Three years ago, the FDA found so many violations at a Nephron Pharmaceuticals manufacturing facility that the U.S. regulator admitted in a warning letter the issues were so numerous they couldn’t all be documented.
Fast-forward to this year, and the plant in West Columbia, South Carolina, is still running afoul of the FDA. In a recent Form 483 report, the agency cited several problems that were evident in an August inspection of the facility. Most of the observations were repeat issues identified in Nephron's previous interactions with the agency.
Most notably, the report identified a lack of procedures to prevent contamination of manufactured products. The procedures are “not established and written,” the FDA said.
“These repeated and systemic lapses demonstrate that your firm has not implemented or enforced adequate aseptic practices to maintain sterility assurance of drug products,” the inspectors wrote.
The inspectors identified a laundry list of sterility issues, including operators failing to wash their hands or to clean IV bags. Trash removal was conducted while filling operations were in progress. Doors to manufacturing rooms were left open during aseptic operations. Sanitizing wipes that are designed for single use were reused after being left on shelves. The report also specified a variety of airflow problems.
The regulator added that the overall lack of procedures to prevent microbial contamination was a “repeated observation” from inspections performed in 2023 and 2024.
The company did not immediately respond to a request for comment.
Nephron is a privately owned contract manufacturer of generic respiratory medications. It also serves as a 503B outsourcing facility, producing medications for U.S. hospitals that are in shortage. The company specializes in blow-fill-seal production. The technology is designed to allow medications to be formed, filled and sealed in a continuous process without human intervention in a sterile, closed area.
In its write-up, the FDA further noted Nephron’s system for monitoring environmental conditions was lacking and that the company had not established an environmental monitoring program. This also was a repeated observation from a 2024 report of an inspection of the plant.
The inspectors also found deficiencies in alarm management, with employees disregarding alerts designed to maintain aseptic conditions. This also was a repeated observation from a 2024 inspection.
“These deficiencies in alarm management and oversight create an unacceptable risk of microbial ingress and contamination of sterile products.” the FDA wrote.
Additionally, Nephron failed to establish adequate written procedures for production and process controls designed to assure drug products meet strength, purity and quality specifications, according to the FDA.
Nephron has previously run afoul of the FDA. In 2013, the company was cited for its marketing of an over-the-counter asthma medication. Two years later, the company recalled 80,000 cartons of the drug over discoloration issues.
In 2022, Nephron came under intense scrutiny when it recalled more than 2 million drug doses—covering a wide variety of products including sodium bicarbonate injections, ephedrine injections and fentanyl citrate bags—because of sterility concerns. In an exhaustive warning letter that year, the FDA identified several of the same issues raised in the most recent report.