By Dan Levine and Marisa Taylor

(Reuters) – A recently recalled batch of Glucagon Emergency Kits, Eli Lilly and Co’s therapy for diabetic patients in crisis, was manufactured at an Indiana factory cited by U.S. health regulators this year for quality-control violations, including several involving that product, according to the company and a Reuters review of federal inspection records.

The Indianapolis-based company on Sept. 24 issued a voluntary U.S. recall of one lot of the kits whose key ingredient is Glucagon, a drug used to treat dangerously low blood sugar in diabetes patients. The company issued a voluntary recall in Canada the following day.

Lilly’s recall notices said that the company had received a report of a patient who experienced seizures even after being injected with the drug, a sign that the treatment was not potent enough to work. The company said the product failure might be related to its manufacturing process, without elaborating.

In response to Reuters’ inquiries, Lilly told the news organization that the affected kits were produced at a company facility in Indianapolis, and that the kit that prompted the recall had been distributed in Canada. As Reuters reported in May, the Indianapolis plant had been cited by U.S. health regulators for substandard sanitation and quality control procedures.

Separately, Lilly is facing a federal criminal investigation into alleged manufacturing irregularities involving another of its U.S. factories in New Jersey, details of which were first reported by Reuters earlier this year. The recall of Glucagon kits made in Indianapolis is the first indication of potential patient harm due to recent manufacturing issues at the company’s plants.

“Lilly is deeply committed to manufacturing high-quality medicines for patients who need them—nothing is more important to us,” the company said in a statement. “We take our obligations seriously and have rigorous quality systems in place to ensure compliance with stringent regulatory requirements.”

In all, roughly 66,000 Glucagon Emergency Kits were affected by the recalls, Lilly spokeswoman Kathryn Beiser told Reuters. She said about 19,000 of those were distributed to U.S. customers and nearly all the rest in Canada. She said the kits were produced at the Indianapolis plant around May 2020. Beiser declined to say whether Lilly has received other reports of adverse events related to the Glucagon kits.

EMERGENCY KITS

The recalled Glucagon Emergency Kit was designed for diabetes patients whose blood sugar is plummeting, and who need to raise it quickly to avoid complications that can include seizures or death. The kit consists of a vial, which is supposed to contain freeze-dried Glucagon powder, and a separate syringe filled with liquid.

Normally, a caregiver inserts the liquid-filled syringe needle into the Glucagon vial in order to dilute the powder before administering it. Lilly’s recall announcement said the vial used by the stricken patient contained liquid, instead of powder.

The company’s Indianapolis plant performs what is known in the industry as “fill and finish” – receiving raw drugs made at other facilities, putting them into vials and syringes, and shipping them to customers.

U.S. Food and Drug Administration inspection records from March 2021 viewed by Reuters cited numerous quality-control violations at that plant, such as staff failing to properly monitor environmental conditions where the finished drugs are made and failing to establish appropriate procedures to prevent contamination.

The FDA inspectors said they observed lapses in the manufacturing of the Glucagon kits as well as in Lilly’s COVID-19 antibody therapy bamlanivimab and several other drugs, according to the inspection records, dated March 16. They concluded that Lilly must take steps to remedy the lapses but did not recommend regulatory action on the part of the FDA.

Lilly spokeswoman Beiser said U.S. distribution of Glucagon Emergency Kits from the lot that was later recalled had ceased by March 25, a little more than a week after the FDA inspection report. Beiser said the distribution of the lot followed its regular process via wholesaler channels and was not related to the FDA report, adding that “any suggestion” it ended for other reasons is false.

Meanwhile, emergency kits from that same batch continued to be distributed in Canada, Beiser said. Distribution of 44,000 kits in Canada began in February 2021 and continued through the middle of September, she said. The patient complaint that triggered the late September recall involved a kit that had been shipped to Canada, Beiser told Reuters.

Beiser declined to comment specifically on why distribution of Glucagon Emergency Kits from the batch continued for another six months in Canada after distribution had ceased in the United States. She did not answer questions about whether the affected patient recovered.

Health Canada, a regulatory agency similar to the U.S. FDA, declined to comment about Lilly’s voluntary recall of the Glucagon Emergency Kits, or why kits from the batch continued to be distributed in Canada for months after they had ceased to be distributed in the United States.

The FDA declined to comment on distribution of the kits, whether it had received other reports of adverse events, had re-inspected Lilly’s Indianapolis facility or if it planned additional actions related to the recall.

“It is important to note that this recall was a voluntary action taken by the company,” FDA spokesman Jeremy Kahn said, without elaborating. “We have been closely evaluating this event and will continue to monitor the marketplace and manufacturing efforts to help ensure the availability of safe products for U.S. consumers.”

FEDERAL PROBE

The recall comes as Lilly faces a criminal investigation by the U.S. Department of Justice into alleged manufacturing irregularities and records-tampering at a separate factory in Branchburg, New Jersey, that produces bamlanivimab and other drugs.

The Justice Department has not accused Lilly of any wrongdoing, and the company said earlier this year that it is cooperating in the probe. Lilly did not respond to a question from Reuters about the status of that investigation. The Justice Department did not respond to a request for comment.

Bamlanivimab, the COVID-19 antibody, manufactured at the Branchburg facility has been sent to the Indianapolis fill-and-finish plant to be put into vials and shipped.

A group of FDA inspectors arrived at the Indianapolis plant in mid-February and stayed for more than two weeks, according to a redacted version of their report, which Reuters obtained via a Freedom of Information Act request.

In their report, the inspectors listed Glucagon as among the drugs where Lilly “failed to establish an adequate system for monitoring environmental conditions,” and noted that Lilly failed to establish and follow appropriate written procedures “to prevent microbiological contamination of drug products purporting to be sterile.”

In addition, the inspectors said Lilly did not properly conduct quality-control sampling of glass components like vials and pharmaceutical ingredients for drugs including Glucagon, bamlanivimab and the cancer drug Cyramza.

In Lilly’s April 6 response to the FDA obtained by Reuters through an open records request, the company said it takes the inspectors’ findings “very seriously” and is implementing actions to resolve concerns “on aggressive timelines.”

Lilly said it has established a comprehensive environmental monitoring program designed to assess microbiological control of manufacturing spaces, the redacted response said. The company did not respond to questions about the status of its efforts to rectify violations noted by the FDA at the Indianapolis plant.

(Reporting by Dan Levine in San Francisco and Marisa Taylor in Washington, DC; Additional reporting by Allison Martell in Toronto; Editing by Michele Gershberg and Marla Dickerson)

---