Bioequivalence and Bioavailability Forum

❝ Does anyone know if Brazil or Mexico accepts bioequivalence study with statistics based on Proc GLM or Proc Mixed?

• Brazil accepts for HVD(P)s reference-scaling by Average Bioequivalence with Expanding Limits (ABEL)¹ like the EMA² and the WHO.³ That means a model with all effects fixed (ANOVA).⁴ In SAS-lingo that’s Proc GLM. By analogy – though not stated in the guideline – also for ABE.
  
• Mexico accepts widening the limits in case of high with-subject variability. No details about the statistical method (also about ABE) are given in the guideline of 2013.⁵ No idea whether a more recent guideline exists.

1. ANVISA. Dispõe sobre os critérios para a condução de estudos de biodisponibilidade relativa/bioequivalência (BD / BE) e estudos farmacocinéticos. Brasilia. 17 August 2022. Online [Portuguese].
   
2. EMA. Guideline on the Investigation of Bioequivalence. London. 20 January 2010. Online.
   
3. WHO. Essential Medicines and Health Products. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. WHO Technical Report Series, No. 1003, Annex 6. Geneva. 28 April 2017. Online.
   
4. EMA. Clinical pharmacology and pharmacokinetics: questions and answers. 3.1 Which statistical method for the analysis of a bioequivalence study does the Agency recommend? London. 21 September 2016. Online.
   
5. Secretario del Salud. NORMA Oficial Mexicana NOM-177-SSA1-2013, Que establece las pruebas y procedimientos para demostrar que un medicamento es intercambiable. 20 September 2013. Web Archive 18 November 2017 [Spanish].