FDA WARNING_LETTER - mallinckrodt inc., - March 13, 2008

On March 11-13, 2008, an FDA inspection of Mallinckrodt, Inc., dba Covidien's pharmaceutical manufacturing facility in Maryland Heights, Missouri, revealed serious deviations from Current Good Manufacturing Practice (CGMP) regulations (21 CFR 210 and 211). These deviations caused their Ultra-TechneKow DTE (Technetium Tc 99m) Generator to be adulterated.

Key violations included: 1. **Failure to establish scientifically sound specifications (21 CFR § 211.160(b)):** The release limit for Molybdenum-99 breakthrough did not assure the specification would be met at (b)(4) hours. The FDA questioned the firm's revised procedure using a predicted calculated ratio instead of a maximum limit at the time of testing. 2. **Failure to establish and follow written in-process controls and validate manufacturing processes (21 CFR § 211.110(a)):** Controls for (b)(4) backwashing, column assembly, and activation were not established, validated, or monitored, leading to molybdenum breakthrough defects. The firm failed to study the impact of washing process and particle size on product quality. 3. **Quality Control Unit (QCU) failures (21 CFR § 211.22(c)):** The QCU failed to ensure appropriate internal