Microbiology FDA 483 : Lack of assurance of manufacturing operations – prevention of contamination of equipment or product by environmental and processing conditions

Observation

There is a lack of assurance that your drug substance manufacturing operations in building at Biologic facility are appropriately designed to ensure the prevention of contamination of equipment or product by environmental and processing conditions that would be expected to have an adverse effect on product quality

Facility Type

Non-Sterile Manufacturing

Firm / Company

AGC Biologics Inc.

System

Quality System

Details

Your firm lacks an established cleaning and sanitization program to prevent the introduction of microbial contamination into controlled manufacturing environments in building  DS manufacturing facility. Specifically,

(a) Your firm’s disinfectant efficacy study (DES), SEA-QR-000*** (version 2, effective l2Jul2022) does not adequately support the sanitization procedures for the antimicrobial and sporicidal effectiveness of the disinfectants and sporicidal agents for all representative manufacturing surfaces in the facility. For example, material used for *** walls, window glass, *** , floor mat, and chairs were not included in the study. In addition, the DES has not established the disinfectant expiration limits.

 

(b) Your cleaning and sanitization procedure for the classified DS manufacturing areas in the facility, SEA-SOP-000*** (version 46, effective l8Oct2O22) and SEA-SOP-000*** “Building *** Personnel and Material Flow” (version 31, effective l0Oct2022), do not require documentation and verification that the treated surfaces are wetted and remain wetted for the contact time(s) validated in the DES.

 

(c) There is a lack of adequate justification for the environmental monitoring (EM) locations specified in SEA-SOP-000*** “Routine Environmental Monitoring Program for Manufacturing Facility” (version 33, effective 30Aug2022). For example,

  • A total of *** surface sampling locations is selected solution Preparation Suit (Room ***) and A total of *** surface sampling locations is selected for Bioreactor Suite (Room***)

Only *** sample locations are selected for the above process suites. According to your firm’s risk assessment, SEA-RIA-000*** “Building *** Environmental Monitoring Program Risk Assessment Summary Report” (version 2, effective 22Aug2022), Risk Mitigation Recommendations for Surface sample locations include to develop EM Sample location map for SEA-SOP-000*** that include location of ***.

 

(d) Your procedure does not require personnel monitoring by the operator performing cell *** steps. On 3Feb2023, observed operator *** performing cell *** of product *** of lot ***. During this cell *** step,  I observed that he did not touch his fingers to the plate media. Your procedure, SEA-SOP-000*** ” Process specific Environmental Monitoring Program” (version 32, effective 19Aug2021), does not require that operators perform personnel monitoring during cell ***.

Record Date

02/2023

FEI Number

3000209996

Country

USA

Citation Type

483

Audit Duration (Days)

9

Investigators

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FDA 483 relevant to Microbiology

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

Microbiology FDA 483 (Jiangsu Hengrui Pharmceuticals): Container closure systems do not provide adequate protection against foreseeable external factors

Jiangsu Hengrui Pharmceuticals Co., Ltd

Your container closure integrity test for *** Injection (USP) ***mg/***ml is inadequate, The test used empty vials instead of fille vials. Microbial Challenge Study was conducted without a positive control. Dye ingress study was conducted using human eye detection with results "not detected" without specifying the limit of detection,

Microbiology FDA 483 (Jiangsu Hengrui Pharmceuticals): Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of the aseptic and sterilization process

Jiangsu Hengrui Pharmceuticals Co., Ltd

Product contact equipment including *** stopper drums, *** were sterilized without outer wrapping and transferred from Grade A cart to Inside of the RABS without cover in Workshop *** Filling Room ***.

Microbiology FDA 483 (Jubilant Radiopharmacies): The movement of first air in the ISO 5 area is blocked or disrupted

Jubilant DraxImage Radiopharmacies Inc.

Specifically, on 03/06/24, during the production of Gozetotide (Illucix) Cold Kit Lot# K-***, your firm's Pharmacy Manager was observed blocking first pass air in the ISO-5 *** flow hood. The following prescriptions were drawn from the cold kit and dispensed: RX*** (13.94 mCi) and RX*** (25.49 mCi).

Microbiology FDA 483 (Jubilant Radiopharmacies): Personnel were observed performing aseptic processing outside of an ISO 5 area

Jubilant DraxImage Radiopharmacies Inc.

Specifically, on 03/06/24, during the production of Gozetotide (Illucix) Cold Kit Lot# K-***, your firm's Pharmacy Manager was observed performing the following aseptic connections in the ISO-7 aseptic processing area: connecting the *** sterile *** to the Gallium Generator and connecting the Sterile *** to the Gallium Generator. The following prescriptions were drawn from the cold kit and dispensed: RX*** (13.94 mCi) and RX*** (25.49 mCi).

Microbiology FDA 483 (Eugia Pharma Specialities): Aseptic processing areas are deficient regarding the system for monitoring environmental conditions

Eugia Pharma Specialities Limited

Surface monitoring of the filling and stoppering machine is not performed in a timely manner following the completion of aseptic filling operations to ensure the data is representative of the environmental conditions at the time of filling. For example:

Microbiology FDA 483 (Eugia Pharma Specialities): Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the equipment to produce aseptic conditions

Eugia Pharma Specialities Limited

On April 29, 2024, *** cleaning wipes packed and ready to be used for *** aseptic cleaning in the Grade A area of the *** Injection *** filling line *** had loose threads and fibers them. The same wipes are also used for *** cleaning in the *** Injection manufacturing line ***. Upon receiving, the wipes are not inspected for the presence of loose threads and fibers.
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