Focusing on the main responsibility and main business of drug production quality supervision, we will strengthen the construction of risk prevention and control capacity, build a risk prevention and control system in the whole process of strict prevention in advance, strict management in the process, and strict strike after the event, serve the high-quality development of the biomedical industry, effectively ensure the safety and effectiveness of people's drug use, and welcome the successful convening of the 20th CPC National Congress with outstanding achievements.
1、 Innovate the mechanism and improve the drug production supervision system
1. Improve the inspection quality of drug production license. We will improve the provincial drug production license acceptance standards, standardize the on-site inspection of drug production license, improve the quality of license inspection, and strictly control the access of drug production license.
2. Improve the daily supervision mechanism of drug production. Formulate detailed rules for the implementation of drug production supervision and inspection, straighten out the daily supervision mechanism of drug production in our province, further standardize drug inspection behavior, and practically improve the ability to prevent and eliminate potential risks.
3. Standardize the management of changes in drug production. To explore the establishment of guidance on the management of changes in regulatory matters related to drug production, standardize and guide the holders of drug marketing licenses and drug manufacturers to carry out changes in regulatory matters related to drug production.
4. Strengthen the informatization construction of drug production supervision. Make full use of our province's intelligent supervision platform, actively connect with the national drug supervision data sharing platform, and achieve intelligent, standardized and traceable drug production supervision. Use the platform's electronic archives of enterprise basic information and regulatory information to conduct multi-dimensional and multi parameter evaluation of enterprises, implement drug production safety credit rating evaluation, formulate accuracy inspection plans, and achieve targeted supervision. Steadily promote the construction of the drug information traceability system, accelerate the use of information technology to record production and inspection data, and ensure the authenticity and reliability of the data.
2、 Identify risks and compact the implementation of corporate main responsibility
5. Strengthen the investigation of potential risks. To carry out the investigation of potential risks in drug production quality and safety, and explore the establishment of a management mechanism for regular reports on the investigation of potential risks; Establish a risk consultation mechanism, hold an enterprise risk analysis, research and judgment meeting, urge enterprises to take the initiative to deeply investigate the causes, take effective measures to eliminate potential risks, let the supervision run ahead, and ensure that no systematic and regional major risks occur.
6. Compacting the main responsibility of the enterprise. Establish the list of main responsibility and negative list of drug production quality and safety implemented by drug marketing license holders, and organize enterprises to carry out self inspection and self correction on the implementation of main responsibility. The provincial drug production enterprise supervision conference was held to strengthen the implementation of the main responsibility of enterprises. Organize the training of key personnel of pharmaceutical manufacturers in the province, strengthen the publicity, implementation and interpretation of laws, regulations and related supporting systems, and further enhance the legal awareness of key personnel of enterprises.
3、 Highlight key points and strengthen supervision over key enterprises and varieties
7. Implement full coverage supervision and inspection. The holder of the drug marketing license and the drug manufacturing enterprise shall be subject to full coverage inspection, and the number of flight inspections shall not be less than 50% of the total annual inspections.
8. Strengthen the supervision and inspection of key enterprises. According to the characteristics of drug varieties and dosage forms, and in combination with the actual situation of drug production in our province, strengthen the supervision of key enterprises and increase the frequency of inspection.
(1) We will focus on the supervision of high-risk enterprises including narcotic drugs, biological products, blood products, Class II psychotropic drugs, radioactive drugs, sterile drugs, and increase the frequency of supervision and inspection. Enterprises including narcotic drugs shall be inspected once a quarter, and other high-risk enterprises shall be inspected at least twice a year, including not less than one flight inspection.
(2) The drug manufacturers of the selected varieties purchased by the State collectively shall be inspected at least twice a year, including at least one flight inspection.
(3) For enterprises with increased risks that do not meet the requirements in the sampling inspection of the previous year, do not meet the GMP requirements in the inspection, find risk clues in exploratory research, have more concentrated adverse reaction reports, and have more complaints and reports from the public, the inspection shall be conducted at least twice a year, including at least one flight inspection.
9. Strengthen the supervision of key varieties. Set up the bottom line thinking and have a clear aim. In the supervision and inspection, strengthen the supervision of the following varieties: (1) blood products, biological products, Class II psychotropic drugs, radioactive drugs, sterile drugs and other high-risk varieties; (2) Selected varieties of national centralized purchase; (3) The varieties of drugs and preparations of medical institutions commissioned for production or commissioned for production; (4) Epidemic prevention and control drugs, children's drugs, pregnant women's drugs, multi-component biochemical drugs, basic drug varieties, export APIs, varieties that have passed the consistency evaluation, varieties of precious fine medicinal materials used for feeding, narcotic drugs and drug precursor chemicals and other special drugs (including compound preparations of special drugs); (5) The varieties with problems found in the daily supervision of the previous year, varieties with major changes in quality standards, varieties that do not meet the requirements in sampling inspection, varieties with risk clues found in exploratory research, varieties with more concentrated adverse reaction reports, and varieties with more complaints and reports from the public.
4、 Focus on key points and strengthen supervision of key production links
10. Strengthen the supervision of key production links. According to the actual situation of the enterprise, focus on key dosage forms and varieties, focus on key links, carry out in-depth inspection, and focus on the following links.
(1) Strengthen the quality control and inspection of raw and auxiliary materials purchase and purchase channels. Focus on the audit of raw and auxiliary materials suppliers, supplier change management, and entrusted inspection of raw and auxiliary materials. The blood products should focus on the supplier audit of the apheresis plasma station and the incoming inspection of raw plasma, and encourage the blood product manufacturers to guide the apheresis plasma station to explore the use of automatic and intelligent equipment and management systems within a certain range.
(2) Strengthen the consistency inspection of drug production process. Focus on checking whether the enterprise produces according to the statutory prescription process, whether there is any act of changing the prescription by adding other substances without registration and approval, changing the production process without authorization or modifying the key process parameters before production; Focus on checking the authenticity of the enterprise's batch production record data, and whether there are forged batch production records; Focus on the management of major deviations, whether the causes of deviations are analyzed in depth and effective countermeasures are proposed. Focus on virus inactivation control, production process change, whole process traceability and other inspections of blood products.
(3) Strengthen post marketing change management inspection. Focus on the inspection of whether the enterprise has carried out research and gone through the change procedures in strict accordance with the requirements of the Measures for the Administration of Post marketing Changes of Drugs (for Trial Implementation) and relevant technical guidelines to ensure that the entire production process continues to meet legal requirements.
(4) Strengthen the reliability inspection of drug inspection data. Focus on checking whether the quality management system of the enterprise can operate effectively, whether the qualification and quantity of quality inspectors match the production requirements, and whether they have the ability to identify Chinese herbal medicines and Chinese herbal pieces; Focus on the authenticity, accuracy, integrity and traceability of the inspection data of the enterprise.
(5) Strengthen the inspection of enterprise storage environment. Urge the manufacturers of traditional Chinese medicine preparations and extracts to do a good job in the maintenance of traditional Chinese medicine and prepared slices of traditional Chinese medicine in the warehouse, and prevent mouldy and deteriorated traditional Chinese medicine and prepared slices of traditional Chinese medicine from being put into production.
(6) Strengthen the inspection of the traceability system of key varieties. Carry out the inspection on the traceability system of key products such as blood products, biological products, Category II psychotropic drugs, and selected varieties of national centralized procurement, continue to compact the main responsibilities of drug marketing license holders (drug manufacturers), ensure 100% of the production and delivery information of key varieties in the drug production process is uploaded, and urge the manufacturers to track the key varieties of the primary wholesalers in a timely manner.
(7) Strengthen the training and inspection of enterprise employees. Focus on checking the adaptability of the number of employees to the variety and scale of production; Focus on checking whether the skills and qualities of personnel in key positions match the corresponding positions; Focus on the inspection of the training intensity and training quality of key personnel in the enterprise, and prevent drug quality and safety incidents caused by inadequate training and improper operation.
5、 Make efforts accurately and define the key supervision and inspection contents
11. Implement hierarchical and classified supervision and inspection. According to the type of enterprise, the characteristics of dosage form, and the varieties of perennial production, a targeted inspection plan is formulated to clarify the key inspection contents, strengthen the inspection efficiency, and effectively prevent and resolve the potential risks of drug production quality and safety.
(1) 50% of the enterprises carry out GMP compliance inspection on their own authority, including key enterprises such as blood products, biological products, Class II psychotropic drugs, radioactive drugs, sterile drugs and selected varieties of national centralized procurement, which carry out GMP compliance inspection on all covered drugs on their own authority, and other enterprises carry out regular supervision and inspection;
(2) Carry out confirmation inspection for enterprises without drug approval number, without registration number, and enterprises reporting to stop production, focusing on whether the quality management system is sound, whether key personnel of the enterprise are on duty, whether the approved production workshop or production line has changed, whether key equipment and facilities are in the verification state, whether drugs are produced and sold in violation of regulations, etc;
(3) For the drug marketing license holder (Certificate B) and the entrusted production enterprise (Certificate C) who entrust others to produce preparations, the inspection shall be carried out with the focus on the implementation of the entrusted production contract and quality agreement, and the focus on the variety. The drug research and development institutions that have obtained the Drug Production License shall carry out flight inspection, focusing on whether the quality management system is sound and whether key personnel of the enterprise are on duty. We will strengthen the supervision of enterprises entrusted by other provinces and multi-point commissions, urge the holders of listing licenses to improve their quality management system, and earnestly assume the main responsibility for quality.
(4) Strengthen the inspection of new enterprises, new production workshops (production lines), reconstruction and expansion of production workshops (production lines), etc. Focus on the inspection of whether drugs are produced and sold in violation of regulations before the GMP compliance inspection, and whether change research and registration changes are carried out in accordance with the Post marketing Change Management Measures (for Trial Implementation) and relevant change guidelines.
6、 Pay attention to actual results and continue to carry out in-depth special inspections
12. Deeply carry out special rectification actions for drug production safety. In accordance with the unified deployment of the work plan of the special rectification action for drug safety of the State Food and Drug Administration, we will severely crack down on unlicensed production, and focus on the inspection of new enterprises, new workshops, reconstruction and expansion of production lines and other enterprises. Focus on the key varieties of Chinese patent medicines for epidemic prevention and control, traditional Chinese medicine injections, and children's drugs, and severely crack down on adulteration, illegal addition, use of dyeing and weight increasing decoction pieces, and false feeding during the production of Chinese patent medicines. Strictly crack down on illegal purchase and use of raw and auxiliary materials; Comprehensively strengthen the supervision and dynamic inspection of drug production process, severely crack down on the fabrication of production records and inspection records, and ensure that the whole process of drug production continues to meet legal requirements. We should make full use of daily supervision, complaint reporting, public opinion monitoring and other channels to investigate illegal information, strengthen the investigation and handling of illegal cases, resolutely implement the most severe punishment for illegal cases, and strictly control drug quality and safety risks.
13. Carry out special inspection on the production of traditional Chinese medicine. In accordance with the unified deployment of the National Bureau, and in combination with the results of the special inspection on the production of traditional Chinese medicine in 2021, the special inspection on the production of traditional Chinese medicine will be further carried out in a continuous and in-depth manner with the problem oriented approach. Focus on Chinese patent medicine for epidemic prevention and control, traditional Chinese medicine injection, Chinese patent medicine for children and other key varieties, and strengthen the supervision and inspection of production and inspection records, production process change management and other key links. Focus on the supervision and extended inspection of supplier quality audit, material balance and continuous production qualification.
14. Carry out special inspection on special drugs. With the production enterprises of Category II psychotropic drugs and pharmaceutical production enterprises producing pharmaceutical preparations with poppy shells as raw materials as the objects of inspection, a comprehensive inspection was conducted on the implementation of special drug safety management by the production enterprises to prevent cheating. Focus on the inspection of whether the special drug management organization of the enterprise operates effectively and ensures the safety management of special drugs, and whether the purchase, acceptance, in warehouse maintenance, ex warehouse review and other links of special drugs conform to the relevant management regulations of special drugs. Conduct a comprehensive inspection on the purchase and sales channels, sales management, shipping management, etc. of the second category of psychotropic drug manufacturers.
15. Carry out special inspection on selected varieties of national centralized purchase. Strengthen the daily supervision of the selected varieties of the national centralized purchase, continue to implement the full coverage of supervision and inspection and sampling inspection, urge the holders of drug marketing licenses to strictly follow the approved prescription process for production, handle post marketing changes as required, and continue to promote the traceability of the selected varieties of the national centralized purchase. Focus on low price selection, major changes after the selection, rising prices of raw and auxiliary materials and other varieties, strengthen the troubleshooting of risks and hidden dangers in a targeted manner, and urge enterprises to continue to produce in compliance. It is necessary to establish a supervision account in accordance with the principle of "one enterprise, one policy, one product, one file", and urge the enterprises to effectively rectify the problems found and cancel their accounts one by one; For those who do not conform to GMP and are suspected of illegal production, the medical insurance department and other departments shall be notified, and joint punishment shall be implemented according to law.
7、 Strengthen deterrence and crack down on violations
16. Strengthen law enforcement. We will resolutely implement the "four strictest" requirements, and severely punish violations of laws and regulations to form a powerful deterrent. We will do a good job in linking up the execution of sentences, strengthen the in-depth excavation of case clues and the coordination of investigation, and form a strong joint force in law enforcement. We will severely crack down on illegal behaviors such as unauthorized changes in prescriptions and production processes, jerry building, adulteration, shoddy goods, illegal additions, and falsification of data, and firmly build a defense line for drug safety.
17. Strictly crack down on illegal lending and renting of drug production sites. Urge enterprises to strictly implement the reporting system of production suspension and resumption, strengthen the supervision and management of production suspension and resumption of drug production enterprises, and strictly punish illegal behaviors such as lending, leasing licenses, plants, facilities and equipment during production suspension.
8、 Strengthen monitoring and improve the construction of pharmacovigilance system18. Strengthen the monitoring of adverse drug reactions. Strengthen the organizational system and capacity building of pharmacovigilance, conduct problem oriented pharmacovigilance inspection, and urge and guide the holders to establish and improve the pharmacovigilance system. Further optimize and improve the working mechanism of adverse drug reaction monitoring and safety evaluation, strengthen risk monitoring and early warning and post marketing safety evaluation, strengthen the analysis and utilization of monitoring data, continue to strengthen the risk investigation, disposal, analysis, research and judgment of aggregated signals, and provide strong technical support for post marketing supervision. Carry out inspection on the implementation of the Pharmacovigilance Quality Management Standard, urge the holders of drug marketing licenses to implement the main responsibilities of pharmacovigilance, establish and improve the pharmacovigilance system, take risk control measures in a timely manner, and achieve early detection, early prevention and early disposal of risks.
9、 Consolidate the foundation and improve the drug production supervision capacity
19. Improve the ability level of drug supervision team. Comprehensively use online and offline training methods, carry out theoretical training and on-site training for drug supervision teams, and effectively improve the level of drug production supervision capability.
20. Strengthen the construction of a clean government. Comprehensively promote the construction of Party conduct and clean government, practice as the initial aspiration of the People's Republic of China, focus on "two safety", always put discipline and rules in front, and effectively build a line of defense against risks of clean government.