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.