Bioanalysis is the quantitative measurement of drugs and their metabolites in the biological fluids. This technique is used early in the drug development process to support drug discovery programs on the metabolic fate and pharmacokinetics of chemicals in living cells and animals. Its use continues throughout the pre-clinical and clinical drug development stages, into post-marketing support, and might occasionally extend into clinical healing drug monitoring.
The bioanalysis role in medicinal drug development is discussed, centering on the actions executed within each phase of the development procedure and the range of sample preparation conditions encountered. Latest developments along with industry trends for speedy sample throughput and data generation are brought together, with examples of how these high throughput requirements are being met in bioanalysis.
The emergence of the field of bioanalysis as a critical tool during the process of drug discovery and development is well understood and internationally accepted. Over the past few decades, various assays have been constantly developed for NCEs to support numerous stages of discovery and development, including assays for essential metabolites.
Moreover, numerous analytical techniques are accessible for generic products and prescription medicines (Rx). Bioanalytical data produced in discovery, as well as pre-clinical programs, are an important guide to initial clinical programs. Plasma concentration-response information from these programs could be compared with those found in humans. Such comparisons are mainly valued during the stage one-initial dosage escalation study. To make the most of this, it is our practice to produce PK data between each dosage increase.
New medication compounds are tested for their effectiveness and safety. The majority of therapeutic molecules, however, don’t make it through the next drug development stage due to issues with efficacy and safety that can’t be explained by their PD features alone. The drug’s clearance rate, biological half-life, protein binding level, and distribution volume all play important roles in determining how quickly and how much the medication reaches its site of action or biophase.
Bioanalytics in the Drug Development
How Significant Are Bioanalytical Studies For New Biologics?
When making new biologic molecules, cautious analysis is required to regulate the dosage, toxicology, safety, and effectiveness factors. Without bioanalytics, critical data points might be missed from new medication development, leading to time and money being lost. Beyond the function of the drug itself, bioanalytics provides vital information to regulatory bodies that could also accelerate development or kill potentially dangerous drugs faster, enabling scientists to move on or alter their drug.
Why Is It Imperative To Conduct Bioanalytical Studies During Development Procedure Of A New Biological Therapeutic?
Compared to new chemical entities (NCEs), well-timed delivery of the nonclinical programs to back first-in-human (FiH) studies for Advanced Therapies and Biologics needs a much closer interaction between bioanalytical and toxicology teams. Therefore, an early understanding of the bioanalytical endpoints is important, as these often impact the design of toxicology studies.
The intelligent design of bioanalytical studies is critical in developing biological treatments. The bioanalytical stages of a development program support defining and shaping vital safety studies along with decision-making. As the analytical support for biologic development is frequently platform diverse or more nuanced than a typical NCE development, engaging with the bioanalyst or hiring Bioanalytical Service as early as possible and throughout the development program is important.
What Type Of Information, In Particular, Does The do FDA Require From Bioanalytical Studies?
All bioanalytical techniques must be fit for purpose. The published guidance clarifies method validation expectations for ligand binding and chromatography assays. A challenge for Advanced Therapeutics and Biologics programs is that there is usually a requirement to use bioanalytical methods not covered by this guidance; PCR, flow cytometry, or ex vivo/in vitro culture systems. The clear documents of the development stage are often of increased importance as key data that informs the validation approach is often derived from this phase.
All governing bodies need bioanalysis to robustly answer the challenging questions posed by drug development. In 2018, FDA published refreshed directions about bioanalytical method validation for chromatographic and ligand binding assays. Although this is a great set of guidelines for supporting routine bioanalysis, challenges remain for other bioanalytical disciplines, for example, molecular biology or immunology.
Regulatory authorities expect robust program decision-making underpinned by high-quality data in these cases. In this respect, initial engagement with controlling authorities and bioanalytical workforces versed in current best-practice is invaluable in developing strategies for biological treatment development.
What Methods Or Approaches Are Best To Plan Early In The Drug Development Process?
For any bioanalytical technique, whether it is classified as pharmacodynamics (PD), pharmacokinetics (PK), or biomarkers, the earlier in the drug development process that the necessary measures for each assay are determined, the better. This includes the availability of reference standards, identification of the analytes, the experimental platform, and considering the biological transport of the molecules. Seeking early input from external partners can also simplify decision-making, even when internal capacity exists.
Drug development is a complex and long process. Early discussion with bioanalytical workers to design the analytical support is important to ensure programs can be delivered efficiently and effectively. The program design, the analytical platform, the analyte itself, and the sourcing of reference standards are all examples where a partnership between bioanalysts and drug developers will produce program benefits.
The need for rigorous Bioanalytical Service/procedures is well understood and valued in the discovery stage and throughout drug development’s pre-clinical and clinical phases. Hence, it is usually accepted that sample preparation and process validation are essential to the analytical results’ reliability and exhibit the method’s performance.
The acceptance measures must be established in a validation design before the commencement of the validation study. The established assay should be necessarily rugged in that it delivers opportunities for minor changes and/or ease of flexibility to suit other bioanalytical requirements, such as applicability to a toxicokinetic study, drug-drug interaction study, and characterization of the plasma levels of the metabolites.