PII-041

Y. Yu,1 S. Teerenstra,2 C. Neef,3 D. Burger,4 M. Maliepaard2; 1CARIM, Maastricht University Medical Centre, Maastricht, Netherlands, 2Medicines Evaluation Board (CBG-MEB), Utrecht, Netherlands, 3CAPHRI, Maastricht University Medical Centre, Maastricht, Netherlands, 4Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

BACKGROUND: Previously, we demonstrated the bioequivalence of different generic drugs for a limited number of antiepileptic drugs. In the current study, the objective was to investigate generic-generic drug interchangeability in a large subset of generic formulations, in order to confirm that our previous conclusions can be generalized to other registered generic drugs.
METHODS: The study was designed as inter-study comparisons of exposure to a number of generic drugs. The predefined random selection yielded atorvastatin, bicalutamide, naratriptan, olanzapine, perindopril and venlafaxine (and cyclosporine, tacrolimus and mycophenolate mofetil as test immunosuppressants). Bioequivalence studies submitted for these generic drugs’ registration before 2012 in the Netherlands were collected, and all studies were conducted using healthy volunteers with oral administration. The 90% CIs for AUCt and Cmax were simulated between generic drugs using a pragmatic method based on the t test.
RESULTS: In total, 120 bioequivalence studies were identified, allowing the simulation of 292 generic-generic drug substitutions. The simulation results indicated that in the vast majority of cases, i.e. 80.5%, the 90% CIs for both AUCt and Cmax fell within the bioequivalence criteria (in 90.1% and 87.0% for AUCt and Cmax, respectively). In most of the cases where the bioequivalence criterion were exceeded in the simulation, i.e., in 23 of the 29 cases for AUCt, and in 25 of the 38 cases for Cmax, the criterion was exceeded by less than 5%.
CONCLUSION: Overall, our study indicates that the exposure-related risk associated with the exchange of different generic drugs in clinical practice is not increased by a relevant extent compared to the situation in which a generic is exchanged with the innovator.