Armstrong Pharmaceuticals says FDA "assured" the firm that it can sell a proposed reformulated epinephrine inhaler OTC, if approved, despite opponents who say asthma relief is an inappropriate self-medication indication.

The Roxbury, Mass.-based generics manufacturer is pursuing approval of a reformulation of its Primatene Mist epinephrine inhaler while helping FDA plan for the original product's withdrawal from the market.

The firm participated in an FDA public workshop in Rockville, Md., Sept. 25 to discuss how to communicate to consumers the phase-out of chlorofluorocarbon-propelled epinephrine inhalers.

Armstrong expects to file an investigational new drug application in October for an epinephrine inhaler that uses hydrofluoroalkane in place of CFCs, which must come off the market by the end of 2011 to comply with FDA's final rule that bans the CFC version (¹ Also see "Primatene Mist To Be Unavailable After 2010 – Proposed Rule" - Pink Sheet, 24 September, 2007.).

"We are approximately a month away from beginning clinicals" to test the safety and efficacy of the new formula, said Stephen Campbell, senior VP of regulatory affairs at Amphastar Pharmaceuticals, Armstrong's parent company.

Campbell explained "there is a 30-day waiting period after an IND is filed while the FDA reviews [the application] and assures itself the trials are appropriate and acceptable. But we do not anticipate any difficulty there because we met a couple of times with the agency to discuss those trials."

Likewise, Campbell said in an interview, the company does not consider stakeholders who oppose OTC treatment of asthma a barrier to OTC approval of the new formula.

"We have been assured by FDA, at this point," that the new formula will go straight to OTC once the agency approves it, he said.

Before the company can sell the product OTC, though, it must complete safety and efficacy trials and submit a new drug application for the product. FDA then must review and approve the application.

However, Campbell said, Armstrong hopes for a speedy and positive NDA review so that the product can be on shelves by the end of 2011.

Indeed, at the workshop, Badrul Chowdhury, director of FDA's Division of Pulmonary and Allergy Products, said the agency is "very enthusiastic and encouraged by" Armstrong's reformulation.

Andrea Leonard-Segal, director of the agency's Division of Nonprescription Clinical Evaluation agreed with Chowdhury that an OTC asthma relief product is important to the agency.

She stressed FDA is removing Primatene Mist from the market only because it uses CFCs, and that the product would stay on the market if it used a different delivery format that is allowed by an international agreement to reduce CFCs for environmental reasons.

She added adverse event reports related to Primatene Mist do not suggest the product is not safe or effective.

Some Stakeholders Disapprove Of OTC Access

Leslie Hendeles, a pharmacy and pediatric professor at the University of Florida, agrees OTC epinephrine is safe and effective for mild, intermittent asthma, and that removing the inhaler from store shelves would disadvantage consumers. However, he maintained at the meeting OTC access to asthma drugs is inappropriate and dangerous.

He explained in an interview before the meeting that "asthma should be diagnosed and managed" by a health care practitioner because it poses a "risk of dying" if mistreated or untreated.

The American Lung Association agrees self-care drugs for asthma are "a bad idea" because they do not improve or stabilize consumers' conditions (² Also see "No Relief In Sight For Future Of OTC Asthma Products" - Pink Sheet, 24 August, 2009.).

For these reasons, Hendeles advocates placing OTC inhalers behind the counter where a pharmacist could administer them after evaluating consumers.

Leonard-Segal said a third class of drugs - a controversial concept that many manufacturers oppose - is something Congress would have to create through legislation.

In response, Marcus Reidenberg, a professor of medicine, pharmacology and public health at Weill Cornell Medical College, urged FDA to "be imaginative" and figure out how to provide easy access to an OTC asthma product - whether it be a reformulation of Primatene Mist or an OTC version of current prescription inhalers.

For example, he asked FDA to consider offering asthma inhalers both OTC and prescription to maximize accessibility and insurance coverage.

Leonard-Segal noted regulations prohibit dual OTC and prescription sale of the same product unless it has a different formula or indications.

FDA Should Tell Users To Talk To Practitioner

Other workshop participants echoed Hendeles' concern that asthma is an inappropriate OTC indication and that consumers need to discuss their symptoms with a health care practitioner. They said the phase-out of CFC Primatene Mist is a good opportunity for FDA to encourage consumers to seek professional care.

Ruth Parker, a professor of medicine at Emory University, called for the agency go one step further and tell consumers that OTC products alone are insufficient asthma treatment.

She said the agency should neither recommend an alternative therapy, other than to see a practitioner, nor inform consumers that a reformulation of Primatine Mist may be available OTC soon.

That said, Parker emphasized the main message FDA needs to deliver is that CFC propelled inhalers will not be available after Dec. 31, 2011. Campbell agreed this is the most important message.

He said FDA already approved label changes that include placing a red banner on the primary display panel of the inhaler's package to notify consumers the product will be discontinued. The package insert also will say this in red type, he said, but the actual inhaler device is too small to bear the message.

Armstrong made the label changes, in case the new formula is not on the market by the end of 2011, Campbell said, but he emphasized Armstrong is "confident we will have a replacement version available by the time the CFC [version] goes off the market."

- Elizabeth Crawford ( ³ e.crawford@elsevier.com )

Armstrong Says FDA "Assured" OTC Access Of Reformulated Primatene Mist

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