Drug development is an intensively complex process, and bioanalytical testing is an integral step. To be successful at bioanalytical testing it’s essential to understand regulatory guidance as well as make smart choices when selecting suitable chromatographic methods and binding assays.
These methods measure the concentrations of drugs or their metabolites in biological samples such as blood, serum, plasma, urine and tissue samples during preclinical and clinical studies.
Assay Development
Assays must be designed in such a way as to efficiently and quickly assess potential therapeutic agents during early phases of drug discovery, with assays designed to quickly and reliably measure their properties. As the new chemical entity (NCE) advances through preclinical development, robust bioanalytical testing will become increasingly crucial in assessing pharmacokinetic and toxicokinetic properties as it progresses through preclinical development and preclinical trials. Furthermore, assay methods must also work on different sample types and species.
Pharmaceutical companies understand the value in partnering with CROs specializing in bioanalytical assay development, validation, and optimization – especially when working on small molecule or biologic drugs – because this will speed up development times while improving efficiency while providing accurate data to support regulatory submissions.
Integral Component
Assay development is an integral component of bioanalytical analysis, providing vital insight into a new compound’s PK, TK and PD profile. However, many scientists find bioanalytical method development an enigmatic task due to biological matrix’s complex nature that require extensive and often intuitive knowledge for successful navigation. Acquiring and maintaining such expertise within their company can be challenging when moving rapidly between research stages while using new technology such as mass spectrometry.
Assay Validation
Producing new therapies for patients requires extensive effort, and bioanalytical analyses play a crucial role. Delivering timely, high-quality data assists in meeting all milestones required of this endeavor – therefore being highly sensitive analytical techniques are also a necessity for successful development processes.
No matter the sample type – small molecules, peptides, proteins, nucleic acids or cells – bioanalytical methods must be highly sensitive and adaptable enough to accommodate even minute volumes of sample. Swab testing or blood sampling could all require sophisticated bioanalytical tools in order to detect small-volume samples quickly.
Bioanalytical laboratories should adhere to the plans and standard operating procedures established by their sponsor to ensure samples are analyzed appropriately. Bioanalytical reports should include information regarding sample, subject number and dose/treatment group as well as bioanalytical results with associated quality control limits (LLOQs) listed for each run. Furthermore, validation characteristics (accuracy precision sensitivity recovery limit of quantification etc) must also be detailed within each run report.
Analytics
Ensuring accurate analytical results and reproducible methods is essential; validation serves this purpose by ensuring they can be reliably reproduced across runs.
Validation typically involves three levels of evaluation: full validation, partial revalidation and cross-validation.
Validating an assay requires taking into account various factors, including the type of sample used, its composition and assay method; target analyte; biological matrix; interference caused by concomitant medication peaks etc. For instance, when testing NCEs using chromatographic assay, flexibility in terms of their adjustment is a must in order to effectively validate an assay.
Due to increased focus on pharmacokinetics and toxicokinetics and increased potency of newer drugs, it is critical that your bioanalytical methods are sensitive and precise. With modern technology easing workflows and producing validated assay data quickly, your assay data production can meet project goals more quickly while meeting regulatory body expectations for quality data delivery.
Assay Optimization
Highly accurate and precise bioanalytical methods are key components of drug development. Unfortunately, meeting project milestones on time can be challenging when working with complex sample matrices or multiple assays that must run simultaneously. Optimizing assays to ensure maximum performance can help decrease overall time needed to perform PK and PD analyses while simultaneously producing results that are robust, reproducible and statistically sound.
Attaining these objectives requires an in-depth knowledge of drug effects and their relationships to various variables such as cell environment, cell line variation, reagents, and sample handling procedures.Â
Testing various combinations
Assay optimization involves iteratively testing various combinations of assay variables until finding one which achieves your desired result. While this process can be both laborious and time-consuming, automating assay reagent preparation, incubation time tracking and data recording can greatly streamline this task while increasing accuracy while shortening assay completion timeframes.
After discovering an optimal bioanalytical method, the method must undergo validation to demonstrate its suitability for its intended use. During this step, the analytical method undergoes stringent experimental conditions to test whether it can consistently and reproducibly measure concentrations of drugs and their metabolites within a specific biological sample matrix from specific species.
Assay Integration
Bioanalytical assays play an integral role in drug development by helping researchers evaluate pharmacokinetic and pharmacodynamic parameters of new chemical entities (NCEs) from discovery through preclinical development to clinical studies, providing researchers with essential data necessary to meet regulatory requirements and ultimately gain approval for their drug products.
Testing results must be accurate, precise, and reproducible if you want accurate, precise, and reproducible results from any target or unwanted substances testing.
Successfully accomplishing this task involves developing and utilizing robust assays, and then validating them against specific sample matrices.
Biological Matrices
Bioanalytical laboratories must consider “pre-analytical variables” that could impede assay performance when utilizing NCEs in multiple biological matrices. This includes addressing factors such as tissue quantity requirements, the chosen sample collection method (needle aspiration vs core biopsy), storage and shipping logistics across multiple sites or internationally during clinical trial duration, matrix effects on assay results, and establishing an appropriate limit of detection for clinical application of the assay.
Validation forms an essential part of quality control system in laboratories, helping ensure data generated are accurate, precise, and repeatable.
For bioanalysis in clinical settings, using a surrogate matrix is key to ensure its robustness and clinical utility. When selecting your surrogate matrix it should not compromise assay performance – for instance pure water, PBS buffered solution or organic solvents like methanol or acetonitrile should not negatively affect assay results.
In the realm of drug development, the significance of bioanalytical services, such as those offered by SpinoS, cannot be overstated. These services, encompassing assay development, validation, and optimization, form a critical backbone for evaluating pharmacokinetic and pharmacodynamic parameters. SpinoS excels in providing accurate, reproducible, and regulatory-compliant bioanalytical solutions, contributing indispensably to successful drug development endeavors
