Guidance On The Bioequivalence And Bioavailability For Drug Discovery

Bioavailability and bioequivalence studies play key roles in the development of new drugs as well as their generic equivalents. They form important characteristics of any drug during discovery, trials, and usage. Bioavailability denotes the fraction or percentage of a drug from an administered dosage, which enters systemic circulation. The rate of the appearance of said drug is also a part of bioavailability.

Bioavailability varies by the form of administration of the drug. Bioavailability is 100% for a medicine administered intravenously. It drops when employing other methods of administration, such as oral use. This is due to factors like incomplete absorption, first-pass metabolism, and other factors that vary from patient-to-patient.

Bioequivalence forms a comparative study of two drugs of the same dosage and form for the same bioavailability. This study forms the basis of comparison between two drugs from different companies that have the same active component. It’s also important to the comparison of generics and branded medicine. The comparison decides if the drugs can be considered to be therapeutically equivalent and/or interchangeable.

Both of these play an important role in understanding the pharmacokinetics of a drug and thus impact drug discovery. Comprehensive in vivo studies and tests are required for both these processes, with bioequivalence needing a greater focus.

Working on Drug Discovery

A very important application of bioavailability and bioequivalence studies is in the field of generics and drug development. As a drug product goes off-patent, an abbreviated new drug application (ANDA) for generic approval. These products have to be identical to the origin drug in the form of formulation, dosage, strength, route of administration, and active ingredients.

Bioanalytical method development is important to demonstrate the intended effects during drug development. This is usually achieved by using a blood plasma study using a graph that represents serum concentration versus time. Peak plasma concentration (max) and the time of peak plasma concentration (Tmax) must be gathered. Other pharmacokinetic data may also be used as part of analytical testing to establish bioequivalence.

Taking a similar route, bioavailability has become a very important aspect of early drug discovery. In recent years, using bioavailability as a factor in early drug development has gained more traction. A favored view is using bioavailability as a factor in early drug development, rather than waiting for clinical trials and in vivo results. This is a way to reduce attrition as most drugs fail at the clinical stage.

By employing bioavailability and bioequivalence studies in the early stages of drug development, collected data can narrow down the list of possible candidates. Many clinical drugs do not fail because of their efficacy. The negative factor in these cases is often related to toxicology and ADME (absorption, distribution, metabolism, excretion) aspects.

Given that bioavailability deals with such factors, there is a possibility of success rates improving. With potential drug candidates already going through toxicology and ADME tests at an early discovery stage, associated investment in time and costs can come down. Measurements of bioavailability in such cases may be done through several methods, including in-vitro dissolution and in-vitro in-vivo correlation.