U.S. FOOD AND DRUG ADMINISTRATION
FORM FDA 483 — INSPECTIONAL OBSERVATIONS
--- SYNTHETIC DEMONSTRATION DOCUMENT — NOT A REAL FDA-483 ---

Inspected Site
Meridian Biopharm, Inc. — Bedford Manufacturing Facility
Bedford, Massachusetts, United States
FDA Establishment Identifier (FEI): 3009654321

Products Manufactured at This Site (in scope of inspection)
    XYLEVA (halomectinib) drug product — contract manufacturer for Halcyon Bio Corp
    (also produces drug product for two additional sponsors not disclosed here)

Inspection Details
Inspector Agency: U.S. Food and Drug Administration (FDA)
Inspection Dates: September 9–15, 2024
Inspection Type: Post-approval GMP surveillance (21 CFR Part 210 & 211)
Overall Outcome: Voluntary Action Indicated (VAI) — 4 observations issued

OBSERVATIONS

Observation 1 [MAJOR]
Batch production and control records for batches XL-2024-047 through XL-2024-053 did not
document investigation of a 3-log excursion in aseptic-filling environmental monitoring
observed on July 22, 2024. Deviation was closed without a documented root-cause analysis
as required by written procedure.
Citation basis: 21 CFR 211.192 (production record review) and 21 CFR 211.113 (control of
microbiological contamination).

Observation 2 [MAJOR]
Environmental monitoring program for the Grade A/B aseptic filling area lacked defined
alert and action limits for two of five sample points identified in the environmental
monitoring plan (documents EMP-2023-004, EMP-2023-005). Corrective action for the July 22
excursion referenced above was not extended to the two undefined sample points.
Citation basis: 21 CFR 211.113.

Observation 3 [OTHER]
Standard operating procedure SOP-QC-018 (Out-of-Specification Result Handling) does not
require documentation of the initial-vs.-retest evaluation logic for laboratory OOS
results, and inspection observed three OOS records without documentation of the analyst's
initial evaluation.
Citation basis: 21 CFR 211.192.

Observation 4 [MAJOR]
Change-control procedure SOP-QA-004 was not applied to a modification of the filling-line
peristaltic pump speed (September 3, 2024). The parameter change was implemented on the
production floor without an approved change-control request. The parameter falls within
the critical-process-parameter (CPP) list per validation report VR-XL-2023-002.
Citation basis: 21 CFR 211.100 (written procedures; deviations).

CORRECTIVE ACTION STATEMENT (submitted by firm October 2024)
Firm has committed to (i) restrictive-batch review of all 2024 XYLEVA production against
the environmental monitoring baseline, (ii) revision of SOP-QC-018 and SOP-QA-004,
(iii) retraining of manufacturing and QA staff, and (iv) engagement of an independent GMP
consultant. FDA review of the response is pending.
