Process Related Impurity Analysis for Biotherapeutics

Impurity testingGyrolab® systems and immunoassays speed up the bioprocessing workflow

Process related impurity concentrations are highly regulated in the manufacture of biologic drugs because of their immunogenic potential. Bioanalytical methods to detect and measure process related impurities must be developed carefully to characterize heterogeneous mixtures of host cell proteins (HCPs) present in samples or the carryover of culture or process impurities such as Protein A along with the therapeutic.

  • Heterogeneous mixtures of host cell proteins (HCPs), for example
    CHO-HCP, E. coli HCP, PLBL-2 and transferrin
  • Process-specific impurities
  • Carryover of culture or process impurities such as Protein A and insulin

Impurity analysis using current ELISA technologies have limitations of labor-intensive protocols, lower throughput and narrow dynamic range. As a result, repeat analysis is common, further delaying project decisions and lot approvals. Automating impurity analysis with Gyrolab miniaturized, microfluidic immunoassays provides fast turn-around time, broad dynamic ranges and reproducibility, and high-quality data, with less hands-on operations offering an ideal technology to support all phases of bioprocess and production for biotherapeutics.

Gyrolab immunoassays provide faster time to data compared to traditional ELISA methods

Gyrolab immunoassays provide faster time to data compared to traditional ELISA methods (data courtesy of Medimmune, the global biologics research and development arm of AstraZeneca).

HCP analysis with expanded dynamic range

One primary goal during HCP assay development is a wide dynamic range for optimized analyte detection, avoiding repeat analysis and additional sample dilutions. A wide dynamic range is especially important for bioprocess HCP analysis, since the concentration range of host cell protein impurities encountered in process samples may be especially wide. Gyrolab assays and kits offer broad analytical ranges, reducing the the number of dilutions required to hit the analytical range, thereby reducing the need for repeat runs. Gyrolab CHO-HCP E3G Kit, (broad dynamic range of ~3 ng/mL – 8000 ng/mL), and Gyrolab CHO-HCP Kit 1 both incorporate antibodies from Cygnus Technologies.

Gyrolab CHO HCP Kit 1

Gyrolab CHO-HCP Kit 1 offers shows a broad analytical range of approximately 2 – 8000 ng/mL compared to 1 – 1000 ng/mL for ELISA.

In situations where assay development with process-specific reagents is required, Gyrolab Bioaffy™ 1000 HC Assay Toolbox provides the flexibility, automation and rapid time to results.

Protein A and culture impurities

Other bioprocess impurities may carry over from purification columns or culture media additives. Gyrolab Protein A kits detect GE Healthcare MabSelect SuRe™ ligands in samples, and carefully tested Gyrolab assay protocols are available for Human Transferrin, Insulin, and Phospholipase B-Like 2 (PLBL2) impurity analysis. The wider analytical range of Gyrolab immunoassays offers several logs working range expansion over ELISA for a wider detection range requiring a lower MRD.

protein A

Ready-to-use Gyrolab Protein A kit covers a broader dynamic range compared to a commercial ELISA kit.

Comparable to ELISA

Gyrolab assays have been shown by many of our customers to be comparable to ELISAs. For example, the correlation of process samples during purification of a therapeutic protein analyzed by both ELISA and Gyrolab immunoassays is shown below.

Correlation-of-Gyrolab-with-ELISA-s--1Correlation of results for samples throughput the purification of a therapeutic protein are show. The error bars indicate that the result from Gyrolab xP workstation are less variable.

Gyrolab immunoassay platform for process impurity analysis

table impurity-1

 

Host-Cell Protein Analysis to Support Downstream Process DevelopmentLearn more about how scientists at Sanofi have successfully implemented Gyrolab immunoassay system as a reliable platform for high-throughput HCP analysis, in combination with a robotic liquid handling system. The results were comparable to their gold-standard ELISA method.

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