When Critical Drugs Run Short, Who You Gonna Call?

When Ferring Pharmaceuticals discontinued production of DDAVP/Stimate (desmopressin acetate) in 2020, a Denver-based, 503B outsourcing facility, stepped in to augment supplies of the product, which is used to treat bleeding in patients with hemophilia A or von Willebrand disease.

The outsourcer, STAQ Pharma, has also been called upon recently to produce supplies of a high-concentration form of albuterol, a critical asthma medication, following the bankruptcy of Akorn Pharmaceuticals. STAQ Pharma was able to produce DDAVP in relatively small quantities, 150 vials a month or so, and albuterol in much larger quantities to supply hemophilia treatment centers and children’s hospitals, respectively.

503B outsourcers can produce in bulk for use as needed, rather than for individual patients, which small compounding pharmacies generally do.

Joe Bagan, CEO of STAQ Pharma

“We are inspected by the FDA, and we adhere to the current good manufacturing practices (cGMP) standard for production. We're not your corner compounding facility,” says Joe Bagan, founder and CEO of STAQ Pharma.

STAQ Pharma is a for-profit company. It contracts with healthcare provider institutions to produce drugs in short supply, and its prices can be competitive with those of the original manufacturer.

“In the case of desmopressin, our cost is much less than what the (Ferring) product was, because that was a global product,” Bagan said. “I'm sure there were a lot more licensing costs and registration fees to file with each government, to get that product on market. As a 503B, we are essentially serving the U.S. market, and we've been able to produce for less. It doesn't always work that way. For albuterol, costs are the same as before.”

STAQ Pharma is providing desmopressin nasal spray at a contracted wholesale acquisition cost (WAC) of $400 per vial, with 6 actualizations or pumps each, down from an average WAC of $480, according to the Hemophilia Alliance, which initiated the contract on behalf of hemophilia treatment centers.

Ferring Pharmaceuticals discontinued producing DDAVP and Stimate, a higher concentration product, because seals on the vials did not close tightly, leading to evaporation and the potential for patients to receive dangerously high concentrations of desmopressin, a synthetic version of vasopressin, a hormone with a wide range of effects.

Ferring announced intentions to resume production, but confidence is low given that nearly three years have elapsed since production was suspended, according to Joe Pugliese, CEO of the Hemophilia Alliance.

Meantime, a shortage of another bleeding control drug, Amicar (aminocaproic acid; fibrinolysis) also developed via the bankruptcy of Akorn Pharmaceuticals, although this drug may not meet FDA criteria for 503B outsourcer production, as several producers remain.

A March 2023 report by the Homeland Security and Government Affairs Committee noted that U.S. drug shortages have been rising and peaked at 295 by the end of 2022.

“The federal government’s inability to comprehensively assess U.S. pharmaceutical supply chain vulnerabilities and address known causes of shortages for critical drugs continues to frustrate attempts to predict drug shortages and effectively mitigate their impact on patient care,” the report states.

The DDAVP/Stimate and albuterol shortages were attributable to packaging quality issues and the bankruptcy of a key supplier, respectively, but the Senate report calls attention to America’s heavy reliance on China and India for active pharmaceutical ingredients (APIs).

“Between 2010 and 2015, the number of Chinese-based API manufacturers that registered with the FDA more than doubled,” the report states. It's unclear how heavily major pharmaceutical companies in the United States rely on individual API producers, and visibility must be improved, the report said.

Bagan said starting materials for APIs could be sourced from elsewhere in the world, but political willingness to source and manufacture APIs in the United States is lacking.

“Where are the raw elements coming from that go into them to be synthesized and create APIs? For albuterol, the API is not short. We have a lot of it. It was the finished drug product that was short,” he said.

Another issue with production of drugs in short supply is simply having enough time to prepare.

“Several of the children’s hospitals that are part of our ownership group were struggling with their patient volumes back in September or October of 2022,” Bagan said. “They called and asked us to watch [the albuterol situation] carefully.

“We need that early warning. We need months to get ready to produce a drug under cGMP. You don’t just start producing it. You’ve got to find suppliers. You’ve got to qualify the suppliers. You’ve got to make sure you can make the drug safely and effectively and successfully. You need to make it and test it…. There’s a lot that goes on in order to get a drug ready,” Bagan said.