Cyclotron SOP · O-18 Enriched Water
The cyclotron GMP file traces input CoA → vial → shot → F-18 batch → downstream radiopharmaceutical → released patient dose. This page is the six-step lot-release SOP, the six-step target-loading and recovery workflow, and the ten CoA fields the inspector reads off the dossier.
Lot release — six steps
Verify the lot arrived within the cold-chain temperature envelope by reading the packed transport logger. Any out-of-envelope excursion is captured in the receipt record and escalated before the lot is opened. The logger trace is filed against the lot in the GMP file.
Match the batch number, manufacture date and expiry on the vial label to the per-batch certificate of analysis. Discrepancies hold the lot in quarantine pending vendor reconciliation. The matched CoA is the input-material qualification record.
Per-batch CoA carries isotopic composition, conductivity, pH, TOC, pyrogen (LAL), sterility, halide / metal / anion panels. Each value is checked against the lot-release spec. Any out-of-spec value holds the lot; in-spec values are signed off as accepted.
Inspect the crimp seal and chlorobutyl septum for tamper evidence; inspect the glass body for cracks, particulates or discolouration. Any failed inspection rejects the vial; passed inspection signs the vial into the working inventory.
The signed CoA + transport log + inspection record + lot-release signature are filed against the lot in the cyclotron GMP file. AERB inspection reads this dossier on every routine inspection — it is the chain-of-custody document for every F-18 batch produced from this lot.
Released lots are added to the working inventory with first-expiry-first-out (FEFO) rotation. Each subsequent target-loading event withdraws from the working inventory and links to the source lot in the per-shot record.
Target loading + recovery — six steps
Verify target body integrity, helium / nitrogen purge as per cyclotron SOP, target foil condition check. Target body issues hold the shot pending engineering — input water is not loaded until the target is qualified.
Draw the target-loading volume from a vial via a sterile dispensing needle into the target-loading syringe. Single-shot or multi-shot draw per site SOP; remaining vial volume is retained for the next shot up to the in-use expiry.
The per-shot record captures: lot number, vial number, draw volume, transfer timestamp, operator signature. The shot record links downstream to the F-18 batch QC record and the FDG synthesis record.
Load the target via the cyclotron transfer line; verify target full / pressure within nominal; release the shot to the beam-on workflow. Beam-on timestamp captured automatically by the cyclotron control system.
After beam-off and target cooling, the irradiated water is pushed through an anion-exchange column. F-18 is retained on the column for elution to the synthesis module; depleted target water can be diverted to recovery / recycling or to waste per site protocol.
The completed per-shot record links input lot CoA → vial → shot → F-18 batch → downstream radiopharmaceutical batch. AERB inspection traces the chain in both directions — from final product back to input CoA, and from input CoA forward to released doses.
CoA fields — what the inspector reads
| Field | Spec limit | Why it is set |
|---|---|---|
| Isotopic composition (atom %) | O-18 ≥ 98 %; O-17 < 3 %; O-16 < 3 % | Sets the per-shot F-18 yield via 18O atom-density × cross-section × beam-current × time |
| Chemical purity (m/m) | > 99.99 % | Organic / inorganic impurities co-irradiate and produce parasitic radionuclides |
| Electrical conductivity | < 3.0 µS/cm | Proxy for ionic-impurity load; gates Na-22 / Co-58 / Cl-38 by-products |
| pH | 6.0–8.0 | Protects target body, transfer line and anion-exchange recovery column |
| Total organic carbon (TOC) | < 2.0 mg/L | Organic load that would deposit on target body or carbonise under beam |
| Pyrogen (LAL) | < 0.25 EU/mL | Bacterial-endotoxin gate; protects downstream radiopharmaceutical product |
| Sterility test | Passed | Microbiological gate; bottle sterilised prior to filling and held sealed |
| Halide panel (F, Cl, Br, I) | ND (each < 0.1 mg/L) | Halides activate to short-lived halide isotopes that contaminate downstream chemistry |
| Metal panel (Ca, Mg, Na, K, Cu, Fe, Zn) | ND per panel limit | Metal activation produces parasitic radionuclides (e.g. Na-22, Co-58, Mn-54) |
| Anion panel (PO4, NO3, SO4, NH4) | ND | Anion / cation panel completes the ionic-impurity-load picture |
Spec limits are per-vendor with reference to IAEA TRS 471, Eur.Ph. monograph 1325 (downstream FDG) and AERB cyclotron-facility consumable expectations. Site lot-release SOP locks the spec limits per supply contract.
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