Microbiology FDA 483 (Eugia SEZ): Procedures designed to prevent microbiological contamination are not followed
Observation
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not followed
Facility Type
Sterile Manufacturing
Firm / Company
Eugia SEZ Private Limited
System
Facility and Equipment System
Details
Specifically,
(A) Your firm failed to follow EP4-PR-SOP-042, “Guidelines for Working in Aseptic Area” and EP4-MB-SOP-028, “Viable Monitoring Program“. The following are examples but are not intended to be a list of all times the procedures were not followed.
(1) Interventions into critical areas during aseptic manufacturing are not replicated during Aseptic Process Simulations, to assess risk and validate the performance of the interventions. For example:
- Removal of stuck vials through *** No. *** at *** during manufacture of *** Injection USP ***mg, Batch No. *** the operator was observed reaching his whole arm, including the *** portion of his arm and the fabric cleanroom gown, into the Grade A filling area to remove vials and stoppers. Aseptic Process Simulation Batch No. *** replicated intervention, occurring between 3:33 PM and 3:35 PM, did not include the operator reaching to the same depth into the Grade A area, nor was the intensity of movement and duration of the intervention accurately replicated.
(2) The written procedure, EP4-MB-SOP-028, mandates that operators perform personnel monitoring after interventions into critical areas (Grade A/ISO 5, while under Grade A air supply, prior to sanitization of hands. Examples of inadequate personnel monitoring, post *** interventions during filling operations of *** Injection USP ***g, Batch No. *** on 02/19-20/2024, on *** Line *** include:
- Removal of vials through *** No. *** at *** on 02/19/2024. The operator was observed reaching his whole arm, including the *** portion of his arm and the fabric cleanroom gown, into the Grade A filling area to remove vials and stoppers from the *** area. No personnel monitoring was performed.
(3) During aseptic filling of *** Injection USP ***g, batch *** February 17, 2024 on *** the following interventions were observed:
- At *** one operator passed a *** spray bottle underneath the *** conveyer to another operator on the other side without either operator first sanitizing their hands or the spray bottle. At *** the same operator left the RABS *** and returned to the *** conveyer where another operator passed a *** box of wipes underneath the conveyer without either operator first sanitizing their hands or the box of wipes. At this time three was *** drug product crossing the conveyer.
- From 2:57PM – 3:07PM, one operator was performing aseptic corrective interventions while placing his entire arm inside the Grade A area and did not clear the vials located directly at the *** conveyer near ***. The operator did not sanitize the area after performing the interventions and did not perform personnel monitoring on his ***as required per EB4-MB-SOP-028-02 Viable Monitoring Program. The operator did not use slow and deliberate movements while performing the interventions. The operator used quick motion to wipe the *** and *** the RABS *** much quicker than the technique used during aseptic process simulations.
(4) During aseptic filling of *** Injection ***g, Batch *** February 16, 2024, on *** the following interventions were observed:
- From *** an operator was performing an aseptic corrective intervention near the ***. He was leaning into the Grade A area over *** vials and touched multiple surfaces with his *** hands. After the manipulations there was no finger plating and one *** vial where manipulations were performed was not cleared from the line.
- From *** an operator *** to perform an aseptic corrective intervention of clearing fallen/stuck vials from the filling conveyer. He was leaning into the Grade A area over the filling line while performing the intervention. The operator touched the filling line tubing with his *** sleeve several times during this intervention. He also adjusted the conveyer with his *** hands and did not sanitize the same areas that were touched. The operator did not perform personnel monitoring on his *** as required per EB4-MB-SOP-02802 Viable Monitoring Program.
Record Date
03/2024
FEI Number
3011905047
Country
India
Citation Type
483
Audit Duration (Days)
9
Investigators
Ashar P Parikh, Marcellinus D Dordunoo
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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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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,
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 ***.
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).
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).
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:
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.