Opko Health submitted a New Drug Application (NDA) for Rayaldee (calcifediol), its oral vitamin D prohormone treatment for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease and vitamin D insufficiency last May.
But yesterday the firm said it had received a complete response letter (CRL) from the US Food and Drug Administration (FDA) indicating “observations of deficiencies at Opko’s third-party contract manufacturer” following an inspection initiated on March 14.
During a call discussing the letter, the firm revealed the deficiencies occurred at Catalent’s primary softgel development and manufacturing in St Petersburg, Florida, which was hit with a Form 483 being issued on March 25.
“While we are aware that the FDA was conducting an ongoing inspection of Catalent, as would be expected with an open NDA, neither we nor Catalent were aware of these deficiencies that would have led to a withholding of approval, until notified in connection with the CRL,” said Opkos’ EVP Steve Rubin.
He did not divulge how many observations there were in the 483 but told stakeholders they are general observations pertaining to Catalent's facility and not to the drug candidate Rayaldee.
“This is not a warning letter. They are observations that Catalent will address by April 15, assuming they have a robust and strong response, which we fully expect from a firm such as Catalent. I can't predict when FDA will respond, but we would expect those resolved, hopefully resolved within 30 days or so after.”
Opko CEO Phillip Frost, added he too is confident Catalent will be able to rectify the issues:
“They are one of the largest contract manufacturers, with over 40 plants, and many of the large pharmaceutical companies use their services. We are quite confident that with their very excellent team, they're going to be able to address the problems expeditiously.”
Catalent did not provide comments to us at the time of going to press.
Beinheim manufacturing still suspended
CDMO Catalent has had a turbulent year across its softgel network. In November, the French health regulator ANSM suspended manufacturing at its site in Beinheim, France, after out-of-place capsules were found in several product batches.
While the firm believes the issue was caused by intentional human interference and has subsequently filed a criminal complaint, revenues have been hit with Catalent reporting expected softgel sales down $21m in its Q2 results.
Jefferies analyst David Windley noted yesterday that while Catalent was aiming to reopen the plant in mid-March, “it also indicated plans to confirm that event by [an SEC filing] 8K, which has not yet happened.”