USFDA 483 to Dr.Reddys (DRL) Cites Cleaning Deficiencies, Building Maintenance Lapses Read More..

Dr.Reddys Laboratories (DRL) Medchal, Telengana site was inspected by USFDA (Investigators Saleem A Akhtar & Pratik S Upadhyay) in October 2023. USFDA has published the 483 issued to DRL(FEI 3002949099), with 10 observations. The major observations include cleaning deficiencies of equipment and area, Inadequate building maintenance of manufacturing areas, lapses in Microbiology analysis, gowning procedures and others.  

USFDA 483

Detailed list of observations

1. Observed unclean area underneath equipment in production area with liquid spillage, residue, colour. Samples collected and analysed from equipment surface show presence of previous product actives in product contact and non-contact areas. Tablet samples analysed also show presence of other actives. Product residue accumulation, wet surface in areas underneath mounted platform of non-dedicated equipment not cleaned since installation. This has potential to spread across manufacturing area and deposit in machine components over several years due to positive pressure in the manufacturing area and also potential for microbial growth. Samples collected underneath mounted platform of equipment showed fungal growth. Observed tiny cracks on equipment surface with potential to contaminate products with tiny pieces from the cracks.
2. Inadequate visual inspection and checks by production operators and IPQA on equipment after major cleaning, preventive maintenance (PM); observed residues of previous product on equipment after major cleaning, broken pieces of sealant after PM.
3. Test for TAMC (Total Aerobic Microbial Count) & TYMC (Total Yeast & Mould Count) in purified water and drug products are deficient. Colony counter in microbiology was not counting all colonies; also observed discrepancy in colonies counted by analyst and reviewer.
4. Failure to investigate deviations thoroughly. Investigation into stability failures and follow up actions (recall) was delayed allowing Out of specification (OOS) product to be available in market till expiry. Inadequate investigation of unknown peaks in chromatograms, peak integration inhibited.  
5. Calibration failure incidents in QC equipment not evaluated adequately for impact on batches tested during calibration cycle. Firm performs preventive maintenance of laboratory equipment before routine calibration. This practice (calibration performed after Preventive Maintenance checks) fail to assess whether equipment was performing accurately & impact of any potential calibration failure on samples analysed within the calibration cycle.
6. Inadequate handling of complaints and follow up actions – e.g. complaints of hair in drug products (hair embedded in tablet, hair observed in capsule bottle); personnel were given training on gowning practices, personnel who scored 0%-60% in training assessment continued to work in manufacturing areas, with no timely retraining and assessment. Procedure for historical evaluation of repeat complaints do not review all batches within valid shelf life.
7. Failure to control cancelled tests and samples in LIMS, no trending or evaluation. In last three years (2021,2022,2023) more than 3,00,00 tests / samples cancelled each year in LIMS.
8. Test methods for TAMC (Total Airobial Microbial Count) for environmental monitoring samples are not validated, suitability not established.
9. Inadequate building maintenance – cracks in wall surfaces, wall coving in Production core areas, broken sealants on equipment, electrical panel, makes it hard to clean, allows for entrapment of water, residue build up and microbial growth.
10. Inadequate gowning procedures – No beard mask available for employees entering production area, most employees in production area have exposed beards; (There were history of complaints of hair in tablets and capsule bottles!!!). Observed operators with damaged shoes.