Fady,

That is an interesting point to bring up. With combination products, if I understand correctly, the company must identify first the necessary center for the primary use of the product. Once it is designated into CDER, CBER, or CDRH then that would specify how the approval process would be for the product. Usually the pre-amendment device (product release before the act of 1976) tends to be the secondary product in these cases that still hold the substantial equivalence. If the device is class III, for instance, it would require a PMA or notice of completion of product development protocol (PDP). But if PMA is not required, then a 510K containing a Class III certification and summary is necessary. This provides details of the search done by company about the device type. Also, it provides verification of the safety and effectiveness for the devices and would be signed by the submitter.

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ucm134578.htm
http://www.schiffandcompany.com/backupFiles/fusra-6ed-201-215.pdf