FDA cites litany of errors at Lonza Houston plant at the center of Bristol Myers CVR debacle

04 Feb 2021
endpts.com
AcquisitionCollaborate
Investors’ somewhat longshot bet on a $9 CVR tied to Bristol Myers Squibb’s acquisition of Celgene came to a screeching halt last month after the FDA took too long to decide on CAR-T candidate liso-cel. One of the potential culprits in that delay, a December inspection of a contract manufacturer, now appears to have played a big role after the FDA cited a number of issues at that plant. In a Form 483 published online this week, the FDA blasted Lonza Houston, one of the contract manufacturers for liso-cel, for a litany of errors, including mislabeling, products for the US and EU drug markets stored in the same bins, “poorly maintained” freezer units, and expired batches of ingredients that weren’t properly disposed of. Those issues were found during an early December inspection and outlined in the four-observation Form 483 . Despite Bristol responding to concerns at the site within eight days, it wasn’t enough to get liso-cel on track for an approval by year-end — one of the key checkpoints for the $9 CVR. Despite those issues, Lonza ultimately believes a delay in the planned inspection at its site due to Covid-19 may have ultimately torpedoed the approval. In a statement Wednesday, Lonza spokesperson Sanna Fowler said the company is “rapidly addressing” the FDA’s observations from the December site inspection, and isn’t aware of any reasons that would further delay the approval of the drug in question—Bristol Myers Squibb’s liso-cel CAR-T therapy. “Lonza regularly receives visits from international regulatory bodies, including the FDA and in a typical year we host around ten FDA inspections,” Fowler wrote in an email. “We take compliance very seriously and do everything we can to ensure that all customers and stakeholders, including regulators, are satisfied. When issues come to our attention, we address them expeditiously and effectively, as is the case here.” Lonza, Fowler said, remains committed to supporting Bristol Myers Squibb “in their goal of bringing liso-cel to patients with relapsed or refractory large B-cell lymphoma.” A weeklong inspection of the Lonza site was part of the liso-cel drug application review. Due to Covid-19 restrictions, though, an inspection initially scheduled for April was significantly delayed to Dec. 3-10. This delay, observations aside, had drastic and expensive ramifications for Bristol investors, who were relying on a PDUFA approval for liso-cel by Dec. 31, 2020 to cash in on a $6.4 billion payday linked to the company’s Celgene merger. While the Form 483 itself isn’t a death nail to an eventual liso-cel approval, it further delayed those regulatory processes and firmly shut the door on any hopes those investors had of the additional payday. When the FDA finally did come to inspect Lonza’s site, it clearly wasn’t quite prepared. The Form 483 notes that among the aforementioned observed issues, facility workers apparently failed to verify the identity of each new batch of raw materials before they were released to the manufacturing processes. Written procedures weren’t always followed, and the inspectors said they observed one case of aseptic operation control that was inadequate. On Jan. 1, Bristol Myers Squibb issued a brief and somewhat cryptic press release updating the status of the liso-cel application, and said that both Lonza and the company “responded expeditiously” to observations from the Dec. 3-10 inspection, but didn’t mention the Form 483. Bristol Myers Squibb hasn’t publicly commented on the liso-cel application process since. In a statement , a company spokesperson said the work to get the drug approved continues but didn’t specifically address its partnership with Lonza, the Form 483 observations or the CVR losses imposed by the delay. “The company continues to work closely with the FDA to support the on-going review of the BLA for liso-cel, the timing of which is set by the FDA,” the spokesperson said. “We are committed to bringing liso-cel to patients with relapsed or refractory large B-cell lymphoma who still have significant unmet needs.”
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