title: A strategy to accelerate protein production from a pool of clones in Chinese hamster ovary cells for toxicology studies.
abstract: In the biopharmaceutical industry, a clonally derived cell line is typically used to generate material for investigational new drug (IND)-enabling toxicology studies. The same cell line is then used to generate material for clinical studies. If a pool of clones can be used to produce material for IND-enabling toxicology studies (Pool for Tox (PFT) strategy) during the time a lead clone is being selected for clinical material production, the toxicology studies can be accelerated significantly (approximately 4 months at Genentech), leading to a potential acceleration of 4 months for the IND submission. We explored the feasibility of the PFT strategy with three antibodies-mAb1, mAb2, and mAb3-at the 2 L scale. For each antibody, two lead cell lines were identified that generated material with similar product quality to the material generated from the associated pool. For two antibody molecules, mAb1 and mAb2, the material generated by the lead cell lines from 2 L bioreactors was tested in an accelerated stability study and was shown to have stability comparable to the material generated by the associated pool. Additionally, we used this approach for two antibody molecules, mAb4 and mAb5, at Tox and GMP production. The materials from the Tox batch at 400 L scale and three GMP batches at 2000 L scale have comparable product quality attributes for both molecules. Our results demonstrate the feasibility of using a pool of clonally derived cell lines to generate material of similar product quality and stability for use in IND-enabling toxicology studies as was derived from the final production clone, which enabled significant acceleration of timelines into clinical development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1449-1455, 2017.
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Zhilan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Wendy
authors.initials: W
authors.lastname: Hsu
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Abby
authors.initials: A
authors.lastname: Pynn
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ng
authors.affiliation: Dept. of Purification Development, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Donna
authors.initials: D
authors.lastname: Quicho
authors.affiliation: Dept. of Pharmaceutical Development, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Yilma
authors.initials: Y
authors.lastname: Adem
authors.affiliation: Dept. of Pharmaceutical Development, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Zephie
authors.initials: Z
authors.lastname: Kwong
authors.affiliation: Dept. of Analytical Development and Quality Control, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Brad
authors.initials: B
authors.lastname: Mauger
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: John
authors.initials: J
authors.lastname: Joly
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Bradley
authors.initials: B
authors.lastname: Snedecor
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Laird
authors.affiliation: Dept. of Pharmaceutical Development, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Andersen
authors.affiliation: Dept. of Early Stage Cell Culture, Genentech Inc., South San Francisco, CA, 94080.
authors.forename: Amy
authors.identifier: 0000-0003-3401-4569
authors.initials: A
authors.lastname: Shen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics; D019149:Bioreactors; D016466:CHO Cells / Q000378:metabolism*; D002999:Clone Cells / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D014116:Toxicology
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins
keywords: Chinese hamster ovary (CHO) cells; Pool for Tox (PFT); monoclonal antibody (mAb)