Metered dose inhalers (MDIs) are pressurised, hand-held devices that use propellants to deliver doses of medication to the lungs of a patient. These delivery devices are critically important to public health and are used to administer various active ingredients for a range of medical conditions. MDIs play a particularly significant role in the treatment of asthma and chronic obstructive pulmonary disease (COPD). The MDI accounts for 70% of all inhalation therapy in the world's fifteen largest patient.

Asthma is a disease of the lungs and airways with symptoms of breathlessness, tightness of the chest, wheezing and cough. At least 300 million people suffer from asthma worldwide, and the prevalence and mortality from asthma is on the rise. Evidence now confirms that asthma prevalence is increasing as urbanisation of developing countries continues. Asthma-related hospital admissions are also increasing, especially among children. However, most asthma deaths and violent attacks are preventable with proper, ongoing treatment. COPD diseases, such as emphysema and chronic bronchitis, produce inflammation, swelling, and mucus in the airway and gradually destroy the surface areas of the lung. COPD is progressive, generally irreversible, and severely restricts a patient's ability to breathe. COPD is the fifth leading cause of death worldwide, with an estimated 600 million cases and three million deaths annually.

The international community agreed -- through the Montreal Protocol -- to phase out chlorofluorocarbon (CFC) production for nearly all uses in the developed world by January 1996. Recognising that CFC alternatives would not be available by that date for certain important products, the Parties established a process for exempting "essential uses" from the phaseout. A use is considered essential if it "is necessary for health, safety or is critical for the functioning of society" and there are no "technically and economically feasible alternatives or substitutes that are acceptable from the standpoint of environment and health." The Parties to the Protocol have confirmed, on an annual basis, that MDIs for asthma and COPD are essential.

MDI manufacturers are currently engaged in an extensive programme to transition out of CFC MDIs. Health regulatory authorities are fully engaged in a multi-year process to grant marketing authorisations on a country-by-country basis for each individual drug product. The challenging but worthwhile progression away from CFC-propelled medications to non-CFC MDIs will involve millions of patients and their healthcare providers in over 100 countries around the world. With the introduction of the first non-CFC MDIs in some countries, this transition period is now just beginning. Ongoing education programmes to teach doctors and patients about the new products are of the utmost importance as patients with respiratory disease are extremely sensitive to even the smallest changes in medication.

In response to the Montreal Protocol, pharmaceutical firms and others evaluated potential non-CFC propellants that could be used safely and effectively in MDIs. In the course of this extensive review, HFCs emerged as the only propellant suitable for pharmaceutical use. No other compound has been proven to meet the stringent criteria for a medical gas to be used for inhalation by patients. A propellant used in a medical inhaler must:

• be a liquefied gas
• have appropriate solvent properties
• have very low toxicity
• have appropriate density
• be chemically stable
• be compatible with a wide range of medicines
• be acceptable to patients (taste and smell)
• be non-flammable

The propellant must also demonstrate these criteria through rigorous testing and assessment to provide the necessary basis for review and approval by the health authorities. The HFCs used in asthma inhalers meet these criteria. HFCs 134a and 227 are the only proven alternatives to CFC propellants for MDIs. These propellants are non-flammable and have been shown to be safe for human inhalation through extensive toxicity testing, which has been to the same detailed level as a new drug. Both have vapour pressures suitable for MDI usage, and both are essentially biologically inert. HFCs do not deplete the ozone layer, and they have significantly lower global warming potentials than the CFCs that they replace in pharmaceutical applications.

MDI companies promote the following principles:

• MDIs, nebulisers, and dry powder inhalers (DPIs) are all important therapy options for asthma and COPD patients; however, these delivery systems are not equally suitable for all patients.
• Treatment of asthma and COPD is not uniform among all patients and must be individualized and is therefore critical that physicians be allowed to select the therapy that provides the best control for the individual patient.
• Because MDIs account for 70% of all inhalation therapy worldwide, the effective treatment of asthma and other respiratory diseases depends on the continuing availability of the MDI.
• Sound MDI manufacturing operations and responsible disposal/recycling are critical to minimising emissions.

The Alliance for Responsible Atmospheric Policy is a leading industry voice which coordinates industry participation in the development of reasonable international and U.S. government policies regarding ozone protection and global climate change.

The International Pharmaceutical Aerosol Consortium is comprised of leading manufacturers of metered dose inhalers and other inhaled therapies. IPAC seeks to ensure that the vital role of the MDI is fully appreciated and accounted for in the implementation of the Montreal and Kyoto Protocols.

The Alliance for Responsible Atmospheric Policy 2111 Wilson Blvd., Suite 850 - Arlington, VA 22201 Phone: (703) 243-0344 - Fax: (703) 243-2874 E-mail: info@arap.org