Drug Review Center Openly Solicites "Guidelines on Pharmaceutical Research Technology at Different Stages of Chinese Medicine New Drugs"

Guide: Speed up the establishment and improvement of the technical evaluation system in line with the characteristics of Chinese medicine, promote the innovation of Chinese medicine research and development, and clarify the contents of pharmaceutical research required to be completed at different stages of Chinese medicine.
In order to speed up the establishment and improvement of the technical evaluation system in line with the characteristics of Chinese medicine, promote innovation in the development and innovation of Chinese medicine, and clarify the contents of pharmaceutical research required to be completed at different stages of Chinese medicine, our center organized the drafting of the "Guidelines for the Technical Guidelines for The Study of Pharmaceutical Research at Different Stages of Chinese Medicine" (Draft for Comments).
the draft of the draft of these guiding principles and the drafting notes (see annex 1, 2) is now published on the Center's website to widely listen to the views and suggestions of all walks of life, welcome the valuable comments and suggestions from all walks of life, and please give us timely feedback.
deadline for comments: August 20, 2020.
your feedback to the following email: zyyxzdyz@cde.org.cn ("Chinese Medicine Guiding Principles" Pinyin initials) Thank you for your participation and support! Drafting note synopsis of the Guiding Principles for The Study of Pharmaceutical Research at Different Stages of Chinese Medicines (Draft for Comments) of the Drug Review Center of the State Drug Administration on July 20, 2020, and drafting the background to encourage the innovation and development of Chinese medicine, and to implement the Drug Administration Law, the Law on Chinese Medicine, the Central Committee of the Communist Party of China and the State Council on promoting innovation in the inheritance and innovation of Chinese medicine. In the spirit of the development opinion s, in accordance with the law of research and development of new Chinese medicine, to improve the quality and efficiency of the research and development of new Chinese medicine, and to guide the applicant to carry out the research on the new chinese medicine reasonably, the National Drug Review Center (CDE) initiated the drafting of the Guiding Principles for the Research Technology of Pharmaceutical Research at Different Stages of Chinese Medicine (hereinafter referred to as the Guiding Principles for Different Stages of Chinese Medicine).
. The drafting process establishes a research group on the subject of "Guidelines for Different Stages" in accordance with the relevant requirements of the revision of the CDE Guiding Principles system.
a launch meeting in June 2018 to identify the basic framework and requirements of the guiding principles, define the division of work, etc.
, as requested by the launch meeting, the Group of Experts prepared a first draft of the guiding principles. the first expert seminar was held in October 2018
to discuss and revise the first draft.
discussed several times after the meeting, resulting in a revised version of the Guiding Principles.
convened a second expert seminar in January 2019 to discuss the revised version.
held a third expert seminar (revised session) in May 2020, following which a draft of the guiding principles was formed.
. On the basis of respecting the theory of Chinese medicine and human experience, the guiding principles of drafting ideas encourage research on the main research purposes of different stages of research, and improve the quality and efficiency of research and development of new Chinese medicine based on the characteristics of Chinese medicine and the general law of research and development of new Chinese medicine.
pharmacology research runs through the whole process of new drug research and development, we should fully understand the gradualdevelopment of the research and development of new Chinese medicine to meet the clinical needs as the goal, and the research of pharmacy should be deepened gradually.
continuously strengthen quality control research, improve the whole process of quality control system, practice the whole life cycle management, promote continuous improvement of product quality, to ensure that drugs safe, effective and quality control.
. 4. The characteristics of Chinese medicine and the law of research and development of new Chinese medicine pharmaceutical research should be in line with the characteristics of Chinese medicine and research and development law, respect human experience, pay attention to the wholeness, systematic and logical process of new drug research and development, explore the overall quality control of Chinese medicine.
encourage research based on the combination of traditional experience and modern science and technology to improve the quality and efficiency of research and development of new Chinese medicines and promote the high-quality development of the Chinese medicine industry.
2. The research stage of the study stage to divide the research and development cycle of new Chinese medicine is a gradual process, according to different stages of research purposes, the corresponding pharmaceutical research.
this guiding principle is mainly based on the general law of the research and development of new Chinese medicine, combined with the relevant provisions of the Measures for the Administration of Drug Registration, for the key nodes of research and development, divided into the application for clinical trials, phase II clinical trials before the start of the phase/III clinical trial, before the application for listing license and post-market research and other stages, the prescription drug taste and its quality, production process, quality and quality standards, stability research and other pharmaceutical content requirements.
3. The purpose of process validation is to assess the maturity, repeatability and product quality stability of the process.
In accordance with the provisions of the Measures for the Administration of Drug Registration, the applicant shall complete the verification of the commercial scale production process before applying for listing.
4. The scope of application Of these guidelines are mainly applicable to new Chinese medicine compound drugs, other categories may be implemented by reference.
the technical guidelines for pharmaceutical research at different stages of Chinese medicine (draft for comments) I, overview ingenuity new drug research is a system engineering involving pharmacy, pharmacological toxicology, clinical research, in which pharmaceutical research mainly includes prescription drug taste and its quality, dosage form selection, production process, quality research and quality standards, stability research and other content. Under the guidance
of the theory of Chinese medicine, the research of new Chinese medicine should be carried out in accordance with the characteristics of Chinese medicine, the general law of new drug research and research and the main purpose of different research stages, carry out targeted research, implement the whole life cycle management of medicine, promote the inheritance and innovation of Chinese medicine, and ensure the safety, effectiveness and quality control of the drug.
this guideline is mainly aimed at the requirements of the main pharmaceutical research content semen that need to be completed in all stages of the application for clinical trial of a new Chinese medicine, the end of phase II clinical trial/PHASE III clinical trial, the application for a listing license and the stage of the post-market research, and provide reference for the research of a new Chinese medicine.
. General Principles (I) To follow the theory of Chinese medicine to guide the study of new Chinese medicine and pharmaceutical research should respect traditional experience and clinical practice under the guidance of Chinese medicine theory, and encourage the use of modern science and technology for research and innovation.
(2) in accordance with the characteristics of Chinese medicine and the law of research and development in accordance with the characteristics of Chinese medicine and the general law of new drug research and development, fully understand the gradual development of new drugs and the main research objectives of different stages of research and development, carry out corresponding research work in stages, pay attention to the integrity and systematic nature of research, improve the quality and efficiency of research and development of new drugs, and promote the inheritance and innovation of Chinese medicine.
(3) Practicing the whole life cycle management of new chinese medicine pharmaceutical research should reflect the whole life cycle management, strengthen the whole process of quality control research of medicinal herbs, beverage tablets, production technology, quality standards, establish and improve the whole process of quality control system in line with the characteristics of Chinese medicine, and with the improvement of product awareness and scientific and technological progress, continuous improvement of product production process, quality control methods and means to promote continuous improvement of product quality.
. (1) Before applying for clinical trials, we should complete the preliminary pharmaceutical research work to provide basically stable quality samples for exploratory clinical trials to meet the needs of clinical trials.
research includes fixing the taste of prescription drugs and the way of administration, clarifying the base and medicinal parts of medicinal herbs, the method of preparation of drinking tablets, preparation process, the study of quality standards, especially the safety-related quality control research is basically completed, the quality of the drug is basically controllable, and the stability of samples used in clinical trials is guaranteed.
1. Prescription drug taste and its quality Of Chinese medicine prescription drug taste, including Chinese medicine tablets and extracts, should be fixed.
to clarify the base origin, medicinal parts, origin, mode of production (wild, cultivation, other ways), collection and processing methods, storage methods and conditions, as well as preliminary quality requirements, drinking tablets and quality standards.
in order to ensure the stability of the quality of new Chinese medicine, we should pay attention to the quality of the medicinal herbs used and the sustainable use of their resources, and the resources of the medicinal herbs used, especially wild herbs, should be evaluated in accordance with the relevant requirements.
should carry out research on cultivation and breeding techniques for the use of rare and endangered wild medicinal herbs.
2. Under the guidance of the theory of Chinese medicine, the preparation process of chinese medicine and the preparation process of new Chinese medicine is carried out in combination with the experience of human use, the physical and chemical properties of the chemical composition contained in each medicine taste and the pharmacological effect.
should carry out dosage form selection, route and main process parameters research, clear dosage form, preparation process, explain the rationality of its choice.
clear pre-treatment, extraction, purification, concentration, drying and other methods and main process parameters, basically clear intermediates (such as dip paste, etc.) and other important process indicators.
to carry out prescription design and molding process research, to clarify the use of accessories, molding process and its main process parameters.
preparation process should be determined by the pilot amplification study, and the process parameters should be clarified.
consider the feasibility and adaptability of large production equipment.
samples for non-clinical safety trials should be tested with samples of scale and above and quality control.
3. Quality research and quality standards for new Chinese medicine medicinal herbs / tablets, intermediates, preparations and accessories for quality control research, the establishment of quality standards.
preparation quality standards should, as far as possible, reflect the quality of the product.
quality studies, such as toxic components, should be carried out on quality control projects affecting drug safety.
with the deepening of research and development, quality research and quality standards should be gradually improved.
. Stability research to carry out preliminary stability research, select suitable packaging materials /containers for direct contact with drugs, study and determine storage conditions, to ensure the stability of samples used in clinical trials.
(II) Samples used in clinical trials prior to the start-up of Phase II clinical trials should generally be prepared using samples of production scale, and production should follow the basic principles of the quality management norms for pharmaceutical production.
before carrying out clinical trials, on the basis of pre-research should be fixed on the basis of medicinal base and medicinal sites, drink-chip concocting methods, etc., to establish safety quality control indicators, complete the production process amplification research, pay attention to the scale of production, equipment and other impact on product quality.
phase II clinical trial end/III clinical trial before the start of the start, should complete the main pharmaceutical research work, in accordance with the identified process at large-scale production conditions can continue to produce stable quality samples.
systematic study (including literature studies) on the effects of the origin, collection period, origin processing and growth of prescription Chinese herbal medicines on the quality of medicinal herbs, perfect and determine the relevant information of medicinal herbs, and ensure the stability of the quality of medicinal herbs.
and should continue to study and improve the quality standards of medicinal herbs, tablets and extracts.
according to clinical trial conditions and research results, under the premise that the route and key process parameters remain unchanged, the process parameters (such as water addition, such as water, etc.), molding process, auxiliary materials, dosage form, specifications, etc. can be optimized research, indicating its rationality and necessity.
should complete large-scale production research, fix the production process and clarify the detailed process parameters to ensure the stable quality of samples used in clinical trials.
if the specifications of drugs, preparation process, etc. change during clinical trials, the research work shall be carried out in accordance with the actual changes, in accordance with the relevant technical guidelines, and if necessary, a supplementary application shall be made.
continue to study drug quality research and improve quality standards, such as increasing the specific properties to identify the taste of the drug, multi-indicator content determination and so on.
research on safety-related indicators (e.g. heavy metals and harmful elements, pesticide residues, fungal toxins) according to the product's specific circumstances, and included in the results to better control product quality.
(3) Before applying for a listing license, we should complete all the pharmaceutical research work, clarify the reasonable scope of the production process and key process parameters, establish basic and perfect quality control methods, and ensure that the product after the market is consistent with the quality of samples used in confirmed clinical trials.
1. The taste of prescription drugs and their quality according to the non-clinical safety test samples, clinical trial samples used in the medicinal herbs / drink tablets, combined with the results of the relevant research results of medicinal herbs / drinking tablets, fixed the base of medicinal herbs, medicinal sites, growth years, harvesting period, processing methods and drink ingested process parameters.
extract should be fixed process parameters, clear key production equipment and production scale and other information.
combined with clinical research and preparation needs, if necessary, improve and improve the quality standards of medicinal herbs, tablets, extracts.
in order to ensure the quality and sustainable use of medicinal herbs, the medicinal herbs involved in prescription drug flavor should be evaluated in accordance with the relevant requirements, and for the use of rare and endangered wild medicinal herbs, should ensure that the cultivation and breeding techniques are feasible to meet the needs of post-marketing production.
2. When applying for listing of the production process, according to the preparation process of samples used in confirmed clinical trials, the control index of the production process is established, the process verification of production scale is carried out, the production process and process parameters of the application for listing are determined, and the consistency of product quality is better controlled. the production process of
shall be stable and feasible, the production scale shall be able to meet the requirements of large-scale production, and the production environment shall meet the requirements of the quality management specification of pharmaceutical production.
, the accessories used shall comply with the relevant requirements for the approval of the related review.
. When applying for listing in quality research and quality standards, we should strengthen the quality research of pharmaceutical materials/drinks tablets, intermediates, preparations and accessories, packaging materials/containers that come into direct contact with pharmaceuticals, pay attention to the quality transmission of the production process, build a perfect quality standard system, and realize the quality control of the whole process of medicine. The quality standards of
preparations shall be based on the test results of samples used in confirmed clinical trials, reflecting the quality status of samples used in clinical trials.
to explore the establishment of fingerprint or feature map, biological activity detection and other projects according to product characteristics.
testing items such as content determination in drug standards should be based on the test results of samples used in confirmed clinical trials, and a reasonable scope should be formulated.
4. Stability studies determine the validity period and storage conditions according to the results of the stability survey of samples of production scale.
clearly define the packaging materials/containers and their quality control requirements for direct contact with samples. The packaging materials/containers used in the
shall comply with the relevant requirements for the approval of the associated review.
(4) Post-marketing research continues to strengthen quality control research, carry out research on cultivation and breeding of wild medicinal herbs, and encourage the establishment of a base for cultivation and breeding of medicinal herbs in accordance with GAP requirements, so as to ensure the stability of the quality of medicinal herbs and the sustainable use of resources.
according to the progress of science and technology, the updating of production equipment, to carry out corresponding research, improve the level of production technology assurance.
combined with actual production and clinical use, and constantly accumulate relevant data, pay attention to product quality stability and safety, improve quality standards, establish and improve the whole process of quality control system, and promote product quality continuous improvement.
IV. Drug Administration Law of the People's Republic of China, 2019. 2. State Administration of Market Supervision and Administration. Measures for the Administration of Drug Registration, 2020.3. Opinions of the State Council of the CPC Central Committee on Promoting innovation and development of Chinese medicine inheritance, 2019.4. Drug Review Center of the State Drug Administration. Technical Guidelines for Quality Control research on new Chinese medicines (trial), to be published.5. Drug Review Center of the State Drug Administration. 《