Microbiology FDA 483 (Biocon Sdn.): Procedures to prevent microbiological contamination are not established, written, or followed

Observation

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written, or followed

Facility Type

Sterile Manufacturing

Firm / Company

Biocon Sdn. Bhd.

System

Quality System, Laboratory Controls, Facility and Equipment System

Details

Specifically,

(A) On 07/10/2023 and 07/12/2023, inspected the post assembly and/ or aseptic filling of *** mL batch *** respectively. Observed the following deficiencies.

  • Aseptic operators blocked HEPA unidirectional airflow when re-plenishing *** stoppers and *** seals to their respective ***.
  • Sterile scissors used to cut open *** bags containing sterile components were held in non-sterile holders when not in use.
  • Section of the *** that was exposed to the Grade B area was not *** before returning to its Grade A position.
  • On 07/10/2023, the inner surfaces (Grade A side) of the RABS *** sectioning off the *** from the Grade B side were not sanitized after performing *** interventions.
  • On 07/12/2023 the aseptic operator stood inside the Grade A area while cleaning the inner surfaces of the RABS *** after *** interventions.
  • BM/PDP/SOP/140 lacks sufficient details on how to clean RABS ***.
  • Insufficient amount of *** was applied to the *** to clean RABS surfaces.

 

(B) Watched videos of your firm’s airflow visualization studies conducted in 06/2023 and observed the following.

  • HEPA unidirectional airflow to the *** was blocked during replenishment of *** stoppers and *** seals.
  • Aseptic operator’s head, right shoulder and arm were seen inside the Grade A area during ***.
  • Aseptic operator’s head, upper chest, both shoulders and arms were seen inside the Grade A area during *** seal ***.
  • Cleaning of the *** RABS *** after *** interventions was not simulated.
  • *** sanitization during *** interventions were not simulated to assess risk of creating Grade A turbulent air by using *** bottles.
  • Demonstration of *** sanitization with *** as different from the routine practice.

 

(C) According to your *** Production Manager *** and your Deputy Manager ***, your firm does not conduct *** integrity testing to ensure that there are no microscopic defects such pinholes and tears that can possibly seen before use in aseptic production of your sterile injectable drug products. At least *** batches of sterile **** and *** batches of sterile vials were manufactured for distribution to the United States since January 2020 where *** integrity testing was not performed therefore, there is no sterility assurance that the *** are adequate for use prior to start of aseptic production.

Record Date

08/2023

FEI Number

3011248248

Country

Malaysia

Citation Type

483

Audit Duration (Days)

Investigators

Eileen A. Liu, Investigator, Patty P. Kaewussdangkul, Daniel Lahar, Rong Guo

More observations from same firm / company

Microbiology FDA 483 (Biocon Sdn.): Failure to have written procedures for connective and preventative actions during loss or reversals of different pressure in classified aseptic areas

Microbiology FDA 483 (Biocon Sdn.): Fails to establish and document the accuracy, sensitivity, specificity, and reproducibility of its test methods

Click here to Download Report form FDA Site
Go to Table
Go to Home
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.

More Observations...

Microbiology FDA 483 (Jiangsu Hengrui Pharmceuticals): Container closure systems do not provide adequate protection against foreseeable external factors
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
Microbiology FDA 483 (Jubilant Radiopharmacies): The movement of first air in the ISO 5 area is blocked or disrupted
Microbiology FDA 483 (Jubilant Radiopharmacies): Personnel were observed performing aseptic processing outside of an ISO 5 area
Microbiology FDA 483 (Eugia Pharma Specialities): Aseptic processing areas are deficient regarding the system for monitoring environmental conditions
Microbiology FDA 483 (Eugia Pharma Specialities): Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the equipment to produce aseptic conditions
Microbiology FDA 483 (Eugia Pharma Specialities): Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations
Microbiology FDA 483 (Eugia Pharma Specialities): There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed
Microbiology FDA 483 (Eugia Pharma Specialities): Procedures to prevent microbiological contamination did not include adequate validation of the aseptic process
Microbiology FDA 483 (Eugia Pharma Specialities): Procedures to prevent microbiological contamination sterile drug product are not established and followed
Microbiology FDA 483 (Zydus Lifesciences): Appropriate controls are not exercised over computers or related systems
Microbiology FDA 483 (Zydus Lifesciences): Aseptic processing areas are deficient for monitoring environmental conditions
Microbiology FDA 483 (Zydus Lifesciences): Procedures to prevent microbiological contamination are not followed
Microbiology FDA 483 (Zydus Lifesciences): Procedures to prevent microbiological contamination did not include adequate validation of the aseptic process
Microbiology FDA 483 (Zydus Lifesciences): Established sampling plans and test procedures are not followed
Microbiology FDA 483 (Precision Equine LLC): Equipment and utensils are not cleaned, maintained and sanitized at appropriate intervals to prevent malfunctions and contamination
Microbiology FDA 483 (Precision Equine LLC): Procedures to prevent microbiological contamination are not established; written and followed
Microbiology FDA 483 (Precision Equine LLC): No written testing program designed to assess the stability characteristics of drug products
Microbiology FDA 483 (Sun Pharmaceutical): The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed
Microbiology FDA 483 (Sun Pharmaceutical): Equipment and utensils are not cleaned and maintained at appropriate intervals to prevent contamination
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.
error: Content is protected !!
Scroll to Top