Immunoinformatic Risk Assessment of Host Cell Proteins During Process Development for Biologic Therapeutics

The identification and removal of host cell proteins (HCPs) from biologic products is a critical step in drug development. Despite recent improvements to purification processes, biologics such as monoclonal antibodies, enzyme replacement therapies, and vaccines that are manufactured in a range of ce...

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Bibliographic Details
Published in:The AAPS journal 2023-09, Vol.25 (5), p.87-87, Article 87
Main Authors: Haltaufderhyde, Kirk, Roberts, Brian J., Khan, Sundos, Terry, Frances, Boyle, Christine M., McAllister, Mitchell, Martin, William, Rosenberg, Amy, De Groot, Anne S.
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal
Antigenic determinants
B cells
Biochemistry
Biological Products
Biomedical and Life Sciences
Biomedicine
Biotechnology
Case studies
Cell Line
Drug Development
Enzymes
Epitopes, T-Lymphocyte
Humans
Immune response
Liraglutide
Monoclonal antibodies
Pharmacology/Toxicology
Pharmacy
Review Article
Risk Assessment
Somatropin
T cells
Vaccines
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Summary:The identification and removal of host cell proteins (HCPs) from biologic products is a critical step in drug development. Despite recent improvements to purification processes, biologics such as monoclonal antibodies, enzyme replacement therapies, and vaccines that are manufactured in a range of cell lines and purified using diverse processes may contain HCP impurities, making it necessary for developers to identify and quantify impurities during process development for each drug product. HCPs that contain sequences that are less conserved with human homologs may be more immunogenic than those that are more conserved. We have developed a computational tool, ISPRI-HCP, that estimates the immunogenic potential of HCP sequences by evaluating and quantifying T cell epitope density and relative conservation with similar T cell epitopes in the human proteome. Here we describe several case studies that support the use of this method for classifying candidate HCP impurities according to their immunogenicity risk. Graphical Abstract
ISSN:1550-7416
1550-7416
DOI:10.1208/s12248-023-00852-z