My name is John Ward and I just want to thank James and the teaching team Georgia Tech inventor labs for inviting me here known James for a couple of years now. I our company a technology consultants is an F.D.A. A. Medical device directive an international global regulatory affairs consultancy so we deal with all things on the regulatory side clinical affairs and quality management systems. And it's what they've asked me to present to you today are a high level view of the F.D.A. regulations and I know based on some of the presentations given this morning that if the A regulations specifically here in the US are going to apply to a lot of the companies here a lot of the teams but it may not apply to all of them so just sort of going into it with with that mindset. In the focus of this being a medical technology. Program we wanted to try to present to you some of the high level pieces of information that you're going to want to consider before your planning processes as they relate to F.D.A. and bringing your products to commercialization. Some of the objectives for today one discuss sort of the regulatory landscape what does it even look like what does F.D.A. look like who is the F.D.A. What do they regulate there's been some real brief discussions about that topic the F.D.A. being taken one of your customers one of the group said she wants to make sure you have early feedback from or at least knowledge gathering of what the requirements are going to be for your device as you're progressing through the commercialization process also we want to become familiar with some of the three. Risk classifications for medical devices and what some of the expectations are related to that nano were sort of pressed on time a little bit and based on hearing your presentations earlier I think we can gloss over some of the Class three. Regulations and topics because I don't think there's anybody in here that's operating in that realm and as James mentioned earlier today if you're going in the class three that's a whole nother ballgame than if you're just a class one or class two so we'll kind of glance over that I'll mention them but I won't spend too much time on that. Real briefly walk through I think we have one slide on what an F.D.A. inspection looks like because if you are in the regulated space and if the A is the governing body for medical devices in the United States plan on them coming to visit you at some point so we'll talk real briefly about what that inspection looks like because it can be a scary proposition and a topic to think about from a from you as a company or a news or as an organization. Also I've got a list of some of the regulatory hurdles some of the mistakes some of the concerns that I've seen over the years and we deal with between one hundred and one hundred fifty different companies on an annual basis so I've seen almost every possible way to do it wrong in every possible way to do it right so what I'm trying to relate to you very quickly are some of those lessons that I've learned and some of the things I've seen were small start up companies have made mistakes when dealing with the F.D.A. and try to get you to just grab on to some of that So as you go into your planning and your commercial commercialization process that you can be cognizant of some of those things and mistakes that other people make. And then. If there's time I've got a list of maybe six or seven things that are sort of currently trending at F.D.A. that they're showing a more intense focus on as it relates to medical devices. Only cover that if we've got time but just so you're aware I will be here for the rest of the today and most of tomorrow I'll probably just be sitting in the back which you can grab me between breaks if you have questions on F.D.A. And obviously if you have questions as we're going through this material please just pipe in and I don't mind an interactive environment. A few assumptions The first is that we've all heard of the Food and Drug Administration if you haven't heard of the Food and Drug Administration and you're developing a medical device it's time to get on board because you're going to need to know about them. Another assumption that F.D.A. regulations are going to apply to most if not all the companies here and after seeing the presentation I think that's still true applies to most I think I counted. Fourteen device companies and five or six sort of in the other categories so most of the companies represented here we do have some application of F.D.A.. In the scope of the discussion not some sort of limiting to medical devices and I V D's are in vitro diagnostics and I think half of the companies in here or maybe close to that are on the I.V. space some type of diagnostic. And there's an assumption that this is not an assumption this is the truth F.D.A. doesn't care how big you are they don't care if you're one guy one gal or a company that's got ten thousand employees like G.E. they just don't care the regulations apply or they don't if they apply if he is going to treat you the same way as it would any other company. Topics for. In regards to the regulatory landscape just going to cover sort of F.D.A. organization from a real high level devise classifications in those expectations related to them and then some of the different. Submissions that you may make or applications you will make to F.D.A. for your devices. Now the F.D.A. is part of the U.S. Department of Health and Human Services F.D.A. as a whole has about fifteen thousand employees. And this is a list of all the things that they regulate. We're going to focus in on the medical devices but just so you're aware that they regulate everything and I heard this quote or read in a magazine somewhere that at the bottom we've heard that laughter is the best medicine so beginning Monday we're going to regulate it. Probably not true a little facetious but if you could box up laughter and make a medical claim about it just what if they would regulate it. And. Who's F.D.A. who are we dealing with here so on the previous slide we looked at a long list of types of products that if to regulate specifically for medical devices we're dealing with the center of devices and Radiological Health so we use the acronym CD or H. and they regulate entities and maybe an individual it may be a company it may be a university it depends on what that university's involvement is or that individual or that company. They can. Be many factures contract manufacturers specification developers and specification developers by definition according to F.E.M.A. is actually a manufacturer whether they make it themselves or not the rules for mania factures apply across the board to. All these different types of entities. Well you'll also be dealing with the Office of device evaluation or this is the group that will review your pre-market applications. And then we also have the Office of compliance compliance one of their primary roles is enforcement so F.D.A. is investigators our law enforcement officers they will show you their badge when they walk into your office and say Hello I'm from the F.D.A. here are my credentials and they are law enforcement officers and you should treat them as such. Disrespecting an officer of the law is not a good thing to do so think about that when you welcome them into your organization. The office of the in vitro diagnostics that's for all the I.V. D.'s all the diagnostics there are several of you here today that represent that space so you'll be dealing with the Office of in vitro diagnostics and then the Office of regulatory affairs they are the group that coordinates with Office of compliance to do the regulatory inspections enforcement. And actually writing the policies the main a jean the inspection process they have. Five regional offices and twenty. More district offices so you're guys are located in the southeast region there's office in here in Atlanta there's one near Orlando and Maitland in New Orleans and there's one in San Juan Puerto Rico so that's sort of that southeast region and then you have a district offices that you you're going to deal with directly and those district offices are the ones that are going to send the inspectors to you or to your companies to do the inspections. And there has been recently some efforts on F.D.A. part to be more transparent so you have the Office of devices. Valuation that's going to review your five ten K. applications or your PM ase or review your. Clinical trial programs and they've recently been very focused on having transparency between the guys that are evaluating new device applications and the ones that are actually out in the field. Seeing what's going on inside of companies historically they didn't talk too much but there has been a more prevalence to where they're talking during pre-market reviews they will go and look at warning letters they will look at forty three observations they will look at the recalls for a company that's making an application and they will talk to each other to see what's going on so that's something just to be thinking about obviously where you guys are now well some of us think of actually commercialize your products but. Where you guys are now sort of in this customer discovery realm. You don't have to worry too much about F.D.A. coming in but start planning on and expecting that they're going to come pay you a visit at some point and these are the groups is a part of the organization that you'll be dealing with. So the next item on the regulatory landscape is device classification. So for F.D.A. We've got three classes class one is the lowest risk. And example being magnifying spectacles I see a few people out here that have spectacles on. Those are typically going to be a class one device so there's less stringency there's less regulatory oversight there are fewer requirements for class one devices. Then we have class two devices which there are moderate risk how many people here have contact lenses. Quite a few Those are medical devices as well those are class two medical devices there are some contact lenses that are actually Class three devices depending on their indications. Use And then we have class three devices an example sort of carry on that and that ocular space are. Lenses which are lenses that are are molded and then. Implanted behind the eye so they're much higher risk then a daily wear contact lens that you may take out or just put on the surface of the ideas are actually implanted behind the eye to. Usually macular degeneration and other types of patients the question. So F.D.A. has already defined that so they so it's typically risk to the patient is from a high level that's what if he is looking at the question was How do you determine what's what's that threshold What's that risk that sort of pushes it over there there is not a fine line for F.D.A. what they do is they define for every single type of device there is a product code and along with that product code goes the definition of what that device does or is so if the A's got something like seventeen hundred eight hundred different product codes so we'll talk a little bit about how do I figure out what mine is a little bit later on so that might that might sort of address your your question there. So we'll get into different types of submissions you'll have and we'll talk. Circle back to the device classifications in a minute but I want to sort of give you a high level view of what are the different types of pre-market submissions that that may be required for your device and after hearing your presentations it's going to apply to most of them. At least those that are regulated by F.D.A. So there is a now has a priest submission program which in my experience has been very very very beneficial. So what they've encouraged is starting a communication. Opportunities with industry and F.D.A. So if you know you have a class three device and I know I have to do a five ten K. but there are certain elements of my submission that aren't clear to me at this point then F.D.A. wants to open up a dialogue with you and start talking through some of those things that you have concerns with or that you think F.D.A. might have concerns with so you will. You do your actual formal application for that pre-market clearance for pre-market approval you'll have already tried to address some of those early concerns and I'm really embracing this the last few years and it's been fantastic for our different clients that have sort of unique technologies but that aren't entirely outside the realm of what's already on the market Yes QUESTION. That's similar to her question there there isn't a line F.D.A. is pre-determined based on their risk analysis that this type of device based on its written risks present that is either going to be a class one the class two or class three. Yes And F.D.A. is behind F.D.A. is behind the times. If the is behind in time so one thing that you can do if you do sort of get in that space where it's not clear is you can do a petition for classification where you say OK Mr F.D.A. This is my device these are the claims I want to make Where is that ball that's called a five thirteen G. It's a quest for classification so if it's not clear based on the eight hundred product codes that already exist then you submit the F.D.A. and say this is what I have you tell me where falls. There is some risk in doing that because now you're obligated to go into that classification and that product is that if the tells you. But it's the main factor is responsibility not if the A's The term what that is if you determine based on your design and development that it's going to fall into this cat. Gauri and that's the regulatory strategy that you don't Poyet then you need to be able to defend that. So the question is what what happens if you misclassify if they will come and pay you a visit and very nicely ask you to do one of a few things they may say stop shipping that because it's an adulterated product they may say recall all of that because that's an adulterated product. They may say because it's a lower risk device and there's not much issue of patient safety they may say stop shipping and file a five ten K. or just file a five ten K. there's several options and most likely regardless of what they tell you you're probably going to get a warning letter because that's not a good thing when we miss classifier devices that's why I mentioned earlier make sure you do some priest submission work if it's if you can fit it into your plan and get that early feedback from of us. Soon as you can there's there's no fee associated with the pre submission packages but what you want to have is you know at least a device description instructions for use you know a defined clinical application. A testing play and what do you plan to do as far as testing from a performance standpoint or from you know from biological standpoint or from a clinical standpoint depending on the type of device if you're going to do a trial or something like that bring that protocol to the table and have them review it. Now now the. The risk you. Have to balance is if you don't have all that stuff finalized the new changes after you get F.D.A. is recommendations you have to just consider how that might play in and you can have an iterative process with the F.D.A. and they may ask you for additional information you may have to go back and forth a little bit. OK. Yes maybe I should just stop the presentation and we'll just have questions. Its use about a thirty day process to set up a meeting and so what F.D.A. will do is you'll send a package of request a meeting I can either be face to face but it's usually over a conference call. And they will respond back to you formally to answer your questions so it's not just a throat over the wall here's this information tell me what you think you have to ask specific questions and if they will address those specific questions and then you have a call to discuss the responses. OK. One of the most common types of pre-market applications is a five ten K. submission is called a pre-market notification it will apply to most Class two devices in some class one devices. There's several different types of five ten K.'s I won't go into that entire process for each one of them just due to limitations of time I do want to address the the bottom three points there though if the A did employee in two thousand and of two thousand and twelve starting in two thousand and thirteen a refused to accept policy so they in order to create efficiencies on there and have put in a a a fifteen day early review process where they're looking at your application from an administrative perspective do you have all the information there and they have about one hundred paid only seventy five page guidance document on that refused to accept policy. Make note of that in your planning in as you're putting your applications together to to review that refused to accept to make sure that we are adequately addressing if the is concerns because what happens is if you don't get through that refused to accept a time frame guess what they refuse to accept it they'll send it back to you and say OK you got to fix this or do that you didn't send the protocols your labeling is wrong you know things like that so they look at it from an administrative perspective before it ever gets to substantial to review and what happens in that substantiated review process is they will look at your entire application with the ultimate goal what you're trying to do here is say my device is substantially equivalent to something that's already on the market. That's why I say everything is not awesome we've heard the term thing Julie said wicked cool technology. That they might be wicked cool but you don't want to tell if the A that especially with the five think a process. Six minutes. We're trying to establish substantially quick once you want to show that is as good at least as good from a safety perspective on a performance perspective than a device that's already on the market and. One of my pet peeves F.D.A. does not approve five ten ks that's like this lovely emblem here if he clears five thousand kids they're giving you clearance to market your device based on its substantial equivalence to something already on the market on the Class three side which will sort of skip over here F.D.A. only approves drugs and pre-market approval applications of drugs and class three devices they do not approve five ten ks you see that all the time in marketing materials F.D.A. approved are five things they know they didn't they are authorized. Unclear due to market that product they did not approve it for anything. All they did is say yep I agree with you that your device is substantially equivalent to one that's already on the market. That. They're looking at clinical safety at that point they're approving a either a drug for its clinical safety in Africa C. or a device for its clinical safety never can see. Through what. That's true F.D.A. cares. They will call they they can call you if you say I have a press release. F.D.A. approved such and such a device you will get a letter potentially and if the A that says we did not approve anything for you we are cleared your device from market under five think a so it is somewhat of a semantic thing but. Please don't approach and if the A reviewer in say anything about approving a five think a because they just don't do it that's that's just one of those things that drives me nuts and I've seen it a couple of times in the presentations we're going to prove something. They didn't approve of I think a yes or. No. Right yeah baby cups are going to most are going to be you know the man you know the manual ones are glass to require five think you know your pulse ox class to devise unless you market it only for sports and aviation. Yes. Agree that I agree with that. So on these sort of how do we determine what our classification is F.D.A. has is really nice database where you can plug in keywords related to your device and they will pull up all the different types of product codes that may be related to it so earlier. We did i glasses or magnifying spectacles if you just typing glasses in this search you'll come up with three. One sunglasses one are magnifying spectacles and one's another one so using your keyword search is going to be very helpful and figuring out what product code and what classification my device is going to fall and. I'm going to scoot on over. So when you plug in your keywords and you find this list of medical devices and product codes you'll see something like this will show up when you select them so this is the one for the magnifying spectacles utilized in a fire the product code the submission type and in this case it says five think exempt so that means I don't have to submit something to five to two to F.D.A. It's device classification is one. But here's something I want you to notice the question about G.M.P. exams. The answer here is no so I often get asked what is G M P G M P is good manufacturing practices this is quality systems related activity so having management controls design controls corrective action process controls and process validations things like that so what this is saying is even though it's a class one device it doesn't require a five ten K. It is not exempt from the quality system requirements that's one of the big mistakes class one companies make is they say I got class one I assume I don't have to have a quality system is simply not the case you have to look at this product. And make that you know determination and there are a very few that say G.M.P. exempt Yes So there's very few companies out there that F.D.A. is not going to regulate. It will skip on this is another example of a class two this is our contact lens so we can see where in this case the submission type it does say five ten K. It says a class two device. And G.M.P. exempt and no I have pointed an arrow there to. The total loss product lifecycle report that's very important when you start looking at identifying your predicate devices so when you do a five to in case of mission we talked about having establishing substantially equivalence that means you're comparing to a device that already has a five think a so when you're selecting your five ten K. your predicate device make sure you review that that total product lifecycle report because you don't want to be using something that's had one hundred adverse events in the last year and it's been recalled three times over the last five years because if you're going to say mine substantially equivalent to that. Guess what if it is not going to be too impressed. This is another database that F.D.A. has for searching the five ten ks to help you find your predicate devices again you can use a keyword search you can look by the company name if you know the five ten K. number for that device you can use that to help pull up all the the devices that are possible for pro to get this. If you're not getting paid for it right. You know that's a good point you won't find that out here in the F.D.A. database but. That's a good point absolutely next couple slides around class threes since I'm already out of time on a skip over those real quick on the F.D.A. inspection process so there's several types of inspections most are considered the routine inspections there are directed inspections and there are premarket approval inspections and what happens is basically if the like I mention the comments that they usually will pre-announce as well you'll find out about five days ahead that they're coming they're coming whether you're there or not so make sure someone is available they'll present their credentials and say I am so and so from F.T. I'm here to perform your inspection Here's a form forty two which gives them authorization to come in it's essentially like a warrant that they have authorization from from the F.D.A. to come in and perform an inspection. I mentioned some of those G M P's those quality system areas they're going to look at management controls design controls corrective action system and process controls virtually every time they come in so that's when I mentioned making sure you have a quality system things plain and in sort of geared up at this point in time start thinking about what processes I'm I going to employ and how can I write procedures and review the F.D.A. regulations related to those at the end of the inspection the issue is called a Form forty three which is a list of observations or deficiency is that they have identified in your quality system and from that you have fifteen days to respond to the district often and say OK these issues thank you for pointing them out here's what I'm going to do to fix them if you can fix them in the fifteen days fix them and send the evidence otherwise present a plan to F.D.A.. Outlining how you're going to address those deficiencies. Do we have a couple minutes are we two minutes thank you. Let me just run through some of these. Things. Common mistakes and hurdles that I've seen companies assume because their have a class one device that they don't have to follow G M P's are good manufacturing practices that is a bad idea make sure that you review that classification that we looked at and if it is if it's G.M.P. example you're good to go this is G M P exempt no make sure you have a quality system failing to establish design controls for class one devices that are software so most class one devices are exempt from design controls However if you have software you automatically have to have full blown design controls whether or not you have to submit a five ten K. that's a big mistake a lot of companies make. Making the assumption that if they will not come and visit you if your class one device if he is pushing this right now they just released the guidance document down classifying about one hundred plus different devices from class to class one well guess what Along with that they're also now inspecting class one device manufacturers to make sure that they actually are class one devices and I've seen that four times in the last three months clients of mine that are class one of the it came to visit just to see if they're truly class one. Failing to adequately review your marketing claims so that sort of goes along with the F.D.A. They're somewhat cynical and don't trust anybody so you prove to me that as a class one device to review your marketing claims and by marketing claims I'm talking about your literature your website. Any brochures and things like that things you talk about it conferences all that sort of thing F.D.A. will look at before they come and visit and make sure that still lines up with the class one regulations and of time. One question. About whether. Homebrews No I mean I know about home brewing beer but that's a different question I think that well more. So draft draft guidances or just that the most of the time if the aide does utilize them somewhat as gospel. So F.D.A. is pushing towards one maybe two. Predicate devices in the past people were sending five Thing case missions and having six or seven predicted devices you're trying to establish substantial equivalents to a device that's already marketed OK. I have my contact information at the end of this presentation so I think you're going to upload that I'll e-mail it to you. But I'll still be around if you're actually what you do yes you're right. He can you follow up with that person we really want to get this right anyway thanks for joining. Us.