The Biopharmaceutics Focus Group – 20 years of Progress in Predicting Oral Absorption

As the Biopharmaceutics Focus Group (FG) has just enjoyed a long overdue change of leadership with Hannah Batchelor (University of Birmingham) replacing me in the FG lead role, I thought I would take the opportunity to reflect on how the fundamental science which drives our understanding of biopharmaceutics has changed over the years. The FG has been in operation since the mid-90s (it’s too long ago for any of us to be more accurate!) and was originally chaired by Jim Murray who was then at AstraZeneca.  After a couple of years, Jim asked me to take over for a year or so and then pass the baton onto someone else. That transfer took much longer than both of us ever envisaged! Part of the reason for staying with the FG for so long is that the science we share, discuss and debate is everchanging and there is always another idea to work on for the next meeting or symposium. Going back in time to the mid-90s when the group was formed, there were significant developments in absorption science making the news and changing the way in which we predict formulation performance. The publication of the theoretical basis for biopharmaceutic drug classification in 19951 provided the BCS framework which was to become the cornerstone for biopharmaceutics risk assessments. In Professor Jennifer Dressman’s labs in Goethe University, Frankfurt, the first publications on biorelevant media were emerging and providing the basis for biorelevant solubility and dissolution measurements for the next 20 years.2 Around the same period, Professor Hans Lennernäs at Uppsala University published his collaborative work with the FDA on the pioneering use of the Loc-I-Gut system to measure human permeability and provide a vital dataset for those of us who were using in vitro systems such as Caco-2 cells to correlate apparent permeability to effective permeability.3, 4 Just a few years later, biopharmaceutics took its first steps into the digital era with early versions of commercial physiologically based pharmacokinetic modelling software reaching what were then the cutting-edge Win 98 based desktop PC systems of biopharmaceutics scientists. 5 It certainly felt like we were on the cusp of a major change in our ability to predict formulation performance, but challenges still remained, notably in our understanding of the range of variability associated with gastrointestinal physiology and the impact on the performance of oral formulations.

As we moved into the 2000’s, life as a biopharmaceutics scientist became more complex as poor solubility became the issue of the day and remained so up until the present day. Of course, formulation research responded with ever more inventive technology approaches (nanoparticles, cyclodextrins, amorphous stabilised dispersions to name but a few) to deliver this challenging new wave of research molecules. We now had the combination of difficult API and complex formulation technologies which would stretch our ability to predict bioperformance to the limit (and in some cases, beyond). This was a hot topic for the APS Biopharmaceutics FG and sharing knowledge and data (not a commonplace activity 15 years ago!) in a pre-competitive collaborative effort to tackle the challenges were being considered. The origins of the IMI OrBiTo project can be traced back to the same problem and when this collaboration started, APS Biopharmaceutics FG members were able to get involved from the planning phase onwards. This ground-breaking collaboration brought together academic, industrial and regulatory scientists to address the fundamental gaps in our knowledge of the GI tract and use this new-found knowledge to underpin the development of the next generation of tools to predict the performance of oral formulations with much more accuracy. Whilst OrBiTo completed in 2019, its impact has been to reignite interest in biopharmaceutics with further EU based projects such as UNGAP and PEARRL picking up where OrBiTo left off and major investment committed by US FDA for new research in oral absorption.

The APS FG has always been at the forefront of sharing ground-breaking science for our UK biopharmaceutics community with regular meetings (including two open science meetings with the IMI OrBiTo programme) and sessions at the annual PharmSci conference. In addition to these events, we also recognised that as our subject area is essentially a multi-disciplinary science, there was a need to support education efforts and provide support for scientists transferring to biopharm from other areas such as analytical or formulation/process design. In June 2019, we ran the second Basic Biopharmaceutics workshop in London and the FG provided multiple speakers for the training presentations which spanned a range of topics from physicochemical profiling to regulatory biopharmaceutics. The impact of twenty years of biopharmaceutics research was evident across all the subject areas we covered and emphasised the need to keep up to date with the latest technologies. After many years of coordinating the activities of the biopharm FG, I’m absolutely delighted to pass on the APS biopharm FG baton to Hannah who will bring new ideas and a fresh approach to leading our FG activities. If you are interested in joining the group on its continuing adventures in biopharm then please contact us by the APS website. Finally, I’d just like to raise a virtual glass and say a huge thank you all those leaders in biopharmaceutics science who have inspired us over the last twenty years and propose a toast to the next generation of biopharmaceutics scientists who will deliver the innovative research we need to move our subject area forward!

Mark McAllister, APS Chair and former lead of the Biopharmaceutics FG

References

  1. Amidon, G., et al. (1995). “A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability.” Pharmaceutical Research 12(3): 413-420.