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
細(xì)胞形態(tài)觀察和血吸附試驗(yàn)	要求	僅形態(tài)觀察
EOPC檢定	IND階段	可在BLA階段
鼠源病毒檢查	可用動(dòng)物抗體產(chǎn)生試驗(yàn)（無病毒具體要求） 雜交瘤細(xì)胞及鼠源性單克隆抗體制品：細(xì)胞/動(dòng)物/雞胚感染性試驗(yàn)； 鼠源第二法Q-PCR法-8種	嚙齒類動(dòng)物材料和細(xì)胞應(yīng)做抗體產(chǎn)生試驗(yàn) MAP-16種，HAP-6種，RAP-11種； 也可用充分驗(yàn)證的Q-PCR法
牛源病毒檢查	指示細(xì)胞感染法及免疫熒光法-6種	指示細(xì)胞感染法及免疫熒光法-7種 基礎(chǔ)上再增加BPyV，IBRV等
豬源病毒檢查	PPV、PCV1/2、TTSuV1/2（未指定方法）	指示細(xì)胞感染法及免疫熒光法PPV、PADV、TGEV、PHEV； 豬牛共患BVDV、Reo3、rabies virus
人源病毒檢查	16種病毒（可用Q-PCR法）	Q-PCR法-18種 易感人類的猿猴病毒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	主細(xì)胞庫(kù)MCB	工作細(xì)胞庫(kù)WCB	生產(chǎn)終末細(xì)胞EOPC	收獲液 UPB
無菌檢查-細(xì)菌真菌（Sterility Test）	無菌檢查直接接種法（Sterility Test (Direct Inoculation)）+方法適用性直接接種法（Method Verification for Sterility (Direct Inoculation)）	√	√	√
	無菌檢查薄膜過濾法（Sterility Test ( Membrane Filtration)）+方法適用薄膜過濾法（Method Verification for Sterility ( Membrane Filtration)）				√
無菌檢查-分枝桿菌（Sterility Test）	無菌檢查-分枝桿菌檢測(cè)（Mycobacteria Testing）	（√）	（√）	（√）	（√）
支原體檢測(cè)（Mycoplasma）	支原體檢測(cè)培養(yǎng)法含干擾試驗(yàn)（ Detection of Mycoplasma by direct culture method IncludingMycoplasmastasis）	√	√	√	√
	支原體檢測(cè)指示細(xì)胞培養(yǎng)法（ Detection of Mycoplasma by indication cell culture method）	√	√	√	√
外源(不定)病毒檢測(cè)（AdventitiousVirus）	體外不同指示細(xì)胞接種培養(yǎng)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	√		√	√
	雞胚 Detection of viruses by embryonated chicken eggs	√		√	√
	豚鼠Detection of viruses by guinea pigs	√		√	√
逆轉(zhuǎn)錄病毒檢測(cè)（Retrovirus)	逆轉(zhuǎn)錄酶活性檢查（Detection of Reverse Transcriptase Activity—PERT Assay）	√		√	√
	感染性試驗(yàn)（Infectivity Test forRetroviruses）	√		√	√
	逆轉(zhuǎn)錄病毒檢測(cè)-透射電鏡觀察（Retroviruses-TEM）	√		√
	病毒顆粒負(fù)染色電鏡定量(Quantitation of Viral Particles by Negative Stain Electron Microscopy)				√
鼠源病毒檢測(cè) （Murine viruses）	Q-PCR法檢測(cè)16種鼠源病毒（Q-PCR based Detection of  LCMV，HFRS，ECTV，HVJ，PVM，Reo-3，MADV，MuLV，MVM，TMEV，MPyV，MTLV，MHV，MRV，LDV viruses）	√
牛源病毒檢測(cè) （Bovineviruses）	細(xì)胞培養(yǎng)法及熒光抗體檢測(cè)8種牛源病毒（In vitro assay for the detection ofBVDV，BAV3，BPV，Rabies，Reo3，PI3，BTV，BRSV viruses）	√
	Q-PCR法檢測(cè)2種牛源病毒（Q-PCR based Detection of BPyV，IBRV viruses）	√
豬源病毒檢測(cè) （Porcineviruses）	細(xì)胞培養(yǎng)法、熒光抗體法及Q-PCR法檢測(cè)6種豬源病毒（In vitroassay and Q-PCR based Detection of PPV，PHEV，PCV，PADV，TGEV，TTSuV viruses）	√
其他病毒檢測(cè)	Q-PCR法檢測(cè)杯狀病毒（Q-PCR based Detection of Vesivirus2117 ）	√
細(xì)胞鑒別 （CellIdentity）	DNA條形碼 （ DNA Barcoding by CO1 geneamplification）	√	√	√