Novartis hit with FDA letter detailing 'significant' Kymriah manufacturing shortfalls

When it comes to manufacturing cell therapies, it's often said that the "process is the product." But churning out these complex, individualized drugs has routinely tripped up even the industry's largest players.

In recent months, Novartis has faced FDA scrutiny due to “significant” production flubs tied to its flagship CAR-T medicine Kymriah, a newly posted letter shows.

This past August, the FDA issued an untitled letter (PDF) after an inspection of Novartis’ Morris Plains, New Jersey, manufacturing facility between Nov. 28 and Dec. 9 of last year. In the wake of the inspection, the agency handed down a Form 483 describing “significant” deviations around Kymriah production.

Novartis responded to the Form 483, according to the letter, but the agency subsequently identified “additional significant deviations" related to the Kymriah manufacturing process.

Endpoints News was the first publication to report on the FDA letter, which was issued this summer but only posted on the agency's website this week.

Chief among Novartis’ production problems, the company’s sampling and testing procedures around the freezing of cryobags could not confirm that the specialized Kymriah containers were free of particulate matter, the FDA said in its letter.

In fact, between late 2018 and the 2022 inspection, the FDA says Novartis flagged 100 batches of Kymriah that were contaminated with foreign particulates such as wood, cellulose, brass and steel. In Nov. 2020, the company concluded the cryobags were the “most probably root cause.”

Novartis, for its part, says it has responded to the FDA and has been working to address the agency’s findings, a company spokesperson explained over email on Wednesday.

“Patient safety is always our top priority,” the spokesperson said. “We remain confident in the quality, purity, and potency of every patient lot of Kymriah manufactured and distributed from our Morris Plains site.”

Aside from the particulate concern, the FDA flagged issues with possible microbial contamination. Between Oct. 2019 and the date of the inspection, the company logged roughly 100 possible contamination instances in the areas where Kymriah is manufactured, according to the FDA.

“Contributing factors identified by your firm include gaps in procedures relating to cleaning and sanitizing of manufacturing areas, equipment cleaning and sanitizing, equipment transport, material handling, personnel gowning, clean room behavior, and handwashing and sanitation as well as failure to follow some of these procedures,” the regulator said.

Because of the infractions, Novartis was summoned to an FDA meeting in October, the regulator said.

The FDA did not respond to a request for comment on the situation.