The 2025 edition of the Chinese Pharmacopoeia has been officially released. As an important technical standard for drug quality control, the new edition has significant updates and improvements regarding drug packaging materials and excipients. The National Pharmacopoeia Committee recently released an interpretation of the implementation of the "Chinese Pharmacopoeia" 2025 edition (Part One), in which Articles 9 and 10 provide clear instructions on the execution of standards for drug packaging materials and excipients, offering important guidance for the industry.Announcement by the National Medical Products Administration and the National Health Commission on the issuance of the 2025 edition of the "Pharmacopoeia of the People's Republic of China" (Announcement No. 29 of 2025) states that the 2025 edition of the "Pharmacopoeia of the People’s Republic of China" will be implemented starting from October 1, 2025. Can it be implemented in advance?Answer: According to the announcement by the National Medical Products Administration and the National Health Commission regarding the issuance of the 2025 edition of the "Pharmacopoeia of the People's Republic of China" (Announcement No. 29 of 2025), the 2025 edition of the "Pharmacopoeia of the People's Republic of China" will be implemented starting from October 1, 2025. During the period from the issuance to the implementation date of the 2025 edition of the "Pharmacopoeia," either the original standards or the 2025 edition may be followed, and this should be noted in the product insert. Regulatory enforcement (including sampling inspections, etc.) will be carried out based on this after the drug is marketed.Drugs produced before the implementation of the 2025 edition of the "Chinese Pharmacopoeia" can continue to be marketed and circulated. If there are other requirements specified by relevant laws and regulations or the National Medical Products Administration, those requirements shall be followed.After the implementation of the 2025 edition of the Pharmacopoeia of China, how should the drug marketing authorization holders conduct the change management?According to Article 8 and Article 31 of the "Regulations on the Administration of Drug Standards," the holder of a drug marketing authorization shall fulfill the primary responsibility for drug quality, promptly pay attention to the progress of the formulation and revision of national drug standards, conduct suitability assessments of the drug standards applicable to the drugs they produce, and carry out relevant research work.After the issuance of the 2025 Edition of the Pharmacopoeia of the People's Republic of China, holders of drug marketing authorizations should promptly carry out relevant comparative studies to assess whether the drug registration standards comply with the requirements of the 2025 Edition of the Pharmacopoeia. For those needing to change the drug registration standards, the holders of drug marketing authorizations should submit supplementary applications, filings, or reports in accordance with the relevant regulations on post-marketing changes and execute them as required.According to the evaluation, changes involving approval should be submitted before the implementation of the 2025 edition of the "Chinese Pharmacopoeia." During the review and approval period, the original standards may still be executed; after the completion of the supplementary application approval, the approved content should be followed.In the 2025 edition of the Chinese Pharmacopoeia, if the content of the varieties remains unchanged, is it necessary to reevaluate the products?Answer: Yes, it is necessary. Even if the content of the varieties listed in the 2025 Edition of the "Chinese Pharmacopoeia" remains unchanged, the general principles and common technical requirements (such as general rules and monographs) involved in the variety texts have been revised and updated. The holders of drug marketing authorization need to assess their products according to the general principles and common technical requirements of the 2025 Edition of the "Chinese Pharmacopoeia" to ensure that their products comply with the relevant requirements.In the 2025 edition of the "Pharmaceutical Standards of China," how should the expression "unless otherwise specified" be understood?Answer: The General Principles of the 2025 Edition of the Chinese Pharmacopoeia stipulate in Article 4 that "the phrase 'unless otherwise specified' in the general principles and common technical requirements indicates that there are inconsistencies with the relevant provisions of the general principles or common technical requirements. In such cases, other provisions are made in the product text, which shall be executed according to the product text."After the release of the new edition of the "Chinese Pharmacopoeia," drug marketing authorization holders and relevant drug manufacturing enterprises should promptly assess the applicability of the drug standards they are implementing in relation to the principles, variety texts, and applicable general technical requirements of the new Pharmacopoeia. If, after assessment, the drug standards they are implementing do not comply with the relevant requirements of the new "Chinese Pharmacopoeia," they should conduct thorough research and verification in accordance with the "Drug Registration Management Measures," "Drug Post-Market Change Management Measures (Trial)," and relevant change research technical guidance principles and Good Manufacturing Practices (GMP) requirements, and then implement them after approval or filing according to the corresponding change category.In the 2025 edition of the Pharmacopoeia of the People's Republic of China, how will the implementation of ICH Q4B-related guidelines be carried out after the transition?The 2025 edition of the "Chinese Pharmacopoeia" has implemented two methods, "direct coordination" and "parallel adoption," for the 16 relevant testing methods involved in ICH Q4B. Among them, 12 methods were coordinated via "direct coordination," while 4 methods were coordinated through "parallel adoption."Direct coordination, that is, revising the original text of the "Pharmacopoeia of China" or fully accepting the requirements of Q4B, to ensure that the relevant content of the "Pharmacopoeia of China" is consistent with Q4B.The direct coordination detection methods include: (1) 0102 injection dosage inspection and 0942 minimum dosage inspection method, (2) 0923 tablet friability test method, (3) 0541 electrophoresis method, (4) 0542 capillary electrophoresis method, (5) 0982 particle size and particle size distribution determination method, (6) 0993 bulk density and tapped density, (7) 0903 insoluble particulate matter inspection method, (8) 1105 microbial limit test for non-sterile products: microbial counting method (excluding standard strains), (9) 1106 microbial limit test for non-sterile products: controlled microorganism inspection method (excluding standard strains), (10) 1107 microbial limit standards for non-sterile drugs (excluding standard strains), (11) 1101 sterility testing method (excluding standard strains), (12) 1143 bacterial endotoxin testing method.Parallel methods refer to the original methods listed in the "Pharmacopoeia of China" as "Method 1" or "Determination Method 1," while the ICH Q4B coordinated method is referred to as "Method 2" or "Determination Method 2." For newly registered products, either method may be chosen, and the adopted method should be indicated under the standard items. For products already on the market, "Method 1" or "Determination Method 1" is the default, but they can also switch to "Method 2" or "Determination Method 2" in accordance with the requirements of the "Measures for the Management of Post-Marketing Changes of Drugs (Trial)," through a supplementary application or filing application. During post-marketing supervision of drugs (including random inspections and testing), execution will follow the approved or filed content.The 2025 Edition of the Chinese Pharmacopoeia includes the method for Determination of Loss on Ignition (0841), which concurrently incorporates the ICH Q4B method based on the original method in the Chinese Pharmacopoeia. The Disintegration Test (0921) and the Dissolution and Release Test (0931) have concurrently included the ICH Q4B judgment methods based on the original judgment methods in the Chinese Pharmacopoeia. The 2025 Edition of the Chinese Pharmacopoeia has also added the Uniformity of Dosage Units Test (0940), which is concurrently included with the Uniformity of Content Test (0941) and the requirements for weight difference in the general principles of formulations.In the 2025 edition of the Chinese Pharmacopoeia, the general rules for the inspection of medicinal materials and decoction pieces include the maximum residue limits for 47 banned pesticides, as well as the requirements for heavy metals and harmful elements in related medicinal materials and decoction pieces. How should production enterprises conduct inspections?Answer: The relevant provisions in the 2025 edition of the Chinese Pharmacopoeia, section 0212 on the inspection specifications for medicinal materials and decoction pieces, serve as general requirements for the quality of traditional Chinese medicine. Relevant production enterprises should adhere to the fundamental principle of ensuring the quality of traditional Chinese medicine and not detecting corresponding exogenous harmful substances (not exceeding relevant limits). Production enterprises should develop inspection and release strategies based on risk levels to ensure that products meet the relevant requirements.How should the abnormal toxicity testing of biological products be conducted?Answer: Drawing on the changes and practices in the management of abnormal toxicity testing internationally, the 2025 edition of the "Pharmacopoeia of the People's Republic of China" (Part III) has added the statement "determine whether to set abnormal toxicity testing items in the quality standards based on the risk assessment results of the product or the inherent quality attributes" in the general chapters on "General Principles for Human Vaccines," "General Principles for Human Recombinant DNA Protein Products," "General Principles for Human Recombinant Monoclonal Antibody Products," "General Principles for Human PEGylated Recombinant Proteins and Peptides," and "General Principles for Human Gene Therapy Products."The 2025 edition of the Pharmacopoeia of the People's Republic of China (Part III) continues to retain the abnormal toxicity testing item in the product specifications. The guidelines specify how to conduct abnormal toxicity testing: for products with an abnormal toxicity item in their specifications, manufacturers may, based on risk assessment results and quality control strategies, not treat it as a mandatory testing item for each batch release but must still conduct periodic checks. When a significant pharmaceutical change occurs, sufficient batches must be tested to determine the safety of the product after the change. If the quality attributes of a specific product do not lend themselves to abnormal toxicity testing, it can be exempted from this test upon providing sufficient justification and undergoing evaluation, subject to approval.In the legend regarding the release inspection of in-process products, it is stated that the abnormal toxicity test can be reduced based on specific circumstances. This is an independent action of the drug marketing authorization holder and does not require further approval. If the pharmacopoeia variety includes an abnormal toxicity item but the drug marketing authorization holder assesses that a certain product does not need to include the abnormal toxicity item in the registration standard, they can proceed according to the relevant procedures such as the "Drug Registration Management Measures," and indicate in the approved drug standard that this test is not required during inspection.In the legend regarding "may omit this inspection with approval," it specifically refers to the situation where the quality attributes of the product itself are not suitable for abnormal toxicity testing. This needs to be considered when submitting the product's market registration application, rather than adding new licensing items. If a pharmacopoeia variety includes an abnormal toxicity item but the quality attributes of a specific product are not suitable for abnormal toxicity testing, this can be noted in the approved drug standard, and the inspection may omit this item during testing.In the 2025 edition of the "Pharmacopoeia of China" (Volume III), for products that have an abnormal toxicity item in their specifications, regardless of whether abnormal toxicity testing is conducted during the release inspection, all other biological products, except those whose quality attributes are not suitable for abnormal toxicity testing, should comply with the specified results if abnormal toxicity testing is performed.Confirm whether it is possible to reduce the work required for abnormal toxicity testing during the release inspection, including but not limited to summarizing and analyzing the GMP compliance status of manufacturing enterprises over the years, GMP inspection results, batch release status of products, and any clinical adverse reactions that may be related to product quality. Additionally, an analysis of the quality control strategy for the product should be conducted to confirm whether the existing quality control measures can comprehensively control product quality. The marketing authorization holder must conduct a comprehensive analysis of the above situations to determine whether the abnormal toxicity testing can be reduced. If it is confirmed that the abnormal toxicity testing can be reduced, the marketing authorization holder should develop an appropriate abnormal toxicity testing plan to ensure product quality.The drug inspection agency will adjust the inspection strategy for registration inspections and batch release inspections based on the situation of the drug marketing authorization holder's exemption from abnormal toxicity testing.Can preventive biological products be co-packaged with therapeutic biological products?Answer: With the rapid development of biotechnology in recent years, new biological products are continuously being launched. In order to meet the requirements for the development of new biological products, the "Regulations on the Sub-packaging and Storage and Transportation Management of Biological Products" in the third part of this pharmacopoeia no longer explicitly requires that preventive biological products and therapeutic biological products must not be co-packaged on the same line. However, this does not mean that the management requirements for co-packaging of biological products have been lowered.According to the "Good Manufacturing Practice for Pharmaceutical Products (2010 Edition)", biological products (such as BCG vaccine or other drugs made from active microorganisms) must be produced in dedicated and independent facilities, production premises, and equipment. Considering the particularity of preventive biological products, preventive biological products and therapeutic biological products should generally not be filled and packaged on the same line. If joint filling and packaging is necessary, it should be carried out in accordance with the "Good Manufacturing Practice for Pharmaceutical Products (2010 Edition)" and other relevant requirements. The concept of quality risk management should be comprehensively implemented, and a full and accurate understanding of the relationship between the hazards, exposure, and risks of joint filling and packaging of preventive and therapeutic biological products should be grasped. Various factors such as the characteristics of the products, production processes, intended use, facilities, and equipment should be综合考虑, and the feasibility of joint production should be assessed. If the assessment permits the use of the same filling area and filling or lyophilization facilities for filling and lyophilization, it should be handled in accordance with the "Pharmaceutical Administration Law" and other relevant requirements in a lawful and compliant manner.After the promulgation of the 2025 edition of the Pharmacopoeia of China, how will the standards for drug packaging materials be implemented?Answer: After the promulgation of the 2025 edition of the "Chinese Pharmacopoeia," the standards for pharmaceutical packaging materials corresponding to the 2020 edition of the "Chinese Pharmacopoeia" and the standards published in the form of the "Announcement on the Release of YBB 00032005-2015 'Sodium Calcium Glass Infusion Bottles' and Other 130 National Standards for Packaging Materials and Containers in Direct Contact with Drugs" (Announcement No. 164, 2015) (hereinafter referred to as the 2015 YBB standard) will be subject to the 2025 edition of the "Chinese Pharmacopoeia." For a detailed comparison, please refer to the section "Comparison of This Edition of the Pharmacopoeia (Volume Four) with the General Testing Methods for Original Pharmaceutical Packaging Materials" in the 2025 edition of the "Chinese Pharmacopoeia."Pharmaceutical packaging material companies should establish quality standards and conduct quality control based on the premise that the packaging materials meet the expected medicinal requirements, in accordance with the relevant regulations of associated review, and by referencing the guidelines for pharmaceutical packaging materials in the 2025 edition of the "Chinese Pharmacopoeia" and the variety standards in the 2015 edition of the YBB standard.Pharmaceutical packaging material companies that change their packaging material standards to comply with the 2025 edition of the "Pharmacopoeia of the People's Republic of China," which only involves changes to the packaging material standards and ensures that these standards meet the requirements of the "Pharmacopoeia," may include the updated packaging material standards in their annual report. The annual report should include the full text of the standards (including standard numbers), necessary validation data, and self-inspection reports, and promptly notify the relevant drug marketing authorization holders. Upon receiving the above notification, drug marketing authorization holders should promptly assess or study the impact of the corresponding changes on the quality of the drug formulation and execute according to the "Announcement on the Implementation of the 2025 Edition of the Pharmacopoeia of the People's Republic of China" and the relevant requirements for associated reviews.How will the standards for excipients be implemented after the issuance of the 2025 edition of the Chinese Pharmacopoeia?The excipients used in the production of formulations should comply with the relevant regulations of the National Medical Products Administration and the requirements outlined in the 2025 edition of the Chinese Pharmacopoeia, General Chapter 0251 on excipients. Excipients claiming compliance with the Chinese Pharmacopoeia must meet the corresponding standards of the Pharmacopoeia. If the standards for excipients listed in this edition of the Pharmacopoeia do not meet the needs of a specific formulation, or if a certain excipient standard has not yet been included in this edition of the Pharmacopoeia, suitable excipients may be selected during formulation development and post-marketing changes, and corresponding standards should be established.Pharmaceutical excipient companies that make changes to excipient standards to comply with the 2025 edition of the "Pharmacopeia of the People's Republic of China" are only required to change the excipient standards that meet the requirements of the "Pharmacopeia." The updated excipient standards should be reflected in the annual report, which must include the full text of the updated standards and the standard number, as well as necessary validation data and self-inspection reports. Relevant drug marketing authorization holders should be notified in a timely manner. Drug marketing authorization holders should promptly assess or study the impact of the corresponding changes on the quality of the drug formulation and comply with the requirements of the "Announcement on the Implementation of the 2025 Edition of the 'Pharmacopeia of the People's Republic of China'" and related review requirements.