Cyclotron SOP · O-18 Enriched Water
From cold-chain receipt to per-shot record —the chain the AERB inspector reads.
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
From cold-chain receipt to GMP-file release
- 1
Cold-chain receipt + transport log review
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.
- 2
Lot identity check against CoA
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.
- 3
CoA acceptance against spec
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.
- 4
Vial integrity inspection
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.
- 5
GMP-file lot release
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.
- 6
Working-inventory sign-in
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
From vial draw to per-shot record close-out
- 1
Target body preparation
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.
- 2
Vial draw + transfer
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.
- 3
Per-shot record entry
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.
- 4
Target loading + beam start
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.
- 5
Post-irradiation recovery
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.
- 6
Per-shot CoA-to-product chain close-out
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
Ten fields, ten spec limits, ten reasons each is set
| 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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