Brief introduction on the development and revision of the Chinese Pharmacopoeia 2025 Edition ^*

Since the establishment of the 12^th Chinese Pharmacopeia Commission (ChPC), all ChPC members have earnestly implemented the "four strictest" requirements and have completed the compilation of the Chinese Pharmacopoeia 2025 Edition in accordance with the "14th Five-Year Plan" for National Drug Safety and High-Quality Development　and the Compilation Outline of Chinese Pharmacopoeia 2025 Edition, relying on the action plan for improving drug standards, under the support and cooperation of drug control agencies, research institutes and associations at all levels after five years. On November 27, 2024, the Executive Committee of the 12th Chinese Pharmacopeia Commission reviewed and adopted the Chinese Pharmacopoeia 2025 Edition (draft). The Chinese Pharmacopoeia 2025 Edition is to be promulgated and implemented in March 2025 with the approval of the National Medical Products Administration （NMPA） and the National Health Commission (NHC). The Chinese Pharmacopoeia is an important part of the national drug standards, the core of the national drug standard system, and the basic requirement on and legal basis for drug manufacture, drug testing, drug use and drug administration. Since the first edition of the Chinese Pharmacopoeia was published in 1953, the Chinese Pharmacopoeia 2025 Edition is the 12th edition. The overall amendments to the Chinese Pharmacopoeia 2025 Edition are described as follows.

1. Overview of the development and revision of Chinese Pharmacopoeia 2025 Edition

The Chinese Pharmacopoeia 2025 Edition contains a total of 6,385 monographs, including 159 new monographs, 1,101 revisions and 32 rejections. Among them, Volume I（TCMs） contains a total of 3,069 monographs of traditional Chinese medicines, including 28 new monographs, 420 revisions and 19 rejections. Volume II (Chemical drug) contains a total of 2,776 monographs of chemical drugs, including 66 new monographs, 483 revisions and 2 rejections of pharmaceutical excipients which are transferred to be included in Volume IV. Volume III （Biologics） contains a total of 153 monographs of biological products, including 13 new monographs, 62 revisions and 13 rejections. Volume IV contains a total of 387 monographs of pharmaceutical excipients, including 52 new monographs and 136 revisions.

This edition of Pharmacopoeia contains a total of 410 general requirements, including 69 new general requirements and 133 revisions; Volume III contains a total of 13 new general chapters (general monographs) of biological products and 31 revisions; Volume IV contains 56 new general chapters and 102 revisions.

This edition of Pharmacopoeia contains a total of 72 guidelines, including 33 new guidelines, 17 revisions and 3 rejections. Among them, Volume III contains 5 new guidelines of biological products. Volume IV contains 28 new guidelines, 17 revisions and 3 rejections (see Table 1).

Tab. 1 Overview of the development and revision of ChP 2025

Note: ^* Changes in the number of traditional Chinese medicine decoction pieces in the Chinese Pharmacopoeia 2020 Edition (Volume I); ^{* *} guidelines included in the Pharmacopeia that are broken down from the general requirements; ^{* * *} corresponding general chapters and guidelines of biological products included.

2 Main changes in the Chinese Pharmacopoeia 2025 Edition

2.1 Steadily promote the Chp monographs included

Adhering to the clinical application orientation, the scope of monographs included in the new edition of the Chphas been further expanded to achieve the coverage of the Catalogue of National Essential Medicines (CNEM) and the Catalogue of Medicines for Basic Medical Insurance (CMBMI) to further improve the controllability of the quality of commonly used clinical drugs (see Figure 1). In the new edition of the Chp, the inclusion of standards for newly approved drugs is accelerated, and new standards for the anti-cancer drugs Lobaplatin for injection and Arsenic Trioxide for injection independently developed by China are included; the Chp is the world’s first to contain the standards for Pegylated Human Growth Hormone injection and Jinpei growth hormone injection independently developed by China and with independent intellectual property rights; the Chpcontains recombinant Bivalent Human Papillomavirus vaccine (Escherichia coli) and 13-valent Pneumococcal Polysaccharide Conjugate Vaccine (TT/DT) with independent property rights in China for the first time; and the Pharmacopoeia contains the standards for five biosimilar drugs including Rituximab, Infliximab, Trastuzumab, Bevacizumab and Adalimumab for the first time, reflecting the new achievements of pharmaceutical innovation and research in China and further meeting the clinical drug needs. Meanwhile, children's drug standards are included, and the evaluation results of the consistency of generic drug quality and efficacy are reflected in the pharmacopoeia standards, further guaranteeing the quality of clinical drugs.

Fig. 1 The amount of the monographs in the previous editions of the ChP

2.2 Continue to improve the national drug standard system

Chinese Pharmacopoeia is the core of the national drug standard system, and the general requirements included in the pharmacopoeia are the "four beams and eight pillars" that constitute the Chinese Pharmacopoeia standard system. A total of 252 general requirements and guidelines have been developed and revised in the new edition of the Pharmacopoeia, accounting for 55% of the total number included. The standard system of the Chinese Pharmacopoeia, with the general notices of the Chinese Pharmacopoeia as the basic requirements, the general chapters (general monographs) as the overall provisions, the guidelines as the technical guidance, and the monographs as the specific requirements, has been further improved, which is of great significance to implement the concept of drug life cycle management, to comprehensively strengthen drug quality control requirements, to systematically standardize drug quality standards, and to improve the overall level of drug quality control in China.

2.2.1 Standardize the requirements of general notices

The "General Notices" of the pharmacopoeia are the basic requirements and common provisions of the pharmacopoeia standards. In the connection with the laws and regulations such as the Drug Administration Law of the People’s Republic of China, the Vaccine Administration Law of the People's Republic of China, the Provisions for Drug Registration, the Measures for the Administration of Drug Standards, and the Special Provisions on the Administration of the Standards for Traditional Chinese Medicine, the harmonization of unified regulations and common contents of the "General Notices" in each volume of the Pharmacopoeia is realized, taking into account the characteristics of the Volume I, Volume II, Volume III and Volume IV of the Pharmacopoeia. (1) In accordance with the relevant provisions of the newly promulgated Measures for the Administration of Drug Standards, the general requirements and guidelines of the Pharmacopoeia have been redefined, their respective positions and roles have been clearly defined, and the guidelines have been taken as recommended technical requirements in order to better reflect the seriousness of the implementation of the Chinese Pharmacopoeia. (2) The "General Notices" in Volume II and Volume IV of the Pharmacopoeia have defined relevant requirements for the transformation and implementation of ICH Q3C/3D Guidelines, further strengthened the concept of risk-based management and specified the control requirements and implementation strategies for elemental impurities, residual solvents, heavy metals and harmful elements as well as genotoxic impurities. (3) In the "General Notices" in Volume I of the Pharmacopoeia, the "Usage and Dosage" in the standards for traditional Chinese medicinal materials and decoction pieces is defined "as the guidance for clinical medication, and clinical use should follow the doctor's advice".

2.2.2 Improve the pharmacopoeia standard system

Continue to build and improve the multi-dimensional standard system of the Chinese Pharmacopoeia, and further strengthen the formulation and revision of general notices, general chapters, general monographs, test methods and guidelines horizontally; establish a standard system encompassing traditional Chinese medicines, chemical drugs, biological products, drug substances, pharmaceutical excipient and pharmaceutical packaging materials vertically, throughout the main line of the management concept of the whole life cycle of drugs to fill in the gaps and improve weak links, continue to improve the quality control requirements of the whole process of drug research and development, production, circulation and use, move the drug quality control threshold forward, strengthen the requirements for drug process and source control and the establishment of relevant test methods, introduce the concept of risk identification and risk management, and establish the quality control strategies based on risk prevention and control to promote the ability of drug manufacturers to identify product risks, better strengthen and implement the responsibilities of manufacturers as the main body of drug quality, and guarantee the drug quality more comprehensively and effectively.

2.2.3 Strengthen the standardization of the establishment of drug test methods

Drug analysis and test method is the basis of drug quality control. Standardizing the establishment of analysis and test methods is an important prerequisite to ensure the applicability, reliability and stability of drug test methods and the consistency of test results from different laboratories. For the various analysis and test methods in the new edition of the Pharmacopoeia, the establishment and application of physical and chemical analysis and testing, microbiological examination, bioactivity detection and molecular biological detection methods have been further standardized, and corresponding technical specifications have been formulated (see Table 2) to lay a solid foundation for ensuring the scientificity, normalization and operability of the Chinese Pharmacopoeia.

Tab. 2 General technical requirements for the test method establishment in ChP 2025

The General Chapter 9101 Guideline for Validation of Analytical Method has been revised to be harmonious with the international mainstream pharmacopoeias; the General Chapter 9307 Guideline for Design, Development and Validation of Bioactivity Assay Methods has been included and the 9401 Guideline for Validation for Biological Activity/Potency Assay of Biological Products has been revised to provide guidance for the establishment of quality control methods for active ingredients in multi-component complex biologics. The Chinese Pharmacopoeia has included the 9213 Guideline for Validation, Verification and Transfer of Microbiological Analytical Methods for Pharmaceuticals for the first time to provide guidance for the establishment and control strategies of methods for controlling microbial contamination of drugs. The development and revision of relevant technical requirements through various analysis and test methods of pharmacopoeia will be more evidence-based in the establishment and applicability study of relevant biological and microbial test methods, more unified and harmonious with international technical requirements, and the establishment and application of drug test methods will be more rigorous and standardized, laying a solid foundation for strengthening the controllability of drug quality.

2.2.4 Continuously improve the standard system of various drugs

Continuously improve the specification system in line with the characteristics of traditional Chinese medicines, chemical drugs and biological products. In terms of traditional Chinese medicines, 0212 General Chapter for Inspection of Crude Drugs and Decoction Pieces, 9302 Guideline for Establishment of Limit for Harmful Residue of Traditional Chinese Medicine and 9305 Guideline for Determination of Mycotoxins in Traditional Chinese Medicine have been improved, focusing on strengthening the safety control requirements of traditional Chinese medicinal materials and decoction pieces. In order to meet the needs of the rapid development of current biologics, the general requirements related to monoclonal antibodies, antibody-drug conjugates and gene therapy products have been developed and improved, and the General Monograph of Human Antibody-Drug Conjugates and General Monograph of Human Gene Therapy Products, etc., have been included for the first time in the world as the current hot field of international drug research and development. The formulation of relevant general monographs will help standardize and guide drug research and development, reduce the risk of original drug research and development, accelerate the development and listing of innovative drugs in China, and further reflect the scientificity, normalization, perspectiveness and guidance of the Chinese Pharmacopoeia.

2.2.5 Improve the relevant requirements of the general chapters for preparations

The General Chapters for Preparations in the Pharmacopoeia is the general regulation on the whole process of products and dosage forms contained in the Pharmacopoeia from the preparation characteristic definition, production preparation, production facilities and preparation inspection to storage and transportation, is the "main line" that connects the relevant technical requirements system of the whole life cycle management of drugs together, and is an important part of drug quality control. This time, 24 of 39 dosage forms under the General Chapters for Preparations in the new edition of the Pharmacopoeia have been revised, focusing on improvement of requirements for production and quality control of high-risk preparations such as injections, preparations for inhalation and ophthalmic preparations; improvement of relevant regulations on pigments; addition of pigment classification into four sub-dosage forms of oral dissolving film, buccal film, sublingual film and oral film; standardization of the use of various bacteriostatic agents, which further improve the safety and effectiveness of drugs (see Table 3).

2.2.6 Continuously improve the standard system of pharmaceutical excipients and pharmaceutical packaging materials

A total of 52 new standards for pharmaceutical excipients have been included and 387 monographs of pharmaceutical excipients have been included in the new edition of the Pharmacopoeia, which can further meet the needs of the standard of commonly used excipients for pharmaceutical preparations in order to ensure the implementation of related review and approval system of drug substances, excipients and packaging materials, provide technical support, continuously build a standard system based on the characteristics of pharmaceutical excipients and pharmaceutical packaging materials, focus on strengthening the safety and functional evaluation requirements of pharmaceutical excipients in terms of the control of pharmaceutical excipients and further promote the harmonization of pharmaceutical excipients with international standards. The 0251 General Requirements for Pharmaceutical Excipients has been revised to strengthen the overall requirements for the manufacture and preparation, applicability research and standard execution of pharmaceutical excipients. The 9601 Guideline for Research and Evaluation on Functionality related Characteristics of Pharmaceutical Excipients has been revised to improve the evaluation index of relevant functional categories, add five functional categories of solubilizer, bacteriostatic agent, osmotic pressure regulator, transdermal penetration enhancer and refrigerant, divide the original "coating agent or plasticizer" into two functional categories of "coating agent" and "plasticizer", and improve functional control items and methods to provide technical support for the applicability evaluation of pharmaceutical excipients used in preparations. In terms of pharmaceutical packaging materials, the 9621 Guideline for General Requirements for Drug Packaging Materials and Containers has been revised based on the 9622 Guideline for Pharmaceutical Glass Materials and Containers originally contained in the Pharmacopoeia to add the guidelines for rubber, plastic and metal packaging materials according to the classification of pharmaceutical packaging materials (see Figure 2), which basically cover the basic requirements for commonly used pharmaceutical packaging materials. On the basis of original 16 test methods for pharmaceutical packaging materials, 42 new physical and chemical, biological, microbial and biological safety test methods for pharmaceutical packaging materials have been included to meet the needs of identification, physical and chemical properties, functional testing and related safety testing of pharmaceutical packaging materials.

Tab. 3 The development and revision of dosage general chapter ChP 2025

Fig. 2 The framework of the pharmaceutical packaging materials in ChP 2025

2.2.7 Introduce the concept of risk assessment to drug quality control The new edition of the Pharmacopoeia is consistent with the guidelines of the International Conference on Harmonisation (ICH) on drug quality control philosophy and has gradually formed a quality control model based on risk assessment that the drug manufacturers take the initiative to carry out risk assessment, analysis and judgment based on product administration routes, production processes, equipment, facilities and raw materials used in drug preparation, and key process links, not just performing drug tests mechanically, in order to guarantee the goal of the quality of final preparations, implement the corresponding risk control strategy, set targeted drug test items and develop reasonable detection limits. For example, the 0212 General Chapters for Inspection of Crude Drugs and Decoction Pieces sets uniform limits for heavy metals and harmful elements in 52 crude drugs and decoction pieces. "General Notices" of Volume III of the Pharmacopoeia defines relevant requirements for the abnormal toxicity test of biological product; the control requirements for the control of residual solvents, elemental impurities and genotoxic impurities in the "General Notices" of Volume II of the Pharmacopoeia reflect the concept of drug quality control risk, corresponding test items based on the risk assessment, and implementation of the product batch release.

2.3 Accelerate the transformation and application of new technologies, new methods, and new tool standards

The Chinese Pharmacopoeia 2025 Edition, benchmarking against the international standards and closely following the forefront of international pharmaceutical development, continues to expand the application of advanced and mature detection techniques in drug quality control, further improves the sensitivity, specificity, applicability and reliability of test methods and plays an important role in strengthening drug quality control, guaranteeing drug quality and improving the drug administration capabilities.

2.3.1 Improve the requirements for drug effectiveness control The new edition of pharmacopoeia benchmarks against the standards European and American pharmacopoeia to strengthen unity and coordination. The “reciprocating holder method” and “diffusion cell method” have been included in 0931 Dissolution and Drug Release Test to provide methods for quality consistency evaluation of oral solid preparations and quality evaluation of related specific dosage forms; the 1402 Determination of Biological Distribution of Radiopharmaceuticals has been included to fill in the domestic gap; internationally, the Chinese Pharmacopoeia has included the 9404 Guideline for Bioassays Based on Genetically Modified Cell Lines ^[9] for the first time, which will help promote the development and quality control of transgenic technology products; the 9405 Guidelines for Glycosylation Analysis of Glycoproteins has been included to provide technical support for the effectiveness evaluation of antibody drugs; three drug substances of low molecular heparin, i.e. enoxaparin sodium, dalteparin sodium and nadroparin calcium, have been identified by hydrogen nuclear magnetic resonance spectrometry, solving the problems of unclear structure and molecular weight difference of the original "low molecular heparin" ^[10], and tending to be consistent with the European and American pharmacopoeia in terms of standard requirements; the application of high performance liquid chromatography and mass spectrometry in the detection of active ingredients of chemical drugs and biological products has been further expanded, and the quality controllability of drugs has been further improved; the 9031 Guideline for Chemical Imaging has been included to be aligned with European Pharmacopoeia standards.

2.3.2 Strengthen drug safety control methods and requirements

The new edition of pharmacopoeia is the first in the world to include the 3309 Test for Pyrogen (Reporter Gene Method), which is of high sensitivity and stability without the use of animals, compared with the traditional rabbit pyrogen test; the new edition of pharmacopoeia has sped up the improvement of technical requirements for molecular biological detection and included the 9110 Guidelines for Microbial Whole-genome Sequencing to provide guidance for the control test of bacteria and virus seeds for production, inspection of adventitious agent contamination, precise identification, traceability analysis and risk identification of microorganisms; the 9016 Guideline for Control of Visible Particulates in Injections has been included to strengthen the control of production process of high risk preparations; based on the characteristics of short efficacy period and small batch size of cell therapy products, the 9406 Guideline for Microbiological Examination of Cell Products has been included to provide control strategies for the control of microbial contamination in specific production processes and specific products, provide strong technical support for the development of innovative drug products, and overcome the technical hurdle of cell therapy product release inspection.

2.3.3 Strengthen drug quality control and testing technology reserves

The enzyme-linked immunocolloidal gold technology has been used for the first time against the Chinese medicine irradiation test method for detection of mycotoxins, and a plant growth regulator detection method has been established to provide an effective detection method for the safety control of traditional Chinese medicines; the 9024 Proteomic Analytical Methods and Microbial Whole-genome Sequencing has been included to continue to improve the molecular biology detection technology requirements in the pharmacopoeia; the 9095 Guideline for Multivariate Statistical Process Control and 9096 Guideline for Chemometrics have been included to guide the development and establishment of production process analytical techniques, which are more suitable for modern production process requirements and provide standardized testing technology support for the realization of whole process quality control. The 0408 Atomic Fluorescence Spectrometry has been included to promote the application of self-developed testing instruments in China.

The Chinese Pharmacopoeia 2025 Edition keeps abreast of international pharmaceutical development, accelerates the transformation of new technologies, new methods, and new tool standards formed by pharmaceutical innovation in hot areas, continuously expands the application of mature advanced detection techniques (see Table 4), and provides test methods with good standardization, strong applicability, stable application, and high reliability for drug quality control to significantly improve the controllability of drug quality.

Tab. 4 Application of advanced analytical testing technologies in the ChP 2025

2.4 Continue to strengthen drug safety control

2.4.1 Improve the safety control requirements of traditional Chinese medicine Conscientiously implement the task plan of Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine. In the Chinese Pharmacopoeia 2025 Edition, the number of prohibited pesticide residues in traditional Chinese medicinal materials and decoction pieces has been increased from the original 33 (55 monomers) to 47 (72 monomers). According to the requirements of GB 2763-2021 National Food Safety Standard - Maximum Residue Limits for Pesticides in Food, new pesticide residue limit standards for 10 kinds of traditional Chinese medicinal materials, such as Wolfberry, Ginseng, Notoginseng, Lily, Chrysanthemum, Dendrobium officinale, Corydalis, Honeysuckle, Fritillaria and Atractylodes macrocephala koidz have been included in the Chinese Pharmacopoeia 2025 Edition; the limit requirements for heavy metals and harmful elements in 54 monographs (including 52 monographs in the General Principle for Inspection of Crude Drugs and Decoction Pieces and 2 varieties in each monograph) of traditional Chinese medicinal materials and prepared slices of Chinese crude drugs have been added; the test item of ochratoxin A has been added for astragalus and areca; the test items of aflatoxin and zearalenone have been added under the item of decocted coix seed with bran; the determination method of plant growth regulator of Chinese medicinal materials has been revised, and the limit requirement of paclobutrazol in ophiopogon has been established; the 9261 Guideline for Optically Stimulated Luminescence Detection of Irradiated Chinese Medicine has been added to guide the irradiation sterilization test of Chinese medicine; the safety of Chinese medicinal materials and decoction pieces will be further improved.

2.4.2 Improve control requirements related to chemicals

Focus on strengthening the control requirements of chemical impurities, continue to carry out qualitative and quantitative research on impurities, improve the separation methods of related substances and pay more attention to the source and classification of impurities, for reasonable control of impurities; add hints for the necessary assessment of genotoxic impurities; the test items of related substances have been added and revised for more than 110 monographs included in the Chinese Pharmacopoeia 2025 Edition.

2.4.3 Improve control requirements related to biological products

The general chapters (general monographs) such as the Requirements for Preparation and Control of Animal Cell Substances Used for Production of Biologics, General Monograph of Vaccines for Human Use, 0233 Management and Quality Control of Bacteria and Virus Seeds for Manufacturing and Testing of Biological Products and 0239 Subpackaging, Storage and Transportation Management of Biological Products have been improved; the 9403 Guideline for Impurity Control of Vaccines for Human Use has been included for the first time in the pharmacopoeia of various countries to guide the development of vaccines and the quality control of marketed products and standardize the use requirements of bacteriostatic agents. The bacteriostatic agents are no longer added to 7 vaccines, i.e. 23-valent pneumococcal polysaccharide vaccine, tick-borne encephalitis vaccine, inactivated, haemorrhagic fever with renal syndrome bivalent vaccine (Vero cell), inactivated, haemorrhagic fever with renal syndrome bivalent vaccine (hamster kidney cell), inactivated, haemorrhagic fever with renal syndrome bivalent vaccine (gerbil kidney cell), inactivated, influenza vaccine (whole virion), inactivated, and influenza vaccine (split virion), inactivated included in Volume III of the new edition of pharmacopoeia to reduce the potential risk of adverse reactions after vaccination and further improve vaccine safety.

2.4.4 Strengthen safety-related control requirements for high-risk preparations

For high-risk preparations such as injections, preparations for inhalation and ophthalmic preparations, the 9016 Guideline for Control of Visible Particulates in Injections, 9017 Guideline for Evaluation of Spray Characteristics of Inhalational and Nasal Preparations and 3903 Test for Particulate Matter in Intraocular Injections of Biological Products have been established; the microbial contamination risk control strategies have been improved and the 9211 Guideline for Application of Water Activity in Microbiological Control of Non-sterile Products, 9212 Guideline for Control of Unacceptable Microbiological Risk of Non-Sterile Products and 1109 Test for Burkholderia Cepacia Complex have been included to strengthen the control and monitoring of pathogenic bacteria contamination in non-sterile products. The microbial control technical standards have been systematically established to cover test methods, environmental monitoring, method validation and risk assessment, etc. (Table 5).

Tab. 5 The system enhances the requirements related to microbial control in the ChP 2025

2.5 Strengthen harmonization with international standards

2.5.1 Transformation and implementation of ICH Q4B relevant guidelines in the Chinese Pharmacopoeia A comparative study has been conducted on ICH guidelines and pharmacopoeia of European, American and Japanese countries. Based on the actual situation in China, the transformation and implementation of all 16 guidelines of ICH Q4B in the Chinese Pharmacopoeia 2025 Edition has been realized through direct harmonization and concurrent inclusion (Table 6). The original method included in the Chinese Pharmacopoeia is method 1 and the method harmonized by “concurrent inclusion” in ICH Q4B is method 2 . Either method can be selected for the newly registered monographs and indicated under the test item. The default method for the marketed monographs is method 1, or the ICH Q4B harmonized method can be applied for through the post-marketing change procedure. The 0861 Determination of Residual Solvents has been improved, the 0862 Elemental Impurities has been included and the 9101 Guideline for Validation of Analytical Method and 9098 Guideline for Uncertainty Evaluation have been revised, achieving coordination and unification with ICH Q3C, Q3D, Q2(R2), Q14 and other guidelines, and making the Chinese Pharmacopoeia 2025 Edition more harmonious with international standards in terms of key quality control requirements for drugs.

2.5.2 Coordinated implementation of other ICH Q guidelines. Relevant test methods and guidelines have been added and revised to realize the harmonization of the Chinese Pharmacopoeia 2025 Edition with ICH Q2(R2) and Q14; the 0861 Determination of Residual Solvents has been revised and the 0862 Elemental Impurities has been included to realize the transformation and harmonization between the Chinese Pharmacopoeia 2025 Edition and ICH Q3C and Q3D guidelines. In view of the large number of products already on the market, the strategy of "gradual implementation and steady transition" is proposed for Q3C and Q3D, and the requirements for test items are still retained in the standards of the monographs involved in the Chinese Pharmacopoeia 2025 Edition, which stipulates that enterprises shall determine whether to test the residual solvents, heavy metals, arsenic salts, etc., in the control of drug substances, excipients and preparations based on risk assessment. The “General Notices” of the Chinese Pharmacopoeia 2025 Edition also makes it clear that any change in methods or limits shall be subject to approval before implementation.

Tab. 6 The Harmonization of ICH Q4B-related guidelines in the ChP 2025

2.5.3 Steadily promote the in vitro tests instead of in vivo tests

In accordance with the international "3R" principle, the in vitro biological methods are promoted to replace animal tests. The General Monograph of Vaccines for Human Use, 9301 Guideline for Application of Safety Tests for Injections and other general monographs and guidelines have specified the requirements for abnormal toxicity test based on risk assessment, reflected the new concept and new measures of abnormal toxicity test for biological products in China in recent years, and provided the possibility for enterprises to simplify the release inspection and better meet international requirements

2.6 Strengthen the connection with the evaluation, inspection and testing guidelines

Strengthen the connection between drug standards and technical requirements such as evaluation, inspection and testing. The guidelines already issued by the Center for Drug Evaluation, such as the Guideline for in vivo Bioavailability and Bioequivalence Studies for Drug Preparations and the Guideline for Validation of Quantitative Analytical Method of Biological Products are no longer included in the Chinese Pharmacopoeia 2025 Edition; the 0239 Subpackaging, Storage and Transportation Management of Biological Products has been revised to apply to cell therapy products; according to the classification standards of experimental animals, microorganisms and parasites in the national standard GB 19422-2022, the 0233 Management and Quality Control of Bacteria and Virus Seeds for Manufacturing and Testing of Biological Products has been revised accordingly for unification with the standards promulgated by relevant technical departments.

2.7 Better reflect the green concept of drug standards

According to the new development concept of innovation, coordination, green, openness and sharing, new monographs of traditional Chinese medicines including endangered wild species are no longer. Alternative guidelines for TCM standard substances for toxicity control (e.g. aconitine, brucine, strychnine, etc.) have been developed and relevant standards have been revised in accordance with the guidelines; in Volume II of the Chinese Pharmacopoeia, the chemical reaction identification method in 332 monographs has been revised and more than 40 highly toxic test drugs and controlled reagents used in them, such as trichloromethane, benzene and mercury reagents, have been deleted or replaced to minimize the use of highly toxic and polluting test reagents, reduce environmental pollution, reduce personnel injury and experimental safety risks. For the preparation method of the water for injection in the 0261 Water for Pharmaceutical Purposes of the new edition of pharmacopoeia, the description “The product is prepared by a purification process equivalent to distillation, and its preparation process shall meet the requirements of the relevant procedures of the regulatory authorities” has been added, further promoting the pharmaceutical industry practice "green, low-carbon, environmentally friendly".

3 Conclusion

The Chinese Pharmacopoeia 2025 Edition is prepared in line with the scientific, advanced, practical and normative principle, closely following the forefront of the development of international drug standards, combined with the actual development of China's pharmaceutical industry. The Chinese Pharmacopeia Commission firmly grasps the bottom line of drug safety, promotes the development of the pharmaceutical industry, further strengthens the position of the Chinese Pharmacopoeia as the core of national drug standards, vigorously carries out the action plan to improve drug standards, accelerates the transformation of pharmaceutical innovation standards, constantly strengthens the harmonization with international advanced standards, and introduces the management concept of international drug quality control, making the characteristics of the Chinese Pharmacopoeia more distinct, the drug standard system more perfect, the standard categories more complete, the quality of drugs more controllable and more in line with international standards. The overall level of drug standards has reached a new level. The promulgation and implementation of the new edition of the pharmacopoeia will certainly play an important role in ensuring drug quality, maintaining public drug safety, strengthening technical support for drug administration, enhancing the international competitiveness of China's pharmaceutical industry, and promoting the high-quality development of the pharmaceutical industry.

(Chinese Pharmacopoeia Commission)