The Way to Improve China's Drug Standard System

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The development level of drug standards is the embodiment of the development level of a country's pharmaceutical industry and the ability of drug supervision. The promotion of drug standards plays a very important role in improving the quality of drugs, improving the level of drug supervision and ensuring the safety of drug use by the public.

Since 2008, through vigorously carrying out the "National Drug Standard Improvement Action Plan", with the "Chinese Pharmacopoeia" as the core, the Ministry/Bureau issued standards as the extension, and the national drug standard system based on drug registration standards has initially taken shape, and the three drug standards are interdependent and interactive. In the future, "opening up channels and mutual assistance between various standards will become the 'common' of drug standard reform '." State Pharmacopoeia Committee Secretary-General Zhang Wei said.

Three types of standards highlight Chinese characteristics

Drug standards are the technical regulations made by the state to ensure the quality of drugs, the quality indicators, inspection methods and production processes of drugs, and are mandatory technical guidelines and legal basis that must be observed in all aspects of drug production, operation, use and supervision and management. "Drug standards make basic technical requirements for a target compound or prescription process, which is one of the important bases for daily inspection or evaluation of drug quality compliance. The perfection of drug standards is the ultimate manifestation of the level of technology, analytical technology, personnel quality and other comprehensive strength, and indirectly represents the level of development of a country's drug industry." Said Tu Jiasheng, professor of pharmacy and doctoral supervisor of China Pharmaceutical University, member of the 10th Pharmacopoeia Committee, and deputy director of the Pharmaceutical Excipients and Package Materials Committee.

According to statistics, there are nearly 20,000 national standards in China, including pharmacopoeia standards, bureau/ministerial standards and registration standards. Among them, the 2015 edition of the Chinese Pharmacopoeia contains a total of 5608 variety standards.

As the core of the national drug standard system, the Chinese Pharmacopoeia is formulated and revised by the State Pharmacopoeia Committee organized by the State Drug Administration. It is a code with national legal effect and records drug standards and specifications. The varieties contained in the "Chinese Pharmacopoeia" must be selected by a strict medical expert committee. It mainly contains varieties that are commonly used in clinical practice, with clear efficacy, mature technology, controllable quality, and relatively complete standards. Other varieties that do not meet the above conditions (including short time to market) or have special circumstances are included in the bureau or ministerial standards. The first part of the pharmacopoeia contains varieties of traditional Chinese medicine, the second part contains varieties of chemical drugs, the third part contains varieties of biological products in the 2005 edition, and the fourth part in the 2015 edition contains general testing technical requirements, standards for pharmaceutical excipients and drug packaging materials.

As the basis of the national drug standard system, the drug registration standard refers to the standard approved by the State Food and Drug Administration to the applicant for a specific drug, and the manufacturer of the drug must implement the registration standard. The provisions of the drug registration standards shall not be lower than the provisions of the Chinese Pharmacopoeia. It is the drug quality control standards for the implementation of the products on the market after the drug evaluation center and technical experts organized by the State Drug Administration to examine the safety, effectiveness and quality control of the drug research data declared by the applicant.

As the extension of the national drug standard system, the standard issued by the Ministry/Bureau is the drug standard after the national drug supervision and administration department organizes the National Pharmacopoeia Committee to unify and standardize the drug registration standards of different enterprises. Generally speaking, the Chinese Pharmacopoeia and the standards issued by the Ministry/Bureau are the most basic quality requirements for drugs. For production enterprises, their factory internal control standards or registration standards should be higher than the unified standards set by the state.

Make concerted efforts to push the plan to the ground

Based on the importance of drug standards, the party and the state have always attached great importance to drug standards. In 1950, China established the National Pharmacopoeia Committee as the earliest standardization organization. Before the reform and opening up, China promulgated three editions of Chinese Pharmacopoeia in 1953, 1963 and 1977, but the drug standard system has not yet been formed. After the reform and opening up, my country has successively promulgated the 1985, 1990, and 1995 editions of the "Chinese Pharmacopoeia" and a series of ministerial standards. Since the beginning of the 21st century, China has successively promulgated the 2000, 2005 and 2010 editions of the Chinese Pharmacopoeia, and has successively completed the work of cleaning up, rectifying and improving local standards." National Pharmacopoeia Commission General Division Deputy Director Hong Xiaoxu said.

In recent years, with the rapid development of China's economy and society, people's health needs are increasing day by day, and the quality and safety of drugs have received unprecedented attention from the whole society. At present, in order to strengthen food and drug safety, the CPC Central Committee and the State Council put forward the "four strictest", requiring the establishment of the strictest food and drug safety supervision system and the improvement of food and drug quality standards and safety access system. Drug safety has risen to the height of the national economy, people's livelihood and national strategy. The preparation of pharmacopoeia and the national drug standard improvement action plan have been included in the national food and drug safety "Eleventh Five-Year", "Twelfth Five-Year" and "Thirteenth Five-Year" plans. They are supported by hundreds of millions of special funds from the central government. The "Healthy China 2030" Planning Outline also puts forward the task requirements for improving the national drug standard system.

On March 29, the State Pharmacopoeia Commission organized domestic drug testing institutions, scientific research institutes, foreign senior experts and large auxiliary material enterprises such as Hunan Erkang, Anhui Shanhe, Liaoning Oak and Huzhou Prospect to hold a "Symposium on Pharmaceutical Auxiliary Material Standards Enterprises" to listen to the opinions and suggestions of enterprises on auxiliary material standards. "This is only a microcosm of the revision process of the Pharmacopoeia. Since the implementation of the 'Action Plan for the Improvement of National Drug Standards' in 2008, the National Pharmacopoeia Commission has repeatedly organized enterprises to participate in the discussion." Anhui Shanhe Pharmaceutical Accessories Co., Ltd. Chairman Yin Zhenglong said.

It is reported that the 2015 edition of the "Chinese Pharmacopoeia" is a concentrated expression of the results of the "National Drug Standard Improvement Action Plan" in recent years, adding and upgrading a number of drug standards and testing methods. The 2015 edition of the Chinese Pharmacopoeia contains a total of 5608 varieties, including 1082 new varieties and 1134 revised varieties, with an increase of 23.7. The general principles of the Chinese Pharmacopoeia are 317, and the general principles of preparation are 38. The general principles of verification methods are 240, including 28 new verification methods, 63 integrated verification methods, 67 revised, and 18 new guidelines and general principles.

Tu Jiasheng said that before the 2015 edition of the Chinese Pharmacopoeia, pharmaceutical excipients were mainly included in two parts, and the 2015 edition began to be concentrated in four parts, aiming to further highlight the role of pharmaceutical excipients in preparations and gradually establish and improve the quality control system of pharmaceutical excipients. The 2015 edition of the Chinese Pharmacopoeia is characterized by five aspects: first, the drafting and approval of nearly 200 standards for pharmaceutical excipients have been completed. The total number of varieties received in the Pharmacopoeia has reached 270, 137 varieties of new excipients have been added, and the increase in varieties received has reached 105, basically covering nearly 50% of the commonly used pharmaceutical excipients in China's preparations at present, making up for the shortage of standards for pharmaceutical excipients in China; the second is to comprehensively revise the general rules of pharmaceutical excipients, strengthen the production, use, quality control and applicability research of excipients, and improve the quality and safety of pharmaceutical excipients as a whole; the third is to strengthen the formulation of standards for excipients for injection and improve the standards for high-risk injections; the fourth is to strengthen the functional control requirements of pharmaceutical excipients to further ensure the stability and batch consistency of preparations; fifth, pay attention to the research on the standard system of pharmaceutical excipients and drug packaging materials and the formulation of technical requirements associated with drugs, so as to provide technical support for the State Administration to implement the review and approval system of pharmaceutical packaging materials, pharmaceutical excipients and drugs. In addition, from the 2015 edition of the "Chinese Pharmacopoeia" began to include the standard general technical requirements of drug packaging materials, covering APIs, preparations, pharmaceutical excipients, drug packaging materials and other important links related to the safety and effectiveness of drugs.

Open the channel to promote the standard promotion

Although China's drug standard system has been initially established, there are still many deep-seated problems in drug standard work that need to be solved urgently. According to statistics, the 2015 edition of the Chinese Pharmacopoeia contains 2603 chemical drugs out of 5608 varieties, while the 37 edition of the United States Pharmacopoeia contains 4303 varieties (mainly chemical drugs), which is far more than the loading capacity of China's Pharmacopoeia. Pharmaceutical excipients China's Pharmacopoeia contains 270 varieties, while the United States Pharmacopoeia contains more than 530 varieties. Although the overall level of the Chinese Pharmacopoeia has initially reached or approached international standards, due to the fact that there are more than 12000 ministerial or bureau standards in my country, accounting for 70% of the total standards, due to historical conditions and the development stage of the pharmaceutical industry, most The standard level is relatively low, and there are problems in varying degrees, such as backward detection methods, weak specificity, inability to accurately determine active ingredients, and inability to truly reflect impurity content, standard aging phenomenon is more prominent.

In the future, the reform of drug standards will be guided by the five development concepts of "innovation, coordination, green, openness and sharing", adhere to the principle of "scientific, advanced, practical and standardized", and adopt the strategy of "establishing high, raising middle and eliminating low.

First of all, the national drug standards to carry out a comprehensive clean-up. In combination with the adjustment of the medical insurance catalogue and the basic drug catalogue, priority will be given to varieties with strong clinical demand, large market sales volume, many manufacturers, large differences in drug prices, poor quality stability and high safety risks to carry out standard improvement research. Combined with market demand, the improved and effective standards will be included in the pharmacopoeia and backward standards will be eliminated. Establish a scientific and standardized drug standard withdrawal mechanism to form a joint force of resource sharing, promotion, improvement and elimination.

Secondly, drug registration standards will become an important source of the Chinese Pharmacopoeia and the standards issued by the Bureau. The registration standard is a specific standard approved by the drug regulatory department to the registration applicant, which has the characteristics of product personalization. When two or more registration standards exist at the same time and there are big differences, the State Pharmacopoeia Commission will start the research and formulation of national unified standards in accordance with the principle of "high is not low", which will greatly mobilize the enthusiasm of advantageous enterprises to participate in the revision of the standard system.

Third, the formulation and revision of national drug standards will be closely integrated with drug quality and efficacy consistency evaluation, drug quality evaluation sampling, drug re-evaluation and other work to further improve the pertinence and purpose of standard formulation and revision. Over the years, the re-evaluation of drugs in our country has a relatively weak foundation. To a certain extent, there are situations where products are "only alive but not dead", standards are "only in and out", and there is no way to eliminate them. With the increasing strengthening of this work in the future, especially the evaluation of the quality and efficacy of generic drugs, the revision of national standards will also be closely tracked and improved, such as the improvement of the dissolution method of oral solid preparations to the original drug. Zhang Wei said, "Due to historical reasons, some generic drugs have a weak medical research foundation when they are on the market. They have not been evaluated by BE (bioequivalence) and have not carried out in vivo and in vitro correlation studies. Therefore, the evaluation of the quality and efficacy consistency of generic drugs is a historic supplementary lesson for Chinese pharmaceutical enterprises, and it is also an opportunity to use technical means to promote the reshuffle of the pharmaceutical industry and the survival of the fittest.

Industry insiders said that the current enterprise in the leading standards of power is insufficient. The market does not encourage registration standards. The state does not have policy support and interest protection measures for enterprises to implement registration standards. After enterprises actively raise the standards, they will not only not benefit, but may also increase the cost of production, inspection and quality control. Enterprises will inevitably change from standard improvement. Participants become bystanders, from active improvement of individual registration standards to passive implementation of common national standards.

On the contrary, industry associations, society-led social group standards gradually become active. On March 28, the Chinese Medicine Association issued two group standards-"Technical Specifications for the Processing of Radix Paeoniae Alba (Radix Paeoniae Alba)" and "Limit Standards for Pesticide Residues and Heavy Metals and Harmful Elements in Pollution-free Panax Notoginseng Medicinal Materials and Decoction Pieces". Zhou Xun, secretary-general of the Chinese herbal medicine market professional Committee of the Chinese herbal medicine association, said that at present, the Chinese herbal medicine association and China Hanguang are organizing the declaration of primary processing standards for the origin of genuine medicinal materials such as chrysanthemum, salvia miltiorrhiza, bupleurum, rehmannia root, yam and ophiopogon japonicus. the association will also organize the formulation of group standards such as specification grade standards and storage standards. In recent years, China Pharmaceutical Packaging Association has also issued "Gelatin Hollow Capsules", "Blow and Potting Integration (BFS) Infusion Technology Guide", "Pharmaceutical Rubber Plug Production Quality Management Standards" and other association standards.

Association standards are formulated and issued by societies, associations, chambers of commerce, federations, and industrial technology alliances with legal personality and corresponding professional capabilities to coordinate relevant market entities and formulate and issue in accordance with market needs. It is a supplement to national standards and has the characteristics of professionalism and recommendation for voluntary adoption by the society. Because the community standard is formulated by the industry organization according to the industry situation, it is also the wind vane of the industry development and has a leading role in the industry standard.

Zhang Wei said, "In the past, my country was mainly dominated by government departments in the formulation and revision of standards. Companies were not enthusiastic about participating in the formulation and revision of national standards and did not pay enough attention. Some companies even did not know after the standards were released and implemented. It is too late to make amendments. In the future, we should further strengthen the implementation of the main responsibility of enterprises in the revision of standards, encourage superior enterprises to lead the revision of standards, and support associations to establish industry standards. The State Pharmacopoeia Commission will also continue to strengthen the interaction and coordination of the formulation and revision of enterprise standards and community standards, so as to adapt to the new normal of the reform and development of drug standard formation mechanism." (our intern reporter zhang chunling)