In its first analysis, the newly formed End Drug Shortages Alliance (EDSA) warns that the recent shuttering of a troubled Teva Pharmaceuticals manufacturing plant in Irvine, California, could affect the availability of 24 generic sterile injectable drugs, including 5 essential medications for which the company had an over 15% market share.
The Israel-based, multinational Teva, one of the world's largest generic drug producers, closed the plant after receiving the latest in a string of warning letters from the US Food and Drug Administration (FDA) about observations of contamination, dirty changing rooms and scrubs, and a years-long lack of sterilization and testing of equipment.
In an October 2021 letter, the FDA detailed possible mold contamination of the company's injectable drugs from unaddressed water leaks. In response, Teva recalled more than 2.5 million vials of injectables used for indications such as cancer, arthritis, schizophrenia, and muscle relaxation for intubation. It also halted production at the facility.
Pivot, redundancy, stewardship urged
The EDSA report, released last week, involved a market analysis of the potentially affected drugs, which include those used to treat cancer, adult and pediatric diabetes, and pancreatic neuroendocrine tumors.
The injectables produced at the closed plant most vulnerable to shortages were the vasodilator alprostadil; the antibiotic amikacin; the chemotherapy drugs bleomycin, dacarbazine, idarubicin, ifosfamide, mitoxantrone, streptozocin, and topotecan; and the hormone octreotide.
Those less likely to be affected are injectable adenosine, daunorubicin, desmopressin, epoprostenol, epoprostenol diluent, etoposide, haloperidol decanoate, leucovorin, medroxyprogesterone, methylprednisolone acetate, metoclopramide, norepinephrine, vecuronium, and vincristine.
The report lists suppliers that may step up production of the drugs to meet needs, estimates the potential impact for each drug, and details strategies to help surmount supply challenges.
Specifically, it advises drug manufacturers to assess their ability to boost production of the affected drugs and pivot or increase capacity, and it recommends that wholesalers keep enough supplies on hand to ensure the medications are available.
The FDA, the EDSA said, should expedite approval of any applications for drugs affected by the plant closure or mull their importation, particularly for those without alternatives (eg, streptozocin). Group purchasing organizations should formulate strategies to provide more redundancy for essential medications, and providers and clinicians should practice good stewardship when ordering, prescribing, and administering the affected drugs, EDSA added.
"Information shared in this report highlights the level of transparency that is required across the supply chain to successfully navigate drug shortages," Terri Lyle Wilson RPh, EDSA vice-chair and director of pharmacy supply chain services at the Children's Hospital Association, said in a news release.
Onshoring will help but is no panacea
EDSA, a collaboration of more than 70 health systems and supply chain and pharmaceutical industry experts formed in November 2021, aims to end drug shortages by boosting transparency, communication, quality, redundancy, and production.
Stephen Schondelmeyer, PharmD, PhD, co-principal investigator of the Resilient Drug Supply Project (RDSP), was a founding member of the EDSA board of directors. RDSP is part of the University of Minnesota's Center for Infectious Disease Research and Policy, publisher of CIDRAP News.
The Teva plant closure is a reminder that a lack of adherence to quality and safety guidance from FDA isn't unique to overseas manufacturing.
While onshoring of drug production will shorten the supply chain and make it easier for the FDA to inspect facilities, onshoring is not always a failsafe solution. Many other US drug manufacturing plants have had serious FDA compliance issues in recent years, including Eli Lilly & Co.'s New Jersey facility, Pfizer's Kansas operation, and Emergent BioSolutions in Baltimore, which led to the disposal of as many as 400 million doses of COVID-19 vaccine in the past 2 years.
"The proximity of making medications in America can be an important factor in strengthening the resilience of our drug supply chain," he said. "However, where a drug is made is not a guarantee of its quality. Quality assurance is essential to a robust drug supply no matter where the drug is made."