What Are Bioequivalence and Bioavailability Studies?
Bioavailability of drugs is the concentration of the drug compound that reaches the systemic circulation or the site of action.
Most of the medicines or pharmaceuticals consumed orally reach the systemic circulation through the gastrointestinal tract. These drug compounds then enter the site of action through the systemic circulation. Bioavailability of drugs is measured by assessing the active ingredient (API) concentration of the drug and any metabolites in plasma or serum. The API concentration also helps in determining the active ingredient release from the drug compounds along with its absorption, distribution, metabolism, and excretion.
The three primary variables of pharmacokinetic studies used in assessing the bioavailability of drugs are i) maximum concentration of the drug in the systemic circulation (Cmax), ii) time to reach this concentration (Tmax), and iii) time-drug concentration area under the curve (AUC).
If the bioavailability of two drug products is similar, the drug products are called bioequivalent.
Importance of Bioequivalence Studies in Drug Development
A bioequivalence study is usually carried out for generic drug product. The study evaluates clinical differences in the bioavailability of two distinct drugs. These studies are conducted to assess the efficacy of a new drug product which may have a few different excipients or inactive ingredients. Bioequivalence of drugs is evaluated to determine whether different formulations would allow the same amount of active ingredient and efficacy in the body. Bioavailability of drugs is assessed to understand what percentage of a drug gets in the systemic circulation when given through non-intravenous routes of administration (e.g., orally). These studies are essential to appraise the efficacy and quality of the new drug products.
The acceptable bioequivalence is when the 90% confidence interval of the ratio of a log-transformed exposure measure (AUC and/or Cmax) falls entirely within the range 80-125%. When the concentration of a drug compound or its metabolites in the plasma or serum is the same for two drug products, the concentration found at the site of action will also be the same. This indicates the result of the two drugs is similar due to similar concentration. Hence, the bioequivalence study demonstrates the comparable safety and efficacy of a new drug product. The purity and manufacturing process of the final product, however, still must be evaluated separately.
Pharmacokinetic Evaluation
The pharmacokinetic method for assessing the bioavailability of drugs is an indirect method which traces the path of medication from absorption in the body until its excretion. The final assessment reveals the therapeutic index and the optimal dose of the drug. The two methods used under pharmacokinetic evaluation are plasma-level and urine-level studies. In plasma-level studies, the relation between the concentration of drug at the site of action and in the plasma is established. In urine-level studies, the urine is analyzed to assess if the drug has not been metabolized and excreted unchanged. It is necessary to analyze urinary drug levels to measure bioequivalence especially when the drug concentration in plasma or serum cannot be reliably measured.
Pharmacodynamic Evaluation
The pharmacodynamic method is the direct way of conducting bioequivalence study which reveals the physiologic and biochemical impact of drugs on a living organism. The pharmacodynamic study uses two methods for bioequivalence evaluation, therapeutic, and acute pharmacological response. In the therapeutic assessment, we test the relationship between the clinical response when the drug concentration moves to the site of action (or reacts to the symptoms it intends to cure). In the acute pharmacological evaluation, the impact of the drug dosage and concentration on ECG, pupil diameter, EEG, etc., are tested and measured.
Bioequivalence and Bioavailability Studies During Drug Discovery, Preclinical, and Clinical Phases
Drug Discovery
At the time of drug discovery, various compounds of the drugs are assessed for bioavailability. Low bioavailability can be a negative factor due to several reasons. Compound with low bioavailability may not reach therapeutic levels in systemic circulation or require very high dose which may be expensive or toxic. These compounds may require further chemical changes to improve bioavailability. These issues are evaluated during drug discovery, and the compound with good bioavailability and therapeutic value is selected for further development. We assist in the effective execution of these drug discovery studies under the supervision of our skilled scientists.
Preclinical Study
NorthEast BioLab strictly follows mandated regulations for preclinical bioavailability and bioequivalence studies, leading to secure execution and valuable data collection. At the end of preclinical investigations, the safe and efficacious drug candidates are shortlisted for further development.
Clinical Study
Once a drug candidate moves to the clinical phase, a suitable formulation with optimum bioavailability is developed. Since the first study needs to be started with a safe dosage, tablets are prepared with only the low dose levels. As the study progresses, higher doses are administered and found safe. At this stage, it becomes necessary to reformulate the drug with higher API concentration. FDA requires that bioequivalence studies be performed to claim that these multiple tablets of smaller dose are bioequivalent to a single tablet of the higher dose.
Why choose NorthEast BioLab for your Bioequivalence and Bioavailability Studies?
With 15+ years experience in bioequivalence and bioavailability studies, our team at NorthEast BioLab leads the pack in benchmarking and reviewing internal standard operating procedures to keep pace with the dynamic regulatory environment. Our scientists and lab analysts develop and utilize robust bioanalytical methods for evaluating the bioavailability and bioequivalence of your drugs. To illustrate, we regularly fulfill Incurred Sample Reanalysis (ISR) requirement for all our bioequivalence studies to show reliability and reproducibility of your data, as well as seek acceptance from the FDA and other regulatory agencies.