Host Cell Protein Detection and Monitoring Using LC-MS
- Dramatically increase the Host Cell Protein population coverage you achieve using only a commercial ELISA kit.
- Identify and quantify individual HCPs present at different stages of your process.
- Track HCPs of concern through your purification steps and develop robust removal strategies.
- Fast, economical and flexible alternative to developing a product-specific ELISA if there is no commercial kit available for your product.
What are Host Cell Proteins?
Host Cell Proteins, or HCPs, are endogenous to the cell line which has been used to express a protein or biopharmaceutical. The presence of HCPs in the final drug product can cause decreased stability, immunogenicity and toxicity to the patient, therefore posing a significant safety risk.
Although HCPs are removed during the manufacturing process using a variety of purification techniques, it is likely that a low-level of HCP material will remain. It is therefore important to continuously monitor the level of host cell protein throughout your process and show a reduction following each purification step.
Acceptable Limits of Host Cell Protein
Regulatory agencies evaluate acceptable limits of HCPs in a biopharmaceutical product on a case-by-case basis, depending on the route of administration, dose and the particular impurity. However, most biotechnology companies work towards total HCP levels of less than 100 ng per mg (100 ppm).
It is important to bear in mind that unknown HCPs at a level lower than this could still cause an immunogenic effect. This is why it is crucial to fully characterize and monitor the HCP profile in your drug using various orthogonal tests, as described in US (21 CFR 610.13, USP 1132), European (ICH Q6B, EMA 3AB1a) and other regulatory guidelines.
HCP Analysis by Mass Spectrometry- an orthogonal method to enhance your ELISA data
Mass Spectrometry is a powerful tool that can be used alongside your commercial ELISA kit to increase coverage so that you detect more of the Host Cell Proteins present in your product.
Not only that, BioPharmaSpec can use their LC-MS based methods to identify and quantify individual HCPs that are present at different stages of your process and in your final product, with little to no development.
Armed with this knowledge, you can track HCPs of concern, such as enzymatic or immunogenic proteins, through your purification steps and develop robust strategies for removing these proteins.
No Commercial Kit Available?
Mass spectrometric methods for Host Cell Protein detection are also ideal if there is no commercial kit available for your product, perhaps due to the cell line you are using.
Putting an LC-MS method in place is a fast, economical and flexible alternative to the development of a product-specific ELISA, which can take months or even years to develop.
In contrast to HCP-ELISA, which relies on the presence of polyclonal antibodies for positive Host Cell Protein detection, Mass Spectrometric (MS) approaches have the advantage of detecting a wider population of HCPs in a de novo manner, with no specialized polyclonal antibody reagents or product and process-specific method development required.
The BioPharmaSpec Approach to Host Cell Protein Analysis
BioPharmaSpec has developed a service for MS based HCP detection and quantitation as an orthogonal support to HCP-ELISA. The service is set up as a phased approach.
Start Using LC-MS for Better HCP Detection and Monitoring
Whether you want to ensure a robust control strategy, gain better process understanding or compare HCP profiles throughout your process and in the final product, contact us today to find out how you can quickly start using LC-MS in your development projects.