Trends and insights in inhalation and respiratory drug delivery

By Dr Matthias Ediger, Head of Life Science at 42T

42T's newly appointed Head of Life Science attended a recent conference in Berlin that was stacked with high-level industry representatives. The focus was on the latest innovation, technological research and modern manufacturing processes and trends in inhalation and respiratory markets.

In this article, Matthias summarises four main themes from this event that are driven by innovation and regulation in the sector.

Low global warming potential (GWP) propellants

The propellants used in pressurised Metered-Dose Inhalers (pMDIs) have undergone multiple step changes over the last 35 years, largely driven by regulation. The first was the Montreal protocol in the late 80s that lead to replacement gases for the then incumbent Chlorofluorocarbons (CFCs).

The main new categories were Hydrofluorocarbons (HFCs) and Per- and Polyfluoroalkyl Substances (PFAS). As the topics of sustainability and climate change came to the forefront across industries, it was discovered that some of these propellants have a GWP compared to carbon monoxide (CO) of 1000s. This is a significant contribution for extensive users, such as the NHS, where it is estimated to account for 3% equivalent of their emissions.

The EU has reacted by bringing in further regulation for these two categories. HFCs need to be phased out by 2050 and reduced by 15% by 2036. A recent proposal outlines a full ban of PFAS by 2025 with an 18-months horizon to comply. These are stark timelines when a change in propellant means at best a reformulation of the drug payload and at worst a significant change in device, both of which typically also require some level of re-certification.

The good news is that low-GWP propellants, such as HFA152a, already exist. However, there is uncertainty which type of propellant to back and full transition to these propellants by the industry is estimated to still require 10 years of urgent, concerted development effort, so the compliance clock is ticking.

Biologics and novel delivery systems

Biologics, a class of medicines developed from blood, proteins, viruses or living organisms, are a hot topic in drug development. Due to their typically viscous properties and often fragile nature delivery of these suspensions can require novel approaches, in particular for the atomisation towards respiratory targeting.

This is where cross-industry fertilisation will become an important factor, as gentle processes with highly uniform particle distributions, such as Surface Acoustic Waves (SAWs) in silicon MEMS and high-viscosity digital printing platforms, are being proposed to be adopted.

Adherence detection and promotion

A theme present in almost all of the conference talks by device manufacturers was advancing the detection and promotion of adherence to the prescribed treatments. The methods used included adding flow and force sensors to the devices, as well as developing companion apps for the patient, their immediate support network and the clinician team involved.

The data gathered showed adherence for certain groups can be as low as 30-35%, with the severity of the condition, the age range, social and psychological indicators all important factors. Targeted interventions using digital solutions were able to boost adherence, in some cases to 75-99%, and large-scale trials have been ongoing since 2015.

On the other hand, coaching of the breathing manoeuvre towards the more effective slow and steady inhale, using haptic and visual feedback from the device, has been shown to significantly reduce variability following an initial learning curve. While it is difficult to directly link higher adherence to better clinical outcomes due to many complicating factors, it has been established as a key quality indicator for Cystic Fibrosis sites by the NHS and can only help when developing and assessing well-defined treatments.

Particle size conditioning for dry powder inhalers

The proliferation of Dry Powder Inhalers (DPI) in the respiratory drug delivery market has gone hand-in-hand with efforts to micronize and condition the powders for efficient delivery to correct part of the lungs as well as stability of the drug crystals to guarantee effectiveness.

Three main topics were discussed across multiple talks at the conference:

• Innovation in industrial processes, where, for example, compressed gas collision chambers can now be modified quickly with sleeves to suit different products and are equipped with additional process control measures, as well as post-milling conditioning add-ons, inline or offline, that can reduce the energy stored in the amorphous crystalline structure making them more stable.
• Packaging of micronisation processes, similar to the gas collision chambers, into cheap direct delivery devices for inline size conditioning of the powder for effective delivery of the drugs. This can yield a higher delivered dose, adherence and faster efficacy over liquid and oral delivery devices, respectively.
• Assessing these particle size distributions and their delivery to the respiratory system for medical approval has long been governed by standard processes, such as the Aerodynamic Particle Size Distribution (APSD). It is being increasingly recognised that the assessment devices used do not take into account the physiology of the respiratory system or the breathing manoeuvre. Novel testing systems that mimic these are being developed and deployed and it looks like the regulatory authorities are open to considering this additional evidence for a more complete picture of the products’ performance.

In summary

Regulation and new trends in the inhaled and respiratory drug delivery market are all underpinned by innovation to adopt new drugs, materials and processes and the mood in many of the talks was buzzing with excitement of the possibilities to improve people’s lives.

The 42T Healthcare and Life Sciences team is ideally placed to help with the associated product and process development challenges, in the timely and efficient manner required.

Interested in Healthcare trends? Sign up to our Healthcare newsletter.

About Matthias

Matthias is an energetic business and technology developer with a keen eye for commercialising products with a strong societal impact. He has a proven track record as a creative innovator in diverse environments from small spin-outs to large corporate R&D and experience in a variety of markets and technologies.

Contact our Head of Life Science, Matthias Ediger

matthias.ediger@42T.com | +44 (0)1480 309461 | LinkedIn: Matthias