Dissolution testing and dirty gaskets: US FDA warns Hetero Labs

The US FDA has sent a warning letter to Hetero Labs Limited citing GMP violations at its finished dose formulations facility in Telangana, India.

The Jadcherla Mandal facility was inspected by the US Food and Drug Administration (FDA) in December last year and found a number of significant violations of current good manufacturing practice (cGMP), according to a warning letter published yesterday.

“Your investigations into process deviations and out-of-specification (OOS) laboratory results are insufficient, and do not include scientifically-supported conclusions,” the Agency said in the letter sent to Hetero Labs on the 15th of this month.

As an example the FDA said a customer complaint from February 2016 stating a lot of tablets had failed dissolution testing was not adequately explained, and “one of your customers found this explanation unacceptable. You subsequently acknowledged to another customer that you had not identified the root cause for the failing dissolution results.”

The FDA has called on Hetero Labs to update its dissolution testing and to provide a “detailed retrospective review of all complaint, manufacturing, and laboratory investigations associated with each product that you produce for the US market.”

Poor condition

Hetero was also pulled up on its failure to clean, maintain, and sterilise manufacturing equipment.

“Our investigators observed multiple (b)(4), which you identified as clean, containing colored residue and/or in poor condition,” the Agency stated.

“For example, (b)(4) PDE-2095 had white (b)(4) residue on and around a white interior gasket. Our investigator documented a gap in the gasket that could allow processed materials to accumulate. The ends of the gasket were also in poor condition.”

And the FDA also found failings with Hetero’s QM001-04 Quality System Manual and CQA012-01 Product Recall procedures.

“On July 8, 2016, you received a complaint that one tablet in a bottle of 5 mg finasteride tablets, lot FIN16002, was approximately double the thickness of the others. You confirmed the defect after receiving the complaint sample on July 27, 2016, but did not initiate a product recall as directed by your own procedures until December 23, 2016. This was nearly a week after our investigators pointed out your failure to take action as directed by your own procedures regarding recalls of defective products.”

Hetero Labs has 15 working days to respond detailing its remediation plan.