Are you aware of the changes to the Chinese Pharmacopoeia 2020 edition, which became effective at the end of December 2020?
Zonghua Song, PhD, Deputy Director, Chinese Pharmacopoeia Commission, provided an overview of the Chinese Pharmacopoeia 2020 edition via a prerecorded talk at the virtual 2020 PDA Pharmacopeia Conference.
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Since 1985, the Chinese Pharmacopoeia Commission has published updated editions of the Pharmacopoeia every five years. All drugs marketed in China must comply with applicable standards contained in the Chinese Pharmacopoeia.
As with the 2015 edition, the Chinese Pharmacopoeia 2020 is divided into four volumes.
- Volume I: Chinese traditional medicine materials, e.g., the “prepared slices of Chinese crude drugs,” single-item preparations, vegetables, oils and fats
- Volume II: Chemical drugs, antibiotics, biochemical drugs, and radioactive drugs
- Volume III: Biological drugs, including vaccines
- Volume IV: Excipients, test methods, standard substances, and testing solutions and reagents
New Features to the 2020 Edition
Song described eight new features in the 2020 edition:
- Increased number of monographs and general chapters
- Improved pharmacopoeia standards
- Inclusion of modern analytical technologies
- Improved safety assurances
- Improved drug efficacy controls
- Higher-level excipient standards
- Strengthened harmonization of drug standards
- Strengthened “Guiding Effect” of Pharmacopoeial Standards
1. Increased Monographs and General Chapters
Compared to the 2015 edition, the number of monographs and chapters has increased by 5.4%. The total number of monographs and general chapters is 5,911. Among these, 319 are newly added and 3,177 are revised.
2. Improved Pharmacopoeia Standards
According to Song, “The Chinese Pharmacopoeia 2020 edition improves China’s drug standards by strengthening the development of general requirements for preparations, general chapters, guidelines, and testing methods. It greatly promotes the quality of listed drugs in China and the implementation of lifecycle management expands to drug quality control from the terminal to the production process and source and moves the risk control forward.”
3. Inclusion of Modern Analytical Technologies
The 2020 Chinese Pharmacopoeia includes more modern analytical technologies than the 2015 edition. For molecular biology testing, general chapters address polymerase chain reaction (PCR) and DNA sequencing technology. New analytical methods to address quality control include X-ray fluorescence spectrometry for element analysis, light obscuration method for testing the size of emulsion particles, genetically modified detection technology for activity detecting recombinant products, and immunochemistry.
The 2020 edition also expands the application of mature analytical technologies and promotes in vitro methods as a replacement for in vivo bioassays.
4. Improved Safety Assurances
Chapters in the 2020 Chinese Pharmacopoeia provide improved safety assurances for Chinese traditional medicine, chemical drugs, biologics, and excipients.
“In terms of chemical drugs, the first is to strengthen drug impurities control,” Song said. Other monographs strengthen safety control requirements for high-risk preparations and standardize sterility and microbial limits.
For biologics, general chapters and monographs strengthen virus safety control, clarify relevant principles of the batching used for stock solutions, and add controls and limits of protein impurities related to recombinant biotechnology products. A new chapter covers quality control of aluminum hydroxide adjuvant.
When it comes to excipients, some monographs add more tests for toxic residual monomers, process impurities, and peroxides.
She added, “at the same time, pay attention to the impact of impurities contained in excipients on preparations.”
5. Improved Drug Efficacy Controls
For chemical drugs, new and updated monographs and general chapters:
- Improve the efficacy tests of preparations (e.g., the acid-neutralizing capacity test is added to hydrotalcite chewable tablets)
- Provide further improvements to the dissolution testing method of oral solid preparations
- Add radionuclear purity tests as an efficacy test for radioactive drugs
Regarding biologics, a new general chapter includes polyethylene glycol recombinant protein and peptide products, mite allergens, and gene therapy products. The chapter on titration determination of live attenuated vaccine is also revised.
In terms of excipients, Song said that the 2020 Chinese Pharmacopoeia refines classification of guidelines in this area, adds general testing methods, develops guidelines for compiling, and improves functionality-related characteristics of monograph requirements.
6. Higher-Level Excipient Standards
The 2020 edition improves standards for excipients via:
- New monographs for commonly used excipients in preparation production
- Improved safety and functional requirements
- An improved pharmacopeial standard system
7. Strengthened Harmonization of Drug Standards
Song said that the 2020 Chinese Pharmacopoeia features six areas harmonized with ICH guidelines:
- Genotoxic impurities (ICH M7: Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk)
- Analytical methods validation (ICH Q2: Validation of analytical method procedures)
- Analysis of drug impurities (ICH Q3A: Impurities in new drug substances and ICH Q3B: Impurities in new drug products)
- Residual solvents (ICH Q3C: Guideline for residual solvents)
- Dissolution testing (flow-through cell, reciprocating cylinder) (ICH Q4B Annex 7: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Dissolution Test General Chapter)
- Bulk density and tapped density of powders (ICH Q4 Annex 13: Bulk density and tapped density of powders)
8. Strengthened “Guiding Effect” of Pharmacopeial Standards
The Chinese Pharmacopoeia Commission sought to strengthen the guiding effect of pharmacopeial standards by following “the trend of international drug standards while taking into account the reality of drug production in China.”
Per Song, the 2020 Chinese Pharmacopoeia improves drug quality control, process control, and testing methods, strengthens guidance for product development, and improves regulatory concepts.
Additionally, “the setting of tests and limits not only guarantees the bottom line of drug safety, but also pays full attention to the availability of clinical drugs.”
The 2020 Chinese Pharmacopoeia became effective Dec. 30, 2020.
[The author thanks conference co-chair Mark Wiggins, Compendial Consultant, for his review of this article.]
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