Microbiology FDA 483 (Cipla Limited): Failure to clean and maintain equipment and utensils to prevent contamination

Observation

Failure to clean and maintain equipment and utensils to prevent contamination or carry-over of a material that would alter the quality of the API beyond the official or other established specifications

Facility Type

Non-Sterile Manufacturing

Firm / Company

Cipla Limited

System

Quality System, Laboratory Controls, Facility and Equipment System

Details

Specifically,

Your firm does not properly clean and maintain ***-405 which is utilized in the manufacture of *** USP active pharmaceutical ingredient intended for the US market as noted below:

  • On 4/2/2024, inspected *** -405 in room (ISO-8). Upon opening the *** we noted what appeared to be two flying insects in the *** bowl of the *** near the ***.
  • On 4/3/2024, we inspected the *** duct of ***-405. The *** duct *** to the *** during API manufacture. The *** duct is located outside of building *** and exposed to external conditions. Upon inspection of the duct, multiple areas of external damage (dents) were observed and a large gap in the duct seal was noted approximately 4 fee from the *** valve), we were able to insert a folder 8×11 inch piece off paper into the dust seal gap and confirmed that the duct seal was non-integral breached. Your firm was unaware of the breach, the cause, and the duration for which the breach has been present.

 

Additionally, what appeared to be white *** caulking was noted to have been applied around the affected duct joint in an attempt to seal around the duct gasket. Your firm has no documentation as to when the *** caulking was applied to the *** duct or the reason(s) why (since 2023). The last preventative maintenance of the *** 405 *** duct was conducted on 2/21/2024 when your firm documented that the gasket/seals were inspected.

 

Additionally, your firm lacks evidence that one of the engineering technicians who performed the preventative maintenance was trained on the associated procedure. Since 2/21/2024, your firm has manufactured *** Lots of *** USP API intended for use in the manufacture of drug products for the US market.

 

On 4/3/2024, we inspected the interior of the ***-405 *** duct directly adjacent to *** valve. We noted various debris in the duct to include what appeared to fragments of duct sealant caulking) material and unknown residue.

Record Date

04/2024

FEI Number

3002806710

Country

India

Citation Type

483

Audit Duration (Days)

6

Investigators

Lori M. Newman, Sean R, Marcsisin

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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

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