We have discussed in this module so far the laboratory network the way you consume which laboratories interact with each other and how they are complex with in a network with users of the laboratory we've talked about people who work in the laboratory and how they become. To have the experience education and training in order to be work their work there one of the main messages that I provided was that laboratories are regulated and not the personnel that work in them so while there are some states that require licensing of laboratory personnel there are a vast minority most states do not require this nor does there as there are any federal requirements that are specifically addressing what education somebody must have or what if they need any sort of examination or experience. There are very general guidelines these are all included in a large number of regulations that impact the pub public health laboratories as well as clinical laboratories. The foremost. Regulation that impacts public health laboratories is the clinical laboratory improvement amendments of the one nine hundred eighty eight also known as clear. Clearly it passed in eighty eight it was implemented in ninety two. It requires that laboratories have a quality assurance program that they have requirements for personnel and I'll go into some detail as to what these are and that they can also there are agencies that can. Approve certify a laboratory in place of the federal program the. Called deemed agencies so these deemed agencies have to be approved by the federal clear program and then they enter and have to have standards that meet or exceed those of clear but then they can go ahead and to be the. Laboratory certifier only the CLIA program can actually issue a license though but they do that on the recommendations of cap or other agencies that might come in and do the same level of assessment of laboratory quality. The F.D.A. is responsible for assuring. Food and cosmetics and drugs are safe. Under that category test kits that are used in laboratories and equipment are also regulated by the F.D.A. laboratories can be very hazardous places to work so there are special OSHA regulations for laboratories and finally especially important for public health laboratories is that we have if we are going to store or manipulate certain toxins in microbial agents there has to be an additional level of security safety scrutiny by the federal government to the select agent program is administered by the C.D.C. and the U.S.D.A. and the labs that kept any of these toxins or microbes have to also be are also regulated by those agencies the C.D.C. is not a laboratory regulating agency and the other way they offer guidelines they have technical support but they do not regulate laboratories they house part of the clear program that isn't in and buys every program an advisory committee to the CLIA program but they don't reg. Late. The CLIA program is in the Department of Health and Human Services organizationally there are regional offices that have responsibilities for several states and then within states there are often clear offices as part of the state regulatory infrastructure that will visit labs that are not deemed by another agency and are required to be inspected and I will explain to you which laboratories require inspection. So again the clean up pro. Regulations applies to all labs that perform testing of specimens of human origin for health assessment diagnosis monitoring or prevention of diseases the gap you can see right here is that it does not include any environmental specimens it does not include animal specimens it does not include surveillance testing so if you're doing some testing strictly for surveillance it does not come under Clio most laboratories public health laboratories have decided to implement a single very stringent quality approach a quality management system that will meet the requirements of clear and they also apply to tests that do not come under clearance purview. Again it's ministered by H.H.S.. C.M.S. Medicaid Medicare services and the collaboration with C.D.C. again is with the. The advisory committee. Washington in New York have their own regulations that meet or exceed CLIA and so they are able to have their own program that is not. That is not overseen. In by the regional or national Clio offices. The first thing to understand about CLIA is that it divides tests into the categories of complexity the first of the wave test these have been cleared by the F.D.A. They are simple and their risk for wrong results are supposed to be minimal for the patient however I do want to remind you that HIV testing there are waived HIV tests and certainly there are CD for tests that are in the regulatory pipeline so it's conceivable that someone could get an HIV test and Rapid City for testing go directly into treatment without any traditional laboratory testing and I would think that the impact for erroneous results in that situation actually is very high however due to a lot of other reasons it was determined that the HIV testing in the United States would be cleared these products. Secondly we have another category that are who are described as a moderately complex test these are tests that require some operator intervention they have more risk for. Incorrect results they require more stringent quality assurance programs the moderately complex tests include a category called provider perform my cross Skippy this category was specifically developed to allow public health clinics to do microscopy on sexually trans for sexually transmitted diseases so these are tests that can't be sent to a region or regional or a central laboratory so this enabled clinical clinic. Services to be provided in a doctor's office sort of clinical setting. Then the final category is high complexity these are. Tests that the F.D.A. has determined require a high level of testing personnel intervention and manipulation they require interpretation you can take a moderate or waive test and do any sort of manipulation on it and it now becomes a high complexity test so if you take a wave test that is approved for a capillaries stick. From a finger and you now use blood from the vein to do the test you change that test now from a wave category to a highly complex test see so when ever you make an intervention like that. And this also includes laboratory developed tests sometimes these are called homebrews a laboratory will purchase or develop the components of a test put them together if they are and there are certain regulations that require labeling of results that come from a laboratory developed oust So in summary three levels of complexity the levels of complexity are then going to determine how much regulation each site that is performing these test receives. So a site that only does wave tests this would be a doctor's office for example that I was only doing strap screens this would be a public health clinic where they're doing HIV testing pregnancy testing things like that all they have to do is follow the manufacturer's instructions they have no personnel requirements that means your lab assistant your office aide your receptionist could do this test there's no inspection except random select. Or if there's a complaint so randomly they're supposed to select a few thousand of these laboratories and then go in and inspect them but actually the resources are so so minimal that they don't really get around to doing as many as they predict they would be doing so if it's easy to do and the F.D.A. says it's it's waived there's no problems right you don't need to do anything else that's really not the case actually even wave tests even though they're simple to do should be done within a quality system the C.D.C.'s provider has developed a set of guidelines about how to assure quality of two of. Wave tests and these are easy to do they do require additional. Activity by the testing personnel other than just doing the results and turning them out so the question I would ask is So are they sensors so easy to use and there's no oversight can anything actually go wrong with them why do you need to do all this quality testing it's a waste of resources well in my experience of twenty two years of working in a public health laboratory we found many situations in which wave tests were being used in correctly interpreted incorrectly and being reported incorrectly so in fact they beings can go on with Wave tests and they most certainly do so there should be some sort of system in place in order to assure quality and this document by C.D.C. is a very good starting place if you have a laboratory within your agency that's doing a wave testing and you don't have a quality surance program check this resource out I also encourage anyone who's in that situation to talk to a pope public health laboratory for assistance in implementing a quality managed. System. So again the P.P.M. certificate these tests can only be done by physicians or mid-level practitioners or dentists and they can only do waive test and microscopic procedures both at P.P. and the wave test certificates are very inexpensive They just cost a little over one hundred dollars. Per fish and sea testing these are tests where you get an unknown specimen sent to you from an provider and you report the results back to that provider so these unknowns then your results are compared to others that receive those samples This is called proficiency testing sometimes called a quick external quality assurance. OK so that's a formal program you subscribe you pay a fee you send your results and they give you feedback you retain that documentation it's not required to be done in exactly that way but you must assure that quality has been documented so there are other ways to do that like you could have somebody retest a specimen. That somebody else had tested so retesting by a different operator you could have a specimen sent to another laboratory in exchange for results that way you're not using a perfect proficiency testing agency but there is some check on quality you should maintain the record so that any problems can be traced back and if quality control is required by the manufacturer and materials are available those then do need to be performed every day that the test is. Offered they there must be some way in which you have to manage the results This means that you have to have a formal process on taking that number off the instrument and getting it into the patients. Correctly with the development of Health Information Systems we are now seeing interfacing of those results directly into the patient's record that's a great way to avoid error but if you don't have that available then you have to have a log that includes the patient's name number. Health System number or something that identifies that patient and then the results then get attached to the appropriate record. And finally quality assurance for P.P.M. personnel competency must be documented this means that you do an initial training you check off and the person doing the training as well as the pre-trained easy both sign off that this person then House received that training they are observed or they're given a test unknown test specimens that they test and then the results are are compared to the expected result or they are observed or a combination of all these factors generally what we're going to do is one before or after training and then if they pass that they can start training or they can start performing testing they are again assessed at six months of testing and then yearly thereafter. Everything else comes under the non wave test category these have are actually inspected every two years surveyors come in they look at records they talk to the people that are doing the testing they look at education documents. They look at transcripts and diplomas they look at quality control results they look at temperature charts equipment everything that's involved in a quality see. System standard again they have proficiency testing done in non waiver high complexity testing you have to actually subscribe to one of these proficiency testing agencies that's been approved by the clear program the personnel requirements are more stringent and quality control must be done not only do you have to do quality control but you have to have evidence that when something is out of range that you've done something to correct the entire system so the quality system standards for high complexity laboratories are much more robust much more involved than at the other two levels. So what are the personnel requirements for a high complexity laboratory first is that you must identify a laboratory director the lab director can be a doctor with a board server certification in. Path ology so pathologist they can have they can be a physician with one year of lab training or two years of experience in the laboratory just being a doctor with two years of experience does not qualify someone to be a lab to Rector of. A high complexity CLIA laboratory or you can have a doctorate degree in an appropriate field like chemistry biology microbiology public health and have a board certification and again the certifying body must be approved by the CLIA program so I for example have a doctorate degree and a board certification and this is what enabled me to be a laboratory director. You must also identify a clinical consultant if the lab director is not an M.D. not a physician OK and they have. To be they have to be a physician and this physicians responsibility then is to review the test menu for appropriateness and the technology to make sure that it is the the right testing for the results that are intended you also have to have technical supervisors and these have people that have a bachelor's in science in one of the laboratory sciences and four years of experience now all the people who do testing have to have any of those requirements or have a bachelor's degree in any laboratory science or an associate's degree or a high school diploma and performing tests before nine hundred ninety five so what we see basically now because these people that were grandfathered in with associates and high school diplomas are now retry mostly retired is that most of the people that are identified now as laboratory personnel have a degree a bachelor's degree and some laboratory science you will see that they are not required to have a certification they are not required to be registered they are not required to have any experience they just have to have a bachelor's degree. So F.D.A. also is involved in the regulation of laboratories by way of them their responsibilities for. Approving in vitro diagnostics of these are called I V D's these devices are a subset of medical devices so they include all the things that we used in the laboratory test kits equipment and they are used for diagnosis management and treatment of people they come in three different categories class one two and three and these are put in these classes according to the risk of getting. A false positive result or a false negative result. Most things come in under class three that are used in the clinical laboratory. So in order to be approved as an F.D.A.. Approved F.D.A. approved test usually a document called a five a one K. is a submitted and this is determines if the test is equivalent to anything that's currently on the market if there is something equivalent on the market then the new product has to at least meet the standards of performance standards of that product. If a test comes in at one classification level and it's used for a long period and has no problems it can be down classified within a so these are the factors that they look at when they determine not just to whether or not it's approved but for what level of testing it's going to be approved at and by level I mean waived moderately complex or highly complex so what's the intended use what was a population in which. It was tested in order to in that population. Are these results are submitted to the F.D.A. in a package which are reviewed where do they intend to use this testing is it going to be done in a traditional laboratory by well trained competent personnel or is it going to be released to be performed by anyone in any setting. The So again you want to look at the performance compared to some reference standard this might be a test currently available on the market or it could be clinically diagnosed cases and from that you develop the performance characteristics and we'll spend a lot of time in this class talking about why. Performance characteristics are how they can be manipulated how they when they are useful and how they are useful and then even the clinical performance so the results of the tests they look at how well did it do in terms of identifying real cases and how were those results used in order to treat or monitor the patient. So products can be identified as F.D.A. cleared which means that they're just about like something that's already in the in the market it's got they have done market notification and they have a request for this clearance so the manufacturers ston those two things. An F.D.A. approved test is one that's already had an analysis of the data that was sent in for this premarket approval and it's been determined that it's safe and effective the analysis also is approved for high risk devices and it's more rigorous than the five A one K. so this you have to actually test out your product in the field and enter studies settings submit data and then have it analyzed by the F.D.A. lab tests that we put together these are called the homebrewed or lab developed test these are we buy components are we make components and they get. They get classified by F.D.A. as a lap and a light specific creations an A.S.R. And so any test that's done in this way is automatically a high complexity test any test that you change from that was once an F.D.A. approved test and you've changed it many. Way It now becomes an SAR So if I take my HIV test that was approved for plasma and I do it on serum it becomes an analyze specific reagent in A.S.R. tested becomes a homebrew or a lab develop test if I take a. Urine specimen and use that for a diagnosis of clue in rapid amplification test that becomes from it goes then I've changed the test so now it goes from being F.D.A. approved which was proof for say Bajan all or cervical swabs now I've changed by changing the specimen type and so now it becomes an A.S.R. what that means is that it's high complexity automatically the lab is not responsible for determining the performance characteristics so you have to go through a much more rigorous process of identifying how specific how sensitive a test is what the lower level of detection is once you've made that change all the things that are of import are provided in the to the F.D.A. and they're marked in their approval process you then have to do in your individual laboratories you cannot take results from another laboratory that that is doing the same changes you and use those in place of your own assessment you must do your own assessment. And finally all results have to be clear flagged as SARS which means that this tick and they have that's very specific that says this test is not F.D.A. approved its performance characteristics have not been determined by the F.D.A. but have been determined by the laboratory providing the results. So laboratories again have special. All regulations in terms of safety because of the type of workplace that they are they they represent they have training excuse me they have requirements for chemical hygiene of course laboratories have a lot of chemicals in them a lot of dangerous chemicals in them and so they have to have special there are OSHA has developed special rules for laboratories and these include training monitoring exposure of people to that work in the laboratory providing medical care providing personal protective equipment these are the gloves the lab coats. They shields and so forth that somebody would wear in order to prove put a barrier between them and the risk they also the laboratories must provide a list of hazardous chemicals that are used in that workplace and they have to have the material safe to safety data sheets available in case there is an accident with that product that that that is available to determine what risks and how to. How to treat or decontaminate someone if they've been exposed to that chemical. And then there are very specific hazards ways in which hazards must be labeled so many of these we see in any work site if you have white out or you have cleaners in your facility you also have to have a chemical hygiene plan it's just that the requirements for laboratories are much more robust. So blood borne pathogens again this is something that's commonly seen in all workplaces where there might be blood or body fluids so these are the same requirements that are that laboratories must meet as those required for other clinical settings. Clinics where patients are seen operating emergency patient care and. Those same blood borne pathogens must be addressed which means of course training they have to be employees have to be offered hepatitis B. vaccination and there must be an exposed exposure control plan and this includes exposing analyzing the risk of sharp exposure you have to have a way in which to investigate the incidence you have to provide engineering controls so an engineering control is different than a P. P. E. and that it provides a mechanical barrier between the employee and the work and example engineering control would be a bio safety cabinet it would be a lock that removes the sharp from the the needle and syringe. And there also has to be some availability of post-exposure treatment and wreck and standards for housekeeping. So labs also have to have bio safety will go into the different levels here later in the course but basically what happens in bio safety levels as we look at that health risk assessment determine what level of laboratory you're working at and then from there determine which engineering controls what ventilation access to limit access limitation. Bio safety cabinets what are necessary to work safely at that level you have to have proper policies and procedures in place for such things like spill cleanup you have to have documented records of training and post exposure and. Any accidents that occur all these things have to be documented and then in the laboratory we also have general laboratory safety because we have a lot of electrical equipment we have compressed gases elect. Coal fire trip fall ergonomics all these things are much more common in laboratories than they are in say an office setting because of the nature of the work and the type of equipment that are being performed there so there's a many many safety concerns that a laboratory administrator has to address so they have. They have multiple layers of regulation. So one other regulation and I bring this into. Show you this about smallpox virus being found in an insect on secure and i Lab This was even a F.D.A. laboratory so I wonder why they needed smallpox in an F.D.A. laboratory. When we haven't had vaccines approved for for many many decades but anyway they had it it was there from the fifty's it was found it was. Appropriately transported to the C.D.C. where it was secured by behind one of two labs that are in the world that are approved to contain stock cultures of smallpox virus. I bring this up because this illustrates how easy it is for very serious microbes to be accidents to occur with them or even people with ill intent to get them and to use them for harmful purposes. This is not an idle threat it is something that has been done and it is in this clearly illustrates that it can be done in the future either unintentionally or intentionally in response to these concerns particularly. The concerns about a foreign national from one of the states that were flagged as you know harboring known terrorist organizations ordered a stock strain of plague bacteria from an age. And see that is very reputable and has been in service for a long time they this person had no known research activity and was able still to order this and so as a response to that and what happened with anthrax in two thousand and one the federal Congress passed the. The select agent Act which is part of the U.S. Patriot Act these select agent rules then say if you have these any toxins or microbes you must be registered. So when you these registration programs are administered by C.D.C. and the U.S.D.A. they specify that if any facility stores uses transfers biological agents a specific list of these are toxins then they have to be registered. If you're registered facility you will be inspected and when you're inspected they will determine whether or not you have a facility that's secure can anybody wander into a laboratory where smallpox is hidden in the back of reserve or are things secured so that's prevented are the personnel suitable to work with the agents this is a real sticking point because it's very difficult almost impossible no one house a good tool that can determine whether somebody is suitable to be working with these agents the intent is is this person going to ferret these out. Somehow smuggle them out of the laboratory and then grown up in their basement to bump off and a neighbor they have a grudge against or even. Amplify them in great numbers and then distribute them in the subway systems so the intent here is making sure that the people who are using them are. Actually stable but again there is no tool that really can do this so it leaves the laboratories in a very impossible situation. They will come in and they will look at how you monitor your inventory they will count the number of vials that you say that you have of something and then they will recount them and make sure that you do indeed have that many They will look at their records to see who took what out when and why they again these inspections are occurring every other ivory third year and they are quite quite stringent. So laboratory administrators have other concerns so not just safety or select agents or even CLIA but they also have other. Quality concerns that are either quads I regulatory or at least recommended for example the C.L.S. I organization a nonprofit group that brings together experts on particular subjects to develop testing guidelines these are not regulated these are no will play in no way required whoever they are the standards of practice for the profession so if you're not using them you should your inspection may result in hard questions as to why you're not using them and they will make the results more comparable from one laboratory to another so it's very important that when these C.S.I. standards are guidelines are available that they're used. Iso is a international quality standards organization the World Health Organization quality system essential oils there that I showed you in the previous part of this lecture is based on these iso standards some laboratories are getting iso certification and they can do that in lieu of having one of the deemed agencies or KLIA this gives them more Internet. Ability to to make claims and statements about the quality of services that they provide the E.P.A. if water testing is being done in a laboratory specifically drinking water they have to be regulated they have to be inspected by a agency within the state and then of course as laboratories because they have a personally identifying information medical information about patients individuals they come under HIPAA requirements for training and providing security and then there's all those employment laws like E E O and A D A and union contracts that laboratories also must laboratory administers administrators must pay attention to so there's a lot of a lot of regulations that a clever Curren laboratories but I think it's also a little shocking when people realize how little regulation there is about the people who do the testing so clearly it is primarily what is used to regulate labs for clinical testing those human specimens the F.D.A. only approved tests as in vitro devices prior to marketing but in no way is F.D.A. approval sufficient to assure quality of a testing F.D.A. approval is very limited and once that test is out in the market it still has to be performed with in a quality system. Labs have unique safety concerns and because of that have robust programs for safety of their employees and they are very regulated but most of them are voluntarily going to be on the regulations in order to assume an order to assure quality of testing in safety. Thank you.