Miami-based Opko was caught off guard last month when the FDA cited concerns over a Catalent ($CTLT) plant in Florida that is producing its drug candidate as the reason the agency was putting off its decision on whether to approve it. Now the FDA has posted its 13-page report, with more than a dozen observations, laying out the issues it finds troubling at the plant.
When it received the CRL, OPKO pointed out that it was not specific to the manufacturing of Rayaldee, its treatment for secondary hyperparathyroidism (SHPT). Instead, it said the problems were general in nature. Rayaldee production is not cited in the report but issues are are rasied about encapsulation of other drugs.
Among the problems cited by an FDA inspector at the 453,000-square-foot softgel plant in St. Petersburg was an episode when it was reported that an unidentified “foreign dark matter” was coming down from the shaft of a gel receiver. The FDA said no one tied the “dark particles” back to seal change on the machinery two days before when a piece of equipment “had leaked all of its lubricant due to a broken seal.” There also was no investigation, the FDA said, to find out if any gel batches produced when the machinery was leaking were affected by the lubricant.
There were two observations tied to half-a-dozen complaints over several years about blue spots showing up on capsules of valproic acid, a drug used to treat a number of conditions, including epilepsy, bipolar disorder and migraines. Catalent had decided that the problem was unrelated to manufacturing, but hadn’t considered the fact it might be tied to encapsulation machines with chipped blue paint, or that operators wear blue gloves. Besides not getting to the root cause of that issue, the inspector noted Catalent had filed an NDA-Field Alert for only two of the 6 complaints.
Other issues the FDA pointed to were potential problems with cleaning some equipment. There also was a lack of controls on some computer equipment and a lack of traceability of some fill and seal thickness in-process checks taken during the encapsulation run of a product.
Catalent Wednesday said that it had met the FDA’s April 15 deadline for submitting a response. It said that Catalent is committed to “ensuring flawless implementation of the submitted plan,” and had already begun implementing it. It pointed out that the plant has had a good track record with previous inspections.
The issue cropped up even as there have been reports that Swiss CDMO Lonza might be talking with Catalent about a buyout. Both companies have declined to comment on the reports.
When Opko announced the CRL, EVP Steve Rubin told investors on a call that OPKO will soon resubmit its NDA for Rayaldee and depending on whether the FDA requires a reinspection, OPKO expected a resolution in 2 to 6 months, which would allow it to launch the drug in Q2 as it had always planned.
- here’s the Form 483 (PDF)
- here's Catalent's statement (PDF)
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