Host Cell Protein Assay
Recombinant biopharmaceuticals can be contaminated by residual host cell proteins (HCP). These proteins produced by the host cell during cell culturing or fermentation can cause an immune response in patients at levels as low as 10 to 100 parts per million (ppm). Their composition is extremely heterogeneous and dependent on the protein product and purification procedure used. Prior to the approval of a biological product for therapeutic use, the level of contaminating host cell proteins in the product must be quantitatively measured according to the ICH and FDA guidelines. |
 Threshold system: host cell protein assay |
Efforts to develop analytical methods for host cell protein analysis should be done in parallel to clinical development:
Early Stage Clinical Development
For in-process controls and product release for early stage clinical trials ORPEGEN offers a basic package of methods consisting of SDS-PAGE/silver stain, HPLC, Western blot and generic immunoassays. ORPEGEN offers generic enzyme immunoassays for the detection of host cell proteins from the following production cell lines: Chinese Hamster Ovary (CHO), hybridoma cell line SP2/0, Human Embryonic Kidney 293 (HEK), insect cell line SF9 and E. coli bacteria.
Assays for other recombinant expression systems are established on request.
Late Stage Clinical Development and Market
Once production development has matured and provides a robust production process, a more sophisticated and custom-tailored approach is needed. A process specific HCP assay is based on polyclonal antibodies produced against host cell proteins obtained from a mock production run. Specific antisera raised in rabbits or goats are quality controlled using 2D electrophoresis and Western blotting. Based on these specific antisera a HCP assay is then developed either using ELISA or ILA (Threshold™ Immunoligand Assay) technology. The sensitivity of the ILA method is usually below 10 ppm.
ORPEGEN also offers validation of the optimised method according to ICH guidelines and routine lot release testing.