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

Area of Science:

• Biopharmaceutical Manufacturing
• Immunology
• Computational Biology

Background:

• Host cell proteins (HCPs) are critical impurities in biologic drug products that require careful identification and removal.
• Diverse manufacturing processes for biologics like monoclonal antibodies, enzyme replacement therapies, and vaccines can lead to varying HCP profiles.
• The immunogenic potential of HCPs is linked to their sequence conservation with human proteins, with less conserved sequences potentially being more immunogenic.

Purpose of the Study:

• To develop and validate a computational tool for estimating the immunogenic potential of HCPs.
• To provide a method for classifying HCP impurities based on their predicted immunogenicity risk.
• To support process development and ensure the safety of biologic drug products.

Main Methods:

• Development of the ISPRI-HCP computational tool.
• Evaluation of T cell epitope density within HCP sequences.
• Quantification of the relative conservation of HCP T cell epitopes with the human proteome.

Main Results:

• The ISPRI-HCP tool effectively estimates the immunogenic potential of HCP sequences.
• Case studies demonstrate the tool's utility in classifying candidate HCP impurities by immunogenicity risk.
• The method provides a quantitative measure of immunogenicity risk for HCPs.

Conclusions:

• ISPRI-HCP is a valuable tool for assessing HCP immunogenicity during biologic drug development.
• This computational approach aids in the risk-based classification of HCP impurities.
• The tool contributes to enhancing the safety and quality of biopharmaceutical products.