Beyond asthma and COPD

The launch of the first pMDI in the 1950s marked a significant stage in the fight against asthma and COPD. Sufferers were provided with a robust, portable and discreet device, relatively easy to use, sufficiently effective, cheap to produce, and which became readily accessible across the world. And the pMDI is still a significant market player. According to Stephen Stein, Senior Research Specialist at 3M, speaking at 2011’s DDL22 in Edinburgh, 1400 pMDI ‘puffs’ are activated around the world every second, representing a staggering 40bn doses delivered every year.

The widespread use of the DPI, launched in the late 1960s, has further strengthened a dominant market position which remains unchallenged to this day, demonstrated in recent findings by BCC Research, which claims that the global pulmonary drug delivery market will be worth $44bn by 2016. Most of this growth is coming from BRIC countries where cases of asthma and COPD unfortunately continue to climb rapidly, and where the next generation of inhaler devices for asthma and COPD will find a ready market.

But these significant new markets are emerging just as many established products are coming off-patent, and as a result pharmaceutical companies looking to actively pursue these opportunities face an important decision: to replicate or innovate in order to gain market share?

The dilemma (explored more fully in the last issue of Insight) is whether to create a fully substitutable device, eligible for shorter and significantly less costly clinical trials and therefore a faster route to market, or to invest in new, innovative solutions which could reshape the market in the longer term. The global market is now so large that many players can profitably coexist for some time – but as regulation evolves in order to push improvements and establish a baseline in inhaler performance, I believe that the optimal strategy is to innovate.

Innovation allows the creation of new and better inhalers which can specifically address problems inherent in inhaler design. For example, co-ordination (especially among users of pMDIs) and technique have long been underlying concerns for regulators. A slow, deep inhalation is often required, but defining ‘slow’ and ‘deep’ is not only difficult but is also open to personal interpretation with the result that most pMDI users rarely breathe at the ideal flow rate. Although DPIs, with necessarily higher airflow resistance, are inherently easier to use correctly, performance still remains unimpressive with many market leading products achieving operational efficiencies of only 25 per cent.

Recent advances in the scientific understanding of the complex physics involved means that many new inhalers currently in development offer significant improvements in efficiency, so we can look forward to a step change in expectations as they reach and populate the mass market. These next-generation devices will also highlight the gulf between old technology and new approaches, putting further pressure on regulators and pharmaceutical companies to drive up standards.

So far I’ve talked about trends in asthma and COPD, but many companies are now actively developing inhalers capable of delivering a much wider range of therapies. These include pain relievers or vaccines, and drugs required to manage conditions such as cystic fibrosis and diabetes – applications where inhalers could offer significant benefits. For example, inhalers could deliver pain relief in seconds rather than minutes by exploiting the lungs’ incredible drug absorption speed – a regular headache or migraine could be addressed virtually immediately, but so could breakthrough cancer pain, radically improving quality of life. And benefits extend beyond the therapeutic. An inhaled vaccination, for example, would eliminate the need for clean, sterile needles; a dry powder vaccine would not need to be chilled until used, greatly simplifying transport and storage; and clinicians could provide groups of users with single dose inhalers, thereby speeding up a vaccination programme. The inhaler therefore offers a realistic alternative to tablets, which take time to metabolise, and injections, which users don’t like doing themselves.

The technology is coming on in leaps and bounds, as is device design, and there is real desire in the sector to modify existing drugs, extend patents, and therefore create new market segments. But if such applications are to be realised then increased efficiency becomes even more important, especially if the drug being inhaled – say an insulin dose or analgesic – could be life-saving, and even more so if the ‘wrong’ dose could be life-threatening. Dose composition, uniformity and delivery will come under much closer regulatory scrutiny, and as a result inhaler design will have to undergo considerable adaptation.

Typical asthma DPI formulations comprise mainly an inert carrier fraction, used simply to ‘dilute’ the few tens of micrograms of drug that is required for each dose, and to improve handling characteristics during production, due to the carrier’s larger particle size. But drugs such as insulin or pain relief therapies do not need to be diluted with a carrier fraction, due to the higher quantities of active drug required. As well as reducing cost and simplifying the filling process, this has marked implications on the technical requirements of the inhaler, as different mechanisms are needed to create a reproducible, respirable aerosol.

The therapeutic indices of these drugs are also often significantly narrower than the usually wide therapeutic indices of drugs for asthma and COPD. As a result, even tighter controls will be needed to ensure the consistency of the delivered dose, and this is likely to be achieved by a combination of improved inhaler design, excellent human factors engineering, and clever particle engineering.

Inhaler design will also have to accommodate different dosing regimes. Current DPI products deliver 60 doses (a typical month’s supply if delivered twice-daily), but new designs may have to deliver doses more frequently, in larger quantities or as single doses, or be ‘ready when / if needed’. As a result, different and improved feedback mechanisms are required so that users know when a dose has been delivered correctly, when the device needs to be replaced, and – crucially – to prevent unknowing overdose. These (and many other) issues have to be thoroughly understood before pMDIs and DPIs can migrate fully into other applications, but the potential benefits and commercial opportunities are so significant that the effort will be worthwhile.

Alongside new application areas, an additional future driver is the need to adapt device design to individual user needs. Inhalers could be used across the whole population, from those with limited physical ability (as a result of their condition or their age) to those who are not even ‘ill’ – such as someone about to be vaccinated. As a result, devices will need to cope with user lung power that could range from just a few Watts to over 50 Watts. In response to these different, but equally valid, user needs one strategy could be to use a central inhalation engine across a range of devices, from a disposable device for vaccinations to a capsule-based inhaler for pain management. This presents a very real opportunity to make best use of R&D budgets through technology-reuse while also generating patents and other IP.

With so many drivers converging, it is not surprising that inhaler technology is now at such an exciting stage. Decades of research, development, and user experience have created a body of knowledge which is leading to innovation in new and unexpected directions, guided by evolving regulations, and supported by constant technological improvements. Device design is changing in response to the current and future drivers influencing the market, and the most successful could have just as much – if not more – impact on global health as those launched over 50 years ago.

This article was taken from issue 2 of Insight magazine. Get your free copy of the latest issue here.