U.S. Medicine Information Central

June 2006

FDA Rule Phases Out Albuterol CFC Inhalers - Daisy Spangler

WASHINGTON-Over the next two years physicians of asthma patients who use certain types of albuterol metered-dose inhalers (MDIs) will have to adjust their treatment due to a Food and Drug Administration (FDA) regulation amending the use of ozone-depleting substances in medical products. In the April 4, 2005, Federal Register, FDA announced their final rule on the issue, which stated the production and sale of single ingredient albuterol MDIs containing chlorofluorocarbons (CFCs) will no longer be permitted after Dec. 31, 2008.

Albuterol MDIs were first approved for use in the United States in 1981, and since have become one of the most widely used drug products for the treatment of asthma and chronic obstructive pulmonary disease. Albuterol is considered a short-acting beta2-agonist capable of quickly relieving sudden or severe asthma symptoms by opening restricted airways. Typically the medication works within 15-20 minutes and can last between four to six hours.

According to an FDA estimate, in the first two quarters of 2004, U.S. consumers bought about 22.7 million generic albuterol MDIs through retail channels. They also estimated that albuterol CFC MDIs are responsible for roughly 1,200 metric tons of CFC emissions annually.

The Issue
In 1978, FDA and the Environmental Protection Agency established rules banning the use of CFCs as propellants in aerosol containers, due to their ozone-depleting properties. The rule allowed for certain exceptions which were deemed "essential." According to the Federal Register, "The third listed essential use was for '[m]etered-dose adrenergic bronchodilator human drugs for oral inhalation.' This language describes albuterol MDIs, so the list of essential uses did not have to be amended in 1981 when Ventolin and Proventil albuterol MDIs were approved by FDA."

Although, the original rule allowed for new essential uses to be expanded, it did not provide a mechanism for removing products from the 'essential' category once safe alternatives were approved. This was altered through U.S. participation in the Montreal Protocol on Substances that Deplete the Ozone Layer in 1989 and amendments to the Clean Air Act during the 1990s.

Since then, medical products containing CFCs can be removed from the essential use listing if there are sufficient non-ozone depleting alternatives available with the same indications and approximate level of convenience. FDA also requires that there is adequate post-marketing data available for the alternative products and that supplies are adequate to meet the demand.

Alternatives
Over the last several years, safe and effective alternatives to CFC-containing albuterol MDIs have been developed. According to FDA's listing in the Federal Register last year, "Currently, there are three non-ODS [non-ozone-depleting substance] albuterol MDIs marketed-Proventil HFA (marketed by Schering-Plough), Ventolin HFA (marketed by GlaxoSmithKline) and a similar product from IVAX. Under [FDA rule], only Proventil HFA and Ventolin HFA can formally be considered as alternatives, because [the product made by] IVAX has only recently marketed its product."

FDA also specified that alternatives have been established only for single ingredient albuterol CFC MDIs. The rule did not affect combination products, such as Combivent MDI which contains albuterol as well as ipratropium. Combination inhalers are still considered essential for medical use.

FDA Comment
Last month, U.S. MEDICINE sought comment from FDA on the final rule regarding albuterol MDIs. Though not permitted to speak with him directly, Dr. Robert Meyer, Director of the Center for Drug Evaluation and Research Office of Drug Evaluation II, responded to U.S. MEDICINE questions via email from an FDA public affairs officer.

When asked whether FDA will monitor the specific pharmaceutical companies to ensure they are producing less inhalers as the Dec. 31, 2008 deadline approaches, Dr. Meyer responded, "FDA will monitor supplies throughout the transition to assure that total available albuterol, be it CFC or HFA [or hydrofluoroalkane, an alternative propellant], is adequate to meet vital patient needs. The phaseout date is essentially a point-of-sale ban, so manufacturers are well aware that they will need to handle their own inventories accordingly."

Dr. Meyer clarified that the actual phase out of CFC-containing albuterol MDIs will occur through the Clean Air Act and EPA regulations, not through FDA. He explained that FDA's role was to determine when products are no longer medically essential uses of CFCs.

U.S. MEDICINE inquired if the FDA expects asthma patients to try to hoard the albuterol inhalers or seek additional prescriptions from their physicians prior to the deadline.

"FDA does not "expect" that and, in fact, we think it vital that to us assuring that patients have adequate supplies of albuterol (CFC and HFA) that patients or large scale buyers do not "hoard" inhalers, since that will make our well-based assumptions on weekly and monthly needs much less applicable to assuring the supply," Dr. Meyer responded.

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