Regulatory Requirements of Sub-visible Particles for Injections in Different Countries and Its Application in Biotech Drugs
Objective:To analyze the regulatory requirements for sub-visible particles in different pharmacopoeias for industry reference,by comparing the regulatory requirements of sub-visible particles of the Chinese Pharmacopoeia 2020 edition(ChP 2020),the 2023 US Pharmacopoeia(USP-NF 2023),European Pharmacopoeia 11.0th edition(EP 11.0),Japanese Pharmacopoeia 18th edition(JP 18).Taking therapeutic protein injection as a representative,combined with the current regulatory requirements for sub-visible particles in injections,it is pointed out that the existing requirements fail to control the small-size particles(0.1-10 μm)which with immunogenic potential in such biotech drugs,and suggestions are put forward from three aspects to improve the quality control to better ensure the safety of patients.Methods:By comparing the sections of sub-visible particles testing in injections in ChP 2020,USP-NF 2023,EP 11.0 and JP 18,the contents of the testing methods,limited standards and system suitability tests are analyzed and summarized.By collecting and summarizing the requirements in pharmacopoeias and technical guidelines for sub-visible particles of biotech drugs in China,US,Japan and Europe,the current regulatory requirements for sub-visible particles in biotech drugs are clarified.Results and Conclusion:(1)For the determination of sub-visible particles,two procedures,Light Obscuration Particle Count Test and Microscopic Particle Count Test are specified in all the 4 pharmacopoeias,but the applicable conditions of each method are different.In addition,for testing methods,the requirements in USP-NF 2023,EP 11.0 and JP 18 are same.The mainly difference in ChP 2020 is the test requirements of the samples which are less than 25 mL.For system suitability testing,the requirements in USP-NF 2023 are more comprehensive,while which in ChP 2020 are less.For particle count and limited standards,the requirements are consistent for the 4 pharmacopoeias.(2)Testing methods for sub-visible particles in biotech drugs are included in USP-NF 2023,EP 11.0,JP 18,except ChP 2020.However,in the 3 pharmacopoeias,the particles with 0.1-10 μm size are not required to count and control.The possible immunogenicity hazards which may be caused by these small-size protein aggregates are still not controlled.Since there is no clear technical requirements and standards for these small-size particles,three suggestions are put forward in methodology research,data collection and development technical requirements,so as to better ensure the drug safety of patients.
NETL
NSTL
万方数据
维普
