 

Article 66 The competent drug administration of province, autonomous region and municipality should increase the regulatory inspection frequency for the marketing authorization holder and drug manufacturer with adverse credit record, and impose joint punishment according to national provisions.

 

Article 67 When the competent drug administration of province, autonomous region and municipality fails to timely find out drug production safety systemic risk, or rule out the drug safety hazard within the regulatory management area or the provincial people’s government fails to perform drug safety responsibility, or timely get rid of serious drug safety hazards within the region, NMPA will interview with the main leader. The interviewed drug administration of province, autonomous region and municipality and the local people's government should immediately take measures, and rectify the drug regulatory management work.

 

The admonition and rectification information should be incorporated into the regulatory management work evaluation and examination record of the drug administration of province, autonomous region and municipality and the local people's government.

Chapter V Legal Responsibilities 

 

Article 68 In case of one of scenarios below, impose punishment according to article 115 of the Drug Administration Law: 

 

(i) The marketing authorization holder and drug manufacturer fail to get approval on the change of production address and scope that should be approved;

 

(ii) Continue production beyond the validity period of drug manufacturing license.

 

Article 69 When the marketing authorization holder and drug manufacturer fails to make production according to GMP, has one of scenarios below, and belongs to the serious scenario as set forth by the article 126 of the Drug Administration Law, the punishment is imposed by law:

 

(i) Fail to provide the special quality leader responsible for drug quality management and regulatory quality management;

 

(ii) The marketing authorization holder doesn’t provide the special qualified person to perform the drug marketing release responsibility;

 

(iii) The drug manufacturer doesn’t provide the special qualified person to perform the drug release responsibility;

 

(iv) Quality management system fails to operate normally, and drug production process control and quality control record and data are not authentic;

 

(v) Identified risks are not timely equipped with effective risk control measures, and product quality cannot be secured;

 

(vi) Other scenario seriously violating GMP.

 

Article 70 When the manufacturer and supplier of expedient and package material and vessel directly contacting the drug fail to abide by the relevant requirements of quality management specification of NMPA, and cannot secure ongoing compliance of quality assurance system, competent drug administration of province, autonomous region and municipality will impose punishment according to article 126 of the Drug Administration Law.

 

Article 71 When the marketing authorization holder and drug manufacturer has one of scenarios below, the competent drug administration of province, autonomous region and municipality will impose a fine of RMB 10,000~30,000:

 

(i) Fail to process the specified registration item change on the company name, venue (business place) and legal representative;

 

(ii) Fail to conduct the yearly health examination on the work staff directly contacting the drug, and establish the health archive;

 

(iii) Fail to make the specified decommissioning reporting on the drug in the national shortage drug list of decommissioning report.

 

Article 72 When the competent drug administration has one of scenarios below, impose penalty on the directly responsible leader and other directly responsible person according to article 149 of the Drug Administration Law:

 

(i) Hide, mislead, delay and miss reporting of drug safety event;

 

(ii) Fail to timely handle the discovered illegal drug safety behavior;

 

(iii) Fail to timely discover the drug safety systemic risk or get rid of drug safety hazard within the regulatory management area, leading to serious influence;

 

(iv) Other failure to perform drug regulatory management responsibility, and cause serious adverse influence or major loss. 

 

Chapter VI Supplementary Provisions

 

Article 73 The term herein is calculated on the work day. The time required for technology review and evaluation, onsite inspection and company rectification in the drug manufacturing license is not credited into the term.

 

Article 74 The venue management document refers to the drug production overview document prepared by the drug manufacturer, and represents a part of quality management documents of the drug manufacturer. The relevant requirements for venue management document are otherwise formulated.

 

The uniform code is granted to the workplace and overseas workplace for the active pharmaceutical ingredient, expedient and package material directly contacting the drug with approval or associated review and approval.

 

Article 75 The letter of admonition refers to the letter issued by law in case of evidence showcasing the safety hazards when the competent drug manufacturer conducts the drug regulatory management.

 

Article 76 The code format of drug manufacturing license is “province abbreviation + four-digit year + four-digit sequence number”. The license item such as company change name and reissuance certificate and original drug manufacturing license remains unchanged.

 

In case of company split, retain the original drug manufacturing license number, and add the new number. In case of company merger, retain one original drug manufacturing license number.

 

Article 77 The category code refers to the English word string for statistics classification of production scope within the license. The capital letter is used to categorize the marketing authorization holder and product category, including: A the marketing authorization holder for self production, B the marketing authorization holder for entrusted production, C the drug manufacturer accepting the entrust, D the manufacturer for active pharmaceutical ingredient; the lower case letter is used to differentiate the preparation attribute, h chemical drug, z Chinese traditional medicine, s biological product, d in vitro diagnostic reagent managed per drug, y TCM decoction piece, q medical gas, t special drug, x others.

 

Article 78 The production scope of drug manufacturing license is filled in according to the general provision of preparation of Chinese pharmacopoeia and other national pharmaceutical standard.

 

Article 79 Any other provisions on the production vaccine, blood product, anesthesia drug, psychotropic drug, medical toxic drug, radioactive drug, sterile drug as provided by the prevailing national laws and regulations should prevail. 

 

Article 80 The import vaccine should conform to the standard of import nation (region) or contract.

 

Article 81 The Provisions is implemented since July 1, 2020. The previous Provisions for the Supervision and Administration of Drug Production (No. 14 Order of the State Food and Drug Administration, August 5, 2004) is superseded.