Maryland: The US Food and Drug Administration (FDA) has warned Brassica Pharma for numerous good manufacturing practice (GMP) violations, including multiple instances of employees falsifying sterility and environmental monitoring data and lax controls to prevent microbiological contamination.
Brassica is a contract development and manufacturing organization (CDMO) that makes sterile eye ointments, gels, prefilled syringes, dermatological, and liquid oral products.
The warning letter, which found four GMP violations, was issued to the company’s Maharashtra, India facility after a four-day inspection in January 2024 and was posted to FDA’s website 23 July. Following the inspection, the company recalled several of its sterile eye ointments.
A recurring theme in the warning letter was the firm’s failure to keep truthful and accurate records. FDA said “laboratory technicians falsified data which is critical to maintaining an ongoing state of control in your aseptic processing facility. Data integrity is critical throughout the CGMP data life cycle, including in the creation, modification, processing, maintenance, archival, retrieval, transmission, and disposition of date after the record’s retention period ends.”
Such data integrity problems emerged after finding the company failed to conduct sterility tests for each batch. FDA said sterility samples should have been under incubation from batches produced just prior to the FDA inspection were not present and a review of sterility test records compared to biometric access data “did not align.”
The sole analyst that conducted the sterility testing told FDA that “it is his routine practice to not test all batches for sterility and fabricate records for those samples not tested.” Upon further sterility testing of batches, investigators found that four batches failed sterility tests.
The company also failed to collect samples for environmental monitoring. When FDA investigators went to collect such samples, they found that a reconciliation of samples required by its procedures and the samples that were physically present “did not match.” Interviews with microbiology staff “revealed that it is their routine practice to fabricate records and results for samples that were not taken.”
Employees also admitted to fabricating data from plate readings in the microbiology lab after investigators found samples on plates in ISO 5 and ISO 7 areas indicating an alert or action. There were 37 action level excursions for ISO 5 area environmental monitoring samples and 17 action level excursions for ISO 7 area.
“Your firm stated that prior to the start of the inspection, where you admitted routine fabrication of environmental monitoring results, no single action level excursion had been documented.”
The company was also lambasted for lax microbiological contamination practices, including operators being observed touching the inside of empty sterile tubes prior to loading tubes onto the filling line and operators leaning over the filling line, exposing their head and torso.
In addition, operators in the aseptic processing activities were wearing gowns that were “stained and torn,” which is a problem in classified spaces where the “risk of product contamination is high.”
Media fills were also not “sufficiently representative” of commercial aseptic manufacturing operations. “It is your routine practice not to document interventions of the filling line, line speed, or line stoppages in the manufacturing batch record during production. Because of this, your program lacks reliable data to determine the type, quantity, and duration of interventions to simulate during media fills.”
The facility’s design also came into question, which FDA stating it had “basic design deficiencies” which “compromise your ability to maintain aseptic conditions.”
The last violation was the failure to keep its equipment clean. For example, pieces of equipment that came into contact with the inside of unfilled sterile tubes could not be removed for cleaning.
The company has said it would suspend production of all drugs for the US market, and FDA placed the company on an import alert on 30 January 2024.
