One of the earliest stages in the drug discovery process is the development of assays that can be used to evaluate the effects of chemical compounds on cellular, molecular, or biochemical processes of interest. Since these assays will form the basis of programs that may run for many years, it’s essential that they are not only specific and reproducible, but they should also be cost-effective. While many researchers perform their own assay development in-house, the process can be extremely time-consuming, tying up valuable internal resource for prolonged periods of time. To overcome this issue, many companies are instead purchasing commercially available assay development tools or outsourcing their assay development process to specialized service providers, with the aim of streamlining drug discovery and driving much-needed pharmaceuticals more quickly to market.
With a vast range of assay types available, researchers are spoiled for choice when it comes to selecting a format to meet their requirements. In some instances an ELISA might be appropriate whereas other options include, but are not limited to, fluorescence polarization, high content immunocytochemistry, and proximity-based assays such as FRET.
According to Clive Mason, director of biology at Discuva, a good assay will meet certain criteria irrespective of the format that is used. “For an assay to fulfil its function of generating data to support a hypothesis that the modulation of a drug target will produce a therapeutic effect, it should be reproducible across assay plates, screening days, and indeed for the entirety of the drug discovery program,” says Mason.
It’s essential to fully evaluate the pharmacological relevance of the assay as early as possible in the drug discovery process.
“Preferred assays tend to utilize simple protocols with few steps, as well as employ stable reagents and rely on instrumentation that demonstrates optimal performance as a result of regular maintenance and quality control measures. Furthermore, it’s essential to fully evaluate the pharmacological relevance of the assay as early as possible in the drug discovery process.”
The vast majority of screening assays are reliant on the use of antibodies, therefore appropriate validation of these reagents is critical to the sensible interpretation of data. Antibodies are extremely powerful building blocks for research, diagnostics, and therapeutics, and significant advances are antibody dependent making their validation paramount. David Chimento, vice president of client solutions at Rockland Immunochemicals, explains that antibody validation involves three antibody properties: the antibody’s sensitivity for the target, its specificity for off-target binding, and reproducibility of results.
“In order to generate reproducible assay results, the properties of any antibody reagents should be consistent from lot to lot,” says Chimento. “Validation of antibodies is immunoassay specific, and here at Rockland we validate the performance of our antibodies in the assay formats that are most commonly used by researchers, including ELISA, Western blotting, and immunohistochemistry. The inclusion of positive and negative controls at every stage of the antibody production process ensures that the correct protein is being targeted, and since our QC standards require the highest possible specificity for antibodies, we deliver unsurpassed reproducibility and minimal lot-to-lot variation in our antibody products.”
Rockland Immunochemicals is a strong advocate for immunoassay-specific validation of all research antibodies and for transparency in how these antibodies are produced, validated, and intended to be used. This is best accomplished by providing the end user with information regarding the nature of the immunogen, the antibody screening criteria during the development process, and the validation release criteria for every lot of antibody produced.
External service providers
When timelines are tight or resources are stretched to the limit, it can be immensely beneficial to hire an external service provider for assay development. Astarte Biologics offers an extensive suite of assay capabilities covering the spectrum of immune cell functions and prides itself on fast turnarounds to keep its clients’ studies on schedule.
“Our scientists have over fifty years of combined experience researching immune cells,” says Anne Lodge, founder and CEO. “Our state-of-the-art laboratory has all the technology and equipment you’ll need and because we’re also a leading provider of immune cell products, we have all the cells, reagents, and protocols required for proof-of-concept experiments. Whether you need a complete outsource research team or want to expand your in-house capacity, our scientists will help you meet your research deadlines with detailed documentation.”
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Charles River Laboratories International offers products and services spanning the entire drug discovery and development continuum, including a range of assay development options. Ian Waddell, executive director of biology, explains that the company’s dedicated assay development service affords access to cutting-edge technology platforms and expert knowledge.
“Our scientists advise and help our clients with all stages of the drug discovery process, across all major therapeutic areas, and this includes development and implementation of relevant and cost-effective assays for screening or evaluation of chemical or biologic compounds. We develop and execute hundreds of customized cell-based assays every year, covering an extensive variety of target classes, and have expertise in developing biochemical and cellular assays for ion channels, epigenetic protein targets, kinases, G-protein coupled receptors (GPCRs), protein-protein interactions, and more.”
Assay development remains a cornerstone of the drug discovery process. Irrespective of whether it is performed in house or is outsourced, the production of safe and effective pharmaceuticals is dependent on assays that are sensitive, specific, robust, and reproducible. With an ever-growing range of high-quality reagents, assay development tools and specialist service providers available, assay development will continue to remain fundamental to drug discovery.
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