Microbiology FDA 483 : SOP or work instructions are not followed or are inadequate

Observation

Standard Operating procedures or work instructions are not followed or are inadequate

Facility Type

Non-Sterile Manufacturing

Firm / Company

AGC Biologics Inc.

System

Quality System, Facility and Equipment System

Details

(A) Your endotoxin procedure, SEA-ANM-0******, “Endotoxin Determination Using the LAL Kinetic Chromogenic Method”, did not state the sample storage hold time of endotoxin, which is inadequate. According to normal practice, the primary samples are allowed to be stored at 2 to 8°C for ***  before being tested, and that is based on the sample storage condition memo, SEA-RCD-00***, 12Aug2O22. However, the memo only referred to scientific publications with study conditions using a storage temperature of ***C, however no enough data have been shown using the same temperature and duration as stated above. In addition, the endotoxin may have adsorbed to the container surface over a period of time. The justification for long-term storage of endotoxin samples at 2- 8°C is insufficient.

 

(B) On February 6, 2023, observed demonstration of *** drug substance (*** simulation) bulk filling process in Rm *** at the ISO5 Laminar Air Flow Workstation (LAFW) . During the filling process, the *** operator was observed to adjust the *** on top of the ***  with her gloved right hand holding an *** wipe. According to the procedure of aseptic practice, SEA-SOP-00**** “Cleanroom Behavior & Aseptic Practices” (version 8 , “moving hands, gowns, sleeves, or any other components over open product are prohibited”. The *** operator failed to follow SOP during the drug substance bulk fill unit operation.

 

(C) On February 6, 2023,  observed the post-use environmental monitoring process after the completion of drug substance bulk filling operation in Room ***. During the personnel hand sampling (finger dab), the *** operators failed to follow the procedure, SEA-SOP-000*** version 18, “Environmental Surface Monitoring”, to roll their fingers with sufficient contact time on the sampling plates. In addition, during the surface monitoring of *** with contact plates, the *** operator was observed to open the lid of contact plate with her gloved right hand holding an *** wipe, and the process is not documented in the SOP.

 

(D) On February 3, 2023, in the QC microbiology laboratory (Rooms ***), observed a QC analyst performing Colony Counting of environmental monitoring (EM) plates with no contemporaneous verification. We were informed that the contemporaneous verification check of the bioburden test is not necessary. It was determined to be low risk after post-mitigation based on the risk assessment report SEA-RIA-000***, “Microbial Colony Counting Contemporaneous Verification Risk Assessment” (version 1). However, the assessment underestimated the risk after post-mitigation and did not consider the criticality of direct product impact processes (IPC, release, PSM). A second analyst verification of the critical manufacturing steps for EM and bioburden plate reading should be implemented from a microbial control perspective to detect any microbial contamination off ***.

 

(E) According to the procedure of operating water baths, SEA-SOP-000*** version 6, “Operation of Water Baths in Manufacturing”, the cleaning procedure is to wipe out residual water from *** with another wiping after *** wipes or ***  are applied. In order to prevent microbial ingress in water baths, a sanitization procedure should be included in the cleaning procedure for decontamination. A documented worklog should also be enforced.

 

Record Date

02/2023

FEI Number

3000209996

Country

USA

Citation Type

483

Audit Duration (Days)

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

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