Laurus USFDA 483: Lapses in investigation of equipment damage, cleaning.

USFDA inspected Laurus Synthesis, Visakh facility in India (FEI: 3011524794) in Dec 2023 by investigators Joseph A. Piechocki and Rafeeq A. Habeeb. The USFDA 483 reports five observations including lapses in investigations of equipment damage and potential particulate contamination; deficiencies in cleaning, verification and maintenance of equipment, product transfer hoses.

.USFDA 483

Summary of the five observations in the Laurus USFDA 483 are:

1. Inadequate Investigations: Damage to manufacturing equipment observed during preventive maintenance, change over cleaning etc; potential particulate contamination in batches of Key starting material, API Intermediate manufactured were not adequately assessed. Investigations and actions were inadequate in incidents of failure of hold time study of Key starting material (Key SM) for impurities; incorrect inprocess sampling which failed to detect failure of sample for impurities, Out of specification (OOS) of Water for TOC (Total Organic Carbon) which was not correlated to TAMC (Total Aerobic Microbial count) and conductivity.
2. Current sampling plan for intermediates fails to obtain a representative sample of the bulk for analysis. Critical quality attributes of assay and impurities of Intermediates are not assessed in any study to ensure these are uniformly distributed within the material though each packaged drum is sampled and analysed.
3. Cleaning and maintenance of Equipment and accessories & cleaning verification is inadequate – observed rust, product residue, dirt, dark residue in cleaned equipment; Room where final packing is done had gaps to outside (through which outside light could be seen). Product transfer hoses are not maintained in a way to ensure residual solvent or water don’t stay inside the hoses after cleaning, debris were observed in hoses; hoses were without sufficient label, identity, cleaning tag.
4. Lapses in Documentation: Accessories like portable gauges for water, transfer hoses etc are not identified and recorded in the BMR (Batch record); Use of process water – performance of the sampling port and transfer hose – are not adequately documented. Documentation of pressure readings during manufacture is inadequate.
5. Lapses in document issue control, reconciliation – Pages for recording weights are printed by Production personnel and attached as annexure to Batch records; These pages are not issued, controlled and reconciled.