State-of-the-Art Bioanalytical Testing
Bioanalysis is an indispensable component of clinical drug development, as it contributes to the pharmacokinetic and pharmacodynamic characterization of novel chemical entities (NCEs). The term bioanalysis encompasses identifying and quantifying different analytes in biological matrices.
Within clinical trials, the examined analytes include NCEs, their metabolites, and can also include potential biomarkers. The biological matrices analyzed in clinical drug development also vary and may consist of blood, plasma, serum, urine, tissue extracts, or cerebrospinal fluid.
The biopharmaceutical properties (such as solubility, permeability, or stability) or pharmacokinetic properties (such as volume of distribution, biological half-life, or clearance rate) of NCEs regulate the extent and rate at which NCEs reach their site of action.
Accordingly, poorly selected biopharmaceutical or pharmacokinetic characteristics are major factors contributing to the failure of clinical drug candidates. The competent and timely implementation of bioanalytical services in clinical trials contributes to the biopharmaceutical and pharmacokinetic characterization of NCEs and empowers timely decisions for clinical drug development.
Bioanalytical Assay Validation
The bioanalytical assays used in clinical trials should be validated. Still, the specific validation requirements may vary depending on the trial’s phase and purpose (a concept known as fit-for-purpose validation). Clinical studies that will be included in filings to regulatory agencies such as investigational new drug applications (INDs), new drug applications (NDAs), or abbreviated new drug applications (ANDAs) to the United States Food and Drug Administration (FDA). The studies require the use of assays with the highest degree of validation. However, exploratory studies may require a lower degree of validation.
Bioanalytical assays should be validated with respect to their analytical and clinical aspects. Analytical assay validation is the most important component of the assay validation process. As a part of it, the assay’s sensitivity, specificity, accuracy, precision, and quantification range should be determined and characterized.
In addition, the effects of dilution, the stability and recovery of the analyte, and the performance of critical reagents, reference standards, and quality controls should be evaluated carefully. After the analytical validation is completed, the relevance of the assay for the clinical outcome of interest and its clinical utility should be assessed.
* The back-up capacity and the alarm system of the freezers storing the samples should be maintained. In addition, all associated documentation that efficiently records and tracks the sample collection, storage, and stability should be preserved.
** The most widely accepted method is probably HPLC coupled with tandem MS (HPLC-MS/MS). Other methods may include HPLC coupled with MS (HPLC-MS), GS coupled with MS (GC-MS), or GC coupled with tandem MS (GC-MS/MS).
Bioanalytical Testing in Early-Phase Clinical Trials
During early-phase clinical trials, the pharmacokinetic disposition of an NCE is evaluated most frequently in normal human volunteers (NHVs). This may include an evaluation of single or multiple doses, an assessment of the relative bioavailability of different formulations, and an evaluation of a food effect potential. The characteristics of early-phase clinical trials pose special requirements to bioanalytical assays used during this stage of drug development.
Developing Robust Bioanalytical Assays for Spsonsors
The robustness of the bioanalytical assays used in clinical trials should be verified to empower reliable data collection.
Sufficient Sample Stability
A demonstration of sample stability is a critical component of bioanalytical method validation. Sample stability (most commonly under frozen conditions) for a sufficiently long period of time is required for bioanalytical assays included in early-phase clinical trials. The stored samples may be used as back-up samples or for potential reanalysis.
Optimizing Assay Turnaround & Throughput
Designing assays with rapid turnaround times and high throughput would facilitate timely decision-making regarding dose escalation.
Ensuring Assay Suitability Quantification Range
It should be confirmed that the sensitivity range of the assay is relevant to the NCE concentration expected to be achieved in the trial or to the expected concentrations of potential metabolites.
Integration with the Expertise of a Full-Service CRO
Our bioanalytical services are fully integrated into the comprehensive solutions for early-phase clinical trials offered by BioPharma Services. The bioanalytical scientists, clinicians, and regulatory scientists in our team collaborate closely with each other. This multidisciplinary approach enables us to select the most suitable bioanalytical assays for our clients’ early-phase clinical trials to facilitate clinical decision-making during the drug development process and to support regulatory filings.
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