Two Indian Drugmakers Warned for cGMP Violations

The FDA has handed fresh warning letters to two Indian pharma companies — Agila Specialties and Aarti Drugs Ltd. — for an array of current good manufacturing practice (cGMP) violations, including recordkeeping shortcomings, deviation investigation shortfalls and aseptic deviations.

Agila, a maker of injectable drugs snapped up by Mylan earlier this year, was warned following a late-June inspection of its Bangalore-based specialty formulations facility (SFF). Agency investigators scrutinized gloves that plant employees use during aseptic processes, noting they were marred with “visible holes and flaking” and had been approved by Agila quality personnel.

In use since at least April, the gloves “are especially concerning in part because they were used to perform manipulations directly over empty vials” — actions FDA investigators observed during a “brief three-hour” monitoring of filing operations at the plant, according to the letter.

Dissatisfied with the company’s response to the concern, the agency questioned Agila’s vendor qualification program and incoming material release system and requested details of the methods the company uses to support those functions.

Noting that the company’s SFF-manufactured products are on hold as it responds to the FDA, the agency also asked for details about Agila’s final disposition plans for those products and whether it intends to rework related batches.

The FDA also rapped the company for “inadequate” media fill studies, citing a lack of reasoning for rejecting certain media fill vials. “Please note that no amount of successful media fills can be used to validate poor aseptic design, operations, controls and practices,” the warning letter states.

And Agila’s investigations into batch failures do not always occur or are conducted without thoroughness, the agency said. The drugmaker promised to review its deviation management system and the FDA said investigators will evaluate its corrections “during our next inspection.”

Requests to Agila for comment were not returned by press time.

During an inspection of Aarti’s Maharashtra facility in October and November of last year, agency investigators noted a failure to record all quality activities in real time. “The investigator observed at least two examples when a manufacturing step was recorded in the batch record before it occurred,” the July 30 letter, posted Sept. 24, states.

Aarti, a maker of active pharmaceutical ingredients (API), has since developed a standard operating procedure and training protocols to address recordkeeping shortfalls but has not provided full details about those efforts, the letter adds.

The drugmaker was also rapped for improper reviews and investigations into production and quality control laboratory deviations. Multiple instances of “servicing due to instrument problems” have not been recorded as deviations per company protocol, the agency said. “Please also note, as a general laboratory practice, any equipment malfunction that may have an impact on quality control testing should be appropriately recorded and investigated,” the letter states.

Other issues related to Aarti’s quality control lab also surfaced during the FDA inspection, including a failure to implement access controls and audit trails for laboratory computer systems.

“It is apparent that you have not implemented a robust quality system at your firm,” the warning letter states. The agency requested Aarti’s corporate management implement a comprehensive evaluation of its global manufacturing operations to ensure compliance with cGMP regulations.

Aarti has appointed Westbury, N.Y.-based Lachman Consultants to conduct third-party remediation at the plant, spokesman A. S. Kulkarni said.

Both Aarti and Agila were told that until corrections are made, their products could be barred from entry into the U.S. and that both companies’ applications for approvals could be delayed.

The letters follow in the wake of stepped-up FDA inspections of Indian facilities. The Indian government in March gave the agency the green light to add seven additional drug investigators to its India office, bringing the total staff to 19.

The FDA emphasizes the importance of cGMPs; this is reflected in the regular letters the agency sends to companies who fail their inspections. But Why are cGMPs So Important? This DVD will answer all of your questions and doubts about cGMPs.