CGMP Violations at Nephron SC

A 3/28-4/20 FDA inspection at the Nephron SC drug manufacturing facility in West Columbia, SC, identified significant violations of current good manufacturing practice (CGMP) regulations for finished drugs. A 10/11 Warning Letter says the firm also failed to submit an NDA Field Alert Report to the agency within three working days of receipt of information concerning significant chemical, physical, or other change or deterioration in a distributed drug product.

Specific CGMP violations were:

• failing to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed;
• failing to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including validation of all aseptic and sterilization processes; and
• failing to establish an adequate system for monitoring environmental conditions in aseptic processing areas.

FDA acknowledges the firm recalled one lot of its ketorolac tromethamine injection and four outsourcing facility compounding drug products following an 8/2 FDA telephone contact. It also acknowledges Nephron’s commitment to temporarily suspend production of some drug products at the facility, with operations to resume on 8/23. “Resumption of manufacturing your drugs terminally sterilized by moist heat should only occur once you have implemented effective corrective and preventive actions and completed appropriate submission requirements,” the letter says.

The agency recommends that the firm retain a qualified consultant to perform a comprehensive audit of Nephron’s entire operation for CGMP compliance, assist the firm in meeting CGMP requirements, and evaluate the completion and efficacy of all identified corrective and preventive actions before the company pursues resolution of its compliance status with FDA.

“We are concerned with the CGMP violations demonstrated at your facility and failure to submit Field Alert Report-related events within three days of becoming aware of a problem,” FDA writes. “Please include in your written response the corrective action you plan to take regarding distributed products manufactured at your facility that may be affected by the violations.”

Nephron was told to correct violations promptly and to respond with a list of specific actions it has taken to correct the violations and prevent their recurrence, with a schedule for completing the corrections.