Which Antimicrobial Is Right For Your Medical Device?

by Lise Moloney, director of business development, healthcare division, Sciessent

Healthcare-associated infections (HAIs), many of which are caused by antibiotic-resistant bacteria, impact one in 25 patients in the United States each year. These preventable infections claim the lives of 75,000 people and cost the healthcare industry between $36 billion and $45 billion annually.

Due to efforts by the Centers for Disease Control and Prevention (CDC), the dangers of HAIs are well known and some progress has been made to combat them. Yet, despite slight reductions in HAIs, the healthcare industry has a long way to go to eliminate them altogether, a goal set by the U.S. Department of Health and Human Services. And with recent Affordable Care Act provisions that penalize hospitals for high infection rates, the stakes have never been higher for prevention. 

Why Aren’t We At Zero? The Need for Broader Infection-Control Strategies

Why is the healthcare industry nowhere near a zero rate for HAIs? While people have spent countless pages discussing the issue, I can break it down for you in five words: Not complying with HAI guidelines.

Less than 40 percent of U.S. hospitals are in full compliance with HAI guidelines. Even something as simple as hand hygiene, only 40 percent of healthcare personnel regularly adhere to guidelines – which leaves a whopping 60 percent who do not. Of course, HAI guidelines are much broader than just hand washing. Insufficient infection-control infrastructures in non-acute care settings also have allowed for major lapses.

Today, in order to significantly reduce HAIs and to combat the increased threat of antibiotic-resistant bacteria, many healthcare organizations are adopting broader, more vigilant infection-control strategies that include following guidelines more thoroughly, changing staff behavior, and adopting antimicrobial-treated medical devices and surfaces.                   

Antimicrobial-Treated Devices To Supplement Infection-Prevention Programs

An increasing number of healthcare organizations are implementing broad infection-control strategies that use antimicrobial-treated medical devices. And, while antimicrobial devices do not replace best practices and guideline recommendations, they can play a major part in further driving down infection rates. 

Recent industry guidelines have fueled the adoption of antimicrobial-protected devices among healthcare facilities. For example, the Society for Healthcare Epidemiology of America stated that best evidence practices for the prevention of central-line associated bloodstream infections (CLABSI) recommend the use of  “silver zeolite-impregnated umbilical catheters in preterm infants” and “antimicrobial-impregnated central venous catheters (CVC) in adult patients” to prevent CLABSI.

With the demand for antimicrobial-protected medical devices growing, manufacturers are exploring how they can develop new technologies to meet the needs of their customers. Yet they often are left with many unanswered questions regarding antimicrobial additives. In this article, I will break down the areas that need to be addressed when selecting an antimicrobial for your medical device.

Choose The Best Technology – Define Requirements

Antimicrobials are not a one-size-fits-all technology. An antimicrobial that is extremely effective in one application might be useless in another. The industry is filled with different antimicrobial technologies, which can be divided into two categories: “naturally occurring” and “synthetic chemicals.” Naturally occurring antimicrobials are elemental ions that include silver salts, metallic, controlled-ion released, and nano-based solutions. Synthetic chemicals include biguanides and others.

As a medical-device manufacturer looking to embed antimicrobials, the first thing you need to do is to define your product’s requirements. This ultimately will act as your guide to finding the best antimicrobial “fit.”

• Define The End-Use Environment: Different environments require different antimicrobial technologies. Is the product a patient-monitoring device that sits by the bedside? Is it cleaned between patient uses? Is it an in-dwelling CVC that sits in the blood stream?
• Define Clinically Relevant Organisms: Is there data showing that certain types of organisms are of concern for this device application? If you know that answer up front, you need to make sure the antimicrobials chosen protect against those pathogens.
• Define Ideal Antimicrobial Performance: Determining specific antimicrobial performance standards in advance helps guide the search for technology that will fulfill as many of those requirements as possible. Is there a product on the market that sets the benchmark? Will your company need to do as well/better? Do you need to have a 3-log reduction in bacteria on the surface?
• Define The Minimum Duration Of Efficacy: Determining how long you want the antimicrobial efficacy to last in the end-use environment is important. Will the device be used for less than 24 hours and then removed? Fewer than 30 days? Or, is it a permanent implant?

Understand Manufacturing Processes And Capabilities

When selecting an antimicrobial technology, you need to understand the current manufacturing process of the device — and the capabilities of the manufacturer and facility — beforehand. Knowing up front where you want to incorporate the antimicrobial (i.e., directly compounding it into the polymers and injection molding the part) is the best way to go.

For example, if you are looking at surface coating, make sure the manufacturing facility has experience with coating devices, or that it can contract out services or bring resources in house. Envisioning how you’d like the process to be done can help you choose the best manufacturing partner and save you headaches down the road. 

Find An Experienced Antimicrobial Supplier

When trying to find the right antimicrobial partner in a crowded market, make sure that the company you choose has deep experience with U.S. Food and Drug Administration (FDA) regulated medical products. While medical device manufacturers are experts in the design and use of their products, most are not experts on antimicrobials. Having an antimicrobial supplier acting as an extension of your core team will ensure that the product development process is smooth and efficient. A supplier with past regulatory experience can also act as a guide and a resource throughout the submission and approval process.  

Know The Regulatory Considerations Inside And Out

One of the biggest considerations when taking on an antimicrobial medical device is knowing the regulatory pathway. In 2007, the FDA released draft guidance for 510(k) submissions for antimicrobial devices. Although this draft guidance was never finalized, this is the best resource available to understand what the FDA is looking for — and you and your regulatory team should know it backward and forward.

Here is a quick overview of some of the items FDA is looking for specific to the antimicrobial additive:

• What Are Your Indications For Use? Carefully specify claims around your planned antimicrobial because, ultimately, you will have to prove them. Those claims will set the tone for what the FDA will expect in the body of the device’s 510(k) submission.
• Do You Have A Predicate Device Comparison? Using a technology that already has been FDA approved gives you a predicate device. Without that, you can’t use the 510(k) process and will have to go through a Premarket Approval (PMA) submission. Typically, you will use two predicates: one for the device itself and one for use of the antimicrobial.
• Can You Detail The Antimicrobial Chemistry? Be prepared to provide a detailed description of the antimicrobial chemistry and any ancillary components. For example, if you use a coating to adhere the antimicrobial to the surface of the device, you’ll have to explain, in detail, the chemistry involved with that. For this step, working with an experienced antimicrobial supplier can come in handy — especially if it can provide these details for you.
• What Is Your Mechanism Of Action? This step tests your device/antimicrobial’s efficacy in combating the clinically relevant organisms that you are targeting. How exactly does the antimicrobial additive kill these organisms? This is another area with which your antimicrobial supplier should be able to help you. 
• How Do The Release Mechanism And Kinetics Function? If the antimicrobial technology is eluting from the surface, you will have to explain the how the release mechanism works, as well as the release kinetics (rate at which the antimicrobial is released from the device). If the antimicrobial is a bound technology, you will have to prove it isn’t releasing from the device.
• What Is The Antimicrobial Concentration? The FDA will want to know the specific concentration of antimicrobial in or on the device, as well as the minimum effective concentration. Again, your antimicrobial supplier can be of service.
• Is Your Antimicrobial Safe? You’ll have to describe your proposed antimicrobial’s distribution kinetics, toxicity, metabolites and degradation in the body, if it is an eluting technology. If not, you’ll have to prove that nothing is eluting into the body.

Leveraging antimicrobials to reduce microbial accumulation on the surfaces of medical devices has been proven to work, but adding antimicrobial features remains a complex procedure filled with many unknown pitfalls. As the call for antimicrobial functionality continues to strengthen, it is imperative that your company embrace this change the right way — by defining requirements, understanding manufacturing capabilities, finding the right antimicrobial supplier, and preparing for the 510(k) submission — in order to be successful.   

About The Author

Lise Moloney is director of business development for the healthcare division of Sciessent, with whom she also has served as a medical device and biotechnology consultant. Moloney possesses a degree in chemical engineering from the University of Connecticut and has industry experience with combination devices, clinical advisory boards, pre-clinical studies, technical collaboration and regulatory submissions.