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Before reaching the market, an innovator drug must clear various clinical trials. These drugs also have several patents and thus have a high market price. When an innovator drug goes off-patent, pharmaceutical companies can manufacture the same drug (or drug formulation) as a generic drug. These drugs do not require extensive clinical trials, consequently, are available at lower prices than the innovator drugs. But the approval and acceptance of a generic drug are based on other studies which can establish an equivalence between a generic drug and its corresponding innovator drug.
Bioequivalence study
Bioequivalence studies compare generic and the innovator drug. According to the bioequivalence definition by the US FDA, bioequivalence means that the bioavailability of two pharmaceutical ingredients at the site of action does not differs significantly, under the same doses and similar conditions. Bioequivalence suggests that both drugs have similar bioavailability and pharmacokinetics/pharmacodynamics (PK/PD) parameters. The bioavailability testing of an active ingredient measures the rate and extent of its absorption into the systemic circulation and availability at the site of action. After all the in vivo and in vitro studies, bioequivalence clinical trials examines the two sets of data obtained for the generic and the innovator drug.
Bioavailability and bioequivalence (BABE) study in clinical research
BABE studies can predict the fate of new or generic drugs in early clinical trials. Moreover, any changes in the formulation of a drug during clinical trials require BABE analysis. Here, the changed formulation is taken as a new drug while the old formulation is regarded as the reference drug.
Risk evaluation and mitigation strategies for bioequivalence studies
Bioequivalence studies are mostly in vivo tests, performed either on healthy human volunteers or patients, thus, have various risks associated with it. Though bioequivalence studies are simple and less stringent than a patient-based clinical trial, compliance with safety guidelines and evaluating and mitigating risk factors is of utmost importance.
In bioequivalence studies, risks are associated with the safety of the drug and the conduct of the tests. For example, the drug can show adverse effects on human volunteers, faults or errors during sample preparation, storage, and delivery, or mismanagement of safety issues. Therefore, a plan is needed for the evaluation and management of risks during bioequivalence studies.
Risk evaluation and mitigation strategies (REMS) is a formal plan that considers the risks associated with the drug and management strategies to minimize the risk. It is an iterative process. The benefit-risk balance is assessed followed by the development and implementation of strategies to reduce the risk factor. The improved risk-benefit balance is reassessed, and the required adjustments are made to further minimize the risk. This process is repeated until no further improvement can be made. However, in the end, the benefits of the drugs should outweigh the associated risk, and the risks that persist must be manageable.
Conclusion
What does bioavailability mean, Pharmaceutical companies should understand and work upon the risk evaluation and mitigation strategies (REMS) during bioequivalence studies to strengthen their assessment reports for a generic drug or abbreviated new drug application (ANDA).
