The FDA's warning letter said the Philadelphia-based manufacturer has put only one fluorescein API lot on stability, has limited data to demonstrate that the API is stable for its recommended retest date, and failed to test stability samples as required by its own procedures.
The company’s stability procedures also fail to address the control of temperature and humidity storage conditions for stability samples, and do not define what testing is to be performed on stability samples or reference documents that do define such testing.
The FDA calls on the firm to go into more depth on what kind of testing will be conducted other than the identity and endotoxin tests performed by a third party. The agency also seeks clarification on how the company’s stability program will monitor the characteristics of the API.
Abbey claims on its website to be the world’s leading manufacturer of fluorescein, which is a sterile liquid dye used in various diagnostic tests, such as those to find corneal abrasions, corneal ulcers and herpetic corneal infections.
In addition, water used in the final purification step contains OOS (out-of-specification) endotoxin and total organic carbon despite “promised actions” to assure reliable water quality, according to a March inspection.
In its response to the 2012 inspection, Abbey said it would conduct a gap analysis of the water system but the company never indicated when the analysis would take place or how it would determine the source of the high levels of endotoxin and organic carbon. Abbey also never documented the OOS results, conducted an investigation to determine the root cause of the recurring failures, or implemented corrective actions, according to the FDA.
The FDA says the gap analysis should evaluate “factors such as feed water quality, whether each component of the purified water system is meeting its performance specifications, and whether the system’s output is reproducible.” Abbey also must demonstrate how its changes have increased the reliability of its water system.
“Executive management of your firm is responsible for assuring quality system effectiveness,” the FDA said. “A basic part of this responsibility is prompt identification and remediation of problems that indicate manufacturing control problems, including an evaluation of the impact of these deviations on the quality of your APIs.”
Both the stability and purification violations are repeat observations from an inspection in 2010 and the FDA said Abbey’s response to the initial observations “lacks sufficient corrective actions.”
Abbey did not respond to request for comment on how it would respond to the warning letter. The company has 15 days following receipt of the letter to respond to it.