Microbiology FDA 483 (Zydus Lifesciences): Aseptic processing areas are deficient regarding the system for monitoring environmental conditions

Observation

Aseptic processing areas are deficient regarding the system for monitoring environmental conditions

Facility Type

Sterile Manufacturing

Firm / Company

Zydus Lifesciences Limited

System

Quality System, Laboratory Controls, Facility and Equipment System

Details

Specifically,

(A) From May 2023 until December 2023, your firm manufactured and distributed human drug products intended to be sterile when your environmental monitoring program for viable microorganisms was not in a state of control. During this time period, you documented 337 action level environmental monitoring excursions for bacterial and fungal recoveries in Grade-A and B aseptic processing areas for aseptic filling line *** to include critical aseptic filling areas, equipment, and personnel. Your firm’s actions in response to the environmental monitoring excursions are inadequate as noted below:

  • Your firm documented moisture and microbial contaminated *** environmental monitoring plates received from your supplier in July 2023 in excursion investigation IMDD-EM/23/010 (media lot ***) Despite the documented contamination of the media plates themselves, your firm attributed multiple action level environmental monitoring excursions for the line *** aseptic manufacturing area and the plate contamination to a contaminated incubator and continued using *** plates from the same supplier until December 2023. In December 2023, your firm again documented *** media lots not meeting your acceptance criteria *** media lots ***. The potentially contaminated plates from *** media lots *** were utilized in aseptic processing areas (line *** drug product manufacture to include for **** Injection *** mg/ml lot *** (media lot ***) which was shipped for the US market on ***.
  • Your firm’s retrospective evaluation of media used in your environmental monitoring program conducted for laboratory investigation LN-0318-2023-0206 (Attachment-XVIII, conducted December 2023) for a failed negative control during aseptic processing line *** environmental monitoring, is inadequate as a media lot with previous unacceptable and failing results was evaluated and documented as compliant. For example, *** lot *** was documented as compliant in the retrospective evaluation conducted in December 2023, however, moisture and microbial contamination (bacterial and fungal) of the media lot was documented 5 months earlier in excursion investigation IMDD-EM/23/010.

 

(B) Your firm’s airflow visualization studies (smoke studies) are inadequate for aseptic filling line *** as they use insufficient smoke to demonstrate unidirectional airflow and they demonstrate inadequate aseptic technique as exampled below:

(a) Insufficient smoke was noted in the 2021 smoke studies videos to include:

    • Shoot 10: During unloading of sterile items from the *** LAF to the RABS, insufficient smoke is visible *** the RABS to demonstrate unidirectional non-turbulent airflow (for example during transfer of *** from 16:24:32-16:27:43 camera ***.
    • Shoot 35: During ***assembly, no smoke is observed over the operator’s hands as critical operations are performed (for example from 10:46:53 to 10:47:11, camera ***
    • Shoot 36: During aseptic connection of fill tubing from the *** vessel to the *** inadequate smoke is observed near the critical area where the fill tubing is aseptically connected to the *** (for example from 11:48:53 to 11:49:49, camera ***)

 

(b) Inadequate Aseptic Technique – In shoot 35-camera *** the operator’s sleeve appears to rest against the fill tubing and *** assembly *** the RABS at 10:47:11 to 10:47:50 and extensively contacts the tubing and *** assembly again at 10:49:43 to 10:50:00. Procedure 0318-SOP-MFG-00028 “Operation of Vial Filling and Stoppering Machine” states in item 6.7.33, “During assembling, ensure that garment should not touch the any machine part of filling and stoppering machine.” The operator’s practices in the smoke study are inconsistent with the instructions in the procedure. Installation of the *** as shown in the video is inadequately designed as it requires the operator to reach over the fill line causing the operator’s gowning to contact the line in multiple areas.

Record Date

04/2024

FEI Number

3007621329

Country

India

Citation Type

483

Audit Duration (Days)

7

Investigators

Sean R Marcsisin, Lori M Newman

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Disclaimer: The purpose of this article is to provide helpful information on FDA 483s related to microbiological issues. This article represents 483 information in Tabular form for quick access and easy navigation. Information for this article is derived from “Form FDA 483” (Inspectional Observation). This article is not intended to replace the information provided by the FDA, nor is it guaranteed to be complete, always refer official FDA site for details.

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Alarm 1 Aseptic Behavior 30 Aseptic Technique 49 Autoclave 1 Biological Indicator 1 Building Maintenance 6 Calibration 1 Clean Room 15 Clean Room Practices 36 Cleaning and Sanitization 29 Cleaning Validation 1 Computerized System 4 Contamination 13 Contemporaneous Verification 1 Data Integrity Issue 10 Disinfectant Efficacy 2 Disinfection 15 Drug Product 1 Endotoxin 1 Environment monitoring 16 Equipment Cleaning 6 Equipment Operation 13 Facilities And Equipment System 13 Facility Design 5 Follow-Up Findings 2 General Cleaning 3 Good documentation Practices 4 Gowning 3 HEPA 4 Hold Time Study 2 HVAC 6 Influx of lesser quality air 1 Investigation 12 Investigation inadequate 5 Investigation incomplete 3 Laboratory Controls 17 Laboratory Practice 16 Maintenance 10 Manufacturing control 9 Media Fill 15 Method Transfer 2 Method Validation 5 Microbial Identification 1 Microbiological Contaminationn 10 No Procedure followed 14 Non-Conformance 1 OOS 5 Personnel Monitoring 3 Procedure 32 Qualification 32 Quality System 33 Risk assessment 6 Service Vendor Audit 1 Smoke studies 14 Specifications 5 Stability Study 2 Sterile Drug Products 5 Sterility Testing 1 sterilizati 2 Sterilization 3 Suitability 1 test procedure 0 Test Procedure (SOP) 10 Trends 1 Usage log 1 Validation 37 Visual Inspection 1 Warehouse 2 Water System 1

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