Microbiology FDA 483 (Aurobindo/Eugia Pharma) : No adequate validation of the aseptic process to prevent microbiological contamination

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

Eugia Pharma Specialities Limited

System

Quality System, Facility and Equipment System

Details

(1) Block *** Line *** re-qualification and *** exposure were not adequately performed:

(a) During *** re-qualification, Chemical Indicators (CI) and Biological Indicators (BI) were not placed at the worst case location of each *** folds in the *** sections of the *** were observed. However, CI and BI were placed only on the smooth surface of each *** during *** qualification cycles.

(b) There is no written procedure on how to use *** appropriately to prepare the *** for cycle. Partially ****** and folds in the *** areas were seen receiving *** prior to commercial manufacturing.

 

(2) The following deficiencies were observed during review of air flow visualization studies (smoke studies):

(a) Smoke studies for Block *** Line *** was not conducted under dynamic condition. Although various interventions were performed, the filling line remained static and did not simulate the commercial manufacturing condition. For example, removal a fallen vial was simulated at the *** location. The operator removed a fallen vial that was staged next to a few standing vials. However, under the true dynamic condition, the *** would be filled with empty vials and moving.

(b) For the Block *** Line *** the operator’s activities in *** sterile *** stoppers obstructed the path of unidirectional flow (first air) by reaching their arm over the ***. The operator also created turbulent air when he shook the canister in quick and short motions to release *** stoppers to the ***.

(c) On filling Line *** the simulation of removing a jammed *** stopper at the *** stopper bowl did not include simulation of reaching into the bowl.

(d) Review of the Air Flow Visualization Studies and the Air Flow Visualization Study Protocol E3-UTL-RQ-P-00***, entitled, “Dynamic Air Flow Visualization Studies”, for Line *** Block *** used to aseptically fill vials for the U.S. market, revealed that the study failed to assess air flow while the filling machine was running (dynamic condition).

The firm management stated the same smoke study approach applies to all Block *** and Block *** aseptic fill lines.

 

(3) Qualification of the HVAC system for the Line *** machine did not demonstrate it can maintain appropriate air quality for aseptic filling of US market *** and *** products.

(a) The *** of the *** occurs in an area that has been classified Grade C with no overhead HEPA coverage. No NVPC data has been collected in this area to demonstrate appropriate particle control. Smoke studies have not evaluated whether air flow from this area would allow air to ingress into the Grade A filling zone.

(b) Smoke studies of the Grade A filling zone demonstrate turbulence near the area where containers are filled. The smoke studies do not evaluate if air from surrounding areas can ingress into the filling zone. There has been no dynamic NVPC data of the Grade A

Record Date

02/2024

FEI Number

3008461619

Country

India

Citation Type

483

Audit Duration (Days)

9

Investigators

Justin A Boyd, Eileen A Liu, & Anastasia M Shields

More observations from same firm / company

http://pharmamicrobiology.com/fda-citation/microbiology-fda-483-aurobindo-eugia-pharma-procedures-not-established-followed-to-prevent-microbiological-contamination-of-sterile-drug-products/

http://pharmamicrobiology.com/fda-citation/microbiology-fda-483-eugia-pharma-laboratory-records-do-not-include-complete-data-data-integrity-issues/

http://pharmamicrobiology.com/fda-citation/microbiology-fda-483-aurobindo-eugia-pharma-batch-production-and-control-records-do-not-include-complete-information/

http://pharmamicrobiology.com/fda-citation/microbiology-fda-483-aurobindo-eugia-pharma-investigation-failed-to-thoroughly-assess-any-other-potential-sources-of-the-microbial-contamination/

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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

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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.

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

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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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