How V5 Ultimate runs a radiopharmaceutical production site, end to end.

PET drugs live under 21 CFR Part 212 — a tailored cGMP that recognises radiopharmaceutical realities: short half-lives, conditional release pending sterility, decay-corrected accountability. Non-PET radiopharmaceuticals (Tc-99m generators, therapy isotopes such as Lu-177, Y-90, I-131, Ac-225) overlay 21 CFR 211, USP <825>, and state-of-the-art radiation-safety programs under 10 CFR 35.

The hazards that drive enforcement are unambiguous: dispensed activity outside the patient-dose tolerance at calibration, missed conditional-release sign-off, sterility failure on a batch already administered, unsealed-source contamination, exposure to a worker above NRC limits.

V5 Ultimate treats every synthesis run, every QC release, every dispense, every retroactive sterility sign-off, and every radiation-safety event as part of the same immutable ledger. Decay-correction is a property of the lot, not a spreadsheet.

Every node carries forward precursor lot, target ID, isotope, T0, decay-corrected activity, operator, hot cell and synthesis module from the node before it. Nothing is re-keyed.

Each precursor and target supplier is qualified per the approved batch formula. Substituting a supplier is a CMC change controlled through the batch formula change process. V5 holds the approved-source list per product and blocks goods-in from any other source.

Synthesis-cassette suppliers are qualified per module (e.g. GE FASTlab, Sofie ELIXYS, IBA Synthera, Trasis AllInOne) and per chemistry. Sterile-filter suppliers carry bacterial-retention certification (USP <797>). Re-qualification is calendar-driven and portal-led.

The receiver scans the BOL, weighs against PO, captures the supplier lot and expiry, performs a contamination survey (where shipping is from another hot-cell facility), and stores the cassette in a controlled environment. V5 mints a goods-receipt lot ID at that moment. Until QC releases against the registered specification, the lot is Quarantine.

Identity verification is component-specific: GC / HPLC assay for precursors that allow it, certificate-of-analysis review for cassettes and filters, source-strength survey for sealed sources. Results link to the receipt lot, instrument, analyst e-signature and supplier CoA.

V5 maintains location attributes: shielding class, contamination zone (controlled / restricted), temperature band, and release status. The pick list shown to the synthesis operator only includes components with current release status and unexpired stability. FEFO is enforced; overrides require reason + dual e-sig.

Each formula holds: drug substance, drug product, route (PET / SPECT / therapy), cyclotron target conditions, synthesis module + cassette ID, precursor BOM, in-process control plan (radiochemical identity, radiochemical purity, chemical purity, residual solvent, pH, appearance, bacterial endotoxin), final-product specification, filter integrity test, container-closure spec, and the registered label artwork.

Effectivity is two-signature: the formulator signs the change, the QA/Authorised Person signs that the change is within the registered batch formula (or that a CBE / amendment has been filed). New work orders pick up the new revision; in-flight work orders keep the snapshot they were released against.

If the batch formula is revised mid-shift, the work order keeps the snapshot it was released against. The auditor sees exactly the synthesis this batch was built to, with the sha256 of the snapshot recorded against release.

Cyclotron parameters (beam current, irradiation time, target pressure / temperature) stream into the work order. The synthesis module's PLC sequence is recorded step-by-step. End-of-synthesis activity is captured by the dose calibrator, decay-corrected to T0, and bound to the lot.

Dispense to unit doses is at calibration time: each vial / syringe is labelled with patient ID (where applicable), activity at calibration, calibration time, volume, expiry, and lot. Mis-pick at dispense (wrong patient, wrong activity, expired lot) hard-stops the step.

Radio-TLC / radio-HPLC for radiochemical purity, GC for residual solvent (acetonitrile, ethanol, DMSO depending on chemistry), pH, appearance, filter bubble-point, half-life confirmation, bacterial endotoxin (LAL or rapid-method) — all scheduled by the work order. Sterility (USP <71>) is post-release: the lot is released conditionally and the sterility sign-off is retroactive.

A single register categorises by event type. Sterility failure on a released lot triggers a defined patient-notification workflow and is a reportable event. Root-cause uses the structured fields the auditor expects.

Per-unit-dose labels carry: patient ID (or 'patient-pending'), drug substance, activity at calibration, calibration time, volume, expiry, lot, syringe shield ID, NRC permit conditions, and DOT shielding category for transport. The retroactive sterility sign-off, when it arrives, is appended to the same batch record and visible to the clinical site through the portal.

Conditional release authorises dispense and administration on the basis of every cGMP test except sterility. Final release on completion of sterility either closes the loop or triggers the failure workflow. Both signatures are identity-verified, both bound to the snapshot.

Every unit dose is shipped against a manifest that carries the lot code and the clinical site. When a recall trigger fires — sterility failure, dose-calibrator out-of-tolerance back-look, precursor recall — V5 walks the ledger in both directions in seconds: every dose made from this synthesis, every clinical site, every patient (where pre-assigned).

For short-half-life PET drugs the practical recall window is bounded by physics; V5 still records the trace and the notifications.

Quality manual, process performance, product quality monitoring, CAPA, change management, management review — all structured workspaces, not Word documents.

Draft → Review → Approved → Effective → Periodic Review → Superseded / Retired. Two qualified signatures effect every release. Operators see only the effective revision; superseded revisions are retained per 21 CFR 212.110 retention rules.

V5 maintains a training matrix per role × isotope × module. NRC Authorised User / Authorised Nuclear Pharmacist status is a bounded credential; an expired or out-of-scope status locks the operator out of the relevant kiosk action.

Every batch's quality signals, every CAPA, every conditional / final release statistic, every NRC event, every customer complaint — all stream into the management-review workspace as they happen.

V5's audit module schedules internal audits, FDA pre-approval and surveillance inspections, NRC inspections, and Agreement-State inspections. When the inspector arrives, the request list is a query.

Sealed-source inventory, leak tests, area-survey schedule, personal dosimetry data import, ALARA reviews — all structured workspaces. Reportable events (10 CFR 20 / 35) auto-open the relevant notification timer.

Dosimetry results import into V5, get associated to the worker, the task, the hot cell. ALARA targets and investigation levels are configurable; an excursion opens a CAPA and routes to the RSO.

V5 holds sanitation procedures per zone × equipment, with frequency, agent, contact time and verification. Aseptic-area particle counts, viable air, surface plates and personnel monitoring are scheduled and trended per EU GMP Annex 1 / USP <797>.

Dose calibrators (constancy, linearity, accuracy, geometry per NRC), well counters, survey meters, HPLC, GC, particle counters — each is a tracked asset with calibration interval, certificate, tolerance, and an out-of-tolerance impact-assessment that triggers a back-look.

Sample sites, frequency, action and alert limits, and corrective actions on a positive (decontamination, hold, re-survey) are all scheduled and tracked.

Intake captures lot, calibration time, site, observed issue, severity, patient outcome. V5 binds the complaint to the batch and surfaces adjacent batches.

Every signed event carries the actor's verified identity, signature meaning, time, and a sha256 of the record. The signature row is append-only. PDF renders are deterministic from the snapshot.

CoAs per lot, conditional and final release sign-offs, dose-calibrator constancy data, transport documentation — all on the portal. Audit-trail of who accessed what is automatic.

A typical site onboards in 6–10 weeks: master data import, batch-formula migration, cyclotron + module integration, kiosk training, parallel-run validation, cutover. The validation pack (URS → IQ → OQ → PQ) is built in.

Abbreviated mapping. Each link opens the full readiness guide.