When I started my fellowship in pulmonary and critical care medicine in 2017, there were no generic inhalers for asthma or chronic obstructive pulmonary disease (COPD) on the US market.

A colorful chart hung in our clinic listing the numerous brand-name products by class, but there were no generics and, regardless of which inhalers I prescribed, I heard a common refrain from patients: inhalers were expensive!

For some patients, the costs were simply too great, and they would forgo therapy, occasionally citing other concerns because they were too embarrassed, I suspected, to acknowledge the financial strain.

The most perplexing component of the problem was that the drugs I was prescribing had been around for decades: beclomethasone since 1976, albuterol since 1981, ipratropium since 1986. Where were all the generics?

These questions set me on a path, culminating in an article this month in Health Affairs, to understand the barriers to generic entry in the inhaler market. Our team built a database of every patent and non-patent exclusivity listed in the Approved Products with Therapeutic Equivalence Evaluations (the Orange Book) on inhalers approved by the FDA from 1986-2020.

During the study period, the FDA approved 53 different brand-name products. Yet, through the end of 2021, only three of these brand-name products had approved generics.

Despite the abundance of brand-name approvals, we found little in the way of meaningful clinical innovation. The only product approved with a new mechanism of action during the study period was Atrovent (ipratropium) in 1986.

For the past thirty-five years, manufacturers have secured FDA approvals by developing products with new active ingredients in the same class, isolating enantiomeric precursors from racemic mixtures, creating longer-acting versions of earlier products, and combining two or more active ingredients into a single inhaler.

With only incremental changes, the inhaled products on the market today all act on the same molecular targets as the inhaled products of the 1970s and 1980s.

Still, brand-name manufacturers have secured long periods of market exclusivity for their products.

They have done so, in part, by obtaining patents on the inhaler devices rather than the active ingredients contained within; more than 50 percent of all patents on inhalers in our cohort were device-patents.

Manufacturers have also engaged in a practice of "device hopping" or shifting ingredients from one inhaler device to the next.

To take just one example, Boehringer Ingelheim received approval for its Combivent (albuterol-ipratropium) inhaler in 1996 with patent protection through 2015 and then obtained approval for Combivent Respimat in 2011 with patents lasting through 2030.

The company is currently enjoying 34 years of uninterrupted patent protection for a product line with active ingredients that were initially approved in 1981 and 1986, respectively.

Across all device hops in our study (spanning 14 originator products with 18 follow-ons), the median duration from approval of the originator product to the last-to-expire patent of follow-ons was 28 years.

Some of these device hops, including Combivent, it should be noted, followed from an FDA ban on ozone-depleting chlorofluorocarbons (CFCs). CFC-containing inhalers were initially exempt from the Montreal Protocol (signed in 1987) until more environmentally friendly inhalers could be developed.

With strong encouragement from the pharmaceutical industry, the FDA phased out CFC-containing inhalers between 2009-2013. While this ban contributed to environment protection, it was implemented without sufficient controls in place to limit costs.

Manufacturers have reaped billions of dollars of revenue since the CFC-ban, far outpacing the investments required for new CFC-free technology.

Perhaps more importantly, most of the device hops in our study involved jumps not from CFC-containing to CFC-free inhalers but from different types of CFC-free products. Sadly for our patients, these new devices offer little demonstrated clinical benefit beyond existing therapy, and yet keep costs high.

We are hopeful that our article in Health Affairs may provide policymakers with new insights into the problems now confronting the inhaler market.

Congress recently passed legislation calling on the FDA and the Government Accountability Office to examine patenting strategies by brand-name manufacturers with a particular focus on drug-device combination products like inhalers.

In our article, we consider several ideas for reform. Two excellent accompanying perspectives—one by Robin Feldman and the other by Scott Hemphill and Bhaven Sampat—lay out further ideas and help put our findings into context.

Without reform, I worry that prices will remain high and the same brand-dominated charts hanging on our clinic walls today will remain for years to come.

Today in Health Affairs Forefront, S. Sean Tu and coauthors suggest changing the patent reference listing process, which currently allows for the issuance of poor-quality drug patents that reduce competition at the expense of patients’ health and finances.

Sean Dickson discusses how reforming the FDA’s Paragraph IV requirement – a statement that the proposed generic drug will not infringe on any patent that the brand manufacturer claims applies to the existing drug – would align patent enforcement in the pharmaceutical sector with other sectors, eliminating the ability of one low-quality, later-filed patent to categorically bar all generic entry.

Elevating Voices: Pride Month: In a Health Affairs Forefront article published in December 2021, Katie Keith discussed how a proposed 2023 payment rule would restore nondiscrimination protections that were eliminated in 2020 and ensure that LGBTQ people are explicitly protected from discrimination by exchanges, states, insurers, and agents and brokers.

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About Health Affairs

Health Affairs is the leading peer-reviewed journal at the intersection of health, health care, and policy. Published monthly by Project HOPE, the journal is available in print and online. Late-breaking content is also found through healthaffairs.org, Health Affairs Today, and Health Affairs Sunday Update.

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