Fed Bioequivalence Studies for Immediate Release Drug Products: Beneficial or Wastage?

Abstract

Aims: The present study was undertaken to understand the need of fed bioequivalence studies for immediate release pharmaceutical products and thereby evaluating the relative appropriateness of guidelines given by the European Medicines Agency (EMA) and the United States Food and Drug Administration (USFDA). Vulnerability to show bioequivalent or non-bioequivalent results on the basis of type of drugs was also assessed. Study Design: The present work is a meta-analysis involving 162 bioequivalence studies conducted on healthy human subjects. Place and Duration of Study: Accutest Research Laboratories (I) Pvt Ltd, A-31, Khairne MIDC, TTC Industrial Area, Khairne, Navi Mumbai, 400 709, India, between June 2013 and February 2014. Methodology: The present meta-analysis included a total of 162 bioequivalence studies of which 81 were conducted under fasted condition and the other 81 studies were conducted under fed condition. The drug products were fixed dose combinations and mono drug products for 22 and 140 studies respectively representing all the classes of Biopharmaceutics Classification System (BCS). The bioequivalence was assessed by standard criteria laid down by regulatory authorities. The results were correlated with the respective condition of study (fasted or fed) and the corresponding BCS class of the drug product. The observations were discussed in the light of available literature. Results: A total of 78 and 74 studies conducted under fasting and fed conditions respectively had bioequivalent results. All studies conducted on fixed dose combination products had bioequivalent results. Five drug products had bioequivalent results only under fasting condition which proportionately contributed to 6.17% (5/81 fasting studies). These drug products complied only with the EMA guidelines and not USFDA defined passing criteria. All drug products belonging to BCS classes I and III showed bioequivalent results whereas drug products belonging to BCS class IV contributed to 80% of the total non-bioequivalent studies. Conclusion: The EMA approach can be followed for BCS class I drugs while USFDA approach looks better for remaining drug products. Further research work is required to confirm the trend observed in our meta-analysis.