FDA Investigators Target Pharmaceutical Water Systems
FDA investigators are paying close attention to pharmaceutical water systems during inspections and the agency has cited water deficiencies in about 17% (10) out of more than 60 Warning Letters issued this year, according to CDER Office of Manufacturing Quality director Francis Godwin. Speaking at the FDA/PDA Regulatory conference in Washington, DC 9/14, Godwin said that out of the 10 letters citing water systems, six included findings related to Burkholderia Cepacia Complex (BCC) contaminations. “That’s a pretty big proportion of the Warning Letters… and so it’s definitely on our mind.”
Godwin said investigators have encountered firms questioning the degree of concern about water systems if their products are non-sterile, have preservatives, or have antimicrobial effects. Such product characteristics do not prevent microbial contamination outright, he emphasized, adding that companies need to demonstrate the effectiveness of their preservative system or antimicrobial activity if those are factored into product release decisions and formulation designs.
“Now, Burkholderia Cepacia has been on the agency's mind for quite some time,” Godwin said, pointing out that with oral drugs, especially liquids, firms may need to consider whether the drugs are also being used in different settings. He cited a recent case where contaminated drugs were being used in the intensive care unit in people on ventilators, which can cause real harm if the bacteria make it into the lungs.
Godwin noted that FDA has released a safety alert on BCC and it is continuing to pose a contamination risk. “It is essential that manufacturing facilities, equipment, and processes are designed to prevent contamination and strict sanitary standards are continually followed,” the agency notice said. “There is a long history of product recalls due to BCC contamination traced back to deviations from current good manufacturing practice requirements.” The agency also recently released a guidance entitled “Microbiological Quality Considerations in Non-sterile Drug Manufacturing” that Godwin recommended firms review. The document provides recommendations to help manufacturers assess the risk of contamination of their non-sterile drugs by objectionable microorganisms in order to establish appropriate specifications and manufacturing controls that prevent such contaminations.
Godwin urged drug manufacturers to read the two documents and “take them to heart. Our investigators have read these documents and take them to heart, and that is why we’re seeing these inspections where we’re looking at the water systems. If we do find problems, we will work with the firm to address them.”