4、病毒清除工藝驗證方案

 On January 21, 2020, the National Medical Products Administration (NMPA) issued the "Announcement on the Application of 11 International Technical Guidelines for Human Drug Registration, including Q2 (R1): Analytical Method Validation: Text and Methodology" (Announcement No. 7 of 2020). The announcement clarified that, starting 6 months after the release of this announcement (i.e., July 10, 2020), pharmaceutical studies (based on the time of experimental record) will apply ICH guidelines, including ICH Q5A (R1) and Q5B. Therefore, the virus clearance validation for human monoclonal antibodies, protein drugs, and other biopharmaceuticals now follows a unified set of standards and principles both domestically and internationally. The recommended validation plan (CHO expression system) is shown in the table below:

Table 2: Currently Recommended Overall Virus Clearance Process Validation Plan for IND and BLA Submissions

Process	臨床Ι期（IND） NMPA/EMA/UDFDA	臨床Ⅲ期后報產（BLA） NMPA/EMA/UDFDA
低 pH 孵育或 S/D 處理	1種病毒（MuLV），重復2次實驗	2 種病毒（MuLV，PRV），重復2次實驗
納米膜過濾	2種病毒（MuLV，MVM），重復2次實驗	4 種病毒（MuLV，PRV，Reo3，MVM），重復2次實驗
陰離子交換層析	2種病毒（MuLV，MVM），重復2次實驗	4 種病毒（MuLV，PRV，Reo3，MVM），重復2次實驗，需評估舊填料的病毒清除能力以及病毒殘留
另外一種層析	可選	4 種病毒（MuLV，PRV，Reo3，MVM），重復2次實驗，需評估舊填料的病毒清除能力以及病毒殘留

 Virus Clearance Process Validation Showcase

 Canvest Bio has provided professional, comprehensive, and reasonable virus clearance process validation services to hundreds of domestic and international biopharmaceutical companies; the approval rate is 100%. We have professional project managers (PM) who respond to customer needs promptly, track project progress, and provide continuous service throughout the submission process, including offering rational suggestions for submission material writing.

Filing Stage: IND

 Agency: Dual filing (domestic and international)

Process and Results:

Process	去除/滅活指數（log10）
	X-MuLv	MVM	PRV
低pH孵育	≥4.30±0.14	/	≥5.20±0.07
陰離子層析	≥5.05±0.00	≥5.9±0.35	/
納米膜過濾	≥4.85±0.07	≥5.15±0.07	/

Filing Stage:BLA

Agency: Domestic declaration

Process and Results:

Process		去除/滅活指數（log10）
		X-MuLv	MVM	PRV	Reo3
低pH孵育		≥5.80±0.28	/	≥5.15±0.07	/
納米膜過濾		≥4.95±0.00	≥4.55±0.00	≥4.30±0.14	≥4.15±0.07
親和層析	新填料	3.38±0.07	3.14±0.38	4.09±0.14	2.43±0.20
	舊填料	3.48±0.07	3.14±0.38	4.09±0.51	2.29±0.16
陰離子層析	新填料	4.30±0.00	4.19±0.07	4.70±0.07	4.64±0.07
	舊填料	4.35±0.00	4.33±0.10	4.66±0.29	4.50±0.14