Would-be manufacturers of antimicrobial-treated devices should familiarize themselves with seven important FDA requirements for 510(k) submissions for these products.

Lise Moloney

Cases of antibiotic-resistant infections have dominated the news, with prevention becoming a top priority for healthcare organizations and consumers alike. And because many of these infections are spread via medical devices of all shapes and sizes, manufacturers have started to take more aggressive steps to ensure their products help combat the problem. Whether it's designing all new products (or altering existing ones) for better infection prevention or leveraging antimicrobials to protect device surfaces, manufacturers are playing an increasingly larger part in ensuring patient safety. 

One area that has impeded some manufacturers from going to market with antimicrobial-treated devices is navigating the U.S. Food and Drug Administration's (FDA) 510(k) submission. In 2007, the FDA released draft guidance for antimicrobial devices--and there is no indication that formal guidelines will ever be released. There are many unknowns and the requirements are murky at best. In fact, the process is seen as so daunting that it has deterred some manufacturers from even pursuing it.

Despite its complexities, 510(k) submission requirements can and have been met. The draft guidelines are the best resource available for what the FDA is looking and there are seven areas that include the most important requirements pertaining to antimicrobials. Manufacturers, their regulatory teams, and their antimicrobials partner should know them back and forth.

1. Indications for use:Knowing what the claims are around the antimicrobial is critical because, ultimately, the manufacturer will have to prove them. Indication for use of the device itself, the primary function, should be well understood by the product development team. But defining an indication for the antimicrobial can prove to be a challenge. 

Whatever a company wants to say about the antimicrobial must be discussed upfront and include key departments within the organization. These claims should guide the test planning for antimicrobial performance. If a manufacturer says its antimicrobial is going to do X, Y, and Z, then it must be tested for X, Y, and Z before it can make that claim in the 510(k) submission.

2. Choose a predicate device: If a manufacturer uses a technology that's already gone through an FDA-approval process, it has a predicate for use of the technology. Without that, the 510(k) process cannot be used, rather the manufacturer has to go through an even more complex and time-intensive Premarket Approval (PMA) submission.

3. Explain the antimicrobial chemistry: A manufacturer has to be prepared to provide a detailed, crystal-clear description of the antimicrobial chemistry. This is often a challenge--while manufacturers are skilled in the world of device design, they are often not fluent in the world of antimicrobial chemistry. This is when working with an antimicrobial provider that has experience with FDA-regulated products and submissions can come in handy. It will likely have this information prepackaged and ready to go for 510(k) submissions.

4. Identify the mechanism of action and spectrum of activity: At the start of the planning process for an antimicrobial-embedded device, the manufacturing team identifies clinically relevant organisms--those that are of critical concern for the device. The antimicrobial technology that is ultimately chosen for the device needs to be effective against those specific organisms. 

For this aspect of the 510(k) submission, FDA wants to know two things: how the antimicrobial kills and what it kills. Does it kill bacteria, fungus, yeast, resistant strains, or a category of microorganisms? And how exactly does it kill those organisms? It also wants to see data supporting these claims.

5. Explain release mechanism and kinetics: FDA is looking to understand how the antimicrobial is released from the device. For example, if the antimicrobial technology is eluting from the surface, the manufacturer will have to explain the release mechanism (how it releases from the device surface) and the release kinetics (how quickly it releases). If it's a bound technology, it will have to prove it isn't releasing from the device. 

Many of the nation's top antimicrobial technology providers have their own inhouse labs for material characterization and analytical testing (and will often work closely with clients to develop the most appropriate testing methodologies). This requires detailed, rigorous chemical analysis to characterize the release of active ingredients from the device. Without the support of industry experts and sophisticated lab facilities, an FDA submission can stall here indefinitely.

6. Explain antimicrobial concentration: FDA will want to know the specific concentration of the antimicrobial within the device in order to evaluate safety and efficacy. Where many manufacturers get stumped during the submission process is around defining the "minimum effective concentration." There are a lot of questions about what FDA means by that term and it has not provided any clarity about what it expects. Again, if your antimicrobial technology provider is experienced with these regulatory submissions, it should have a good sense of what FDA expects when proving the safety and efficacy of your product.  

7. Document distribution kinetics, toxicity, metabolites and degradation: To ensure product safety, FDA expects manufacturers to describe the following:

Ideally, data will already exist on the safety of the antimicrobial technology. In cases of novel technologies, biocompatibility and toxicity studies will need to be conducted.

The demand for antimicrobial-treated medical devices is steadily on the rise, but far too many manufacturers have hesitated, stalled, or given up on projects due to uncertainty around FDA's 510(k) process. By following a set of proven best practices, manufacturers can (and do) get their products through to approval. 

Lise Moloney is the director of business development for healthcare at Sciessent, a provider of antimicrobial, anti-odor, and water repellent products. 

[Image courtesy of RENJITH KRISHNAN/FREEDIGITALPHOTOS.NET]