Regulatory Focus™ > News Articles > Form 483 Details Deficiencies at Catalent Facility Linked to Recent CRL

Form 483 Details Deficiencies at Catalent Facility Linked to Recent CRL

Posted 19 April 2016 | By

Form 483 Details Deficiencies at Catalent Facility Linked to Recent CRL

The US Food and Drug Administration (FDA) last week released an inspection report citing major deficiencies at pharmaceutical contract manufacturer Catalent's Saint Petersburg, FL facility.

The 14 deficiencies came to light in March after Opko Health announced it received a complete response letter from FDA for its prohormone drug Rayaldee (calcifediol) because of the "observations and deficiencies" at Catalent's manufacturing site.

According to Catalent, the facility develops and manufactures softgel capsules, hormone products and other controlled substances.

Chris Halling, senior manager of global communications at Catalent, told Focus the company has already submitted "a comprehensive response" to the 483 and is "implementing measures to address some of the improvements noted in FDA observations, and will continue to work to address these and the remaining points."

In the last year, Catalent has been cited for deficiencies uncovered during two separate inspections carried out by FDA and France's drug regulators, l'Agence National de Sécurité du Médicament et des produits de santé (ANSM).

In July, FDA issued a 483 for another Catalent facility in Morrisville, NC for failing to review unexplained discrepancies and inadequate process control and testing procedures. Then, in November, ANSM suspended production at Catalent's facility Beinheim, France after inspectors discovered "out-of-place softgel capsules in several product batches."

Failure to Review Discrepancies

In the inspection report, FDA says Catalent found foreign matter contaminating a gel receiver in its facility. The agency says that while Catalent investigated the issue and ultimately replaced a seal to correct the problem, the company did not inspect earlier batches that could have been affected.

Furthermore, FDA says Catalent failed to follow its own standard operating procedures by opening the investigation into the foreign matter 11 days after the incidents.

FDA also found that Catalent did not properly document actions taken after a refrigerator at the site malfunctioned.

Blue Spots

In another deficiency, FDA says Catalent failed to adequately respond to six complaints of blue spots appearing on finished valporic acid capsules.

FDA notes that Catalent failed to document an assessment of potential causes, including chipped blue paint on encapsulation machines near where the capsules are manufactured, and blue colored gloves used by workers involved in routine manufacturing.

According to FDA, Catalent's claim that the blue spots were "not related to manufacturing operations at [the] firm … is unsubstantiated and potentially incomplete."

FDA also cites Catalent for failing to issue field reports for four of the six complaints related to the blue spots. Furthermore, the one field report Catalent did issue was issued after the company had received two complaints pertaining to the same batch.

Production and Process Controls

In another observation, FDA says that Catalent lacked "written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess."

According to FDA, Catalent's Site Validation Master Plan specifies an inadequate method for continuous process verification, and FDA also says it identified two trends showing a shift in assay results for commercially released batches of lubiprostone capsules that were previously unknown to the company.



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