RT Journal Article SR Electronic T1 Biopharmaceutical Industry Practices for Sequence Variant Analyses of Recombinant Protein Therapeutics JF PDA Journal of Pharmaceutical Science and Technology JO PDA J Pharm Sci Technol FD Parenteral Drug Association (PDA) SP 622 OP 634 DO 10.5731/pdajpst.2019.010009 VO 73 IS 6 A1 Valliere-Douglass, John A1 Marzilli, Lisa A1 Deora, Aparna A1 Du, Zhimei A1 He, Luhong A1 Kumar, Sampath R. A1 Liu, Yan-Hui A1 Mueller, Hans-Martin A1 Nwosu, Charles A1 Stults, John A1 Wang, Yan A1 Yaghmour, Sam A1 Zhou, Yizhou YR 2019 UL http://journal.pda.org/content/73/6/622.abstract AB The application of advanced methodologies such as next-generation sequencing (NGS) and mass spectrometry (MS) to the characterization of cell lines and recombinant proteins has enabled the highly sensitive detection of sequence variants (SVs). However, although these approaches can be leveraged to provide deep insight into product microheterogeneity caused by SVs, they are not used in a standardized manner across the industry. Currently, there is little clarity and consensus on the utilization, timing, and significance of SV findings. This white paper addresses the current practices, logistics, and strategies for the analysis of SVs using a benchmarking survey coordinated by the International Consortium for Innovation & Quality in Pharmaceutical Development (IQ) as well as a series of deliberations among a panel of experts assembled from across the biopharmaceutical industry. Discussion includes current industry experiences including approaches for detection and quantitation of SVs during cell-line and process development, risk assessments, and regulatory feedback. Although SVs are a potential issue for all recombinant protein therapeutics, the scope of this discussion will be limited to SVs produced in mammalian cells. Ultimately, it is our hope that the findings from the survey and deliberations of the committee are useful to decision makers in industry and positions them to respond to findings of SVs in recombinant proteins that are destined for clinical or commercial use in a strategic manner.LAY ABSTRACT: This white paper addresses the current practices, logistics, and strategies for the analysis of amino acid sequence variants using a benchmarking survey coordinated by the International Consortium for Innovation & Quality in Pharmaceutical Development (IQ) as well as a series of deliberations among a panel of experts assembled from across the biopharmaceutical industry. Discussion includes current industry experiences regarding detection and quantitation of SVs during cell-line and process development, risk assessments, and regulatory feedback.