OR WAIT null SECS
By John Roark
It starts with an idea, says PatBraden, chief chemist and vice president of research and development for MedicalChemical Corporation. Someone says, I think this is going to work betterthan whats out there, or, Something out there works, and lets dothat too. You start with an idea, and then you do the background studies is it going to work? How can it be optimized? Once you get something that youthink is workable, thats when you start looking at clinical studies.
Obviously, each company would like to be first on theblock, says Jeanne Medvick, clinical studies group manager for STERISCorporation. We hold brainstorming sessions with the scientists, with themarketing personnel and anybody else who has an idea. You can sometimes get anidea about something thats already on the market, and you think, Thatsa good product, could we make it better? How can we distinguish ourselves from it? and also eventsin the world start you thinking about new ideas or new applications of what youalready have.
Medvick cites recent incidents involving anthrax distributedthrough letters. We asked: do we have anything to combat that? Do we alreadyhave it, or can we develop something? Things like that can also stimulate creativity. Yourealways trying to think ahead you would like to be ready to meet the needs,rather than be reacting once it hits. Whoever would have thought that thecoronavirus that causes SARS would be a problem? Coronaviruses have been around for a very long time. What werethe factors that made them so virulent in 2003?
I have been around microbiology for more than 30 years, Medvick continues. Back in the 1980s I thought, nothing newwill ever be needed; well always have a chemical for every organism either an antibiotic to kill it in humans, or one of the chemicals to wipe itoff surfaces. Im so very humbled now I almost get this feeling that wereback in the pre-antibiotic era. Humans have evolved stronger we live longer,we look younger than our ancestors and thats because weve adapted.Unfortunately the harmful microorganisms have adapted too.
I think all industries that have anything to do withhealthcare take their customer seriously, whether they manufacture handsanitizers, germicides or sterilizers, says Medvick. They recognize thatthey have to have input from their customers in order to bring something tomarket thats going to be helpful in controlling hospital-acquired infections,and to be able to develop a viable product that customers need. Its kind ofdifficult because some customers have really grand ideas they are very, verygood. But sometimes its hard to put all the good ideas into one package rightaway.
Customer input can reach manufacturers in a variety of ways.Information relayed back via the sales force, focus groups, surveys andattendance at healthcare conferences. We seek out customers on an individualbasis and through professional organizations, and also keep updated with theregulations and guidelines from the CDC, the FDA, and the EPA theyre ourcustomers also, says Medvick.
When evaluating germicides from a clinical perspective, NancyBjerke, RN, MPH, CIC, an infection control consultant in Texas, asks a lot ofquestions. Youve got to decide what it is you want it to work forand basically list the characteristics that you want a basic product to have,she says. Is it effective against the environment? Is it multi-purpose can you use it on the floors, the walls, the furniture? Is it fast-acting? Whatis its spectrum of microbial activity? Does it get all the viruses, all the bacteria? Is it EPA orFDA approved, depending on what its uses are going to be? Is it safe andeffective in actual use? Does it destroy any of the building materials orinstrument surfaces? Does it come full-strength or is it concentrated? What are the human factor requirements in point of use doyou have to wear personal protective attire? Does it have to be awell-ventilated room? Does the label claim meet the requirements of proper use,instruction on use of the product, counter-indications, and cautions if there isan exposure that occurs? It should also have a contact number on the label, as well asthe EPA registration number so that you can go to a website and actually checkthat yes, it is effective. You can also call into any of the EPA sites and see if therehave been any adverse reports on it.
What would be on the ICPs wish list for the perfectgermicide? You would have an active agent, either a germicide or a sterilant that you knew wouldkill absolutely everything in sight: bacteria, viruses, fungi, micobacteriumtuberculosi, says Medvick. Yet it would be compatible with all thesubstrates (the material components and surfaces of instruments and devices),even those used for very delicate operations. For example, instruments usedfor eye surgery are made of titanium or brass and copper; metals flexible enoughto be used in tiny areas, but softer, which means they can be adversely affectedby chemicals that are relatively strong. You want a germicide with broadspectrum activity, and you want something thats compatible with whatever isbeing disinfected or sterilized. Because lets face it those instrumentsare very expensive to replace, and you want them to last.
A clinician would look for something thats asuper-killer of microorganisms, yet can be handled safely by humans on aday-to-day basis, says Medvick. Not only the humans who are using it, butwhoevers going to come into contact with it afterwards, such as the patientlying in bed. You want to clean and disinfect their room, but you dont wantto overwhelm them with anything that has such a potent fragrance or odor that itwould make them uncomfortable, or irritate membranes or skin.
I would venture to say that most of us would like somethingthat is totally biodegradable, says Bjerke. Its not going to harm uswhen we get it on us, whether we use PPE or not, and that we can dispose of itsafely down our normal sewer system. If it comes in a concentrated form that wecan dilute, thats better. The ideal product would be something that is notcausing occupational exposure and damaging materials.
Truly, anything that will not corrode or be flammable ordangerous, destroying or deteriorating any of the surfaces that the agent isgoing to come into contact with would be the ideal, continues Bjerke. Plus,it takes care of the full spectrum of known and unknown microbes that weredealing with in a healthcare facility. From the vendors perspective, can weuse it in the acute care facility, but also in private practice? What I findwhen I consult and go into doctors offices or clinics whether theyredental or radiology, surgical or endoscopic, their cleaning procedures leave alot to be desired. And in many cases there is none behind the reception room. Soif you could get something that would be applicable in all of those areas wherebioburden is truly a risk factor, that would be very advantageous.
The road is not a short one, with many products taking as longas five years to be granted approval. The EPA and the FDA have jurisdiction overproduct approval. That is a real pain in the neck, says Braden. Low-leveldisinfectant sterilants are EPA registered and high level are FDA registered. Deciding between the two can be an issue, and its notreally straightforward. When they split up the jurisdictions, they basically claimedthat it wouldnt be a problem. Its a problem.
Lets say that we have a product thats used as ahigh-level disinfectant/ sterilant, continues Braden. We know that it alsocould work well for low-level stuff people would just as soon use that. Youcan not mention low level on your lable anywhere. You cannot even explain whatlow level disinfectants are. We originally included information about how todecide if you need a low-level or a high-level disinfectant in our insert. TheFDA made us take out all references to low-level, period. We couldnt even usethe word. They said that would be an EPA claim, just using the word. They seem to be jealously guarding their territory.
Theres a lot of toxicity testing thats involved not only toxicity relative to humans, but toxicity relative to the environment,says Martin Favero, PhD, director of clinical and scientific affairs, AdvancedSterilization Products. A lot of the constraints and standards that areextant today werent in existence 12 to15 years ago. There was a time when weliterally didnt have an EPA. No one really worried if you put a product downthe drain if it was going to kill some fish.
The way that the process goes is we submit whats calleda 510(k), continues Favero. These types of germicides are referred toas whats called a Class 2 device. The FDA says to be classified as ahigh-level, a disinfectant it needs to do A, B, C, D. We perform tests, andsubmit those data to the FDA for review. Quite often we meet with them before wesubmit, just so that we can introduce them to our protocols and so forth, andsee if they have suggestions.
You can get guidance from the FDA, says Medvick. Theywont tell you how to develop a product, but you can always ask genericquestions to see if youre on the right track. You have to be prettysophisticated to develop a product. Its not something that someone can do ina quick snap.
Once you have the idea of what you want to attack, you haveto look at what are considered active ingredients that the EPA and the FDAaccept as antimicrobial or antiseptic ingredients. Theyve got certainingredients that they know are germicidal. Youre going to use an ingredientthat has been identified as antimicrobial by either one of those two regulatorybodies. Then you have to make sure through feasibility studies, that when youcome up with a formula, youre going to test it for efficacy. Youre alsogoing to also do stability tests. Theres no point in bringing a product outthats only going to be stable for 24 hours. Youre also going to have to dosome safety testing even, for example, inhalation testing to make sure itsnot harmful. So, theres a whole process even before you get out there withthe final formula. Plus, once youve done all of these studies, youve gotto present them to the EPA for registration.
It was decided about 10 years ago was that the FDA wouldregulate sterilants, continues Medvick. A sterilant is something that willkill absolutely everything that we know of today. For example, bacterial sporessuch as anthrax that is the hardest thing to kill. Then you go to Micobacteriumtuberculosis. Then you have some viruses. Then you have fungi, then Staphylococcusaureus. The FDA regulates those sterilants used for surgical instrumentsthat are going to cut into a body. You want absolutely nothing on them.
The EPA regulates what we call disinfectants that we usefrom a concentrate, diluted with water, will kill Micobacterium tuberculosis,fungi, viruses, and Staphylococcus pseudomonas. Most disinfectants arenot sporicidal because they will not kill 100 percent of spores. Thats whyyou wouldnt use them for surgical instruments.
For products being reviewed by either the EPA or the FDA,criteria must be met, says Medvick. For example, lets discussdisinfectants and the EPA. If you say you have broad-spectrum activity, youvegot to show them test results done on bacteria, fungi, and viruses. The testingmethods have to be recognized by the EPA as standard testing methods. If you dont,how can you compare one companys product to another companys product? Youshow them the methods and the results. Also you have to show them any safetystudies you have done to prove that your new product is nontoxic to humans. Andstability testing is important, too. You have to go in front of the EPA anddefend your product: show that you knew exactly how it was tested. Its a veryrigorous process.
Not only are the testing methods important, but themicrobiology laboratories where you tested whether internal or external must be in compliance with Good Laboratory Practices (GLP). They willquestion you on calibration of your scales and your temperature controls,says Medvick. Everything is scrutinized. After all, neither amanufacturer nor the EPA wants to bring out a product thats going to putanybody at risk, because they are assuring the user of that product that if itsused correctly, according to the directions, the user will have a decontaminatedor disinfected surface.
As part of the development process, certain technical itemsmust be written and published. If you ever took a look at the label of adisinfectant, youll be there for two days you have to list everything,says Medvick. The EPA has strict regulations as to what should appear on alabel: the name and the registration number should be front and center so itsnot missed; all the activity against the different microorganisms, how you storeit safely, how you dispose of it safely, and also during the use of thedisinfectant, using personal protective equipment (PPE). Thats because yourearound potentially contaminated organic soils, but also, if its aconcentrate, some companies may have you wear protective equipment when youdilute it to protect your eyes. A concentrate can be very powerful, and you dontwant any splashing to occur.
Anything you need to know about a disinfectant can be found onthe label, especially the directions for use.
Thats what a lot of people have a hard timeunderstanding: if a company says one ounce per gallon, thats exactly what youshould use says Medvick. Im sure you know people who say, If oneounce is OK, then two ounces will be better. Thats so dangerous.
Every product must have a material safety data sheet (MSDS).This is required to list all hazardous ingredients contained in the finalformulation, says Medvick. The EPA has certain chemical levels that theydefine as hazardous. The MSDS is also used to define anything that may becarcinogenic. And obviously, most companies stay away from any of thoseingredients. But you may find that its necessary for a complete formula.
What Happens Tomorrow?
Is there a brand new germicide on the horizon, a new entitywhich will surpass the products of today? A lot of products come on themarket, but when you look at them theyre just reformulations, says Favero.Usually the only thing new about them is the marketing hyperbole that goesalong with it.
Bjerke agrees. When vendors come in with new andimproved, we want to know, really, is it? They cant release theformulation or the recipe as we say, because thats patented. What wehave experienced is that some of the manufacturers just slap on a new label thatsays New and Improved, and they have not changed formulations. If you lookclosely, the EPA number may not have changed, but the label did. The label maybe new and improved, but the contents are not. And then they can charge more forit. You have to be pretty astute when youre evaluating your products fromthat perspective.
Probably the biggest need is to come up with standards,says Favero. Everyone agrees that cleaning is a very important step, but howdo you know that? We have biological indicators and chemical indicators, but wedont have any clean indicators. There are some companies that are approachingthat, but basically what it comes down to with practice is visual inspection.Does it look clean? If the answer is yes, then they assume its clean. Butrelatively little is published in the literature on this. People are working onthis. Theres a committee for the Association for the Advancement of MedicalInstrumentation (AAMI) thats working on five or six methods. Some are easy todo, some are hard to do. None of them have caught on yet.
Im a strong advocate of objective productstandardization in the facility, no matter how big or how small you are saysBjerke. And this is an area that is not really touted a whole lot by any ofthe professional groups. When I see CDC mention subjective criteria, forselecting product, I have some real concerns about that. But thats allopinionated, and somebody ultimately has to make the decision, so what do theymake the decision on? The most yea votes, or the most reasonable? Many times itcomes down to financial decisions which is the cheaper that we can get,whether its the best investment for the dollar or not.