Microbiology FDA 483 (Catalent Indiana): Procedures to prevent microbiological contamination did not include adequate validation of the aseptic process

Observation

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of the aseptic process

Facility Type

Sterile Manufacturing

Firm / Company

Catalent Indiana, LLC

System

Quality System, Laboratory Controls, Facility and Equipment System

Details

Specifically,

(A) The designs of Vial Line *** systems ( ***), Vial Line *** (System ***), Flexible Fill Line *** (System ***), Syringe Line *** (System ***), and Syringe Line *** (System **) do not allow all *** to be *** with ***. These include, but are not limited to, the following:

  • *** (Vial Line ***) *** and ***)
  • *** (Vial Line ***) : ***
  • *** (Flexible Filling Line) : ***, *** and ***
  • *** (Syrine Line ***) ***, *** and ***
  • *** (Syrine Line ***) ***, *** and ***

Qualification of the *** decontamination cycles for ***lines did not always include biological indicators (BIs) placed in the *** furthest away from airflow to demonstrate that the *** during *** are sufficiently decontaminated.

 

(B) The design of the *** systems for Vial Line *** systems ***, Vial Line *** system***, Flexible Fill Line *** system ***, Syringe Line *** system ***, and Syringe Line *** all require all environmental monitoring (EM) plates to be transported to a central location. To do this, operators enter numerous *** *** to form a *** and proceed to pass EM plates through the *** to the centralized location. Airflow visualization studies do not include visualization of these interventions in their entirety; only the action of changing plates is visualized, and not the transport of new plates from and old plates to the central location.

 

(C) Written procedures designed to prevent microbiological contamination of products purporting to be sterile during aseptic processing are not adequate. For example, the following was observed:

  1. On 31 OCT 2023, Investigators observed operators’ bare face/skin and gowns touching *** while performing interventions *** start-up and at end of fill *** system *** (Grade A) and Grade C areas in Room 820). One operator was observed blowing air from his mouth (not masked) into the surrounding environment while his face was touching *** during an intervention that he was performing
  2. *** appear stained / soiled. For example, *** *** on Vial Line ***, on Vial Line *** and *** on Syringe Line, and *** on the Flexible Fill (Flexi) line were observed with apparent ink over the ***. Additionally, *** on Flexi and *** on Syringe Line *** were observed to have an apparent brown residue.
  3. On 31 OCT 2023, Investigators observed operators performing aseptic connection of the product storage bag to the filling line. Observed that after connection of the connectors to the fill line outside the *** the unused backup connector outlets were hanging down towards the floor and contacting a *** Barrier that was used and stepped over by operators during the aseptic connection process.
  4. On 01 NOV 2023, during aseptic set-up of the stopper bowl on Vial Line *** prior to ***, investigators observed that the operators appeared to have difficulty in removing the *** cover off the installed stopper bowl, potentially causing unnecessary perturbations of the unidirectional air flow in the ***.
  5. On Oct 31, 2023, Investigator observed that on one of the staging carts in Filling Room 820 Grade C area, one of the wheels of the cart was observed to have *** materials lodged within and around the *** wheel, which may prevent adequate sanitization.

Record Date

03/2024

FEI Number

3005949964

Country

Indiana

Citation Type

483

Audit Duration (Days)

9

Investigators

Jacob G Lutz, Rafeeq A Habeeb, Wendy G Tan, Yuan-Chia Kuo, Alan L Truong

More observations from same firm / company

Microbiology FDA 483 (Catalent Indiana): Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures

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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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