For an antibiotic-releasing hip-stem
Device Type: combination device
The primary mode of action: Hip-stem, structural replacing a bone- holding up a hip.
Agency has governance over it: CDRH
Class: Class II
Regulatory Pathway: CDRH->Class II-> 510(k)
510(k) defined "is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device (21 CFR §807.92(a)(3)) that is not subject to premarket approval"
Claim: Replaces bone of a hip with enhanced titanium steel structure as substantially equivalent titanium hip stem prosthetic devices
For a CDRH-> Class II, No IDE is required. If it was a CDRH/Class III then yes it would require and IDE/Pivotal Trials/PMA

In regards to the antibiotic-releasing hip-stem implant this medical device would be considered a combination device since the product has two functionalities; however the overall primary mode of action is that of a hip-stem, to structurally support the hip. Since this product falls under a medical device, the government agency that would oversee and make decisions would be CDRH. This device would be a class II medical device since it has a special control being antibiotic release to lower the percentage of body rejection. The Regulatory pathway would be CDRH -> RFD -> Class II > 510 (k). The claim for this device would be just that it helps in supporting the hip by using a titanium steel structure or chromium cobalt and is coated with an antibiotic agent to fight off infection in the bone and reduces the hip failure due to body rejection. Any further claims for the device could be used against the company if not proven and the FDA would raise further questions about the product which could make this device a possibly class III if it has further other utilities that is unique to the hip-stem market. By matching this device in terms of materials with other predicate devices in the market would allow this device to receive a 510 (k). Since this product is a class II it does not need an IDE, only it the device would be a class III or could not file for a 510 (k) which would lead this device to file for a PMA which would be accompanied by an IDE and clinical trials.

An antibiotic-releasing hip stem would count as a combination device since it has the characteristics of a drug and a device. However, since its primary mode of action will be as a hip implant that will the user in regaining their lost function, it would count as a Class 3 device. The antibiotic within the implant is simply supplementary as it only helps the user accept the foreign implant. The hip stem as a drug-delivery device would not make sense and would be extraneous and so, it makes sense that the hip stem only restores lost hip function while the drug is simply for a better compatibility of the device with the user. Although it may not be necessary, I think that an IDE would do more benefit than harm because it will, overall, include the efficacy of the product. Since this device will be inside the body, in-vitro and in-vivo studies must also be done.

An antibiotic-releasing hip stem would fall under various categories including: device combined with a drug. This is due to the nature of the product. The device portion stems from the provider or carrier of the drug while the drug is the actual functional biologic attached the device. Therefore, an antibiotic-releasing stem would be a combination of both a device and drug. Now the primary mode of action for this product would be to regain hip mobility through providing the connection between the hip socket to the femur. This allows the user to walk. The overall high level goal of the hip stem is to allow functional mobility. That is the primary mode of action. Now, this device would fall under Class III. The product falls under this class due to the fact that the device can had serious adverse effects on the user that come originate from either the material contact interface or the antibiotic or pure mechanical shear. The claims that I would recommend for this product that the hip stem aids in mobility by supplementing the hip while fighting off infection through the use of antibiotics. Such reduction in infection wards off chances of the body rejecting the implant. Some studies that could be done in pre-clinical phase would be to test these implants or equivalent size variants in rats. Possibly running studies on how the antibiotic functions within mice/rat. Then upgrade to a system that is more comparable to that of a human being. I believe having an IDE would benefit this situation because it can be used to prove the safety and efficacy of the device. Definitiely studies both in-vitro and in-vivo can support the device development.

It falls under combination products per the definitions below:
Combination products are products that combine drugs, devices and or biological products.
1. A product comprised of two or more regulated components
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 investigation plan or proposed labeling is intended for use only with an approved individually specified drug
https://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm118332.htm
The primary mode of action is defined as “the single mode of action of a combination product that provides the most important therapeutic action of the combination product.”
https://www.mddionline.com/combination-products-primary-mode-action-refined

Its primary mode of action is intended to replace a defective bone to support the hip.
Class II device
The claim would be the implant will treat infection in a single procedure.
Pre-clinical Research
The tests should include cytotoxicity, genotoxicity, irritation, system Tox, hemocompatability, implantation, Toxikokinetics
IDE is required for significant risk device study:
It is considered significant risk if the implant poses a serious risk to health, safety or welfare and it sustains life. Being that that hip stem is not supporting life an IDE is not required.
https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf

I would think this is a combination drug/device. The primary mode of action would be the function of the hip stem so structural support. This would be under the CDRH and be class 3. The regulatory pathway would like the one outlined on slide 36 and 31. The pathway in chronological order is RFD, "Pre" Pre-IDE, Pre-IDE, IDE, Pivotal Trials, and finally, PMA. I would claim that it provides structural support similar or better than the actual bone it is replacing. I would prove this by doing tensile tests as well as shock testing on a donated cadaver body bone (assuming some hospital provides this to companies) and the combination drug/device. I would also claim that is does not rust and do a ASTM corrosion test to determine this (when you cant wait a long period of time to test a material you have to create extreme conditions). I would also state that it fights infections and do a mouse model of some kind to demonstrate this. I would recommend Phase 1,2, and 3 clinical trials due to this being something that is going into someone's body for a long period of time.

Antibiotic-releasing hip stem would be consider a combination device, it will follow in to CDRH based on the primary function of the device which is to replacing the bone. This device will be consider a class 3 because we will implant this in to a human body so definitely we PMA for this device. I said class 3 instead of class 2 because I am assuming this something which will implant inside the body and most important thing we don't know what kind of drug we are using, so if are using something completely then how the drug will react with the body and does it react with the metal so for all that reason I would say it should be class 3 and it need PMA. I think the claim should be that this device used to support the hip and it also deliver the drug to fight infection to be specific we can say if overcomes immune rejection. For pre-clinical studies I will test it on rats and also perform some test based on ISO 10993-1 and on progress of the project I will file an IDE to test this in Humans.

What kind of regulatory pathway would be required for an antibiotic-releasing hip stem?
It is the CDRH
Is it a device, drug, biologic, or combination?
It is the combination device
What is its “primary mode of action?
It is to provide the support to the bone.
Is it Class I, II, II?
Class II (510(k))
What claims would you recommend we make for it?Drawing on some of your experience from the week we did pre-clinical research, what pre-clinical research studies would you recommend be done to prove the claims?
I think it is the pre-clinical research. It has to insert the antibodies into the hip-stem. And implant into the rat or other animals to see whether it works or even better works than the material before. What's more, whether there are immune reaction in vivo.

Guessing as best you can, what sorts of clinical trials would you recommend in the IDE? Does it need an IDE at all?
Since it is the classII of CDRH, the IDE is not required. But it is better to do that, even there are no problem in animals.

An antibiotic hip stem would be considered a combination product “as defined by 21 CFR 3.2 (e)”. The primary mode of action of this hip stem would be to provide similar functionality and support of a hip and the antibiotic portion would be considered an additional effect of the implant, and the CDRH would be responsible for this device. Also since this is a combination implantable product it would be considered a Class III device by the FDA . There can be exceptions to this if for example, if the device already has a predicate device with the same design and antimicrobial agent, however the FDA is strict in its definition of antimicrobial agents and the formulations used due to resistance. The claim for the device would be the functionality and support the hip implant provides along with it’s ability to counteract infection and provide stability for the patient with the antibiotic portion. Animal trials would be necessary in preclinical research to prove the infection claim and along with this biocompatibility studies would be key as well. An IDE would be necessary as well in order to receive data from in vivo environment and determine whether the benefits of the antibiotic outweighs the clinical risk of resistance.

Source
https://www.fda.gov/RegulatoryInformation/Guidances/ucm071380.htm#5

What kind of regulatory pathway would be required for an antibiotic-releasing hip stem?
CDRH Regulatory. Class 2 – Special Controls

Is it a device, drug, biologic, or combination?
Combination

What is its “primary mode of action?
Treatment of hip joint infection with hip stem. Releasing antibiotics on a fully weight-bearing implants

Is it Class I, II, II?
Class II

What claims would you recommend we make for it? An example of a claim is “fights infection in bone (osteomyelitis) and reduces incidence of hip implant failure”. Any claim that you say, you have to lay out a plan to prove it.
Suffering from hip pain due to common injuries, hip arthritis, avascular necrosis or osteonecrosis.

Drawing on some of your experience from the week we did pre-clinical research, what pre-clinical research studies would you recommend be done to prove the claims?
Preclinical in vivo and vitro studies would be recommend. Also, biocompatibility testing of a material prior to clinical studies will be required.

Guessing as best you can, what sorts of clinical trials would you recommend in the IDE? Does it need an IDE at all?
CDRH ->Class 1,2 ->510(k). Investigational Device Exemption (IDE) is not need at all for clinical trial.

We will learn later than an IDE is required for any clinical trial that poses significant risk, and usually this means that if you change the standard of care for a patient in the clinical trial, it is significant risk and thus needs an IDE. So, even if this device fell into Class II, it would need an IDE trial.

The path of an antibiotic releasing hip stem would certainly start out with an RFD. Although the primary function of this device is the physical hip stem, the antibiotic releasing portion is the aspect of the device that would make it class 3. If it were just a hip stem, it would be class 2. If found that it falls under CDER, the pathway would include and IND, phase trials, and an NDA. However, I would argue that the hip stem portion also warrants a 510(k). The device would get an NDA because the antibiotic portion is the class 3 component, not the stem. The claims that trials should back up are that the antibiotics reduce the rate of infection post-surgery, it does not reduce bone adhesion, and the antibiotics mitigate an immune reaction against the hip stem. This could use in vitro and in vivo clinical trials on pigs. Rats/mice would be unfeasible due to the small proportions.

An antibiotic-releasing hip stem is a combination product. If I was the regulatory person working with this product, the first thing I do would be to submit a request for designation to the office of combination products. They will determine which center has lead responsibility based on the mode of action and the device will then follow that center’s regulatory pathway. The primary role of action in this case providing structural support and stability to the patient. I would assume this makes it a device and therefore falls under CDRH. It would be a class II medical device. The claims would be that the device will provide structural support to patients to carry out daily activities, such as walking or running, while at the same time preventing infections by releasing antibiotics. I would want to perform mechanical testing (cyclic testing) on the device to see if it can sustain its function of supporting the patient physically long term. Also, I would do biocompatibility testing to see if the material used for the hip stem is biocompatible or not. The product does need an IDE so that it can be tested on humans before its marketed to the public.

Device: Antibiotic-Releasing Hip Stem
Type: Combination of a device (hip stem component) and a drug (antibiotic component) but the primary mode of action is as the hip implant. This product will then need a Request For Designation (RFD) to allocate it to whichever department the FDA deems appropriate. This will most likely be the Center for Devices and Radiological Health (CDRH) since it is primarily a device, which you will have to make that case with a strong argument.
Class: I would determine this to be a Class II product since it is not life sustaining/supporting and also is not a novel idea, it only adds the extra healing component to an already existing concept.
Claims/Trials: Since the hip implant is already proven to be effective on its own, we should test the antibiotic agent on different animals in case which they may have broken bones or modified implants of their own. A control group will not be given the healing agent and the experimental group will. Whichever benefits can be seen in the experimental group should be used as claims for this product.
Approvals: This product will need an IDE since it introduces new risk to the patient and will need to be evaluated in human trials before gaining market approval.