A combination device is a device with multiple components that serve different purposes. Typically for a combination device, it is reviewed by the department in the FDA based on its primary mode of action. Sometimes the primary mode of action is unclear. In that scenario, you would file an RFD, request for designation, to the FDA. It would only be class I, II, or III if it were being reviewed by the CDRH. If the primary mode of action was drug delivery, it would be reviewed by CDER. After the device is designated and the primary mode of action is determined, you can than continue through the approval process for the respective department of regulatory affairs at the FDA.

Surgical Mesh with Antibiotic coating is a combination product which can follow either CDRH or CDER regulatory guidelines. Based on my understanding the primary mode of action would to treat it as a class two medical device. But to verify that it should follow CDRH guidelines an RFD (request for designation) must be completed. If it is assigned to CDRH then it would require a Pre-market Notification (510K). Since this is a surgical device it will need clinical trials therefore an IDE must be completed. It would be classified as a class II device because it is not a life supporting or sustaining device. A surgical mesh can have substantial equivalence to a medical device previous to 1976. The claim of this device leads it to the pathway of class II regulations.

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=16336

Combination product is a product composed of any combination (i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic). Infuse bone graft is a combination product which consists a protein that is found in everyone’s body and a natural carrier for delivery. Infuse bone graft eliminates the need for the harvest surgery, avoiding the pain associated with the bone harvest procedure. It would be classified as a class III device because it sustains or supports life present potential unreasonable risk of illness or injury. Depending on the nature of a tissue engineered product can be assigned to CBER or CDRH and required PMA. Company must submit RFD request for designation to FDA. Through “Pre” pre-IDE process interact with FDA that allows developers to obtain initial feedback of preclinical and clinical testing that necessary which can saves time and cost. Clinical animal studies for IDE trial written by clinical department; however, regulatory guides through this process. Last regulatory assembles information for PMA’s and entire team.

An example of a combination product would be Stryker's Vitagel Hemostat ( http://www.stryker.com/en-us/products/Orthobiologicals/SoftTissue/Vitagel/index.htm). The delivery system for this product is a syringe and the primary mode of providing a therapeutic effect comes from the contents of the syringe which is the combination of microbibrillar collagen with thrombin, fibrinogen, and platelets. If I had to determine what approval channel this material would go through I would have assumed CBER, since it uses biologics to achieve it's end goal. However, while researching I found that this specific device was approved by CDRH. Attached is the letter of approval ( https://www.accessdata.fda.gov/cdrh_docs/pdf5/P050044A.pdf). Since this product underwent the CDRH approval it would require a PMA and clinical trials to show efficacy of the product and this is exactly what was done. Any thoughts on why it was CDRH that evaluated this product and not CBE?

More details on the product approval. ( https://www.accessdata.fda.gov/cdrh_docs/pdf5/P050044B.pdf)

Another example of a combination product is a drug-eluting stent. This product can fall under CDER or CDRH guidelines. But a request for designation by the FDA would likely place this under CDRH jurisdiction since its primary mode of action is to act as a stent, which is a medical device. The secondary action of the device is to elute drug(s) to prevent restenosis. Because this stent is typically critical to maintenance of stenosed arteries, it would fall under Class III and require a PMA. Undoubtedly, because of its class III designation, a clinical trial would be required (IDE application).

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm?ID=NIQ

One of the example which we got in our course is Spermicidal lubricated condoms which are are special condoms that have an added lube to it. The lubrication used is a spermicide, a substance that can destroy sperms. It follows then, that when this special type of condom is worn, the user gets twice the protection.
The lube element present is a spermicide which kills or damages the sperm. This is a combination device which is used to prevent pregnancies. Spermicidal lubes are gels which consist of chemical called nonoxynol-9. This chemical acts as a vaginal lubricant also.

Photodynamic therapy with PHOTOFRIN is an example of combination device that comprises of two stages. In the first stage, an intravenous injection of PHOTOFRIN is given to the patient. It gets cleared from most of the tissues over 40-72 hours, but tumors, skin, and organs of the reticuloendothelial system that includes
liver and spleen retain PHOTOFRIN for a longer period. In the second phase, it is illuminated with 630 nm wavelength laser light to selectively treat tumor. So it a combination product that uses laser light with the drug called PHOTOFRIN. To get the FDA approval, this product was filed under NDA and it is class 3 device and it had clinical trials done on the patients in their last stage of the tumor. It got the PMA done along with IDE for the clinical trials.

Combination devices include segments that would regularly be directed under various sorts of administrative experts, and habitually by various FDA Centers, they raise challenging regulatory, strategy, and audit administration challenges. Contrasts in administrative pathways for every part can affect the administrative procedures for all parts of item improvement and administration, including preclinical testing, clinical examination, marketing applications, assembling and quality control, advancement and promoting, and post-approval modifications.

An example of a combination product: Bone morphogenetic proteins (BMPs are a class of proteins) that induce bone formation. New technology in orthopedic repair combines BMPs with a carrier matrix to create a combination product that, when implanted in a bony defect, initiates bone formation (osteoinduction) and provides local containment and cell adhesion (osteoconduction).
Example :FDA approved INFUSE bone graft, which contains a recombinant human bone morphogenetic protein (rhBMP-2),which consists of:Recombinant human bone morphogenetic protein (rhBMP-2); absorbable collagen sponge; sterile water. Class III
Applications submitted:Separate applications submitted to CDRH and CDER: 510(k) (controller), NDA (patch)
Manufacturer: Vyteris
https://www.fda.gov/downloads/combinationproducts/meetingsconferencesworkshops/ucm116740.pdf

Catheter with antimicrobial coating is another example of a combination product. This allows the catheter to function as it is intended but prevents catheter-associated urinary tract infections (CAUTI). This allows the user to use a catheter with the same function as one with no coating on it, but with less risk of infection. This is submitted to the FDA as a class II device.

An example of a combination product would the halo bone fracture apparatus. Since this apparatus has wires that will keep the halos in place it is a combination of multiple parts. This device is classified as a class II device, because the wires will have to puncture the skin. The medical wires used are of a biologically acceptable material, so as to not produce a immune response and they have special coatings to prevent inflammation or patient immune response. The outside metal component or the halo is what the wires bind to and they help immobilize the fractured bone of the patient. To go through FDA protocol, the wire must first go through clinical testing to show that the coatings used provide a safe environment for patient and do not elicit any negative health effects. They would have to conduct animal testing first to provide relative lab results.

Combination products: The term combination product includes:

1- A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic. 

2- Two or more separate products packaged together in a single package.

3- A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use.

I believe combining products might be a smart shortcut for the company when it yields successful results. Working for a Big Pharma company that produces many different types of drugs and vaccines, you have access to numerous amount of projects in different areas. Since my company announced to be working on COVID treatment/Vaccine, my team has been doing intensive research in combining different vaccines/ treatment to produce a COVID treatment. FDA has recently waived a lot of the regulations to help pharmaceutical companies help the world and produce vaccine/treatment as soon as possible. that being said the FDA didn't waive any regulations that would endanger the quality of the product. 

Many of the insulin therapy products used by individuals with diabetes can be considered combination products. The insulin itself is considered a drug, since it has the metabolic effect of lowering blood sugar, and the mechanism of administering the insulin is considered a medical device. One such product is the insulin pen, which is typically manufactured by the same company that makes the pre-filled insulin, such as Novolog or Humalog. So with insulin pens, the drug and medical device are packaged together. There's also insulin pumps, which are typically manufactured by medical device companies like Medtronic, and require that insulin is purchased seperately in vials. If an insulin pump is used together with a continuous glucose monitor, the FDA considers it a Class III device, because there is a high risk to the patient if it were to malfunction and cause hyper or hypoglycemia. So as a result it requires PMA in order to be approved.

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm?ID=OYC