1. Announcement No. 29 of 2025 by the National Medical Products Administration and the National Health Commission on the Promulgation of the 2025 Edition of the Pharmacopoeia of the People's Republic of China stipulates that the 2025 edition of the Chinese Pharmacopoeia will come into effect on October 1, 2025. Can it be implemented earlier?

A: According to Announcement No. 29 of 2025 by the National Medical Products Administration and the National Health Commission on the Promulgation of the 2025 Edition of the Pharmacopoeia of the People's Republic of China, the 2025 edition of the Chinese Pharmacopoeia will come into effect on October 1, 2025. Between the promulgation and implementation dates of the 2025 edition of the Chinese Pharmacopoeia, the original standard or the 2025 edition of the Chinese Pharmacopoeia may be implemented, with a note in the instructions for use. Post-market drug supervision (including spot checks) will be conducted accordingly.

Drugs produced before the implementation date of the 2025 edition of the Chinese Pharmacopoeia may continue to be marketed and circulated. If there are other requirements in relevant laws, regulations, or by the National Medical Products Administration, follow those requirements.

2. After the implementation of the 2025 edition of the Chinese Pharmacopoeia, how should the drug marketing authorization holder carry out the change work?

A: According to Articles 8 and 31 of the Measures for the Administration of Drug Standards, the drug marketing authorization holder shall implement the main responsibility for drug quality, pay close attention to the development and revision of national drug standards, conduct suitability assessments of the drug standards implemented for its produced drugs, and carry out relevant research work.

After the promulgation of the 2025 edition of the Chinese Pharmacopoeia, for those implementing drug registration standards, the drug marketing authorization holder shall promptly conduct relevant comparative research work and assess whether the drug registration standards meet the requirements of the 2025 edition of the Chinese Pharmacopoeia. For those requiring changes to the drug registration standards, the drug marketing authorization holder shall submit a supplementary application, filing, or report in accordance with the relevant regulations on post-market changes of drugs, and implement them as required.

After assessment, for changes that involve approval, they should be submitted before the implementation date of the 2025 edition of the Chinese Pharmacopoeia; the original standard can still be implemented during the review and approval period; after the supplementary application is approved, implement according to the approved content.

3. If the main content of the varieties included in the 2025 edition of the Chinese Pharmacopoeia remains unchanged, is it necessary to re-evaluate the products?

A: Yes. Even if the main content of the varieties included in the 2025 edition of the Chinese Pharmacopoeia remains unchanged, due to the additions and revisions to the general notices and general technical requirements (general rules and general discussions) involved in the main text of the varieties, the drug marketing authorization holder needs to conduct corresponding assessments of their products based on the general notices and general technical requirements of the 2025 edition of the Chinese Pharmacopoeia to ensure that the products meet the relevant requirements of the 2025 edition of the Chinese Pharmacopoeia.

4. How should the statement "unless otherwise specified" in the 2025 edition of the Chinese Pharmacopoeia be understood?

A: Article 4 of the General Rules of the General Notices in the 2025 edition of the Chinese Pharmacopoeia clearly states that "the term 'unless otherwise specified' used in the general notices and general technical requirements indicates that if there are inconsistencies with the provisions of the general notices or general technical requirements, then separate provisions are made in the main text of the variety, and the main text of the variety shall be followed."

After the promulgation of the new edition of the Chinese Pharmacopoeia, drug marketing authorization holders and relevant drug manufacturers should promptly assess the applicability of the drug standards they implement to the general notices, main text of varieties, and referenced general technical requirements of the new edition of the pharmacopoeia. After assessment, if the drug standards they implement are not applicable to the relevant requirements of the new edition of the Chinese Pharmacopoeia, they should conduct sufficient research and verification in accordance with the Drug Registration Management Measures, the Measures for the Administration of Post-Market Changes of Drugs (Trial), relevant technical guidelines for change research, and Good Manufacturing Practices for Drugs, and implement them after approval or filing according to the corresponding change category.

5. In the 2025 edition of the Chinese Pharmacopoeia, how should the ICH Q4B-related guidelines be implemented after their conversion and implementation?

A: The 2025 edition of the Chinese Pharmacopoeia uses two methods, "direct coordination" and "parallel inclusion," to implement the 16 related testing methods involved in ICH Q4B. Twelve of them use "direct coordination," and four use "parallel inclusion."

Direct coordination means revising the original text of the Chinese Pharmacopoeia or fully accepting the requirements of Q4B to make the relevant content of the Chinese Pharmacopoeia consistent with Q4B.
The testing methods using direct coordination are: (1) 0102 Injections [Content] test and 0942 Minimum Content test 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 particles test method, (8) 1105 Microbial limits test for non-sterile products: Microbial count method (excluding standard strains), (9) 1106 Microbial limits test for non-sterile products: Control bacteria test method (excluding standard strains), (10) 1107 Microbial limits standard for non-sterile drugs (excluding standard strains), (11) 1101 Sterility test method (excluding standard strains), (12) 1143 Bacterial endotoxins test method.

Parallel inclusion means that the original method included in the Chinese Pharmacopoeia is "Method 1" or "Determination Method 1," and the ICH Q4B coordinated method is "Method 2" or "Determination Method 2." For newly registered products, either method can be selected, and the method used is indicated under the standard item. For products already on the market, "Method 1" or "Determination Method 1" is implemented by default, but "Method 2" or "Determination Method 2" can also be implemented through a supplementary application or filing application in accordance with the Measures for the Administration of Post-Market Changes of Drugs (Trial). Post-market drug supervision (including spot checks) will be conducted according to the approved or filed content.

The 0841 Residue on ignition test method included in the 2025 edition of the Chinese Pharmacopoeia includes the ICH Q4B method in parallel with the original method included in the Chinese Pharmacopoeia; the 0921 Disintegration time test method and 0931 Dissolution and release determination method include the ICH Q4B determination method in parallel with the original determination method included in the Chinese Pharmacopoeia; the 2025 edition of the Chinese Pharmacopoeia adds the 0940 Unit dose uniformity test method, which is included in parallel with the 0941 Content uniformity test method and the requirements for weight (content) difference in the general rules for preparations.

6. The 0212 General methods for the examination of crude drugs and processed drugs in the 2025 edition of the Chinese Pharmacopoeia includes the maximum residue limits of 47 prohibited pesticides, relevant crude drugs and processed drugs, and the requirements for heavy metals and harmful elements in relevant crude drugs and processed drugs. How should production enterprises conduct inspections?

A: The relevant provisions in the 0212 General methods for the examination of crude drugs and processed drugs in the 2025 edition of the Chinese Pharmacopoeia are general requirements for the quality of traditional Chinese medicine. Relevant production enterprises should adhere to the basic principle of ensuring the quality of traditional Chinese medicine and not detecting corresponding exogenous harmful substances (not exceeding the relevant limits). Production enterprises should develop inspection release strategies based on the degree of risk to ensure that products meet the relevant requirements.

7. How should the abnormal toxicity test of biological products be implemented?

A: Drawing on the changes and practices in the international supervision and management of abnormal toxicity testing, the 2025 edition of the Chinese Pharmacopoeia (Part III) adds the statement "Determine whether to set abnormal toxicity testing items in the quality standards based on the risk assessment results or the quality attribute characteristics of the product itself" in five general chapters, including "General Chapter on Human Vaccines", "General Chapter on Human Recombinant DNA Protein Products", "General Chapter on Human Recombinant Monoclonal Antibody Products", "General Chapter on Human Polyethylene Glycol-modified Recombinant Proteins and Polypeptide Products", and "General Chapter on Human Gene Therapy Products".

The 2025 edition of the Chinese Pharmacopoeia (Part III) still retains abnormal toxicity testing items in the monograph, and clearly requires how to perform abnormal toxicity testing in the preface, namely: For products with abnormal toxicity testing items in the monograph, production enterprises can combine risk assessment results and quality control strategies, and it is not a mandatory test item for each batch release, but it still needs to be checked irregularly; when major pharmaceutical changes occur, a sufficient number of batches must be tested to determine the safety of the changed product; if the quality attributes of a certain product itself are not suitable for abnormal toxicity testing, it can be exempted after providing sufficient evidence and undergoing evaluation.

The statement in the preface about reducing abnormal toxicity testing during product release testing according to specific circumstances is an autonomous act of the marketing authorization holder and does not require separate approval. In this edition of the pharmacopoeia, if the monograph has abnormal toxicity items, and the marketing authorization holder believes after evaluation that a certain product does not need to set abnormal toxicity items in the registration standard, it can be handled according to the relevant procedures of the "Drug Registration Management Measures", etc., and noted in the approved drug standard, and this test can be omitted during inspection.

The statement in the preface about "can be exempted after approval" only applies to situations where the quality attributes of the product itself are not suitable for abnormal toxicity testing, and needs to be considered when submitting an application for product marketing registration, rather than adding new licensing items. In this edition of the pharmacopoeia, if the monograph has abnormal toxicity items, and the quality attributes of a certain product itself are not suitable for abnormal toxicity testing, it can be noted in the approved drug standard, and this test can be omitted during inspection.

In the 2025 edition of the Chinese Pharmacopoeia (Part III), for products with abnormal toxicity testing items in the monograph, regardless of whether abnormal toxicity testing is performed during product release testing, except for products whose quality attributes are not suitable for abnormal toxicity testing, the test results of other biological products that conduct abnormal toxicity testing should meet the regulations.

The work to be done to confirm whether abnormal toxicity testing can be reduced during release testing includes, but is not limited to, summarizing and analyzing the GMP implementation, GMP inspection, and batch release situations of production enterprises over the years, as well as clinical adverse reactions that may be related to product quality; it is also necessary to analyze the product's quality control strategy and confirm whether the existing quality control measures can comprehensively control product quality. The marketing authorization holder needs to comprehensively analyze the above situations to decide whether abnormal toxicity testing can be reduced. If it is confirmed that abnormal toxicity testing can be reduced after evaluation, the marketing authorization holder should develop a suitable abnormal toxicity testing plan to ensure product quality.

The drug inspection institution will adjust the inspection strategies for registration testing, batch release testing, etc., according to the marketing authorization holder's reduction or exemption of abnormal toxicity testing for the product.

8. Can preventive biological products be co-packaged with therapeutic biological products on the same production line?

A: With the rapid development of biotechnology in recent years, new biological products are constantly being launched. To meet the requirements of the development of new biological products, the general chapter "Packaging and Transportation Management of Biological Products" in Part III of this edition of the pharmacopoeia no longer explicitly requires that preventive biological products and therapeutic biological products cannot be co-packaged on the same production line, but this does not mean that the requirements for the management of co-packaging of biological products on the same production line have been lowered.

The "Good Manufacturing Practice for Drugs (2010 edition)" stipulates that biological products (such as BCG vaccine or drugs prepared from other active microorganisms) must use dedicated and independent workshops, production facilities, and equipment. Considering the particularity of preventive biological products, preventive biological products and therapeutic biological products should not be co-packaged on the same production line in principle. If co-packaging on the same production line is necessary, it should be implemented in accordance with the relevant requirements of the "Good Manufacturing Practice for Drugs (2010 edition)", etc., and the concept of quality risk management should be fully implemented. The relationship between the hazards, exposure, and risks of co-packaging preventive biological products and therapeutic biological products on the same production line should be fully and accurately understood and grasped, and various factors such as product characteristics, production process, intended use, workshop facilities and equipment should be comprehensively considered to evaluate the feasibility of co-production on the same production line. If it is evaluated that the same packaging room and packaging and freeze-drying facilities can be used for packaging and freeze-drying, it should be handled in accordance with the law and regulations in accordance with the "Drug Administration Law" and other relevant requirements.

9. After the promulgation of the 2025 edition of the Chinese Pharmacopoeia, how should the standards for pharmaceutical packaging materials be implemented?

A: After the promulgation of the 2025 edition of the Chinese Pharmacopoeia, the corresponding method-based pharmaceutical packaging material standards in the 2020 edition of the Chinese Pharmacopoeia and the standards issued in the form of "Announcement on the Release of YBB 00032005-2015 and 130 other national standards for packaging materials and containers in direct contact with drugs" (No. 164, 2015) (hereinafter referred to as the 2015 YBB standards) shall be subject to the 2025 edition of the Chinese Pharmacopoeia. For a detailed comparison table, see "Comparison of this edition of the Pharmacopoeia (Part IV) with the original general testing methods for pharmaceutical packaging materials" in the 2025 edition of the Chinese Pharmacopoeia.

Pharmaceutical packaging material enterprises should determine the quality standards and conduct quality control by referring to the relevant guiding principles for pharmaceutical packaging materials in the 2025 edition of the Chinese Pharmacopoeia and the product standards in the 2015 YBB standards, based on the confirmation that the pharmaceutical packaging materials meet the expected pharmaceutical requirements and in accordance with the relevant regulations of the linked review.

Changes to pharmaceutical packaging material standards made by pharmaceutical packaging material enterprises to meet the requirements of the 2025 edition of the Chinese Pharmacopoeia, only involving changes to pharmaceutical packaging material standards and the standards meeting the requirements of the Chinese Pharmacopoeia, can be reflected in the annual report. The annual report should include the full text of the standard (including the standard number), necessary verification data, and self-inspection reports, etc., and promptly notify the relevant marketing authorization holders. After receiving the above notification, the marketing authorization holder should promptly evaluate or study the impact of the corresponding changes on the quality of the drug preparation, and implement it in accordance with the "Announcement on the Implementation of the 2025 edition of the Pharmacopoeia of the People's Republic of China" and the relevant requirements of the linked review.

10. After the promulgation of the 2025 edition of the Chinese Pharmacopoeia, how should the standards for pharmaceutical excipients be implemented?

A: Pharmaceutical excipients used in the production of preparations should comply with the relevant regulations of the national drug supervision and administration department and the relevant requirements of General Chapter 0251 Pharmaceutical Excipients in the 2025 edition of the Chinese Pharmacopoeia. Pharmaceutical excipients claiming to comply with the Chinese Pharmacopoeia must comply with the corresponding standards of the Chinese Pharmacopoeia. If the pharmaceutical excipient standards included in this edition of the pharmacopoeia cannot meet the needs of a certain preparation, or if this edition of the pharmacopoeia has not yet included a certain pharmaceutical excipient standard, suitable pharmaceutical excipients can be selected during the research and development and post-marketing changes of the preparation, and corresponding standards can be formulated.

Changes to pharmaceutical excipient standards made by pharmaceutical excipient companies to meet the requirements of the 2025 edition of the Chinese Pharmacopoeia, which only involve changes to pharmaceutical excipient standards that meet the requirements of the Chinese Pharmacopoeia, can be reflected in the annual report. The annual report should include the full text and standard number of the updated standards, as well as necessary validation data and self-inspection reports, and promptly notify the relevant drug marketing authorization holders. Drug marketing authorization holders should promptly assess or study the impact of the corresponding changes on the quality of drug preparations, and implement them in accordance with the "Announcement on the Implementation of Relevant Matters of the 2025 Edition of the Pharmacopoeia of the People's Republic of China" and the requirements of related reviews.