Validation of the BacT/ALERT 3D System for Sterility Testing 18F-FDG
Bibliographic record
Abstract
3018 Objectives: Sterility testing of radiopharmaceuticals is critical to meeting Good Manufacturing Practice (GMP) requirements. Product sterility is traditionally determined as per USP , which is a requirement of the general USP Positron Emission Tomography Drugs guidance. However, given limitations in handling radiopharmaceuticals, and the need to allow for decay prior to shipping to and initiating testing at a lab that not licensed for handling radioactive materials, an alternative, in-house method was required. In order to initiate timely sterility testing of 18F-Fludeoxyglucose (18F-FDG) in accordance to the FDG USP monograph, we validated a rapid sterility test method using the BacT/ALERT 3D® Dual T System. Methods: The BacT/ALERT 3D Dual T System is an automated microbial detection system manufactured by bioMerieux (bioMerieux, Nurtingen, Germany). The system consists of a low temperature (22.5 °C) incubator and a high temperature (32.5 °C) incubator, and is capable of incubating 240 samples simultaneously. Anaerobic (iNST) and aerobic (iAST) media bottles were used and incubated at 32.5 °C and 22.5 °C, respectively. Validation was performed using microbial strains described in USP : Clostridium sporogenes(NCTC12935), Staphylococcus aureus(NCTC 10788), Aspergillus brasiliensis(NCPF 2275), Bacillus subtilis(NCTC 10400), Candida albicans(NCPF 3179) and Pseudomonas aeruginosa(NCTC 12924). These organisms were purchased as Bioballs (bioMerieux, BioBall Mixed Multi-Shot). Microbial verification was performed during bottle inoculation as well as for bottles determined positive for microbial growth by the BacT/ALERT®3D system. Decayed 18F-FDG was spiked with each microorganism and inoculated into media bottles in triplicate. Bottles were inoculated at a concentration of <1 CFU/bottle. Method blanks, positive and negative controls were included in the study. Results: 18F-FDG was prepared and released in accordance to in-house procedures at BC Cancer. Product samples were allowed to decay completely prior to initiation of the study. Bioballs were reconstituted and serially diluted to achieve an initial concentration of 10 CFU/mL. Aliquots of each organism were plated on growth media and in all instances confirmed the viability of organism and the target CFU concentration. From these dilutions, six samples of decayed 18F-FDG were inoculated respectively. iAST and iNST bottles were inoculated in triplicate at <1 CFU/bottle. Incubation of the inoculated bottles was initiated within 2 hours. All bottles expected to be positive for microbial growth were positive in less than 8 days. Confirmatory plating of bottles determined positive by the BacT/ALERT system was performed. The limit-of-detection was determined to be <1 CFU/bottle. Negative controls and method blanks were negative for growth. Conclusions: The BacT/ALERT®3D Dual T System was successfully validated for sterility testing of 18F-FDG at BC Cancer. The system demonstrated a higher degree of specificity, repeatability, intermediate precision and robustness. The system also exhibits a superior limit-of-detection as compared to USP . The system is ideal for radiopharmaceutical manufacturers looking to perform in-house sterility testing where traditional microbiology infrastructure is not available.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".