21 CFR 312.8 requires that the sponsor demonstrate that it could not conduct the clinical trial without charging for the investigational drug because the cost of the drug is extraordinary to the sponsor. The cost of a drug may be considered extraordinary to a sponsor because of manufacturing complexity, scarcity of a natural resource, the large quantity of the drug needed (e.g. based on the size or duration of the trial), or some combination of these or other extraordinary circumstances (e.g. resources available to a sponsor). For example, a cost that is considered extraordinary to a small start-up company may not be considered extraordinary to a large established company.

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