Contamination issues lead to FDA warning letter for South Carolina manufacturing facility – Endpoints News
A contract manufacturing facility in South Carolina that makes a saline solution to help replenish lost water and salt has received a warning letter from the FDA about several issues related to cross-contamination and other quality issues.
An inspection earlier this year noted that the site had found drug cross-contamination in at least “three lots of drug products”, while Nephron did not properly investigate why this happened. The warning letter, which was issued on October 11, was sent to contract manufacturer Nephron due to problems noted at its West Columbia, SC facility.
Nephron attributed the contamination to a “combination of the nature of terminal sterilization cycles and the permeability of the container closure system (CCS) used to manufacture drugs.” Errors were found in IV bag CCS of other lots of drugs produced in the regular sterilization equipment.
“Our inspection found that you continued to manufacture drug products with the same CCS and autoclave cycles. Only after FDA’s inspection did you conduct additional investigations and CAPA. Their lack of a timely and comprehensive investigation failed to identify the extent of the cross-contamination hazard of marketed drug products,” the letter said .
While Nephron’s response provided an update on the cross-contamination investigation and expanded it to other drug products, this was not satisfactory to the US regulator. The investigation did not consider other sources of contamination and, with only limited data, concluded that the level of cross-contamination was “negligible”. Other potential root causes were also not addressed.
“Your survey does not adequately consider failures associated with your CCS and determine whether it provides adequate protection against the exit and entry of cross-contaminants. Your response lacks a commitment to assess your CCS for raw material quality and supplier reliability. This concern applies not only to your current medicinal products, but also your medicinal products waiting to apply,” the letter continued.
It also noted that Nephron had not implemented measures to prevent microbial contamination as well. The bacteria Pseudomonas aeruginosa, which can cause illness in humans, was discovered in cooling water and elsewhere. While some measures were taken to try to remedy the situation, the FDA gave the company more detailed instructions on what it must do to ensure compliance.
Another important observation was that proper environmental monitoring measures were not established in an area where drugs are most vulnerable to pollution. While Nephron has claimed that it investigated microbial contamination in the area, this was not enough for the FDA as a comprehensive assessment was not done nor was an assessment of monitoring provided.
The FDA recommends that Nephron bring in a consultant to achieve compliance and respond more quickly to regulators when contamination occurs.
The site itself manufactures a wide range of items, including filling syringes, IV bags, IV bottles and luer-lock vials, among others.
News about endpoints contacted Nephron for comment, but did not hear back by press time.