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 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.”
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 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)
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