Nanopharm’s SmartTrack® platform is on the brink of delivering a change that the inhalation field has long been waiting for: a modelling pathway intended, once validated, to support applications for approval of generic Orally Inhaled and Nasal Drug Products (OINDPs) with fewer costly, risky and time-consuming clinical endpoint studies and the ability to derisk remaining in vitro and clinical bioequivalence studies.
On the one side, innovation is essential; it is that unquenchable thirst to find new and better ways of meeting patient needs that drives so many to pursue a profession in pharma. After all, without the requisite scientific curiosity, Sir David Jack and his team would never have discovered a way to ease the symptoms of so many with asthma and COPD.
Conversely, innovation is a risky business, layered with uncertainty, burdened with costs and often paralyzed by delay, as iteration after iteration is tested and either accepted or rejected.
Then, there is the utopia in medical innovation: to discover a smarter outcome that enables better patient care without the restrictive paradigm of time/cost/risk.
We have found a Smart way…
The SmartTrack® journey began almost a decade ago, driven by a scientific and practical curiosity: how to significantly reduce the need for comparative clinical endpoint (CCEP) studies in generic OINDPs, by creating a validated in‑vitro/in‑silico pathway with regulatory credibility.
As with any project worth undertaking, there were some interesting barriers to overcome, both perceptual and practical, one being regulatory acceptance: if a model is to influence approval decisions, it must be verified and validated to ensure it can be relied upon, somewhat similarly to manufacturing processes and analytical methods, and in line with the FDA’s recognition of the ASME V&V40 framework and the recent publication in June 2026 of the ICH M15 guidance on the “General Principles for Model-Informed Drug Development”.
This is green field territory: we are not aware of any inhalation modelling tool that has previously completed a full V&V40 style credibility assessment for this specific context of use. And, of course, there is the challenge of cost; we realized we could not expect sponsors to use the models to reduce the reliance on clinical trials if the only way to validate those models for use is to run other clinical trials instead!
The simple yet Smart way forward
Leaning on a significant internal investment, the strategy is to complete one central, dedicated clinical study (designed following extensive FDA interactions) that is intended to validate SmartTrack® once and to be filed into a Model Master File (MMF) – aligned with the DMF type V framework. This approach is intended to remove the burden on every sponsor to perform product specific validations; creating a reusable, trusted modelling platform for multiple inhalation products that fall within the validated operating window.
The unique complexity of inhalation modelling requires Smart thinking
In comparison to oral or topical products, inhaled therapies are considerably more difficult to model. We must be able to capture how the dose navigates variable, complex airway geometries and breathing patterns to reach the lungs. We must also account for disease-specific changes in lung function that affect deposition and subsequent absorption. And finally, regional deposition patterns need to be translated into both systemic and local pharmacokinetic (PK) profiles over time, connecting deposition to clinical effect.
The SmartTrack® validation program embraces and addresses this complexity, linking in vitro data, advanced computational fluid dynamics (CFD), PBPK modelling, and clinical imaging/PK outputs into one robust, repeatable methodology designed to meet regulatory credibility expectations.
The design of the SmartTrack® clinical validation study
We are now underway with our clinical study, taking the first step in transforming SmartTrack® into a Model Master File intended to be submitted to FDA for review.
The study is designed to deliver three key outcomes. First, validate the lung deposition model, second, validate the PK model, and third demonstrate credibility across multiple distinct drug products.
Select products are dosed to participants and imaged using advanced lung deposition techniques to generate measured regional lung deposition data for each product.
In parallel, a PK study is also being performed, providing independent systemic concentration vs time profiles.
Making the Smart connection: deposition to PK
Imaging and PK measurements are then compared directly with the deposition and Simhalation™ PBPK simulations, creating a model-based reconstruction of where drug lands and how it behaves over time.
As a result, SmartTrack® must predict lung deposition distribution, predict subsequent PK behavior and demonstrate that both predictions align with independent clinical datasets. Across multiple products. With one model.
Only when all links hold consistently across all inhalers can we claim that SmartTrack® is not just accurate when refined on a product by product basis, but can robustly discriminate across a realistic operating window of product properties to meet the credibility expectations of regulatory bodies with one unified model platform.
This is no mean feat, but thanks to our long-term engagement with FDA and major industry partners, our objective is for SmartTrack® to transition from a development tool to a validated platform for its defined context of use. More to come…
To find out more about SmartTrack® visit: https://nanopharm.co.uk/smarttrack-home/
Legal notices
SmartTrack® is a registered trademark of Nanopharm Ltd, an AptarGroup company, in the UK and EU. Simhalation™ is a trademark of Nanopharm Ltd. All other trademarks are the property of their respective owners.
This article describes an ongoing research and validation programme. References to interactions with the U.S. Food and Drug Administration do not constitute FDA endorsement, approval or qualification of SmartTrack®, Simhalation™ or of any model or method described here. Statements about future events, including the outcome, timing or regulatory acceptance of the validation programme, are forward-looking and subject to risks and uncertainties; actual results may differ materially and no obligation to update them is undertaken. Nothing here is a guarantee of any regulatory outcome, or advice on which a sponsor should rely in designing its own development or regulatory strategy.
