Gyrolab Spin Blog

Careful platform choice generates data with higher quality to support DOE

Harnessing the power of cell and gene therapy involves a large range of analytical methods that can deliver robust results to support rapid data driven decision-making. One assay development team has used immunoassays to track a transgene IgG product. Their choice of immunoassay platform enabled them to generate high quality data that supported Design of Experiments to quickly optimize cell culture.

How to detect vector immunogenicity 24× faster and with 10× less sample

Cell and gene therapy promises to revolutionize medicine by correcting underlying genetic causes of disease or conferring new functions to cells to combat disease and has already seen spectacular successes in health care, ranging from curing rare eye diseases, to the treatment of sickle cell disease and a number of cancers. Immunoassays can be important analytical tools in cell and gene therapy and the careful choice of an immunoassay platform can improve productivity by boosting workflows, data quality and greatly reducing the consumption of precious samples, for example in detecting antibodies against lentivirus vectors that are commonly used in cell and gene therapy.

Smaller, simpler biotherapeutics pave the way for new production methods

Mammalian expression systems have driven the rise of biotherapeutics. Their ability to introduce proper protein folding, post-translational modifications, and product assembly means that they are currently used to produce almost all therapeutic antibodies to ensure correct structure and minimize the risk of immunogenicity. But the advent of smaller, simpler biotherapeutics means that prokaryote expression systems such Escherichia coli (E. coli) are playing a new role in antibody therapy. These bacteria can deliver high expression levels, with simpler bioprocessing at a lower cost together with an extensive molecular toolbox based on well-characterized genetics. This development is increasing the need for sensitive methods to monitor bioprocess development and manufacturing based on E. coli-based expression systems, including the sensitive analysis of host cell proteins. 

Novel approaches include bifunctional peptide-based drugs

Obesity has become a devastating pandemic, with 108 million obese children and 604 million obese adults worldwide in 2015, and the problem is increasing (1). The result is an escalation in serious conditions such as type 2 diabetes mellitus (T2DM), cardiovascular disease, hypertension, dyslipidemia and several cancer forms, mainly gastrointestinal. Obesity is very difficult to treat through life style changes and surgery has become the most effective and long-lasting route to sustained weight loss, although it is only available to a small subset of individuals, and is both costly and risky. The search for more widely applicable treatment has driven the development of peptide-based pharmaceuticals that can meet key challenges of obesity, including control over satiety, blood sugar and LDL cholesterol levels.   

The value of affinity determination in assay development and throughout drug development

The drive to lower drug dosage, improve healthcare and reduce costs has lead to the search for therapeutic antibodies with high target affinity. As a consequence, optimizing and monitoring the specificity and affinity of drug candidates to the target molecule has become critical in the development of therapeutic antibodies – from early screening of hybridomas or recombinant antibodies from phage display libraries, to affinity maturation and antibody engineering to improve the efficacy, safety and manufacturability of the final antibody drug product. Characterizing affinity is also important when selecting reagents for quantitative assays or assessing drug product activity in manufacturing release tests. The question is, how can high affinity be measured in the best possible way?

Minimize incubation times with flow-through immunoassays

Matrix interference can be a major challenge in the development of immunoassays to study a number of disease states. Kathi Williams and her colleagues at Genentech Inc., USA, experienced considerable problems with matrix interference when developing an ELISA for Phase III studies of a humanized monoclonal antibody when a new patient group was introduced. The solution was to transfer the assay to the Gyrolab platform that, thanks to its flow-through technology helped minimizing matrix effects by reducing the incubation times with the capture reagent antibody.

This year, Bioprocess International West brings together attendees from different departments to share challenges and discuss the “solutions needed to improve the speed, lower the cost and increase the quality of biologics development”. We are proud to announce a new system that is aimed at doing exactly that: Gyrolab® xPand.

Singlicate Gyrolab immunoassays prove their worth (again)

In a previous post, ‘How to get it right first time’, we looked at the reliability and reproducibility of Gyrolab™ assays that lead to the idea of running singlicates instead of duplicates (Clark et al, 2016). This publication inspired Hao Jiang and colleagues in a group based at Bristol-Myers Squibb in Princeton, USA to apply Gyrolab technology to run assays of their monoclonal antibody in singlicate in a clinical study. They were encouraged by the results.

Guidance with immunoassays from initial assay design to final validation

The drive to achieve regulatory approval of protein-based drugs quickly and efficiently demands methods that can deliver reliable data to support studies in pharmacokinetics, toxicokinetics, pharmacodynamics, biomarker analysis, and immunogenicity. This need has powered the development of a wide and somewhat perplexing range of ligand binding assays (LBAs) and technology platforms designed to function in a regulated environment, from non-clinical studies to post approval. Added to that, developing an assay that is ready for validation can be a real challenge. If you need guidance in this area then you would do well to read ‘Ligand Binding Assays in the Regulated Bioanalytical Laboratory’, a book chapter authored by Johanna Mora , Charles Hottenstein, and Binodh DeSilva at Bristol-Myers Squibb and GlaxoSmithKline (1).

The extreme reliability of Gyrolab assays

Whatever your needs in immunoassays, you will almost certainly appreciate an assay that consistently delivers high precision and accuracy. Scientists at Pfizer have reported a retrospective study of pharmacokinetics (PK) data that highlights the reliability of Gyrolab assays.