1. Announcement No. 29 of 2025 issued 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 shall come into effect on October 1, 2025. Can it be implemented ahead of schedule?

Answer: According to Announcement No. 29 of 2025 issued 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 shall come into effect on October 1, 2025. Between the date of promulgation and the date of implementation of the 2025 edition of the Chinese Pharmacopoeia, the original standard or the 2025 edition of the Chinese Pharmacopoeia may be implemented, and this shall be indicated in the instructions. During post-market supervision of drugs (including spot checks, etc.), the implementation shall be based on this.

Drugs produced before the implementation 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 the National Medical Products Administration, they shall be implemented in accordance with those requirements.

2. How should the drug marketing authorization holder carry out the change work after the implementation of the 2025 edition of the Chinese Pharmacopoeia?

Answer: According to Articles 8 and 31 of the Measures for the Administration of Drug Standards, drug marketing authorization holders shall implement the main responsibility for drug quality, pay close attention to the development and revision of national drug standards, conduct applicability assessments of the drug standards implemented for their manufactured 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 should promptly conduct relevant comparative research work to assess whether the drug registration standards meet the relevant requirements of the 2025 edition of the Chinese Pharmacopoeia standard. For those requiring changes to the drug registration standard, the drug marketing authorization holder shall submit a supplementary application, filing or report in accordance with the relevant provisions on post-market change management of drugs, and implement them as required.

After the assessment, for changes that require approval, they should be submitted before the implementation 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, it shall be implemented 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 product?

Answer: 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 preface and general technical requirements (general rules and general discussions, etc.) in the main text of the varieties, the drug marketing authorization holder needs to conduct corresponding evaluations of their products based on the preface 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 expression "unless otherwise specified" in the 2025 edition of the Chinese Pharmacopoeia be understood?

Answer: Article 4 of the General Preface to the General Rules of the 2025 edition of the Chinese Pharmacopoeia clearly states that "the term 'unless otherwise specified' used in the preface and general technical requirements indicates that if there are inconsistencies with the provisions of the preface or general technical requirements, then the provisions shall be made separately in the main text of the variety and implemented according to the main text of the variety."

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 new edition of the Pharmacopoeia's preface, main text of varieties and the referenced general technical requirements. After the assessment, if the drug standards implemented do not apply to the relevant requirements of the new edition of the Chinese Pharmacopoeia, they shall conduct sufficient research and verification in accordance with the "Regulations on Drug Registration Management", "Provisional Measures for the Management of Post-Market Changes of Drugs", relevant technical guidelines on 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 implementation of the ICH Q4B guidelines be implemented after their transformation?

Answer: The 2025 edition of the Chinese Pharmacopoeia adopts two methods for the implementation of the 16 relevant testing methods involved in ICH Q4B: "direct coordination" and "parallel inclusion". 12 items use "direct coordination", and 4 items 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 [Filling] Inspection and 0942 Minimum Filling Inspection Method, (2) 0923 Tablet Friability Inspection 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 Limits Test for Non-Sterile Products: Microbial Count Method (except for standard strains), (9) 1106 Microbial Limits Test for Non-Sterile Products: Control Microbial Test (except for standard strains), (10) 1107 Microbial Limits Standard for Non-Sterile Drugs (except for standard strains), (11) 1101 Sterility Test (except for standard strains), (12) 1143 Bacterial Endotoxins Test.

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 shall be indicated under the standard item. For products that have already been marketed, "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 "Provisional Measures for the Management of Post-Market Changes of Drugs". During post-market supervision (including spot checks), implementation shall be based on the approved or filed content.

In the 2025 edition of the Chinese Pharmacopoeia, the ICH Q4B method is included in parallel with the original method for 0841 Residue on Ignition Test; the ICH Q4B determination method is included in parallel with the original determination method for 0921 Disintegration Time Test and 0931 Dissolution and Release Test; the 0940 Uniformity of Dosage Units Test is added in the 2025 edition of the Chinese Pharmacopoeia, and is included in parallel with the 0941 Content Uniformity Test and the requirements for weight (filling) difference in the general chapter of preparations.

6. The 2025 edition of the Chinese Pharmacopoeia 0212 General Chapter for the Examination of Crude Drugs and Slices includes the maximum residue limits of 47 prohibited pesticides, relevant crude drugs and slices, as well as the requirements for heavy metals and harmful elements in relevant crude drugs and slices. How should production enterprises conduct inspections?

Answer: The relevant provisions in 0212 General Chapter for the Examination of Crude Drugs and Slices of 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 formulate inspection release strategies based on the risk level to ensure that products meet the relevant requirements.

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

Answer: Drawing on the changes and practices in the international management of abnormal toxicity testing, the 2025 edition of the Chinese Pharmacopoeia (Part III) adds the statement "Determine whether to set abnormal toxicity test items in the quality standards based on the results of product risk assessment or its own quality attribute characteristics" in the five general chapters: "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 Protein 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 varieties with abnormal toxicity items in the monograph, production enterprises can combine the risk assessment results and quality control strategies without making it a must-test item for each batch release, but still need irregular checks; when major pharmaceutical changes occur, sufficient batches must be tested to determine the safety of the changed product; if the quality attributes of a certain product of this variety are not suitable for abnormal toxicity testing, after providing sufficient evidence and assessment, it can be exempted with approval."

The statement in the preface about reducing abnormal toxicity testing during product release testing according to specific circumstances is the autonomous behavior of the drug marketing authorization holder and does not require separate approval. In this version of the Pharmacopoeia, if the monograph has abnormal toxicity items but the drug marketing authorization holder considers, after assessment, that a certain product does not need to set abnormal toxicity items in the registration standard, they can follow the relevant procedures such as the "Drug Registration Management Measures" and specify it in the approved drug standard. Testing can then omit this item."

In the preface, "exemption with approval" only applies to situations where the product's quality attributes are unsuitable for abnormal toxicity testing. This needs to be considered when submitting a product's marketing authorization application, not as a new licensing matter. If the monograph in this version of the Pharmacopoeia has abnormal toxicity testing items but a certain product's quality attributes are unsuitable for abnormal toxicity testing, this can be noted in the approved drug standard; the test may be omitted."

In the 2025 edition of the Chinese Pharmacopoeia (Part III), for varieties with abnormal toxicity 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, if abnormal toxicity testing is carried out, shall comply with the regulations."

The work needed to confirm whether abnormal toxicity testing can be reduced during release testing includes, but is not limited to, summarizing and analyzing the GMP implementation status, GMP inspection status, and product batch release status 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 quality control strategy of the product and confirm whether the existing quality control measures can comprehensively control the product quality. The drug marketing authorization holder needs to comprehensively analyze the above situations to determine whether abnormal toxicity testing can be reduced. If it is confirmed that abnormal toxicity testing can be reduced after evaluation, the drug marketing authorization holder shall formulate a suitable abnormal toxicity testing plan to ensure product quality."

Drug testing institutions will adjust the testing strategies for registration testing, batch release testing, etc., according to the situation of drug marketing authorization holders reducing or exempting abnormal toxicity testing for products."

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

Answer: With the rapid development of biotechnology in recent years, new biological products are constantly being marketed. To meet the requirements of the development of new biological products, the general chapter "Packaging and Storage and Transportation Management of Biological Products" in Part III of this version 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 Practices for Drug Production (2010 edition)" stipulates that biological products (such as BCG vaccine or other drugs prepared from 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 required, it should be implemented in accordance with the relevant requirements of the "Good Manufacturing Practices for Drug Production (2010 edition)", etc. The concept of quality risk management should be fully implemented, and the relationship between the hazards, exposures, and risks of co-packaging preventive and therapeutic biological products on the same production line should be fully and accurately understood and grasped, comprehensively considering the product characteristics, production process, intended Applications, workshops, facilities, and equipment, etc., and assessing the feasibility of co-line production. If co-packaging and freeze-drying can be performed using the same packaging room and packaging and freeze-drying facilities after evaluation, it should be handled in accordance with the law 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 pharmaceutical packaging material standards be implemented?

Answer: After the promulgation of the 2025 edition of the Chinese Pharmacopoeia, the corresponding method-type pharmaceutical packaging material standards in the 2020 edition of the Chinese Pharmacopoeia and the standards published in the form of "Announcement on the Release of YBB 00032005-2015 and other 130 national standards for packaging materials and containers that directly contact drugs" (No. 164 of 2015) (hereinafter referred to as the 2015 YBB standards) shall be in accordance with the 2025 edition of the Chinese Pharmacopoeia. For a detailed comparison table, see the "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 carry out quality control in accordance with the relevant regulations of associated review, referring to the relevant guiding principles for pharmaceutical packaging materials in the 2025 edition of the Chinese Pharmacopoeia and the variety standards in the 2015 YBB standards, based on the confirmation that the pharmaceutical packaging materials meet the expected pharmaceutical requirements."

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 drug marketing authorization holders. After receiving the above notification, the drug marketing authorization holder should promptly assess or study the impact of the corresponding changes on the quality of the drug preparation and follow the requirements of the "Announcement on Implementing Relevant Matters of the 2025 Edition of the Pharmacopoeia of the People's Republic of China" and associated review."

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

Answer: 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 in the research and development and post-market change research of the preparation, and corresponding standards can be formulated.

Changes to pharmaceutical excipient standards made by pharmaceutical excipient companies to comply with the 2025 edition of the Chinese Pharmacopoeia, which only involve changes to the standards and meet the requirements of the Chinese Pharmacopoeia, can be reflected in the annual report. The annual report should include the full text and number of the updated standards, as well as necessary verification 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 the 2025 Edition of the Pharmacopoeia of the People's Republic of China" and the relevant requirements of the associated review.