(1) Microbiologists responsible for collecting environmental monitoring and personnel monitoring samples confirmed they do not collect all samples due to workload. Microbiologists also explained personnel monitoring samples may not be collected due to production personnel that refuse to submit to personnel monitoring. For samples that are not collected, a result is still recorded in the reported laboratory records that is below the alert limit and within trend of previous data. The practice of not collecting all samples, but still reporting conforming results has been occurring for at least one year.

(a) Inspection of the incubators in the microbiology laboratory on October 12, 2023, identified environmental monitoring and personnel monitoring samples that were supposed to have been collected during aseptic manufacturing on *** Lines *** and *** were not present. Logbooks with testing dates and incubator use logs documented samples, which were not present. Examples of missing samples included:

• Personnel monitoring samples including *** plates from *** body locations and *** finger dab plates for each person that had worked in the aseptic fill room for each day. From October 6-11, 2023, the aseptic entry and exit log documented there should have been approximately 102 sets of plates, containing *** plates for each person, under incubation. Only 3 sets of plates were present in the incubator.
• All post filling swab sample of surfaces inside the filling *** associated w *** batches ***, *** were missing from the ***.
• Active air monitoring samples in the filling *** associated with *** batches ***, and *** were missing from the incubator.
• Settle plate samples were missing from the incubator including:
  • Sample 11.6b (Grade A) on October 7, 2023, associated with ***.
  • Samples 11.5b and 11.5c (Grade A) on October 9, 2023, associated with batch ***.
  • Samples 66.1, 66.2, 66.3, and 66.4 (Grade B) on October 9, 2023, associated with batch ***.

(b) Review of video recordings of *** room for Line *** showed the settle plate and active air Grade A samples from the LAF sink hood were not collected on October 3, 4, or 5, 2023.

(c) Review of aseptic area entry logs identified times when no microbiologist was present to collect the environmental and personnel monitoring samples. For example, on October 4, 2023, during US market batch *** the microbiologist did not enter the filling room until after cleaning had been completed and the filling operators had left.

(d) Review of video recordings show there were no settle plates exposed in the microbiology corridor on October 9, 2023, even though records document these samples were collected.

(2) Review of video recordings from the *** room outside of Line *** showed the portable non-viable particle counter never entered the *** to the filling area on October 5, 2023. A microbiologist confirmed the samples were collected from a laminar flow hood in the microbiology laboratory and the printouts were made to represent samples had been collected from inside the *** Grade A filling barrier.

(3) A microbiologist confirmed that when samples are collected, if they are over an alert or action limit, they are verbally reported to the microbiology manager. The microbiology manager verbally requests additional cleaning be performed by production personnel and verbally informs QA, but there is no documentation made of the result that exceeded the limit. A result below the alert limit is recorded on the documentation for the sample that exceeded the limit. The microbiologist reported this occurs 2-3 times per month.

(4) On October 12, 2023, settle plate 11.5c(I) collected on October 9, 2023, from a Grade A location on the *** during *** batch *** was observed in a waste area. It contained ** CFU, an action level result. The plate was not due to finish incubation until October 14, 2023, and no result had been recorded.

(5) On October 16, 2023, settle plate 11.5a(I) collected on October I l, 2023, from a Grade A area on batch *** during *** batch *** was inspected after it had been read by a microbiologist that reported the result as “Nil”. The plate contained ** CFU, an action level result.

Over the last five years the microbiology laboratory reported no action level result and four alert level results from environmental monitoring and personnel monitoring. When samples from aseptic filling areas associated with batches were collected during the inspection and read on October 16-18, 2023, there were 39 excursions. This included 15 Grade A action level results, 5 Grade B action level results, 1 Grade B alert level, 13 personnel monitoring action level results, and 5 personnel monitoring alert level results.

The microbiology laboratory reported no sterility failures in the past five years. When the incubators were inspected on October 20, 2023, the following was observed:

• Empty sterile bottles taken from the bottle *** on line *** during a validation study associated with batch *** were inoculated directly into *** and showed turbidity.
• Incoming bottle lot ***, ***, Bottle *** showed a change in *** media that made the media completely pink. This bottle type is used for the US market product ***, ***, *** and ***, ***.