USFDA 483 to Panacea Biotec Cites Inadequate Aseptic Operation Controls

Panacea Biotec, Baddi facility was inspected by USFDA in Oct 2023- investigators Sandra A Boyd and Muna Algharibeh – resulting in issuance of Form 483 with 9 observations. The 483 observations highlight inadequate aseptic operations and controls, inadequate laboratory controls and quality oversight.

1. Inadequate procedures for microbiological contamination control -poor operator practices, peeling tapes used in RABS for identification, second operator entering LAF area though not addressed in Media fill studies. Multiple operators are involved in set up during media fill, but it is not documented who perform what activity – qualification and traceability of personnel inadequate, also qualification do not address engineers, supervisors, IPQA personnel in aseptic area.
2. Non viable particle count (NVPC) monitoring, location of NVPC probes, investigation of excursions are inadequate; Operators who perform set up in RABS in aseptic areas and stand in the extended Grade A area, are only held to Grade B gowning specifications for personal monitoring.
3. Training & qualification of personnel are lacking – visual inspection qualification kit do not include defects for fibres, hair, air bubble, chipped vials; repeat and consecutive use of same kits for qualification and requalifications can cause operator familiarity; visual inspection qualification procedure do not address inspector fatigue and worst cases; discrepancies in records of qualification of visual inspectors with time overlapping for different inspectors, time recorded for qualification of microbiologist visual inspectors is not justifiable.
4. Inadequate validation of aseptic processes – smoke studies do not demonstrate unidirectional air flow during operations, smoke are not placed above areas of operator intervention; all RABS interventions are not documented; trending of individual number and type of interventions for individual batches are not performed (to help in evaluating and designing interventions for media fill studies).
5. Failure to investigate discrepancies – excursions in non-viable counts during machine parts assembly are not investigated
6. Cleaning procedures are inadequate -do not contain enough detail to ensure reproducibility of cleaning between operators, do not address order to be followed in cleaning
7. Inadequate laboratory controls – no supplemental destructive testing for visible particulates; media seen pulled away from dehydrated media plates (contact plates); no scientific justification for rejection limits in visual inspection; analyst are able to check area counts in chromatograms without having to save chromatograms while changing processing methods; no prior approval by QC head practiced as defined in procedure when analysts perform manual integrations.
8. Inadequate Quality oversight – Aseptic areas are not designed to permit viewing through windows, Realtime viewing of aseptic operations through camera by Quality unit and IPQA are inadequate
9. Facility deficiencies, flaking / peeling off of location markings on the floor.

USFDA 483