Study of regulatory requirements for the conduct of bioequivalence studies in US, Europe, Canada, India, ASEAN and SADC countries: Impact on generic drug substitution

Abstract

In the last one decade, due to expiry of patented products as well as their exclusivity period, a drastic decline of branded pharmaceutical products and up streaming of generic drug market has been observed in developed as well as developing nations. This up rise in generic drug market is expected to rise in future till the arrival of new brand in market. This prevailing conditions could result in proliferation of generic drug manufacturing companies. The fact that generics do not undergo thorough extensive trials like innovator drugs, fuels further fears regarding their inferiority. Moreover, due to the hard competition amongst various companies to market their generics, the frequency of fraud and corruption have embarked doubts in consumers mind to reality. In order to blow away the doubts and re-establishing the credibility of generics in market, bioequivalence (BE) guidelines with stricter regulation should be the demand. The present study highlights the relevant regulatory guidelines for the conduct of bioequivalence studies in US, Europe, Canada, India, South Africa and South East Asian Nations. A comparative study of the differences in study design and specifications have also been addressed.

Interplay of the Quality of Ciprofloxacin and Antibiotic Resistance in Developing Countries

“…Generic equivalents of brand-name drugs (innovator drugs) have been introduced in the global healthcare market to lower the cost of medications ( Kaushal et al, 2016 ). A generic drug product is assumed to be bioequivalent to the brand-name drug product (innovator drug serve as the reference) if there is no statistically significant difference in the rate and extent of absorption of the active ingredient when administered at similar dose ( Turner, 2016 ).…”

“…Currently, approaches to determine bioavailability and bioequivalence of pharmaceutical products has been largely standardized. In United States, the sale of generic drugs is approved by Food and Drug Administration when they meet all the regulatory requirements provided in the Code of Federal Regulations ( Kaushal et al, 2016 ). The regulatory environment of the country of marketing is important to assure the assessment of bioequivalence of drug products.…”

Bioequivalence metrics for absorption rates: linearity, specificity, sensitivity

“…There is general consensus on the criteria for evaluating the equivalence of the extent of absorption in two drug products which exhibit simple linear kinetics, following their single administration to individuals [1]. In contrast, there is no agreement on testing parameters for absorption rates.…”

Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs

“…An application for marketing approval of a generic drug product must provide evidence of its bioequivalence (BE) to a reference product that was approved based on clinical trials [ 7 – 9 ]. Although there are some differences among regulatory agencies worldwide [ 7 – 9 ], for immediate-release drugs, average bioequivalence (BE) testing is commonly performed in a single-dose, crossover study on healthy volunteers under fasting condition; with measurement of parent drug blood concentration, non-compartmental analysis of logarithmically transformed area-under-the-concentration-time curve (AUC) and maximum concentration (C max ) data, and computation of the 90% confidence interval (CI) on the test/reference geometric mean ratio, which should generally fall within the 80–125% BE range [ 10 , 11 ].…”