Decree of the Ministry of Health of the People's Republic of China

　　No. 81

　　The Provisions for Adverse Drug Reaction Reporting and Monitoring, adopted at the executive meeting of the Ministry of Health on December 13, 2010, is hereby promulgated and shall go into effect as of July 1, 2011.

　　Minister: Chen Zhu

　　May 4, 2011

　　Provisions for Adverse Drug Reaction Reporting and Monitoring

　　Chapter I General Provisions

　　Article 1 These Provisions are formulated in accordance with the Drug Administration Law of the People's Republic of China and other relevant laws and regulations in order to reinforce the post-marketing supervision and administration of drugs, standardize adverse drug reaction (ADR) reporting and monitoring, control drug risks promptly and effectively, and ensure safety of drug use for the public.

　　Article 2 These Provisions are applicable to ADR reporting, monitoring, supervision and administration carried out within the territory of the People's Republic of China.

　　Article 3 The State implements anADR reporting system. Drug manufacturers (including overseas pharmaceutical manufacturers of imported drugs), drug distributors and medical institutions shall report ADRsas regulated.

　　Article 4 The State Food and Drug Administration (SFDA) is in charge of ADR reporting and monitoring nationwide; local drug regulatory departments at all levels are in charge of ADR reporting and monitoring within their respective administrative regions. The health administrative departments at all levels are responsible for the management relevant to the implementation of ADR reporting system in medical institutions within their respective administrative regions.

　　The local drug regulatory departments at all levels shall establish and improve ADR monitoring institutions to be responsible for the technical work of ADR reporting and monitoring within their respective administrative regions.

　　Article 5 The State encourages citizens, legal persons and other organizations to report ADRs.

　　Chapter II Responsibilities

　　Article 6 SFDA is responsible for the management of ADR reporting and monitoring nationwide, and fulfills the following main responsibilities:

　　(I) In conjunction with the Ministry of Health, formulate provisions and policies on ADR reporting and monitoring and supervise the implementation thereof;

　　(II) Jointly with the Ministry of Health, organize and carry out investigation and handling of adverse drug event (ADE) clusters that have a national impact and result in serious consequences, and release relevant information;

　　(III) Take emergency control measures for drugs that have been verified for causing serious ADRs or ADE clusters, make administrative handling decisions, and announce the decisions to the public;

　　(IV) Circulate information of ADR reporting and monitoring nationwide;

　　(V) Organize inspection of ADR reporting and monitoring carried out by drug manufacturers and distributors; organize inspection of ADR reporting and monitoring carried out by medical institutions jointly with the Ministry of Health.

　　Article 7 Drug regulatory departments of the provinces, autonomous regions and municipalities directly under the Central Government are responsible for management of ADR reporting and monitoring within their respective administrative regions, and fulfill the following main responsibilities:

　　(I) In conjunction with the health administrative departments at the same level, formulate management regulations on ADR reporting and monitoring within their administrative regions in accordance with these Provisions, and supervise the implementation thereof;

　　(II) Jointly with the health administrative departments at the same level, organize and carry out investigation and handling of ADE clusters that have a major impact within their administrative regions, and release relevant information;

　　(III) Take emergency control measures for drugs that have been verified for causing serious ADRs or ADE clusters, make administrative handling decisions, and announce the decisions to the public;

　　(IV) Circulate information of ADR reporting and monitoring within their administrative regions;

　　(V) Organize inspection of ADR reporting and monitoring carried out by drug manufacturers and distributors within their administrative regions; jointly with the health administrative departments at the same level, organize inspection of ADR reporting and monitoring carried out by medical institutions within their administrative regions.

　　(VI) Organize and carry out publicity and training on ADR reporting and monitoring within their administrative regions.

　　Article 8 Drug regulatory departments of municipalities with districts and of counties are responsible for management of ADR reporting and monitoring within their respective administrative regions; organize and carry out investigation on ADE clusters occurred within their administrative regions and take necessary control measures in conjunction with the health administrative departments at the same level; and organize and carry out publicity and training on ADR reporting and monitoring within their administrative regions.

　　Article 9 Health administrative departments at or above the county level shall strengthen supervision and management of clinical drug use in medical institutions and take emergency control measures on verified serious ADRs or ADE clusters as per their duties in accordance with laws and regulations.

　　Article 10 The National Center for ADR Monitoring is responsible for the technical work of ADR reporting and monitoring nationwide, and fulfills the following main responsibilities:

　　(I) Undertake the collection, evaluation, feedback and reporting of ADR reporting and monitoring data nationwide, and set up and maintain the national information network for ADR monitoring;

　　(II) Formulate the technical standards and norms for ADR reporting and monitoring and provide technical guidance to local ADR monitoring institutions at all levels;

　　(III) Organize and carry out investigation and evaluation on serious ADRs and assist relevant departments in investigating ADE clusters;

　　(IV) Release ADR warning information;

　　(V) Undertake the publicity, training, study and international exchange on ADR reporting and monitoring.

　　Article 11 Provincial ADR monitoring institutions are responsible for the technical work of ADR reporting and monitoring within their respective administrative regions and exercise the following main responsibilities:

　　(I) Undertake the collection, evaluation, feedback and reporting of ADR reporting and monitoring data, and maintain and manage the information network for ADR monitoring within their respective administrative regions;

　　(II) Provide technical guidance to the ADR monitoring institutions of municipalities with districts and counties;

　　(III) Organize and carry out investigation and evaluation on serious ADRs within their respective administrative regions and assist relevant departments in investigating ADE clusters;

　　(IV) Organize and carry out publicity and training on ADR reporting and monitoring within their respective administrative regions.

　　Article 12 The ADR monitoring institutions of municipalities with districts and of counties are responsible for the collection, verification, evaluation, feedback, and reporting of ADR reporting and monitoring data within their respective administrative regions; conduct investigation and evaluation on serious ADRs within their respective administrative regions; assist relevant departments in investigating ADE clusters; and carry out publicity and training on ADR reporting and monitoring.

　　Article 13 Drug manufacturers, distributors and medical institutions shall establish ADR reporting and monitoring management systems. To undertake the task of ADR reporting and monitoring within the enterprises or institutions, drug manufacturers shall establish specialized departments and allocate full-time personnel while drug distributors and medical institutions shall establish or designate departments and allocate full-time or part-time personnel.

　　Article 14 Staff engaged in ADR reporting and monitoring shall have relevant professional knowledge on medicine, pharmacology, epidemiology or statistics, etc. and are capable of scientifically analyzing and evaluating ADRs.

　　Chapter III Reporting and Handling

　　Section I Basic Requirements

　　Article 15 Drug manufacturers, distributors and medical institutions shall report through the national ADR monitoring information network any drug-related adverse reactions that they become aware of or discover; if online reporting conditions are unavailable, they shall send paper reports to local ADR monitoring institutions and the local ADR monitoring institutions shall submit online reports on their behalf.

　　The reports shall be authentic, complete and accurate.

　　Article 16 The ADR monitoring institutions at all levels shall evaluate and manage the ADR reporting and monitoring data within their respective administrative regions.

　　Article 17 Drug manufacturers, distributors and medical institutions shall cooperate with drug regulatory departments, health administrative departments and ADR monitoring institutions in investigating ADRs or ADE clusters and provide materials necessary for the investigation.

　　Article 18 Drug manufacturers, distributors and medical institutions shall establish and maintain archives for ADR reporting and monitoring.

　　Section 2 Individual ADR Cases

　　Article 19 Drug manufacturers, distributors and medical institutions shall spontaneously collect ADRs. When an ADR is known or discovered, it shall be recorded, analyzed and handled in detail, and a Form for ADR/ADE Report (see Attached Table 1) shall be filled out and submitted.

　　Article 20 All ADRs shall be reported for domestic drug products within the New Drug Observation Period; new and serious ADRs shall be reported for other domestic drug products.

　　All ADRs shall be reported for imported drugs within 5 years from the date of first approval for import; new and serious ADRs shall be reported for drugs that have been imported for more than 5 years.

　　Article 21 Drug manufacturers, distributors and medical institutions shall report any new and serious ADRs no later than 15 days from discovering or becoming aware of the information, death case shall be reported immediately, and other ADRs shall be reported no later than 30 days. Follow-up information (if any) shall be reported in a timely manner.

　　Article 22 Drug manufacturers shall investigate known death cases to have a detailed understanding of the basic information about the case, information of drug use, and occurrence, diagnosis and treatment of the adverse reaction, etc. The investigation report shall be completed within 15 days and submitted to the provincial ADR monitoring institution where the drug manufacturer is located.

　　Article 23 Individuals, when discovering new or serious ADRs may report to their physicians or drug manufacturers, distributors or local ADR monitoring institutions; if necessary, relevant medical records shall be provided.

　　Article 24 ADR monitoring institutions of municipalities with districts and counties shall review the authenticity, completeness and accuracy of ADR reports received. The review and evaluation of serious ADR reports shall be completed within 3 working days after receiving the reports; the review and evaluation of other reports shall be completed within 15 working days.

　　ADR monitoring institutions of municipalities with districts and counties shall investigate death cases to have a detailed understanding of the basic information about the case, information of drug use, and occurrence, diagnosis and treatment of the adverse reactions, etc. The investigation report shall be completed within 15 days after receiving the case report and submitted to the drug regulatory department and health administrative department at the same level and the ADR monitoring institution at a higher level.

　　Article 25 Provincial ADR monitoring institutions shall complete the evaluation within 7 working days after receiving the serious ADR evaluation statements submitted by the ADR monitoring institution at a lower level.

　　For death cases, the provincial ADR monitoring institutions where the event occurs and where the drug manufacturer is located shall analyze and evaluate the event based on the investigation report in a timely manner, conduct on-site investigation when necessary, and report the evaluation results to the provincial drug regulatory departments and health administrative departments and the National Center for ADR Monitoring.

　　Article 26 The National Center for ADR Monitoring shall analyze and evaluate the death cases and report the evaluation results to the SFDA and the Ministry of Health in a timely manner.

　　Section 3 Adverse Drug Event Clusters

　　Article 27 Drug manufacturers, distributors and medical institutions shall, upon knowing or discovering ADE clusters, immediately report to the county-level drug regulatory departments, health administrative departments and ADR monitoring institutions where they are located by telephone or by fax; when necessary, they may report directly to authorities at a higher level; at the same time, a Form for Basic Information of ADE Clusters (see Attached Table 2) and a Form for ADR/ADE Report for each case shall be filled out promptly and submitted via the national ADR monitoring information network.

　　Article 28 Drug regulatory departments of municipalities with districts and counties shall, upon knowing of ADE clusters, immediately conduct on-site investigation jointly with the health administrative departments at the same level, and promptly report the investigation results level by level to the provincial drug regulatory departments and health administrative departments.

　　Provincial drug regulatory departments, jointly with the health administrative departments at the same level, shall supervise and guide the investigation conducted by drug regulatory departments of municipalities with districts and counties, analyze and evaluate ADE clusters, and organize on-site investigation on ADE clusters that occur within their administrative regions and have a major impact. The evaluation and investigation results shall be reported to the SFDA and the Ministry of Health in a timely manner.

　　SFDA shall, jointly with the Ministry of Health, conduct investigation on ADE clusters that have a major impact nationwide and result in serious consequences.

　　Article 29 Upon knowing of any ADE cluster, a drug manufacturer shall immediately carry out investigation to have a detailed understanding of the occurrence of ADE cluster, information of drug use, diagnosis and treatment of patients involved, and production, storage, distribution and previous similar adverse events of the drug, etc., complete the investigation report within 7 days, and submit it to the provincial drug regulatory department and the ADR monitoring institution where the manufacturer is located. At the same time, the drug manufacturer shall rapidly conduct self-inspection, analyze the cause of the events, suspend production, sales and use, recall relevant drugs when necessary, and report to the provincial drug regulatory department where it is located.

　　Article 30 Upon discovering any ADE cluster, a drug distributor shall immediately inform the drug manufacturer and rapidly conduct self-inspection at the same time, temporarily suspend drug sales when necessary, and assist the drug manufacturer in taking relevant control measures.

　　Article 31 Upon discovering any ADE cluster, a medical institution shall actively treat patients, conduct clinical investigation rapidly, analyze cause of the event, and take emergency measures such as suspending drug use when necessary.

　　Article 32 Drug regulatory departments may take such control measures as suspension of production, sales and use or recall of drugs. Health administrative departments shall take active measures to organize treatment of patients.

　　Section 4 Serious ADRs Occurred Overseas

　　Article 33 Where serious ADRs (including those collected from spontaneous reporting systems, discovered during post-marketing clinical study, and published in literatures) of imported drugs and domestic drugs occur overseas, a Form for Overseas ADR/ADE Report (see Attached Table 3) shall be filled out by the drug manufacturer and submitted to the National Center for ADR Monitoring within 30 days after knowledge of the event. If the original report and relevant information are requested by the National Center for ADR Monitoring, they shall be submitted within 5 days by the drug manufacturer.

　　Article 34 The National Center for ADR Monitoring shall analyze and evaluate ADR reports received and report to the SFDA and the Ministry of Health semiannually; once information indicating potential drug safety risks is identified, reports shall be submitted in a timely manner.

　　Article 35 Where imported drugs and domestic drugs are suspended from sale and use or withdrawn from market due to ADRs occurred overseas, the drug manufacturer shall submit a written report to the SFDA and the National Center for ADR monitoring within 24 hours after knowing the event.

　　Section 5 Periodic Safety Update Report (PSUR)

　　Article 36 Drug manufacturers shall regularly summarize and analyze the ADR reporting and monitoring data of drugs they manufactured, collect domestic and overseas safety information, conduct risk-benefit assessment, and prepare PSURs. The specifications for preparing PSURs shall be developed by the National Center for ADR monitoring.

　　Article 37 For domestic drugs with a New Drug Observation Period, PSURs shall be submitted every year from the date when approval documents are obtained to the date of first re-registration; thereafter, the reports shall be submitted every 5 years. For other domestic products, PSURs shall be submitted every 5 years.

　　For drugs imported for the first time, PSURs shall be submitted every year from the date when approval documents for imported drugs are obtained to the date of first re-registration; thereafter, the PSURs shall be submitted every 5 years.

　　The time interval covered in PSURs shall be counted starting from the date when drug approval documents are obtained. The submission date shall bewithin 60 days after the date of data lock point.

　　Article 38 PSURs for domestic drugs shall be submitted to the provincial ADR monitoring institutions where the drug manufacturers are located. PSURs for imported drugs (including sub-packaged imported drugs) shall be submitted to the National Center for ADR Monitoring.

　　Article 39 Provincial ADR monitoring institutions shall summarize, analyze and evaluate PSURs received and report the statistics and the analysis and evaluation results of previous year's PSURs to the provincial drug regulatory departments and the National Center for ADR Monitoring before April 1 each year.

　　Article 40 The National Center for ADR Monitoring shall summarize, analyze and evaluate PSURs received and report the statistics and the analysis and evaluation results of previous year's PSURs for domestic and imported drugs to the SFDA and the Ministry of Health before July 1 each year.

　　Chapter IV Drug Intensive Surveillance

　　Article 41 Drug manufacturers shall frequently examine the safety of their drug products and conduct intensive surveillance on drugs within the New Drug Observation Period and on imported drugs within 5 years after first importation, and they shall summarize, analyze, evaluate and report the monitoring data as required. For other drugs products, intensive surveillance shall be conducted voluntarily based on the drug safety information.

　　Article 42 Drug regulatory departments at or above the provincial level may request drug manufacturers to conduct intensive surveillance on specific drugs based on information of clinical drug use and ADR monitoring; when necessary, they may directly organize ADR monitoring institutions, medical institutions and scientific research institutions to conduct intensified drug monitoring.

　　Article 43 ADR monitoring institutions at or above the provincial level shall be responsible for the supervision and inspection of intensive surveillance carried out by drug manufacturers, and conducting technical evaluation of the monitoring reports.

　　Article 44 Drug regulatory departments at or above the provincial level may, jointly with the health administrative departments at the same level, designate medical institutions as surveillance sites undertaking drug intensive surveillance.

　　Chapter V Evaluation and Control

　　Article 45 Drug manufacturers shall analyze and evaluate the ADR reporting and monitoring data collected and spontaneously conduct drug safety studies.

　　For drugs that have been verified as causing serious ADRs, drug manufacturers shall promptly inform the health professionals, patients and the public of the ADRs and information on rational drug use by various effective means; measures such as revising labels and package inserts, suspension of production, sales and use, and recall shall be taken to reduce and prevent the recurrence of ADRs. For drugs causing significant adverse reactions, drug manufacturers shall voluntarily apply for canceling the approval documents.

　　Drug manufacturers shall report the drug safety information and measures taken to the provincial drug regulatory departments where the enterprises are located and to the SFDA.

　　Article 46 Drug distributors and medical institutions shall analyze and evaluate the ADR monitoring and reporting data collected and take effective measures to reduce and prevent the reoccurrence of ADRs.

　　Article 47 Provincial ADR monitoring institutions shall conduct comprehensive analysis on ADR reports received quarterly, extract and evaluate safety information that needs attention, propose risk management measures, and promptly report to drug regulatory departments and health administrative departments at the provincial level and the National Center for ADR Monitoring.

　　Provincial drug regulatory departments may, based on the results of analysis and evaluation, take such measures as suspension of production, sales and use, and drug recall, and carry out supervision and inspection; at the same time, they shall inform health administrative departments at the same level of the measures taken.

　　Article 48 The National Center for ADR Monitoring shall conduct comprehensive analysis on serious ADR reports received quarterly, extract and evaluate safety information that needs attention, propose risk management measures, and promptly report to the SFDA and the Ministry of Health.

　　Article 49 Based on the results of drug analysis and assessment, the SFDA may request enterprises to conduct studies on drug safety and effectiveness. When necessary, measures such as ordering enterprises to revise package inserts, suspension of production, sales and use, and drug recall shall be taken; for drugs with serious adverse reactions, the drug approval documents shall be revoked; and the Ministry of Health shall be informed of all measures in a timely manner.

　　Article 50 ADR monitoring institutions at or above the provincial level may, based on the need for analysis and evaluation, request drug manufacturers, distributors and medical institutions to provide relevant materials, and relevant units shall actively provide support.2019-12-16

Chapter VI Information Management

　　Article 51 ADR monitoring institutions at all levels shall conduct statistical analysis on the ADR reporting and monitoring data received and provide feedback in appropriate forms.

　　Article 52 The National Center for ADR Monitoring shall release ADR warning information in a timely manner based on results of comprehensive analysis and evaluation on ADR reporting and monitoring data.

　　Article 53 Drug regulatory departments at or above the provincial level shall regularly release information on ADR reporting and monitoring.

　　Article 54 The following information shall be released in a unified manner by the SFDA and the Ministry of Health:

　　(I) ADE clusters that have a major impact and result in serious consequences;

　　(II) Other important ADR information and information necessary for uniform release.

　　Information defined in the preceding paragraph that needs unified release may also be released by provincial drug regulatory departments and health administrative departments under the authorization of the SFDA and the Ministry of Health.

　　Article 55 Commercial secrets, personal privacy, and patient and reporter information obtained during the process of ADR reporting and monitoring shall be kept confidential.

　　Article 56 Medical institutions, drug manufacturers and distributors shall be encouraged to share ADR information.

　　Article 57 The contents and statistical data of ADR reports are the basis for strengthening drug regulation and providing guidance for rational drug use.

Chapter VII Legal Liabilities

　　Article 58 Under any of the following circumstances, a drug manufacturer shall be given a warning and ordered to make corrections within a specified time limit, and may be imposed a penalty of not less than RMB 5,000 yuan but not more than RMB 30,000 yuan by the local drug regulatory department where the enterprise is located:

　　(I) Having not established an ADR reporting and monitoring management system as required, or having no specialized department or full-time personnel in charge of ADR reporting and monitoring within the enterprise;

　　(II) Having not established and maintained achieves for ADR monitoring;

　　(III) Having not conducted the reporting, investigation, evaluation, and handling of ADRs or ADE clusters as required;

　　(IV) Having not submitted PSURs as required;

　　(V) Having not conducted intensive surveillance as required;

　　(VI) Not cooperating with the investigation of serious ADRs or ADE clusters;

　　(VII) Other violations against these Provisions.

　　Where a drug manufacturer violates Item (IV) or (V) of the preceding paragraph, re-registration of relevant drugs shall be prohibited in accordance with requirements of theProvisions for Drug Registration.

　　Article 59 Under any of the following circumstances, a drug distributor shall be given a warning and ordered to make corrections within a specified time limit by the local drug regulatory department where the enterprise is located; where corrections are not made within the time limit, a penalty of not more than RMB 30,000 yuan shall be imposed:

　　(I) Having no full-time or part-time personnel in charge of ADR monitoring within the enterprise;

　　(II) Having not conducted the reporting, investigation, evaluation, and handling of ADRs or ADE clusters as required;

　　(III) Not cooperating with the investigation of serious ADRs or ADE clusters.

　　Article 60 Under any of the following circumstances, a medical institution shall be given a warning and ordered to make corrections within a specified time limit by the local health administrative department where the medical institution is located; where corrections are not made within the time limit, a penalty of not more than RMB 30,000 yuan shall be imposed. In serious circumstances that cause serious consequences, administrative sanctions shall be given by the local health administrative department to the relevant responsible person:

　　(I) Having no full-time or part-time personnel in charge of ADR monitoring within the institution;

　　(II) Having not conducted the reporting, investigation, evaluation, and handling of ADRs or ADE clusters as required;

　　(III) Not cooperating with the investigation of serious ADRs and ADE clusters.

　　Where any violation by a medical institution defined in the preceding paragraph is identified by the drug regulatory department, the case shall be transferred to the health administrative department at the same level for handling.

　　Where the health administrative department decides to give administrative penalty to a medical institution, the drug regulatory department at the same level shall be informed promptly.

　　Article 61 Where drug regulatory departments, health administrative departments and ADR monitoring institutions at all levels and their staff violate these Provisions in the management of ADR reporting and monitoring and cause serious consequences, administrative sanctions shall be given in accordance with relevant provisions.

　　Article 62 Drug manufacturers, distributors and medical institutions shall be liable for compensation in accordance with law if they violate relevant regulations and cause harm to drug users.

Chapter VIII Supplementary Provisions

　　Article 63 Terms used in these Provisions are defined as follows:

　　(I) An adverse drug reaction refers to an unintended noxious response to a drug of acceptable quality used at normal usage.

　　(II) ADR reporting and monitoring refers to the process of detecting, reporting, evaluating and controlling ADRs.

　　(III) A serious ADR is a response leading to any of the following damages caused by drug use:

　　1. Resulting in death;

　　2. Life threatening;

　　3. Causing cancer, malformation or congenital anomaly;

　　4. Resulting in significant or permanent disability or organ damage;

　　5. Requiring inpatient hospitalization or resulting in prolongation of existing hospitalization;

　　6. Other medically important events that without treatment could lead to the aforementioned outcomes.

　　(IV) A new ADR refers to any adverse reaction that is not listed on the package insert. An ADR that is listed but is in consistent with or more severe than that described on the package insert in nature, severity, outcome and frequency shall be handled as a new ADR.

　　(V) An ADE cluster refers to an event which causes damage or threat to the health or life of a certain number of people in a relatively concentrated time span and region during the use of the same drug and needs to be handled urgently.

　　The same drug refers to drugs of the same name, dosage form and strength manufactured by the same drug manufacturer.

　　(VI) Drug intensive surveillance refers to drug safety monitoring activities conducted in order to further understand the clinical use of drugs and occurrence of adverse reactions and study the characteristics, severity, and incidence rate, etc. of adverse reactions.

　　Article 64 An overseas drug manufacturer of imported drugs may authorize its representative office or its agency within the territory of China to fulfill the obligations for ADR reporting and monitoring in accordance with the requirements of these Provisions for drug manufacturers.

　　Article 65 Where other provisions are formulated by the Ministry of Health and the SFDA on the reporting and monitoring of vaccine adverse reactions, such provisions shall prevail.

　　Article 66 Provisions on adverse reaction reporting and monitoring for pharmaceutical preparations of medical institutions shall be developed by the drug regulatory departments of provinces, autonomous regions and municipalities directly under the Central Government together with the health administrative departments at the same level.

　　Article 67 These Provisions shall go into force as of July 1, 2011. The Provisions for Adverse Drug Reaction Reporting and Monitoring (SFDA Order No.7) promulgated by the SFDA and the Ministry of Health on March 4, 2004 shall be repealed simultaneously.

　　Note: In case of any difference in interpretation between the English version and the Chinese version, the Chinese version shall prevail.