Battling a bottleneck in biotherapeutics

Although a variety of technical solutions have been developed, immunoassay is still seen as the workhorse in the biotherapeutic workflow - however improvements must be made in the performance and productivity of the technique in order to remove a bottleneck in the industry

Enzyme-linked immunosorbent assay (ELISA) is known as the “workhorse” of immunoassay formats. Established for over four decades, ELISA has commanded widespread popularity, owed primarily to its unmatched specificity, even at very low concentrations or with subtle differences in structure.  ELISA remains a key step in the biotherapeutic workflow. However, to achieve quality results requires specialist skills, tedious and time-consuming methodologies, and typically, at least 2-3 weeks for development and optimisation of each new assay. In terms of assay performance, high signal-to-noise ratios and CVs that do not meet with regulatory authority requirements commonly create additional challenges.

In recent years, the immunoassay field has seen numerous improvements, including the introduction of kits to reduce assay development times and improve reproducibility; multiplex assay platforms to negotiate large sample volume, long turn-around times and increase productivity, as well as robotics to automate manual steps, such as sample dilutions. However, drawbacks still remain: multiplex assays suffer from cross-reactivity, cross-talk and matrix interferences, and robotics systems are not fully integrated and remain open to user error. At the same time, as pharmaceutical companies increasingly look to outsource to CROs and CMOs, the challenge of assay transfer between locations or into GxP environments risks slowing down the development process. Whether or not the outsourcing trend continues, scientists will need a solution to improve robustness and the ease of transfer between laboratories, to ensure that assays can be used throughout the biotherapeutic workflow.

Increasing financial pressure on the biopharmaceutical industry is pushing organisations to identify ways to improve efficiency and output. On top of this, scientists are faced with balancing the need to perform a larger range of analytical investigations, to meet research and regulatory demands, against limited sample availability. Researchers need to perform multiple applications, from biomarker monitoring, pharmacokinetic and pharmacodynamic analyses, to product and host cell protein quantification. However, each application brings its own challenges. For example, for biomarker studies, as the demand grows to analyse and monitor an increasing number of biomarkers, analytical techniques must be able to extract as much information as possible from the limited samples, whereas for immunogenicity (anti-drug antibody) assays, which are used to quantify and characterise an immune response to a biotherapeutic, the drug tolerance of an assay format and the ease with which assays can be transferred from development through to clinical trials is most crucial. Increasingly, a multi-application solution, in an open format suitable for a broad spectrum of assays will be essential. Scientists need to be able to work at the nanolitre scale, both to cut consumption of reagents, but also to gain as much information as possible from small amounts of sample. In addition, increased automation will allow laboratories to meet productivity demands, while cutting project timelines, eliminating user error, and enabling increased testing.

Looking ahead, immunoassays seem set to remain a critical part of the biotherapeutic workflow, and key pharmaceutical, CRO and CMO organisations are leading the way in the search for a solution to improve productivity and performance. When considering the options currently available, one major consideration has to be an assurance that an increase in lab productivity can still provide high quality data. Striving to meet this requirement has been a priority of the Gyros’ research and development team during development of the company’s nanolitre-scale immunoassay platform. Today, with over 80 Gyrolab workstations installed in industrial laboratories, the platform has been proven to address this issue and many other challenges: the speed with which new assays can be up and running, reduction in the number of dilutions and repeats, the ability to measure multiple analytes using low sample volumes, and the ease with which assays can be transferred between labs or into regulated environments requiring CFR Part 11 compliance. Only by meeting these challenges can immunoassays cease to be a bottleneck in the biotherapeutic workflow.

The Author 

Günther Reichenberger, Senior Product Manager, Gyros AB