Apotex spokesman Steve Giuli told us the company submitted its response to the FDA on Tuesday and is “committed to working with the Agency to resolve all the identified issues.”
The warning letter calls out Apotex primarily for its data integrity issues, which the company did not investigate far enough into the past to meet the FDA’s needs. The company’s response highlighted inconsistencies and noted that examples cited by the agency “resulted from a number of factors ranging from system suitability parameters not being met to equipment malfunction to available in-process test data results that were inconsistent with release results.”
Apotex reviewed data from August and September 2013 and found additional incidents “in which extra testing was performed without maintaining appropriate laboratory records.”
But the FDA chides the company for failing to expand its investigation once these incidents were found “to discover the full scope of such variances from established procedures. Based on findings from these two months, it would be reasonable to believe that improper variances occurred in prior months as well,” the FDA says.
In response to the warning letter, the FDA calls on Apotex to “provide evidence of the additional investigation conducted and the corrective actions implemented to prevent the omission of data. Provide records of all complaints relating to your APIs, including returned API and the disposition of each returned batch… Furthermore, explain the failure of your firm’s complaint system and how you will implement proper management oversight to ensure adequate corrections to this deficiency.”
The company is also asked to provide a comprehensive evaluation of how many of its records were destroyed, inaccurate or unreliable, as well as a risk assessment on the potential impact on the quality of products, and a comprehensive corrective and preventive action plan.
The agency also lays out seven actions to be taken by the company’s third-party auditor, and requests a list of all the batches of APIs in distribution and those intended to be shipped to the US market that relied upon missing, inaccurate, or unreliable test data.
The warning letter comes as this API facility was hit with an import alert in April, following the same inspection from January that the FDA conducted. In 2012 the company sued the FDA over another import alert, which it called devastating to its business.
Antibiotic Shortage Resolved
Despite the bad news on the API plant, Apotex offered some encouraging news in terms of its ongoing issues with dealing with a shortage of the antibiotic cefazolin.
“Manufacturing of the product has resumed and is back in distribution as of the last week in May 2014,” the company said on the FDA website. “The ongoing manufacturing will enable the resolution of the shortage.”