Significant cGMP violations at Tubilux Pharma
- Tubilux Pharma, based in Rome, Italy, has been given 15 days to respond to a warning letter from the Food and Drug Administration's Center for Drug Evaluation and Research (CDER) detailing significant violations of current good manufacturing practice regulations for finished pharmaceuticals.
- The inspection, carried out in December 2016, found risk of contamination in the aseptic processing line, demonstrated by turbulence in the airflow. The company sent the CDER additional data from studies, but these also showed turbulence.
- The CDER also pointed out issues with how personnel handle the materials, as well as problems with particulate and sterility testing, and with impurities causing clogs during batch manufacturing.
Current good manufacturing practice regulations ensure the safety of patients, especially those who are particularly vulnerable, and protect people from drugs that are contaminated or don't meet quality guidelines.
The CDER inspection drew attention to the aseptic processing line, showing where Tubilux had failed to rectify an issue that had already been pointed out. "During the inspection, our investigator reviewed and noted turbulent airflow in the September 2015 smoke studies… where you manufacture… for the U.S. market. This turbulent airflow poses a significant contamination hazard to your product. In your response, you submitted additional smoke studies conducted in December 2016. Like your September 2015 studies, the December 2016 smoke studies show turbulent airflow in multiple locations on the aseptic filling line," the warning letter said.
Tubilux now needs to identify contamination hazards, complete and submit a formal risk assessment and prepare and submit a corrective action and preventive action (CAPA) plan, as well as providing an implementation plan for particulate testing. If the requirements cited in the letter aren't complied with, the FDA may withhold approval of any new applications, and prevent Tubilux's products from entering the U.S.
According to an analysis by Unger Consulting, the number of GMP warning letters from the FDA is increasing, with 42 in fiscal year 2015 rising to 102 in fiscal year 2016. The numbers going to active pharmaceutical ingredient (API) and drug product sites grew from nine violations for each in 2015, to 19 and 23, respectively, over the same period, suggesting a crackdown by the agency.
Tubilux Pharma manufactures ophthalmic ointments, ophthalmic gels and eyedrops, as well as providing laboratory, regulatory and R&D support services.
- FDA Warning letter
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