Pharmaceutical quality of generic isotretinoin products, compared with Roaccutane

Abstract

ABSTRACTBackground: Isotretinoin is the drug of choice for the management of severe recalcitrant nodular acne. Several generic products are available. However, their pharmaceutical quality, in particular particle size distribution, which may affect safety and efficacy is unknown. Hence, prescribing of some generic products may be problematic.Objectives: To assess the pharmaceutical quality of 14 generic isotretinoin products compared with Roaccutane (F. Hoffmann-La Roche Ltd).Research design and methods: Tests were performed according to Roche standard procedures, European and US pharmacopoeia specifications. Tests included isotretinoin content, identity and amount of impurities and degradation products, effect of accelerated shelf-life studies on stability, particle size distribution and composition of non-active ingredients.Results: The 14 isotretinoin products differed by 30‐fold in median particle size and showed variation in their non-active ingredients.The average isotretinoin content of Acnotin and Acne-Tretin fell outside the 95–105% Roche specifications. Following accelerated shelf-life tests, only four products retained isotretinoin content within Roche specifications, whilst Acne-Tretin (the only powder formulation) lost 72.5% isotretinoin content. Two generic products exceeded the ± 2% specification (Ph.Eur.) and a further three exceeded the ± 1% (USP) for tretinoin content, eight exceeded the 2.54% specification for total impurities and six contained ≥ 5 unknown impurities. Isotretinoin-5.6-epoxide content exceeded the 1.04% specification in five generic products.Conclusions: Thirteen generic products failed to match Roaccutane in one or more tests and 11 failed in three or more tests. It cannot be assumed that all generic isotretinoin products are as therapeutically effective or safe as Roaccutane.