Study on quality control of new medicinal materials of traditional Chinese Medicine
Technical guidelines (Trial)
1、 Overview
Medicinal materials are the source of R & D and production of new Chinese medicine, and their quality is the key factor affecting the safety, effectiveness and quality control of new Chinese medicine. In order to improve the quality control system of traditional Chinese medicine preparations, strengthen the traceability of drug quality, and provide safe, effective and stable quality medicinal materials for traditional Chinese medicine preparations, based on the concept of whole process quality control and risk control, this technical guiding principle is formulated for the key links and key quality control points of medicinal material production.
This guiding principle mainly includes the medicinal material base and medicinal parts, origin, planting and breeding, harvesting and origin processing, packaging and storage, quality standards, etc,The aim is to provide reference for the quality control research of new medicinal materials of traditional Chinese medicine.
2、 Basic principles
（1） Respecting the tradition and characteristics of traditional Chinese Medicine
The research on quality control of medicinal materials should follow the theory of traditional Chinese medicine and respect the traditional experience and characteristics of traditional Chinese medicine. Traditional experience should be respected in the appropriate place of origin, production mode, growth years, harvesting time, processing methods in the place of origin and quality evaluation of medicinal materials. Encourage the inheritance of traditional experience and technology, and encourage the application of modern science and technology to characterize traditional quality evaluation experience and indicators.
（2） Meet the needs of research and design of new drugs of traditional Chinese Medicine
. Take necessary measures, such as fixing the base, medicinal parts, origin, etc., to ensure the quality of new medicinal materials of traditional Chinese medicine is basically stable.
（3） Strengthen the quality control of the whole production process
We should strengthen the quality control research of the whole production process of medicinal materials, such as the origin, origin, planting and breeding, harvesting and processing, packaging and storage. It is encouraged to refer to the production quality management norms of Chinese medicinal materials（GAP）According to the requirements of the project, the cultivation of medicinal materials should be carried out, and the corresponding quality control and management measures should be established for the collection, production processing, packaging and storage of wild medicinal materials. The source of medicinal materials shall be traceable,Encourage the use of modern information technology to establish a drug traceability system。
（4） Pay attention to the sustainable utilization of medicinal resources
We should deal with the relationship between rational utilization of medicinal materials and resource protection, carry out resource assessment, and ensure the sustainable utilization of medicinal materials resources. The use of medicinal materials derived from wild animals and plants should comply with the relevant national regulations and requirements on the management of wild animals and plants. Traditional Chinese medicine and new drugs should strictly restrict the use of medicinal materials derived from wild animals. In principle, medicinal materials derived from rare and endangered wild animals and plants should not be used. If they need to be used, they should be strictly required to carry out planting and breeding or wild tending research as soon as possible to ensure the sustainable utilization of resources. The use of paleontological fossils should comply with the relevant laws and regulations and requirements of the state on the protection and management of paleontological fossils.
3、 Main contents
（1） Origin and medicinal parts
The accuracy of the original is the basis of ensuring the quality of medicinal materials. /Chinese name, Latin scientific name and medicinal parts of animals. For multi base crude drugs, generally one base should be fixed. If more than one base should be used, sufficient basis should be provided, and the proportion of use should be fixed to ensure the stability of the quality of the preparation. If there is a clearly selected variety of cultivated medicinal materials, the variety information shall be generally stated. Mineral medicine shall specify the type, family, ore or rock name and main composition of the mineral.
Measures should be taken to ensure the accuracy of the medicinal materials and medicinal parts used. In principle, original plants should be collected for new medicinal materials, medicinal materials that are easy to be confused and difficult to determine the origin/move/The certificate specimens of minerals shall be identified by experts or qualified institutions, and the specimens, photos and relevant data shall be retained. If necessary, it is also necessary to conduct a comparative study with the fake products, and confirm the origin of the medicinal materials in combination with the investigation of the origin. New medicinal materials should describe the relevant information of the medicinal materials in detail, such as the original plant/Animal morphological characteristics and medicinal parts, indicating the original plant/The growth environment, habits, origin, distribution and resources of animals. If there are easily confused species of wild medicinal materials in the same growth area and the same harvest time, the study on the identification of the original and the difference between them should be carried out.
（2） Origin
The place of origin is one of the important factors affecting the quality of medicinal materials, and fixing the place of origin is an important measure to ensure the relatively stable quality of medicinal materials. Through literature research, origin investigation and other methods, understand the real production area, main production area, core distribution area and suitable production area of medicinal materials, understand the quality differences of medicinal materials from different origins, and strengthen the research on the quality laws of medicinal materials from different origins. The geological environment and associated minerals of mineral medicine producing areas are closely related to heavy metals and other impurities in medicinal materials, and targeted research should be strengthened.
. Genuine production areas are encouraged to be used as the places of origin of medicinal materials. Medicinal materials can also be grown in areas with similar ecological environment to genuine production areas.
Generally, the producing area is a specific growing area of medicinal materials with similar ecological environment. The scope of producing area should be determined according to the quality changes of the medicinal materials produced. The quality of medicinal materials produced in the same producing area should be relatively stable. On the premise of ensuring the stability of the quality of medicinal materials, multiple origins can be selected.
（3） Planting and breeding
Planting and breeding of medicinal materials should be used for antidote/The growth and development rules or living habits of animals. Considering the characteristics of traditional Chinese medicine and the law of research and development of new traditional Chinese medicine, especially after the listing of new traditional Chinese medicine, we should pay attention to the management of all aspects of planting and breeding of traditional Chinese medicine, focusing on the following:
1. Seed seedling
. Encourage the selection of seeds and seedlings from genuine local germplasm or excellent varieties. If the variety is changed, sufficient risk assessment and research should be carried out to prove its safety, effectiveness and quality control, and ensure the consistency of the quality of medicinal materials before and after the change.
2. Agricultural inputs
In the process of planting medicinal plants, the management of pesticides, fertilizers and other inputs should be strengthened. The type, dosage and application method of pesticides should be reasonably determined in combination with the growth characteristics of medicinal materials, the control effect of pests and diseases, the residue situation and the pollution risk, and should be used at the lowest dose and times as much as possible. The use of pesticides shall comply with the relevant national regulations, and timely pay attention to the list of banned and restricted pesticides issued by the relevant national departments. The regulations of relevant national departments on animal breeding and safe use of veterinary drugs should be strictly observed in the process of pharmaceutical animal breeding.
The document management of planting and breeding medicinal materials should be strengthened. The agricultural inputs such as pesticides, fertilizers or veterinary drugs used shall be recorded in detail, including the name, dosage, frequency, time, safe interval of use, etc.
3. Research on planting and breeding
Encourage the research of planting and breeding such as ecological planting of medicinal materials, wild tending and bionic cultivation technology, explore the law of the formation of the quality and yield of medicinal materials, study the key technologies affecting the quality of medicinal materials, and establish quality control methods. . Medicinal plant/In the long-term cultivation and breeding of animals, measures should be taken to ensure the stability of germplasm and prevent the variation and degradation of medicinal germplasm.
（4） Harvesting and processing
Harvesting and processing are important links that affect the quality of medicinal materials. Generally, we should respect traditional experience and adhere to the principle of giving priority to quality and giving consideration to output. Focus on the following:
1. recovery
According to the characteristics and growth phenology of medicinal materials, the growth years, harvest time and harvest method should be determined for the harvesting of medicinal materials. When the growth years and harvest time are inconsistent with traditional experience, there should be sufficient basis.
A scientific and reasonable harvesting plan should be formulated for the harvesting of wild medicinal materials to ensure the sustainable utilization of resources. During the harvesting process, it is necessary to avoid the mixing of mining and harvesting, non medicinal parts or impurities. The training of harvesting personnel and the management of information such as the location, time and quantity of harvesting should be strengthened.
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2. Processing in origin
Traditional experience should be followed in the processing of medicinal materials in producing areas. According to the characteristics of medicinal materials and the needs of preparations, appropriate processing methods in producing areas should be studied and determined, and the key process parameters should be clarified. Encourage the use of efficient and intensive processing technology in production areas with scientific basis and proven by production practice. .
（5） Packaging and storage
The packaging and storage of medicinal materials have an important impact on their quality. The packaging of medicinal materials should be able to protect the quality of medicinal materials and facilitate circulation.
1. Packaging and labeling
The packaging materials shall comply with the relevant national regulations, which is conducive to maintaining the stability of the quality of medicinal materials and not polluting the medicinal materials. Appropriate packaging materials should be selected according to the characteristics of medicinal materials, and the packaging of special medicinal materials such as volatile, polluted, damp and deteriorated should be paid attention to. The base source, origin and harvest date of medicinal materials in the same package should be consistent. Labels shall be printed or pasted on the package according to regulations, and the contents of the labels shall meet the requirements of laws and regulations.
2. Storage conditions
The storage of medicinal materials should meet the requirements of traditional Chinese medicine maintenance. According to the characteristics of medicinal materials and traditional experience, research should be carried out on the influence of storage conditions (such as temperature, humidity, light, etc.) and storage time on the quality of medicinal materials, especially for medicinal materials that are easy to moth, mildew, rot, oil, etc. according to the research results, reasonable quality control indicators should be established, reasonable storage conditions should be determined, and quality control should be strengthened. Encourage the research and application of new storage technologies that are conducive to ensuring the quality of medicinal materials.
（6） Quality research and quality standards
The quality standards of new medicinal materials of traditional Chinese medicine should be studied and improved according to the needs of preparation quality control. The quality standard of medicinal materials should conform to the characteristics of traditional Chinese medicine, reflect the quality status of medicinal materials, reflect the overall quality control concept, and be conducive to ensuring the stability of the quality of medicinal materials. We should pay attention to the combination of scientificity and practicality, the combination of traditional methods and new technologies and methods, and explore the correlation between traditional quality evaluation experience and modern detection indicators. Focus on the following:
1. Ensure the accuracy of the original
The specific identification method of medicinal materials should be established to ensure the accurate source of medicinal materials and avoid problems such as confusion and adulteration. The appropriate reference medicinal materials, reference extracts, standard atlas, etc. can be selected as the control, and if necessary, comparative study with the fake products is also required to explain the specificity of the method. . It is encouraged to establish effective identification methods based on the progress of basic scientific research and the exploratory research results of national drug sampling.
2. Control safety risks
For the traditional toxic (highly toxic) and toxic medicinal materials, as well as the toxic medicinal materials (such as Aristolochiaceae medicinal materials) found in modern research, we should strengthen the basic research of toxic ingredients, and determine the reasonable quality control indicators and limit requirements in combination with the preparation safety and risk assessment results. Relevant research should be paid attention to the medicinal materials containing the same family and genus as the found toxic ingredients.
If the purchased medicinal materials have common problems such as dyeing weight gain and adulteration, research should be strengthened. According to the needs of risk management, targeted test items should be added with reference to relevant national supplementary test methods or research, and included in internal control standards when necessary.
The study of exogenous pollutants in medicinal materials should be strengthened. According to the use of pesticides, veterinary drugs, fumigants, etc. in the production process of medicinal materials, as well as the risk of possible pollution by heavy metals, harmful elements, mycotoxins, etc., combined with the production process of processing and corresponding preparations, a comprehensive evaluation is carried out. If necessary, the detection items of relevant exogenous pollutants are established in the quality standards, and according to the research results, the control standards of exogenous pollutants are formulated by regions and varieties. . Animal medicinal materials should pay attention to the problem of carrying pathogenic microorganisms and other issues to prevent biosafety risks, especially medicinal materials derived from wild animals.
3. Stable and controllable quality
The quality standard should reflect the overall quality attributes of medicinal materials, and should pay attention to the correlation between the detection items and indicators and the key quality attributes of preparations. The reasonable quality requirements should be determined according to the quality status of medicinal materials and the research and design requirements of new drugs of traditional Chinese medicine. Encourage research and establishment of multi index inspection and detection methods, such as extract determination and fingerprint/The characteristic map, the content determination of major components, and the content determination of multi index components are used to control the quality of medicinal materials as a whole and ensure the stability of the quality of preparations.
4、 References
1. State Food and Drug Administration.,2005year.
2. State Food and Drug Administration.Technical requirements for new drug research of natural drugs,2013year.