Armed with a Google search engine, one does not need to look far to determine how utterly bad a patient’s prognosis could turn if whatever put that person in the hospital gets compounded with an infection. Heaping that problem onto an ailment always makes it worse: diabetes with infection, stroke with infection, bone fracture with infection. It is never good. If cancer does not get you, the drain circling initiated by an infected something added to your problem very well could. It is really quite common, and as an example orthopedic literature gives ranges of 30 to 60% of all open fractures becoming infected. For urinary catheters, the rate is 100% if the patient keeps it in long enough. With this huge problem, where are all of the medical devices that can help curb it?
They are there, but they are slow to emerge, and there are not enough of them. However, let us back up for one minute and address the usual way of taking antibiotics via pills or IV. Why do we need an antibiotic or antimicrobial releasing medical device when the patient can just take a pill or a needle? The answer is simple: concentration. If an infection at a localized area, like a bone fracture or a urethra, gets too advanced the concentration of antibiotic needed to kill it and ensure no resistance is created is quite high. That high concentration also needs to be applied for long periods of time in some cases. However, when administering an IV or a pill, the concentration needed to kill the infection is established throughout the entire bloodstream and tissues, bringing up the distinct possibility of toxicity. The very antibiotic used to heal becomes a poison. By contrast, if a medical device is used to deliver an antibiotic or antimicrobial to the local area, the concentration of the therapeutic agent can become extremely high, but only at that area. This poses a much lower risk to the patient because the areas outside of the injury are not as affected.
That covers the basics. Now it is time to consider the question of where these devices are. For good and ill, we live in a regulated society and in the case of medical devices the regulatory agency in the US is the FDA, and for Europe it is a combination of several types of government branches, individual competent authorities, and notified bodies contracted by the government. To get something onto the market, one must go through these bodies. It is the difficulty in doing so that many hopeful device manufacturers, physicians, and self-made entrepreneurs do not understand. Too many times, I have seen great ideas for antimicrobials and antibiotic releasing platforms go by the wayside because of this disconnect. I have in fact even argued against my supervisors for starting development projects involving these devices several times in the past. It is not that they cannot work. It is that proving they work to the satisfaction of the regulatory bodies kills the projects on cost.
Taking the US as an example as it stands right now, any time an antibiotic is introduced onto an implantable device, several things become fact more or less.
1) No matter what you claim the antibiotics are doing on that device, the FDA will assert that you must prove they fight infection.
2) Fighting infection and proving a reduction in infection rate requires a large clinical trial. The actual size of the trial will depend on how far you claim to reduce the infection rate overall and how many patients you need to see that reduction. Good luck picking a device with a 5% infection rate normally and trying to prove it reduces that rate to 2%.
3) The device is a combination device. Whatever the “primary mode of action” is for that combo device will determine which FDA agency takes the lead on development. If you are a device company and know nothing about drug development, and CDER becomes your lead agency, you are in for a wild and expensive ride as you move towards your Phase I, II, and III clinical trials. Device trials do not have phases like drug trials do and are often seen as a faster and cheaper pathway, meaning “only” tens of millions of dollars.
If a company understands this and truly gives up on the idea of getting this type of device through with a 510(k) for a Class II designation, it will be better off. If the company has the funding to do this, even better. If either of these things is missing, time is wasted. Better to get real. Remember, this is still true even if the implantable device without the antibiotic is already a Class II.
Getting a disposable device like a catheter approved with an antimicrobial is and has been much easier. However, it still requires clinical trials. The story in the EU is also a bit easier, and there are many more antibiotic containing devices approved over there than in the US. However, that is because the EU regulatory system puts more stress on international trade and personal risk, as opposed to the FDA which is a health and human safety organization concerned primarily with efficacy and risk. In 2013, I visited around 75 different device companies personally. Some of them were developing antimicrobial or antibiotic releasing devices, though not all of them. Invariably, however, all of them were looking to take their devices for approval in the EU before the US for these reasons.
In the end, the main thing that causes antibiotic/antimicrobial technologies to tank is not their lack of science or research, but a lack of understanding of the regulatory pathway, or more accurately a voluntary blindness to the issues as such. Each company seems to think it will be the one to get the approval without the clinical trial and without the tens of millions spent on the PMA, and each one is wrong.
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