CFC-Containing Albuterol Phase-Out Review To Begin January 2003

FDA will begin the phase-out process for CFC-containing albuterol and beclomethasone products after Jan. 20, 2003, when its final rule on ozone-depleting substances goes into effect.

The July 23 final rule shortened by six months the effective date for FDA's "moiety-by-moiety" review of products with non-CFC containing alternatives. The original one-year period was outlined in the agency's Sept. 1, 1999 proposed rule.

FDA said it shortened the period because of "the length of this rulemaking process, the anticipated length of future rulemaking to remove essential-use exemptions, and the importance of eliminating ODS' in a timely manner."

The existence of two CFC-free albuterol alternatives, GlaxoSmithKline's Ventolin HFA and Schering-Plough's Proventil HFA , make albuterol the first moiety with an essential-use exemption likely to undergo review. While the brand name companies have developed CFC-free versions of albuterol, generic companies continue to market CFC-containing albuterol MDIs.

Review of beclomethasone also is likely, since there is a CFC-free alternative: Qvar currently is marketed in the U.S. by Ivax under a licensing agreement with 3M. CFC-containing beclomethasone inhalers on the U.S. market are sold by Glaxo Wellcome ( Beclovent / Beconase ) and Schering ( Vanceril / Vancenase ).

While only one CFC-free alternative to beclomethasone is available, that would not stop FDA from proceeding with removal of the CFC products, FDA suggested. The agency said it is eliminating its proposal that CFC products be replaced by at least two non-ozone depleting products.

FDA plans to eliminate the essential-use exemption for steroid metered dose nasal inhalers on July 24, 2003. All CFC-containing nasally inhaled steroid products will be taken off the market.

The final rule also says that FDA will begin on Jan. 1, 2005 to review all CFC-containing products, even products for which there is no CFC-free alternative.

FDA had originally proposed only to evaluate products with CFC-free alternatives. The agency noted that it intends to consult with an advisory committee and pursue notice-and-comment rulemaking before making such a determination.

The final rule also says active moieties marketed in multiple distinct strengths need not be replaced by products marketed under more than one NDA (¹ (Also see "CFC-Free Inhalers Would Not Need To Replace All Strengths – FDA Final Rule" - Pink Sheet, 22 Jul, 2002.), p. 15).

Epinephrine is another moiety that FDA could review once the rule becomes effective. Three metered-dose inhalants are available over-the-counter: Whitehall-Robins' Primatene Mist , Bayer's Bronkaid Mist and Menley & James' Asthmahaler Mist .

The rule also provides for a petition process under which stakeholders can ask the agency to consider adding new "essential uses" for an active moiety.

"FDA will consider adding a new essential use if the use is for a product that will provide an unavailable important public health benefit. FDA believes that it is possible, under this criterion, for a product that offers a compelling therapeutic benefit for a significant, albeit small, subpopulation to qualify for an essential use," the rule states.

In response to comments expressing concern that FDA should not eliminate an essential use unless a CFC-free generic is available for that use, FDA noted that the only generic CFC-containing metered dose inhaler available is albuterol.

"It would seem inappropriate to require the availability of a non-ODS generic drug product when there is no generic version currently on the market and we have no guaranty that a generic drug will ever be developed for any given moiety," FDA said.

FDA abandoned its proposal to require at least one year of postmarketing data in response to comments. The agency plans "to consider foreign data supportive of U.S. postmarketing use data if U.S. and foreign formulations, patient populations, and clinical practices were the same or substantially similar."

The final rule brings FDA into accordance with the 1987 Montreal Protocol, which calls for the phase-out of ozone-depleting substances.