A foreign sponsor is required to have a U.S. permanent-resident agent in order to file a request for an orphan drug designation. See 21CFR 316.22 for full details.
A U.S. agent can be anyone residing in the U.S. who is responsible for the paperwork involved with the designation request and if a designation is granted, will serve as the contact person afterwards. Generally a U.S. sponsor is associated with a regulatory consulting firm or a contact person at a U.S. university. If the sponsor’s agent changes, then OOPD must be notified immediately.
OOPD requires that all correspondence to and from OOPD related to international sponsors go through the U.S. agent. This includes submitting subsequent annual reports after a product is designated.
