AusPAR: Clobetasol propionate - Therapeutic Goods Administration

Therapeutic Goods Administration– Ensure that drug substances from both nominated manufacturing sites areincluded in future validation and stability trial protocols.6. The Product Information (PI) and Consumer Medicine Information (CMI). The PI andCMI for both products should be amended to bring clarity to the composition anddirections of use of the products.7. There is no requirement for this submission to be reviewed again by the PSC before itis presented for consideration by the Advisory Committee on Prescription Medicines(ACPM).It has not been possible to fully resolve all of the pharmaceutical issues; note previouscomments regarding shelf life.The recommendation relating to the Spray is now not relevant.Quality summary and conclusionsThere are some outstanding chemistry and quality control aspects. To allow considerationnow by the ACPM, the product should only be approved with an impractically short shelflife. This will need to be extended by a variation application after registration whichresolves these issues.The investigation of systemic exposure following Shampoo doses did not use analyticalmethods available today which would better quantify blood levels.III. Nonclinical findingsIntroductionThe toxicity profile of CP has been extensively described in published literature of acute,subacute and chronic studies by several routes of administration (including oral,subcutaneous and topical).Scope and quality of the dossierThe TGA adopted EU "Guideline on the non-clinical documentation for mixed marketingauthorisation applications" 2 notes that “a combination of limited nonclinical studies andof literature references from published pharmaco-toxicological information includingscientifically accepted monographs and clinical trials, as well as results of postmarketingexperience gained by widespread clinical use in man” constitute a reasonable body ofknowledge for products with a long history of clinical use. Accordingly, the sponsorhas submitted literature references along with the following nonclinical studies tosupport the registration of CP shampoo and spray:• In vitro human skin absorption data and in vivo absorption data in rats with various CPformulations but not the CP spray or shampoo.• Repeated dermal safety of CP shampoo in minipigs (≤3months).• Genotoxicity evaluation of CP in vitro in a chromosome aberration assay in ChinieseHamster Ovary (CHO) cells and in vivo in a micronucleus assay in mice.2 CPMP/SWP/799/95, April 2006. AusPAR Clobex clobetasol propionate Galderma Australia Pty Ltd PM-2011-01596-3-5Final 22 May 2013Page 11 of 45