Testing and Inspection Technology Platform

4、病毒清除工艺验证方案

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	临床Ι期（IND） NMPA/EMA/UDFDA	临床Ⅲ期后报产（BLA） NMPA/EMA/UDFDA
低 pH 孵育或 S/D 处理	1种病毒（MuLV），重复2次实验	2 种病毒（MuLV，PRV），重复2次实验
纳米膜过滤	2种病毒（MuLV，MVM），重复2次实验	4 种病毒（MuLV，PRV，Reo3，MVM），重复2次实验
阴离子交换层析	2种病毒（MuLV，MVM），重复2次实验	4 种病毒（MuLV，PRV，Reo3，MVM），重复2次实验，需评估旧填料的病毒清除能力以及病毒残留
另外一种层析	可选	4 种病毒（MuLV，PRV，Reo3，MVM），重复2次实验，需评估旧填料的病毒清除能力以及病毒残留

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/灭活指数（log10）
	X-MuLv	MVM	PRV
低pH孵育	≥4.30±0.14	/	≥5.20±0.07
阴离子层析	≥5.05±0.00	≥5.9±0.35	/
纳米膜过滤	≥4.85±0.07	≥5.15±0.07	/

Filing Stage:BLA

Agency: Domestic declaration

Process and Results:

Process		去除/灭活指数（log10）
		X-MuLv	MVM	PRV	Reo3
低pH孵育		≥5.80±0.28	/	≥5.15±0.07	/
纳米膜过滤		≥4.95±0.00	≥4.55±0.00	≥4.30±0.14	≥4.15±0.07
亲和层析	新填料	3.38±0.07	3.14±0.38	4.09±0.14	2.43±0.20
	旧填料	3.48±0.07	3.14±0.38	4.09±0.51	2.29±0.16
阴离子层析	新填料	4.30±0.00	4.19±0.07	4.70±0.07	4.64±0.07
	旧填料	4.35±0.00	4.33±0.10	4.66±0.29	4.50±0.14