Mylan Pharmaceuticals Draws Form 483 for Poor Quality Controls

Regulatory NewsRegulatory News | 29 June 2018 |  By 

Mylan Pharmaceuticals’ manufacturing facility in Morgantown, WV, received an FDA Form 483 listing inspectional observations, some of which were due to failures of its quality control unit.
Agency investigators who visited the firm during a 12-day site inspection earlier this year noted 13 situations of noncompliance to good manufacturing practices in the 32-page Form 483—posted on FDA's website Wednesday.
From a lack of appropriate oversight and documentation on written procedures changes to an inadequately validated cleaning process and established time limits on drug products, seven observations described the firm’s quality control unit.
In response to the citations, Mylan told Focus it submitted a “comprehensive response to the agency and committed to a robust improvement plan. We remain confident in the quality, safety and efficacy of our drug products, including those in distribution, and we continue to manufacture and ship product from the site.”
The quality unit was unable to provide documentation for each manufacturing change made within the lab information management system that had not been assigned a change control since November 2016 “as these changes are not tracked, reviewed or approved,” FDA wrote.
Further, the quality unit had opened a total of 462 investigations since November 2016 into a hold time set for each drug manufacturing phase that was being “frequently exceeded” by the production department without implementing any corrective and preventive actions.
Sweeping across seven pages of the 483, the most extensive observation cited the quality unit’s failure to “adequately validate the cleaning processes of all manufacturing equipment and utensils shared between [the firm’s] 230 oral dosage drug products (potent and non-potent) to ensure no cross-contamination of active ingredients and detergent occur between products.”
Deficiencies in the firm’s cleaning processes are explained in six examples in the 483, including a lack of “sound scientific rationale” for the quality unit’s decision to invalidate certain swab results based on re-swab results in a different location of the selected manufacturing equipment.
The investigators also pointed to three instances of poor cleanliness of equipment that had been released by the quality unit. These include an “unknown crystal-like yellow residue” seen on equipment that had been used to manufacture Verpamil HCI SR tablets, as well as residue observed on an encapsulator used in the manufacturing of Diltiazem HCI ER capsules.
Cleaning procedures were also of major issue at the time of the firm’s site inspection. For example, laboratory analyses were being repeated until obtaining passing results in cleaning verification tests for products or detergent residues, according to the 483.
The investigators observed at least 10 instances dating back to August 2016 of equipment components being re-cleaned and re-swabbed until the analyses showed the desired results.
In addition, the quality unit’s retrospective review of liquid chromatography systems, conducted per its comment to FDA, failed to include folders on cleaning and method validations.
Other issues cited in the 483 relate to a failure to conduct visual examinations of reserve samples from sample lots or batches, follow written production and process control procedures, and follow-up on written records of drug complaint investigations.
Mylan Pharmaceuticals Inc, Morgantown, WV. 483 issued 4/12/2018


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