Microbiology FDA 483 (Aurobindo/Eugia Pharma) : Laboratory records do not include complete data (data integrity issues)

Observation

Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards.

Facility Type

Sterile Manufacturing

Firm / Company

Eugia Pharma Specialities Limited

System

Quality System, Facility and Equipment System

Details

(1) The Line *** contains a total of *** and integrity testing of all *** is perfo1med after *** batch. Review of CCTV video recordings showed *** integrity testing was not perfo1med on ***  during post fill *** integrity testing associated with aseptically filled ***. Injection batches *** and *** lnject1on batch *** (all U.S. batches) . However, passing integrity test results were generated for all *** that were not tested.

Production personnel stated they repeatedly test the same *** while assigning *** IDs from other *** that are not actually tested. This practice was observed to nave occurred following batch *** (2 out of the *** were actually tested), batch *** ( 4 out of the *** were actually tested), and batch *** (10 out of the *** were actually tested). Production personnel stated not all *** were tested because some of the *** would not pass.

On Janua1y 26, 2024, *** did not pass after three attempts to integrity test it, resulting in a product non-confo1mance investigation. The Line *** Assistant Manager for Production stated that no previous *** integrity failures were reported for Line *** from November 2019 to date.

 

(2) Environmental monitoring data worksheets for Grade A swab surface monitoring associated with aseptically filled Injection batches *** and *** Injection batches *** (all U.S. batches), documented collection of samples that were never taken. IPQA personnel confirmed swabbing of Grade A  *** tools and equipment surfaces was not performed. There are a total of *** swab sampling locations including but not limited to “on the *** *** *** “, and “on the *** near *** IPQA personnel confirmed the unexposed swabs were delivered to the Microbiology QC laboratory for processing, incubation, and enumeration. Results of the swabs were reviewed and released with no reported growth for batches *** and *** and *** despite sampling that did not occur.

 

(3) Environmental monitoring data worksheets for Grade A *** surface monitoring ***  associated with aseptically filled. Injection batches *** and *** Injection batches *** (all U.S. batches), documented collection of samples that were never taken. IPQA personnel confirmed that only 10 out of the *** were sampled for batch ***. None of the *** were sampled for either batch *** or batch ***.  IPQA personnel stated all *** media plates (used and not used for sampling) were delivered to the Microbiology QC laboratory for incubation and enumeration. Results for these plates were reviewed and released with no reported growth for batches *** and *** and *** despite sampling that did not occur.

 

(4) *** non-viable particle counts (NVPC) taken in Grade A and Grade B aseptic processing areas are reported without collecting samples in the documented locations.

(a) Production personnel involved in Line *** filling *** Injectable Suspension *** Vial batch *** (US market) on January 17-18, 2024, stated *** Grade A and Grade B non-viable particle count samples are not taken in the fill room at the documented sample locations. Rather, they are taken from an *** in the the aseptic corridor outside of the filling room. These samples are taken after the corresponding aseptic filling activities have occurred. To get the time and date that appears on the NVPC printout to match, the operators change the time and date on the NVPC instrument by backdating it to when the sample should have been collected.

A production operator stated the samples are taken in the aseptic corridor *** ‘because the tests do not always pass when taken in the filling room at the designated locations. The operator acknowledged there have been previous failing results that were not repo1ied. These failing printouts were discarded and the tests were repeated in the aseptic corridor ***.

A production supervisor for aseptic filling Lines *** and *** stated he was aware of this ongoing practice for the past year. He stated he initially instructed employees to take samples in the aseptic corridor when the NVPC device was not functional because it was not charged. He acknowledged production employees continued the practice.

(b) Production personnel involved in Line *** filling *** batch *** (US market) confirmed the *** Grade A and Grade B nonviable particle count samples were not taken in the filling room. Samples were taken in the aseptic corridor ***, but documents were made to indicate they were taken in the filling room by changing the time and date on the NVPC instrument.

(c) Production personnel responsible for *** NVPC monitoring during the filling of *** Injection, Batch *** (US market), on January 18, 2024, stated NVPC samples for the grade B of Line *** Block *** were actually collected in the *** and not in the filling room in the designated sample locations. The operators changed the time and date on the instrument by backdating it to when the sample should have been collected to get the time and date to match for reporting in the records.

Interviews with production personnel and recordings of previous media fills demonstrate this is an ongoing practice. Media fills perfo1med in September 2022 (Block *** Line ***), April 2023 (Block *** Line ***),  September 2023 (Block *** Line ***), November 2023 (Block *** Line *** ) and December 2023 (Block *** Line ***) similarly showed NVPC samples were not taken at the times and locations documented in the records.

 

(5) *** non-viable *** air samples taken in Grade A and Grade B aseptic processing areas are submitted to the microbiology laborato1y without exposing plates at the specified locations. Samples are collected in an aseptic corridor *** on *** instead of the specified locations in the filling room. Records are made to appear as if the samples were collected at the specified locations and times in the filling room. For example:

(a) IPQA personnel involved in monitoring during *** Injectable Suspension *** Vial batch *** (US market) on January 17-18, 2024,  stated the *** air sampling documented in the records, including both Grade A and Grade B sample locations, were not exposed in the filling room at the documented locations.

(b) IPQA personnel involved in monitoring during *** batch *** (US market) on January 21-22, 2024, confirmed *** air sampling documented in the records were not exposed in the filling room at the documented locations.

(c) IPQA personnel involved in monitoring during *** batch *** (US market) on Janua1y 20, 2024, confirmed *** air sampling documented in the records were not exposed in the filling room at the documented locations.

(d) IPQA personnel involved in filling *** Injection, batch *** (US market), on Janua1y 18, 2024, stated the samples from sampling points *** *** *** in the Grade B area of Block *** Line *** were not exposed in the filling room at the documented locations. Instead, these samples were taken in the ***. These samples were submitted to the laboratory and placed on incubation without ever being exposed to the environment in the filling room.

Interviews with IPQA personnel and recordings of previous media fills demonstrate this is an ongoing practice. Media fills perfo1med in September 2022 (Block *** Line ***), April 2023 (Block *** Line ***), September 2023 (Block *** Line ***), November 2023 (Block *** Line ***) and December 2023 (Block *** Line ***) similarly showed *** air samples were not taken at the times and locations documented in the records.

 

(6) Review of the CCTV footage from Block *** revealed that on Janua1y 18, 2024, operators were observed performing post filling, environmental surface monitoring of the Grade A RABs *** used to perform interventions during aseptic filling. Per SOP E3 -QC-MIC-GEN-00***, the *** are to touch the media plate *** ***. The RABs *** being sampled were observed to never touch the *** plate. For example:

(a) Block *** Line *** (CCTV CAM2) the RABs *** was placed just above the surface of the *** never touching the plate. Monitoring was associated with aseptically filled batch *** Injection, US market.

(b) Block *** Line *** (CCTV C.AM3) the RABs *** was observed over the  *** plate during EM monitoring, the *** never touching the plate. Monitoring was associated with aseptically filled batch *** Inj. US market.

 

(7) For surface swabbing SOP E3-QC-MIC-GEN-00**, “The sampling area covered should be greater than or equal to *** cm2 but no larger than *** cm2 or sampling shall be done such that it covers the maximum surface of the intended location.” Review of the CCTV footage from Block *** Line *** CAM3, from January 18, 2024, showed an operator performing Grade A swab sampling on the tweezers used to perform interventions on open sterile unfilled vials that are used to hold the aseptically filled drug product. Post filling of Batch *** Inj . US market, the operator did not touch the surface of one side of the tweezers with the swab and only touched a small section of the other side of the tweezers with the swab.

(8) Production personnel only print the passing *** integrity testing results. If there are failure leaks, interrupted tests, or alarms, the results are not printed to be included with the batch record for QA review. For example:

(a) Line *** post *** integrity for *** Injection batch *** failed to include two failing and two leaking results.
(b) Line *** post *** integrity for *** Injection batch *** failed to include one failing, four interrupted, and three alarms.

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-aurobindo-eugia-pharma-batch-production-and-control-records-do-not-include-complete-information/

http://pharmamicrobiology.com/fda-citation/microbiology-fda-483-aurobindo-eugia-pharma-no-adequate-validation-of-the-aseptic-process-to-prevent-microbiological-contamination/

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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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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