By Dan Levine and Marisa Taylor
(Reuters) – Eli Lilly & Co (NYSE:) employees have accused a factory executive of altering documents required by government regulators in an effort to downplay serious quality control problems at the U.S. plant producing the drugmaker’s COVID-19 treatment, according to an internal Lilly complaint and a source familiar with the matter.
The unsigned report, filed April 8 in Lilly’s confidential employee complaint system and reviewed by Reuters, is the latest sign of manufacturing problems at the drug giant. The complaint asserts that the executive, a top quality official at the company’s factory in Branchburg, New Jersey, rewrote findings by Lilly technical experts at the plant, which has been under investigation by the U.S. Food and Drug Administration, to make the conclusions appear more favorable to the company.
The source, who spoke on condition of anonymity, said the findings involved the production of drugs including Lilly’s COVID-19 therapy, whose use in the United States is funded by the federal government. The coronavirus antibody treatment, bamlanivimab, has been authorized by the FDA for emergency use in combination with a second Lilly drug for mild to moderate infections in people at high risk of severe illness.
Separately, FDA inspectors in March identified numerous manufacturing lapses at a second Lilly facility in Indianapolis that bottles the COVID-19 therapy and other drugs. The problems included substandard sanitation and quality control procedures, according to a preliminary FDA inspection report released to Reuters under open records laws. The Indianapolis inspection findings have not been previously reported.
The troubles at the two factories, along with a succession of internal complaints in recent years, deepen the regulatory, production and leadership issues facing Lilly, one of the largest drugmakers in the world. In addition to the FDA investigations, Lilly’s chief financial officer resigned in February over what the company called “inappropriate personal communications” with an employee. He has declined to comment in the past and could not be reached Tuesday.
As Reuters reported in March 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, a human resources officer at the Branchburg factory said she was forced out of her job after raising concerns about quality control, record-keeping and staff shortages in the Branchburg factory. The company has denied any retaliation against employees.
Contacted by Reuters for this story, Lilly confirmed it had received the recent employee complaint about the Branchburg plant. The company said it could not comment further given that an investigation was underway by an independent third party, which it did not identify.
“Depending on the outcome of that investigation, we will take appropriate action,” said Lilly spokeswoman Kathryn Beiser. “Lilly has long-standing policies and procedures designed to enable – and encourage – individuals to come forward with information about any potential issues or concerns without fear of retribution.”
Lilly also confirmed that it had submitted a response to the FDA about its recent inspection of the Indianapolis plant. The company declined to share the document with Reuters, and said none of the issues identified by the FDA at either plant has affected the quality of products released in the marketplace.
Amid the escalating manufacturing problems, however, the Branchburg plant has not shipped new batches of the COVID-19 drug bamlanivimab in nearly two months, according to the employee complaint and the source familiar with the matter. Reuters could not independently confirm that the Branchburg plant was not releasing bamlanivimab to the Indianapolis bottling plant or other facilities.
Lilly did not respond to questions about whether shipments have stalled at Branchburg, though the company said it expected to meet its production commitments for the COVID-19 treatment.
The Branchburg factory executive named in the complaint, Lydia Wible, did not respond to requests for comment made via email and telephone. On her behalf, Lilly said she declined to comment.
Lilly did not make Chief Executive Officer David Ricks available for comment. Reuters found no evidence he knew of the problems described in the complaint.
The new complaint about the Branchburg facility refers to “13 employees involved in this investigation.” It does not identify them, saying they fear retaliation. The source familiar with the matter said the group that submitted the complaint comprises more than 10 employees, including managers.
The source claimed that many of the staffers had seen the relevant documents both before and after they were altered.
The complaint did not specify what alterations the employees believed were made to the documents but said Wible “rewrites factual data provided by subject matter experts to formulate responses she feels are more beneficial.”
It is not clear whether any of the documents have been submitted to the FDA, although the agency routinely reviews such records.
The FDA declined to answer questions on the Lilly inspections or the employee complaint, but said “the agency takes the safety and quality of FDA-regulated products seriously” and noted that it imposed quality control measures when it authorized bamlanivimab.
The U.S. Department of Health and Human Services, which oversees vaccine and therapeutics production, did not respond to requests for comment.
Nathan Cortez, a law professor who specializes in FDA regulation at Southern Methodist University in Texas, said the employee accusations regarding Branchburg and Indianapolis could amplify Lilly’s problems with regulators.
“If you have a string of manufacturing problems across multiple facilities and you’re starting to develop a not-so-great manufacturing track record, the FDA will probably consider harder responses,” he said. Referring to the internal complaint, he said: “If somebody is sticking their neck out, that strikes me as a pretty big deal and evidence of some deeper problems within the company.”
DISCOMFORT AND DISMAY
The April complaint asserts that Wible, the Branchburg factory executive, altered information provided by internal technical experts, saying she is “solely responsible for providing written responses to the FDA” regarding the types of quality control problems that regulators flagged.
The complaint said that Wible – who did not respond to questions from Reuters – used “her authority to rewrite technical investigations for which she has little or no experience.”
According to the complaint, staff members who gather information for the FDA were concerned about presenting altered material to regulators. They “are uncomfortable and do not feel confident in defending the reformulated responses in the event they are called upon by the FDA,” the complaint said.
The complaint also expressed impatience with company leaders.
“How long is it going to take for the company to pay attention and do something about this?” it said, referring to the accusations against Wible. “We are all working very hard to meet the commitments to the FDA and cannot do so under these conditions.”
The complaint said Wible had, prior to recently altering the records required by the FDA, provided “fabricated” information including “fictitious numbers” to a Branchburg human resources investigator looking into potential manufacturing lapses.
Asked by Reuters about the matter, former human resources investigator Amrit Mula confirmed that she had concluded through an internal inquiry in 2018 that Wible had given her fabricated information. Mula said she was looking into unsanitary conditions in a warehouse, as well as information about the improper disposal of quality-control records for Trulicity, a blockbuster diabetes drug then made at the plant.
Reuters reported in March that Mula claimed to have identified serious violations of FDA manufacturing rules at the plant and to have been forced out of the company in early 2019. Mula has since sought compensation from Lilly, arguing the company retaliated against her for raising legitimate concerns as part of her job.
Senior executives at Lilly headquarters in Indianapolis, including Leanne Hickman, vice president of quality, knew about the alleged fabrications and retaliation and protected Wible, doing nothing to address the problems, according to the complaint.
Hickman did not respond to requests for comment conveyed by email and telephone. On her behalf, Lilly said she declined to comment.
In November 2019, roughly eight months after Mula’s departure, FDA inspectors showed up at the Branchburg plant for a routine inspection and cited some of the same problems Mula said she had repeatedly flagged to her bosses. The preliminary FDA report found that quality control data on various manufacturing processes had been deleted and not appropriately audited.
The FDA red-flagged the problems as “Official Action Indicated,” or OAI, which is its most serious category of violation. If not addressed, an OAI can lead to a prohibition on the sale of drugs from a facility, regulatory experts say. The FDA has not taken further public action.
Inspectors returned in July and found several more problems, including that the company failed to properly investigate quality-control problems to prevent recurrence and that batches of drugs had been discarded because of manufacturing mistakes.
In October, the Trump administration ordered $ 375 million worth of bamlanivimab and shortly afterward authorized its use on an emergency basis to help curb the pandemic. Bamlanivimab is combined with a second Lilly drug, called etesevimab, to treat COVID-19.
‘A LOT OF WORK TO DO’
A condition of the emergency authorization was that an outside auditor inspect batches of bamlanivimab to ensure they met FDA standards. Lilly and the FDA have not responded to questions from Reuters about whether this requirement was carried out.
Lilly said in March that its combination antibody therapy reduced the risk of hospitalization and death by 87% in a study of more than 750 high-risk COVID-19 patients.
Around he same time, the FDA inspected the Indianapolis plant, which receives the kinds of injectable drugs manufactured in New Jersey, fills them into vials and syringes, and distributes them to customers.
Preliminary FDA reports, which are partially redacted, show inspectors found that procedures to ensure certain areas remain sterile were substandard and that Lilly failed to thoroughly investigate drug batches that had failed quality control tests. In addition, when vials from outside vendors were discarded as defective, the company failed to thoroughly investigate.
“The FDA found serious concerns on multiple fronts,” said Steven Lynn, a former head of the FDA’s Office of Manufacturing and Product Quality, who reviewed the inspection report for Reuters. “Lilly has a lot of work to do.”
(Dan Levine reported from San Francisco and Marisa Taylor from Washington, D.C. Editing by Michele Gershberg and Julie Marquis)
This post originally appeared on Stock Market News