Inhaled Drug Delivery: Market Opinion

The market for asthma and Chronic Obstructive Pulmonary Disease (COPD) products is the third largest global pharmaceutical category. Expansion is set to continue, driven by an underlying increase in patients, and the diagnosis and treatment of these medical conditions.

This trend can be observed in Asia, especially in the rapidly growing Chinese market, as patients gain access to a wider range of treatments.

Growing Needs

Asthma and COPD are becoming increasingly prevalent on a global scale. The World Health Organization has predicted that there are 300 million asthma and 230 million COPD sufferers worldwide (many in developing countries). It is now estimated that up to 50 percent of smokers will develop COPD, a figure that is much higher than previous estimates. This, combined with pressures on the cost of health care, has led to an increased focus on the cost of treatment in recent years – driving pharma companies, especially in developing countries, to develop their products in the more cost effective pMDI delivery system.

Inhalation drug delivery has been the mainstay of treatment for respiratory diseases since 1956, which saw the pioneering of the world's first pressurized Metered-Dose Inhalers (pMDI). During the last 50 years, the industry has witnessed improvements to the original pMDI design, as well as the introduction of a range of Dry Powder Inhaler (DPI) devices.

With a plethora of devices that are available through which to deliver New Chemical Entities (NCE) or new presentations of generic drugs – and with the patient becoming increasingly influential in determining which products will be prescribed – a pharmaceutical company’s decision criteria must include patient preferences. In addition, regulatory-drivers and cost-drivers remain a focus for developers.

Environmentally Friendly Alternative

Another major change for the inhalation market has been the transition away from chlorofluorocarbon (CFC) propellants, in favor of the “ozone friendly” hydrofluoroalkane (HFA) propellants. Whilst many companies have chosen to invest in transitioning pMDI products to the newer HFA propellants, other developers have focused on developing alternative DPI devices. This has led to a change in market dynamics and where pMDIs were once the dominant delivery system in terms of volume and retail sales, DPIs now account for almost half of global sales.

This expansion in the availability of device options has had an impact upon patients: unlike the pMDI, which is effectively a generic delivery system that can deliver proprietary molecules and/or formulations, each DPI device is unique. Different DPIs use different actuation and aerolization mechanisms, which in turn influence dose delivery.

This means that there is no “one device fits all” solution for DPIs and therefore it is not yet believed to be possible to develop a generic product using a DPI. This poses a problem in the US because CFC-containing albuterol inhalers have been banned from January 1, 2009 as a result of the Montreal Protocol.

Patients have had to get used to the different sensation with the use of HFA-containing pMDIs. Because there is also no generic asthma/COPD product that has been approved by the US Food and Drug Administration (FDA), patients and insurers are forced to pay higher prices for their medication. The race is on to develop generic HFA-containing albuterol pMDIs for the US market, opening up opportunities for pharma companies worldwide. Europe and the US are not the only markets with a current cost focus. With the increases in rates of occurrence and diagnosis of asthma and COPD in the major Asian markets – evidenced by growth in the sales of such products in China and India – many companies are looking to utilize existing technologies to enter these markets.

Market Segmentation

In developing countries, it is likely that two market segments will co-exist: the first consists of branded, differentiated products with a “device-edge” which appeal to affluent, urban-dwelling patients, and command a premium-price; the second consists of generic products in simple delivery devices, such as the pMDI, which offer a low-cost route to market.

The latter devices are familiar to regulators – facilitating the product registration process; and also to patients, thereby not requiring extensive education before use. In addition, technologies offering single dose administration in a low cost disposable device, such as the Conix DPI, could have utility.

However not all changes are focused on reducing costs. The FDA has introduced guidance requiring all new pMDIs being submitted for registration to incorporate a dose counter. A dose counter is a safety mechanism that informs patients as to the number of doses of medication they have left, and to help them to determine when to replace the inhaler.

Before the introduction of dose counters, patients used various techniques to determine when they needed to order a repeat prescription, such as floating their inhaler in water or shaking it to gauge the amount of drug remaining. As these techniques are subjective, it is likely that many patients have been using their inhaler past the number of prescribed doses, thereby exposing them to the risk of sub-optimal dose medication. Research with patients has shown that the introduction of dose counters (mandated in the US and encouraged in Europe) can provide a sense of security, enabling the former to monitor remaining doses in their inhaler more accurately.

Patient Involvement

The patient’s opinion has become increasingly important in pharmaceutical device development, and developers acknowledge that the patient’s interface with the device is crucial. Evolution in inhaler design will be driven by more informed consumers, confident to demand products to meet their needs and fit their lifestyles. Patients currently demand a list of attributes including: discretion in use; small enough to fit in the purse or pocket; ease of use; organic-feel to mouthpiece; legible and accurate dose counter; looks like a consumer product rather than a medical product.

In the current economic climate, especially in the pharmaceutical industry where pipelines have been shrinking and products are taking more time and investment to commercialize, a convincing business case must be made for developing devices. Whilst the inhaler is a complex device with small changes requiring significant investments, patient preferences have come to the fore in the design and development of improved devices today.

Drug delivery innovators believe that pharmaceutical products, although heavily regulated, should not be any less consumer-researched and design-optimized than other products. Achieving a “device-edge” is possible and worthwhile in this large and competitive market.

The vision must be to make asthma and COPD patients’ lives better, bringing devices to give them more confidence and control over their conditions and minimizing the negative effects on their quality of life.

Clinicians have highlighted patient non-compliance as a major cause of poor disease control for many years. A lack of motivation, confusion over the different types of inhalers prescribed, or simple forgetfulness are some of the main reasons for the non-compliance. The pharmaceutical industry has responded by developing combination products such as Seretide (GlaxoSmith-Kline, UK) , Symbicort (AstraZeneca, UK) and Foster (Chiesi, Italy) which incorporate inhaled corticosteroids with long-acting betaagonists to provide patient-convenience and ease of use. These products have been successful in recent years.

Other pharmaceutical companies have moved towards “one puff once a day” products – for example the inhaled corticosteroid ciclesonide, marketed as Alvesco (Nycomed, Switzerland) – as a way of improving compliance. Innovations in drug delivery technologies such as the Face Seal Valve will make more “one-shot” products possible in the future and will allow the reformulation of existing brand leaders into more convenient dosage regimes.

Design Considerations

Inhaler design is also a factor which influences patient compliance. The historical issue for pMDIs was the difficulty that patients have had in coordinating breath inspiration with the timing of the press-and-breathe valve mechanism, which releases the drug dose. A solution to this problem was provided through the introduction of the Autohaler breath-actuated inhaler, which uses the patient’s inspiratory breath to trigger the valve to release the drug dose. Similarly, DPIs rely on patients to activate the release of the dose through inspiration, some of which are passive and rely on the patient inspiratory rate (which has implications of its own), and others include active mechanisms to provide energy for aerosolization. Patients can also have difficulty in understanding how to operate multiple devices.

These problems have resulted in efforts to resolve the common issues that patients tend to experience when using inhalers. It has also prompted developers to consider the opinions of the patient during the design and development of new devices. Ease of use has become a critical requirement, particularly for DPIs, where the variety of options available means that prescribers and patients must intuitively understand the steps that are required to use a device correctly.

Patient research projects have shown that “feeling secure” is a critical emotion for patients, given the potentially life-threatening nature of respiratory disease and the fact that it can be a frightening and debilitating disease state. Therefore, familiarity of the device is a key attribute. Other features can also enhance the feeling of security: confidence in the number of doses remaining in the inhaler and feedback that the dose has been taken correctly.

In the case of pMDIs, feedback is an inherent feature (because of the taste and the sensation of the plume passing through the mouth and throat). Many patients have also identified feedback that the dose has been taken, as a primary need when using DPI products. This can be addressed in two ways: either through the incorporation of a simple audible click which occurs when the dose is released; or in the case of more advanced devices such as the Taper DPI, a visual “ready” indicator that is used to show patients that the dose has been inhaled.

Issues in Design

Research with specialist asthma nurses, points device developers toward a similar direction: a discreet device that is well designed so as not to look too “medical” will facilitate compliance; and feedback to the patient or carer that the dose has been taken correctly, results in a feeling of confidence in disease management.

The nurses also stress the importance of simplicity in device usage – minimizing the number of steps and making them as intuitive as possible. This helps to instill patient confidence to use the device correctly while assisting in compliance. In the case of particular patient groups such as children or the elderly, the need for these design factors is magnified.

The worldwide market for asthma and COPD products is vast. It is growing rapidly, especially in Asia. In the process of designing products to meet the needs of health professionals and regulators, developers are increasingly focusing on patient needs when developing new and improved devices.

In addition, cost will continue to be a major driver of device design as the Asian market in particular develops into two sub-markets: a market for low-priced, tried-and-trusted pMDI devices to deliver generic drugs to the less wealthy patients; and innovative drug products with a “device-edge” which can command a premium price in the more affluent patient population.

For both patient segments, ease of use, discretion, a nonmedical appearance and a feeling of security are key design attributes. Both the established pMDIs and the innovative DPIs are being designed and redesigned to meet these patient needs.