Ensuring Patient Care - 2nd Edition

Introduction

The purpose of this Paper is to inform decision makers who are involved in policy discussions on climate change about the critical role of the hydrofluorocarbon (HFC)-propelled metered dose inhaler (MDI) in the treatment of respiratory disease.

The MDI is a vital therapeutic option for the estimated 300 million people worldwide who suffer from asthma and the many millions more afflicted by a variety of other respiratory diseases. This pocket-sized, portable therapy provides patients and physicians with quick, proven delivery of pulmonary medication.

MDIs are aerosol devices that rely on propellants to deliver precisely-metered doses of medication to the patient’s lungs. For approximately forty years, MDIs have used chlorofluorocarbons (CFCs) as propellants. Due to growing awareness that CFCs contributed to the depletion of stratospheric ozone, however, in the mid-1980s the pharmaceutical industry began an intensive search for alternatives to the CFC-propelled MDI. Three major initiatives resulted: testing of alternative propellants and reformulation of MDIs with these propellants; acceleration of programmes to improve existing non-propellant delivery systems, such as nebulisers and dry powder inhalers (DPIs); and expansion of efforts to develop new, innovative delivery systems. The first initiative, development of the non-CFC MDI, is the primary subject of this Paper.

This Paper begins by giving a brief overview of respiratory disease and by providing perspective on MDIs and other therapy options. Next, it discusses the impact of the Montreal Protocol and the extensive search for a CFC substitute. It then explains why, given the stringent technical criteria for MDI propellants, HFCs emerged as the only viable alternative to CFCs. It continues by outlining the processes of reformulation and regulatory approval and the ongoing research into alternative delivery systems. Finally, this Paper discusses the minimal contribution of the HFC MDI to climate change and explains the enormous health benefits provided by this device.


Executive Summary

Principal Themes

• Asthma and other respiratory conditions impose great hardship on the millions of patients around the world who suffer from these diseases. Proper treatment makes a critical difference in these patients’ ability to lead full and active lives. For some asthma patients, it may mean the difference between life and death.
• Metered dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulisers are all important therapy options, and all must coexist. Each possesses a unique set of characteristics that differentiates its use. Physicians must be allowed to choose the therapy that is best for the individual patient.
• The MDI has special benefits for many patients. Effective treatment of asthma and other respiratory diseases depends on the continuing availability of the MDI.
• Hydrofluorocarbons (HFCs) are the only suitable alternative to CFC propellants for MDIs. No other compounds are proven to meet the stringent criteria required for an MDI propellant.
• In addition to improving existing therapies, the pharmaceutical industry is continuous- ly seeking new means of delivering medication to the lungs. However, there is no guarantee that any new technology would have universal application and replace the MDI in respiratory therapy.
• The projected environmental impact of the HFC MDI is extremely small. The MDI¹s enormous contribution to public health must be clearly understood, respected, and taken into account in all relevant policy discussions.

Summary of Paper

Respiratory Disease
Asthma is a chronic and potentially life-threatening disease which affects 300 million people around the world. Many millions more suffer from other pulmonary disorders such as chronic bronchitis and emphysema. Each year, millions of people die from these diseases. Most asthma deaths are preventable with proper treatment.

Therapy
Physicians may select from a broad range of medications for treating respiratory disease. Patient response to medication can be highly idiosyncratic; thus, the physician must attempt to determine the best available treatment for each individual patient.

There is international consensus that treatment by inhalation is the preferred form of treatment for asthma sufferers. Three types of inhalation delivery systems are available: nebulisers, MDIs, and DPIs. An examination of the characteristics of these delivery systems demonstrates that each system has particular strengths and weaknesses. It is essential to maintain each of these therapeutic options in order to meet individual patient needs.

Although no one therapy is suitable for all patients, an estimated 70 million patients in 100 countries around the world rely on MDIs for treatment of respiratory disease. MDIs assist the patient by providing the energy needed for drug delivery in the form of a propellant; they meter out doses independent of the patient’s inspiratory effort; they are adaptable to a variety of needs and situations, including use by young children and infants; they provide good protection for the drug substance from atmospheric humidity and the patient’s respiration; they can be used for all of the most commonly prescribed respiratory medications; and they are widely available. No other inhalation system provides the same range of benefits as the MDI.

The Montreal Protocol and CFC MDIs
The CFC MDI for the treatment of asthma and other respiratory diseases has been declared an “essential use” of CFCs under the Montreal Protocol, because it is vital to public health and there is no other therapy that can take its place. The expert scientific panel created by the Parties to the Protocol has reaffirmed the essentiality of the CFC MDI annually since 1992, with the understanding that the CFC MDI eventually will be replaced by HFC MDIs.

Transition to Non-CFC MDIs
An MDI propellant must be a gas that can be liquefied in a closed container at room temperature. It must have appropriate pressure, density, and solvency characteristics and very low toxicity. It must be chemically stable, and acceptable to patients in terms of taste and smell.

In response to the Montreal Protocol, pharmaceutical firms and others evaluated potential alternative propellants for safety and MDI performance. In the course of this review, HFCs 134a and 227 emerged as the only propellants suitable for pharmaceutical use.

The process of developing HFC MDIs has been challenging. The MDI is a complex device consisting of a canister, a valve, elastomer gaskets, and an actuator. It contains formulations of drug substances, propellants, lubricants, co-solvents, and surfactants. Most of these components and compounds must be redesigned or developed for use with HFCs to ensure the quality of the product and to meet today’s strict regulatory requirements. The new formulations must also undergo extensive safety and clinical testing, followed by extensive regulatory review. From start to finish, the process will take up to ten years or longer, depending on the product.

Potential Future Technologies
Competitive forces are driving pharmaceutical firms to intensify the search for new means of delivering medication to the lungs. It is unlikely, however, that the current mix of therapeutic options will change significantly in the near future. Considerable time is required for development, clinical studies, regulatory approval, and acceptance of a new drug delivery system by patients and the medical community. In addition, any new treatment option may not be appropriate as a universal substitute for the range of currently available therapies.

The HFC MDI
There is a large and growing need for effective treatment of respiratory disease. On a worldwide basis, the great majority of patients who receive inhalation therapy rely on the MDI for delivery of their medication. MDIs account for 70 percent of all inhalation therapy in the countries with the largest populations of patients with respiratory disease.

The quantity of HFCs needed for MDIs is extremely small. Other greenhouse gas emissions vastly overshadow expected emissions from HFC MDIs. It is estimated that the contribution to climate change of HFCs from MDIs in the year 2010 will be no more than 0.02 percent of all global greenhouse gas emissions. (See Section VIII). Unlike CFCs, HFCs do not contribute to ozone depletion, and they have significantly lower global warming potentials than the CFCs which they replace.

All manufactured devices have some impact on the environment. Medical devices are no exception. However, the environmental effects of medical devices must be viewed in the context of their critical role in patient care.

Conclusion
MDIs provide a high level of assurance to the many millions of patients who depend on them. The HFC-alternative to the CFC MDI will play a crucial role in securing the future of patient care.

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