Sun Pharma Baska Facility Classified OAI for Aseptic Operation Deficiencies

The USFDA has classified Sun Pharma’s Baska (Halol) facility (FEI: 3002957541) as Official Action Indicated (OAI) following an inspection in September 2025. The inspection, conducted by investigators Eileen A. Liu and Claudia Perez-Kasmarski, resulted in a Form 483 citing significant lapses in aseptic process controls, operator practices, and investigations into microbial excursions at the sterile drug manufacturing site.

Operators Failure to Follow Aseptic Techniques

Microbial contamination control procedures were not adequately followed. Multiple lapses in aseptic behaviour while performing assembly and set up operations, sterile connections, and material transfers to Grade A area were observed.

Operators unfamiliar with Sterile connection Process: While making a S2S (sterile-to-sterile) connection between the Sterile product transfer tank in Grade B area and the Filling Machine in Grade A area operator used unsanitised hands to open cover from sterile connectors. Hands were sanitised only after completing the connection, though Media fill study video showed operators sanitise hands before making the S2S connection.

Validation of Sterilisation Cycles: Components, accessories cleaned and sterilised between batches, however sterilisation cycles are not validated.

Lapses in sanitisation during transfers:  Wrapper of sterilised items for making sterile assembly installation were removed in Grade B filling room and without sanitising wrapper surfaces, bag was transferred to Grade A filling line with unsanitised hands. Operator was touching the Grade A surfaces with unsanitised hands for finding correct orientation for installation.  Wrapper of bag containing sterile stoppers was cut open in Grade B area and bag moved to Grade A filling line without sanitising surfaces of the wrapper.

During assembly and set-up operations, hands were not sanitised before entering Grade A filling line, and sanitised only after they were already inside the Grade A filling line. And during hand sanitisation the sanitising agent was sprayed near the Grade A Environmental Monitoring (EM) settle plates and active air sampler, possibly contaminating the media.

Blocking of First Air during interventions: Operators were blocking first air in the filling area during interventions like addition of stoppers to bowl, removing fallen vials.

Inappropriate Cleaning Technique: During cleaning of Grade A areas, clean room operators were seen to be using same side of wipe upto 3 times, instead of the appropriate technique of using clean side of the wipe each time to apply parallel unidirectional and overlapping strokes.

Skin Exposure in Aseptic Areas: Goggles used by operators have holes on top of frame, with risk of exposed skin and contamination of clean room environment impacting product sterility.

Uncontrolled Personnel Movement: Personnel movement between Grade B sterile corridor and filling room not carefully controlled.

Deficient Airflow Visualisation Studies

The airflow visualisation study videos showed inadequate smoke coverage, turbulent airflow, and video did not show how articles were moved from Grade B to Grade A areas. Strong horizontal /turbulent airflow was seen coming out of location where bags containing sterile bottles / caps were staged inside Grade A area. Operators were blocking first air during set up operations. Also Media fill did not include simulation of all interventions performed during vial sealing operations of commercial batches.

Environmental and Personnel Monitoring (EM/PM) Deficiencies

Recurring excursions and No effective CAPA:

Several batches of sterile drug products were rejected due to Environmental (EM) or Personnel Monitoring (PM) excursions since 2023, showing a negative trend with 122 PM Grade B area action limit excursions and 5 Grade A area excursions. Microorganisms isolated include Gram positive skin flora species (staphylococcus, micrococcus), Bacillus species, gram negative species (pseudomonas, Moraxella, vibro), Mold species (aspergillus, penicillium). No effective corrective actions were implemented despite excursions.

NVPC Monitoring: Filling line vial sealing RABS were classified Grade B / C without adequate justification. Though Grade A air is claimed to be supplied to the RABS and Non-viable Particle count (NVPC) monitored as per Grade A standard, there was no NVPC monitoring during production, only pre or post batch NVPC were monitored.

Inadequate Investigation of Microbiological Excursions

Multiple cases of microbiological or bacteriological contamination incidents during aseptic process simulation (APS) study batches were not thoroughly investigated

No Root cause/ CAPA for APS Batch Failures:

• In a case where positive growth of staphylococcus hominis observed in all vials before incubation of an APS batch root cause was identified as integrity failure. But there were no investigations into reasons for the integrity failure or CAPAs to assure the failure will not recur.
• Positive growth of microorganisms was observed in container units in an APS requalification batch. Incorrect size of stoppers was identified as root cause for contamination. Contaminating microorganisms included Kocuria Rhizophila, Kocuria palustris, aspergillus tubinggensis/vandensis, staphylococcus haemolyticus, staphylococcus epidermidis, micrococcus luteus, brachybacterium conclomeratum / paracnglomeratum and brachybacterium squillarum. Investigations did not look into what caused ingress of contaminating microorganisms. There was a likelihood of contamination being introduced from the Grade C area surrounding the Grade B sealing RABS. Even then vial sealing RABS was further downgraded from Grade B to Grade C, exposing sealing operation to lesser controlled environment.

Removal of Media fill vials with growth before completion of incubation

During Media fill failure investigations containers that showed positive growth were immediately removed and tested for microbial identification prior to completion of incubation. Removal of containers prior to completion of incubation prevent detection of slow-growing microorganisms, damaged microorganisms or microorganisms having different temperature requirement sufficient time to recover and proliferate.

Takeaways:

Observations show gaps in operator awareness and discipline during sterile connections, transfers, and interventions. Continuous training, reinforcement of aseptic techniques, and vigilant personnel monitoring are essential to prevent contamination risks in sterile operations. Robust root cause analysis in failure investigations and implementation of CAPAs to prevent recurrence, simulation of real interventions in media fills, and continuous EM/PM trending are vital for sterility assurance in aseptic manufacturing facilities.

USFDA 483 to Sun Pharmaceuticals Medicare Ltd (September 2025)