FDA WARNING_LETTER - PharmaKon Pharmaceuticals - April 08, 2014

On May 21, 2015, the FDA issued a Warning Letter to Pharmakon Pharmaceuticals, an outsourcing facility, following inspections from March 5-13, 2014, and April 2-8, 2014. The second inspection was prompted by adverse event reports of over-sedation in infants due to incorrectly concentrated midazolam.

The FDA identified serious deficiencies in sterile drug production, leading to adulterated and misbranded products. Violations included insanitary conditions (e.g., technicians touching non-sterile surfaces then performing aseptic manipulations without re-disinfecting gloves), failure to demonstrate adequate ISO 5 area protection, and significant Current Good Manufacturing Practice (CGMP) violations. Specific CGMP failures included inadequate labeling material examination, lack of validated aseptic and sterilization procedures, insufficient equipment maintenance for aseptic conditions, improper personnel clothing, inadequate cleaning/disinfection systems, insufficient environmental monitoring, and lack of final product conformance testing for sterile batches.

Additionally, midazolam injection products were found to be super-potent (180.4% and 187.3% of declared concentration), violating USP standards and rendering them adulterated under FDCA section 501(b). The facility also failed to meet 503B outsourcing facility conditions, such as incomplete labeling (missing address, phone, dosage form, "This is a compounded drug" statement, and inactive ingredients) and failure to submit