FDA sends Warning Letter to Apotex of Canada

Inspections continue to find repeated deficiencies in quality systems at facilities

Canadian generics manufacturer Apotex has been warned by the US Food & Drug Administration (FDA) about cGMP violations at its Signet Drive, Toronto and Richmond Hill, Ontario plants following an inspection last August.

The FDA said Apotex had failed to establish and follow proper procedures to prevent microbiological contamination of drug products at the Toronto plant.

For example, the company did not perform adequate unidirectional airflow pattern studies (i.e. smoke studies) for the aseptic filling line.

The inspectors said Apotex also failed to establish maximum holding times for vials used in media fills prior to incubation and did not investigate thoroughly any unexplained discrepancy or failure of a batch or any of its components.

Black specks were also observed on a batch of tablets and a portion was rejected, but Apotex was unable to determine a definitive root cause and the actions taken did not prevent a recurrence of the problem, the FDA said.

We remain concerned about the lots affected by this practice and released into distribution

‘We remain concerned about the lots affected by this practice and released into distribution; your response did not provide information to show that a thorough investigation to determine the cause of each unexplained discrepancy or failure to meet specifications had been conducted,’ the FDA said.

The regulator suggested that Apotex’s practice of rejecting portions of drug product batches was an indication that the firm did not have well-controlled manufacturing processes.

Additionally, the FDA said it was concerned about the firm’s approach to process validation since its report failed to include any analysis or characterisation of the hardness variability of product.

The regulator said Apotex should provide a summary of the in-process hardness data, an appropriate statistical analysis of the data and characterisation of the hardness variability in the individual validation lots and overall.

At the Richmond Hill, Ontario plant Apotex failed to investigate thoroughly any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications.

The firm also failed to record the incubation dates of the microbiological plates in the validation study of solutions and spray products.

The inspections continue to find repeated deficiencies in your quality systems

The FDA said: ‘The evidence suggests that Apotex has failed to implement adequate global and sustainable corrective and preventive actions, and that it continues to manufacture and distribute pharmaceutical product without upholding its legal obligation to comply with cGMP. The inspections continue to find repeated deficiencies in your quality systems.’

The FDA recommended that ‘appropriate resources be used to conduct a thorough retrospective evaluation of past deficiencies and that appropriate permanent changes be implemented’ to ensure that Apotex manufactures pharmaceutical products using a sustainable quality platform in all of its facilities.

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