FDA hears objections to banning CFC inhalers

September 3, 2007

Chlorofluorocarbons substances responsible for thinning the ozone layer, have been almost phased out of use. A few uses deemed essential are still allowed, including some inhalers for asthma and chronic obstructive pulmonary disease.

The Food & Drug Administration, in light of three decades of regulation and international agreements on CFCs, wants to ban seven of those uses by the end of 2009 but may consider different deadlines for different uses. The agency said therapeutic alternatives for these drugs are available with all the important benefits. Some manufacturers, doctors, and patients, however, are asking for more time so that medications now delivered only in CFC formulations can be reworked to stay on the market. Otherwise, they warn, the bans could put some vulnerable patients at risk because the alternative medications are more difficult to use or are not optimal for some patients.

The medications affected are Aerobid and Aerobid-M (both from Forest Laboratories), Azmacort (Kos Pharmaceuticals), Alupent (Boehringer Ingelheim), Maxair (Graceway Pharmaceuticals), Intal (King Pharmaceuticals), Tilade (Sanofi-Aventis), and Combivent (Boehringer). The 2005 sales of these products were enough to treat about 1.2 million COPD and asthma patients for a year, FDA estimates.

Barbara Rogers, head of the National Emphysema/COPD Association, said reliance on two inhalers in some cases could necessitate using 16 to 32 inhaler puffs a day- difficult even for a healthy person. But COPD patients, many of whom are elderly and have multiple chronic conditions, may simply become noncompliant, she said. Hand-eye coordination and the need to pay two co-pays are other factors. Research has indicated that when the two medications are taken individually, compliance drops and emergency visits and hospitalizations go up. Combivent's maker said it is planning to move to a CFC-free version in the near term, possibly by the end of 2010.

In the testimony on Maxair, used for asthma, James Lee, M.D., chief medical officer of its manufacturer, Graceway, said the product is the only pirbuterol metered-dose inhaler and the only breath-actuated rescue inhaler available. More than a quarter of a million patients use it, he said. Citing substantial technical and economic barriers to reformulation of the product, which it acquired only last December, Lee asked the FDA to allow adequate time for development and transition to a non-CFC version.

Testifying in support of the company was Marc Boguniewicz, M.D., of Denver's National Jewish Medical and Research Center. Noting that asthma is the leading cause of hospitalization for children, he estimated that he has treated 10,000 pediatric asthma patients over 17 years and urged that Maxair remain available as a treatment option. "I think we have just started to recognize that asthma is much more complex and has unique phenotypes or subtypes-and that individual patients will respond or fail to respond or will have problems with specific medications." He went on to say that he uses Maxair for patients who either don't tolerate or have suboptimal responses to albuterol or other short-acting beta agonists and for "the many patients" who won't or can't use spacers.

Nancy Sander, founder of Allergy & Asthma Network Mothers of Asthmatics, noted that the manufacturer has indicated it will be at least five years until HFA (hydrofluoroalkane HFA-134a) pirbuterol is ready. She said patients might do better to transition to other medications rather than continue using Maxair with no assurance that the product will ever be reformulated and remain on the market.

Documents on the issue are in the June 11 Federal Register ( http://www.gpoaccess.gov/) and in the FDA docket (2006N-0454) http://www.fda.gov/ohrms/dockets/. Comments may be submitted through Sept. 10.

THE AUTHOR is a writer based in the Washington, D.C., area.