Amid the company’s efforts to resolve issues raised during an FDA inspection early last year, Novo Nordisk’s Plainsboro, N.J., operations, which had already received an updated Form 483, was hit with the more serious consequences of a warning letter.
Novo acknowledged the letter, available on the FDA’s website, in its own communiqué on Tuesday, emphasizing confidence that the letter would address the U.S. regulator’s concerns.
The Plainsboro tangle began when the FDA first inspected Novo’s site, which serves as its U.S. headquarters, from Jan. 13 to Feb. 7, 2025, as part of a review of the company’s compliance with post-marketing adverse drug event (PADE) regulations, the FDA explained in the letter.
The company handed Novo a Form 483 on February 7, 2025, after a number of side effects investigations and reporting concerns were flagged, the company announced in a press release this week.
“We have since worked diligently to address these findings,” Novo said, explaining that it has developed a corrective and preventive action plan and has sent FDA updates on its progress seven times since its initial response granting the Form 483.
Novo indicated that the warning letter “primarily seeks further details regarding these measures to ensure current and future regulatory compliance,” adding that the document does not draw any conclusions about the quality or safety of the company’s medicines.
Stripping away the substance of the FDA complaint, regulators in the letter emphasized Novo’s obligation to develop written procedures to investigate, receive, evaluate, and report post-market side effects to FDA, naming and opening up products containing ingredients such as liraglutide, nedosilan sodium, estradiol, and semaglutide, the molecule behind Novo’s blockbuster GLP-1 drugs Ozempic and Wigovy.
Despite the popularity of GLP-1s like Wegovy for weight loss purposes, the high side effect burden (mainly gastrointestinal) of this class is well documented.
However, the FDA argues in the letter that Novo’s procedures for tracking adverse events are insufficient.
FDA’s issues with Novo’s process included concerns about the timing of adverse event reports to regulators, provisions allowing Novo to reject or cancel reports it receives, and the length of the medical review associated with the reports.
The FDA acknowledged that Novo had taken steps to correct the vessels at the Plainsboro site, but the regulator said those remediation plans were not detailed enough to determine whether they would prevent similar violations in the future.
The FDA harshly reprimanded the company, saying Novo’s “failure” to identify and assess the root cause of the problem “raises concerns about your ability to monitor the safety of your products.”
FDA added: “Given the results of our inspection and the nature of your written responses and communications, we have serious concerns about the scope and impact of these violations on your entire product portfolio.”
Novo reiterated its confidence in its ability to address the FDA’s concerns and also took time to address a series of recent regulatory actions in the United States in a press statement this week.
“Novo Nordisk takes PADE reporting requirements seriously and plans to address requests for warning letters promptly and comprehensively,” Anna Windle, head of clinical development, medical and regulatory affairs at Novo Nordisk US, said in a statement. “We are confident that we will resolve the issues identified in the warning letter to the FDA’s full satisfaction.”
As for the company’s other recent FDA reports, Novo received two so-called untitled letters related to the marketing of Ozempic and Wigoby, which the company says are “under control.” It also received another warning letter on its Bloomington, Indiana, site as part of Novo Holdings’ acquisition of CDMO Catalent.
In a statement Tuesday, Novo referenced the discipline in Plainsboro and Bloomington, stressing, “I have full confidence that we can comprehensively and expeditiously address the matters identified in each letter of warning.”
Novo’s willingness to acknowledge the latest warning letter is somewhat unusual for the industry and may reflect the fact that the Danish drugmaker has had a rough marketing campaign in recent months.
The ongoing problems at Novo’s Indiana plant, formerly operated by Catalent, are apparently related to several recent FDA drug rejections, including a complete response letter given last month to Incyte’s PD-1 inhibitor Zynyz as a first-line treatment for non-small cell lung cancer.
Novo’s acquisition of the Bloomington facility is a known fact, but third-party manufacturing sites are typically not named when companies or the FDA itself communicate drug rejections that have affected production. But in Novo’s case, the CRL related to the Indiana plant led to a series of negative production headlines for the Danish drugmaker.
