Microbiology FDA 483 (Eugia SEZ): Written records are not always made of investigations into unexplained discrepancies

Observation

Written records are not always made of investigations into unexplained discrepancies

Facility Type

Sterile Manufacturing

Firm / Company

Eugia SEZ Private Limited

System

Facility and Equipment System, Laboratory Controls, Quality System

Details

Specifically,

(A) During finished product testing for *** injection USP ***g, batch *** your firm received OOS results for bacterial endotoxin testing. Your investigation initiated on September 26, 2023, determined the source of the endotoxin was attributed to the *** API used to manufacture these batches.

 

The investigation at the API manufacturer did not identify a definitive root cause but determined the probable cause of the OOS was “operating person might have missed to apply the *** to release the *** present inside the *** and this might have resulted in hold up of *** in *** in the stated batches. Considering the scope of proliferation on storage and stagnation of *** in any given system, there is a scope for the microbial proliferation, which in turn might have probably contributed for the development of endotoxins in the *** which would have forwarded with the further manufacturing process pertaining to subject batches.” This probable cause was not confirmed to be the source of endotoxin and this probable cause is also not limited specifically to the *** API batches *** used to manufacture the OOS finished product batches.

 

Furthermore, on December 2, 2023, your raw material testing for *** API confirmed three batches tested positive for endotoxin. The API manufacturer investigation again did not identify a definitive root cause but identified additional probable causes. These causes were not specific to these three batches but were identified as “no specific cleaning procedure *** (*** cleaning procedure) after usage of *** dedicated for ***% solution, ***. As a preventive action, your firm rejected the confirmed OOS finished product and API batches, and tested all remaining API batches/containers in stock for bacterial endotoxin. All batches that tested negative were released for production.

 

Your firm utilized approximately *** other *** API batches after the initial OOS that were manufactured by this supplier before the supplier made any corrections to their manufacturing processes that resulted from their investigation.

 

(B) While reviewing the test result for *** sampling point *** from February 5 2024, a *** result of *** was observed, which is above the action limit of ***. According to your SOP EP4-QC-SOP-005-00, “Sampling procedure for *** Samples”, when the test exceeds the action limit, a process non-conformance has to be initiated. Your firm failed to initiate a non-conformance to investigate this out of limit result.

Record Date

03/2024

FEI Number

3011905047

Country

India

Citation Type

483

Audit Duration (Days)

9

Investigators

Ashar P Parikh, Marcellinus D Dordunoo

More observations from same firm / company

Microbiology FDA 483 (Eugia SEZ): Equipment is not suitably located to facilitate operations for its intended use

Microbiology FDA 483 (Eugia SEZ): Procedures designed to prevent microbiological contamination are not followed

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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

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

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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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