Clinical significance of bioequivalence study.pptx

M.Pharm 2nd semester

1. Clinical significance of bioequivalence study Submitted by, Submitted to, Mohd Sufiyan Dr. Poonam Kushwaha M.Pharm (Pharmaceutics)

2. Bioequivalence It is a relative term which denotes that the drug substance in two or more identical dosage forms, reaches the systemic circulation at the same relative rate and to the same relative extent i.e. their plasma concentration-time profiles will be identical without significant statistical differences . When statistically significant differences are observed in the bioavailability of two or more drug products, bio- inequivalence is indicated. The absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.

3. Clinical Significance

4. Products Require BE Studies Products requiring be studies are mainly drugs with narrow margin of safety, e.g . digoxin, antiarrhythmic, anticoagulants, cytostatics , lithium , phenytoin, cyclosporine, sulphonylureas , theo - phylline critical use drugs, i.e. drugs indicated for serious conditions requiring assured therapeutic response, e.g. antiinfectives , cardiovascular drugs, antiepileptics , antiasthmatics ; and sustained or modified release products, due to the difficult formulation.

5. Drug Interchangeability In practice, bioequivalence in drug absorption has been interpreted that the confidence interval for the ratio of means (of drug absorption) is within bioequivalence limits. The FDA, however, does not indicate that approved generic drug products and the innovative drug products can be used interchangeably. The FDA only indicates that an approved generic drug product can be used as a substitute to the innovative drug product. Basically, drug interchangeability can be classified either as drug prescribability or drug switchability

6. Comparing Generic and Innovator Drugs Bioequivalence (BE) study is required to show whether a generic copy product can be interchangeable with the brand innovator product. E.g.: BE studies of clopidogrel generics : Clopidogrel is a prodrug that must undergo hepatic metabolism to become the active metabolite. The active metabolite is highly unstable and thus difficult to measure. Therefore, the BE study of clopidogrel may be a pharmacokinetic study or a pharmacodynamic study. The pharmacokinetic BE study of clopidogrel is based on the measurement of clopidogrel parent compound.

7. Drug Formulations Bioequivalence for most of oral tablets or capsules is demonstrated in vivo by comparing the rate and extent of absorption that is bioavailability of the generic product with that of the innovator product. This is done by measuring the active ingredient concentration in blood, plasma, serum or other biological fluids over a certain period of time for both the generic and innovator products, also called test and reference drugs respectively. By doing so the bioequivalence studies frequently rely on pharmacokinetic measures such as area under the concentration-time curve (AUC) and peak drug concentration ( Cmax )

8. Drug Development Bioequivalence studies are very important for the development of a pharmaceutical preparation in the pharmaceutical industry . Their rationale is the monitoring of pharmacokinetic and pharmacodynamics parameters after the administration of tested drugs . The target of such study is to evaluate the therapeutic compatibility of tested drugs (pharmaceutical equivalents or pharmaceutical alternatives).

9. Clinical Interpretation Clinical interpretation is important in evaluating the results of a bioequivalence study. Bioequivalence studies should be conducted for the comparison of two medicinal products containing the same active substance. Two products marketed by different licensees, containing same active ingredient(s), must be shown to be therapeutically equivalent to one another in order to be considered interchangeable. Differences of less than 20% in AUC & Cmax between drug products are unlikely to be clinically significant in patients. Minimize product to product variability by different manufactures & lot to lot variability with a single manufacture.

10. Reference Palylyk -Colwell E, Jamali F, Dryden W, Friesen E et al.: Bioquivalance and interchangeability of narrow therapeutic range drugs. Canadian Society of Pharmaceutical Sciences Discussion 1. Journal of Pharmacy and Pharmaceutical Sciences. 1998 (in press). Wagner JG, Welling PG, Lee KP and Walker JE: In vivo and in vitro availability of commercial Warfarin tablets. Journal of Pharmaceutical Sciences. 1971;60:666-677. Ruedy J, Davies RO, Gagnon MA, McLean WM, Thompson WG, Vitti TG, et al: Drug bioavailability. Canadian Medical Association Journal. 1976;115:105. McGilveray IJ, Midha KK, Cooper JK: Bioavailability of Canadian tablet formulations of Warfarin Sodium and Potassium. Canadian Journal of Pharmaceutical Sciences. 1978;13:9-11. 5. Muller FO, Steyn JM, Hundt HKL, Luus HG: Warfarin bioavailability, a comparison of four products. South African Medical Journal. 1988;74:566-567.

11. Thank You…