5 Factors That Impact A Bioequivalence Study During Drug Development

Two drug products are considered bioequivalent when they don’t have significant differences in their bioavailability. However, what is bioavailability? Bioavailability is the rate and extent to which a drug compound is absorbed into the systemic circulation and presents itself at the site of action. Hence, bioavailability testing is a core component of bioequivalence analysis. Although bioequivalence clinical trials are often associated with generic drugs, there are certain situations when researchers conduct bioequivalence studies for brand-name drugs. These scenarios include:

  • Between different formulations used in trials and the marketed product or between early and late trial formulations.
  • Post-marketing changes of a brand name drug. For example, when changes are made in excipients.

Bioequivalence studies are surrogate trials, as clinical studies usually are  not needed for generic products. For oral drug products, similar blood concentrations of the generic and reference-listed drugs are generally accepted. For other dosage forms, researchers demonstrate bioequivalence through comparative testing such as pharmaceutical properties and comparative pharmacodynamic studies coupled with comparative bioavailability studies. Thus, bioequivalence assays are crucial elements of the drug discovery workflow of generic products. Hence, it is critical to comprehend the factors influencing bioequivalence studies. The current article highlights five factors impacting bioequivalence studies in different steps of drug discovery and development processes.

Acceptance criteria

AUC and Cmax are crucial components of bioequivalence studies. The AUC and Cmax of generic drugs and the reference-listed drug must not have a difference of more than 20%. The 90% confidence interval for the AUC ratio and Cmax ratio should lie between 0.8 to 1.25. In practice, mean value ratios must be close to 100% so that the upper and lower limits are within the range.

Healthy vs. patient population

While developing a brand-name drug, sponsors test them in both healthy and patient populations. However, this is not the case for generic products. Generic drugs are tested only in a healthy population. Hence, the safety and efficacy of a generic drug in the patient population often raises concerns. However, scientifically the brand name drug and the generic drug have similar active ingredients, and therefore, they will have similar biochemical responses.

Potential effects of excipient

Bioequivalence studies are usually single-dose studies. Hence, excipients in the generic formulation could behave differently in steady-state studies. However, this is highly unlikely. The potential difference observed is comparatively negligible to the differences produced due to variability in the GI tract of patients.

Adverse effects of excipients

An individual may have some reactions when switching between a generic and brand-name drug. However, these situations are rare. Generally, these reactions are caused due to intolerance or allergy, such as lactose intolerance. Hence, if individuals are aware of their intolerance or allergy, they should check the datasheet to confirm the presence of any allergens or intolerances.

Non-interchangeable medicines

Certain limited medicines such as phenytoin, digoxin, and carbamazepine have a narrow therapeutic range, and any minute variation in systemic concentration can cause toxicity or altered therapeutic response. Hence, individuals should never change between different brands of these medicines.

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