Exemplar Pharmaceuticals LLC – FDA 483, Mar 21, 2012

During an inspection on March 21, 2012, the U.S. Food and Drug Administration (FDA) issued a Form 483 to Exemplar Pharmaceuticals LLC, a manufacturer located in Fall River, MA. The inspection revealed significant deficiencies in the company's manufacturing and process controls, indicating non-compliance with Current Good Manufacturing Practices.

A primary observation highlighted inadequate in-process control procedures. Specifically, the firm lacked proper examination of mixing adequacy and did not have controls for its pressurized filling system to ensure content uniformity, particularly concerning propellant loss and potential increases in drug substance concentration. Inconsistent total content results for sampled canisters illustrated this issue.

Furthermore, the FDA noted the absence of written procedures for production and process controls, which are essential to guarantee drug products meet identity, strength, quality, and purity standards. This included a lack of mechanisms to ensure total content specifications are met when product flow or pressure is disrupted, as evidenced by a catastrophic failure in one lot. The firm also failed to evaluate the impact of using only one filling station after another failed and lacked data to demonstrate product stability through its lifecycle. Critically, a release specification for total content was changed for a specific lot without proper change control, justification, or assessment of its impact, including on stability data.

Exemplar Pharmaceuticals LLC is required to address these observations to ensure compliance with regulatory standards and prevent future recurrence of these issues.