Bioequivalence and Bioavailability Forum

Dear all,

the EMA published a set of product-specific guidances updating previous versions to be in accordance with ICH M13A. They will be effective with November 1^st, 2025.

Here I show PSGs where additionally to AUC_0–t and C_max, either t_max or partial AUC can be used as main PK variables.
Partial AUC is a new option, though I have strong doubts that – due to the high variability – it will be possible to demonstrate BE within the conventional limits of 80.00–125.00% and a feasible sample size. Power of pAUC_0–tmax was shown to be extremely poor.* Re­fe­rence-scaling is not mentioned because the methodology will be covered in ICH M13C.

• Ibuprofen oral use immediate release formulations 200 – 800 mg product-specific bioequivalence guidance – Revision 2
  
• Paracetamol oral use immediate release formulations product-specific bioequivalence guidance – Revision 2
  
• Tadalafil film-coated tablets 2.5 mg, 5 mg, 10 mg and 20 mg product-specific bioequivalence guidance – Revision 3

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• Lacey LF, Keene ON, Duquesnoy C, Bye A. Evaluation of Different Indirect Measures of Rate of Drug Absorption in Comparative Pharmacokinetic Studies. J Pharm Sci. 1994; 83(2): 212–5. doi:10.1002/jps.2600830219.