FDA 483 - Cipla Limited - September 27, 2019

An FDA 483 was issued to the company following an inspection between September 16 and 23, 2019, identifying significant deviations from Current Good Manufacturing Practices (CGMP). The primary concerns revolve around equipment cleaning, environmental control, and aseptic processing conditions.Observation 1 highlighted inadequate cleaning and maintenance of manufacturing equipment. Specifically, colored drug product residue was found in the air outlet ducts of multiple non-dedicated units used to produce various drug products for the U.S. market. The company's cleaning and preventive maintenance procedures lacked provisions for routinely cleaning these integral air ducts. Furthermore, stoppers used in aseptic filling showed visible scoring and rough surfaces, indicating non-cleanable designs.Observation 2 detailed insufficient controls over air pressure, microorganisms, and dust in drug manufacturing areas. The facility's actual room classifications during dynamic aseptic filling operations (Grade C/ISO 7) contradicted documented classifications (Grade B/ISO 5 or Class 1,000). There was also a notable absence of non-viable particle (NVP) data to support the declared area classifications or to validate monitoring locations.Observation 3 revealed deficiencies in maintaining aseptic conditions, particularly regarding non-viable particle monitoring in Grade A (ISO-5) aseptic processing areas. Critical areas, including the Grade A room itself and transfer points, were not routinely monitored for NVP during operations. There were also gaps in monitoring between key aseptic processing stations and during dynamic transfers of sterile parts.These observations collectively indicate systemic failures in maintaining a state of control for drug manufacturing, necessitating comprehensive corrective actions, including revisions to cleaning and maintenance protocols, re-evaluation of facility classifications, and enhancement of environmental monitoring programs to ensure product quality and patient safety.