FDA tells Dutch API producer to clean up its equipment act

Regulatory NewsRegulatory News | 01 July 2022 |  By 

A Dutch producer of active pharmaceutical ingredients (APIs) was put on notice to adopt more robust equipment cleaning practices and use better safeguards to prevent cross-contamination in a warning letter from the US Food and Drug Administration (FDA) dated 14 June. FDA found the presence of “visible powder residue” on non-dedicated equipment.
The warning letter pertained to Fagron Group B.V.’s manufacturing site in Saint Paul, MN. The company is headquartered in the Netherlands.
Investigators found three good manufacturing practice (GMP) deficiencies following an inspection conducted last November, including the failure to show adequate cleaning studies were performed to prevent potential cross-contamination. FDA said the firm failed to conduct adequate cleaning validation studies during its API repackaging and relabeling operations for highly potent drugs such as testosterone, estradiol, betamethasone, tamoxifen and opioids.
The firm “was unable to provide a completed cleaning validation study” to support its cleaning practices. “During the inspection, you acknowledged that your 2008 cleaning validation studies did not represent your current cleaning practice and your cleaning procedures needed to be revalidated,” said FDA.
In addition, after the company said its cleaning validations were complete, investigators observed “visible powder residue on non-dedicated equipment” after the repackaging of progesterone.
The company also said it was unable to provide cleaning logs for its repackaging of lidocaine HC1, asserting the logs were “destroyed.”
FDA said the firm also failed to adequately investigate and document out-of-specification results. For example, even though a June 2020 production of an API showed a high bioburden count, the firm did not initiate an investigation into its water systems, which is a component used to manufacture the drug.
Lastly, FDA said the company had a weak quality unit (QU); investigators found that computers connected to CGMP related laboratory equipment allowed changes to be made to the data supporting the drug’s release without restrictions.
In addition, the firm acknowledged its QU did not qualify the contract laboratories used to support product release, attributing this failure to “resource issues.” Yet FDA said this violation was a repeat observation from its 2017 inspection. (RELATED: FDA warns Mexican OTC Drugmaker, Dutch Drugmaker, San Francisco Device Company, Regulatory Focus 18 September 2018)
FDA told the firm to consult the International Council for Harmonization’s (ICH) Q7 guidance on GMPs for APIs. The agency also advised it to hire a GMP consultant.
The firm must submit a plan for addressing these deficiencies within 15 days of receiving the letter, and FDA warned that failure to correct these violations may cause the agency to withhold export certificates or withhold approval of new drug applications and supplements listing the firm as a manufacturer.
 FDA warning letter


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