Temperature Excursion and a Already-Dosed Participant
At a satellite clinic, the research pharmacist receives a shipment of 24 kits of an investigational monoclonal antibody for a Phase II asthma study. The data logger inside the shipment shows a 5-hour excursion to 31.2°C during transit; the label requires storage at 2–8°C and says 'do not freeze.' The pharmacist quarantines the shipment but notices that two kits from the same lot had already been transferred to the clinic's refrigerator the previous week and one was dispensed to a participant, who received the first subcutaneous dose yesterday. The sponsor's IP manual says temperature excursions must be assessed before use and that affected kits must not be dispensed. The coordinator has a scheduled visit tomorrow and wants to know whether to replace the participant's next dose with a new kit. The participant reports no injection-site reaction or fever.
1. What immediate actions should the site take for the shipment, the quarantined kits, and the participant who was already dosed?
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First, secure the supply chain. Keep all 24 kits from the excursion shipment quarantined and physically segregated, with a sign and a manual count; do not dispense, destroy, or return them until the sponsor gives written disposition. Download and preserve the original logger data and file it with the shipment records. Notify the sponsor's IP manager and the monitor immediately, not at tomorrow's visit, and provide the logger file, lot number, kit numbers, excursion duration, and maximum temperature.
Second, trace the two kits transferred earlier from the same lot. Determine whether they were part of the excursion shipment or a separate shipment with valid storage. If they were from the same lot but a different, properly stored shipment, they may not be affected; the lot number alone does not prove exposure. Quarantine any remaining kit from that transfer until the sponsor assesses it. For the participant who received the first dose, notify the PI the same day and assess for injection-site reactions, fever, and other symptoms. Document the exposure, lot and kit number, date and time of dose, and the temperature excursion facts. Report the deviation to the sponsor and IRB per policy; do not assume the dose was ineffective or unsafe without the sponsor's assessment.
2. How should the site handle the participant's next dose and the documentation and CAPA needed?
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Do not use any kit from the affected lot or transfer until the sponsor releases it in writing. If the next dose is due and an unaffected, properly stored replacement lot is available, the pharmacist may assign a new kit according to the randomization or kit-assignment procedure, with PI approval and sponsor notification. If no replacement is available, follow the protocol's dose-delay window rather than substituting an unapproved kit. Do not 'replace' the dose by using a quarantined kit just because the participant is asymptomatic.
Document the excursion, quarantine, sponsor notification, lot and kit numbers, participant exposure, PI assessment, and dose decision in the pharmacy and study files. Update the IP accountability record so the quarantined kits are not counted as available. The CAPA should address receipt and transfer procedures: check logger data before accepting shipment, quarantine new shipments until review, train clinic staff on temperature excursion SOPs, and add a second check before any kit leaves the pharmacy. The monitor should review the CAPA at the next visit, and the site should verify that no other participant received kits from the affected transfer.