FDA EIR - BioConnection B.V. - June 01, 2018

An FDA inspection of Bioconnection B.V. in Oss, Netherlands, took place from May 28 to June 1, 2018, under the Compliance Program for Biological Drug Products and cGMP regulations. This initial cGMP inspection followed a pre-license inspection.

The inspection identified several significant deficiencies, resulting in a seven-item FDA-483. Main issues included inadequate validation of bioburden testing, lacking acceptance criteria and sufficient test repetitions. The company also approved and used a culture media lot that failed growth promotion specifications. Additionally, growth promotion studies failed to assure consistent organism recoveries, leading to a media lot rejection during the inspection.

Crucially, manufacturing and analytical changes, such as updates to certain process conditions and bacterial reference materials for bioburden testing, were not properly reported to the FDA by the license holder. A manufactured lot underwent an unapproved re-processing step not permitted under its U.S. license, yet was released to the market. The specific (b)(4) process was found to be inappropriately validated, with deficiencies like missing records and incomplete coverage of conditions. Lastly, there was a lack of adequate verification to ensure the accuracy of growth promotion data prior to media release.

Bioconnection B.V.'s management committed to submitting a written response to the FDA within 15 business days addressing these observations.