Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

BCS-based biowaivers in the context of ICH M9 and its implications on the pharmaceutical industry ***

Dr. Katharina Holl (Abschlußjahr: 2019)

Summary
Language: English
The concept of biowaivers based on the biopharmaceutical classification system (BCS) takes into account the solubility and intestinal permeability of the active substance as well as the dissolution properties of the drug product. Since its initial establishment in 1995, the concept has been further developed and is used in order to demonstrate bioequivalence based on in vitro data, thus helping to reduce the number of in vivo bioequivalence studies.
To date, BCS-based biowaivers are widely accepted for immediate-release oral drug products containing active substances of BCS class I (high solubility, high permeability) and class III (high solubility, low permeability). Major regulatory institutions associated with the ICH, namely the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the World Health Organization (WHO), have issued respective guidance documents, while the concept of BCS-based biowaivers is currently not accepted in Japan, one important ICH region and a major market for medicinal products.
Over the years, harmonization between the single ICH regions has taken place. The requirements set by EMA and WHO have already been harmonized to a large extent. In contrast, significant differences do still exist in comparison with the FDA requirements. These include the dose used for solubility testing (highest single dose versus highest dose strength), which influences the interpretation of literature data and the assignment of active substances to BCS classes. Furthermore, the acceptance of different in vitro methods to be used for the determination of intestinal permeability as well as the methodology used for dissolution testing are not entirely harmonized.
Hence, a need for further harmonization was identified by ICH, resulting in the publication of the Draft ICH guideline M9 in 2018. With this document, a consensus could be reached with regard to the above-mentioned points. The resulting harmonized guideline will represent a milestone of harmonization with regard to BCS-based biowaivers as it provides more detailed guidance on general eligibility and testing requirements. This will further facilitate global approaches in drug development for the pharmaceutical industry. On the other hand, clear requirements will also be beneficial in terms of assessment by regulatory authorities.
It will be interesting to see whether the concept of BCS-based biowaivers will be fully accepted throughout the ICH and thus has the potential to further reduce the need of in vivo bioequivalence studies. As a conclusion, the adoption of ICH M9 will most certainly have a positive impact for the pharmaceutical industry as well as for regulatory authorities.
Pages: 56