The necessary regulation to get FDA approval of a combination product is first the company has to request for designation (RFD), in which companies have to outline the rationale of the product. Then, the company has to submit the “pre”pre-investigational device exemption(“Pre”pre-IDE) and the pre-IDE are regulatory meeting. The pre”pre-investigational device exemption is a not a real documented official procedure; it is just when the company calls up the FDA to ask a question regarding their research and the way they set up the clinical experiments. Pre-IDE is a document that proposes pre-clinical research necessary in order to start the human trial. The next step is the IDE which is written by the clinical research and the regulatory guides give a pathway required by the FDA to precisely present the data. The last step is the premarket notification or the 510(k), which must demonstrate if a device has “substantial equivalence” to a “predicate device”.

A. The CDER’s steps of regulation is (1) IND, (2) Phase 1,2,3 and NDA
B. CBER’s step of regulation is (1) IND, (2) Phase 1,2,3 or the pivotal trials (3) BLA
C. CDRH’s steps of regulations for class 1,2 is just the 510 (k); for class 3: it goes through IDE, pivotal trials, PMA

The necessary steps to take in order for a combination product to get FDA approval is to first find out what is the main purpose of the product itself. I just want to highlight how important it is for a product to identify its main functional requirement. There were a couple of examples from lecture of how there can be a different combination of Drugs, Devices, and Biologics. To recall, there could be a drug that's injected by a syringe. It's main rationale would most likely be the drug because of its metabolic effect. Another would be a antibiotic coated hip stem. The main rationale of this would be the hip stem, because at the end of the day it is a physical device meant to provide structural support.

It's very important that the company stipulate what category it would fall under when submitting the RFD to the Office of Combination Products. Once their designation is determined, it is binding. This could cause difficulty to companies who aren't very familiar with Drugs or Biologics if their reputation is primarily in devices. Any decision can be appealed to Ombudsman.

All steps whether it's a Drug, Biologic, or Device can be highlighted from what djr32 shared. The end goal for a Drug is to get an NDA approval, a biologic is to get a BLA approval, and a device is to get a 510k or PMA.

First of all, person/company needs to find out if this product even required RFD because not all product required RFD submission. The necessary step to take before submitting RFD with a better understanding of how the product works and then contact OCP (Office of Combination product) if you have question about type of information should include in RFD if not sure enough; from my point of view correct me if I am wrong, this step will help you minimize RFD rejection. The RFD should be submitted before filing any investigational or marketing application for the product. This will avoid expending unnecessary time and resources.
US FDA has three key concepts it uses in the regulation of combination products
• Constituent parts retain regulatory status and duties
• Combination products are a distinct regulatory class
• Comprehensive, effective oversight without undue redundancy
All other necessary steps to get FDA approval of a combination products are well described by jvv6 and djr32.
Reference
http://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/