Depending on the scope of work, CROs can either fall under subcontractors or Fee-for-service (see Line item G6 for NSF budget guidelines). Most of the times, fee-for-service is the best category as CROs are often used to complete work tasks that require specialized equipment or facilities that are not available to the applicant, but the work is carried out to the applicant’s specifications and is considered “routine”. However, if the CRO would contribute a considerable amount of original input (innovation), it would be best captured under a subcontract.
As for the domestic requirement, any funds for a CRO that is included in the budget will have to be substantiated with an invoice or price quote in the budget justification. This will have to be provided by a US-registered company that is doing business in the United States. If that entity also has offices or sites in other countries, this does not disqualify them as long as the work you request from them is completed in the US. The only requirement that NSF states is that “Additionally, NSF SBIR/STTR only supports work that is performed in the United States (including work performed by subawardees and consultants).”