In order to implement the Opinions on Deepening the Reform of the Review and Approval System to Encourage Innovation in Drugs and Medical Devices (Office Letter [2017] No. 42) issued by the General Office of the CPC Central Committee and the General Office of the State Council, further improve the drug adverse reaction monitoring system, and fulfill the main responsibility of drug marketing authorization holders (including drug manufacturers holding drug approval numbers, hereinafter referred to as holders) for adverse reaction reporting, the State Food and Drug Administration announces the following matters regarding the direct reporting of adverse reactions by holders:
1. Holders must report all adverse reactions/events known to them. Holders should report drug adverse reactions/events directly to the National Drug Adverse Reaction Monitoring System in accordance with the principle of reporting immediately upon suspicion. The reporting scope includes adverse reactions that are unrelated to the purpose of medication when qualified drugs are used in normal usage and dosage, as well as other adverse events caused by drug quality problems or that may be caused by off-label medication, overdose medication, contraindication medication, medication errors, etc.
Medical institutions and individuals shall continue to report adverse reactions/events through the original channels, and are encouraged to report directly to the holders. Drug management and distribution companies shall report directly to the holders. The National Adverse Drug Reaction Monitoring System will provide the holder with real-time feedback on the collected adverse drug reaction/event information. The holder does not need to report the information fed back by the monitoring system repeatedly, except for follow-up information.
2. Holders should report adverse drug reactions/events in a timely manner. Holders should strengthen the monitoring of adverse drug reactions/events, establish effective information collection channels directly facing doctors, pharmacists and patients, and actively collect adverse reaction/event information involved in clinical trials, market projects, academic literature and website forums. All new and serious adverse reactions/events must be reported within 15 days, serious adverse reactions/events that cause serious personal injury or death must be reported immediately, and other types of adverse reactions/events must be reported within 30 days. Holders should follow up on key information missing from serious adverse reaction/event reports, conduct investigations on death cases and submit investigation reports as required.
3. Holders should strengthen the analysis and evaluation of adverse reaction monitoring data. The holder shall promptly evaluate the individual adverse drug reactions/events learned; regularly evaluate the adverse drug reaction monitoring data, clinical research, literature and other materials, pay special attention to the abnormal increase in the number of reports or the trend of batch number aggregation, and report to the regulatory authorities when necessary; regularly and comprehensively evaluate the safety of drugs, actively identify potential risks of drugs, study the mechanism and causes of risk occurrence, conduct post-marketing research, and continuously evaluate the risks and benefits of drugs.
The holder shall summarize the annual situation, including adverse reaction/event reporting, risk identification and control, post-marketing research, risk control measures taken, etc., and submit a summary report of the previous year to the provincial adverse drug reaction monitoring technical agency before January 31 each year. In addition, the holder shall prepare and report the regular safety update report of drugs in accordance with the requirements.
4. The holder shall take effective risk control measures on his own initiative. The holder shall formulate positive and effective risk control measures based on the analysis and evaluation results, and disclose them to the public in a timely manner. If adverse reactions not stated in the instructions are found, timely analysis and evaluation shall be conducted. For safety information that needs to be reminded to patients and medical staff, the instructions and labels shall be modified, the archive information of drug varieties shall be updated, and necessary risk communication shall be carried out. For varieties that may have safety risks, a risk management plan shall be formulated, and risk control measures such as restricting drug use, actively conducting post-marketing research, suspending drug production, sales or recalling drugs shall be adopted. For varieties where the risks of drugs are greater than the benefits, the drug approval certificate shall be cancelled on its own initiative.
For drugs that may have quality and safety problems and other serious safety risks, the holder shall immediately take measures such as suspending sales and use, actively recalling, and actively conducting risk investigation. The risk information and disposal situation shall be reviewed and met by the drug review agency before the sales and use can be resumed. For serious adverse reactions/events that cause serious personal injury or death, the holder shall immediately take measures to properly handle them, and report the details of the adverse reactions/events directly to the provincial drug adverse reaction monitoring technical agency within 24 hours, and report to the provincial food and drug regulatory department at the same time. The holder shall actively disclose risk information and disposal situations to the public.
5. The holder shall assume the main responsibility for drug vigilance. Pharmacovigilance is a scientific activity to discover, evaluate, recognize and prevent adverse drug reactions and other drug safety issues. The holder is the responsible entity for pharmacovigilance work and should set up a special organization independent of the quality management department, equip full-time personnel, establish and improve relevant management systems, directly report adverse drug reactions/events, regularly conduct drug risk-benefit assessments, and take effective risk control measures.
For holders who do not have the conditions to carry out pharmacovigilance, they should entrust institutions with pharmacovigilance capabilities to carry out pharmacovigilance work and sign a commission contract. The holder should do a good job of supervision and management of the trustee and bear the corresponding legal responsibilities. Imported drugs should designate companies with independent legal person qualifications as authorized agents to assume pharmacovigilance responsibilities.
6. Strengthen the technical review of the holder's pharmacovigilance work. For individual adverse drug reaction/event reports received, the drug adverse reaction monitoring technical agency should perform analysis and evaluation work according to its duties. The technical institutions for drug adverse reaction monitoring at or above the provincial level shall conduct regular analysis and evaluation of monitoring data and put forward risk management suggestions; organize technical review of regular safety update reports and provide timely feedback on review opinions; urge holders to submit annual drug vigilance summary reports on time and review the reports; promptly handle other safety issues reported by holders; conduct monitoring and evaluation of adverse event aggregation signals; and conduct quality assessment of adverse reaction/event reports.
7. Provincial food and drug regulatory departments shall assume local regulatory responsibilities. Provincial food and drug regulatory departments shall attach great importance to the direct reporting of adverse reactions by holders, organize inspections of holders' drug vigilance-related work, conduct cause-based inspections for major safety hazards or violations, and organize extended inspections of entrusted departments for drug vigilance work entrusted by holders. Provincial food and drug regulatory departments shall formulate annual supervision and inspection plans. Drug vigilance inspections can be carried out separately or in combination with drug GMP inspections, flight inspections, etc.
8. Severe penalties shall be imposed on holders for failure to perform direct reporting responsibilities. If the holder fails to establish a drug vigilance system, a corresponding organization, or a drug vigilance system document within the prescribed time limit, the food and drug regulatory authorities at or above the provincial level shall order the suspension of sales. The holder shall take remedial measures and resume sales only after the food and drug regulatory authorities at or above the provincial level have checked and found that they meet the requirements.
If the holder fails to fulfill the responsibility of directly reporting adverse reactions, conceals or fails to report, fails to report within the prescribed time limit, or provides false reports, once the relevant adverse reactions/events are reported through other channels and verified through the prescribed procedures, the food and drug regulatory authorities at or above the provincial level shall take warnings, fines, and other measures in accordance with the law; any serious adverse reactions/events that cause serious personal injury or death, or cause adverse effects, shall be suspended from sales until the drug approval certificate is revoked, and the legal representative of the enterprise shall be included in the list of dishonest persons.
If the holder discloses risk information in an untimely, incomplete, inaccurate, misleading manner to patients and the public, or fails to disclose risk information and disposal, the food and drug regulatory authorities at or above the provincial level shall warn it in accordance with the law, order it to disclose information completely and accurately, and suspend the sale of related products. After the holder fully and accurately discloses information and takes corresponding remedial measures to effectively protect the interests of patients, he or she may apply to the local provincial food and drug regulatory department. Sales can only be resumed after the provincial and higher food and drug regulatory departments have inspected and confirmed compliance and the interests of patients have been fully protected.
This announcement will take effect from July 1, 2018.
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