Gyrolab Spin Blog

A generic detection reagent makes all the difference

Pharmacokinetic (PK) studies of therapeutic proteins in early preclinical development demand great flexibility in bioanalytical methods. This is a real challenge during lead candidate selection when, for example, limited amounts of specific reagents must be labeled for immunoassays. Gregor Jordan and his colleagues at the Pharma Research & Early Development (pRED) department at Roche in Munich, Germany saw the advantages of transferring their ELISAs to the Gyrolab™ platform – low reagent consumption, semi-automation and fast assay turnaround – but wanted to go one step further in conserving critical resources. They therefore developed a generic detection reagent that would allow them to use the same antibody reagents on both ELISA and Gyrolab platforms.

Gyrolab system delivers

Determining the immunogenic potential of a therapeutic antibody is a regulatory requirement during clinical development since anti-drug antibodies (ADA) can cause undesirable effects, ranging from loss of drug exposure and efficacy to serious adverse events. Justine Brose and her colleagues at Novimmune SA, Geneva, Switzerland evaluated four platforms to determine which platform and sample pre-treatment procedures could deliver a fit-for-purpose assay for ADA analysis to determine the immunogenicity of the therapeutic antibody Novimab. Of the platforms tested (ELISA and Gyrolab, Meso Scale Discovery, and AlphaLISA platforms) only Gyrolab and MSD platforms met all of their pre-specified assay requirements.

Gyros’ technology overcomes matrix effects in a Phase III PK assay

It is not unusual for a pharmacokinetics assay used early on in a study proves to lack the robustness needed to see the drug candidate through to more advanced clinical studies. A team at Genentech experienced just that and they solved the problem by transferring their ELISA to the Gyrolab platform.

Review of critical factors, analytical methods and experimental approaches

Therapeutic proteins have revolutionized the treatment of many diseases and have a promising future with more than forty monoclonal antibodies and Fc-fusion therapeutics already on the US market and over 400 more in clinical development stages. Therapeutic proteins are, however, hit hard by a high attrition rate, mainly to poor efficacy, which results in only one in ten making it to market. Increasing the success rate relies on many factors, including the study of absorption, distribution, metabolism and excretion (ADME), as Jay Tibbitts at UCB Celltech, UK, and his coauthors point out in their extensive review on the subject.

High-throughput immunoassays underpin efficiency and productivity

Automation is being applied at many levels to power future development of recombinant therapeutic proteins, including screening for the most promising recombinant protein clones. Gregory Keil and co-authors at Merck & Co. have reviewed how this screening can be transformed by combining high-throughput screening methods, analytical techniques and automation to increase capacity, reduce manual operations and risk for error, lower operational costs, and shorten development timelines (see reference).

Matching scale-down high throughput screening with efficient analytical methods makes the most of precious material

Combining high throughput and small-scale purification methods is a key strategy in bioprocess development. John Welsh and his colleagues at Merck & Co. Inc, USA could develop three orthogonal purification steps using less than 200 mg of a domain antibody fragment, orders of magnitude less than what would typically be required for process development. 

The value and challenges in using ligand-binding assays to analyze Antibody-Drug Conjugates

Antibody-Drug Conjugates (ADCs) offer great potential in directing therapeutic agents directly to the target, but the complexity of their structure and dynamics in vivo present many bioanalytical challenges. In a recent review article, Seema Kumar and her colleagues at Pfizer Global R&D in the USA present a comprehensive analysis of how Ligand Binding Assays (LBAs) can be used in ADC analysis in preclinical studies.

Analyzing challenging matrices

While many preclinical and clinical studies require analysis of plasma, serum or blood, some involve more challenging matrices, such as vitreous and aqueous humor, tears, synovial fluid, and bronchoalveolar lavage. These matrices often have high viscosity, high protein concentration and low analyte concentration. Added to that, the samples are almost invariably very small, expensive and difficult to source. Analytical methods must therefore match the matrix’s complex qualities and also the small volumes available. 

Anti-Drug Antibody analysis dominates the Gyrolab related posters

The AAPS National Biotechnology Conference, held June 8–10 in San Francisco, USA, was presented as THE pharmaceutical biotechnology meeting. The conference certainly generated a high concentration of scientists from the pharmaceutical and biotechnology industry, ready to network and find out about the latest developments in science and analysis platforms. Gyros Inc. was there with Gyrolab xP workstation and Gyrolab xPlore and we enjoyed a lot of activity at our booth, supported by five independent posters presented during the meeting. Four of these focused on Anti-Drug Antibodies (ADA):

May 14-15, San Francisco, USA

Reliable HCP assays that confirm low levels of Host Cell Protein impurities in your biological drug can be crucial to achieving regulatory approval. With this in mind, Biopharmaceutical Emerging Best Practices Association (bebpa.org) hosted a two-day conference/workshop dedicated to the development, validation and use of HCP assays.