For an antibiotic-releasing hip-stem the device Type is a combination device which are products that combine drugs, devices and or biological products. Next, the primary mode of action is intended to replace a defective bone to support the hip (holding up a hip). The agency that has governance over it is CDRH. It is a class II device.The claim would be the implant will treat infection in a single procedure and to Replaces bone of a hip with enhanced titanium steel structure as substantially equivalent titanium hip stem prosthetic devices. Regulatory Pathway is CDRH->Class II-> 510(k). Furthermore, it's a 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
What kind of regulatory pathway would be required for an antibiotic-releasing hip stem?
The regulatory pathway that would be required for an antibiotic-releasing hip steam is first being reviewed by and approved by the Center for Devices and Radiological Health (CDRH). Since it is a class two device, a 510(k) application can be used. An IDE will be needed.
Is it a device, drug, biologic, or combination?
The antibiotic-releasing hip steam is a combination device of a drug (the antibiotic) and device (hip stem).
What is its “primary mode of action?
The "primary mode" of the antibiotic-releasing hip stem is to replace under performing natural bone and will support the hip in place of the natural bone.
Is it Class I, II, II?
The device is a Class II device.
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.
The claim that would be recommended is "replaces the natural hip bone, while decreasing infection potential at install location."
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?
The pre-clinical resesarch studies that I would recommend are all the required tests per the ISO 10993-1 Test Matrix. I would also recommend adding at least the "Irritation or Intracutaneous Reactivity" Test in order to monitor how the antibiotic reacts with the implant 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?
I would recommend monitoring how effective the antibiotic is, as well as standard clinical trials for hip stem devices.
What kind of regulatory pathway would be required for an antibiotic-releasing hip stem?
The regulatory pathway that would be required for an antibiotic-releasing hip steam is first being reviewed by and approved by the Center for Devices and Radiological Health (CDRH). Since it is a class two device, a 510(k) application can be used. An IDE will be needed.
Is it a device, drug, biologic, or combination?
The antibiotic-releasing hip steam is a combination device of a drug (the antibiotic) and device (hip stem).
What is its “primary mode of action?
The "primary mode" of the antibiotic-releasing hip stem is to replace under performing natural bone and will support the hip in place of the natural bone.
Is it Class I, II, II?
The device is a Class II device.
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.
The claim that would be recommended is "replaces the natural hip bone, while decreasing infection potential at install location."
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?
The pre-clinical resesarch studies that I would recommend are all the required tests per the ISO 10993-1 Test Matrix. I would also recommend adding at least the "Irritation or Intracutaneous Reactivity" Test in order to monitor how the antibiotic reacts with the implant 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?
I would recommend monitoring how effective the antibiotic is, as well as standard clinical trials for hip stem devices!
An antibiotic-releasing hip stem would undergo a 510k pathway as it classifies as a Class II combination device of a drug and device-based product. It does not sustain life so it may not require a PMA, but it is an implantable device that intimately interacts with human tissue, so at the very least, pre-clinical and clinical data is required. It's primary mode of action would be to act as a mechanical stabilizer within a patient's skeletal muscular system while secondarily preventing infection to the healing bone.
The claim should be stated in a way that is not to direct but not too ambiguous. One such claim should state: "This combination device will enhance hip function following hip failure while reducing the likelihood of infection at the implant site." According to lecture, the FDA is very sensitive to the wording used when introducing a medical device to the regulatory pathways, therefore it's important to use terms like "enhance" and "reduce" rather than "restore" and "eliminate" since the more definitive you are, the more you will have to prove in your studies.
An online search shows a sheep model as ideal for the aseptic loosening of a hip prosthesis because sheep display a similar extent of biochemical changes that resemble those found in human patients, such as bone resorption and membrane formation at the hip stem interface (1). A regular hip stem replacement is already an FDA-approved marketed device, so an IDE is not required since it can be proven to have substantial equivalence to predicate hip stems currently in the market. An antibiotic-releasing hip stem on the other hand is different because it is actively releasing a compound into the blood, a dual effect that most likely requires more studies that fall under an IDE.
(1) El-Warrak A, Olmstead M, Schneider R et al (2004b) An experimental animal model of aseptic loosening of hip prostheses in sheep to study early biochemical changes at the interface membrane. BMC Musculoskelet Disord 5:7
An antibiotic-releasing hip stem implant would be considered a device/drug combination. The primary mode of action would be to restore mobility, as it is more than likely the patient would not have undergone surgery if they needed drugs to be released to the surrounding tissues. The regulatory pathway would be: CDRH, Class 2, 510(k). CDRH because its primary purpose is a medical device, and Class 2 because it is an improvement of the already designed hip implant. An IDE would only be necessary if this was a Class 3. A claim I would make is, “restores mobility and eliminates arthritic pain while self-releasing antibiotics heal the surgical area.” To prove these claims, three different studies including animal subjects would need to be conducted to ensure the device and drug first work well separately and then together.
What kind of regulatory pathway would be required for an antibiotic-releasing hip stem?
CDRH Regulatory because it is mainly classified as a medical device, not a drug or biologic.
Is it a device, drug, biologic, or combination?
It is a combination device involving drugs and biologics as well.
What is its “primary mode of action?
The primary mode is a medical device because you are affecting the structure of the human body, the other modes come into play due to it being a device that is placed within the body.
Is it Class I, II, II?
Would initially fall under a class 3 until proven to be class 2, so considering that it is a hip implant ultimately, it’s a class 2. Therefore, a 510K will be necessary.
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.
Provides structure to the hip to allow the person to have a proper gait and movement while being accepted by the body and growing into the bone it fights infecction with its antibiotics.
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?
In regard to pre-clinical research, Biocompatibility testing (ISO 10993-1) will need to be conducted to evaluate the biological effects and it’s duration.
Guessing as best you can, what sorts of clinical trials would you recommend in the IDE? Does it need an IDE at all?
Contrary to what my collegaues have been mentioning, I believe an IDE is required because this is a foreign device that's being introduced to the body and can be considered a significant risk device since it is being permanently placed within the body. I would reccomend in vitro trials for the antibiotics as well as, we want to make sure that the antibiotics are effective to avoid infections.
I believe that is drug is a combination of both a drug and a device; the primary mode of action, however, would be a device as it is acting in place of the bone and without it there would be no device. The antibiotic in theory would be shorter lasting than the bone that is expected to remain in the patient. I would classify this as a Class II device unless the antibiotic has never been tested in humans before. Otherwise, there are other hip implants and antibiotics currently used.
In terms of claims, I would want to be able to claim that this device will replace the bone of the hip and that the antibiotics released will prevent infection upon implantation. To do this, you would need to show that this will successfully be implanted and accepted by the body, that patients are able to walk again without pain, and that the antibiotic fights off infection at the site of the replacement through clinical trial data. This would also show to the FDA that this device has been derived through a device currently approved; this would allow the new device to remain in Class II. Before this reaches the clinical trial level, it would need in vivo and in vitro work, with a bigger animal to which I have found pigs have been previously used. I do not think that it would require an IDE if it is very similar and has no new technology. If the FDA thought this was a new device, then it would need an IDE. I believe it would require clinical trials, in vitro, and in vivo work because you are putting this device inside a human and these studies will only aid in the claims that the company would like to make on the product.
An antibiotic releasing hip stem is an orthotic implant with a novel coating that fights osteomyelitis. This would fall under the CDRH sub-organization, and would need to pass premarket approval. It would most likely be classified as a class 3 combination device, with it's primary function being to replace the hip joint. We can make several claims about the stem to make it marketable and show it as a viable alternative to current norms. The hip stem leeches no harmful metal deposits into surrounding tissue, it kills 80% of osteomyelitis causing factors, its young's modulus is exactly that of bone. These claims can be tested by doing stability testing in rat models, in vitro testing of the anti-osteomyelitis factors, and mechanical testing of the stem. Clinical trials in patients prone to osteomyelitis would be the most beneficial research. Results from this study compared to a control group would shed light on the efficacy and safety of the device, and show the regulatory bodies the viability of the stem.
What kind of regulatory pathway would be required for an antibiotic-releasing hip stem?
The regulatory pathway would involve clinical trials and FDA pre-market approval to prove safety and efficacy, unless there is already a antibiotic-releasing hip stem in the market to which you can prove substantial equivalency and file a 510(k)
Is it a device, drug, biologic, or combination?
Combination (given serves as both a device and drug)
What is its "primary mode of action"?
The "primary mode of action" is a single action of a combination product that provides therapeutic action, in this case to replace a worn or damaged hip joint that causes pain and reduces mobility.
Is it Class I, II, III?
Class 3 (given it is an implant and has a high risk to the patient if the implant fails/is rejected)
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.
It is important to be clear about the implants intended use. Obviously, the hip stem component is an orthopedic implant used in hip replacement surgery, however, it is not clear as to what purpose the antibiotic serves. What exact infection is the antibiotic supposed to prevent and how often? Therefore, an in vitro and in vivo study could be set up to evaluate the effectiveness and susceptibility of the antibiotic. Next, it is important to ensure biocompatibility which includes evaluating cytotoxicity through a cytotoxicity elution test and osseointegration through an MTT assay. Lastly, it is also important to test the hip stem to ensure it is suitable for a hip replacement, therefore, you should test its' mechanical properties through wear, fatigue, and static testing to validate the implants durability and performance over an extended period of time (not sure if this implant is permanent or temporary which is necessary to clarify) and to determine what patients the implant is suitable for based on their weight and femur size.
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?
As discussed last week, prior to getting to human trials, any drug, device, or combination product requires both in vitro and in vivo studies to prove safety and efficacy as well as to validate the products intended use.
Guessing as best you can, what sorts of clinical trials would you recommend in the IDE? Does it need an IDE at all?
The hip stem would require an investigational device exemption in order to prove safety and efficacy so that it can be marketed for use.
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Upon reviewing my peers responses I would not recommend filing a 513(g)/request for designation because it could lead to an unfavorable outcome. For those who believe it would be considered a class 2 medical device, I did find an example of an antibiotic releasing hip stem ( https://osteoremedies.com/wp-content/uploads/2020/06/Z1G183_REMEDY_SPECTRUM_GV_HIP_SURGEON_IFU-1-20-V3.pdf) for which you could use to file a 510(k) and prove similar indications of use. Also given it is a combination device but "primary mode of action" is as a hip stem I agree that the implant would be evaluated by the CDRH.
I believe that the antibiotic-releasing hip stem is combination object that should be classified as a Class III medical device, considering that implants generally fall into this category due to their elevated risk profile. Since the device is regulated by the U.S. FDA, it falls under the preview of the Center for Devices and Radiological Health (CDRH). To proceed with its development and approval, the first step would involve securing an Investigational Device Exemption (IDE), allowing for clinical studies to collect safety and effectiveness data. Once the IDE is approved, clinical studies can begin, aimed at gathering crucial data in the intended patient population. Subsequently, a Premarket Approval (PMA) application would be submitted to the FDA, presenting comprehensive evidence supporting the device's safety and efficacy. After FDA review and approval, there would be ongoing post-market surveillance to monitor the device's performance and safety in real-world clinical settings. Throughout this process, it is vital to collaborate closely with regulatory experts and stay updated on evolving regulations and guidance documents to ensure a successful regulatory pathway for the antibiotic-releasing hip stem.
