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Speaker Interview with Boehringer Ingelheim

Predictive exposure modelling

Ahead of Extractables and Leachables Europe 2021, we spoke to E&L expert Thomas Egert, Analytical Development at Boehringer Ingelheim Pharmaceuticals. 

Our exclusive interview covered an exclusive preview of his presentation on 'The future of Mass Transport Modelling in support of leachable risk management', as well as why there is increasing interest in predictive exposure modelling, what is most critical for increased use and acceptance of predictive concepts, what is on the horizon in predictive exposure modelling, and more.

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Thomas, your presentation will look at predictive exposure modelling - could you please tell us why you chose this topic?

The notion that leaching and sorption are physically forseeable and can be numerically estimated inspired me from early on when working on safety and compatibility of, initially, plastics for food applications. The concept of Migration Modeling, as it is established in the food industry, offers vast knowledge to extrapolate between extractables and leachables and yet as largely ignored in our industry.

Gradually, and fortunately, this appears to have changed and I think there is great potential value for all stakeholders. Predicted data are definitely of value to complement experimental information and to fill experimental gaps. Oddly enough, in toxicology, in-silico methods have been routinely used for a long time, with their uncertainties widely accepted. Arguably, in a modern risk-based framework, this should apply to chemical characterisation too.

We note that there is increasing interest in predictive modelling among our attendees. Can you explain why this is happening now?

This appears to result from coincidental technical progress and strategic awareness both in the industry and at regulatory agencies. Technically, there is steady progress with reports pouring in on advanced methods, for example to estimate the mobility (diffusion) of leachables in polymers and their solubilisation in pharmaceutical preparations. 

Alongside it is the ever-increasing capability of databases, numerical algorithms and software. In combination, this offers the realisation of toolboxes, which make the inherent complexity of data and models accessible to practitioners. For example, extractables data can now be scaled and extrapolated within multiple single-use components covering the fate of leachables in complete manufacturing systems. For this, there is pressing need in the industry and potential to fill data gaps or generate information which is experimentally unavailable.

What do you see as most critical for an increased use and acceptance of predictive concepts - is there anything evolutionary / revolutionary on the horizon?

Firstly, one of the most exciting challenges towards efficiently leveraging predictive information requires a certain degree of industry collaboration and joint forces. Further development of toolsets and their validation which ideally operate with curated databases of materials information (materials and their chemical constituents), physiochemical parameters and numerical algorithms involves the collaboration of multiple stakeholders, e.g. material suppliers, software providers and users.

Second, strategically, it gradually becomes evident that a regulatory accepted risk framework offering guidance on the modalities of predicted data use might ultimately be decisive. The ICH Q3E effort has the potential to offer such a framework.

What are you most looking forward to hearing about and discussing with your peers at E&L Europe 2021?

As a CMC work package, E&L has always held a unique position. There is simultaneously a niche role and inherent complexity at each stage of the discipline, be it material logistics, associated space of chemicals, analytical data and documentation, and ultimately toxicological assessment and lifecycle management. 

Here, the E&L community is steadily shifting the complexity towards a coherent big picture of patient safety. Constant exchange of ideas is clearly key to this with a decent part occurring at meetings like this one. They provide one of the rare platforms where all stakeholders can come together for discussion and settlement. 

Regarding predictive concepts in particular, I am looking forward to any kind of exchange and feedback on how to move forward, both practically and strategically.

Thomas will be presenting as part of the Modelling of E&Ls session at E&L Europe 2021 on 17 November. Other presentations in the session include:

  • Physics-based exposure models for medical device leachables - David M. Saylor, US Food and Drug Administration
  • Extractables goes in-silico: The Extractables Management and Calculation Tool Sim - Dr. Armin Hauk, Sartorius Stedim Biotech