Cytiva Strategy for Host Cell Protein Control

Advances in the life sciences industry have led to the creation of therapies that change lives and transform human health. A critical aspect of therapeutic development and manufacturing is the detection, quantification, and removal of host cell proteins (HCPs) from drug substances, to ensure efficacy and prevent immunogenicity.

These processes require robust technologies that deliver built-in performance, backed by trusted expertise. As a global provider of technologies and services that advance and accelerate the development and manufacturing of new therapies, Cytiva offers a range of solutions to help scientists and developers create an effective HCP control strategy.

Living systems, including microorganisms, are used as cellular factories for the production of biological products. These systems also produce endogenous proteins (HCPs), which can have important implications for the efficacy, toxicity, and immunogenicity of the final drug product, and must be removed during manufacturing. As such, there are numerous regulatory guidelines relating to the detection and removal of PHCs from pharmaceutical products.

Each host cell line expresses a unique signature of proteins that are affected by culture conditions, including temperature, acidity, nutrient supply, and other factors. Therefore, it is essential to use tests to detect the product's unique HCP combination. Thereafter, developers should implement appropriate downstream purification processes to reduce the HCP content and ensure product safety and efficacy. The enzyme-linked immunosorbent assay (ELISA) is considered the gold standard method for the quantification of HCPs, as it offers the high sensitivity and selectivity needed to detect the complex mixture of an HCP population. ELISAs can also be automated to support high-throughput assays.

Biologics developers and manufacturers need highly accurate and reliable ELISAs to ensure product integrity. Cytiva solutions are designed to detect and quantify HCPs in process-derived samples harvested from Chinese Hamster Ovary (CHO) cell lines and overcome many of the limitations of existing assay products.

Highly sensitive antibody with high HCP coverage minimizes undetected HCPs. In addition, low inter- and intra-plate variation ensures reproducible data. The combination of wide dynamic range, high dilution linearity, and sensitive antibody with high HCP coverage ensures proper coverage of the complex HCP population and minimizes undetected proteins.

This in turn reduces the risk of immunogenicity associated with PHCs in process-derived samples. Cytiva HCP solutions give you confidence in your results.

Although ELISA is the gold standard approach for the detection and quantification of HCPs, even the most robust assay still fails to provide 100% coverage of all HCPs. Thus, various regulatory bodies require manufacturers to validate the tests they use. The data in Figure 1 shows that different HCP ELISA kits provide different HCP values ​​even on already approved biologics. It is essential to choose an ELISA kit suitable for your samples using careful validation of the ELISA.

As part of the end-to-end solutions for HCP analysis, Cytiva also offers 2D differential in-blot electrophoresis (2D-DIBE) solutions for its coverage assay. By using fluorescent multiplexed methodology, 2D-DIBE overcomes the challenges associated with 2D gel electrophoresis and colorimetric Western blot.