Testing and Inspection Technology Platform

In the context of rapid growth in the global and Chinese biopharmaceutical markets, supported by continuous technological innovations and increasingly prominent supply chain advantages, domestic biopharmaceutical companies are beginning to expand overseas and explore international markets. Since China joined the International Conference on Harmonisation (ICH) in 2017, dual filing in both China and the US has become a new trend for local enterprises applying for innovative drugs. There are many differences between China and the US in terms of regulations and requirements, with both opportunities and challenges. Along with advancements in technology and drug development, the pharmaceutical market is maturing, and the US FDA's regulatory policies and drug review systems are continually evolving. Domestic pharmaceutical companies need to continuously study these changes to develop beneficial and effective dual filing strategies for both China and the US.

Among the various elements of biopharmaceutical application materials, cell bank testing is a very important aspect. Both Chinese and foreign regulations have essentially the same overall requirements: the Master Cell Bank (MCB) and Working Cell Bank (WCB) are critical risk control points for key materials, and these are mandatory requirements. The End-of-Production Cell (EOPC) and Unprocessed Bulk (UPB) testing are also mandatory process product control points. EOPC, as a part of the process research data, only requires one batch (retesting is needed if the process changes), while UPB, as a process product, requires testing for each batch. Due to differences in the industrial phase of biopharmaceuticals, regulatory systems, and the application of new technologies, there are variations in the applicability and details of the guidelines between China and the US, as well as in the execution and communication. The key differences in the technical methods and execution of cell bank testing are shown in the table below:

Difference	China	USA
细胞形态观察和血吸附试验	要求	仅形态观察
EOPC检定	IND阶段	可在BLA阶段
鼠源病毒检查	可用动物抗体产生试验（无病毒具体要求） 杂交瘤细胞及鼠源性单克隆抗体制品：细胞/动物/鸡胚感染性试验； 鼠源第二法Q-PCR法-8种	啮齿类动物材料和细胞应做抗体产生试验 MAP-16种，HAP-6种，RAP-11种； 也可用充分验证的Q-PCR法
牛源病毒检查	指示细胞感染法及免疫荧光法-6种	指示细胞感染法及免疫荧光法-7种 基础上再增加BPyV，IBRV等
猪源病毒检查	PPV、PCV1/2、TTSuV1/2（未指定方法）	指示细胞感染法及免疫荧光法PPV、PADV、TGEV、PHEV； 猪牛共患BVDV、Reo3、rabies virus
人源病毒检查	16种病毒（可用Q-PCR法）	Q-PCR法-18种 易感人类的猿猴病毒SV40等

Canvest Bio has completed the optimization and upgrading of relevant testing technologies in compliance with 9 CFR, ICH guidelines, United States Pharmacopeia (USP) requirements, and current USP edition references. We provide comprehensive cell bank testing services covering:

Test	Testing Item	主细胞库MCB	工作细胞库WCB	生产终末细胞EOPC	收获液 UPB
无菌检查-细菌真菌（Sterility Test）	无菌检查直接接种法（Sterility Test (Direct Inoculation)）+方法适用性直接接种法（Method Verification for Sterility (Direct Inoculation)）	√	√	√
	无菌检查薄膜过滤法（Sterility Test ( Membrane Filtration)）+方法适用薄膜过滤法（Method Verification for Sterility ( Membrane Filtration)）				√
无菌检查-分枝杆菌（Sterility Test）	无菌检查-分枝杆菌检测（Mycobacteria Testing）	（√）	（√）	（√）	（√）
支原体检测（Mycoplasma）	支原体检测培养法含干扰试验（ Detection of Mycoplasma by direct culture method IncludingMycoplasmastasis）	√	√	√	√
	支原体检测指示细胞培养法（ Detection of Mycoplasma by indication cell culture method）	√	√	√	√
外源(不定)病毒检测（AdventitiousVirus）	体外不同指示细胞接种培养法28天（In-Vitro Indicator Cell Culture Assayfor Adventitious Virus Contaminants）	√	√	√	√
	乳鼠和成鼠 Detection of viruses by sucking mice and adult mice	√		√	√
	鸡胚 Detection of viruses by embryonated chicken eggs	√		√	√
	豚鼠Detection of viruses by guinea pigs	√		√	√
逆转录病毒检测（Retrovirus)	逆转录酶活性检查（Detection of Reverse Transcriptase Activity—PERT Assay）	√		√	√
	感染性试验（Infectivity Test forRetroviruses）	√		√	√
	逆转录病毒检测-透射电镜观察（Retroviruses-TEM）	√		√
	病毒颗粒负染色电镜定量(Quantitation of Viral Particles by Negative Stain Electron Microscopy)				√
鼠源病毒检测 （Murine viruses）	Q-PCR法检测16种鼠源病毒（Q-PCR based Detection of  LCMV，HFRS，ECTV，HVJ，PVM，Reo-3，MADV，MuLV，MVM，TMEV，MPyV，MTLV，MHV，MRV，LDV viruses）	√
牛源病毒检测 （Bovineviruses）	细胞培养法及荧光抗体检测8种牛源病毒（In vitro assay for the detection ofBVDV，BAV3，BPV，Rabies，Reo3，PI3，BTV，BRSV viruses）	√
	Q-PCR法检测2种牛源病毒（Q-PCR based Detection of BPyV，IBRV viruses）	√
猪源病毒检测 （Porcineviruses）	细胞培养法、荧光抗体法及Q-PCR法检测6种猪源病毒（In vitroassay and Q-PCR based Detection of PPV，PHEV，PCV，PADV，TGEV，TTSuV viruses）	√
其他病毒检测	Q-PCR法检测杯状病毒（Q-PCR based Detection of Vesivirus2117 ）	√
细胞鉴别 （CellIdentity）	DNA条形码 （ DNA Barcoding by CO1 geneamplification）	√	√	√