CRO Diaries: The Bioanalytical Assay Development To Adopt When Screening A Potential Drug Candidate

Bioanalytical studies involving the qualitative and quantitative evaluations of biological products are critical for understanding disease mechanisms and progression in drug discovery and development. Technological advancements over the years have made significant progress in bioanalytical sciences. These advances have made bioanalytical assay development and validation the center of drug discovery, drug DMPK properties, and toxicological assessments. In addition, improvements in conventional techniques such as mass spectrometry, genomic assays, and high-throughput sample analysis have helped bioanalytical studies meet the increasing demands of clinical and preclinical pharmaceutical needs.

High-throughput screening is one promising method used for screening a potential drug candidate. High-throughput screening (HTS) employs detectors, robots, and software to streamline the whole drug screening process. HTS analyzes numerous chemical compounds in a short period and evaluates the affinity of biological composition, which is necessary to determine drug toxicity. However, HTS assay method validation will need to address crucial validation parameters for reliable assay results. So let us dive deep into HTS assay development for screening drug molecules.

HTS assay development for screening a potential drug candidate

Over the last 2-3 decades, HTS has become a routine analysis in clinical and preclinical studies. Today it is commonly employed by both industrial scientists as well as academicians. HTS screens and assays multiple biological effectors and modulators against specific targets. HTS can screen different libraries, including genomics, combinatorial chemistry, and peptide libraries.

The primary advantage of using the HTS technique is that it accelerates the drug discovery process by screening a couple of thousand compounds per day or week. This combinatorial and parallel data processing generates substantial data to identify several novel drug compounds. HTS can also help bioanalytical scientists uncover crucial pharmacokinetic, metabolic, and toxicological drug data. In addition, HTS is comparatively less costly for drug development. The fundamental steps of the HTS technique include target identification, compound management, assay development, reagent preparation, and high-throughput library screening.

Highly dense micro reaction plates are increasingly used in clinical and pharmaceutical drug discovery studies. Initially, these plates had 96-wells, but today they are replaced by microplates with 1586-wells in each assay plate. These microplates need an average of 5μL samples per well. Despite the availability of highly dense microplates, current studies are moving towards further miniaturization, with research reporting the use of 3456-well microplates. Such enhanced miniaturization means scientists can screen up to 10,000 compounds a day. Furthermore, Ultra-HTS can perform even 100,000 assays a day. 

HTS testing is performed in two steps, primary and secondary screening. Primary HTS testing is less quantitative than biological tests. Once a compound gives a positive HIT, researchers subject the potential compound to more specific secondary screening. However, HTS assay reagents should be optimized and remain uncontaminated. For this reason, bioanalytical scientists often use Aptamers in HTS analysis.

Conclusion

Currently, most bioanalytical techniques are moving towards automation and miniaturization. The miniaturization of bioanalytical techniques has made companies focus on laboratory-on-a-chip technology. Advances in automation and miniaturization will help reduce costs and resources and ease the difficulty of transport and space requirements. Hence, employing advanced techniques such as HTS will help sponsors screen potential drug compounds.

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