Marisa and Dan Levine

(Reuters) – A recently recalled batch of Glucagon Emergency Kits, Eli Lilly (NYSE:) 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.

On Sept. 24, the Indianapolis-based company issued a voluntary U.S. recall for one lot of kits whose main ingredient was Glucagon. This drug is used to treat diabetes patients with dangerously low blood sugar. Canada received a voluntary recall the day after.

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. Without providing further information, the company suggested that product failure could be due to manufacturing defects.

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 https://www.reuters.com/business/healthcare-pharmaceuticals/exclusive-lilly-hit-by-staff-accusations-fda-scrutiny-covid-drug-factories-2021-05-05 for substandard sanitation and quality control procedures.

Separately, Lilly is facing a federal criminal investigation https://www.reuters.com/business/legal/exclusive-us-opens-criminal-probe-into-alleged-lapses-eli-lilly-plant-2021-05-27 into alleged manufacturing irregularities involving another of its U.S. factories in New Jersey, details of which were first reported by Reuters https://www.reuters.com/article/us-health-elililly-special-report/special-report-insider-alleges-eli-lilly-blocked-her-efforts-to-sound-alarms-about-u-s-drug-factory-idUSKBN2B31K5 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.”

Kathryn Beiser spoke on behalf of Lilly and said that recalls had affected roughly 66,000 Glucagon Emergency Kits. About 19,000 kits were distributed to U.S. clients, with the majority remaining in Canada. According to her, the kits were made at the Indianapolis factory in May 2020. Beiser did not say whether Lilly received additional reports about adverse effects from the Glucagon Kits.

EMERGENCY KITS

This recalled Glucagon Crisis Kit is for patients with diabetes who have their blood sugar dropping and must quickly get it up to avoid seizures or death. It consists of a vial that contains freeze-dried Glucagon powder and a separate syringe containing liquid.

Normally, a caregiver will insert the liquid-filled syringe into the Glucagon vial. This is to mix the powder and prepare it for administration. Lilly announced that the liquid contained in the vial of the patient with the flu was liquid.

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.

Reuters reviewed U.S. Food and Drug Administration records from March 2021. They cited many quality control violations at the plant. These included staff failure to monitor environment conditions in which drugs are manufactured and failure to set up appropriate protocols to avoid 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. Although they recommended that Lilly take action to correct the errors, the FDA did not endorse their recommendation.

Beiser spoke for Lilly and stated that U.S. distribution of Glucagon Emergency Kits was halted by March 25, a little over a week after FDA inspection. 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.

Beiser noted that the distribution of emergency kits from this same batch was continuing in Canada. According to Beiser, the distribution of 44,000 kits throughout Canada started in February 2021. It continued into September. Beiser explained to Reuters that the kit involved in the patient complaint which triggered Canada’s late September recall was shipped from Canada.

Beiser did not comment on the reason why the distribution of Glucagon Emergency Kits from this batch continued for six additional months in Canada, after it had been discontinued in the United States. The question of whether or not the patient was able to recover from her injuries did not get answered by Beiser.

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.

FDA did not comment on the distribution of the kit, or whether other adverse event reports had been received. It also declined to say if the FDA planned to re-inspect Lilly’s Indianapolis facility, or take any additional action related to this 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

As a result of a U.S. Department of Justice criminal investigation into Lilly’s manufacturing errors and records-tampering at Branchburg, New Jersey plant that manufactures bamlanivimab as well as other drugs, the recall was initiated.

Lilly has been cleared by the Justice Department of all wrongdoing. The company also stated earlier in this year that they are cooperating with the investigation. Reuters asked Lilly about the progress of this investigation. The Justice Department didn’t respond to our request for comment.

Bamlanivimab (the COVID-19 antigen) was manufactured in Branchburg and sent to Indianapolis to be packed into vials for shipping.

According to Reuters, a report redacted by the FDA inspectors that was obtained through a Freedom of Information Act request, they arrived at the Indianapolis plant mid-February. They stayed there for over two weeks.

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.”

Inspectors also found that Lilly failed to properly sample glass components such as vials, and pharmaceutical ingredients, for drugs like Cyramza, Glucagon and bamlanivimab.

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.”

According to the redacted response, Lilly stated that it had established an extensive environmental monitoring program for microbiological control in manufacturing areas. Questions about its progress in rectifying violations at the Indianapolis facility were not answered by Lilly.