|
Medical network - March 8 March 6, CDE release studies of listed Chinese medicine production process changes to technical guiding principles (draft) (hereinafter referred to as "guiding principles" in 2017, the same below), it is 2011 listed Chinese medicine changes research technical guidelines (a) "(hereinafter referred to as" guiding principles "in 2011, the same below) for the first time after the release date. Whether 2017 guidelines or 2017 guidelines, no consists of TCM injections change research guidelines.
After January 10, has released the listed chemicals production process change research technical guiding principles (draft), is expected as the biological products production process changes already on the market research technical guidelines "(draft) to be released, all production process change research technical guidelines will be updated completely.
1, pay more attention to medicinal material pretreatment, extraction and purification, and molding process
2011 guiding principle pay more attention to the supplement of projects, such as change the drug specifications or packaging specifications, change medicine prescription for the requirements of the medicinal materials, changes in production process, change the validity of drugs or storage conditions, when changing the drug packaging materials and containers, the drug manufacturing sites, etc.
The 2017 edition is more interested in Chinese traditional medicine production process becomes involved medicinal material pretreatment, extraction, isolation, purification, concentration, drying, molding process of change, classified into three categories, respectively "medicinal materials before processing the change classification" sort "extraction and purification of change" and "sort molding process changes". Change in drug specifications or packaging specifications of these projects is more in the "production process change research and declared" embodied.
"The classification of" medicinal materials before processing changes, 2017 version of the guiding principles for the change of granularity has more explicit classification requirements: "Ⅰ class changes" as "a variety of herbs alone shattering change to mix after crushing, such as separate grinding flour extraction rate are higher, and the flour yield and particle size changes very little change before and after". "Ⅱ class changes" for the "herbal granularity of contains a powder in the pharmacopoeia grade change in pharmacopoeia contains another kind of powder level". "Ⅲ class changes" for the "herbal pieces of granularity for superfine powder by powder changes".
Sort the extraction and purification of "change", 2017) are very strict guidelines, dosage of solvent extraction of change requests are carried out in accordance with the Ⅲ class changes research. It is worth noting that the 2017 version of the guidelines will be under "Ⅲ class changes" in different categories - "process change" "process change" segment "process parameters change".
Process parameters such as "change", 2011 guidelines just mention "including alcohol setting process alcohol alcohol content changes, extraction times change, such as". 2017 guidelines include: 1) the change of extraction solvent concentration, frequency, temperature or time. 2) change in alcohol/water sink sinking process of the main process parameters, such as alcohol/water sink sink sink before the relative density of liquids, alcohol content of alcohol/water sink sink with water, alcohol/water temperature, etc. 3) change the purification process in clarifying agent types, such as chitosan to clarifying agent ZTC1 + 1. 4) change column chromatography purification process of main process parameters, such as the dosage of column packing type and model, packing, sample amount, elution solvent type and dosage, eluent, pH value, elution end, etc. 5) change the main technical parameters of supercritical fluid extraction technology, such as equipment scale, extraction pressure, extraction temperature, extraction time, separation reactor pressure, separation reactor temperature, velocity, etc.
"Sort molding process changes to" pay more attention to changes in preparation. What kind of change, for a specific formulation corresponding 2017 guidelines have more specific requirements: oral solid preparation forming process to join order of zhongyuan complementary makings is changed; Pills pellet method changes, such as generic method, extrusion rolling method, pressing method, change, or change by manual generic pills for pelletizing machine; Polishing process of pill, capsule, tablet increase; Tablet change of coating process, by the package icing process change for package type gastric soluble film process; Capsule filling process changes, such as powder filler to fill after granulating; Excluding volatile, heat-sensitive ingredients, oral liquid preparations by the flow of steam sterilization change for terminal aseptic filling technology, or increase the circulation of steam sterilization process; Dropping drops in the process of change order, lower the temperature in the ingredients, temperature, the temperature of condensate, change from. The above belong to "Ⅰ class changes", involving more than the manufacturer should change can breathe a sigh of relief. In addition, "containing volatile components, heat sensitive components, oral liquid preparations by the flow of steam sterilization change for terminal aseptic filling technology, or increase the wet and heat sterilization process" for "Ⅱ class changes"; "The slow release/controlled release preparations in kind or amount of slow-release material change" belong to "Ⅲ class changes".
2, the exemption conditions
2017 guiding principle is proposed for the first time, if by other scientific research to obtain sufficient evidence, proof of process change on drug safety, efficacy and quality controllable will not have a negative impact, can not completely make changes according to the requirement of the 2017 guidelines research exemption. However, due to the definition of "other scientific research" is vague and difficult to determine which scientific research is the CFDA recognition of evidence.
Divided by 2017 guidelines Ⅰ, Ⅱ or Ⅲ class changes research, according to the research data showed that changes of fully the material basis of drugs and utilization degree of the impact of: such as the class is divided into Ⅱ or Ⅲ changes, if there is sufficient research data showed that changes the material basis of drugs and won't impact absorption use, can be in accordance with the requirements for Ⅰ class changes were studied.
In addition, the 2017 version of the guidelines is mainly suitable for ordinary Chinese medicine preparations, for prescription containing toxic herbs, biological activity strongly or security window narrower corresponding was studied according to the actual situation of traditional Chinese medicines.
3, the first mention of "quality is the result of design ideas and concepts
2017 version of the guiding principles in "the basic principles of Chinese medicine process change research already on the market" in the "necessary, scientific and reasonable" principle in the mentioned for the first time, to "quality is the result of design ideas and concept to carry out the production process change research, the factors that may affect the quality of traditional Chinese medicine (TCM) to carry on the design and control.
For the first time in this principle, also mention the production equipment is the concept of service for drug quality, and the choice of production equipment should accord with the requirement of production process, the enterprise must in order to meet the production equipment and production technology to provide necessary and reasonable change evidence.
4, fingerprint possible comprehensive application
In view of traditional Chinese medicine (TCM) usually contains chemical composition is complicated, the stable quality of the uniform need through the whole production process quality control to ensure that, after the 2017 edition of the guidelines require production process changes need to be from the aspects of product quality, stability, biological properties and so on to conduct a comprehensive study, especially clear requirements must provide changes involved in the quality contrast research of production process quality control indexes of comparative research materials, (3) the change process and the sample with the original samples (10) production process quality control index in the quality standard of comparison research materials.
Quality and the quality standard research, 2017 guidelines put forward can use appropriate quality control method based on the characteristics of products, increase the circumstances such as fingerprint (feature maps), dissolution test and other test items, sample quality comparison research, in as much as possible through the inspection before and after the change of the consistency of product quality.
In no better establish systematic methodology study traditional Chinese medicine formula ingredients, fingerprint (feature maps) may be a way there is no way. To establish fingerprint (feature maps) is the basis of research on medicinal herbs have been fully, this would be the greatest obstacle of many pharmaceutical factory is hard to continue to study.
5, provide information more clearly
2017 guidelines will declare data format for the standardization of requirements will be good for enterprise to fill in format. For example "Ⅱ class change research and reporting data requirements", you need to provide clinical trials or bioequivalence study more information. Some clinical trials in the number of cases of not less than 100 for clinical trials, used in a number of diseases, every major disease cases of not less than 60 to; Pharmacology and toxicology test data according to the need to provide.
"Ⅲ class change research and reporting data requirements" pharmacology and toxicology test is required to provide the related research and Ⅱ, Ⅲ period or bioequivalence research, clinical trials to prove that change will not negatively impact the quality of medicines.
2017 version of the guiding principles of "Ⅱ class change research and reporting data requirements" and "Ⅲ class change research and declare the information requirements for different preparations of material changes to the proposed data have different requirements, external preparation materials change as part of the Ⅱ change or Ⅲ class changes, the need to provide preparation non-clinical safety studies data; Slow release/controlled release preparation materials as part of the Ⅲ change change, pharmacokinetic research data should be provided.
In 2017 version of the guidelines, however, did not belong to which kinds of change for change in the external preparation materials are defined, in the 2011 version of the guidelines can query to the relevant principles - "local role and used for whole body damage or decay of the skin, the function of the absorption and use of drugs in external preparation will not produce significant effect of kind or amount of auxiliary materials change" belong to "Ⅱ class changes"; "Add or remove the external preparation have obvious effects on drug absorption use accessories; local role and used for whole body damage or decay of the skin, the function of external preparation of the change of the kind or amount of permeation promoter" belong to "Ⅲ class changes".
Summary < < <
Overall, 2017 guiding principle embodies the spirit of national of proprietary Chinese medicine management, and embodies the country think of TCM quality control key points for the medicinal material pretreatment, extraction and purification, and molding process. Fingerprint, and dissolution of these two quality standard method mentioned again and again, the author in this bold prediction Chinese medicine for oral administration and evaluation of the key methodologies will be associated with the two methods. |
