The Key to Safe Biotherapeutics
The key to delivering safe and effective biotherapeutics is not only understanding the active pharmaceutical ingredient (API) itself but also understanding process-related residual components that will inevitably make their way into the final product. Identifying and quantifying these components is not just a hot topic for the regulators, it also feeds back into process control mechanisms resulting in improved quality drug manufacturing.
Process Related Impurities and Residuals-What are they?
During the many complex operations involved in biomanufacturing, a wide range of chemicals are used which can then potentially become unwanted Process Related Impurities in the final product. Analytical guidelines such as ICH Q6B mandate that these components should be evaluated and monitored to ensure removal or reduction to acceptable low levels via efficient purification processes. For some specific products, deliberate chemical modifications (e.g. PEGylation) may also be the source of unwanted residual chemicals.
As described in the ICH Q6B guidelines, Process Related Impurities fall into 3 main categories:
- Cell substrate-derived impurities: protein/nucleic acid derived from the host organism e.g. Host Cell protein and DNA (HCP/DNA)
- Cell culture-derived impurities: a wide range of chemicals such as inducers, antibiotics, serum and other media components.
- Downstream-derived impurities: enzymes, chemical and biochemical purification and processing reagents such as cyanogen bromide, guanidine, oxidizing and reducing agents, inorganic salts, solvents, carriers, ligands and others.
Detection of residual Antifoam C with ELS Detection, Acquity APC (top) vs. LC/MRM, Xevo TQ-S (bottom). The two samples (5ppm preparations) were analyzed with the same buffer system, column and method conditions.
The Extent of the Analytical Challenge
Although a robust downstream purification process can be designed to remove or minimize process residuals, methods should be developed to allow detection and quantitation, even at very low levels, via analysis at various stages including process intermediates, drug substance and final drug product.
Monitoring these extraneous chemicals is essential as some may cause deterioration during the product’s shelf life through aggregation for example, or even be capable of generating an adverse biological response. Detection methods should be sufficiently sensitive to monitor that these impurities are at or below the maximum permitted levels and in line with any product-specific regulatory guidelines.
Working with a trusted CRO partner for process-related impurities and residual testing
BioPharmaSpec’s wide range of detection methods for the identification and quantitation of process-related impurities, including Host Cell Proteins (HCPs), is used by global biopharmaceutical developers to identify and quantitate residuals to demonstrate that downstream purification is reducing or removing these chemicals.
BioPharmaSpec also develops bespoke methods for new or unusual process additives and novel excipients. Key aspects of the service include:
- Extensive experience in the analysis of a wide range of impurities
- Proficiency in method development for tailored analysis of your impurities
- Highly skilled in the application of high-sensitivity instrumentation including mass spectrometry and ELSD
- Proven background in chemical treatments of impurities for efficient method development
Learn more about how you can access BioPharmaSpec’s extensive range of off-the-shelf methods for identification and quantitation of process-related impurities.