Good Manufacturing Practice for Chinese Materia Medica
A brief analysis of the background of the revision and the main revision contents
After nearly 6 years of revision, the State Drug Administration, the Ministry of Agriculture and Rural Affairs, the State Forestry and Grassland Administration, and the State Administration of Traditional Chinese Medicine jointly issued the official version of the revised official version - "Good Manufacturing Practice for Chinese Materia Medica" (hereinafter referred to as the new version of GAP) jointly issued by the State Drug Administration, the Ministry of Agriculture and Rural Affairs, the State Administration of Traditional Chinese Medicine. In the announcement, the scope of application, objects, management departments and local governments of the new version of Chinese herbal medicine GAP are clarified. In particular, the implementation method of GAP is not a certification system, nor a filing system, but an "extended inspection" of Chinese herbal medicine production enterprises through supervision and inspection of Chinese medicine production enterprises. Chinese medicine manufacturers using raw materials that meet the requirements of the new version of the GAP of Chinese herbal medicines may mark "medicinal materials meet gap requirements" in the appropriate position of the drug label as required.
The new version of Chinese herbal medicine GAP is the technical guiding principle of standardized production of Chinese herbal medicine production enterprises, the technical standard for the quality audit of suppliers of Chinese medicine production enterprises, and the technical basis for the extended inspection of drug supervision and management departments, which will become the starting point for base enterprises, Chinese medicine enterprises, industry authorities and local people's governments to develop Chinese herbal medicines. The author is fortunate to participate in the revision of the new version of the Chinese herbal medicine GAP throughout the process. In order to promote the implementation of the new version of the GAP of Chinese herbal medicines, promote the construction of the standardized production base of the GAP of Chinese herbal medicines, and promote the high-quality development of the Chinese medicine industry, this paper explains the background process, main revision ideas, and key issues of concern to the new version of the GAP of Chinese herbal medicines, so as to facilitate the industry colleagues to understand and understand the new version of the Gap of Chinese herbal medicines from different angles and better promote its implementation.
1
Revision background and process
Chinese herbal medicine is the material basis for the development of traditional Chinese medicine, and is the main raw material of the traditional Chinese medicine industry and the great health industry, and it is extremely important to ensure the quality of the source Chinese herbal medicines. In 2002, the former State Drug Administration issued a trial version of the GAP for Chinese herbal medicines, and the study determined the use of certification management; in 2003, the certification was launched after the issuance of certification management measures and certification inspection and evaluation standards; in 2016, the GAP certification was cancelled. At this stage, a total of 177 GAP bases of Chinese herbal medicines have been certified, involving 71 kinds of Chinese medicinal materials in 110 enterprises in 26 provinces across the country.
The implementation of GAP has improved the industry's emphasis on the quality of raw materials and medicinal materials, cultivated a team of talents, and played a certain role in exploring and promoting the standardization and large-scale production of Chinese herbal medicines and improving the quality of Chinese herbal medicines. Especially in recent years, the production of Chinese herbal medicines and the construction of bases have achieved remarkable results, which has improved the modernization level of traditional Chinese medicine agriculture in the mainland. However, the trial version of the Chinese herbal medicine GAP has gradually emerged some problems that do not adapt to the development of the industry for more than 10 years, such as its content is too general, the concept of quality risk control has not been well implemented, and some important links affecting the quality of Chinese herbal medicines lack clear requirements; the technical regulations are relatively vague, the production organization method is uncertain, and it is difficult for enterprises to understand and master and implement operations.
In March 2016, GAP certification was cancelled in accordance with the Decision of the State Council on Canceling and Adjusting a Number of Administrative Examination and Approval Items and Other Matters. The industry looks forward to revising the trial version of the GAP of Chinese herbal medicines and exploring new implementation methods to better meet the actual needs and new regulatory methods of the rapid development of Chinese herbal medicines. To this end, in November 2015, the former State Food and Drug Administration officially launched the revision of the pilot version of the GAP of Chinese herbal medicines and entrusted the Institute of Medicinal Plants of the Chinese Academy of Medical Sciences to establish a technical expert group. After discussions by experts at different levels, relevant departments of the State Council, relevant departments and subordinate units of the National Drug Supervision and Administration System, the revised draft was basically finalized after soliciting opinions from the whole society in October 2017 and July 2018, respectively. Since then, the focus has been on the repeated study of the release form, release department, implementation method, supporting policies, etc., and it has been determined that the new version of the Chinese herbal medicine GAP will be released after the trial version of the Chinese herbal medicine GAP is abolished. After consultation, it was finally clarified that it was jointly issued by the State Drug Administration, the Ministry of Agriculture and Rural Affairs, the State Forestry and Grassland Administration, and the State Administration of Traditional Chinese Medicine, and the implementation methods and responsibilities of all parties in the announcement also clarified the implementation methods and responsibilities of all parties in the new version of the Chinese herbal medicine GAP. On March 17, 2022, the new version of the Chinese herbal medicine GAP and its announcement were officially released.
2
Chapter modifications and changes
The new version of the Chinese herbal medicine GAP has a total of 14 chapters and 144 articles, compared with the trial version of the Chinese herbal medicine GAP, 4 chapters and 87 articles, except for the added chapters, the structure of other chapters has basically not changed, but the title and content have been greatly modified (Table 1). Three new chapters have been added, namely "Chapter 11 Quality Inspection", "Chapter 12 Internal Audit", "Chapter 13 Complaints, Returns and Recalls", which are split from the trial version of the Chinese herbal medicine GAP "Personnel and Equipment" into 2 chapters, which are "Chapter 3 Institutions and Personnel" and "Chapter 4 Facilities, Equipment and Tools". The trial version of GAP only has a section on "Cultivation and Breeding Management", and the new version of the Chinese herbal medicine GAP chapter 6 to 9 is divided into sections.
Table 1 Comparison of the main chapters and articles of the new version of chinese herbal medicine GAP and the trial version of Chinese herbal medicine GAP
In order to highlight quality management, the original chapter of "quality management" was added to 3 chapters of "quality management", "quality inspection" and "internal audit". In order to reflect the concept of formulating technical regulations (or requirements) before implementing management, special provisions are made in Chapter 2 on the technical procedures and standards that must be formulated. Chapters 5 to 9, the previous provisions of each chapter are the requirements for how to formulate technical regulations, and then the requirements for implementing management according to technical regulations. In chapters 6 to 9, this body is directly embodied in different "sections", such as the first and third sections of "Chapter 7 Planting and Breeding" are "Planting Technical Regulations" and "Breeding Technical Regulations", and the second and fourth sections are "Planting Management" and "Breeding Management".
3
Main revision ideas
3.1 Emphasize the implementation of key management in key links that have a significant impact on the quality of Chinese herbal medicines, while attaching importance to the detailed management of the whole process and establishing the concept of risk management and control
There are many production links of Chinese herbal medicines and complex quality management, so in order to achieve standardized production, it is necessary to grasp the key links, so as to effectively control production and management costs. Drawing on the Idea of Good Manufacturing Practice (GMP) and the Good Manufacturing Practice (GACP) for the cultivation and collection of medicinal plants issued by countries around the world and the World Health Organization, the new version of chinese herbal medicine GAP starts from the concept of risk control and proposes that enterprises should "clarify the key links affecting the quality of Chinese herbal medicines" and "achieve on-site guidance, supervision and recording of key links". Paying attention to the "key links" is the core concept of the new version of the Chinese herbal medicine GAP throughout, and it is also the core concept of guiding the revision of the specification and striving to better guide the production. To this end, the new version of the Chinese herbal medicine GAP has refined and clarified the key links affecting the quality of Chinese herbal medicines as much as possible, highlighting the management, control, prevention, prohibition and construction of key links, and for the first time introduced a unified planning and production base, unified supply of seeds, seedlings or other propagating materials, unified fertilizer, pesticides, feed, veterinary drugs and other input management measures, unified planting or breeding technical regulations, unified harvesting and origin processing technical regulations, unified packaging and storage technical regulations (hereinafter referred to as "six unifications") concept. It is required that the key links in the whole process of Chinese herbal medicine production can be traced, and "six unifications" + "traceability" have become the concentrated embodiment of the concept of key links in the new version of gap control of Chinese herbal medicines.
In the trial version of the Chinese herbal medicine GAP, the quality management is only 1 chapter and 5 articles, which is too general, it is difficult to regulate the quality management behavior of the enterprise well, and the implementation of the enterprise comparison is also more difficult. Quality management is adjusted to 3 chapters, "quality management" chapter proposes to establish the quality management concept of key links in the whole process as a whole, while strengthening risk management and control; the new "quality inspection" chapter clarifies the requirements of inspection qualifications and sample retention, highlighting the standardization and operability of inspection; the new "internal audit" chapter proposes that enterprises should regularly carry out internal audit of the implementation of the norms, which is to learn from GMP's first introduction of gap management concepts and improve the quality management system for the production of Chinese herbal medicines.
3.2 Emphasize high standards and strict requirements, take into account the actual situation of Chinese herbal medicine production and the current technical level, and strive to avoid "losing to strictness" or "losing to leniency"
The overall requirements of the trial version of the Chinese herbal medicine GAP are low, but some of the requirements in the certification standards are unreasonable, such as the processing of medicinal materials needs to be centralized, the testing laboratory must be built by itself, and the breeding of fine seeds must be carried out. The high standards and strict requirements of the new version of Chinese herbal medicine GAP are mainly reflected in the major key links affecting the quality, such as the place of origin should generally choose the authentic area, do not allow the use of germplasm that may affect the quality of Chinese herbal medicines and the data is not clear (such as transgenic varieties, polyploid varieties, etc.), prohibit the use of growth regulators such as Zhuang Genling, Bulkin and other growth regulators to regulate the growth of Chinese herbal medicine harvest organs, prohibit sulfur fumigation in the processing and storage of the place of origin, and prohibit the use of highly toxic fumigants banned by the state.
Realistic adjustments have been made to the links stipulated in the trial version of the Chinese herbal medicine GAP, but are actually difficult to achieve due to technical or economic constraints. For example, herbicides are not banned, but their use is required to be minimized or avoided; farms, forest farms, companies + farmers or cooperatives can be used; fertilizer regulations are mainly organic fertilizers, and chemical fertilizers are used to a limited extent; processing in the place of origin does not need to be centralized, but technical regulations need to be unified; quality can be self-tested or third-party testing; breeding of new varieties is encouraged but not necessary, and the source of seed sources is required to be clear and the supply is uniform.
3.3 Implement "write what I want to do, do what I write, remember what I do", and set technical regulations and quality standards in advance as the premise and basis for implementing base construction and management
The trial version of the Chinese herbal medicine GAP does not specify that enterprises should first formulate technical regulations and standards, and there are fewer relevant requirements for the formulation of technical regulations and standards, and there is no clear that the enterprise construction base is managed according to technical regulations and related systems, that is, the concept of "writing what I want to do, doing what I write, and remembering what I do" is not implemented. Therefore, the emergence of GAP certification and the actual management of enterprise bases "two skins". The new version of the Chinese herbal medicine GAP not only proposes that enterprises should first formulate the technical regulations (requirements) for the production of Chinese herbal medicines and the internal control quality standards of Chinese herbal medicine enterprises, but also defines in detail what technical regulations and standards need to be formulated, how to formulate these technical regulations, and what the technical regulations and standards should contain.
The new version of the Chinese herbal medicine GAP reflects the "write I want to do, do what I write, remember what I do", the implementation of technical regulations is the guide to management, management is the implementation of the regulations, records are the key data guiding ideology of management, and strive to make the new version of Chinese herbal medicine GAP a feasible specification for enterprises to guide production, and strive to GAP work can be truly organically combined with the construction of Chinese herbal medicine bases and production management, and strive to eliminate the form and do the model. The technical regulations are formulated by the enterprise according to the requirements of the new version of the Chinese herbal medicine GAP, and the bottom line is not to violate the prohibitive clauses in the new version of the Chinese herbal medicine GAP, and to clarify the preventive and encouraging provisions. However, once the technical regulations are formulated, the enterprise needs to comply with the implementation, and the key management process data needs to be truthfully recorded to ensure that the whole process can be traced.
3.4 Based on the characteristics and inheritance of traditional Chinese medicine, encourage the adoption of applicable new technologies and methods
The new version of Chinese herbal medicine GAP fully reflects the inheritance and innovation of the development path of traditional Chinese medicine, such as inheritance is reflected in the preferred road real estate area of the place of origin, interspecific grafting materials are allowed to be used if they are traditional habits, harvesting period and harvesting methods must indeed refer to traditional harvesting experience, and processing methods in the place of origin must indeed refer to excellent traditional methods. On the other hand, encourage the use of new technologies and new equipment to improve the modernization level of the production of Chinese herbal medicines, such as clearly encouraging enterprises to use modern information technology to build a traceability system, encouraging the use of efficient mechanized harvesting technology, modern storage and storage of new technologies, new equipment, efficient drying technology, intensive drying technology, modern packaging methods and appliances.
3.5 Emphasize the unification of standardized production of Chinese herbal medicines and ecological environmental protection
The fundamental purpose of GAP is to guide the production of high-quality medicinal herbs. To this end, on the one hand, the new version of the Chinese herbal medicine GAP emphasizes the need to consider the impact of environmental conditions on the production and quality of Chinese herbal medicines, reasonable and effective intervention and regulation; on the other hand, in order to implement the national ecological civilization construction and ecological environmental protection strategy, it is also clear in many places to avoid the adverse impact of planting and breeding on the ecological environment, such as the site selection and construction of production bases, the use of pesticides, the use of fertilizers, the harvesting of medicinal materials, the primary processing of medicinal materials, etc., so as to achieve the sustainable development of the production of Chinese herbal medicines.
3.6 Strengthen the management of the flow of medicinal materials, and add management contents such as release, complaints, returns and recalls
The trial version of the Chinese herbal medicine GAP does not have management contents such as release, complaints, returns and recalls. Considering that there are still a series of links that affect the quality of medicinal materials used by Chinese medicine enterprises in the links from the production of the base to the final flow to the market, the new version of the Chinese herbal medicine GAP draws on GMP and for the first time introduces the management of release, complaints, returns and recalls, which are separately written into chapters and sections. These management contents are all process risk management and control, and they are all management links after the production, processing and packaging of medicinal materials, which may be relatively unfamiliar to Chinese herbal medicine enterprises and bases. However, these management basically do not involve production bases and farmers, and enterprises are easy to establish corresponding management systems and processes, which are relatively easy to implement.
4
Treatment of priority issues of concern
4.1 Scope of Application
The new version of the Chinese herbal medicine GAP is suitable for the cultivation and breeding of Chinese herbal medicines, and is also suitable for wild care and imitation wild cultivation. This is mainly due to the increasing number of production methods in the latter 2 in recent years. These methods are collectively referred to as standardized production according to GAP production. About 70% of the types of Chinese medicinal materials used in clinical practice come from wild resources, and wild Chinese medicinal materials do not involve planting and breeding processes, but all aspects from harvesting and processing also need to be standardized to ensure quality. To this end, the new version of the Chinese herbal medicine GAP pointed out that the harvesting and processing of wild Chinese medicinal materials can refer to this specification, but it is not mandatory. Due to the small number of mineral drugs and the origin of non-biological, their natural properties, production process and biological drugs are very different, and they are not included in the scope of application of the new version of Chinese herbal medicine GAP.
4.2 About the "Six Unifications"
In order to implement the concept of risk management and control, focusing on the key aspects affecting quality, the new version of Chinese herbal medicine GAP put forward the concept of "six unifications" for the first time. This is an important highlight of the new version of the Chinese herbal medicine GAP, and it is also the core point of building a standardized production base according to the new version of the Chinese herbal medicine GAP. In order to make the "six unifications" better landed, taking into account the current actual situation and technical level of chinese herbal medicine production, the new version of Chinese herbal medicine GAP is based on the degree of influence on the quality of Chinese herbal medicines, and the requirements for "six unifications" are hierarchical, which is specifically manifested as: 1) The planning of the production base, such as the selection of origin and the layout of the base, needs to be unified planning. 2) The seeds, seedlings or other propagating materials used in the base need to be supplied uniformly. This is one of the most stringent regulations in the new version of the Chinese herbal medicine GAP, because germplasm is the foundation of the quality of medicinal materials. Al-Qaida can be organized in such a way as a company + farmer, but the seeds, seedlings or other propagating materials used in the base must be supplied by the enterprise in a unified manner. 3) Fertilizers, pesticides, feed, veterinary drugs and other inputs do not require unified supply, but require unified management measures; for planting or breeding, harvesting and processing, packaging and storage of origin, there is no requirement to be uniformly implemented by enterprises, but the technical regulations required to guide the implementation must be unified. Therefore, enterprises must uniformly formulate management measures and technical regulations for these links, and implement unified measures and procedures into production and base construction through training and other means.
4.3 About Quality Standards
For the quality of Chinese herbal medicines, the core goal of GAP is to ensure that the quality of the medicinal materials produced at the base is stable and meets the established quality standards. According to the requirements of the new version of the Chinese herbal medicine GAP, enterprises must first formulate their own quality standards for medicinal materials, as the guiding goal of base construction, and need to clarify the standards of seeds, seedlings or other propagating materials used at the same time. To this end, the new version of the Chinese herbal medicine GAP proposes that enterprises should formulate quality standards for Chinese herbal medicines, the standards should not be lower than the current statutory standards, should formulate standards for Seeds, Seedlings or other propagating materials of Chinese herbal medicines, and if necessary, can formulate quality standards for Chinese medicinal materials in intermediate links such as harvesting, processing and acquisition. Among them, the standard for formulating seeds, seedlings or other propagating materials for Chinese herbal medicines is a new mandatory requirement for the new version of Chinese herbal medicine GAP, reflecting the importance attached to seeds and seedlings as the source of medicinal material quality.
For medicinal material standards, enterprises can adopt the standards of the Pharmacopoeia of the People's Republic of China (hereinafter referred to as the "Chinese Pharmacopoeia"), and can also formulate higher standards that better reflect the management and production level of the enterprise base, including intermediate links, such as harvesting, processing and acquisition of medicinal materials quality standards. In order to facilitate the implementation of enterprises, the new version of Chinese herbal medicine GAP gives reference quality standard indicators, such as medicinal material traits, inspection items, physical and chemical identification, leachables, fingerprints or feature maps, indicators or active ingredient content, medicinal pesticide residues or veterinary drug residues, heavy metals and harmful elements, mycotoxins and other toxic and harmful substances control standards.
4.4 About the way production is organized
The production organization of Chinese herbal medicines determines to a certain extent whether enterprises can implement standardized production in accordance with GAP requirements. Depending on the way production is organized, production management, quality control and preventive measures will vary greatly. The trial version of the Chinese herbal medicine GAP does not define this, and the implementation of enterprises often "flashes its words", and there are also so-called "listing" bases. In the past 20 years, the intensive production of Chinese herbal medicines in the mainland has made great progress, and Chinese medicine enterprises have built a large number of bases by means of self-construction, co-construction and sharing, and explored many ways of base construction and organization, of which most of them are in the way of companies + farmers, while there are fewer farm-style intensive bases. Therefore, the new version of the Chinese herbal medicine GAP proposes that the production base of Chinese herbal medicines can be built by using the organizational methods of farms, forest farms, companies + farmers or cooperatives. It contains three meanings, one is that the enterprise must clarify the organization of the base construction, the second is not to force the farm, the forest farm base, the third is to list 4 representative organizational methods as an example, the enterprise can also take other ways, but must be clear.
4.5 Regarding origin
The choice of origin is one of the key links affecting the quality of Chinese herbal medicines, and the selection of the Dao real estate area is an effective measure to ensure the quality of Chinese herbal medicines. To this end, the new version of the Chinese herbal medicine GAP proposes that the production base of Chinese herbal medicines should generally be located in the Dao real estate area. Considering that there are disputes in the Dao real estate area of some medicinal materials, such as the continuous changes in the Dao real estate area of some medicinal materials in history, the non-historical Dao real estate area of the current main production area of some medicinal materials and the fact that the authenticity of some medicinal materials is not obvious, the new version of Chinese herbal medicine GAP takes into account the actual production and proposes that the site can be selected in the non-Dao real estate area, but sufficient literature or scientific data should be provided to prove its suitability.
4.6 About germplasm
The provisions on germplasm issues are controversial. Chinese herbal medicines are the raw materials for drinking tablets, formula granules, proprietary Chinese medicines, etc., and germplasm is the material basis for the safety, effectiveness and controllable quality of Chinese herbal medicines. After many discussions, the consensus formed by experts is that the germplasm use of Chinese herbal medicines must be strictly limited. In order to ensure the purity of the germplasm of Chinese herbal medicines, reduce the risks caused by uncertain germplasm, and encourage the breeding of excellent new varieties and promote the production of Chinese herbal medicines, the new version of Chinese herbal medicine GAP encourages enterprises to carry out the breeding of excellent varieties of Chinese herbal medicines. In view of the breeding methods with major changes in germplasm characteristics and high quality risk, the new version of chinese herbal medicine GAP adopts a relatively conservative attitude, stipulating that artificial breeding of polyploid or haploid varieties, interspecific hybrid varieties and transgenic varieties is prohibited. For breeding methods with relatively low quality risks, they are relatively open,000, stipulating that if they need to use interspecific grafting materials used in non-traditional customs, artificial mutagenesis varieties (including physical, chemical, space mutagenesis, etc.) and other biotechnology breeding varieties, enterprises should provide sufficient risk assessment and experimental data to prove that new varieties are safe, effective and of controllable quality.
4.7 About pesticide use
Pesticide use is a "dilemma" in the revision. The trial version of the Chinese herbal medicine GAP stipulates that if pesticides must be applied, the minimum effective dose and high-efficiency, low-toxicity and low-residue pesticides should be used in accordance with the provisions of the Regulations of the People's Republic of China on the Administration of Pesticides, so as to reduce pesticide residues and heavy metal pollution and protect the ecological environment. According to the Regulations of the People's Republic of China on the Administration of Pesticides before and after the revision in 2017, pesticides need to be registered by the national pesticide administration before they can be used. However, as of July 2017, only 7 kinds of Chinese medicinal materials in the country, such as ginseng, panax ginseng, goji berries, Hangbai chrysanthemum, Bai Shu, Yan hu suo, and Dendrobium officinale, have registered 39 kinds of pesticides, which means that most Of the Chinese herbal medicines have no pesticides available. In recent years, the agricultural and rural departments have accelerated the registration of pesticides for small crops, and the grouping of chinese herbal medicine efficacy tests and the filing of emergency drug applications have been listed as one of the key tasks, but as of February 2022, there are only 21 kinds of Chinese herbal medicines with 490 registered pesticides.
For Chinese herbal medicines with serious pests and diseases, it is difficult to have a complete replacement of pesticides, more effective and more economical control methods, especially in recent years, the lack of rural labor resources, labor costs have increased significantly, and many intensive planting bases have to use herbicides. To this end, the new version of the Chinese herbal medicine GAP proposes that the use of pesticides should meet the principle requirements of relevant regulations, prohibit the use of highly toxic, highly toxic, high residue pesticides prohibited by the competent administrative department of agriculture and rural affairs under the State Council, and other pesticides restricted to the use of traditional Chinese medicinal materials, and proposes to give priority to the use of high-efficiency, low-toxicity biological pesticides, and should minimize or avoid the use of chemical pesticides such as herbicides, insecticides and fungicides.
4.8 About the use of growth regulators such as Strongrolin and Bulkin
The use of growth regulators is also a controversial issue. After many discussions, expert opinions tend to be consistent, that is, ensuring the quality of Chinese herbal medicines is the first starting point for the standardized production of Chinese herbal medicines. The main goal of the use of production regulators such as Zhuanggenling and Bulkin is to increase production, and the existing research data show that its use has obvious adverse effects on the quality of Chinese herbal medicines, and it should be banned in The residue of Chinese herbal medicines and soils. Based on this, in order to ensure that growth regulators can still be used in seeds, seedling treatment and other links, after comprehensive consideration, the new version of the Chinese herbal medicine GAP regulations prohibit the use of growth regulators such as Zhuang gen ling, expanding hormone and so on to regulate the growth of Chinese herbal medicine harvest organs.
4.9 About sulfur fumigation and aluminium phosphide fumigation
The 2020 edition of the Chinese Pharmacopoeia stipulates the residue limit standards for sulfur dioxide in Chinese herbal medicines, of which 10 Chinese medicinal materials (yam, ox knee, pink kudzu, tiandong, tianma, smallpox pollen, baihe, bai peony, bai shu, dang ginseng) are 400 mg·kg–1, and the others are 150 mg·kg–1. According to production feedback, if sulfur fumigation is used, the limit standard of 150 mg·kg–1 will generally be exceeded. Therefore, most Chinese medicinal herbs cannot be smoked with sulfur. In recent years, the modern drying technology of Chinese herbal medicines has begun to be popularized and applied, and the State Drug Administration has agreed to carry out the pilot work of fresh cutting of Chinese herbal medicines in Gansu and Anhui. GAP is the benchmark for the standardized production of Chinese herbal medicines, for this reason, the new version of Chinese herbal medicine GAP clearly prohibits the use of toxic and harmful substances for mildew, anti-corrosion and moth prevention in the processing of the place of origin, and prohibits the use of sulfur fumigation in the storage process.
The use of highly toxic fumigants (such as aluminum phosphide) in the storage of Chinese herbal medicines. The Notice of the General Office of the Ministry of Commerce on Accelerating the Guiding Opinions on Accelerating the Construction of a Modern Logistics System for Chinese Materia Medica (Shangban Rank Letter [2014] No. 809) clearly proposes to eliminate the phenomenon of aluminum phosphide fumigation. In response to problems such as the use of aluminum phosphide fumigation in grain storage, in 2017, the former Ministry of Agriculture's Announcement 2567 listed aluminum phosphide as one of the 25 pesticides restricted; as early as 2011, the former Ministry of Agriculture Announcement No. 1586 jointly issued by 5 departments stopped the registration and acceptance of aluminum phosphide pesticide products, and the existing 31 were allowed to produce aluminum phosphide pesticides with registration numbers at the latest until April 2022, after which they were not allowed to be reproduced. To this end, the new version of the Chinese herbal medicine GAP stipulates that the highly toxic fumigator banned by the state must not be used in the storage process.
4.10 Regarding technical regulations and standard operating procedures
In the implementation process of the trial version of the Chinese herbal medicine GAP, some enterprises confuse the technical regulations with the standard operating procedures, and take the standard operating procedures as technical regulations, and some enterprises even display hundreds of "technical regulations" when they are certified and inspected, which is actually the standard operating procedures of the enterprise, not the technical regulations. The new edition of the Chinese herbal medicine GAP explains the meaning of the two terms in Chapter 14 "Supplementary Provisions". Technical regulations refer to the technical regulations and requirements for the smooth and orderly development of the production of Chinese herbal medicines, the quality of Chinese medicinal materials, the site selection of the base for the production of Chinese medicinal materials, seed seedlings or other propagating materials, planting, breeding, wild care or imitation wild cultivation, harvesting and processing of origin, packaging, release and storage and transportation. Standard operating procedures, also known as standard operating procedures, are based on technical procedures to describe the steps and standards of a certain operation in a unified format to guide daily production work. Therefore, the technical regulations are the basis for the formulation of standard operating procedures, and the standard operating procedures are a series of action steps and requirements that need to be completed to achieve the requirements of technical regulations.
Nearly 1/3 of the content in the new version of the Chinese herbal medicine GAP is to inform enterprises how to formulate technical regulations. For the same medicinal material, even if it is a different enterprise and a different base, the technical procedures are generally similar. However, the standard operating procedures are measures for enterprises to implement personalized management in accordance with technical regulations, because the management mode of enterprises and bases may be very different. In order to better guide enterprises to formulate technical regulations, the author organized the national force, based on the new version of Chinese herbal medicine GAP, has compiled and issued the Chinese Association of Traditional Chinese Medicine group standard "Standardized Production Of Chinese Herbal Medicines Technical Regulations for Plant Medicinal Materials" General Rules, as well as 164 kinds of Standardized Production Technical Regulations for Chinese Herbal Medicines, which can be used for reference by enterprises.
4.11 Traceability system for the production quality of Chinese herbal medicines
In recent years, the state attaches great importance to the construction of the drug traceability system, and the Traditional Chinese Medicine Law of the People's Republic of China and the Guiding Opinions of the State Food and Drug Administration on the Construction of the Drug Informatization Traceability System have all advocated the establishment of a traceability system. The trial version of the Chinese herbal medicine GAP does not have the relevant content of the production quality traceability system. The new version of the Chinese herbal medicine GAP clearly proposes that enterprises should establish a traceability system for the production quality of Chinese herbal medicines, ensure that the key links in the whole process from production plots, seeds, seedlings or other propagating materials, planting and breeding, harvesting and processing, packaging, storage and transportation to the place of origin can be traced, and encourage enterprises to use modern information technology to build a traceability system.
"Establishing a traceability system" is another important highlight and essence of the new version of the Chinese herbal medicine GAP in addition to the "six unifications", and it is also another core point of the construction of a standardized production base according to the new version of the Chinese herbal medicine GAP, which is a main line that runs through the whole process of the production of Chinese herbal medicines. Regarding traceability, the industry has a good foundation, many Chinese herbal medicine production bases, Chinese herbal medicine enterprises have established a whole process traceability system, the National Development and Reform Commission and the State Administration of Traditional Chinese Medicine in the implementation of the national Chinese medicine standardization project, also require enterprises to establish a traceability system for the production of Chinese herbal medicines.
4.12 About the Batch
Although the trial version of the Chinese herbal medicine GAP has provisions on batch packaging records, batch numbers, etc., the concept of batch management and corresponding measures are weak. The new version of the Chinese herbal medicine GAP focuses on strengthening the concept of "batch", in the "quality management" chapter very clearly proposed that enterprises should clarify the production batch of Chinese herbal medicines, to ensure the consistency and traceability of the quality of each batch of Chinese herbal medicines, and in chapter 14, the "batch" is defined as the same place of origin and the ecological and environmental conditions of the planting place, breeding land, wild breeding or imitation wild cultivation land are basically the same, the source of seeds, seedlings or other propagating materials is the same, the production cycle is the same, the production management measures are basically the same, and the harvest period and the processing method of the place of origin are basically the same , the quality of Chinese herbal medicines is basically uniform. "Batch" is the smallest unit of product management, batch management is the development of production-oriented enterprises to the scientific management stage, in the production and quality management and traceability management commonly used methods, "batch" is also quality inspection, return and recall and other product management units must be clear.
5
The content and description need to be further refined in the Guide
At the same time as the drafting of the new version of the GAP version of Chinese herbal medicines, the Department of Drug Supervision and Administration of the State Drug Administration has entrusted the Institute of Medicinal Plants of the Chinese Academy of Medical Sciences to organize a national force to carry out the preparation of the "Technical Guidelines for the Implementation of the New Version of the GAP of Chinese Materia Medica" (hereinafter referred to as the "Guidelines") for the new version of the GAP of Chinese Medicinal Materials. The Guidelines will elaborate on gap provisions, particularly with regard to quality management systems, animal medicinal materials, wild care and imitation wild cultivation, processing of origins, and construction of traceability systems.
Reference format
WEI Jianhe,WANG Wenquan,WANG Qiuling,QIAO Xu,CHEN Jun,XU Changqing,SUI Chun,LIU Sai,JI Hongliang,WANG Miaomiao,JIN Yu,JIN Jiangqun,TIAN Ting,GUO Xinxing,YANG Chengmin,SU Kun,CHEN Ying,YANG Xiaoyu,XIN Yuanyao. Background and main revisions of good manufacturing practices for Chinese Materia Medica[J/OL].Modern Chinese Medicines: 1-12[2022-04-22]. DOI:10.13313/j.issn.1673-4890.20220405001.