Regulatory Focus™ > News Articles > Warning Letter to Baxter Alleges Presence of Mold in Sterile Manufacturing Process

Warning Letter to Baxter Alleges Presence of Mold in Sterile Manufacturing Process

Posted 11 June 2013 | By Alexander Gaffney, RAC

Pharmaceutical manufacturing giant Baxter was sent a Warning Letter earlier this month by the US Food and Drug Administration (FDA) alleging that two of the company's facilities exhibited significant deficiencies related to quality manufacturing of finished pharmaceuticals and reporting procedures, respectively.

Repeated Mold Observations

Warning Letters are used by FDA to identify major failings of US regulations or law, and generally follow inspections of a facility and an FDA Form 483 letter identifying found deficiencies.

In the case of Baxter's Marion, N.C. manufacturing facility, FDA said it found "significant violations" of current good manufacturing practice (CGMP) regulations under 21 CFR 211. The regulations are intended to make sure pharmaceutical products are manufactured to standards that render them of appropriate quality, and FDA's letter notes that the company manufactures sterile injectable products.

But, according to FDA's letter, Baxter's facility exhibited a number of troubling lapses, including HEPA filters that were discolored, had chipped paint, "multicolored coalescing droplets," and-worst of all-"clumps of dark material that FDA testing later revealed was mold." This, FDA added, was a repeat observation from a similar August 2012 inspection at the same facility.

Though Baxter said operations on the fill line with those HEPA filters ceased once the violation was observed, FDA said it had neglected to conduct a root cause investigation or explain how long the violation had been present, leaving FDA to deem its response to the Warning Letter as "inadequate."

"Without identifying, correcting, and preventing the root cause of the mold growth at your sterile fill lines, the contamination hazard to the products manufactured on those lines could continue and potentially pose risk to patients," FDA said.

Environmental Monitoring Problems

In another instance, FDA said it found evidence that Baxter's maintenance staff had found "visible discoloration" and stains indicating mold on the "clean" side of HEPA filters supplying air to manufacturing lines since at least July 2010. Those findings were improperly investigated and went un-remediated, according to FDA, which noted that this observation was again a repeat one from August 2012.

In addition, FDA alleged that the company's sampling plans for environmental monitoring were conducted without adequate scientific justification. "Your environmental monitoring program was insufficient to detect contamination of concern, including mold observed on the clean side of the air filters supplying air to the sterile filling areas," FDA wrote to Baxter, adding that records also failed to identify the locations from which environmental testing results were obtained.

Baxter explained that the effects on product sterility should be negligible due to its terminal sterilization process before release. This response was not acceptable to FDA, which explained that "sterile products should be protected from microbiological contamination during processing, even when terminally sterilized, in order to minimize sterilization challenge and byproducts of excessive bioburden."

Recall Issues

FDA's letter also references Baxter's Jayuya, Puerto Rico manufacturing facility, which exhibited a number of alleged failures during a February 2012 inspection. FDA said the company had been made aware of several unexplained failures resulting in deficient products, and ultimately discarded 25 lots of a finished drug product. However, FDA noted that the company "did not take any actions to mitigate risks posed by affected product" that had already been distributed to the market. Regulators added that Baxter had received a number of complaints as a result, and ultimately initiated a recall after FDA brought the matter to Baxter's attention.

FDA's inspection goes on to note that it found investigations that had been left open for as long as six months, which regulators said were inconsistent with the company's own procedures. The company also allegedly failed to submit a Field Alert Report (FAR) within the required three working days after first receiving information regarding a product defect, which regulators noted was a repeat violation from a January 2011 inspection.

A Third Facility

In addition to the Marion and Jayuya facilities, FDA said a third, unnamed facility had also received an FDA Form 483 that did not ultimately result in a warning letter.

"Be advised that a recent FDA inspection at another Baxter facility cited a pattern of inadequate corrections and interventions concerning sterile facility sanitization," FDA wrote. "While the response to that location's deficiencies appears adequate, we expect appropriate correction at all Baxter facilities in this critical area."

FDA Warning Letter to Baxter

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