The Montreal Protocol is a landmark, international treaty designed to enhance air quality and to protect the upper-most (or stratospheric) ozone layer. In 1987, 24 countries, as well as the European Economic Community, negotiated and signed The Montreal Protocol on Substances that Deplete the Ozone Layer. The initial protocol aimed to decrease the use of ozone-depleting, man-made chemicals by 50% by the year 1999. Additional supplements to the Montreal Protocol, known as the London, Copenhagen, and Beijing Amendments, were adopted in 1990, 1992, and 1999, respectively, and further addressed the use and production of various ozone-depleting chemicals, as well as a timetable for their phaseout.
Ozone is a molecule made up of three oxygen atoms and is an essential constituent of our atmosphere. About 90% of the ozone resides in a layer between 6 and 25 miles above the earth’s surface in a zone called the stratosphere. The presence of the correct amount of ozone in the earth’s stratosphere is crucial for absorbing dangerous radiation emanating from the sun. The stratosphere’s ozone envelops our planet in a kind of protective envelope. For example, increased exposure to the sun’s ultraviolet rays, as would occur from depletion of the earth’s protective ozone layer, is associated with an increased risk of developing skin cancer and ocular cataracts in humans. Ozone depletion may also adversely affect animal and plant life.
Studies over the last 30 years have revealed a significant decline in the earth’s protective ozone layer over Antarctica. The first report of holes in the stratospheric ozone layer by British scientists in May 1985 has been subsequently con-firmed and detailed. A widely used class of synthetic chemicals called chlorofluorocarbons (CFCs) has been implicated as a major source of atmospheric ozone depletion. CFCs contain chlorine, fluorine, and carbon atoms. CFCs were invented in the 1920s, and are, in many ways, ideal compounds.
CFCs are nontoxic, noncorrosive, and nonflammable. They are inert and nonreactive with most substances. In the second half of the 20th century, CFCs found extensive use as propellants in aerosols and spray cans, as coolants in refrigerators and air conditioners, as solvents in cleaners—particularly for electronic circuit boards—and as a blowing agent in the production of foam in devices such as fire extinguishers. Freon, for example, is a familiar brand of a class of CFCs that was used in refrigeration.
CFCs are very stable, and it is now recognized that they can persist in the atmosphere for up to 100 years. Any CFC released into the air rises. When CFCs reach the stratosphere, sunlight causes them to break down and release atomic chlorine. The chlorine derived from the CFC is responsible for damaging the ozone layer. Even though the production and release of CFCs have been greatly curtailed, the damage to the ozone layer from past use will continue well into the current century.
The Montreal Protocol was codified by Congress into law in Title VI of the Clean Air Act and stipulated that the production of CFCs in the United States would be banned as of January 1, 1996. Existing medical products that contained CFCs were exempt from the ban until acceptable alternatives could be developed. An essential medical use of CFCs especially relevant to persons with lung disease is the use of CFCs as a propellant in MDIs.
MDIs are used extensively in the treatment of asthma, emphysema, and chronic obstructive bronchitis. Although CFCs were no longer used in the manufacture of aerosol spray cans, air conditioners, or refrigeration units after January 1996, they were still produced for pharmaceutical use in some MDIs. Because MDIs are essential for asthma treatment, the Environmental Protection Agency (EPA) and the U.S. Food and Drug Administration (FDA) extended the timeline banning CFC manufacture, and proposed and oversaw the gradual phaseout of all MDIs containing CFCs (MDI-CFC).
No CFC-containing MDIs were removed from the market until safe and effective equivalent medicines became available. A complete ban on the production and sale of single-ingredient albuterol inhalers containing CFCs went into effect in the United States on December 31, 2008, as part of the planet-wide CFC phaseout. Several inhalers in the marketplace now offer CFC-free alternatives.
Pharmaceutical manufacturers have either reformulated their MDI propellants to be CFC free or developed inhaled drug-delivery systems that do not require any propellant at all. Reformulated albuterol MDIs substitute a different, non-CFC type of propellant called hydrofluoroalkane (HFA).
The FDA has approved HFA CFC-free MDIs for albuterol, levalbuterol, beclomethasone, fluticasone, and combinations of fluticasone/ salmeterol and budesonide/formoterol. The products include ProAir, Proventil HFA, Ventolin HFA, Xopenex, Qvar, MDI Advair, and MDI Symbicort.
Other CFC-free products are available in Europe but are not currently approved by the FDA for use in the United States. In addition to producing HFA-propelled MDIs, pharmaceutical manufacturers have devised novel inhalers that do not rely on any propellant whatsoever. Several different controller asthma medicines are now available as DPIs in the United States, and more are sure to follow.