III. Policies and Measures Concerning Drug Safety Supervision
Based on its national conditions and learning from international advanced experience, China has formulated policies and measures concerning the improvement of drug safety, effectiveness and quality control, and established a regulatory system covering research, production, distribution and use of drugs.
? Drug Market Access System
In order to guarantee drug safety from the source, China has adopted approval procedures and qualification system with regard to drug products, drug manufacturers and distributors, and related personnel.
-- Implementing drug registration. New drugs, generic drugs and imported drugs applied for marketing are subject to rigorous technical evaluation and administrative examination and approval. Within Chinese territory, only those who have obtained Drug Approval Number or Drug Registration Certificate for imported drugs are allowed to engage in drug production or sales. In accordance with research and technical requirements specified in drug applications, the national drug regulatory department has formulated, promulgated and implemented 54 technical research guidelines, and basically established a technical evaluation system for drug registration which conforms to China's conditions.
-- Implementing a market access system for pharmaceutical enterprises. All enterprises that apply for drug manufacturing or distribution shall be subject to examination in terms of staff qualifications, factory environment, equipment and facilities, business site, storage conditions and organization of quality management. Production or sales licenses are granted only when enterprises meet the requirements. Since the adoption of the drug licensing system, Chinese drug regulatory departments have identified qualified pharmaceutical enterprises through regular inspections and re-issuing of certificates after examination. The same licensing system is carried out for the management of enterprises that produce drug substances. Only licensed enterprises are allowed to produce or deal in drug substances.
-- Implementing batch release system for biological products. China conducts compulsory inspection and approval for each batch of biological products before the products leave the factories for marketing, or are imported. Items which fail the inspection or approval shall not be allowed to be marketed or imported. Since 2001, China has gradually implemented the batch release system for such biological products as vaccines, blood products and in-vitro diagnostic reagents used for blood screening tests. Since January 1, 2006, all preventative vaccine products have been subject to approval by this batch release system; starting from January 1, 2008, all blood products must be subject to the batch release system. This batch release system for biological products plays a vital role in controlling infectious diseases like AIDS, as well as in safeguarding the public health.
-- Implementing examination and approval system for drug packaging, labeling and insert sheet. Drug packaging, labeling and insert sheet are major ways for the public to obtain drug information. In China, packaging containers and materials that are in direct contact with drugs must meet the standards for drug use. Drug labels shall be printed on or attached to drug packaging and insert sheet shall be included. Drug regulatory departments shall archive review or record for drug packaging, labeling and insert sheet in accordance with the Provisions on the Administration of Drug Insert Sheet and Labeling.
-- Implementing a certification system for registered pharmacists. In order to guarantee the quality of drugs and improve pharmacy service, professionals in pharmaceutical enterprises are required to take qualification examinations, participate in continuous training and be registered. Since the implementation of the certification system for registered pharmacists, drug regulatory departments have established a number of agencies for the management of qualification examination and registration, improved continuous training, and a complete working system is almost formed. By the end of 2007, a total of 150,000 people in China had obtained pharmacist's qualifications.
? Quality Control Practice
China practices a certification system for the quality control over drug research, manufacturing and distribution, aiming to tighten drug safety control in an all-round way.
-- Promoting Good Laboratory Practice (GLP) certification for non-clinical drug research. To improve the quality of non-clinical drug research and ensure the authenticity, integrity and reliability of experimental data, China promulgated the Good Laboratory Practice (GLP) for Non-clinical Laboratory Studies in 1999, and began the work of GLP certification in April 2007. So far, a total of 27 non-clinical drug research institutions have obtained GLP certification. Starting from January 1, 2007, all non-clinical drug safety research must be carried out in GLP-certified laboratories in the case of the evaluation of new drugs, which include chemical drug substances and their preparations, and biological products not yet marketed in China; effective components and organs extracted from plants, animals and minerals as well as their preparations not yet sold on the domestic market; effective components extracted from traditional Chinese medicine (TCM) and natural medicines as well as their preparations, and TCM injections.
-- Promoting Good Clinical Practice (GCP) certification for drug clinical trials. To ensure scientifically accurate reflection and reliability of results as well as test subjects' rights and interests during clinical trials, China promulgated the Good Clinical Practice (GCP) for pharmaceutical products in 1999, and began the work of GCP certification on March 1, 2004. By the end of 2007, a total of 178 institutions conducting clinical trials had obtained GCP certification. GCP certification has greatly improved the quality of drug clinical trials in China. Meanwhile, an increasing number of international multi-centered clinical trials are being carried out in China.
-- Implementing Good Manufacturing Practice (GMP) certification for pharmaceutical manufacturers. In order to bring drug manufacturing under control, in the late 1970s and early 1980s, China introduced the GMP concept, and promulgated the Good Manufacturing Practice for Pharmaceutical Products in 1988, and began to handle applications for GMP certification in 1995. The present GMP is the 1998 revised edition. Based on its national conditions, and in light of different drug dosage forms, China has implemented GMP standards for pharmaceutical manufacturers step by step, completing GMP certification for manufacturers of blood products in 1998, for manufacturers of sterile powder for injections, sterile freeze-dried powder for injections, large-volume injections and gene engineering products in 2000, and for manufacturers of small-volume injections in 2002. The year 2004 saw the attainment of the goals for the manufacturing of chemical drug substances and all drug preparations according to GMP standards. Manufacturers which failed GMP certification were ordered to stop production. Since January 1, 2006, the goals for the manufacturing of biological in-vitro diagnostic reagents, medical gas and prepared slices of Chinese crude drugs according to GMP standards have been reached step by step. Through GMP certification, we have eliminated pharmaceutical enterprises which failed to meet GMP standards, improved quality management among enterprises, and promoted structural adjustment in the pharmaceutical industry.
-- Implementing Good Supply Practice (GSP) certification for the drugs distributions. In order to prevent factors that might damage quality at each link of drug distribution and eliminate relevant potential quality risks, China promulgated the Good Supply Practice for Pharmaceutical Products in 2000. The work of GSP certification has gone through three stages: launching certification experimental trials in 2001, handling applications in 2002, and organizing certification in 2003 by the drug regulatory departments in provinces, autonomous regions and municipalities directly under the central government. Through GSP certification, China's pharmaceutical distributors have made great progress in terms of their overall strength and business conditions, with some unqualified enterprises eliminated.
? Drug Classification System
Since 1995 China has been working on a drug classification system. In 1999 the country promulgated the Measures for the Administration of Classification of Prescription and OTC Drugs (trial), gradually implementing the classification management between prescription and OTC drugs. In order to select, examine and approve OTC drug types as well as make necessary distinctions between some prescription and OTC drugs, China has successively publicized 4,610 types of OTC drugs, including Chinese patent medicines. China regulated the administration of OTC drugs, formulated a prototype manual for OTC drugs with detailed contents, and publicized a specific logo for OTC drugs. The drug regulatory departments have integrated the drug classification management with GSP certification for drug retailing enterprises, and promulgated regulations that prescription and OTC drugs must be displayed in separate shelves, no open-shelf self-service for prescription drugs, and classification management for pharmacies. In recent years, China has increasingly tightened its supervision of prescription drugs and the administration of advertisements for prescription drugs, and stopped the mass media carrying advertisements for prescription drugs. China has steadily promoted a management mode of selling prescription drugs only to people with doctor's prescriptions, and successively promulgated compulsory measures for the sale of 11 categories of prescription drugs, including injections, and antibacterial and hormone drugs that can be bought only with prescriptions. Through publicity and training, China has made efforts to increase people's awareness and understanding of the necessity of the drug classification system.
? Regulation of Controlled Medicines
The Chinese government has always attached importance to the regulation of controlled medicines, such as narcotics and psychotropic substances, as well as precursor chemicals and stimulants, to prevent them from flowing into illicit channels. As signatory to the 1961 Single Convention on Narcotic Drugs, 1971 Convention on Psychotropic Substances, UN Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, and International Convention Against Doping in Sport, China has formulated laws and regulations concerning narcotic drugs, psychotropic substances, precursor chemicals and stimulants, made a list of controlled medicines and further revised its contents, established a comprehensive supervision system in which related departments coordinate their efforts, and actively tighten control over controlled medicines. Over many years, China has regulated the production and circulation of narcotics, psychotropic substances and precursor chemicals, established a monitoring network to achieve proper supervision over the whereabouts and quantities of controlled medicines. It has also set up and improved a drug-abuse monitoring network to examine the details and trends of drug abuse, as well as to give pre-warnings in case of emergencies during the management of narcotics and psychotropic substances. In response to cases in recent years involving the traffic of caffeine, manufacturing of crystal methamphetamine (known as ?°ice?±) and ketamine abuse, China has organized specific inspections regarding caffeine markets, strengthened the supervision of ephedrine (the substance used to produce ?°ice?±), and adjusted the list of narcotics and psychotropic substances by putting more relevant substances under controlled medicines list.
? Regulation of Medical Devices
In 2000, China promulgated the Regulations for the Supervision and Administration of Medical Devices, and primarily established an administrative system focusing on pre-marketing product examination and approval, and post-marketing surveillance and vigilance, as well as the supervision of manufacturers. The scope of vigilance mainly covers adverse event monitoring, product re-evaluation, alert and recall. The supervision of manufacturers includes random checks, routine inspection, checks for specific items and examination of the quality management system. China implements a registration system for medical devices. Registration review includes product tests, clinical trials and on-site inspection of product quality management system. In accordance with the level of potential risks, medical devices are classified into three classes. Among which, Class III products refer to those which are implanted into the human body, or are used to support life, and pose a potential danger to the human body. Therefore, their safety and effectiveness must be rigorously brought under control. For domestic Class III medical devices and all classes of overseas medical devices, technical review for registration are carried out by the state evaluation institutions. Technical review for registration of Class I and II medical devices are conducted by provincial evaluation authorities. In accordance with the current Catalog of Medical Device Classification, 108 types of medical devices are grouped in Class I, 127 in Class II and 71 in Class III.
? National Essential Medicine System
China regards a national essential medicine system as an important basis for guaranteeing the public's primary health care, and plays an active role in establishing and improving such a system. China has systematically selected essential medicines twice, and adjusted the list of essential medicines four times. The list covers both pharmaceutical products and TCM. In July 2006, China launched a project to list essential medicines in urban communities and rural areas, successively announcing the first list of essential medicines for urban communities and rural areas, a list of the first group of enterprises designated for the production of essential medicines and a list of the first group of medicines produced by designated manufacturers. In addition, the country implemented a system of setting separate prices for medicines produced by designated manufacturers, and guided pharmaceutical manufacturers to supply cheap, commonly used medicines to medical institutions in both urban communities and rural areas. Work related to the essential medicine system has played a positive role in meeting the public's demands for essential medicines, and providing guidance to the public for the rational use of medicines.