Overview of policy development and quality standard development of traditional Chinese medicine formula granules

Overview of policy development and quality standard development of traditional Chinese medicine formula granules

Wuyuanbo Zhang Hong Leng Hong Wen Wang Wei Liu Yuzheng

Jiangxi Academy of Medical Sciences

Abstract: Traditional Chinese medicine formula granule is a new form of traditional Chinese medicine, which has been widely used in traditional Chinese medicine clinic due to its many advantages, and is also increasingly accepted by doctors and patients. The development process of the policy and quality standard of traditional Chinese medicine formula granules was reviewed for reference.

Policy development of traditional Chinese medicine formula granules

Since the 1960s, Japan, South Korea, Taiwan and Hong Kong have successively developed traditional Chinese medicine granules, such as Han formula granules, "concentrated traditional Chinese medicine" or "scientific medicine", which are mainly compound granules and supplemented by single ingredient granules[3]Traditional Chinese medicine formula granules started relatively late in mainland China, and have been paid attention to since 1990s, and entered a period of stable development[4]In 1993, traditional Chinese medicine formula granules were listed in the "spark plan" of the national science and Technology Commission, and later included in the "Tenth Five Year Plan" for the development of traditional Chinese medicine and the "action plan for the modernization of science and technology industry of traditional Chinese medicine"[4]In July, 2001, the State Drug Administration issued the Interim Provisions on the administration of traditional Chinese medicine formula granules[5]According to the document, the formula granules of traditional Chinese medicine will be included in the management of traditional Chinese medicine decoction pieces from December 1, 2001, and the approval number management will be implemented. Before the implementation of the approval number management is started, it is still in the scientific research stage. In this stage, pilot enterprises will be selected for research and production, and pilot clinical hospitals will be used. The "Interim Provisions on the administration of traditional Chinese medicine formula granules" first stipulates the management, research, pilot production, clinical use and other aspects of traditional Chinese medicine formula granules from the legal level, and puts forward technical requirements for the quality standard research of traditional Chinese medicine formula granules. . Since then, the development of traditional Chinese medicine formula particles has stepped into a fast lane. In June, 2013, the State Food and Drug Administration issued the notice on the strict processing specifications of Chinese herbal pieces and the management of the pilot study of Chinese herbal formula particles[6]This notice strictly administers the pilot study of traditional Chinese medicine formula granules, emphasizing that the traditional Chinese medicine formula granules are still in the scientific research pilot study, and the provincial food and drug administration departments shall not approve the production of traditional Chinese medicine formula granules under any name. In February 2016, TCM formula granules were included in the outline of the strategic planning for the development of traditional Chinese medicine 2016-2030[7]The outline of the plan proposes to improve the quality standard system of traditional Chinese medicine, strengthen the quality management of traditional Chinese medicine, and focus on strengthening the formulation and quality management of relevant standards of traditional Chinese medicine, including traditional Chinese medicine formula particles. By the end of 2020, China's traditional Chinese medicine formula granules have been in the experimental research stage, and the state has adopted the policy of pilot production and strict control of production enterprises.

In February, 2021, the announcement of the State Food and drug administration, the State Administration of traditional Chinese medicine, the National Health Commission, and the National Medical Insurance Bureau on ending the pilot work of drug formula particles (hereinafter referred to as the "announcement")[8]Issued, and decided to end the pilot work of traditional Chinese medicine formula granules, implement the filing management for the varieties of traditional Chinese medicine formula granules, do not implement the approval number management, and report to the local provincial drug supervision and administration department for filing before listing. . The announcement will standardize the production of traditional Chinese medicine formula granules, guide the healthy development of the industry, better meet the clinical needs of traditional Chinese medicine, and the development of traditional Chinese medicine formula granules industry will enter a new stage.

In February 2021, the State Drug Administration officially issued the technical requirements for quality control and standard formulation of traditional Chinese medicine formula granules (hereinafter referred to as the technical requirements) on the basis of the draft for comments[1]This document will be released simultaneously with the announcement. .

Development of quality standards for traditional Chinese medicine formula granules

In July, 2001, the State Drug Administration issued the Interim Provisions on the administration of traditional Chinese medicine formula granules (hereinafter referred to as the provisions)[5]The technical requirements for the quality standard research of traditional Chinese medicine formula granules were put forward, and the quality standard of traditional Chinese medicine formula granules should include: drug name, source, processing, preparation method, character, identification, inspection, extract, content determination, function and indications, usage and dosage, attention, specification, storage and other items, and the requirements for the preparation of quality standard drafting instructions were put forward. The promulgation of the regulation regulated the pilot production and use of Chinese medicine formula granules in China, and the technical requirements for the quality standard of Chinese medicine formula granules in the regulation reached the advanced level of Chinese medicine quality control at that time. The quality standard of traditional Chinese medicine formula granules is explored and studied by the pilot production enterprises according to the annex "technical requirements for quality standard research of traditional Chinese medicine formula granules" of the provisions, and the quality standard research materials are provided. The state drug administration organizes experts to review the quality standards of the varieties declared by the pilot production enterprises. The varieties that meet the requirements shall be reviewed by the Provincial Institute for drug control where the enterprise is located. The reviewed qualified quality standards shall be used as the basis for production by the production enterprises and clinical hospitals. Six pilot production enterprises of formula granules reported quality standards according to the above procedures. After approval, the enterprises organized production and clinical hospitals used them accordingly, but the quality standards of formula granules produced by each enterprise were not unified. The pilot production enterprises adopt different processes and methods, there are differences in quality control projects, product specifications are difficult to unify, and clinical conversion is not consistent, which brings great inconvenience to market supervision and clinical use, and also hinders the healthy development of the traditional Chinese medicine formula granule industry[3,9]。

Since then, in the development process of traditional Chinese medicine formula granules, some provinces have issued quality standards for traditional Chinese medicine formula granules, which unify the quality standards of traditional Chinese medicine formula granules within the same province. In October 2012, Guangdong Province officially promulgated the earliest provincial legal quality standard for traditional Chinese medicine formula granules - "Guangdong provincial standard for traditional Chinese medicine formula granules" (Volume I)[10]This volume of standards contains 102 kinds of traditional Chinese medicine formula granules, which are commonly used in Clinical Prescriptions of traditional Chinese medicine. There are two pilot manufacturers in Guangdong, namely China Resources Sanjiu Pharmaceutical Co., Ltd. and Guangdong Yifang Pharmaceutical Co., Ltd. When formulating provincial quality standards, Guangdong Province confirmed and unified according to the actual production of the two production enterprises, defined the feeding amount, the total amount of finished products and the addition of auxiliary materials, etc., and unified the quality control items and product specifications, realizing the uniform and stable quality of the same variety of traditional Chinese medicine prescription granules in the same province. Since then, in September 2015, the standard of traditional Chinese medicine formula granules in Guangdong Province (Volume II)[11]Published and distributed, the ministry standard contains 101 varieties of traditional Chinese medicine formula granules. Quality standard for traditional Chinese medicine formula granules in Guangxi Zhuang Autonomous Region (Volume I), may 2016[12]Promulgated, a total of 120 varieties of traditional Chinese medicine formula granules were collected. [13]303 varieties of traditional Chinese medicine formula granules were collected. In November, 2018, Beijing issued the quality standard of Beijing Traditional Chinese medicine formula granules[14]A total of 276 varieties of traditional Chinese medicine formula granules were collected. As a legal technical standard for the production, use, inspection, supervision and management of traditional Chinese medicine formula granules within a province, the provincial quality standard of traditional Chinese medicine formula granules provides strong technical support for supervision and pilot research, and also provides reference for the introduction of national standards for traditional Chinese medicine formula granules.

In February 2021, the State Drug Administration issued the technical requirements for quality control and standard formulation of traditional Chinese medicine formula granules[1]According to the technical requirements, the standard decoction is the material benchmark to measure whether the single traditional Chinese medicine formula particles are basically consistent with the corresponding single traditional Chinese medicine decoction pieces, and all pharmaceutical studies of traditional Chinese medicine formula particles must be compared with the standard decoction. The standard decoction was prepared by standardized decoction, solid-liquid separation, low-temperature concentration and freeze-drying. . Therefore, the standard decoction has built a "bridge" between the traditional Chinese medicine formula particles and the decoction, forming the material benchmark of the traditional Chinese medicine formula particles. Since the traditional Chinese medicine formula granules have no longer possessed the characteristics of the identification of the characteristics of traditional Chinese medicine decoction pieces, it is necessary to strengthen the specific identification and multi-component, overall quality control, establish the content determination items of active ingredients or index ingredients related to the efficacy, and use the methods of characteristic Atlas or fingerprint to evaluate the overall quality. The standard contents of traditional Chinese medicine formula granules mainly include: name, source, preparation method, character, identification, inspection, extract, characteristic map or fingerprint, content determination, specification, storage, etc[1]。

In February, 2021, the National Pharmacopoeia Commission issued the notice on the formulation of drug standards for traditional Chinese medicine formula granules[15]The notice points out that the national pharmacopoeia committee has formed a total of 160 draft national drug standards for traditional Chinese medicine formula particles, which have been publicized and will be submitted to the State Drug Administration for approval and promulgation according to the procedures in the near future. In addition, 39 national drug standards for traditional Chinese medicine formula granules are under review, and enterprises are carrying out standard research on another 246 varieties of traditional Chinese medicine formula granules.

In April 2021, the National Pharmacopoeia Commission issued the notice on matters related to the implementation of the national drug standards for traditional Chinese medicine formula granules (hereinafter referred to as the notice)[16]The notice announced the official national drug standards for the first 160 TCM formula granules. The national drug standard of traditional Chinese medicine formula granules has a high technical level, with the following characteristics: (1) for the source of multi-source traditional Chinese medicine, fix a source, so that the source of traditional Chinese medicine can be controlled and more accurate; (2) ; (3) The setting of detection items is reasonable, which can effectively control the quality of traditional Chinese medicine formula granules, especially the wide application of characteristic atlas in quality standards, which is conducive to the identification of specificity and the overall quality control of multiple components; (4) The requirements for exogenous harmful residues can better ensure the safety of people's medication. The notice stipulates that the pesticide residues, heavy metals and harmful elements, mycotoxins and sulfur dioxide residues in its standards shall be implemented according to the provisions of the current version of Chinese pharmacopoeia for decoction pieces of traditional Chinese medicine; (5) Make unified and reasonable provisions for specifications, which greatly facilitates clinical use; (6) Reasonable storage conditions can ensure the quality of traditional Chinese medicine formula granules.

Announcement of the State Food and drug administration, the State Administration of traditional Chinese medicine, the National Health Commission, and the National Medical Insurance Bureau on ending the pilot work of drug formula granules[8]It is stipulated that the traditional Chinese medicine formula granules shall be produced according to the production process recorded and conform to the national drug standards. If there are no provisions in the national drug standards, they shall conform to the standards formulated by the provincial drug regulatory department. While the national drug standards for TCM formula granules are promulgated and subsequently formulated, the provincial drug supervision and administration departments are also stepping up the formulation of provincial standards for TCM formula granules as a powerful supplement to the national drug standards for TCM formula granules. . By the end of June 2021, Shandong Provincial Drug Administration has organized and completed the standard review of 60 varieties and made it public[17]The drug administration of Gansu Province has organized and completed the standard review of 31 varieties and publicized them[18]The Zhejiang Provincial Drug Administration organized the standard review, inspection and technical review of the quality standards of traditional Chinese medicine formula granules developed by relevant enterprises, and formed the first batch of 10 standards to be publicized for traditional Chinese medicine formula granules[19]The Sichuan Provincial Drug Administration has completed the formulation of the provincial standards (public draft) for the first batch of eight varieties of traditional Chinese medicine formula granules and has publicly solicited opinions[20]In addition, Guangdong, Jiangsu, Guangxi, Hubei, Henan, Guizhou and other provinces and regions have successively issued relevant documents such as the working procedures for the formulation of provincial standards for traditional Chinese medicine formula granules and the requirements for application materials, actively promoting the formulation of provincial standards for traditional Chinese medicine formula granules.

epilogue

The pilot research work of traditional Chinese medicine formula granules in China originated in 1993. After more than 20 years of research and 20 years of pilot production and use, the industrial scale has become larger and larger, and the acceptance among doctors and patients has become higher and higher. It has become an important supplement to the form of traditional Chinese medicine decoction pieces, and has played a positive role in the cause of people's health. With the gradual improvement of relevant supporting regulations and policies of traditional Chinese medicine formula granules, the national drug standards of traditional Chinese medicine formula granules and the standards formulated by the provincial drug supervision and administration departments have been successively issued, and the regulatory responsibilities have become clearer. The traditional Chinese medicine formula granules industry will gradually embark on the track of healthy development, and traditional Chinese medicine formula granules will also play an important and unique role in the clinical medication system of traditional Chinese medicine.

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