New Rules and Possible Shortages Could Spur Drug-Delivery Innovation

By Maximillian Del Rey

Generic albuterol inhalers utilizing CFC propellants are already informing users that they will soon be discontinued.

Metered-dose inhalers (MDIs) for the lifesaving asthma drug albuterol will undergo a significant change in propellant for the first time since the product was introduced in 1981. Chlorofluorocarbon (CFC) propellants, deemed by the U.S. Environmental Protection Agency (EPA) as ozone layer–depleting substances (ODSs), must be replaced by hydrofluoroalkane (HFA) propellants in all MDIs by December 31, 2008, FDA has an­nounced. After this date, no CFCs may be marketed for inhaler use.

Until the FDA decision, albuterol MDIs had been protected as an essential use of ODSs; however, the marketing of two HFA-propelled inhalers made CFC use dispensable.

The ruling also relates to the United States’ participation in the Montreal Protocol, which seeks to eliminate the production and use of ODSs. The caucus provides stringent regulations for CFC use; it additionally requires nations to submit action plans to phase out essential uses of CFCs.

Since 1978, FDA and EPA have strictly limited the trafficking of ODSs for all purposes except essential uses in an effort to counteract depletion of the ozone layer. Because no contemporary, viable alternative to CFCs existed to deliver albuterol in MDIs, the act reserved the right to continue use of the compounds.

This upcoming ban leaves the four patent holders of HFA MDIs as the sole producers of albuterol in­halers, eliminating generic competition.

A name-brand market might drive up the price of albuterol inhalers, FDA announced, and could significantly benefit HFA inhaler manufacturers as well as others serving the industry.

The U.S. inhaler market has already begun preparing for the loss of generic producers, says Katheryn Symank, a research analyst for Frost & Sullivan consulting group. The remaining MDI producers must prepare for the logistical challenges of meeting the needs of the United States’ 20 million asthmatics. According to a 1998 FDA study, more than 25 million Americans use MDIs to relieve symptoms of asthma, chronic obstructive pulmonary disease, and other lung diseases characterized by obstructed airflow and shortness of breath.

HFA technology will take time to implement. In 2006, 74% of all inhalers distributed in the United States were generic, CFC MDIs, Symank says. FDA estimates 90 million to 435 million fewer inhalers will reach consumers because of the upcoming change, in part because of patents that prevent the development of generic HFA alternatives until at least 2010 and possibly until as late as 2017. FDA lists albuterol on its Drug Shortages list because of this transition.

The CFC phase out could inspire drug manufacturers to create new, innovative drug-delivery methods, Symank says.

The ruling might mean the MDI industry will see increased competition from such delivery methods as dry powder inhalers (DPIs). DPIs use blisters, capsules, or other cavities to deliver a premetered dose of inhalant either powered solely by respiration or by another power source.


No votes yet