The US Food and Drug Administration (FDA) has posted a Warning Letter to Mylan regarding current good manufacturing practices (cGMP) violations of three Mylan facilities in India based on FDA inspections made in 2014 and 2015. The GMP violations were for sterile manufacturing facilities for finished pharmaceuticals in Bangalore, India in which Mylan gained as part of its $1.75 billlion acquisition of Agila Specialties in 2013.

The inspections were conducted as follows: February 6-13, 2015 at Mylan Laboratories Limited OTL, in Bangalore; September 23, 2014 through October 3, 2014 at Agila Specialties Private Ltd., Specialty Formulation Facility in Bangalore; and August 1-8, 2014, Agila Specialties Private Ltd., Sterile Product Division in Bangalore. The FDA noted the firm's responses of August 29 and October 27, 2014, and March 9, 2015 and said that they lacked sufficient corrective actions. The agency also received additional correspondence of November 14, November 26, December 16, and December 19, 2014 and January 19, February 13, March 16, and April 20, 2015.

Mylan CEO Heather Bresch commented in a company statement: “Since Mylan acquired the Agila injectables businesses in December 2013 to create a leading global injectables platform, we have been taking extensive action to integrate the Agila business into Mylan’s One Quality Standard, and to ensure our leading position as a high quality, reliable source of injectables for the long term. As part of this ongoing process, we have a deep and unwavering commitment to quality everywhere we operate. We have been and will continue to work diligently to address all of the FDA’s observations and have made important progress.”

Among the violations cited by the FDA were quality control violations. The agency said that the firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, including validation of all aseptic and sterilization processes as well as appropriate integrity testing of gloves and gowns and related operator procedure. The agency also cited the firm for not following appropriate environmental monitoring protocol for sterility assurance. The agency further said that the firm failed to establish laboratory controls that included scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity.

The FDA also requested that the company provide a progress report on identifying the root cause of particulate contamination that resulted in Mylan recalling select lots of injectables. The FDA noted that in March and April, 2015, the company voluntarily recalled seven for injection lots of gemcitabine 200 mg/vial, gemcitabine 2 g, gemcitabine 1 g, carboplatin 10 mg/mL, methotrexate 25 mg/mL, and cytarabine 20 mg/mL and in June, 2015, the company expanded its recall to an additional eight lots of gemcitabine and methotrexate. The FDA requested that the company specify its product quality assessment protocol, including analysis of retain samples, corrective actions and preventive actions, and risk assessments to evaluate the product quality effects of its aseptic processing activities and environmental monitoring program. The Warning Letter also noted other violations for sterility assurance, including issues with media-fill practices and procedures, environmental monitoring, properly identifying gram-negative contamination, and for investigating out-of-specification results.

In its letter, the FDA noted that: “These items found at three different sites, together with other deficiencies found by our investigators, raise questions about the ability of your current corporate quality system to achieve overall compliance with cGMP. Furthermore, several violations are recurrent and long-standing. Although we acknowledge that the Agila facilities were acquired by Mylan recently, you were on notice of the violations in Warning Letter 320-13-26, dated September 9, 2013. Even without this Warning Letter, your corporate quality system should have detected and corrected the forgoing violations without FDA intervention.”

Source: FDA and Mylan