RT Journal Article
SR Electronic
T1 Proceedings of the 2023 Viral Clearance Symposium, Session 6: Viral Inactivation
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 187
OP 195
DO 10.5731/pdajpst.2024.002246
VO 78
IS 2
A1 Ma, Junfen
A1 Roush, David
YR 2024
UL http://journal.pda.org/content/78/2/187.abstract
AB The use of detergents or low pH hold are commonly employed techniques in biologics downstream processing to inactivate enveloped viruses. These approaches have been demonstrated to be robust and are detailed in ASTM E2888 (low pH) and ASTM E3042-16 (Triton X-100), accordingly. One of the recent challenges is the need for a replacement of Triton X-100 with a more environmentally friendly detergent with similar log10 reduction value (LRV) achieved. The presentations in this session focused on a detailed assessment of a range of detergents. The most well characterized and potentially robust detergents identified were TDAO (n-Tetradecyl-N,N-dimethylamine-N-oxide) and Simulsol SL 11 W. Key performance factors assessed (in direct comparison with the industry standard Triton X-100) were viral inactivation kinetics (total elapsed time to achieve equilibrium), LRV achieved of enveloped viruses, toxicity, potential impact on product quality and process performance, clearance of residual detergent in subsequent downstream steps, assays to support assessment with appropriate limit of quantification, and commercial supply of detergent of the appropriate quality standard. Both TDAO and Simulsol SL11 had similar overall LRV as Triton-100. In addition, for the low pH viral inactivation, reduced LRV was observed at pH > 3.70 and low salt concentration (outside of the ASTM range), which is a cautionary note when applying low pH inactivation to labile proteins.