US FDA Slams Zydus For Flawed Investigation, ‘Unofficial’ Books
This article was originally published in PharmAsia News
Executive Summary
A US FDA warning letter against Zydus Cadila's Indian sites contains some sharp references to the firm's flawed investigations into warfarin tablet failures, controls over computerized systems and poor documentation practices.
Details have emerged of the US FDA’s recent warning letter to Indian firm Zydus Cadila, which said that the recurrence of product quality failures at its Moraiya site with respect to warfarin following the completion of the firm's investigation indicates that its corrective and preventive actions were ineffective.
"The recurrence of these failures is apparently due to inadequate identification of root causes and lack of action to resolve this manufacturing problem. These persistent failures indicate that your manufacturing process is not in a state of control," details in the letter stated.
Cadila Healthcare Ltd. announced on Dec. 31 that it had received a warning letter against its Moraiya formulation facility and its oncology active pharmaceutical ingredients site (API) in Ahmedabad (Zyfine). Among a string of observations, the Moraiya unit also received flak for failing to establish and follow adequate written procedures describing the handling of written and oral complaints concerning a drug.
The agency noted that while Zydus planned to conduct a retrospective review of product complaints, deviations, and product failures from January 2013 to August 2014, the review appeared to focus on solid oral dosage products and is conducted over a limited period.
The FDA termed the retrospective review period as "insufficient" and said that it does not appear to address whether other dosage forms made at the site may also be "vulnerable to mix-ups or other major defects."
The FDA has sought a series of corrective actions and details of the specific changes made to ensure prompt identification, correction, and follow-up for problems associated with the firm's products. The Moraiya site accounts for about 60% of Zydus Cadila's US formulation revenues and roughly 40% of the firm's oral solid dosage filings for the US.
Some analysts tracking the development said that the warning letter appeared worse than expected, though much of the downside appeared to have been factored into the company's stock price. Cadila shares were pounded on the Bombay Stock Exchange last week.
API Site
The FDA also made some stinging references to poor documentation practices and record keeping at Zydus's API site, though the company recently clarified that the plant had not made supplies to the US and had recently been de-registered.
The FDA said it found some employees at the site use "rough or unofficial notebooks" to document various CGMP activities during its investigations. One such book found in the engineering office referred to pseudomonas present in the water system and a water system activity investigation.
However, Zydus was unable to provide the investigators with any documentation regarding Pseudomonas sp. found and the related investigation.
Zydus had explained that the failure occurred during qualification of its water system, which was still in progress at the time of its response. The FDA, though, warned that the company must document all CGMP activities at the time they are performed, including equipment qualification and any deviations observed during such activities.
The FDA also noted how the company failed to exercise sufficient controls over computerized systems to prevent unauthorized access or changes to data. Other areas of concern pertained to the deletion of electronic records.
(This story also appears in Scrip Intelligence
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