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
細胞形(xing)態觀察和血吸附試驗	要求(qiu)	僅形(xing)態觀察
EOPC檢定	IND階段	可在(zai)BLA階段(duan)
鼠源病(bing)毒(du)檢查(cha)	可用動(dong)物抗體(ti)(ti)產生試(shi)驗（無病(bing)毒(du)具體(ti)(ti)要求） 雜交瘤細胞及(ji)鼠源性單克隆抗體制品：細胞/動物/雞胚感染性試驗； 鼠源第二法Q-PCR法-8種	嚙齒類動物材料和細胞應做抗體產生試驗 MAP-16種，HAP-6種，RAP-11種； 也可用充分驗證的Q-PCR法
牛源病毒檢(jian)查	指示細胞感(gan)染法及免疫熒光法-6種	指(zhi)示細胞感(gan)染法及免疫(yi)熒光法-7種 基礎上再增加BPyV，IBRV等(deng)
豬源病毒檢查	PPV、PCV1/2、TTSuV1/2（未指(zhi)定方法）	指示細胞感染法(fa)及免疫熒光(guang)法(fa)PPV、PADV、TGEV、PHEV； 豬牛共患(huan)BVDV、Reo3、rabies virus
人源(yuan)病毒檢查	16種病(bing)毒（可用Q-PCR法）	Q-PCR法(fa)-18種 易感人類(lei)的猿猴(hou)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	主細胞(bao)庫MCB	工(gong)作細胞庫WCB	生產終末(mo)細胞EOPC	收獲液 UPB
無菌檢查-細菌(jun)真菌(jun)（Sterility Test）	無菌檢(jian)查直(zhi)接接種法(fa)（Sterility Test (Direct Inoculation)）+方(fang)法適用(yong)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(fa)適用薄膜(mo)過濾法(fa)（Method Verification for Sterility ( Membrane Filtration)）				√
無菌(jun)檢(jian)查-分枝桿(gan)菌(jun)（Sterility Test）	無菌檢查-分枝桿菌檢測（Mycobacteria Testing）	（√）	（√）	（√）	（√）
支(zhi)原體檢測（Mycoplasma）	支原(yuan)體檢測培養(yang)法含干擾(rao)試驗（ Detection of Mycoplasma by direct culture method IncludingMycoplasmastasis）	√	√	√	√
	支原體檢測指(zhi)示(shi)細(xi)胞(bao)培養法（ Detection of Mycoplasma by indication cell culture method）	√	√	√	√
外源(不定)病毒檢測（AdventitiousVirus）	體(ti)外不同指示(shi)細胞接種培(pei)養法28天（In-Vitro Indicator Cell Culture Assayfor Adventitious Virus Contaminants）	√	√	√	√
	乳(ru)鼠和成鼠 Detection of viruses by sucking mice and adult mice	√		√	√
	雞胚(pei) Detection of viruses by embryonated chicken eggs	√		√	√
	豚(tun)鼠Detection of viruses by guinea pigs	√		√	√
逆轉錄病毒檢測（Retrovirus)	逆轉(zhuan)錄酶活性(xing)檢查（Detection of Reverse Transcriptase Activity—PERT Assay）	√		√	√
	感染性試驗（Infectivity Test forRetroviruses）	√		√	√
	逆轉錄病(bing)毒檢測(ce)-透(tou)射電鏡觀察（Retroviruses-TEM）	√		√
	病(bing)毒顆粒負(fu)染色(se)電鏡定量(Quantitation of Viral Particles by Negative Stain Electron Microscopy)				√
鼠源(yuan)病毒檢(jian)測 （Murine viruses）	Q-PCR法檢測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(yuan)病毒(du)檢測 （Bovineviruses）	細胞(bao)培養法及(ji)熒(ying)光抗體檢測(ce)8種牛源病(bing)毒(du)（In vitro assay for the detection ofBVDV，BAV3，BPV，Rabies，Reo3，PI3，BTV，BRSV viruses）	√
	Q-PCR法檢測(ce)2種(zhong)牛源病毒（Q-PCR based Detection of BPyV，IBRV viruses）	√
豬(zhu)源病毒檢測 （Porcineviruses）	細胞培養(yang)法、熒光(guang)抗體法及Q-PCR法檢測6種(zhong)豬(zhu)源(yuan)病毒（In vitroassay and Q-PCR based Detection of PPV，PHEV，PCV，PADV，TGEV，TTSuV viruses）	√
其他(ta)病(bing)毒檢(jian)測	Q-PCR法(fa)檢測杯狀病毒（Q-PCR based Detection of Vesivirus2117 ）	√
細胞(bao)鑒別 （CellIdentity）	DNA條(tiao)形碼 （ DNA Barcoding by CO1 geneamplification）	√	√	√