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Regulatory Focus™ > News Articles > 2020 > 9 > FDA warns Mylan, Acella Pharmaceuticals over GMP violations

FDA warns Mylan, Acella Pharmaceuticals over GMP violations

Posted 01 September 2020 | By Michael Mezher 

FDA warns Mylan, Acella Pharmaceuticals over GMP violations

The US Food and Drug Administration (FDA) last month warned Mylan Laboratories and Acella Pharmaceuticals over good manufacturing practice (GMP) violations.
 
Mylan Laboratories
 
FDA’s warning letter to Mylan comes after the agency inspected the company’s facility in the Sangareddy District of Telangana, India over the course of a week last February.
 
The warning letter, which cites the company for issues related to its cleaning procedures and handling of recovered solvents, contains repeat deviations from a warning letter sent to Mylan in November 2019 concerning a different facility in India. RELATED: FDA warns Mylan’s Indian API facility over contamination concerns, Regulatory Focus 12 November 2019)
 
During the inspection, FDA investigators found issues with Mylan’s cleaning procedures and record-keeping for its non-dedicated bulk storage tanks used for numerous active pharmaceutical ingredient (API) manufacturing processes at the facility.
 
When investigators asked Mylan staff for cleaning records for the tanks, they were provided with records for cleaning activities conducted after October 2019 and were told that records were not kept prior to then.
 
FDA found the company had not performed complete impurity profiles of solvents recovered from the tanks. “Coupled with inadequate cleaning records, there are limited assurances that your non-dedicated equipment would not contribute to cross-contamination or carry-over of residual impurities,” FDA writes, noting that one of the companies contracted to recover the solvents was placed on import alert and issued a warning letter for inadequate impurity profiles of recovered solvents between 2018 and 2019.
 
The agency also cites the company for failing to adequately validate its cleaning methods and for failing to implement procedures to evaluate and control impurity risks associated with solvents.
 
“During a review of incoming raw material acceptance testing between 2015 to 2019, the impurity profiles did not match for multiple lots of recovered [solvent] … Specifically, unknown peaks were detected in the recovered solvent,” FDA writes.
 
Acella Pharmaceuticals
 
The warning letter sent to Acella follows a three-week inspection that ran from December 2019 into January 2020 and uncovered issues with the company’s NP Thyroid products that led to the company recalling 13 lots of the tablets due to super potency in May.
 
“The active ingredient assay specification you developed with your [contract manufacturing organization] CMO for levothyroxine and liothyronine in your NP Thyroid products were not appropriate,” FDA writes, noting that the United States Pharmacopeia (USP) monograph for thyroid tablets specifies different levothyroxine and liothyronine assay acceptance criteria.
 
During the inspection, FDA sampled the company’s NP Thyroid tablets and found some had low, out-of-specification results for both ingredients. “Because of the narrow therapeutic range of this product, content uniformity is critical and it is especially important to prevent patients with hypothyroidism from receiving insufficient or excessive doses,” FDA writes, noting that the company did not distribute the affected lot.
 
The warning letter also cites Acella for its quality unit’s failure to adequately oversee its CMO.
 
“Your quality control unit failed to provide adequate oversight of your CMO to ensure that expiration dating claims were supported by adequate stability data,” FDA writes, noting that the company did not have long-term stability data to support batches of drugs manufactured with a new API supplier. “The validation batches manufactured by your CMO using the new API supplier were made in May and June 2019, yet were not placed into a long-term stability study until May 1, 2020.”

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