Fill the void! Technical guidelines for the quality research of new Chinese medicines have been attacked.

Introduction: To promote the high-quality development of the Chinese medicine industry, the Drug Review Center of the State Drug Administration (hereinafter referred to as CDE) organized research and formulated the Technical Guidelines for the Quality Research of Chinese Medicine New Medicines (Draft for Comments).
. In order to speed up the establishment and improvement of the technical evaluation system in line with the characteristics of Chinese medicine, clarify the pharmaceutical research content required for the quality research of new Chinese medicine, improve the quality and efficiency of enterprise research and development, our center drafted the Technical Guidelines for the Quality Research of Chinese Medicine, which has been discussed by the center and has formed a draft for comments.
we sincerely welcome all sectors of the community to the draft for comments and suggestions, and timely feedback to us, in order to follow up the improvement.
for comments shall be one month from the date of publication.
your feedback please send to the following mailbox: zyyxzdyz@cde.org.cn (email named "Chinese Medicine Guidelines" Pinyin initials) thank you for your participation and support! On September 1, 2020, the Drug Review Center of the State Drug Administration drafted the Technical Guidelines for the Study of the Quality of New Chinese Medicines (Draft for Comments) Note 1. Drafting background quality research is an important part of the research on new Chinese medicines, and is of great significance to the control of the production process, the determination of the key quality attributes of the drug, the establishment of quality standards and the stability and control of the quality of the drug.
At present, China does not have a special technical guidelines for the quality research of new Chinese medicines, in order to further standardize and guide the quality research of new Chinese medicines, meet the requirements of safe, effective and controllable quality of chinese medicine, and promote the high-quality development of the Chinese medicine industry, the Drug Review Center of the State Drug Administration (hereinafter referred to as CDE) has organized research and formulated the Technical Guidelines for the Quality Research of Chinese Medicines (draft for comments) (hereinafter referred to as the guiding principles).
, the drafting process in May 2018, the CDE initiated the development of these guidelines and established a group of experts to draft the guidelines.
followed by a launch meeting of the Guiding Principles with the participation of experts, which established the framework and basic requirements for the Guiding Principles.
the meeting, the first draft of the guiding principles was drafted by experts.
november 2018, the first expert seminar on guiding principles was held, which fully discussed and revised the first draft of the Guiding Principles, which resulted in a revised version of the Guiding Principles.
through extensive consultation with enterprises, research and development units and other industry experts, after many discussions and amendments, formed a draft of this guiding principles for comments.
3. The main drafting ideas This guiding principle is under the guidance of the theory of Chinese medicine, to ensure the safety, effective and quality control of drugs as the goal, to guide researchers through the quality research of medicinal herbs/drink tablets, key intermediates and preparations and the whole process, to build a quality control system in line with the characteristics of Traditional Chinese medicine, to ensure that the quality of new Chinese medicine is stable and controllable.
4. Questions to be explained (1) The main sense of responsibility of drug quality research These Guiding Principles are intended to provide reference for the quality research of Chinese medicine, and the licensed holders or production enterprises of medicines have the main responsibility for the quality of medicines, and the quality research and quality control of the whole process of the production of Chinese medicines should be strengthened.
(2) We should respect the traditional Chinese medicine theory and practice, innovate research ideas and methods, and attach importance to the application and inheritance of quality identification methods based on traditional experience when carrying out quality research.
encourage the use of new technologies and methods to carry out research on the quality of new Chinese medicine.
(iii) Emphasize that the quality research of key intermediate quality research is very important in the quality research of new Chinese medicine, and its physical nature research is the basis of prescription design of preparations, chemical composition research and bioactive measurement are the basis for the establishment of production process control and quality standards, and more attention should be paid to quality research related to safety.
(iv) Focus on the study of security-related factors and security-related factors should be in-depth study and control.
should be based on the characteristics of prescription drug taste and process, clear need to control the safety indicators, control links, control methods and limits.
Technical guidelines for the study of the quality of new Chinese medicines (draft for comments) I. The quality research of new Chinese medicines is a process of determining the key quality attributes of medicines by using various techniques, methods and means under the guidance of the theory of Chinese medicine.
the purpose of quality research is to determine quality control indicators and acceptable range, to provide a basis for drug production process control and quality standards, to ensure the safety, effectiveness and quality control of drugs.
Based on the characteristics of the complex system of multi-component Chinese medicine, the quality research of chinese medicine new medicine should be guided by clinical value and demand, follow the theory of Chinese medicine, adhere to the combination of inheritance and innovation, and analyze the quality characteristics of medicine from many angles using physical, chemical or biological methods.
At the same time, quality research should also reflect the concept of quality derived from design, whole process quality control and risk management, and continuously improve the quality control level of Traditional Chinese medicine through the study of medicinal substances and key quality properties between different links, through the study of medicinal herbs/drink tablets, key intermediates, pharmaceutical substances and key quality properties.
principles are not legally binding and represent only the current views and understandings of the pharmaceutical regulatory authorities, and will continue to improve the relevant content of these Guidelines in accordance with scientific research and the development of Chinese medicine.
2. The basic principles (1) follow the chinese medicine theory to guide the complex material basis of Chinese medicine, especially compound preparations, in the quality research should respect the traditional Chinese medicine theory and practice, according to the characteristics of different drugs, the use of various research techniques and methods, targeted quality research, reflecting the overall quality of Chinese medicine.
)The traditional quality control method and the modern quality research method are of great significance to the quality research and quality control of Traditional Chinese medicine, and encourage the use of modern science and technology to study the traditional methods and establish quantifiable identification and control methods.
The quality research of traditional Chinese medicine should innovate the research ideas and methods, analyze the quality characteristics of medicines by using modern research methods such as physics, chemistry or biology, and study the quality evaluation methods, quality characteristics, key quality attributes and quality transfer laws, so as to effectively reflect the quality of drugs.
(iii) The quality control methods and indicators of new drugs in quality research should reflect the safety and effectiveness of drugs.
Medicinal herbs/drink tablets, key intermediates, preparations of medicinal substances and key quality properties, quality transmission law is the main content of quality research, should be around the safety and effectiveness of the selection of research methods and quality control indicators, to objectively characterize the quality characteristics of Traditional Chinese medicine, to provide a scientific basis for the quality control of Traditional Chinese medicine.
(4) The research of medicinal substances is an important part of quality research, which should be guided by the theory and clinical practice of Chinese medicine, and be embodied in the process of quality research of new Chinese medicine.
through medicinal substances and related research, the safety and effectiveness of new Chinese medicines are basically clarified, providing scientific basis for production process control and quality standards.
(v) Quality research should run through the whole process of chinese medicine quality control drug quality research should be reflected in the raw material quality, production process and equipment selection, process control and management, preparation quality standards, etc. , to build a chinese medicine in line with the characteristics of the whole process of quality control system, to ensure that the quality of new Chinese medicine is relatively stable.
, the main content (i) medicinal herbs / drink tablets / drink tablets as the source of preparations, its quality directly affects the quality of preparations, should strengthen the whole process of pharmaceutical / beverage tablets production quality research and control.
encourage the application of modern information technology to establish a traceability system for medicinal herbs/drink tablets.
The quality control of new medicinal herbs/drink tablets should not only refer to the systematic research results of medicinal herbs/drink tablets, but also combine the results of the correlation studies of medicinal herbs/drink tablets, key intermediates and preparations to determine the quality control index of medicinal herbs/drink tablets to meet the quality design requirements of new Chinese medicines.
Should pay attention to the quality of herbs in special circumstances, such as the prescription contains animal taste, should pay attention to the possibility of introducing pathogens, at the same time, should pay attention to the use of hormones in animal medicine, antibiotics, as well as some medicinal mold-produced fungal toxin pollution, etc., if necessary, the establishment of special safety control methods;
(ii) The study of key intermediate key intermediates is an important part of the quality research of traditional Chinese medicine, according to the different characteristics of drugs, the study of the physical and chemical properties of key intermediates, chemical components, biological activity, pharmacogenetic characteristics and related factors related to safety and effectiveness.
attention should be paid to the retention or amassing of safety-related substances in key intermediates.
if the subject is multiple key intermediates, it is suggested that each key intermediate should be studied according to the characteristics of its preparation process.
1. The study of the physical and chemical properties of physical and chemical properties is of great significance to the quality control of key intermediates and the study of subsequent preparations.
the study of the overall physical and chemical properties of Chinese medicine compound preparations with complex chemical composition and unclear active ingredients.
For liquids and semi-solids, the key quality attributes affecting the quality of the drug should be determined from the quality information such as luster, relative density, pH, clarity, fluidity and content according to the needs of subsequent preparations and the study of the composition of medicinal substances.
the tablets without extraction directly crushed into the drug, should focus on the powder crushing particle size and particle size distribution.
For dipping powder, on the basis of ordinary powder research (including fluidity, moisture absorption, etc.), the overall characteristics of dipping paste should also be studied, according to the nature of the drug itself and the requirements of subsequent preparations, to determine its key quality properties.
2. The chemical composition of Chinese medicine is complex and diverse, and a focused systematic study should be carried out according to the characteristics of new Chinese medicine.
2.1 The quality study of Chinese medicine compound preparation should be carried out under the guidance of Chinese medicine theory, combined with functional treatment and past use.
pay full attention to the literature research of prescription drug misochemical composition, understand the chemical category, structure, content and analysis and determination methods of various components.
focus on the chemical composition related to the safety and effectiveness of Chinese medicine, and pay attention to the prescription of Chinese medicine, expensive fine drugs or the chemical composition or components of a larger amount of drug flavor.
to carry out a targeted study on the medicinal substances obtained from the identified route and study the key quality properties.
2.2 Extracts extracted from a single plant, animal, mineral and other substances and their preparations Such traditional Chinese medicines in the preparation process purposefully rich chemical composition/ composition groups related to the physics of the drug, should focus on the systematic study of the composition, content and proportion of extracts, and through a single composition content, large-group composition content and composition, fingerprint / characteristic map and other ways to fully characterize.
the type and content of ingredients other than active ingredients in the extract should be studied to ensure the stability and control of medicinal substances.
3. Where toxic toxicity components are prescribed in the prescription of safety-related factors 3.1, the endotoxic toxicity should be reasonably analyzed in the light of toxicological studies, and attention should also be paid to the taste of the drug containing ingredients similar to the chemical structure of the found toxic components, as well as the taste of the drug in the same genus as the known toxicity drug.
For the pharmaceutical toxicity components clear, should establish a limit of toxic ingredients inspection methods, clear safety limits or regulations may not be detected, if the toxic ingredients are also active ingredients, should be based on literature and safety, ability of research results to develop the content range (upper and lower limits).
toxicity is clear but the toxic composition is not yet clear, in-depth study of toxic composition should be carried out to strengthen quality control.
3.2 Exogenetic contaminants mainly include pesticide residues introduced from medicinal herbs/drink tablets, plant growth regulators and their degradations, heavy metals, etc., organic solvent residues, resin residues, and microorganisms and fungal toxins bred during storage (if applicable).
Through systematic research and analysis of exogenetic pollutants contained in key intermediates, the retention of pesticide residues and heavy metals that may be introduced from medicinal herbs/drink tablets should be analysed and the necessary methods of pesticide residues and heavy metals inspection established should be studied.
for the use of organic solvents and resins in the preparation of key intermediate systems, the retention or avotation of them in key intermediates should be studied and analyzed, safety risks assessed, and reasonable control methods should be developed.
For medicinal herbs/drink tablets found to be susceptible to fungal toxin contamination, if the original powder is used, the fungal toxin control method of the medicinal herbs/drink tablets should be determined in the light of the results of the results of the study of key intermediates and the stability of the new drug.
if there are herbs/drink tablets (e.g. curvatures, etc.) that contain the fermentation process, the possible detection of fungal toxins should be controlled accordingly.
4. On the basis of the characteristic control quality of physical and chemical methods, combined with the results of pharmacological or toxicological studies, bioactive assays are encouraged to be explored, bioactive assays are established as supplements to conventional physical and chemical methods, and the correlation with the functional treatment (adaptation) of new Chinese medicines is improved.
(iii) preparation 1. Dosage form characteristic dosage form is one of the important factors affecting the quality of new Chinese medicine.
Chinese medicine new drugs are generally based on clinical use needs, taking into account the composition of drug prescriptions, the physical and chemical properties of medicinal substances, reference to different dosage forms of the load, clinical dosage, patient compliance and other factors to choose the route of administration and determine the dosage form.
chinese medicine should be based on the characteristics and requirements of different dosage forms, research and establish the corresponding quality control projects to characterize the characteristics of the selected dosage form.
requirements for different types of preparations may be based on the general rules of the Chinese Pharmacopoeia to set key control indicators.
such as the time limit for the disintegration of oral solid preparations, the time limit for melting of supposits, etc.
2. The prescription of preparations and the prescription of molding process preparations should refer to the results of research on the physical and chemical properties, chemical components and biological activity of key intermediates, and should also consider the properties of pre-preparation pharmaceutical substances, the role of selected accessories and the interaction between raw materials in combination with the characteristics of dosage forms, and study the effects of the molding process on medicinal substances and quality control methods.
Attention should be paid to the effects of solvents, accessories and various processing conditions on pharmaceutical substances in the preparation process, in particular the quality effects of volatile components, thermally sensitive components, other unstable components in drying, excessive temperature and loss of ingredients caused by excessive heat duration during sterilization.
should also refer to the preliminary stability research results to determine the key control points and control objectives of the preparation process to ensure the quality of the drug.