By Kelly M. Pyrek
Manufacturers make claims about their products' efficacy in killing disease-causing pathogens, but what do infection preventionists really know about the validity of these claims? In a series of articles, we'll take a look at what practitioners in infection prevention should understand about the science behind label claims and marketing hype, including the FDA clearance and EPA registration processes, as well as testing protocols that preceded a product's appearance in the marketplace. In this first article, we talk to Wallace Puckett, PhD, vice president of science and technology for STERIS Corporation, about the knowledge gaps that currently exist relating to research and development of disinfectants, antibacterials, antimicrobials, microbicides and sporicides.
Q: Why isn't there more dialogue about the science behind products used to combat healthcare-acquired infections (HAIs) in the healthcare setting?
A: We in the industry many times do not pursue efforts to make educational presentations on the basic science of products at professional meetings and conferences. There are not enough of us talking about what goes on with the science behind these products and technologies currently in the marketplace. Perhaps it's because we have not done a good enough job of convincing professional organizations to set aside time during their meetings for a session on basic science. Another reason is that we in the industry have had a tendency in the past to not have a scientist do the presentations. The industry must do a better job of building a reputation with organizations such as SHEA or IDSA that when we make presentations, they will be free of commercial bias and we are going to be talking about science and technology, not selling a product. And that we are going to avoid making disparaging comments about our competitors and their products and instead focus on educating people on issues in infection control. Scientists should also attend the meetings for infection preventionists, as well as to the meetings for attendees who are actually using our products; the infectious disease physicians rarely make product-purchasing decisions. Having said that, everyone must be informed about the science behind these products.
Q: What should infection preventionists know about the research and development (R&D) being conducted these days?
A: There has been a huge change in the way for-profit companies conduct their R&D activities. There used to be a significant emphasis on the research part of the R&D equation, in part driven by the World War II era when U.S. government officials began to realize we were woefully behind the rest of the world on technology development in general. So a lot of money and effort was expended at the university and corporate levels. In the 1980s, the strategy began to change -- there was much less basic research and far more applications development. What's happening today is that other than the pharmaceutical companies and certain chemical and device manufacturers, we really conduct very limited and focused basic research. We call it R&D but for most companies it's really a very small "R" and a really big "D." These days, it's difficult to put new chemistries, whether they are for hand hygiene or for surface disinfection, on the market. So we spend our time developing new applications for existing active ingredients. It's very difficult to make a business justification for doing the basic research and taking the risk of developing a new active ingredient when the world is full of gaps and opportunities for new applications of these existing active ingredients. Companies like STERIS and other big players in the industry spend much of their time on developing applications of existing technologies and chemicals, leaving it to the university and the government labs as well as the entrepreneurial start-ups to do the high-risk work of new active-ingredient development. We have found ourselves in a race around a few active ingredients to uncover features, benefits or advantages in the products we produce to give ourselves a leg up on the competition.
Q: What has been the primary focus of this applications work lately?
A: We are driven by needs in the marketplace, and recently there has been a big push to help healthcare professionals reduce the time it takes to get a surgical instrument reprocessed -- properly cleaned and sterilized or high level disinfected so it is available for the next procedure. So our emphasis in new product development has been on how we reduce that "skin-to-skin" cycle time, or getting an instrument from one patient to the next patient in a timely fashion while reducing the complexity of that process.
Q: So what's the common reaction to hearing about the science behind the products?
A: The current regulatory climate drives a set of standards for testing, but it's so complex and ever-changing, and that's why when you talk to a healthcare professional about science, many times you see their eyes glaze over. We say our products are tuberculocidal in X minutes or sporicidal in X minutes, and people look at me with a blank stare and they say, "Just tell me if the product works."
Q: But aren't they missing critical information?
A: There are many nuances that are missed when this happens. For example, when you look at a particular active ingredient, the formulation is the most critical component of whether or not that active ingredient is effective or not. You get into things like lipophilicity or cationic compatibility; a difficult concept which can be challenging to understand. Other critical nuances relate to compatibility among antimicrobials. For instance, for surgical site preparation, clinicians might use one kind of soap to clean the surface of the skin and then use a second product that's not compatible with the first . Even though the surgical site prep product was validated to produce a specific reduction of microorganisms on the skin, when it was used with another, incompatible product, the overall effectiveness was diminished because the products were used together unknowingly -- and that important nuance might be lost. So then you have vendors calling on the hospital and saying, "Hey, I've got this great soap you can use to clean the skin before you do your surgical prep." Unfortunately they may not be sophisticated enough to question what surgical site preps the hospital staff is already using. The vendor needs to say, "Because if you are using povidone iodine, I'll sell you this product because it is compatible with povidone iodine; if you are using ChloraPrep, I'm going to sell you another one because it is compatible with that prep." But unfortunately we don't always have that level of critical thinking among vendors.
Q: What are the ramifications of this kind of mistake?
A: What causes people to start wondering what's wrong is if they begin to see an uptick in infections, such as surgical site infections (SSIs), that have no other explanation and they will start to investigate. So then you have one hospital that has been educated about this lapse, but it is not their job to tell their brethren at other hospitals -- unless you are lucky enough to have an infection preventionist who wants to write a paper about their investigation to help share knowledge. There is a critical need for people who can present complex information like this in simple terms so it has impact on practice I don't see many people out there doing this.
Q: What kind of impact does product-related science have on practices?
A: I hear talk about evidence-based practices but I would prefer to call it fact-based, or data-based. Even though they are advocates of data-based practices, I see both regulatory agencies and standards groups making statements that are not data-based. What concerns me is that dated information is being included in recommendations, data that may have been accepted years ago but has been refuted since then. Regulations and statements are being made based on this dated information that may not be accurate. There's a lot of that in healthcare -- look at the proliferation of alcohol-based hand hygiene products, for instance. They are a wonderful adjunct to a comprehensive hand hygiene program, but because of their convenience and ease of use, it appears they are becoming the dominant hand hygiene practice. Here's my fear though -- the leading cause of HAIs is no longer MRSA, it's C. difficile. It exists as a spore in the environment and it is unaffected by alcohol-based products. So the only way to help combat C. diff, especially as it is transported on healthcare workers' hands, is by washing hands with soap and water. We need to get the knowledge out to everyone, the MDROs are changing, and the regimens required to prevent the spread of infectious organisms are different for C. diff than for MRSA. There is the pervasive dogma that alcohol kills everything. And we allow that to happen by not publishing, teaching and conducting the in-services we should to re-educate healthcare professionals. Not only must we continually educate, but we must probe to see if they understand what we are teaching them; we presume we have communicated the message but we don't follow up on people's actual comprehension of the message, and this case, it's the importance of the physical removal of bacteria and spores with a hospital-grade wash-off hand soap. If we are serious about promoting evidence-based practices, it's about the data -- don't just tell me the product works, show me the data that has been validated and reviewed, so I can believe the data and not just someone's words. There is no way a vendor can be looked at without a jaundiced eye, and we encourage our customers to check the data and gather enough information to make an informed choice about products and technologies. That requires a lot of work, but when we talk about making evidence-based decisions, that's what we must do. That will require looking at things differently.
Q: Practitioners see FDA approval and EPA registration as the necessary stamp of approval for products and technologies; why is this misleading?
A: The FDA generally has a procedure by which one can prove the efficacy and safety of a product to the extent one is able to do that. The concern, however, is that this tends to be a moving target. At the end of the day, if you have an FDA 510k-cleared product, you at least have met some expectation with regard to showing efficacy and safety, and the same is true with the EPA. But just because I have a product registered with the EPA, does that mean it's going to do the work the hospital believes it is going to in the healthcare environment? That's a separate set of studies required at the hospital level but not required at the EPA level. There are some studies required for each of those regulatory approvals that do go to clinical practice, but they are not comprehensive. I have seen hospital-grade disinfectants for surfaces that are EPA-registered that don't work because their registration was done a few years ago against standard organisms and now they are being applied in the hospital against a resistant organism. So it goes back to the need to demonstrate that a product will work in a particular facility when combating their problem organisms. We assisted an infection preventionist at a local hospital a few years ago in overcoming an Acinetobacter baumanii outbreak. It turned out that the hospital-grade surface disinfectant they were using, while it was EPA registered, was ineffective against that organism or perhaps the method of application utilized. That is not the fault of the vendor -- they got the EPA registration by doing the appropriate studies, but the organisms change their stripes over time. And this organism had become somewhat resistant to the standard cleaning products. Even when the infection preventionist was rounding with the environmental services staff, and watched them scrub those surfaces, when she sampled those surfaces, she still found that organism after the cleaning was done. While EPA registration or FDA clearance is legally required to sell a product, it may not also infer the product is effective in a particular situation. For example, during the H1N1 outbreak, there were some unscrupulous companies making statements that their products were effective against the virus. There were no protocols provided by either the FDA or the EPA allowing one to make that statement. They were perhaps EPA-registered products, but EPA had not yet provided a protocol by which a manufacturer could make a claim about H1N1. This is another example of a product registered for use on surfaces against viruses but not registered for H1N1. So what the EPA said, is that while it doesn't have a registration for it, the agency believes the product would be effective based on the kind of virus this is. It's no one's fault; no one had the time to put a protocol together or do a trial. That's why we need a data-based approach.
Q: Knowing this, are manufacturers ensuring that their products and technologies are being used correctly in healthcare facilities?
A: Most manufacturers conduct in-services. For example, scope manufacturers will show healthcare workers the appropriate way to clean, disinfect and sterilize their devices, including providing specific instructions, manuals and wall charts. But knowing the kind of staff turnover hospitals have, facilities must have diligent training processes to maintain that training level so the processes are properly passed down to each new person who comes in to clean that device. Because we develop new products for reprocessing, as part of the FDA's 510k clearance process we are required to do clinical in-use studies, where we take our new reprocessing device into a hospital environment and we actually reprocess devices with this new system in the hospital setting. Those devices have to be processed by a legally cleared method before they can be used, so no one is being treated with a device that has not been reprocessed with an FDA cleared reprocessor. As we observe staff going through their normal procedure of cleaning the scope, we will sometimes find that their understanding of the cleaning, decontamination and sterilization procedures are unclear. The challenge is that when we validate a reprocessing device, we validate it upon a properly cleaned device. Fortunately, we use the overkill method, part of the regulatory strategy that we have to go through with FDA and with the EPA, which is that for our laboratory studies we must always test against the most resistant organism. All of the organisms encountered at the hospital will most likely be less resistant. And when we do use that highly resistant organism, we are required to show that under the worst-case scenario, with the worst-case organism, you will achieve the claimed kill rate. Remember though that our validations in the clinical setting (in-use) are done on properly cleaned medical devices, and you must always demand that the scope must be properly cleaned and decontaminated before you can have confidence in the validated process. Because we validate our methods this way, we see better results in hospitals than we otherwise might.