An increased presence of bioanalysis is seen in all aspects of drug discovery. Bioanalytical methods are used for drug discovery and introduction of NCE, all the way to market authorization. In the modern environment, it is conventional for pharmaceutical companies to employ a bioanalytical lab or CRO for bioanalytical analysis.
Bioanalytical assays form a key role in this process. A robust assay and its validation provide quantitative information related to xenobiotics and biotics in a biological system. Validation can also provide information on the validity and efficacy of a proposed drug.
Guidelines and Applications of Bioanalytical Assays
In the initial stages, assay development can focus on finding a New Chemical Entity (NCE). There is a fair amount of complexity involved in each stage, and assay development itself can be fairly challenging. Automation, in silico, and in vitro methods find use as the means of reducing cost and time investment while increasing efficiency.
It is quite common to use non-GLP methods in the earliest stages to speed up the process. However, any candidate submitted to the FDA, as a New Drug Application (NDA), must follow Good Lab Practices in pre-clinical trials.
Since bioanalytical assays play a central role in development and validation, the FDA has released method development guidelines. These guidelines lay the groundwork for assay validation and development. Additionally, method validation ensures the reliability of the data provided.
As part of preclinical studies, bioanalytical ADME assays find use in testing pharmacokinetic, pharmacodynamic, and toxicokinetic profiles of the drug. A mix of in vivo and in vitro studies can be conducted to analyze and validate the assays. These preclinical studies generally employ animal subjects and the results are useful for developing safety, efficacy, and toxicity profiles for a drug before it enters the clinical phase of the trial.
Depending on the goals and requirements, a bioanalytical lab may use several types of assays. These include:
- LC-MS-MS assay
- ELISA assay
- Biomarker testing assay
- Immunogenicity testing assay
- Cytotoxicity testing assay
- ADME assay
- Cell-based proliferation viability assay
- Other assays, as necessary
Assay Validation, Drug Safety, and Efficacy
As is seen above, bioanalytical assays play a key role in drug development. They find diverse uses, starting with lead selection and NCE, all the way to safety profiles and drug efficacy in clinical trials. Full assay validation that follows bioanalytical method validation (BMV) is important for preclinical and clinical trials.
To achieve these goals and follow diverse requirements, there has to be a thorough understanding of the study goals. A fairly large number of assays is available to researchers. A good method avoids being wasteful with assays and uses fit-for-purpose assays that match study requirements. Customized assays may be used depending on the needs and case-to-case basis.
The use of an assay can change with the stage of development. The requirements related to robustness, reproducibility, and sensitivity of an assay form the basis of the bioanalytical process. For example, robust assay development and validation during preclinical studies help translate the data so acquired into requirements for human use. Setting a safe dose for humans and monitoring the efficiency and possibility of toxic/adverse side effects depend on useful development and validation of bioanalytical assays.