In 2010, two companies learned their vaccines for a childhood infection (rotavirus) had another virus present: porcine circovirus. Both companies couldn't detect the virus lurking in a key material used for vaccine manufacture, and it went undetected until an academic lab discovered with new technology.
Virologist and Vaccine Developer Dick Hesse from Kansas State University joins me and Diane to discuss vaccine contamination. We are also joined by Julia Schaar with Medgene Labs (https://www.medgenelabs.com/) a local livestock vaccine developer to share best practices for preventing product contamination.
In 2010, two companies learned their vaccines for a childhood infection (rotavirus) had another virus present: porcine circovirus. Both companies couldn't detect the virus lurking in a key material used for vaccine manufacture, and it went undetected until an academic lab discovered with new technology.
Virologist and Vaccine Developer Dick Hesse from Kansas State University joins me and Diane to discuss vaccine contamination. We are also joined by Julia Schaar with Medgene Labs (https://www.medgenelabs.com/) a local livestock vaccine developer to share best practices for preventing product contamination.
Hi, I'm Aaron Harmon.
Diane Cox:And I'm Diane Cox
Aaron Harmon:Welcome to Inside Out quality both fan and I build an implement quality systems in the biotech and medical device industry. But we often get asked, Is this really necessary that we know if we are doing too much too early? Or do we even need a quality system?
Diane Cox:Our goal is to explore questions like these through real life events and experiences shared by our guests from various regulated industries. We will show you why quality is not just about compliance and how when it's done right, it can help your product and company improve lives and make a difference.
Aaron Harmon:A paper published in the Journal of virology in 2010 exposed a complex problem for the FDA and vaccine manufacturers. The problem was a pig virus called porcine circovirus one or PCV. One, this widespread virus doesn't appear to cause disease in pigs. However, in the mid 1990s, a new strain of PCB was found that caused wasting and poor growth and mortality in weaning piglets. Researchers named this virus PCB to for porcine circovirus to the paper in 2010. Didn't report anything new about these viruses in terms of disease, or pigs, but instead, it was where they were found in children's vaccines. Rotarix in particular which was used to protect kids against rotavirus infections. On March 22. The FDA immediately recommended Rotarix is used to be suspended. Anyways, there was another vaccine in the market for childhood rotavirus called rota tech. Polling researchers looked hard enough, it was announced on May 6, that they discovered the virus in there as well. These vaccines had been in the market since 2006. In 2008, they have been through extensive safety tests and into millions of children without issues, Rotavirus on the other hand caused more than 200,000 Er trips annually before vaccines became available in the US and globally kills 450,000 children under the age of five annually. Based on the information and expert meetings, the FDA chose to allow the vaccines to remain on the market. Merck and GSK went to work removing the contaminants. How does this happen? And how can companies reduce the chances of a complicated product recall? Once products have reached the market? These are the questions of this episode. And with us to help answer them is Dr. DE Kesey. Dr. hesi, can you tell us how you got into neurology? I know you get quite a history.
Dick Hesse:So yeah, with a college I got graduated with major and biology and minors and chemistry and teaching. And my last two years of college I worked full time at a packing house. And when I when it came time to graduate, I discovered that I would take about a $5,000 cut in salary to from being a meat cutter to being a teacher, and sighs already married and had one kid, I decided that probably wasn't a very good thing to do. I remember some of my childhood heroes, and one of those was Walter Reed. And I thought, Wow, I wonder if the army has something for me since I already have my degree. I looked into it and lo and behold, they did. The program was called oh one H 20. And I went down and actually signed up for the program to take a qualifying test. I took it and asked with flying colors. And then a month later I found myself at Fort Detrick, Maryland at the United States Army Medical Research Institute of Infectious Diseases and smartest thing I ever did. I knew that I was going into the virology section. Um, I got to work with Dr. Pete darling. And we worked on really, really interesting diseases and stuff, colitis viruses, Eastern Western Venezuelan, and then eventually I graduated to the BSL four agents, where I worked with predominant Lassa fever virus in the spacesuits and the training I got in the army for virology was absolutely wonderful. From there, I went on and finished my master's degree and PhD and that's how it all started is
Aaron Harmon:I told they and your story about getting your your suit punctured.
Dick Hesse:Yeah, that's a really interesting time. You know, we're working on on Lhasa, and we had a roomful of hot monkeys about I don't know, probably 20 monkeys. And I was connecting and disconnecting from airlines into the spacesuit. And I I pulled the one and also my spacesuit went flat. And I looked down, there was a probably eight inch tear in my space. And once again with a roomful of hot monkeys that we had just challenged. Actually, they were infectious at that point some, some were clinical. And, you know, at that point, I was pissed off, I went back through the chemical shower, and then through the regular shower. And I have you ever read the hot zone? Yep. Yeah. So that's where I used to work. And yeah, I ended up a recent hell with our NCIC, the sergeant command, and he said, specialist, so he's staying right where you're at. They called the commander of the Institute, and all the division chiefs. And a half hour later, I met with him all they sent me back to the to Lhasa land. And about a half hour after that, they escorted me to the slammer. And I spent the next two weeks in isolation with under lock and key, bulletproof break proof glass windows? Yeah, they're waiting to see if I'd live or die. There was no real therapy, no virus or anything at that point in time. Fortunately, nothing happened. But yes, Tom real life?
Aaron Harmon:Yeah, I love how they sent you back to work first go?
Dick Hesse:Well, you know, they have the gray portion of last land in the hot portion. So I was in the gray portion. That way, you know, I was contained this one it was, yeah, special clearance in order to get in there. Only a few people could do it. So that's a way of containing. Interesting story.
Aaron Harmon:So in the case of Rotarix and murder tech, they ended up with this PCV, one and two contamination. Contamination occur in vaccines like this,
Dick Hesse:well, using biological components in the cell, called fetal calf serum or calf serum or serum of some type, often has adventitious agents in it. And I've been to stage and is whatever happened to be present in one of the animals that this biological sample can cool the biological component things better. Obviously, serum you use that to grow cell cultures, as a critical ingredient, fetal calcium, in particular, has quite a number of different adventitious agents that come along with it, and some of these infected calves are bled, they don't know that they're in low numbers. In the case of the circovirus, it wasn't probably wasn't so much serum, but the trypsin that was probably contaminated with certain virus one, and or circovirus. Two. And, you know, these viruses get into animals as part of their, their normal environment, they become infected, if they're having to be harvested, their tissues are harvested for preparation of cell cultures, propagation of cell cultures, whatever the case is, then, of interest agents show up. And over time, they become amplified in normal biological application. And that's where they come from.
Diane Cox:Are these contaminants obvious? So, you know, for example, how did PCV make it to the market without detection?
Dick Hesse:So a lot of them are not at all that they don't generate? First of all, if you're not looking forward, you're not going to find it. Um, if the virus in question happens to be a non cytopathic virus, or a mildly cytopathic virus, or has a cytopathic characteristics similar to and here I'm being a little bit cautious similar to the vaccine virus, it would be masked. Now, having said that, you should be running negative control cultures, that's a negative, but some of them don't say negative all the time, or it could be a delayed delayed growth pattern. If it's a low level contaminant. Now, they're only going to hold the cultures for a period of time. And if it's a slow grower, then it can be growing in the culture and not show up. But in the case of certain viruses, they really are a pathogenic as far as causing cytopathic effect in the cells that the human vaccine was growing. In this particular case. You're not gonna be Animal vaccines, because a lot of these super viruses get into multiple cell cultures and coffin girl. So this isn't a problem of human vaccines, or animal vaccines is generally all that. And it can be chicken viruses, circle viruses, cattle viruses, there are just quite a number of viruses out there that will grow in multiple cell cultures. And that's where they come
Diane Cox:from. You had mentioned, you know, negative controls, and you mentioned, the timing that some of these viruses might take to show. Right, and I'm wondering, I guess, are there other other ways to identify these contaminants?
Dick Hesse:Well, the classical method, yeah, has been cell culture, does it cause cytopathic? CPE. Yeah, there's a lot of other ways to do it. And, you know, we thought we're doing a fine job when we're using fluorescent antibody testing, and labeling antibodies against viruses X, Y, or Z with a, with a fluorescent tag, and then looking for the presence of these non psychopathic buyers in the cell cultures, and that, you know, usually works good, but that's directed test. If you happen to have a non psychopathic virus, that you don't know is there and you don't have the proper antibody with a fluorescent tag on it, you're gonna miss it. This is a period of many, many, many years, where, you know, the testing has evolved and has improved all the time. In the case of the rotavirus, human rotavirus vaccines that were contaminated, they picked that up with Pyro sequencing. And then also McG hybridization with both fire sequencing, next generation sequencing. And the the pan microarrays, they're detecting nucleic acid and the test sample. And the nice thing about those is, they're, in both cases, they're specific for nucleic acid, but a given class of viral nucleic acid from a given pathogen. And it works because you know, it, it'll pick up a spare, very sensitive, pick up a small amount of nucleic acid and give a positive signal. Those are directed tests, where you have a specific target that's embedded, or one that's cross reactive. And that'll give you hints as to what you're dealing with, if you get a positive signal, probably better techniques that are out there right now as next generation sequencing. And basically, that sequences everything amplifies and sequences everything in a given sample. And then you get the nucleotide readouts, and it assembles everything. And that's, that's by far the best procedure that we won't be using nowadays.
Diane Cox:Are these methods part of traditional development now for vaccines, whether it's anti human?
Dick Hesse:Yes or no? So, once again, on the human side, the 21 CFR, I don't know exactly what the rules and regulations are on the nine CFR side, they are starting to be. And the reason I'm saying that is a number of vaccine contaminants that have shown up in say, the modified live DVD vaccines, went through the standard testing, and they went through and pass with flying colors. But wild type, pathogenic wild type virus was still present in the in actually the master seed. And if they would have been using next generation sequencing, they would have got a whole bunch of sequences, they would have been able to align, and shown that there were actually two very, very closely related viruses, but one had a, a gap in sequence. And then they, you know, look at that, and actually figure out that there's a different virus there that shouldn't be there. And then from that, they could have figured out what was going on. The other part of that is we had evidence from the field that this particular vaccine was causing disease in capital and at a much greater rate than what would have been expected. When you vaccinate a stress cattle and won't be all the way through the diagnostic lab. We applied a modern diagnostic techniques to it. And we certainly can figure it out. The other thing that's nice about next generation sequencing is if you do find a pathogen present or a unexpected virus present in the sample, you can you already get sequence from that particular procedure. You can pick out conserved areas, do alignments with other viruses in that same category, that same class of viruses. You can pick out consistent areas, or unique areas of the genome, and then develop PCRs, which are even more sensitive, and the next gen sequencing. So did that answer that a little bit? Yeah, next gen sequencing is wonderful. But it's not the end all be all. Because there's a lot of contaminating nucleic acid. Like I said, it amplifies everything. And if the contaminating viruses present in the lesser amount than what the other nucleic acid does, let you know that you're trying to help by then you'll miss it, or only get a partial reads on it.
Aaron Harmon:Now we'll take a quick break to hear from one of our sponsors.
Unknown:Today's startups become tomorrow's growth engines. In South Dakota, we're entering a new stage of expansion for our biotech industry, and you'll want to be part of it. Hi, I'm Tony Johnson, Executive Director of South Dakota biotech, where the state affiliate of the International bio organization and we're proud to be leading a state that's driving innovation to feed, fuel and heal the world. South Dakota biotech is here to inform, to connect, and to advocate for our critical industry. Whether you're directly involved in biotechnology, or looking to learn more about it, we want to hear from you. Find us at www that stdio.org. Now, back to the show.
Aaron Harmon:Dr. Hesse, could you explain for us how a vaccine manufacturer would make a vaccine similar to the rotavirus vaccines?
Dick Hesse:Yeah, there are many different vaccines out there. And we're talking about traditional vaccines in that traditional in the fact that these competent viruses are grown in cell cultures. So viruses need cells in order to live and replicate. So what you do for any vaccine and any traditional vaccine production system, especially the modified Live Once you find a cell culture that the virus likes to grow in you, through a variety of testing will purify the virus and purify the cell line. And then you'll inoculate the virus into the cell line. And the virus will grow and you harvest the virus from the infected cells. And if it's going to be a killed vaccine, you'll kill it and throw an adjuvant in after it's been concentrated with the right antigenic mass immunogenic mass and with some modified live, you will dilute it to the proper titer are the proper amount of live virus and then put it in a stabilizer. It's usually a sugar protein mixture and then freeze dry it. And then at the time of vaccination, you would rehydrate the modified live and inject that into the animal or if it's a world vaccine heated to a morally in the case of the kill vaccines. They are killed and then mixed with an adjuvant something that will stimulate an immune response. Those two are mixed together and then at the time of injection, or at the time of vaccination, that adjuvant virus killed virus mixture are injected into animals or by animals, so people or animals too. So I mean, that's that's, you know, the 50,000 view of vaccines have traditionally produced vaccines anymore. There's a variety of other ways of doing it where you take a portion of the viral genome that is causing disease, say Coronavirus, let's talk Coronavirus. The spike protein on the outside of the virion there's a little spike. That's why they're called Kronos and they're all the way around. That happens to be the point of attachment for the virus to the cells of the animal, the human or pig or cow or whatever. And it attaches to The either the respiratory epithelium or say enterocytes. And you make antibodies to that spike protein that attaches to the cell, that the virus would, in fact, in the case of disease, well, the antibodies are against that attachment point, in this case, the spike protein. When they come in contact with the virus, they'll actually bind to it and prevent the virus the the wild type virus from attaching to the cell and infecting it. So that's basically how vaccines tend to work. You can do that antibody against a spike by having a conventional vaccine. Or you can actually take the viral the portion of the viral genome that codes for the spike protein, and insert that into an expression vector of some kind. If they're another virus or a bacteria were many different ways of doing yeas the just a lot of different ways to do it. And then generate lots of that spike protein and harvest that and include that as a vaccine, the even another way of doing it, and that's what some of the COVID vaccines are this the mRNA, where they'll actually take in mRNA, that from a virus and that portion of it, and that will code for the spike protein. And they can actually inject messenger RNA into an individual. And if they get everything right, as far as concentrations and sites of replication uptake into the cells is probably a better way of saying that, then it will produce that spike protein, and then the body will generate an immune response to that.
Aaron Harmon:So it sounds like there's a there's a number of different ways to make vaccines. And you know, with that there's probably other examples where some of those materials could have had contaminants, other other cases of contaminated vaccines that you've heard of, oh, yeah, a lot
Dick Hesse:on the human side, as well as on on the animal side. So the first one that I ever became aware of was back in the days when I was in the army at Fort Dietrich, and we, you know, I used to work with a lot of the Arvo viruses, yellow fever, Eastern Western, Eastern equine encephalomyelitis, as those vaccines were traditionally made, some of them were modified live they so the yellow fever was, or the sample and supplies versus Eastern Western V, they were all killed. There. Well, Eastern western world V is still alive. But they were drawn in chick embryo fibroblasts. And the one that my boss told me about was the yellow fever vaccine. And that was a very, very effective vaccine was a modified live. Yeah, it was really stopped yellow fever in its tracks. And if you're working the tropics, you want to make sure that you had it. But when they started looking closer, they found that it was contaminated with avian leukosis virus. And avian leukosis was from the chick cells, that the yellow fever virus strain was grown. They knew it was there. But in order to clean it up, they would have to basically abolish that vaccine that have proven efficacy, and proven safety. And there was no good evidence that avian leukosis was causing any problems at all. So at that point in time, they had made a decision that just leave well enough alone. And we'll keep the vaccine imperfect as it is, in its existing form and and move on from there. And that was back in the 70s. When I first learned about that, since that point in time, there's been you know, a number of other different vaccine contaminants that have shown up on the human side and on the animal side, mainly on the animal side that I'm aware of. And some don't cause any problems at all some real major problems. So there's not you know, in a perfect world, there would not be any contaminants present. But in the end In perfect world, if there is a contaminant present, and it doesn't cause a problem, and the vaccine itself is really beneficial, then you leave that particular generation of vaccine alone and then move on to the next one.
Diane Cox:So given that there are issues where there's contamination that do cause problems, I guess what advice would you offer manufacturers developing products where the contamination could be an issue?
Dick Hesse:Yeah, so in here, I'll speak on on the nine CFR on the animal vaccines, that's what I have the most experience with. So obviously, all the Masters sell stocks, the master seeds that are used to produce vaccines, they have a working range, and that's x through x plus five. And you can only make vaccine through those five passes a master See, they're always checked, and at the beginning of the end, and to make sure that everything's clean. And once that happens, then you make the assumption that And historically, with the assumption has been that they're going to be good. There won't be reversion to virulence, or, you know, everything will be stable, other advantageous stages didn't show up during that initial testing. So you make the assumption that that master seed is clean. But while you're doing that, you're passing it in cells. And the cell cultures themselves the master cell stock that's also been tested for habitus agents, and then you usually freeze down master lots of that master cell stock. And you have usually 20 passes historically 20 Working passages that you can make vaccine from. And the assumption is all the ingredients that go into it have been tested according to nine CFR, and they're all shown to be free of contaminants. Well, that isn't always the case. And sometimes, some of the working stocks of viruses at the x plus three or x plus four level, they're grown in higher passage production cells that have a contaminant that don't show up. And even though the initial master seed testing was good, 20 years ago, different lots of biological materials trypsin or fetal calf serum have been used and have been introduced and contaminants can come in under under those conditions. And then yeah, then at that point, it's contaminated. It's really compounded and the vaccine I'm thinking of right here happened to be was a five way bovine respiratory disease vaccine and the bovine respiratory syncytial virus working stock at the x plus three level turns out to be contaminated with a Bvd, a non cytopathic Bvd virus. And all the other the IVR is real clean the Bvd stocks were clean DVD, one DVD to the PI three was clean. But the RSV was contaminated with a non cytopathic Bvd. So that, you know that turned out to be a really bad and contaminating. problem that costs basically cost the company millions and millions of dollars, and the abolishment of that particular vaccine strain, which in its earlier passages was quite beneficial but efficacious
Aaron Harmon:early, hard work to make sure everything is clean, will pay off in the long run.
Dick Hesse:Well, early hard work, that's a requirement that's absolutely required before the government will allow these vaccines to be produced. They have to be shown to be free of adventitious agents to the best of that ability. But my advice to the companies is don't rest on your laurels and don't rely on old fashioned nine CFR or 21 CFR testing for adventitious agents using the traditional methods the indirect resin antibody testing or you know, appearance of cell culture or things like that. And always look on the materials that you buy the raw materials don't look for just the presence in a single passage of that, that component of the cell culture system, look for multiple passes, and look for and use modern technology. deep sequencing, next generation sequencing, same thing, use some of those techniques at path one and then pass it, you know, 510 15 times and see if there's any amplification in the signal. And if there is, then you know that you've got a contaminant present, and it's infectious Bvd most cell cultures most live, while most cell cultures, like fetal calf serum, but Bvd is present in almost every single lot of fetal calf serum that you'll ever see. The solution for that is to, quote kill the Bvd that's present in the fetal calf serum lots. I don't know if people are aware, but they collect slunk calves in the packing houses and they suck the blood out of them out of the slump calves that are coming down the chute. And that's what they they use for fetal cows calf serum that goes into cell culture. There are in utero infected calves. In these lats virtually every lot will have some. And that's what the source of the virus, what has been done in the past is they'll inactivate the fetal calf serum with either gamma radiation or beta probe lactone treatment to kill adventitious agents in the serum. And that seems to be a possible solution for this, of the problem with that, that philosophy that killing with gamma radiation or BPL inactivation is the level of contamination. Most of these techniques were are 99.999% effective. And that sounds really good, doesn't it? 99.999. That's killing everything, right? Well, that's actually five logs, contamination, and some of these fetuses can be upwards of 10, logs, 10, logs, base 10. So if you kill five logs of that base, 1010 Block material, you still have 100,000 virus particles that haven't been touched. So when you do the math, if there's a lot of contaminating virus present in a lot, you know, you're not going to get it off,
Aaron Harmon:and some will sneak through.
Dick Hesse:And the other part of that, if you don't get it all, but you got most of it, some of these lots, you know, as well, 1000 leaders, well over the course of 1000 leaders growing in cell culture, one or two particles get out and they're amplified in a cell culture system, and you keep propagating those cells, eventually, it'll break out. Most people just don't realize the math behind that the geometric expansion of the viruses that's occurring. So even though you think it's, you know, just really, really good, it might not be as good as you think. So all that just what I wanted to say is test the early passage stuff, but make sure you test the later passage stuff, and use the modern technology used next gen sequencing, deep sequencing, so you can pick up anything and everything that's there. Once you have a hint that something there, obviously go with PCRs. They will, they're even more sensitive, quite, quite a bit more sensitive, and you can amplify contaminants out and clearly show what what's there but adding an even greater level of sensitivity. But things change, and of the nucleic acid changed minor changes in the genome, then your PCR might not work anywhere anymore. And that's why I like to use a method a specific methodology, such as PCR and the whole pick up you know, a given region of a genome versus the nonspecific, like next generation that picks up everything and amplifies from there.
Aaron Harmon:Are you seeing companies take a more preventive approach to contamination like using ingredients that are not animal origin?
Dick Hesse:The short answer is yes they are. And usually plant origins, what they're trying to look at. And that works for some things. Some of the key key ingredients we used to have a media interview that was developed they call them Benji media. It was ironic because the person who developed it was a vegetarian. One sobered everyone into being vegan, including his cell cultures or the cell cultures. The interesting thing like as these mammalian cells didn't always like, the veggie media and some of their characteristics dramatically changed as far as your ability to support virus replication, let's say started switching out some of these media components, animal origin components for plant origin components. So there are attempts to do it, but they don't always work. Or sometimes they even work better. One thing that we found with big media is we could take acreage and dependent cells and start growing in the presence of veggie media and all of a sudden, they became anchorage independent. And that really lends itself to growing large, large batches of cells in bioreactors.
Diane Cox:I'm not sure if this is relevant, or if we should include it. But I just out of curiosity, I'm wondering if there are other contaminants during the manufacturing process, maybe not related to the actual components of the vaccine, but
Dick Hesse:there there, there certainly are. And, you know, those, those traditional ones usually get picked up downstream before a final release. So a lot of times mold will show up. You know, one of the biggest ingredients that's in almost all the veterinary vaccines is thimerosal Mercury compounds. And that's really good for keeping bacteria and mold down. The problem is, you know what, with the autism thing, and blaming autism with five Marisol with mercury, they tried to get that out of the vaccines. Well, when they did that, they found all these little contaminants that were showing up that were being suppressed by the thimerosal again, raw ash and cotton Ryan Korean, but in the vaccine containing material that was needed for further manufacturing.
Aaron Harmon:If you look at government requirements, whether it be USDA or FDA, there are a number of things raw material that you use, and it has to have specifications, and you have to have the testing that you do of it. And you have to look at risks of those components. So if I'm using FBS, I have to be aware that there could be contaminants, and I plan to how I'm going to test for that. And if I do that, and follow those requirements, and do it well, and even integrate new technology as it becomes available, then I can prevent having to, at some time later in the future, possibly recall my product, or have to do a lot of rework because of the contamination,
Dick Hesse:right. Medieval? Yep, the rework that goes exactly with the question that you just asked, we had a really expensive horse vaccine to make. And at one point, it showed up with a contaminant, external contaminant that was, you know, after after each component was grown up, and then put together into a final vaccine. Then the contaminant showed up in the I think it was a mold or something. Well, they because it was so expensive. The manager of the plant said rework it, and kill it, make sure it doesn't show up, but make sure that it passes all the potency tests. So they did rework it. It did. They killed the contaminants and it passed all the potency tests. But that was illegal. They went ahead and pushed it through and then somebody blew the whistle on and it ended up costing half of middle management at that particular company, their jobs and rightfully so. Because they they reluctantly were stiff arm into doing something that was illegal, but they're not welcome, Robin. Well, we
Aaron Harmon:had Doug and Robert on the first episode, so yeah,
Dick Hesse:yeah, well done. Robert and my best friend so.
Aaron Harmon:Yeah, I heard a lot of stories about you from Doug.
Dick Hesse:Which one you remember the most
Aaron Harmon:the sandwich?
Dick Hesse:Yeah, that's funny.
Aaron Harmon:So the set from what from what I've heard of the sandwich story, and made sandwiches for a fishing trip. You're both on the boat. It was
Dick Hesse:coming
Aaron Harmon:A dog takes a bite and thought it was not that good. So he threw it overboard.
Dick Hesse:It have mayonnaise in it. Well, Doug didn't bring a lunch and I did. So I shared my lunch with him. And he doesn't like mayonnaise. He took a bite. And then, you know, next thing I see is the sandwich I gave him by me, and I'm
Diane Cox:perfectly good soon.
Aaron Harmon:Well, thanks a lot.
Dick Hesse:Well, have a great day. And we'll talk to you later. You too. Thank
Aaron Harmon:you so much. That was great talking with Dick. But with a say we also have Julia Shar from med gene. They're a local company, and doing a lot of great work in vaccines. Welcome to the show, Julia.
Julia Schaar:Thank you very much.
Aaron Harmon:We have heard a lot of great things about messaging. Can you tell the listeners about your company,
Julia Schaar:Medgene Labs is a company in Brookings, South Dakota is where we're based, we are licensed to manufacture and sell animal biologics. We help veterinarians and animal producers protect their livestock by using precisely constructed immunological products and services. So what that means, essentially, is that we work very closely with a veterinarian, and we work very closely with the producer, to provide them with products to help improve their immunological programs, so that we make sure that we get out to the field to help those producers only use what is required in their herds. So we don't want to sell them or insist that they use a bunch of product that really they're not seeing disease pressure from.
Diane Cox:So we heard today about something going wrong in a few vaccines, but so many vaccines get it right, what contributes to med gene success in the vaccine space,
Julia Schaar:it comes down to our company's mission. It is our mission to provide the immunological solutions designed with the attention to the precision, sound technology and to science. So we work to ensure that those products that we produce are needed to protect those animals. And again, lower the production cost for the producers. We work to build those relationships with herd health teams provide solutions with what is needed and do not require the producers, like I mentioned earlier to put products into their herds that are not needed.
Aaron Harmon:So in the traditional vaccine world with animal health, I'm used to large multivalent vaccines where it is this vaccine goes every animal, yeah, but they're getting a lot of antigens that may not be relevant to their herd,
Julia Schaar:right. So if they're in those types of situations where they are commercially licensed products, you're stuck with what what is already in that product. So you may not have that disease pressure from a specific outside force, so to speak, or an outside disease pressure. So we don't want to have to have those animals be forced to use that that type of system in their herd health, where we are much more focused based on what really the problem is to help them get control over those disease pressures.
Aaron Harmon:So in the story with Rotateq and Rotarix vaccines, there was the contamination that kind of snuck through there any tips that you've learned, kind of in your role to help or for listeners on how to prevent contamination, their products, our best
Julia Schaar:approach to making sure that our quality assurance program is sound, is that we ensure that we use very trusted services and very trusted sources. So that's where really where we start, we know that we need to put out a good solid product out into the field, we know that we have to put out a product that has our name written on it. So we're not going to jeopardize our inputs on our products, without ensuring that the inputs come from a trusted, valuable source. So that's really where we start. We make sure that everything that we use in our product is is backed up, we have had several meetings, working internally with our QA department to ensure that we have specific levels met that we have outlined very definitively what the requirements are for those inputs before we'll allow them into our production scheme.
Aaron Harmon:That sounds like a very sort of looking for robust, systematic,
Julia Schaar:very, it's, it takes a lot of effort, a lot of work on the front side of it, it takes a lot of time, a lot of patience to get it right. But once we get it right, we know that what we're putting out into that into the field into those animals we're very confident in and the other thing that I'd like to encourage our listeners to not be afraid to do is to rely on. Other experts rely on the people who have experienced some of these hiccups, so to speak or have really hard, solid, good quality assurance programs rely on those People who have gone through the process to make sure that they can pick up some tips and tricks. But I
Aaron Harmon:made the the comment that it sounds very systematic that sounds they kind of the approaching medical devices. So we work off of specifications and knowing that if I'm going to have this component in my device, I have these specifications that I need from the supplier. Yep. And when it comes in, I can test it back to those specifications and ensure that what's coming in is what I need. And then it's going to work. Right? That sounds like that's exactly what you guys are doing as well.
Julia Schaar:Absolutely. The other thing that we have a very robust system on is any recall scenarios, we've tried to think through what that recall scenario would look like in the event that something happens, where we need to check and validate our information that's come back from those producers. And that's exactly what we have done is we've worked really hard on the forefront to ensure that everything is in order, and everything is black and white, because once we get those situations in whether it be a recall, or even just some questions back from from the user, we are very solid, and we know exactly where something has come, we know exactly that we'll be able to pinpoint what where something may have may have fallen, fallen short,
Diane Cox:it's interesting not not a lot of companies will kind of do that, that forefront thinking about where the product will end up, they kind of just are assuming there aren't going to be these problems or you know, of course, they they had these kind of rosy glasses when they're going to lunch that everything's fine. And we don't expect complaints we don't expect to recall. And then, you know, when one does happen, then it's kind of the scramble, right that they have to go through. So really, really important to prepare for those types of events.
Aaron Harmon:In the case, these two vaccines, throat or ex murder Tech, I think it would be kind of hard to for see this contamination, because at the time, there wasn't some of the tools in place that we have now. But what I think helped those vaccines stay in the market. And they were effective, despite having the contamination is that they had gone through all the safety trials. So I do I wouldn't be surprised if we see something similar to this happen again. But that is why there's all the safety trials that go in and all the work showing that the benefit outweighs the risk. Absolutely.
Julia Schaar:And I think part of moving forward, what's going to be helpful and beneficial is having those open conversations and not trying to hide behind a wall trying to hide behind the the what happens if or what could we have done? Or why shouldn't we have or let's not talk about that. I think that when it comes to internal quality assurance, having those conversations with everybody involved is making sure that it's not a finger pointing exercise, it is one of those situations where this happened, we could not have done anything in the forefront to prevent it. Let's talk about it. Let's address it. And let's make sure that that what we have done today, we can ensure it doesn't happen again in the future, learn from
Diane Cox:your mistakes. Or others I should say learn from other mistakes.
Aaron Harmon:I will add that it for medical devices for pharmaceuticals. In the GMP space, you're required to test all material coming in, if it's going to go into product has to be some kind of test and it may be a CMA, depending on the risk level of that item coming in. And it may go all the way down to very detailed analysis of what it is and what other contaminants could be in there. There's been the two recent or recent cases with the FDA have recalls on I should say that there have been the recent cases in the drug space of blood pressure medication, where there was a change that happened at a supplier. And the result of that was the introduction of a carcinogen. And the FDA had to go down the same thought pattern of do we pull this off the market because of the risk of cancer. And if we do that we take away someone's medication from regulating blood pressure. And they ended up leaving those on the market while the companies went to resolve the problem with the carcinogen getting introduced. But similar scenario just on the drugs fed. Sure.
Julia Schaar:Yeah, it's it's really interesting from our perspective, where we're a little bit different because we're governed by the USDA versus the FDA. So things are a little different for us from a GMP requirement from what we are required to do to get product out the door where everything has to meet specific specifications prior to us being able to release it, tying down our processes tying down our areas and our systems and our facilities. But there really isn't a lot of hard structure on all of these books. cuts that we have to fill that the CVB puts out. So are from the USDA, they don't they don't give you your 45 pages of these are exactly what you have to do. So we kind of, we do what we have to do to make sure that we can put out the best product where where we have some of the flexibility to ensure that our systems are are put in appropriately.
Aaron Harmon:I think that's the right approach. If you have the end product, and your goal is the best product for your customers, then that should lead all the activities up to it. Absolutely.
Julia Schaar:No, no, and that's, you know, imagenes new, I think I was just thinking about this on the way down, we've been licensed our facility has been licensed, I think for almost two and a half years going on three years. So we're new, and a lot of the people that we have employed with med gene today don't have hundreds of years of cumulative experience producing animal vaccines. So we're, it's it's fun, because it's it's exciting. And it's something new and it's something to really approach from a non standard thought process. How can we make things that were how can we make the vaccines that we're sending out the door as good as they can be? And yet having some of the new technology, some of the new innovative pieces that are out there that we can utilize till it's kind of fun.
Aaron Harmon:Well, thank you for being with us today.
Julia Schaar:Thank you very much. This was this was awesome, and I appreciate the opportunity.
Aaron Harmon:And for those listening out there. Thank you for joining us, and we look forward to making more episodes and hopefully you will enjoy it also.
Diane Cox:We hope you enjoyed this episode. This was brought to you thanks to South Dakota biotech Association. If you have a story you'd like us to explore and share, let us know by visiting www.sd bio.org.
Aaron Harmon:Other resources for quality include the University of South Dakota is biomedical engineering department where you can find courses on quality systems, regulatory affairs, and medical product development. Also, if you live in the Sioux Falls area, check out quit a local Quality Assurance Professionals Network. You can find out more about pivot by clicking on the link on our website to Diane and I would like to thank several people but a few who stand out or Nate peple for his support with audio mixing Barbara Durrell, Christian or support with graphics design and web. And lastly, the support from South Dakota bio