Purpose. Mycophenolate Mofetil (MMF) is the most used immunosuppressant in solid organ transplantation. Concerns have been raised about substitution between brand and generic MMF tablets. We assessed pharmaceutical quality and bioequivalence data of the 11 approved generic MMF tablets to evaluate FDA claims that the generic MMF are therapeutically equivalent to the RLD and substitutions to generic MMF are safe. Methods. The point-estimate T/R ratios of AUC0-t and Cmax under fasting and fed conditions were summarized for the 11 generics. Formulation composition, manufacturing process, impurity profiles, and in vitro dissolution were compared. For 3 generics, the lower bound 95% confidence interval of minimum process performance index (CL-Ppk) for some critical quality attributes (CQAs) of the product was calculated to estimate the consistency of product manufacturing. Higher CL-Ppk value suggests a more robust process. Reports from 2000 to 2011 on MMF in the FDA database of field alerts, product complaints, and recalls were also collected. Results. Of the 11 generic products, the mean point estimates of T/R ratio of AUC0-t and Cmax were 100.3% (92-104%) and 99.8% (94-108%) under fasting conditions, and 98.8% (93-102%) and 94.4% (89-104%) under fed conditions. The formulation composition of the generic products was similar to that of the RLD. The generic MMF tablets were manufactured by wet granulation (5/11), dry granulation (5/11), or direct compression (1/11) processes. Despite differences in the manufacturing process, for all the generics throughout their shelf life, the level of total impurities remained less than 0.5% and assay was in the range of 96-104%. The in vitro dissolution profiles of generic and brand were comparable. The CL-Ppk values of the generics were similar to those of RLD.

The FDA database search did not suggest that the efficacy and safety of the generic MMF was compromised. Conclusions. Pre- and post-approval data of generic MMF tablet indicated that all approved generic MMF are well within the FDA bioequivalence and quality requirements, and comparable to Cellcept. Process capability data indicate that there is no significant difference in manufacturing consistency between sampled generics and the RLD.

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