Background
Demonstration of equivalent amounts of the same active pharmaceutical ingredient (API) between generic and innovator products (pharmaceutical equivalence) is a basic requirement of regulatory agencies for intravenous generic drugs prior to clinical use, and constitutes the pivotal point to assume therapeutic equivalence. Physicochemical
Conclusion
The proposed method allows rapid, cost-saving, precise, and accurate determination of pharmaceutical equivalence of drugs in pharmaceutical dosage-form, and may be used as a technique for testing generic antibiotics prior to their approval for human use.
Methods
The assay is based on the concentration-dependent variation of the inhibitory effect of antibiotics on reference bacteria (B. subtilis ATCC 6633, S. aureus ATCC 6538p and S. epidermidis ATCC 12228) in a seeded agar (Difco Antibiotic Media), producing a concentration-response linear relationship with two parameters: y-intercept (concentration) and slope (potency). We compared the parameters of 22 generic products (amikacin 4, gentamicin 15, and vancomycin 3 products) against the innovator and the reference powder by Overall Test for Coincidence of the Regression Lines (Graphpad Prism 5.0).
Results
The validation method yielded excellent results for linearity (r(2) > or = 0.98), precision (intra-assay variation < or = 11%; inter-assay variation < or = 10%), accuracy, and specificity tests according to international pharmacopoeial requirements. Except for one generic of vancomycin that had 25% more API (P(y-intercept) = 0.001), the pharmaceutical equivalence was demonstrated in 21 generics with undistinguishable slopes and intercepts (P > 0.66). Potency estimates were 99.8 to 100.5, 99.7 to 100.2 and 98.5 to 99.9% for generic products of amikacin, gentamicin and vancomycin, respectively.