Controlling host cell proteins in drug development

The ability to harness a cell’s innate machinery to produce assay (ELISA) is considered the gold standard1,3 because of specific agents was revolutionary for drug development. its sensitivity, relative ease of use, and higher throughput Today, fields from biopharmaceutical production to food potential. ELISA accuracy depends on the antibodies processing use biomanufacturing. However, cell-based used, which must bind to a plethora of HCP targets that production methods bring their own caveats, one of which could potentially be present in the sample. To design an is the presence of host cell proteins (HCPs). ELISA antibody panel that is sufficiently sensitive and relevant entails accounting for molecules similar to the HCPs are proteins endogenous to the cellular production produced agent as well as the cell type used for production. vehicle. Day-to-day cellular activity produces them, Moreover, panel design is impacted by clinical development but they can also be a result of cellular damage during stage, with later stages requiring more stringent and biomanufacturing.1 As such, scientists routinely take precise assays.4 These factors combine to create a steps to remove HCPs during the purification phase of the challenging situation for researchers. manufacturing workflow. Nonetheless, residual HCPs might remain in the final product. Since most production vehicles, Product suites like the Amersham™ HCPQuant CHO ELISA including the popular Chinese hamster ovary (CHO) cells, are Kit and Anti-CHO HCP Antibody reagents from Cytiva genetically dissimilar to humans, residual HCPs are potentially help scientists track HCP levels throughout the biologics immunogenic.2 This carries significant implications for manufacturing process. The HCPQuant CHO ELISA Kit and therapeutic biologics such as recombinant antibodies. Anti-CHO HCP Antibody reagents emphasize flexibility, sensitivity, and reproducibility. Its wide dynamic range means HCP is an umbrella term for a wide range of molecules, that a single kit can be used for a broad number of situations so it is impossible to set a threshold limit for HCP across a manufacturing workflow. Higher sensitivity translates contamination. Today, regulatory bodies generally evaluate into fewer undetected HCPs, which is especially important in HCP levels on a case-by-case basis depending on factors later drug development phases. Finally, consistently low inter- such as clinical applicability, dosing levels/frequency, and intra-plate variation provides greater data validity. These and route of administration.2 The U.S. Food and Drug three factors are key to strong HCP detection and robust HCP Administration, the European Medicines Agency, and the management strategies. Japanese Pharmaceuticals and Medical Devices Agency all stress that manufacturers should minimize HCP levels, With over 50 years of experience working with the and they emphasize the need for accurate and stringent biopharmaceutical industry, Cytiva has a long-established detection methods. track record of assisting researchers in their goals. Cytiva aims to work closely with customers, pursuing collaborations You can detect HCPs using a variety of methods. Gel for research around the world, and to this end currently electrophoresis enables visualization, while mass employs 7,000 associates operating in 40 countries. spectrometry facilitates characterizing individual HCPs. However, these methods lack sufficient sensitivity and Cytiva has a broad range of products, including reproducibility when working with complex samples. chromatography resins, culture media and reagents tailored As such, antibody-based assays are recommended by for specific cell lines, ELISA kits for HCP detection, imagers/ regulatory authorities. The enzyme-linked immunosorbent scanners, and analysis software to help in every stage of the biopharmaceutical production process. In particular, References Cytiva highlights the Melanie™ 9 coverage software, a comprehensive suite for determining the proportion of 1. C.E. Hogwood et al., “Measurement and control of the total HCP population within a sample detectable host cell proteins (HCPs) in CHO cell bioprocesses,” by an antibody reagent. Melanie software analyzes 2D Curr Opin Biotechnol, 30, 153-60, 2014. differential in-blot electrophoresis (2D DIBE) and other 2D 2. X. Wang et al., “Host cell proteins in biologics gel electrophoresis images with ease, guiding users step- development: Identification, quantitation and risk by-step to deliver quick results. assessment,” Biotechnol Bioeng. 103(3):446-58, 2009. 3. A.L. Tscheliessnig et al., “Host cell protein analysis HCPs are a natural by-product of using cellular in therapeutic protein bioprocessing - methods and factories for biomanufacturing and must be removed applications,” Biotechnol J, 8(6), 655-70, 2013. during the manufacturing process, especially 4. S. Wohlrab et al., “Tracking host cell proteins for products intended for therapeutic use. HCP during biopharmaceutical manufacturing: management strategies that lack range, sensitivity, Advanced methodologies to ensure high product or reproducibility can result in ineffective and unsafe quality,” Am Pharm Rev, 21(1), 2018. https://www. final products. Let Cytiva help reduce the risk of americanpharmaceuticalreview.com/Featured- unexpected HCPs and maximize the efficiency of your Articles/347250-Tracking-Host-Cell-Proteins-During- HCP management strategy. Biopharmaceutical-Manufacturing-Advanced- Methodologies-to-Ensure-High-Product-Quality/ Accessed October 28, 2020. For more information or to purchase these products, please visit: www.cytiva.com/HCPQuantCHO