A Fridge Excursion, an Unreported SAE and a 'Minor' Paediatric Amendment
A Ugandan sponsor is running a Phase III trial of a malaria vaccine candidate at two Kenyan sites. The investigational product must be kept at 2-8°C. On 3 March the fridge at site B fails overnight and 40 doses reach 14°C for about six hours. The trial pharmacist quarantines the affected vials and informs the principal investigator. On 10 March a participant at site A has a serious adverse event - severe anaemia requiring transfusion - and the PI emails the sponsor only. The sponsor now wants to enrol 300 more participants and add a sub-study in children aged 6-11 years, describing it as a 'minor amendment' so that enrolment need not pause. The PPB has received neither the cold-chain deviation report nor the serious adverse event report. The site's delegation log does not list the pharmacist as a delegated investigator for IMP accountability.
1. Prioritise the actions and the reporting timelines.
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Cold-chain deviation (3 March). Keep the 40 affected doses quarantined; do not use them. Check the accountability log to establish whether any affected doses were administered before quarantine - the delegation gap makes this harder and must be fixed. Obtain the manufacturer's stability data on excursion at 14°C for six hours; if supportive stability data are unavailable, the doses must be destroyed. Report the deviation to the sponsor and to the PPB and ethics committee per the protocol and the applicable clinical trial guidelines - commonly within 24–72 hours, and at the latest in the next progress report. Document corrective action: alarm, backup power, calibrated logger.
SAE (10 March). Severe anaemia requiring transfusion is serious; expectedness depends on the investigator's brochure. The investigator has an independent duty to notify the PPB and the ethics committee, not only the sponsor - the pharmacist should escalate this immediately rather than wait for the sponsor. Initial reports typically go within 7 days for fatal or life-threatening events and 15 days for other serious events, with follow-up; confirm the current PPB clinical trials guideline before quoting a deadline in writing.
Delegation log. The pharmacist performing IMP accountability without delegation is a GCP deviation. Correct the log with the PI's signature, document retraining, and state the correction in the deviation report.
2. Is the paediatric sub-study a minor amendment? Advise the sponsor.
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No. Three features make it substantial: a new population (children aged 6–11), a likely change in risk–benefit and dosing, and new consent and assent procedures with a different vulnerability profile. A substantial amendment requires prior PPB and ethics committee approval before any participant is consented or enrolled into the sub-study.
Advise the sponsor that the regulator, not the sponsor, determines the classification; labelling an amendment 'minor' to avoid a pause does not make it so. Enrolment into the existing adult protocol may continue if the amendment does not affect those participants' safety or consent and no other hold applies - but that is a separate question from the sub-study.
Also require: an updated investigator's brochure, a paediatric investigation plan position, assent forms, and confirmation of site capacity and paediatric expertise. Separately, the unreported SAE and the unreported cold-chain deviation are compliance findings in their own right and should be addressed in the same correspondence, with a corrective action plan and a timeline. Consider whether a site inspection is warranted given three concurrent GCP failures at two sites.