Explanation of the Drafting Principles for "Guidance on Standardized Expression of Specifications for Traditional Chinese Patent Medicines"
I. Purpose and Process of Drafting
Drug specifications are a critical component of drug standards and labeling. Their importance necessitates clear and accurate statements of active ingredients and dosages to inform relevant agencies, physicians, and the public, ensuring proper sale, storage, transport, distribution, use, and regulatory oversight.
Most Chinese patent medicines are compound formulations with complex, numerous ingredients and undefined active components, making their specifications unique. Currently, the majority of marketed TCM preparations cannot label active ingredient content. Although standardization efforts, unified national drug approval numbers, and package insert revisions have significantly improved specification labeling compliance, many standards still lack proper specification details, and some even omit them entirely despite having approval numbers. This issue has drawn widespread concern.
Non-standardized labeling of Traditional Chinese Medicine (TCM) specifications has led to misuse or misunderstanding in drug regulation, R&D, clinical use, pricing, and procurement. During drug evaluation, applications for TCM specification changes are among the most common supplementary submissions for TCMs. Rejections due to unreasonable specifications or requests for additional data are frequent. Currently, the primary basis for evaluating TCM specification changes is: Attachment to the "Drug Registration Management Measures".4Registration Details5“Change Drug Specification”; "Technical Guidelines for Research on Changes of Marketed Traditional Chinese Medicines (I)"; Relevant notices from the National Food and Drug Administration and the China Food and Drug AdministrationCenter for Drug Evaluation (hereinafter referred to as the CDE)Meeting minutes, etc. However, there is no unified understanding of Chinese medicine specifications in the industry; the "Chinese Pharmacopoeia" (2015The descriptions of Chinese patent medicine specifications in the [Year] Edition and other marketed drug standards, as well as in the "Technical Guidance Principles for Research on Changes to Marketed Traditional Chinese Medicines (I)," are not entirely consistent. Currently, there are no dedicated technical requirements or regulatory provisions specifically addressing TCM specifications, which poses challenges in evaluating their rationality.
Regarding the issues with labeling specifications of currently marketed traditional Chinese medicine products,2015Year8The Drug and Cosmetics Registration Division of the State Food and Drug Administration (hereinafter referred to as the Division) commissioned a research team from Shanghai University of Traditional Chinese Medicine to study issues related to specifications of proprietary Chinese medicines. Following the project's initiation, the team conducted a literature review to establish a database of Chinese medicine species and their specifications. Based on this database, we systematically reviewed the current state of Chinese medicine specifications, held focused discussions on identified issues, and carried out enterprise surveys.2016Year6The National Medical Products Administration's Center for Drug Evaluation organized a special meeting on Chinese medicine specifications in Beijing, bringing together experts from drug regulatory bodies, testing institutions, clinical settings, R&D departments, and the drug evaluation system nationwide. The research team presented its preliminary survey findings, and participating experts discussed the standardization of specifications.Meaningdeeply discussed expression methods and other aspects to reach a consensus among experts.To understand the unique characteristics of ethnic medicines, the research team2016Year8Visited Xinjiang to conduct research on Uyghur medicine manufacturing companies.，Under the organization of the Food and Drug Administration of Xinjiang Uygur Autonomous Region, a special seminar was convened to discussUighur MedicineDiscussed special issues regarding specifications.2016Year12The Drug and Cosmetic Registration Administration of the General Administration convened a project completion meeting in Shanghai, organized experts to further discuss key issues related to the draft guidelines, and based on these discussions, the project team drafted the "Guiding Principles for Expression of Specifications of Traditional Chinese Medicine Products (Proposed Draft)." Subsequently, the Drug and Cosmetic Registration Administration of the General Administration...CompanyIncorporating feedback from the National Pharmacopoeia Commission and the Center for Drug Evaluation of the State Administration, the draft guidelines were revised to produce the "Technical Guidelines for Expression of Specifications of Traditional Chinese Medicine Preparations (Draft for Comments)," which was issued on2017Year10Month11Day—31Public comments are being solicited on the official website of the China Food and Drug Administration today.2017Year12Month6The National Medical Products Administration's Department of Drug and Cosmetics Registration, in collaboration with the National Pharmacopoeia Commission and the Center for Drug Evaluation, convened a finalization meeting to thoroughly review all submitted comments and revise and refine the draft technical guidance principles.
II. Important Notes
(I) Current Status and Issues of Traditional Chinese Medicine Specifications
Based on the research group's database (including60194(in the traditional Chinese medicine preparation registration number)Description and statistics of each document number specification; currently, among marketed products, there are31Specification format. For single-dose medicationsweight or fill volume expression70%Above, items without specifications are included.15%. Near90%The Chinese medicine approval number is not indicated in the "Specification" section of the instructions.Single-dose medicationThe specification is expressed in terms of weight or fill volume rather than drug content, which does not comply with the required content for drug specifications.
Additionally, the following issues currently exist with Chinese patent medicine specifications:
1.Inconsistent and non-standard terminology in specification descriptions
There are significant inconsistencies in the specification terminology, including the use of both Chinese and English for units:fromIn terms of the distribution of document numbers, English expressions are more common. There are varying descriptions for measure words in specifications: such as“each pill***” “***/grain”，by“each pill***”Majority. Adverbs in the specifications include“***equivalent to***”and“***quite***”Two, including“***equivalent to***”The majority. Specifications may express the amount of crude drug in several ways:“***raw medicinal materials***” “***Herbal Medicine***” “***Decoction pieces***”used in specificationsofverbIncluding：“Redo”and“Install”。“Redo”Commonly found in tablets, pills, ointments, etc., expressed as“Weight per piece (pill)***” “Net weight per sheet***”；“Install”Commonly found in mixtures, capsules, granules, etc., expressed as“Per Bottle***” “Per bag***” “Per capsule***”。
2.The specification does not correlate well with dosage instructions.
In some drug standards, the labeled specifications are not sufficiently linked to dosage and administration instructions. For example, a product with a specific approval number lists its specification as "bottle size" without further clarification.60g, and the dosage is per20granules; neither doctors nor patients know each20What is the capsule weight and the amount of processed medicine per capsule? If the specification is changed to "equivalent to... per capsule,"Decoction pieces0.15gdoctors or patients can see at a glance. Chinese Pharmacopoeia2015The Huashan Shen Tablets listed in the annual edition are prepared from Huashan Shen extract as the starting material.itsSpecifications:0.12mg。Content limit:“This product contains alkaloids, including hyoscyamine (C17H23NO3should be {0}% of the labeled amount80.0%—120.0%”。Dosage and Administration:“Oral. Usual dose, one time1—2Slice, one day3times; maximum dose, once4Slice, one day3times”Neither doctors nor patients know how much extract is in each tablet.0.12mgStillcontains hyoscyamine0.12mgFurthermore, this product contains alkaloids calculated as hyoscyamine; it is not a single-component preparation and therefore cannot have its strength labeled as such. This information is also unrelated to the dosage and administration instructions.
3.Inconsistent labeling for the same product specification
Current practice is to specify the strength of unit dosage forms by weight or fill volume.《Guiding Principles for Research on Changes to Marketed Traditional Chinese Medicines (Part I)》CNof“3. Change Drug or Packaging Specifications”BelowPoint out：“Specification refers to the weight, volume, or concentration of a drug in a unit dosage form or single packaging container. Generally, specifications for tablets, capsules, suppositories, and pills are expressed as weight per tablet, capsule, or pill; while specifications for granules, ointments, and syrups are expressed as the weight or volume of the drug in a single packaging container.”
byWeight or quantityLabelThe specification is influenced not only by the content of the active pharmaceutical ingredient and the extraction/purification process, but also closely by the excipient dosage. It is difficult to accurately reflect the amount of active substance per unit dosage form and can vary significantly due to differences in process and excipients.
4.Issues with labeling specifications for single-herb preparations
Single-ingredient preparations list only one component, which fails to fully represent the product and may lead to misunderstanding. For example, Leonurus tablets are compressed extracts of Leonurus; their label specifies each tablet contains stachydrine hydrochloride.15mg, which does not indicate the equivalent amount of Leonurus herbal decoction pieces. For example, for Jinlianhua tablets, the specification only states that each tablet contains not less than a certain amount of total flavonoids.42mg。
5.Issues with labeling specifications for compound preparations
Some drug standards list compound formulas but specify only the content of a single ingredient in the dosage form. This incomplete labeling can be misleading. For example, Compound Berberine Tablets (sugar-coated) contain Berberine Hydrochloride...30gMuxiang116gEvodia40g, White Peony Root162GBComposition: Each tablet contains Berberine Hydrochloride30mgThe dosages of other herbs in the compound formula are not specified, missing a core element.
(II) On the Connotation and Expression of Drug Specifications
1.FDAAboutContent and Expression of Drug Specifications
FDADrug strength refers to the amount of active ingredient in a single-dose medication.The strength of a drug product indicates the amount of active ingredient per dosage unit.). For example, the firstFDAApproved Herbal MedicinesVeregen®Ointment，Its specifications are“15%”, meaning everygThe ointment contains active ingredients.sinecatechins 150mg(mixture). Another was in the United StatesFDASustained-release tablets of approved herbal medicinesFULYZAQ，Its specifications are"125mg", i.e., each tablet contains active ingredient(s) (mixture)Crofelemer 125mg。
2.Relevant provisions in our country's regulations regardingDrug Specification
In the "Cihai," "specification" refers to standards set by production units for finished products or raw materials, including weight, density, color, impurity content, chemical composition, mechanical properties, and internal/external dimensions. Compared with the definition in the United States Pharmacopeia (USP), this definition is far more comprehensive, encompassing not only drug content but also indicators such as weight and dimensions.
"Measures for the Administration of Drug Registration" (National Medical Products AdministrationLet28No.) Attachment4“Requirements for Registration Matters and Submission Materials for Drug Supplemental Applications”in“Registration Details5.Change Drug Specification"RequirementsFor：“The applied specification shall match the approved specifications for the same product. If they differ, the deviation must be scientifically justified, reasonable, and necessary. The applied specification should be determined based on the drug's dosing regimen and generally shall not be less than the minimum single dose or exceed the maximum single dose.”This file does not specify the specifications for traditional Chinese medicine.makeSpecial Notes.
Technical Guidelines for Research on Changes of Listed Traditional Chinese Medicines (I)The current specifications primarily address changes to already marketed drugs and do not provide a systematic framework for specification labeling.
Regarding issues with supplementary applications for specification changes, the originalNational Medical Products AdministrationThe Drug Evaluation Center successively issued the "Notice on Strengthening the Management of Drug Specifications and Packaging Specifications" (CFDA)Note〔2004〕91No.), "Notice on Printing and Distributing the Basic Technical Requirements for Traditional Chinese Medicine and Natural Drug Injections" (CFDA)Note〔2007〕743meeting minutes and electronic publications regarding the specifications, which summarize that: the added drug specifications must not alter the original dosage, administration method, or target population;If the drug specification being applied for differs from existing market specifications of the same product, it must adhere to principles of scientific validity, rationality, and necessity. It must undergo thorough justification to avoid confusion in clinical prescribing practices. Drug packaging sizes should be economical and convenient. For drugs with defined treatment courses, packaging sizes should generally align with those courses.Unless the new specification is clinically necessary (provide sufficient pharmacological, toxicological, and clinical data demonstrating its safety and efficacy).ResearchBased on the following criteria, and to facilitate medication administration for physicians, nurses, and patients, as well as drug management by the pharmacy department. Otherwise, adding new specifications is not recommended.Overall, China currently lacks specific regulatory documents that systematically define specifications.
(3) Difference between Drug Specifications and Fill Volume Specifications
Drug specifications are typically expressed as the amount of active ingredient per unit dosage form (e.g., per tablet, capsule, gram, milliliter, or pill). However, traditional Chinese medicines (TCMs) are mostly compound formulations with complex compositions. Therefore, TCM drug labels should generally indicate the theoretical or declared equivalent amount of herbal ingredients from the prescription (including processed slices, extracts, and active components) contained in each unit dosage form.
The package size specification indicates the quantity of the drug formulation contained in the smallest packaging unit. For example, in tea bags:“Per bag2.2gPer bag4.4gThis should reflect the dosage strength. Products of the same type with identical drug content per unit dosage form shall be considered to have the same specification. For example“each10Net Weight2GBequivalent to medicinal powder5Gand“each20Net Weight2GBequivalent to medicinal powder5GThis indicates different fill volumes but the same drug specification. For the same product and drug specification, the fill volume may vary.
(IV) Coordination of Drug Specifications, Dosage and Administration, and Fill Volume
Drug specifications should align with the "Dosage and Administration" and "Packaging" sections of the package insert to facilitate patient medication guidance. For example, when the "Dosage and Administration" for granules is“Oral. One dose.**g..."When, [Specification] can be expressed as“each1 GBequivalent to decoction pieces**g, while the quantity specification for [Packaging] is expressed as“Per bag**gThe drug specification must ensure accurate dosing. Typically, a single dose should not be taken all at once.1/3bag (bottle) or1/4Bags, bottles, or similar packaging. For prescription drugs involving toxic ingredients or highly active pharmaceuticals where dosage accuracy is critical, the drug specifications must comply with safe medication requirements.
(5) Correspondence between Chinese medicine specification descriptions and prescription ingredients
Due to the diversity of TCM material categories, specification expressions vary slightly. For preparations using active ingredients or extracts as raw materials, specifications can be directly stated by the amount of active ingredient or extract contained per unit dosage form. If a preparation contains two or more types of raw materials, all must be reflected in the specification statement. For example, Compound Berberine Tablets contain Berberine Hydrochloride...30gMuxiang116gEvodia40g, White Peony Root162GBComposition, which includes two types: herbal slices and active ingredients. The specification description is suggested as follows:“Each piece is equivalent to a decoction piece.0.318g, containing berberine hydrochloride30mg. If a medication contains both Traditional Chinese Medicine (TCM) and Western medicine components, its specification should reflect both. For example, Xiaoke Wan is composed of Pueraria lobata, Rehmannia glutinosa, Astragalus membranaceus, Trichosanthes kirilowii, Corn silk, Schisandra chinensis, Dioscorea opposita, and Glibenclamide. The recommended revision for its specification statement is:“Each pill is equivalent to a decoction piece**g, containing glibenclamide0.25mg”。
(VI) Standard Terminology for Describing Traditional Chinese Medicine Specifications
grams, millilitersg、machine learningetc., such asEach granule is equivalent to one dose of the decoction piece.** GB, each1 mlequivalent to decoction pieces**mgWait, not adopted“equivalent to decoction pieces**g/particles per milliliterequivalent to decoction pieces**mg”other ways of expression.Other dosage units such as pills, bags, and granules shall be expressed in Chinese.Over-the-CounterUnits in traditional Chinese medicine specifications, such as grams and milliliters, are also expressed in Chinese.For drugs with decoction pieces as the input material, use the following standard:“equivalent to”language, such as“Each granule is equivalent to one dose of the decoction piece.**g, not adopted“Equivalent to each piece of decoction**glanguage.