Standard Decoction of Classical Chinese Medicine Compound Formulas
Submission Requirements
(Draft for Comments)
I. Submission Materials Items
(1) Overview Materials
1. Medication Name
2. Proof of Document
3. Prescription Source and Historical Development
4. Evolution of the Formula Principle
5. Clinical Applications
6. Summary and evaluation of key research findings
(II) Pharmaceutical Research Data
7. Summary of Pharmaceutical Research Data
7.1 Summary of Key Research Findings
7.2 Analysis & Evaluation
8. Herbal medicine
8.1 Source
8.2 Resource Assessment
8.3 Quality Rating
8.4 References
9. Decoction Piece Processing
9.1 Determination of Processing Methods and Parameters
9.2 Quality Rating
9.3 References
10. “Standard decoction”preparation
10.1 Process Research
10.2 Herbs, Decoction Pieces, and“Standard decoction”hierarchy of value transfer
10.3 References
11. “Standard decoction”quality control
11.1 Basic Requirements
11.2 Research on Chemical Composition and Critical Quality Attributes
11.3 Quality Research
11.4 Standard Body
11.5 Sample Inspection Report
11.6 References
II. Instructions for Preparing Application Materials
(I) Overview
1. Medication Name
Drug names include:
①Chinese Name;
②Pinyin Name
③Naming basis.
The name of a TCM compound preparation derived from an ancient classic formula (hereinafter referred to as a "classic formula") shall, in principle, match the formula name found in ancient medical texts.
2. Proof of Document
Supporting documents include:
①Copies of the applicant's legally registered proof documents, "Drug Production License," and "Good Manufacturing Practice for Drugs" certification.
②Copy of the registration certificate or approval number for packaging materials (or containers) in direct contact with pharmaceutical products;
③Other supporting documents.
3. Prescription Source and Historical Development
The prescription composition, dosages of each ingredient, functions and indications, as well as the proposed administration and dosage should be clearly stated.
Clearly specify the source of the prescription (title and author), including the dynasty or period of origin. Provide the original text's record of herbal ingredients, processing methods, and dosages, along with the standardized names for each herb. Also include the original text's description of functions, indications, usage, and dosage. Attach the relevant excerpt from the original work as supporting documentation.
Provide a comprehensive review of the prescription's historical evolution, citing all relevant pharmacopoeia and literature with full references (including author, publication year, and edition).
4. Evolution of the Formula Principle
Apply TCM theory to analyze the etiology, pathogenesis, treatment principles, and methods of classic formula indications. Examine the formula's combination principles (such as Emperor, Minister, Assistant, and Guide) and the interrelationships among its ingredients. Systematically review the evolution of formula interpretations and corresponding treatment methods throughout history, citing relevant sources.
5. Clinical Applications
Apply the literature research method to systematically review past study results and clinical applications. Summarize and analyze existing clinical data reflecting the safety and efficacy of classic formulas, emphasizing their value in contemporary clinical practice. Additionally, provide a discussion on market prospects.
Ensure that cited references are authentic and relevant, clearly indicate their sources, and verify their credibility and reliability.
6. Summary and evaluation of key research findings
Provide a summary and evaluation of the key research findings by the applicant.
(II) Pharmaceutical Research
7. Summary of Pharmaceutical Research Data
The pharmaceutical research data summary is a conclusion, analysis, and evaluation of the pharmaceutical research results conducted by the applicant.
7.1 Summary of Key Research Findings
7.1.1 Prescription Herbal Resource Assessment
Clarify the source, origin, dosage form, administration method, and dosage of the prescription, along with its usage in recent and modern times. Briefly describe newly established quality control methods and acceptance limits for the ingredients in the prescription.
Briefly describe the assessment of medicinal material resources.
7.1.2 Decoction Piece Processing
Clarify the processing of medicinal herb slices in15Batch“Standard decoction”consistency.
If changes are necessary, specify the timing, content, and justification, and confirm compliance with relevant standards.
7.1.3 Process Research
Briefly summarize the batch, scale, and quality inspection results of the process development samples. Analyze whether the process is stable, reasonable, and feasible, using the mean value as the baseline. Furthermore,“Standard decoction”analyze the process parameters.
7.1.4 Drug Standards
Briefly describe the main components of drug standards. Specify the number of batches tested for assay, the proposed assay limits, and the basis for their determination. Provide details on the reference standard's source and purity. If a non-statutory reference standard is used, confirm whether it has been calibrated by a statutory authority.
7.2 Analysis & Evaluation
Summarize findings from research on medicinal resource assessment, preparation processes, and quality control, and analyze the interrelationships among these results. Integrate historical literature to interpret pharmaceutical research outcomes. Evaluate process feasibility and quality controllability.
8. Herbal medicine
8.1 Source
8.1.1 Prescription Drug Taste
Summarize the source, supporting documents, and applicable standards for each ingredient in the prescription in a list format. Example:
Table1.Prescription Drug Flavor List
Name | Standard | Origin (up to county level) | Origin (Identification Basis, Expert Witness | Collect time, batch, quantity, etc. |
8.1.2 Herbal Material Authentication and Source Identification
Describe the historical evolution of the herbs used in classic famous formulas, identify their species origins, and specify the botanical sources of the medicinal materials employed in standard decoction studies.
Provide documentation on the actual medicinal materials used, including family name, Chinese name, Latin binomial, plant part used, origin, harvest period, initial processing method at the place of production, and whether it is cultivated./Information on aquaculture (artificial production) or wild-sourced materials. Ecological environment, morphological description, growth characteristics, and cultivation or breeding (artificial production) techniques for medicinal herbs.
For medicinal materials with easily confused botanical origins, a botanical origin identification report must be provided. For multi-origin medicinal materials, in addition to meeting quality standards, the botanical origin must be fixed, and the rationale for the selected origin must be documented.
When medicinal material quality varies significantly by origin, the source should be standardized., Fixed origin does not mean a single plot of land, but rather a designated region where medicinal quality remains relatively consistent with minimal variation. The use of authentic regional herbs (Dao-di herbs) is encouraged.
When medicinal quality varies significantly across harvest times, the harvest period should be standardized.
8.2 Resource Assessment
Manufacturers should conduct herb resource assessments during the project initiation, development, and post-market phases to ensure stable sourcing of Chinese medicinal materials, promote sustainable resource use, and minimize environmental impact.
Herbal resource assessment refers to the scientific evaluation process and resulting data and conclusions by which manufacturers analyze, based on their production capacity, the relationship between projected consumption and projected availability of herbal resources over a specified period, as well as the potential impact of product manufacturing on the sustainable use of these resources.
Details on the content and conclusions of the herbal resource assessment are provided in the "Technical Guidelines for TCM Resource Assessment."
8.3 Quality Rating
Conduct activities for medicinal herbs, processed slices, and“Standard decoction”quality overview study,from ointment yield, content determination, fingerprint profiles, or characteristic profilesConsider herbs comprehensively-Decoction pieces-“Standard decoction”correlation, identify key quality attributes of the medicinal material, establish corresponding quality evaluation indicators and methods, and define a scientifically sound and reasonable quality standard for the medicinal material.
Quality profile refers to the overall description of a drug's quality attributes, considering both its safety and efficacy, and theoretically ensuring that the drug meets expected quality requirements. Quality attributes are physical, chemical, or biological properties that affect a drug's safety, efficacy, or consistency. Critical quality attributes (CQAs) are those quality attributes that have a significant impact on the drug's quality.
8.3.1 Quality Evaluation Metrics
Quality evaluation indicators for medicinal materials should correspond to the corresponding“Standard decoction”show a good correlation with quality and clinical efficacy, while meeting requirements for measurability, accuracy, durability, and low cost. EncourageDNAExploratory Research and Application of Barcode Detection
Common quality evaluation criteria for medicinal herbs include:
——Qualitative indicators, such as origin,Medicinal Part, Origin, Harvest Time, Post-Harvest ProcessingTraitsValid/Target Components;
——Quantitative metrics, such as effectiveness/Active Ingredient ContentMoisture, impurities, pesticide residues, heavy metals and harmful elements, mycotoxinsWaitExternal contaminationLimited quantities, etc. If no testing is performed, provide a valid justification.
8.3.2 Prescription drug flavors must first comply with national drug standards, including《Chinese Pharmacopoeia》as well as the original Ministry-issued standards for Chinese medicinal materials. Additionally, enterprises must establish internal standards that meet or exceed national requirements.
Establishing enterprise standards must effectively control the quality of relevant Chinese herbal materials. If critical quality risk points identified during formulation quality evaluation cannot be controlled through existing material standards, those standards must be revised to include appropriate control methods and specifications. Submit a draft standard and its rationale; if new reference substances are required, provide both physical samples and written specifications along with supporting documentation, and file in compliance with applicable regulations. For exogenous impurities such as pesticide residues, mycotoxins, heavy metals, and harmful elements potentially present in herbal materials, establish control limits in accordance with relevant guidelines.
8.3.3 Quality Analysis
at least3not less than {0} from the following origins:15Analyze quality attributes of batch medicinal materials. Identify quality risk points related to origin, harvest period, and primary processing.
8.3.4 Provide the batch inspection reports for three batches of prescription drugs.
Provide sources for citations and files。
9.1 Determination of Processing Methods and Parameters
Describe the historical evolution of decoction processing methods used in classic famous formulas, determine their specific processing techniques—including cleaning, slicing, and frying—with detailed procedures, and provide the rationale for these processes.
Provide the standard basis for the adopted processing method.
9.1.1 Herb Purification
For processed medicinal materials, describe the purification method in detail (e.g., sorting, winnowing, water washing, sieving, trimming, cutting, scraping, peeling, removal of impurities, brushing, rubbing, grinding, pounding, extraction, or pressing). The purified materials must meet pharmaceutical standards.
9.1.2 Herb Slicing
For sliced medicinal herbs, the rationale for determining the slicing type and specifications must be clearly documented. If softening treatment is required prior to slicing, key parameters that may affect active ingredient loss or degradation—including softening duration, water absorption rate, temperature, and technical specifications of the soaking equipment—must be explicitly specified.
9.1.3 Herbal Processing
Processed medicinal materials must clearly specify the processing method (e.g., stir-frying, roasting, baking, calcining, steaming, boiling, scalding, stewing,霜-making, wet grinding) and specific process parameters. For materials processed with excipients, the source, type, quantity, and applicable standards of the excipients must be clearly stated.
Clearly specify the processing methods and conditions for medicinal slices, key production equipment, scale, yield, packaging, storage conditions, and relevant in-process quality control methods.
9.2 Quality Rating
Conduct activities for medicinal herbs, processed slices, and“Standard decoction”Quality profile study, comprehensively considering medicinal materials-Decoction pieces-“Standard decoction”Based on relevance, determine the critical quality attributes of the medicinal slices, establish corresponding quality evaluation indicators and methods, and define scientifically sound standards for the medicinal slices.
9.2.1 Quality Evaluation Metrics
Quality evaluation criteria for decoction pieces should correspond to the respective“Standard decoction”quality and clinical efficacy show good correlation, and are associated with corresponding“Standard decoction”The quality evaluation indicators for medicinal materials correspond well. Encouraging furtherDNAExploratory Research and Application of Barcode Detection
Quality evaluation indicators for medicinal slices typically include:
（1Qualitative indicators, such as herb source, botanical origin, physical characteristics, and active constituents/marker components, etc.;
（2) Quantitative metrics, such as effective/Active Ingredient ContentMoisture, impurities, pesticide residues, heavy metals and harmful elements, mycotoxinsWaitExternal contaminationLimited quantities, etc. If no testing is performed, provide a valid justification.
Quality evaluation related to processing techniques includes:
（1Establish a consistency evaluation method for processed slices to characterize batch-to-batch consistency.
（2Establish a system for critical process parameters and in-process quality control indicators to manage the production process, processing equipment, manufacturing facilities, and raw materials.
Drug quality control methods should be designed in parallel with pharmaceutical processes, equipment, production facilities, process controls, process management, material quality control, material testing, drug quality inspection, and engineering validation. This integration ensures that quality control is embedded within the manufacturing approach, guaranteeing a scientific, rational, and reliable production model and quality assurance system. As a result, Chinese medicine manufacturing workshops can consistently produce drugs that meet requirements for safety, efficacy, and quality consistency.
9.2.2 Standard
Decoction pieces used in preparations of classic famous formulas must be processed according to the methods recorded in the original source and comply with the general processing standards of the current edition of the Chinese Pharmacopoeia.
Establishing proprietary standards for processed herbal pieces must ensure effective quality control. If critical quality risks identified during dosage form evaluation are not addressed by control indicators in the current piece standards, those standards must be revised to include appropriate control methods and indicators. A draft standard and accompanying rationale must be provided; other requirements remain consistent with those for crude herbs.
9.2.3 Provide the inspection report for the medicinal herbs.
9.3 References
Provide source citations for references and documents.
10. “Standard decoction”preparation
Classic Prescription Preparations“Standard decoction”Preparation shall, in principle, be based on methods recorded in ancient texts. The method, equipment, process parameters, and operating procedures must be standardized.Establish corresponding process control methods.Verified through oil yield, content determination, fingerprint profiles, or characteristic profiles, etc.Keep“Standard decoction”Consistent and traceable quality across batches.This is illustrated using decoction in water as an example.
Classic Prescription Preparations“Standard decoction”Prepared by decocting processed medicinal ingredients according to the prescribed formula and dosage, followed by physical solid-liquid separation, concentration, and drying to form the final product.“Standard decoction”In the form of concentrated extract or freeze-dried product. All pharmaceutical research on classic formula preparations must be consistent with“Standard decoction”Reach consensus. By no less than15Obtained by decocting, concentrating (and drying), etc., from a batch of raw medicinal slices.15Approve“Standard decoction”, using its mean as the baseline.
10.1 Process Research and Flowchart
10.1.1 Simmer
EveryThe decocted herbs are measured according to daily therapeutic dosages. The preparation method follows the records in the Catalogue of Classic Formulas, in conjunction with the "Management Standards for TCM Decoction Rooms in Medical Institutions" issued by the Ministry of Health and the State Administration of Traditional Chinese Medicine (Guo Zhong Yi Yao Fa [2009〕3Boil the decoction. Determine reference values for key parameters in the fixed herbal preparation process, including pre-treatment methods, particle size, number of decoctions, water volume, and boiling time. The experimental report and submission documents must clearly describe the research process.
10.1.2 Filtration, Concentration, and Drying
Select appropriate filter media and filter while hot. The resulting decoction may be concentrated to produce the specified amount of extract or dried using a suitable method to obtain a dry product, ensuring stability of its substance basis and ease of dissolution.，No additional ingredients added.
Strengthen research on the impact of concentration and drying methods on critical quality attributes (CQAs). Based on the selected method, investigate how process parameters affect the material's chemical and physical properties. Once key parameters are fixed, finalize the method, equipment, process parameters, and operating procedures.
10.1.3 Process Flow Diagram
Provide a complete, intuitive, and concise guide based on the preparation process steps.“Standard decoction”Process flow diagram covering all processing steps, with key process parameters and extraction solvents indicated. Describe the process by unit operations (including packaging), specifying operating procedures, process parameters, and ranges.
10.2 Herbs, Decoction Pieces, and“Standard decoction”hierarchy of value transfer
Based on oil yield, content determination of active (or indicator) ingredients, and fingerprint or characteristic profiles, describe the medicinal materials, processed slices, and“Standard decoction”value transfer relationship.
10.2.1 Yield rate: Calculate15Approve“Standard decoction”extract yield, and calculate the relative standard deviation. If discrete data (exceeding3xRSDor at the mean70%—130%Otherwise, provide analysis data and explain the reasons.
10.2.2 Assay of active (or indicator) components: Determination in crude drugs and processed slices, respectively“Standard decoction”content of effective (or indicator) components, calculate the transfer rate. If the transfer rate shows scattered data (exceeding3xRSDor at the mean70%—130%Otherwise, provide analysis data and explain the reasons.
10.2.3 Fingerprint or characteristic profile:采UseHPLCorGCmethods for separately collecting medicinal herbs, decoction pieces, and“Standard decoction”fingerprint or characteristic fingerprint of multiple batches“Standard decoction”Similarity of fingerprint spectra; or comparison of the number of major component peaks, relative retention times, and peak ratios.
Compare herbs, slices, and“Standard decoction”fingerprint, and the attribution of major chromatographic peaks shall be demonstrated through methods such as preparation and determination of negative control samples or peak identification.
10.3 References
Provide source citations for references and documents.
11. “Standard decoction”quality control
To effectively control“Standard decoction”Quality control across all preparation stages should cover raw materials, processed slices, and“Standard decoction”Study of quality profile, identification of critical quality attributes, and implementation of end-to-end quality control,Ensure“Standard decoction”Consistent and traceable quality across batches.
11.1 Basic Requirements
Standard research should comply with“Technical Requirements for the Development of Standards on Chinese Materia Medica in the Pharmacopoeia of the People's Republic of China”as stipulated in. Provide“Standard decoction”Draft pharmaceutical standard and explanatory notes, along with reference standards and related documentation.
The following issues need to be addressed:
（1Basis for Drug Standard Development: Quality evaluation indicators should align with“Standard decoction”The manufacturing process and clinical efficacy show strong correlation, while meeting requirements for measurability, accuracy, durability, and cost-effectiveness. The rationale for each quality control item must be explained. Summarize and analyze the basis for selecting testing methods and setting limits, and provide considerations and justification for items excluded from the standards.
（2Overall control measures: Establish fingerprint or characteristic profile methods and encourage exploration of bioactivity testing to reflect the overall quality status of the product as comprehensively as possible through inspection. Quality requirements such as assay limits in drug standards should have reasonable ranges; generally, a range can be adopted.15Batch“Standard decoction”The acceptable content range is determined based on test data.
（3Reference Standards: If reference standards from the Chinese Pharmacopoeia were used during development, specify their source and provide the certificate of analysis and batch number. For self-prepared reference standards, provide documentation certifying that they were standardized by the National Institutes for Food and Drug Control (NIFDC).
11.2 Research on Chemical Composition and Critical Quality Attributes
11.2.1 Literature Review on Chemical Composition Research
Provide literature on chemical composition research, analyzing and describing the main chemical constituents related to extraction processes along with their physicochemical properties.
11.2.2 Research data on chemical component confirmation
Provide experimental data on chemical composition studies, including systematic research (extraction, isolation, structural identification) and analytical data with relevant spectra.
11.2.3 Documentation on Critical Quality Attributes
Provide test data that clearly defines the determination methods and limits for physicochemical, biological activity, and batch-to-batch consistency indicators affecting safety, efficacy, and quality.“Standard decoction”key quality attributes and their influencing factors.
Table2.“Standard decoction”Key Quality Attributes Summary
Project (AsxxIngredients | Drug Standards (e.g., upper and lower limits of content) | |
Key quality attributes related to efficacy | ||
Key Quality Attributes Related to Security | ||
Process-related Critical Quality Attributes | ||
Other Key Quality Attributes |
11.3 Quality Research
SubmitExperimental and literature data for quality research. Typically includes the following:
11.3.1 Analysis Method: List the testing methods for each item specified in the drug standard.
Table3. Test Items
Project Evaluation | Detection Method | Limit Requirements | Test Basis |
Traits | |||
Verify | |||
moisture | |||
Content | |||
Fingerprint or characteristic fingerprint | |||
Check | |||
Other Projects |
11.3.2 Method Validation
Method validation for inclusion in standard projects，Provide method validation data and corresponding analytical chromatograms in accordance with the relevant guidelines of the current edition of the Chinese Pharmacopoeia, item by item.
11.3.3 Exogenous Contaminant Analysis
For impurities such as pesticide residues, heavy metals, arsenic salts, mycotoxins, solvent residues, and resin residues, analyze their sources. Based on relevant guidelines, establish control limits. Provide justification for whether each impurity is controlled in the final quality standard and for the specified limits.
11.4 Standard Body
Submit the formulated“Standard decoction”Standard body text.
[Prescription] The botanical source of each herb in the prescription must be clearly specified. [Preparation] A brief description of the processing methods used to convert each herb into decoction pieces shall be provided, and“Standard decoction”Manufacturing process, including batch size, preparation procedure, key parameters, extract yield range, excipients and their dosage ranges, and final product quantity.A fingerprint or characteristic profile check item should be established. The assay item shall specify the transfer rate of active (or marker) components and acceptable variation ranges.
11.5 Sample Inspection Report
Provide continuous3Inspection report for the sample batch.
11.6 References
Provide source citations for references and documents.