Recombinant protein drug products are often contaminated with proteins from the host cell system from which they were derived. Called host cell proteins (HCP), these contaminating proteins often co-purify along with the therapeutic protein from its growth media. There are thousands of HCP variants, and while some may not be deleterious others can reduce drug efficacy or cause immunologic responses in patients during clinical investigation, which can halt the progress of a promising drug candidate.
The challenge for biotherapeutics manufacturers is not only the proper identification and quantitation of HCPs, but also the development of techniques to remove HCPs from the production process in the early stages of drug development. While there are off-the-shelf tools available to identify and quantify HCPs, they are not thorough or specific. Additionally, methods for the elimination of HCPs contaminants are not ubiquitously effective. Having such variability in possible protein contaminants ensures that the customization of detection and mitigation solutions is necessary.
A myriad of methods are available to assist in the identification and quantitation of HCPs in a sample. However, due to the complexities involved in sample analysis multiple techniques must be used in concert in order to get a complete picture. What’s more, the expertise to not only develop and execute, but also to interpret the results from, the variety of analytical methods often does not exist under one roof. At HBS, it does.
Haemtech Biopharma Services offers an all-in-one solution to biotherapeutics manufacturers to solve their HCP challenges. Using ELISA and HRMS, HBS provides identification and quantification of specific HCPs in biotherapeutic products from early development at the cell line selection stage, through to cGMP release testing from pre-clinical to commercialization. Additionally, using HRMS, HBS can verify quality attributes for your biotherapeutics via peptide sequencing, post translational modification profiling including key modifications such as N-glycosylation, O-glycosylation, acetylation, methylation, sulfation, phosphorylation, among others. Combined with its expertise with potency and kinetics assays, HBS is the company of choice for biotherapeutics manufacturing and development.
Available methods include:
- High Resolution Mass Spectrometry proteomic analysis for HCP identity and quantity in drug substance/product samples.
- 1D/2D SDS-PAGE
- SEC-HPLC for HMW impurities in product-or process-related samples
- IEX-HPLC and RP-HPLC for impurity analysis or impurity collection and identification
- 1D/2D Western Blot – for HCPs, product protein
- Run a commercial HCP ELISA
- Evaluate a commercial HCP ELISA for appropriateness
- LC-MRM targeted quantitative proteomics analysis of in-process samples
- Develop, validate, and run ELISAs for specific HCPs in product
- Develop, validate, and run process-specific HCP ELISAs
- Specialized immunochemical methods for immunogenic HCP identification in cases where patients have developed anti-HCP antibodies
Applicable drug substances:
- Monoclonal antibodies
- Recombinant protein therapeutics such as enzyme replacement therapies and zymogen (e.g. Factor IX and VII) therapies for hemophilia
- Gene therapies