China Food and Drug Administration issued a sterile drug implementation of the newly revised drug GMP related matters announcement


Release time:

2013-12-31

On December 31, 2013, the State Food and Drug Administration issued an announcement on the implementation of the "Good Manufacturing Practice for Drugs (Revised in 2010)" for sterile drugs. According to the implementation plan of "good manufacturing practice (revised in 2010)" (hereinafter referred to as the newly revised drug GMP), the production of sterile drugs such as blood products, vaccines and injections must meet the requirements of the newly revised drug GMP before December 31, 2013. The announcement pointed out that since January 1, 2014, all sterile drug manufacturers or production workshops such as blood products, vaccines, and injections that have not passed the newly revised drug GMP certification will stop production. Products produced before December 31, 2013 can continue to be sold; products that have completed the final packaging before December 31, 2013 but have not yet completed the inspection can continue to be inspected and can only be sold after passing the inspection. Sterile drug manufacturers or production workshops that have passed the on-site inspection of the newly revised GMP certification before December 31, 2013 and have been publicized can continue to produce after January 1, 2014. However, its products should be available for sale only after obtaining a new GMP Certificate. After January 1, 2014, sterile drug manufacturers or production workshops that have not passed the newly revised drug GMP certification can still apply for certification in accordance with relevant regulations; production can be resumed only after passing the certification. Continue to adhere to high standards and strict requirements to ensure the consistency of the newly revised GMP implementation standards. As of December 31, 2013, all or part of the workshops of 796 sterile drug manufacturers have passed the newly revised drug GMP certification. There are 1319 sterile drug manufacturers nationwide, 60.3 of which have passed certification. The varieties produced by these enterprises cover all sterile drugs included in the National Essential Drug List (2012 Edition). The coverage rate of sterile drugs included in the National Medical Insurance Drug List (2013) also reached 98.7. The overall production capacity has reached more than 160 of the actual demand for sterile drugs in 2012, which can meet the market supply. Through the implementation of the newly revised GMP, the quality assurance ability and risk control level of China's pharmaceutical manufacturers have been significantly enhanced, the industrial concentration has been further improved, and the trend of industrial structure optimization is obvious. The announcement requires that food and drug regulatory authorities at all levels should strengthen the supervision and inspection of sterile drug production in accordance with the above requirements. For those who have passed the newly revised drug GMP certification, we must increase the intensity of follow-up inspection; for those who have not passed the certification and must stop production, we must strictly prevent illegal production activities; once problems are found, we must resolutely investigate and deal with them in accordance with the law. Interpretation and Q & A on the Implementation of Good Manufacturing Practice (2010 Revision) On December 31, 2013, the State Food and Drug Administration issued the "Implementation of Sterile Drugs".<药品生产质量管理规范>(2010 Revision) Notice on Related Matters. The release of the announcement marks the implementation of the newly revised drug GMP has achieved phased results. In order to enable all walks of life to fully understand and accurately grasp the relevant situation of the implementation of the newly revised drug GMP, the relevant issues are now interpreted as follows: 1. from January 1, 2014, sterile drug manufacturers that have not passed the newly revised GMP certification must stop production. Interpretation: According to the "Drug Administration Law" and the former Ministry of Health Order No. 79, and submitted to the State Council for approval, the former State Food and Drug Administration issued the "On Implementation"<药品生产质量管理规范(2010年修订)>(State Food and Drug Administration An [2011] No. 101). The notice stipulates that all pharmaceutical manufacturers should meet the newly revised GMP requirements before the end of 2015, and sterile pharmaceutical manufacturers should meet the newly revised GMP requirements before December 31, 2013. According to the relevant requirements of the transitional period of the implementation plan, December 31, 2013 is the deadline for enterprises to implement the 98 version of GMP to produce sterile drugs. From January 1, 2014, sterile drug manufacturers (or production workshops) that have not passed the newly revised GMP certification must stop production. What is the situation of 2. sterile drug manufacturers passing the newly revised GMP certification? A: There are 1319 sterile drug manufacturers in China. As of December 31, 2013, 870 have applied for newly revised GMP certification, accounting for 66% of the total number of enterprises. Among them, 855 have completed on-site inspection. There are 796 enterprises that have passed the inspection and announcement, accounting for 60.3 per cent of the total number of enterprises. Can the drug production capacity and varieties of enterprises that have passed the newly revised drug GMP certification in the 3. meet the supply of China's drug market? Answer: According to the estimation of my country's drug market demand in 2012, the total production capacity of the four main dosage forms of sterile drugs of the newly revised GMP certified enterprises in my country has reached 160, which can fully meet the market demand. From the analysis of varieties, the National catalogue of essential drugs (2012 edition) contains 171 sterile drugs, all of which have been produced by certified enterprises. The National Medical Insurance Drug Catalogue (2013 Edition) and clinical commonly used drugs contain 629 and 563 sterile drugs respectively, of which 621 and 556 can be produced by certified enterprises, accounting for 98.7 per cent of the total. Individual varieties that have not yet been covered have also completed product reserves. Overall, it can effectively ensure the supply of drugs in the market. According to statistics in recent years, under normal circumstances, there will be a shortage of supply of some varieties (including various dosage forms) every year, such as methimazole, human coagulation factor VIII, snake venom antiserum, etc., which are caused by raw materials, prices, markets and other reasons. It has no internal connection with the implementation of the newly revised drug GMP. How does the 4. define shutdown? Can the enterprise continue to apply for certification after shutdown? Can the previously produced products continue to be sold? Answer: In order to accurately define the shutdown behavior and take into account the continuity of production in some enterprises, the Announcement clearly states that the shutdown behavior is determined by the completion of the final packaging, that is, for those who have completed the final packaging before December 31, 2013 and have not yet completed the inspection, they can continue to carry out the inspection work and be released after passing the inspection, allowing them to continue to be listed and sold. Vaccine products need to be issued in batches as required. Vaccine products produced and sent for batch issuance before December 31, 2013 can still be marketed after the batch issuance is qualified. Enterprises that have not passed GMP certification can continue to sell products produced before December 31, 2013, that is to say, products produced before December 31, 2013 will still be on the market in 2014. For enterprises that have passed the certification on-site inspection and publicity before December 31, 2013, they can continue to produce after January 1, 2014, and the products can only be sold after obtaining the new "Drug GMP Certificate. After the enterprise stops production, if the GMP transformation is completed, it can continue to apply for certification. For enterprises that give up certification, they can also choose their own varieties of technology transfer, merger and reorganization of enterprises and other ways to withdraw in an orderly manner. What is the impact of the implementation of the newly revised GMP in 5. on China's pharmaceutical industry? Answer: The newly revised drug GMP fully refers to the World Health Organization, the European Union and other international advanced standards, and has greatly improved the requirements for the production of sterile drugs. More importantly, it emphasizes the effective operation of the whole process quality management system and the whole process of drug production. Risk control throughout the process to more effectively ensure drug quality and safety. The steady implementation of the newly revised GMP provides a historic opportunity for the survival of the fittest, merger and reorganization of the pharmaceutical industry. Some enterprises with small scale, poor efficiency, no market for products and backward quality management level will be gradually eliminated. The dominant enterprises with production scale, management level and market dominance also took advantage of this opportunity to adjust the variety layout and enhance the industrial concentration. Taking large-volume injections as an example, the top 5 manufacturers in my country have occupied nearly 50% of the national market. The newly revised GMP has effectively promoted the integration of China's pharmaceutical industry with international standards and accelerated the pace of China's pharmaceutical products entering the international market. By the end of 2013, 450 raw materials of 160 enterprises and 143 preparation varieties of 103 enterprises had passed the GMP certification inspection of foreign drugs. On October 9, 2013, the live attenuated Japanese encephalitis vaccine of Chengdu Institute of Biological Products passed the World Health Organization vaccine pre-certification and entered the international procurement catalog for the first time, which is a milestone. 6. after January 1, 2014, will the shutdown of uncertified enterprises have an impact on the industry? A: According to statistics, only 22 of the top 500 pharmaceutical enterprises involved in injection production have not applied for the newly revised GMP certification. Of the top 100, 99 have passed, and only one has submitted an application for certification. The new revision of GMP is not only the improvement of technical requirements, but also the choice made by the market in the new stage of industrial development. However, we are still in the transformation of the temporary shutdown of the enterprise and did not close the door to certification. As long as the enterprise applies for certification, on the basis of adhering to high standards and strict requirements, it will continue to organize certification inspections, and production can be resumed after passing the certification. How does 7. ensure the quality of certification and inspection during the implementation of the newly revised GMP? Answer: In the entire implementation process of the newly revised drug GMP, the food and drug regulatory department has always adhered to high standards and strict requirements, issued relevant annexes and certification inspection guidelines in a timely manner, revised the original quality manual and 34 procedural documents, and added 4 documents, Further improve the drug GMP certification inspection from the system. Strengthen the professional and disciplinary training of inspectors. Since the implementation of the newly revised GMP, 117 inspection team leaders have been trained first, then 163 key inspectors have been trained, and 600 inspectors have been trained in the later period. In 2012 and 2013, 550 GMP inspectors who have been engaged in inspection work for a long time were retrained in various forms, including the combination of aseptic theory study and on-site operation, eight special vaccine training sessions jointly held with the World Health Organization, and the World Health Organization sent experts to observe and inspect the inspection and teaching inspection of Chinese inspectors, so as to ensure the inspection ability of GMP certified inspectors. The quality system of drug inspection has been continuously improved. At the beginning of 2011, the former National Vaccine Regulatory System of the State Food and Drug Administration passed the evaluation of my country's national vaccine supervision by the World Health Organization. In 2012, the drug certification management center passed the ISO9000 certification, and the drug inspection quality management system was well received by experts. Clear technical standards and discipline requirements for inspection certification. The results of the certification inspection shall be publicized. Follow up and inspect the certification inspection, find out the implementation of standards and disciplines in the implementation process in time, and correct the problems found in time. What measures will be taken by the General Administration of 8. to supervise the enterprises that have not passed the certification to ensure that the shutdown measures are in place? A: The General Administration of the next step requires: All localities must earnestly implement the requirements of the "Announcement". All sterile drug manufacturers or production workshops that have not passed the certification of blood products, vaccines, injections, etc., must stop production from January 1, 2014. All localities are requested to immediately notify the enterprises that have not passed the GMP certification of drugs to stop drug production activities in accordance with the requirements of the Announcement. All localities should strengthen the supervision and inspection of enterprises or production workshops that should stop production in administrative areas. The food and drug administrations of all counties (cities and districts) shall comprehensively sort out the enterprises that have stopped production and conduct on-site inspection one by one to confirm the suspension status. The food and drug administrations of all provinces (autonomous regions and municipalities) shall summarize the suspension of production and inspection, and report to the Drug and Cosmetics Supervision Department of the General Administration before January 10, 2014. At the same time, we should pay close attention to the situation of enterprises that have stopped production, and those who fail to stop production in accordance with the regulations should be investigated and dealt with in accordance with the "Drug Administration Law" and relevant regulations. All localities should closely monitor the raw materials and packaging materials of the enterprises that have stopped production, and take effective control measures. In particular, it is necessary to strengthen the supervision and management of the original and auxiliary materials of special drug manufacturers such as narcotic drugs, psychotropic drugs, toxic drugs for medical use, and radioactive drugs that have stopped production, and take strict control measures and affil seals to prevent them from flowing into illegal channels and bringing harm to society. All localities should unify their thinking, raise awareness, and earnestly implement the requirements of the "Announcement. In the process of implementation, if any new problems are found, they shall be reported to the drug and cosmetics supervision department of the general administration in a timely manner. Why should 9. implement the new revision of drug GMP? Answer: The Good Manufacturing Practice for Drugs (GMP) is an internationally accepted basic standard for drug production quality management. It is an important technical standard that must be followed in drug production. It has become an international evaluation of drug quality assurance systems and participation in drug international trade. Basic content and standard. Drug GMP has scientific, reasonable and standardized regulations and requirements on the conditions and methods of the whole production process of pharmaceutical production, such as the procurement and inspection of raw materials, production and feeding, preparation processing, quality inspection, storage and storage, and product release, so as to ensure that pharmaceutical production enterprises can continuously and steadily produce qualified drugs. China began to gradually implement drug GMP in 1988. After two revisions and legal implementation in 1992 and 1998, the goal of all drugs being produced in compliance with GMP was achieved on July 1, 2004. Through the implementation of drug GMP, China's drug supply security level has been greatly improved, product quality has been continuously improved, and good social and economic benefits have been achieved. However, the original drug GMP has been promulgated and implemented for more than 10 years. Due to the economic development and technical conditions at that time, some of the regulations are too broad, and some systems are missing, which can no longer meet the target requirements of drug production management and quality control under the new situation. In terms of concepts, systems and standards, it has lagged behind the more advanced international drug GMP standards. In order to comprehensively improve the quality management level of China's pharmaceutical manufacturing enterprises, drug production is more standardized, quality is more controllable, and learn from international advanced experience, it is necessary to revise and promote the implementation of China's drug GMP. What are the characteristics of the new revision of GMP in 10? Answer: The revision of drug GMP was started in 2005. Based on the principles of openness and transparency, starting from national conditions, and giving priority to improving quality management and personnel quality, based on the reference to the World Health Organization drug GMP standards, combined with the actual situation of my country's pharmaceutical industry, and Revise the current situation of my country's drug quality and the problems exposed by previous drug quality incidents. The newly revised GMP consists of the text and appendix, paying more attention to the details of quality management, and the length of the content has been increased from 88 to 313. Compared with the original drug GMP, the newly revised drug GMP has higher standard requirements, more comprehensive content, more specific and operable systems and measures, and basically meets the World Health Organization drug GMP standards. The main features of the newly revised GMP are: first, it clearly requires enterprises to establish and improve the quality management system, and puts forward higher requirements in terms of organization, responsibilities, procedures, activities and resources, which can ensure the effective implementation of GMP; second, it improves the qualification requirements of enterprise employees, clearly list the person in charge of the enterprise, the person in charge of production management, the person in charge of quality management, and the person authorized by quality as the key personnel of the pharmaceutical production enterprise; the third is to refine the operating procedures, production records and other document management regulations to increase guidance and operability. The fourth is to improve the production environment standard of sterile drugs. Adopts the World Health Organization's latest drug GMP air purification A, B, C, D classification standards, and increase the production environment online monitoring requirements. At the same time, according to the production area, storage area, quality control area and auxiliary area, the design requirements of plant facilities are put forward, and the design, installation, maintenance and use of equipment are also specified. Fifth, a series of new systems have been added around quality risk management. The concept of quality risk management is introduced, and new systems and measures such as supplier audit, change control, corrective and preventive measures, product quality review and analysis are added from the aspects of raw and auxiliary materials procurement, production process change, deviation handling in operation, investigation and correction of problems found, and drug quality monitoring after marketing, so as to manage and control the risks that may occur in each link and actively prevent the occurrence of quality accidents. 11. What is the goal of implementing the newly revised GMP? Answer: The implementation of the newly revised drug GMP can comprehensively improve the quality management level of drug production, strengthen drug quality management from the source, and ensure drug quality and safety; on the other hand, it can improve the access conditions of the pharmaceutical industry and eliminate backward productivity. Conducive to the pharmaceutical industry to become bigger and stronger, thereby promoting the upgrading and structural adjustment of the pharmaceutical industry. At the same time, it is conducive to promoting the transformation of my country's pharmaceutical manufacturers and integrating with international standards, and accelerating the entry of pharmaceutical products into the international mainstream market. What is the implementation plan for the newly revised drug GMP? Answer: After the release and implementation of the newly revised drug GMP, the former State Food and Drug Administration formulated a detailed implementation plan in February 2011. The plan fully considers the transition time and variety risk factors of enterprise upgrading and transformation, and determines the plan to be implemented in two stages. First, the production of sterile drugs such as injections is required to meet the requirements of the newly revised GMP before December 31, 2013. Second, all drugs other than sterile drugs should meet the requirements of the newly revised GMP before December 31, 2015. At that time, enterprises (workshops) that do not meet the requirements within the prescribed time limit shall not continue to produce drugs. Thirteen, the implementation of the new revised drug GMP promotion measures? Answer: In view of the slow progress in some areas and the waiting and waiting of enterprises in the initial stage of implementation, the problem of uneven implementation progress is more prominent, especially the task of sterile drug production to achieve the expected goals by the end of 2013 is particularly urgent. Therefore, the food and drug regulatory authorities, the Development and Reform Commission, the Ministry of Industry and Information Technology, and the former Ministry of Health have increased their support in terms of drug technology transfer, bidding and procurement, drug prices, and encouragement of mergers and reorganizations, and encouraged companies to accelerate the newly revised drug GMP certification. Encourage drug production to concentrate on advantageous enterprises. In February and October 2013, in order to do a good job in the transfer of enterprise document numbers during the transition period of the implementation of the newly revised drug GMP, the food and drug regulatory authorities continuously issued relevant notices to encourage the orderly flow of drug technology in enterprises, promote the smooth implementation of the newly revised drug GMP, and promote the optimal allocation of enterprise resources. In October 2013, the food and drug regulatory department issued a notice on matters related to the newly revised drug GMP inspection, and introduced a number of systems and measures in the connection between the old and new workshops, the registration site inspection and the drug GMP inspection, etc., to ensure the newly revised drug GMP The certification work was carried out smoothly.