Validation of the BacT/ALERT 3D System for Sterility Testing 18F-FDG
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,006 | 0,008 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,002 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,004 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».