Bioequivalence and Bioavailability Forum

Dear all,

yesterday EMA published their first set of five adopted guidances. They are given as appendices to the “Compilation of individual product-specific guidance on demonstration of bio­equi­va­lence” (EMA/CHMP/736403/2014) and will be effective with 1 June 2015. Direct links:

• Dasatinib
  
• Emtricitabine/Ten­ofo­vir Dis­pro­xil
  
• Erlotinib
  
• Miglustat
  
• Repaglinide

See also this thread discussing the drafts. No big chances, except in the footnotes:

* As drug variability has not been reviewed, this guidance is not applicable to highly variables drugs. ⇒
* As intra-subject variability of the reference product has not been reviewed to elaborate this pro­duct-specific bioequivalence guideline, it is not possible to recommend at this stage the use of a replicate design to demonstrate high intra-subject variability and widen the acceptance range of C_max. If high intra-individual variability (CV_intra > 30%) is expected, the applicants might follow res­pec­tive guideline recom­mendations.

** The BCS classification should be confirmed by the Applicant at time of submission based on available data (solubility experiments, literature, etc.). If a drug substance has been classified as BCS class II or IV, no further solubility investigations are needed. ⇒
** This tentative BCS classification of the drug substance serves to define whether in vivo studies seems to be mandatory (BCS class II and IV) or, on the contrary, (BCS Class I and III) the Appli­cant may choose between two options: in vivo approach or in vitro approach based on a BCS bio­­waiver. In this latter case, the BCS classification of the drug substance should be confirmed by the Applicant at the time of submission based on available data (solubility experiments, literature, etc.). However, a BCS-based biowaiver might not be feasible due to product specific charac­te­ris­tics despite the drug substance being BCS class I or III (e.g. in vitro dissolution being less than 85 % within 15 min (BCS class III) or 30 min (BCS class I) either for test or reference, or unac­cept­able differences in the excipient composition).