The FDA Patent History of Asthma Inhalers

Even though asthma takes an enormous toll on patients throughout the United States, many struggle to afford asthma medication. This piece focuses on one of contributing factors for the scarcity of affordable alternatives: systemic gamesmanship of FDA law as a way to thwart generic entrance. 

Drawing on my forthcoming article, The American Asthma Patient, this piece focuses on a specific type of medication: albuterol inhalers, the most commonly prescribed inhaled medication for asthma and chronic obstructive pulmonary disease (COPD). 

The Emergence of Metered-Dose Inhalers

Albuterol inhalers are drug-device combination products. The drug albuterol is a widely prescribed bronchodilator used by patients in need of quick-relief or rescue medication. It was discovered in the mid-20th century. The U.S. patent covering albuterol was issued in 1972 and expired in 1989.

The most common way to deliver albuterol (as well as other drugs used in the treatment of asthma and COPD) is through a pressurized metered-dose inhaler (MDI). MDIs were developed in the 1950s and entered the U.S. market in 1956. The first U.S. patent on an MDI issued in 1959. For decades there was barely any innovation in MDI technology.

But from the 1980s onwards there was an explosion in inhaler patenting activity. These patents cover the device itself, or components thereof but not the drug it distributes. While some inhalers dispense newer, patented drugs, albuterol itself remains off patent.

Complicating the picture, until the 2000s, the propellant used in most inhalers made in the U.S. relied on chlorofluorocarbons (CFCs). After these man-made chemicals were linked to the depletion of the ozone layer, the Montreal Protocol created a timeline to phase them out and the FDA banned the use of CFCs from 2009 onward, causing manufacturers to switch to hydrofluoroalkane (HFA) propellants. Commentators have framed that switch to HFA inhalers as a main contributing factor for the recent rise in price of asthma inhalers. 

Yet another factor soon came into play, in the form of gamesmanship of the FDA-administered Orange Book patent listing system. 

Gamesmanship of the Drug-Device FDA Listing System

FDA law requires the sponsor of a new drug to disclose information about relevant patents,  but only permits sponsors to list patents covering “the drug for which the applicant submitted the application and is a drug substance (active ingredient) patent or a drug product (formulation or composition) patent.” This information is then collected in the Orange Book and is used as the basis for any potential patent challenges when generic manufacturers apply to bring their products to market. These challenges are resource-consuming and time-consuming. One of these types of challenges, for example, triggers a stay of FDA’s review of a generic company’s application for up to 30 months.

It shouldn’t be possible to list drug-device combination products like albuterol inhalers in the Orange Book. The drug is no longer patented, and FDA law only allows the listing of drugs, not devices. In practice, however, companies routinely do it. This forces generic competitors into the costly and time-consuming process of challenging these patents – or may dissuade them from coming to market altogether.

A 2023 investigation performed by the Federal Trade Commission (FTC) identified more than 100 improperly listed Orange Book patents. Among the most common products were albuterol (and other asthma) inhalers, as well as epinephrine autoinjectors (drug-device combos such as the EpiPen). 

In 2024, the FTC expanded its investigation, uncovering more than 300 improper Orange Book listings. Asthma and COPD medication (predominantly through inhalers) is still one of the main areas in which gamesmanship occurs, but the FTC probe also found that some companies have begun using this strategy for newer products. For instance, the FTC sent a warning letter to the pharmaceutical company Novo Nordisk for improper Orange Book listing of patents related to Ozempic, its blockbuster drug used in the treatment of diabetes.

Addressing the Gamesmanship Problem

Today, the FTC is the only federal regulator actively patrolling the Orange Book improper listing space. But while FTC probes and warning letters might have some immediate dissuading effect, the agency is only capable of remedial interventions in this area. As commentators have pointed out, relying on the FTC to initiate the rooting out of impermissible listing is inefficient. Furthermore, the FTC itself is subject to politically driven shifts in policy. In the early 2000s, the agency made it a policy priority to monitor improper Orange Book listings and even brought charges under the FTC Act against some pharmaceutical companies. But between 2002 and the 2023-24 probes — as the drug-device combo improper listing were brewing — the FTC changed tactics, acting mostly through the submission of amici briefs opposing specific listings.

Arguably, the best-positioned regulator in this area is the FDA. After all, the Orange Book listing scheme is a product of FDA law – also, the gamesmanship portal opens when applications are submitted to the FDA. As early as 2002, the FTC was making this point and calling for the FDA to substantively review patents prior to being listed in the Orange Book. Yet, the FDA itself continuously reiterates that it has (and can only have) a purely ministerial role in administering the Orange Book. In other words, it does not have the resources, expertise or inclination to enmesh itself in intellectual property judgements.

There also are arguments in favor of nudging the Patent and Trademark Office (PTO) to play a more robust role in precluding Orange Book gamesmanship. As both the intellectual property expert and the earliest actor in the administrative state to deal with drug and device patents, the PTO could be called into action early. For instance, some commentators have proposed a system through which patent applicants would be forced to disclose their intention to list a patent in the Orange Book as part of its patent application. 

More likely, any kind of successful reform aimed at scrutinizing Orange Book listings would have the FDA and the PTO share the burden and collaborate. They could do so minimally by exchanging information about patent and listing status; or more robustly by co-administering a review mechanism (perhaps based on an FDA referral to the PTO).

Law- and policymakers have never seriously pursued any of these lines of reform. With recent cuts to both the FDA and the PTO, it seems unlikely that the roots causes of the opportunity for gamesmanship will be addressed in the near future. This will come at a cost for many asthma patients.