Beyond the label: extra-label drug use and food safety - Part 1

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00:01:00: This is going to include some discussions about what's on label versus extra-label product use.

00:01:06: We'll talk a bit about compounded products, their role in antimicrobial stewardship and What does zero really mean?

00:01:13: In terms of withdrawal times Joining me to discuss this topic I have with today Dr Patricia Dowling.

00:01:20: Doctor Dowling as a professor emeritus at the Western College of Veterinary Medicine And in fact i was once a student of doctor dowlings way back when when she was teaching clinical pharmacology to me.

00:01:32: I did pass her class, i'm not sure if...I don't think I was at the top of the class though.

00:01:37: welcome Trisha!

00:01:39: Thank you very much and very happy to join you today.

00:01:42: Why didn't tell us a little bit about yourself?

00:01:43: Well

00:01:44: Sure Tim..i am an original space brat.

00:01:47: So there was sort of a New York, New Mexico, Maryland Texas journey.

00:01:51: My father actually ran the machine shop that built The Lunar Modules and we used to do things as kids like drive the lunar rover around the shop and things like that.

00:02:00: so Sorta finish growing up in Houston, Texas And then had an intense love of animals.

00:02:06: who is an original horse girl?

00:02:08: Then went off to Texas A&M where I got a BS in animal science and started cleaning stalls at the vet hospital and fell in love totally with veterinary medicine.

00:02:20: So then I graduated from Texas A&M in nineteen eighty seven, And i did want to specialize in large animals and felt like I didn't quite know enough.

00:02:29: so applied for an internship and so moved off to North Carolina State University for a year .And I wanted go on into residency but they didnt get selected right away.

00:02:39: ,so I practiced here in Cleveland Ohio for another year, and then I did get accepted for residency in large animal internal medicine at Auburn University.

00:02:51: And so while i was doing that they said that I had to get a master's degree in something... and Auburn was kind of noted for bovine therogenology!

00:03:01: ...and I decided that wasn't really what I was interested in.... and they said well..I could do a masters in other areas as long it you know is concentrated.

00:03:12: And at that time, the College of Veterinary Clinical Pharmacology was forming.

00:03:16: They didn't have enough diplomats to just have pharmacology residency.

00:03:21: so they said we could do it while doing another residency.

00:03:24: So I went over and found the head of department in pharmacology.

00:03:28: He thought this is a great idea To have clinician who understood drug therapy you know recognize the disease and treat it appropriately because certainly we do see a lot of inappropriate drug use out there.

00:03:41: So that's what I did, i did a master's degree with him and we had a school of pharmacy there at Auburn.

00:03:46: so that was very helpful for classes...so I did a pharmacokinetic study with ciprofloxacin in ponies ...and then when I finished up I needed a job!

00:03:54: And uh horse and cow doctors were kind of a dime-a-dozen.

00:03:58: I'm down in the States, but clinical pharmacologists were quite rare.

00:04:02: And so the position had opened up at The Western College of Veterinary Medicine and i thought well why not apply?

00:04:07: They flew me up there!

00:04:09: I was like ooh Canada cool what's with the colored

00:04:12: money?!

00:04:14: But anyway uh they offered me the job.

00:04:17: So came for a short time and I married a local guy.

00:04:20: Thirty-one years later, I'm still in Canada and...

00:04:23: It's great to have you on here today.

00:04:25: Again i always seem to learn something new!

00:04:27: I did not know about the lunar rover there as part of your family history.

00:04:31: Well let's get started talking about our topic today.

00:04:35: You are kind of really an expert because you're one of the founding members of CGFerrad.

00:04:43: Can you give us a brief rundown what CGFERRAD is?

00:04:49: All right, so the original idea was from The United States which of course is where I'm from and So I had made use Of the service of the food animal residue avoidance data bank.

00:05:00: So that's the US name of it.

00:05:02: And when i came to Canada they would let me call down there for information on withdrawal times For questions That Came To Me.

00:05:12: but then in two thousand one we were all at a meeting and They Said okay We want the other countries to get their own ferrads and they had an idea of having a global network of ferrad centers that could share information.

00:05:26: Unfortunately, that global network didn't work out so well except for us.

00:05:30: we've been the shining success.

00:05:44: Part of the fun is that, of course we're bilingual in Canada.

00:05:48: So global food animal residue avoidance data bank don't give you those same letters.

00:05:53: and Canada.

00:05:54: so to be politically correct We're sort of just a CG Farad and we don't spell it out Right but that's really what it stands for.

00:06:04: So in two thousand and two with the help of Dr.

00:06:07: Tim Blackwell from Guelph, we went after some federal money And we got enough to start this database.

00:06:13: so it's been an operation since the year.

00:06:16: two thousand into

00:06:17: Excellent!

00:06:18: And what is your purpose behind CGFARID?

00:06:21: What are you really... Your main kind of roles involved in industry?

00:06:26: then?

00:06:27: It really is centered on extra-label drug use by food animal veterinarians.

00:06:32: And so Dr.

00:06:34: Steve Sunloff in the United States, who founded The US Ferrad.

00:06:38: he looked at issues and production animal medicine and realized that there's not enough approved on-label claims for our use of drugs that veterinarians to practice quality medicine have to use drugs in an extra label manner.

00:06:54: but when you look a product That's based on the label dose and the label condition, The label pathogen if it is an antibiotic.

00:07:07: And veterinarians while we give you a really good education Tim You have to remember lot of things.

00:07:13: Figuring out drug residue withdrawal times Is pretty specialized set Of knowledge factors.

00:07:21: So he came up with idea having this database that Practitioners could contact and ask for such guidance To make sure that we keep the human food supply safe.

00:07:32: That's our number one goal, is that we don't want anything dangerous going out there.

00:07:38: and then because Food Animal Products are tested different degrees, different amounts differences between countries whatever but still Food Animal products are tested to ensure that antibiotic and other drug residues Don't enter the food supply We wanna Keep Our Colleagues Veterinarians and then the producers themselves out of trouble from residue violations.

00:08:01: So that's also part of the mission,

00:08:04: And in more

00:08:05: recent years we've been asked to play an increasing role promoting antibiotic stewardship.

00:08:10: We do this because probably by far and away The number one type request is for withdrawal time information For the use of extra-label antibiotics.

00:08:25: provide a withdrawal recommendation will also make some comments on such antibiotic use.

00:08:32: And if we find that it's not valid, It's not substantiated by science We will heavily refuse to give a recommendation and for some of the commodity groups products won't go to slaughter For the animal or market them for products like milk If we won't give a Recommendation.

00:08:50: so we do have a little bit of a stick that we can use if we think that drug use is irrational.

00:08:56: And so I'm board certified in large animal and turtle medicine, how products can be tested to ensure that they're safe.

00:09:25: Right, some of the other things you've kind of come around with as well I think in probably more recent years is even looking at doing studies depletion studies to try and establish some guidelines or even some withdrawal times for different medications too?

00:09:42: Is that right?

00:09:43: Yes!

00:09:44: And that's another very big part.

00:09:46: our service so the database containing data back is very searchable, we created it that way.

00:09:56: And so I basically can click a button and say what are they using in the cows in Quebec last week?

00:10:03: Inter-Mammary.

00:10:04: Yeah

00:10:05: right.

00:10:05: It pops up The Answer!

00:10:07: We publish reports every year on our website where look at different drug uses by the different commodity groups and then we also look at it by like disease condition or whatever condition is being treated in an extra-label manner.

00:10:23: And that allows us to identify drug use, maybe nobody had realized was an issue...and the very first one was the use of fennbendazol in turkeys!

00:10:34: And sort of no body has noticed there's a lot of extra label use of Fennbendsal in Turkeys?

00:10:39: There really wasn't any good withdrawal information.

00:10:42: So that eventually led us to do a study and then eventually lead to withdrawal, official label withdraw times for the product.

00:10:51: If you look at our studies.

00:10:53: when we post the PDFs of them on their website they look a little weird because they bounce around but there are all started with questions in the CGFARAD.

00:11:03: so Rodenticide Residues & Pigs.

00:11:07: We'll talk about Dexamethasone Study beef and dairy cattle.

00:11:13: So that's kind of fun, we can give directly back to our colleagues in the industries by answering these kinds of questions because of research expertise.

00:11:24: Right!

00:11:25: Because when there is an information available but you see a need for it...you have this opportunity here which is great.

00:11:35: We should probably define maybe a little bit for our listeners, I'm sure the vets that are listening would know this.

00:11:41: but can you define it?

00:11:43: You already mentioned extra label use what.

00:11:46: how do we define that really?

00:11:47: from specific regulatory perspective?

00:11:50: i guess

00:11:51: okay.

00:11:51: so unlabeled use merely means an approved veterinary drug label directions.

00:12:00: So first thing you do is, look at the label and want to look for a DIN number.

00:12:05: Drug Identification Number That tells that it's an approved veterinary drug And then read the label directions.

00:12:12: It'll say something about species and dose and duration of treatment If its food producing animal there has information on withdrawal times for meat milk eggs whatever.

00:12:25: so extra labeled drugs use includes a lot of different things.

00:12:29: It could be using an approved veterinary drug, but you're using it in way not explicitly stated on the label.

00:12:37: so your doubling the dose.

00:12:39: You are giving more doses.

00:12:41: we see that often with intramamory products and cattle treating a bison instead of a cow.

00:12:50: Treating a goat, it may be a different indication.

00:12:54: so especially nowadays when the drug gets approved they're very specific on the label.

00:13:02: So for example a BRD drug bovine respiratory disease drug May say its for treating manheimia but doesn't specifically say treating mycoplasma bovis

00:13:15: Right?

00:13:16: So if you are treating the case of mycoplasma bovis, You're technically going extra label because it's not on that label product.

00:13:23: Right Yeah definitely The new labels Are a lot more specific when I look at More recently approved products.

00:13:31: Oh yeah If we look at an old penicillin Label It basically says for anything That might be sensitive to Penicillins.

00:13:38: But now you won't get that claim Unless you can prove that its effective For that specific bacteria or disease condition.

00:13:47: And

00:13:47: that's where again, that founding philosophy was that veterinarians to practice good medicine have to go extra label.

00:13:54: Right we need to have that available as just be able to treat the things that were treating.

00:14:01: Now in food animal medicine it is not common as a small animal or companion Animal Medicine.

00:14:06: but any drug approved for human use But not veterinary use Is considered Extra Label including over-the counter products.

00:14:15: And that one usually sort of kind of catches my students off guard.

00:14:19: That technically, if a veterinarian tells the client to go down to the drugstore and pick an over-the counter product and use it its extra label actually requires a prescription.

00:14:32: but nobody seems ever enforced that one.

00:14:34: But we should keep track of that.

00:14:37: in any case.

00:14:38: food animals It's our responsibility to make withdrawal guidance, give good withdrawal guidance for that.

00:14:45: Right because we have the responsibility to ensure providing a safe product.

00:14:51: at the end of this I always remember these animals wind up in food chains.

00:14:56: so...

00:14:57: Exactly!

00:14:58: And then one area thats really big is combination of separate approved drugs and same batch feed.

00:15:06: So In United States under their law, it's illegal to use drugs extra label and feed.

00:15:14: And so any of their combination products are approved that way.

00:15:18: in Canada we don't have as big a market for the products and there hasn't been the financial incentive to go ahead and get these combinations on the labels.

00:15:29: So but we don' t have a lot prohibiting that especially in poultry and swine.

00:15:35: this is very common makes up a great deal of the request to this service.

00:15:41: Again, kind of make sense especially when we think about how commonly these kinds of combination treatments are done—especially in those class of animals?

00:15:49: So we've been talking about withdrawal times —how do we establish withdraw time for drug?

00:15:56: There's number steps into coming-up with a withdrawal time.

00:15:59: that is going be on the approved labeling and so just some considerations will go.

00:16:07: is the inherent safety of a drug for human consumption.

00:16:11: So, if we look at some products like keto-profen that's approved for use in cattle and swine or horses... Keto-prophen is also a human drug!

00:16:20: That will tell us right off the hop it won't have really long withdrawal times because it already has safe drugs.

00:16:28: so residues aren't going to be as much an issue.

00:16:31: On other hand there are issues with safety concerns.

00:16:36: Totrazorol would be one.

00:16:38: There's lots of active metabolites, they're long-lasting.

00:16:41: that's going to get more stringent and conservative with drawl times on the label.

00:16:46: so... They do this thing where they come up with an acceptable daily intake.

00:16:50: So how much should we take to choke a rat or do some other lab animal species?

00:16:56: Do these toxicology studies then figure out How you could eat daily over lifetime And not have any appreciable health risk?

00:17:06: So that's the ADI.

00:17:08: Then they take The ADI and look at what people eat, And They Look At Consumer Consumption Factors.

00:17:18: This is where it gets really different between countries.

00:17:21: You've got to realize That their very conservative here.

00:17:24: so... They look a maximum amount of drug that can end up in meat, liver, kidney milk & eggs.

00:17:32: And they kind of come up with this sort a total, and we laugh because an MRL meal believes that we drink a liter-and-a half of milk every day.

00:17:45: And I think it's... Oh off the top of my head!

00:17:47: ...I think at six hundred grams of meat.

00:17:50: It also includes liver & kidney.

00:17:54: I know what those organs do and i'm not eating them, but there are people who like liver steak and kidney pie.

00:18:03: Right yeah.

00:18:04: And then an egg and I don't even eat an egg every day.

00:18:07: So students often ask questions well What about ethnic groups that you know?

00:18:12: Eat this or that Or whatever?

00:18:13: it's like man.

00:18:14: This is just so conservative.

00:18:16: You're right off the bat that those are not real concerns, but you will see differences between The countries and Canadians or thought to eat more meat and drink more milk than Americans

00:18:27: So oftentimes.

00:18:28: That's why we see those longer withdrawal times compared to sometimes the same product in the US

00:18:33: Exactly And so kind of wonder.

00:18:36: well, you know the Americans have a shorter withdrawal time.

00:18:38: Does that mean it's not as safe?

00:18:40: It's like.

00:18:40: no these are just very very conservative.

00:18:45: finding evidence of real human harm from drug residues in food animal products, it's really hard to find.

00:18:52: It is hard to document but its' really hard.

00:18:55: any real evidence

00:18:56: for sure?

00:18:58: you know on a daily basis I'm not worried about my lunch killing me.

00:19:02: i got other things to worry about

00:19:04: right.

00:19:05: yeah.

00:19:06: so we talk the these maximum residue limits.

00:19:09: then as far drug or byproduct, I guess of those drugs as well.

00:19:18: Those are for approved products and on label.

00:19:23: what happens in an extra-label situation?

00:19:26: Or when we're using an unapproved product?

00:19:29: So that's where it gets complicated.

00:19:31: so When that MRL is established pharmaceutical companies want to have an approved product.

00:19:37: They have to go back to the veterinary Drugs Directorate And show residue depletion studies when their products are going to have residues that drop below the target, maximum residue limit at the MRL.

00:19:52: So this is a target for Canadian Food Inspection Agency in an approved drug species and they publish those MRLs.

00:20:01: so these are easily found on the Veterinary Drugs Directorate website.

00:20:06: The problem if it's being used as an extra label manner especially with different species.

00:20:12: You know, when a product is tested at the plant or whatever they don't know.

00:20:16: you used it for different indication.

00:20:18: But that different indication may impact the withdrawal time because of effected... The animals health was affected.

00:20:26: So um That's what happens When you have an approved drug your target as the MRL For extra labeled drug use especially in a species from whom its not approve.

00:20:35: There are no MRLs.

00:20:37: So that's where the target becomes zero, which we'll talk about as a moving target.

00:20:43: But basically it's the limit of detection of the assay from the Canadian Food Inspection Agency.

00:20:49: Right?

00:20:49: The test that were using to assess those levels in meat or milk or egg whatever product you're talking about right... Exactly!

00:20:59: If look at something like ivermectin that is approved for use in cattle And I'm just going to pull numbers out of my head, but for the injectable it might be like thirty-five days and that's meeting a target of two hundred parts per billion in the liver.

00:21:13: But if i treat a bison...a bison is not a cow!

00:21:17: So instead of the target being two hundred its now the limit detection of the CFIAs assay which usually about one part per billion.

00:21:26: so thirty five days isn't gonna cut

00:21:30: No, and that's something where I think is an important thing to recognize especially when you look at these minor species.

00:21:40: Bison sheep goats.

00:21:43: we really don't have a lot of approved products for sheep let alone for goats or bison.

00:21:50: That's why this makes it critical Because

00:21:57: that's what we do.

00:21:58: We have the time and expertise to look worldwide for drug depletion data, right?

00:22:03: And so we have friends in other countries—we access databases out of different countries

00:22:12: —and also there are resources where you can find information.

00:22:16: a lot of practitioners won't be

00:22:18: able to access them.

00:22:21: Unfortunately though sometimes And we are concerned of human safety or residue detection and you have to say, We can't give an answer.

00:22:33: Right?

00:22:34: That puts the onus for coming up with withdrawal time back in a practitioner if they couldn't find an answer.

00:22:39: They're going to be having hard times In cases like weird drug use.

00:22:45: we prefer that you contact us before giving it And then again maybe we can offer suitable alternative instead of ending up in a situation where no one could provide an adequate withdrawal time.

00:23:00: Right, right here's the question and so how do people put it on request?

00:23:06: when I say people like us were probably talking mainly veterinarians that

00:23:11: Yeah, so the service is designed to be specific for veterinarians because it's a veterinarian who has responsibility legally For providing them withdrawal guidance and we feel that our advice Is part of their legal medical record?

00:23:26: So The database is really centered around veterinarians Who have an extra label drug use That they need help with And They become clients Of Our Service or they Have Their Own Accounts and they can use drop-down menus to tell us the information we need to help them.

00:23:45: So, you need to know that species are a class of animals.

00:23:48: so lactating dairy cows versus veal calves meat goat vs.

00:23:53: A Dairy Goat That sort of thing.

00:23:55: And then I spent alot time building separate drop down menu for different species.

00:24:02: We have like route of administration You go intramammary in a dairy cow but not chicken Great And things like that and units for the dosing.

00:24:12: so you know, for feed it's usually parts per million.

00:24:15: For injectables its gonna be milligrams per kilogram.

00:24:19: we want the veterinarians to give us a dose accurately.

00:24:22: We don't wanna be doing mills per hundred pounds and make math errors.

00:24:27: So have the veterinarian do.

00:24:28: that then makes data searchable.

00:24:31: It is nice this way.

00:24:32: Then class of system affected and diseases under.

00:24:39: So let me think here, so respiratory tract.

00:24:42: and then you could have bovine respiratory disease.

00:24:45: And you can have Menheimia's etiology.

00:24:48: it could be etiology unknown but by knowing the disease process that helps us with our recommendations.

00:24:55: because if the animal is relatively healthy—so we're talking say a tranquilizer or a dewormer —the animals health status doesn't come up into play.

00:25:05: But If We're Talking A Cow With Coliform Mastitis That animal is quite often dehydrated.

00:25:11: And if you do something like inject a drug subcutaneously, well that's going to affect its absorption and then it's also gonna effect the drug distribution and depletion.

00:25:23: so we're going to look at that and take more conservative factors into account.

00:25:29: .And thats why this service is by veterinarians for veterinarian.

00:25:33: sometimes people ask Why don't just put all your recommendations up on our website?

00:25:38: it's not that easy.

00:25:39: It depends on the circumstance of the animal, and so we believe that extra-labeled drug use in Canada is a privilege—not a right—and that it needs to be specific to that

00:25:52: situation.".

00:25:54: So we highly discourage asking us once for recommendation for one situation... ...and then just using it sort of willy nilly and never checking back with us!

00:26:04: The service is free, it's available twenty-four seven.

00:26:07: What not to love?

00:26:10: Well and the situations can be what might not seem grossly different.

00:26:15: you know when your first look at it... ...the situation will be quite different depending on the disease that we are dealing with.

00:26:22: so as I said an animal that has a coliform mastitis is different than like you say deworming or maybe treating a foot rot, something like that.

00:26:36: Exactly!

00:26:39: And the other danger of course is information changing constantly.

00:26:45: so we stand by our recommendation on day it was made.

00:26:50: if you choose to use this two years later and in meantime have got new information The onus isn't on us to try and hunt you down, saying oh by the way that thing about two years has changed.

00:27:08: People say well should we call once a year or every six months?

00:27:12: All I can say is no!

00:27:14: I might get new data tomorrow.

00:27:15: Luckily most of times when i got new data i've been able to shorten recommendations.

00:27:21: but there are instances where we have had lengthened them significantly.

00:27:27: And then even when we talk about, you know extra label use and especially in a species not on the label.

00:27:34: If it's zero detectable so many of our tests nowadays they seem to be getting more and more sensitive all the time that violation residue level is getting lower and lower.

00:27:45: So I'm sure that probably plays a role In that withdrawal recommendation too which winds up becoming moving target.

00:27:53: So so just to kind of take that a little further.

00:27:56: I have a really good example using a paperclip.

00:28:00: Yeah, you know how to give you an idea of how sensitive our tests are?

00:28:04: I mean analytical chemists do.

00:28:06: what analytical chemist Do?

00:28:07: they just get better test.

00:28:09: and sometimes i see my friends at the cvaa And i Just go stop it.

00:28:13: yeah

00:28:14: Stop It!

00:28:14: I don't need them.

00:28:15: That low right

00:28:16: Right.

00:28:16: its not pharmacologically or toxicologically significant.

00:28:21: It's not a human safety issue at that point anymore, right?

00:28:24: But

00:28:24: if it's zero then zero is getting lower all the time.

00:28:28: Right.

00:28:28: So Tim If you take a paperclip...it weighs about a gram.

00:28:33: Great!

00:28:33: ...if You Take That One Gram Paperclip And You Divide Into A Thousand Pieces Each Of Those Pieces Is Going To Weigh A Milligram.

00:28:41: Yeah If You Take THAT and You Divided into A ThousAnd Pieces each of those pieces weighs a microgram or part per million.

00:28:49: So when I first got started in pharmacology, most of the analytical laboratories were working on this part per million range.

00:28:57: And for most of our drugs that have withdrawals and approvals and approve withdrawal times... The MRLs are in this part-per-million range

00:29:07: which is an infinitesimally small amount when you give the paperclip example.

00:29:12: We haven't

00:29:13: gotten infinitesimal yet, so if you take one of those microgram pieces and divide it into a thousand pieces.

00:29:19: that weighs a nanogram or apart per billion.

00:29:23: all of the analytical labs are down now around a part per billion.

00:29:28: So...that's kind of typically what we target with extra-label drug use Is how long is it gonna take to get apart per billion?

00:29:37: and that's usually reasonable from human food safety.

00:29:40: but then you can do things like import export issues.

00:29:45: Oh if u take one of those nanogram pieces in divided into a thousand pieces each of those ways apica gram or part per trillion.

00:29:54: so we have ractopamine approved in north and south america for growth promotion.

00:30:00: the rest of world kinda hates us.

00:30:03: And so the European Union has a seven part per trillion analytical assay for rectopomy.

00:30:10: So these are the kinds of things that while the approved use would be safe in North America, it could still cause a violative residue if the products are shipped to another country.

00:30:23: and again our expertise there is knowing what other countries are interested.

00:30:28: And then to blow your mind, you could take a picogram piece and divide that into a thousand pieces.

00:30:34: You have a pentagram or part per quadrillion.

00:30:38: Some of the assays are working in this

00:30:40: area.".

00:30:42: That is incredible!

00:30:43: So yeah...that's what I said.

00:30:45: Zero was a moving number for

00:30:47: us.

00:30:47: Which again highlights the need and still expect it to be valid today.

00:31:02: You know, especially when we're talking extra label use and being having-to-be at zero so really highlights that you are always kind of having to keep up in changing keeping up with the times.

00:31:16: I guess as far is the data that you have on tests available?

00:31:20: And again no shade practitioners.

00:31:23: even just trying When you're a practitioner is so difficult that again, we are here to help out our colleagues because this is what we do.

00:31:36: And so were good at it.

00:31:37: and where fast at it?

00:31:39: We just hear the health

00:31:41: right.

00:31:41: one thing we haven't talked about but I think kind of important addresses when we talk about You know compounded products.

00:31:50: So we don't have an approved animal product animal drug or an approved human product to use but now we're using a compounded product.

00:31:59: What's unique about those?

00:32:02: So in Canada, we have guidelines.

00:32:04: the United States they codified extra-label drug use under a law that refer to as MDUCA The Animal Medicinal Use and Clarification Act.

00:32:16: so ours are guidelines.

00:32:18: But there very good guidelines And we should follow them.

00:32:21: They kind of referred it is a cascade system.

00:32:24: And so as a veterinarian, when you encounter situation.

00:32:28: You should use an approved veterinary drug first for treatment and if you can't find the exact label say the indication needs to be different... ...you still should choose the veterinary approved product first.. ..and go extra-labeled that way change the dose changed the indication change the route any of those sorts things.

00:32:48: The next best choice is there's no veterinary approve products.

00:32:54: manipulate in some way, is to choose an approved human drug.

00:32:59: Because at least we're still working on the area of approved drugs where Health Canada is overseeing everything—the manufacture stability those sorts things.

00:33:10: if there's ever any issue products get recalled right so really protecting people and animals and certainly the consumers.

00:33:18: Only if there are no approved human or veterinary drug products that can be manipulated in a particular way, should veterinarians choose what we call a compounded drug product?

00:33:32: So this is going to be a product where typically a pharmacist will do this but also veterinarian sometimes.

00:33:42: But it's combining two or more ingredients of which at least one is a drug, or pharmacologically active ingredient to recreate final product in an appropriate form for dosing.

00:33:54: So what we often see as things like cats are hard-to-pill right?

00:33:59: So somebody may ask the farmers take the pill and mush into liver paste so that about Acceptable as compounding can get because you're taking the approved formulation.

00:34:13: You are just adding something to it, fish paste or whatever so that you could get the animal to consume it.

00:34:20: but sometimes we see compounding from things we call active pharmaceutical ingredients or APIs and these are the bulk.

00:34:29: drugs come in barrels when a pharmaceutical company may get their API's But before their product is put into that nicely labeled bottle, they have done all kinds of tests to ensure what it's supposed be and its composition.

00:34:49: That there are no contaminants... And then the other stuff gets added in order for you know-and-trust and has a backing on health Canada And in Canada, that's actually still legal for pharmacies to import these APIs and then compound a drug formulation.

00:35:13: So take a powder make it liquid add other things to it so on and so forth.

00:35:19: It is supposed be on an individual case basis.

00:35:24: Yes!

00:35:25: There are regulations about how compounding should be done um...and-that sort of thing.

00:35:32: But unfortunately, in a lot of cases it is much less expensive to produce a final product from this route because you don't have all the checks and balances of an approved drug.

00:35:49: Fortunately if someone or veterinarian chooses to prescribe one of these products The CG Farad can help you.

00:35:58: we won't Because we don't know what that stuff is.

00:36:01: We don't if the original product was supposed to be, and sometimes products are not when they're tested You know?

00:36:10: We look at movement of chemicals on a global basis And sometimes things get substituted.

00:36:18: So the sefty fear isn't Sefty Fear it's Safazolin Things like That.

00:36:24: Then because of formulation how it's going to be absorbed, distributed metabolized or ultimately eliminated.

00:36:35: So we don't know had a come up with the number.

00:36:37: so basically our line is you make up a number.

00:36:41: I'm not gonna Make A Number.

00:36:42: i can put my scientific reputation on The Line for a product that?

00:36:47: Don't have any faith in How It's Going To Be Hate.

00:36:51: Without The Quality Checks and Balances That Are Behind An Approved Product As you said, it's really hard to provide any guidance on that because you can't be sure what is in the product.

00:37:08: In all cases cheaper is not supposed a valid reason for compounding but certainly companion animals are often the reasons for it and thats quite unfortunate especially when we have bona fide approved products food animal side, probably the number one case for this is tultraseral.

00:37:31: And so we sometimes have to be on the lookout for people will in our database you're supposed choose brand name and they'll choose the brand name for Tultrasural.

00:37:41: but then we look at it go are using compounded stuff?

00:37:46: Then they say yes and we have to say sorry because that's a drug that should not be compounded.

00:37:55: And then there is an available approved product

00:37:58: in that instance as well.

00:38:00: But the wine, it's expensive.

00:38:02: Yes

00:38:04: Recalls are expensive too.

00:38:09: So if someone chooses to prescribe a compounded product They're responsible for providing withdrawal guidance For some animals who go to slaughter.

00:38:20: If that's detected It may result into hold and test situation Right.

00:38:24: And that costs a lot of money for anybody, it is very difficult to hold carcasses.

00:38:30: you know one swine carcass or beef carcasse is one thing.

00:38:32: sixty thousand broiler carcases on hold Is another huge issue.

00:38:37: so yes That's what we want to try to avoid.

00:38:40: Yeah and comes back to your comment about you know reach out To us before You know doing some Of these things just too.

00:38:48: don't come asking For information after the fact in A lot of those cases right

00:38:52: And for requests that are fairly routine, you know we see often.

00:38:56: We get back off in within twenty-four forty eight hours if it's a little more complicated and then have to do some research...and that sort of thing may take more time than.

00:39:07: But usually our service turnaround is really quick.

00:39:09: And if it's an emergency situation, all emails and phone calls, phone messages to the CG Farad come into my personal phone...

00:39:17: You talked about this a lot already I mean- A lot of your requests are related to antimicrobials.

00:39:23: um maybe talk a little bit about uh The role of CG farad with regards to antimikrobial stewardship.

00:39:30: Sure, so as I said our mandate originally was to protect the human food supply and keep our friends and producers out of trouble but antimicrobial stewardship has become a very big issue.

00:39:41: As we've seen the rise of antimicrobiol resistance worldwide it's its major threat to humans and animal health.

00:39:48: And there are lots of concerns about use of antibiotics in animals.

00:39:52: There is lots of concern about you know extra-labeled uses of antibiotics maybe shouldn't even be allowed legally which would put us in a world of hurt because we would have sick animals.

00:40:03: and you know if you have animals they're starting to get sick.

00:40:06: You're going to send them for slaughter quick, And then we might increase risk humans and all that sort of stuff.

00:40:12: so it seemed fairly natural.

00:40:14: as I said i'm bordered on large animal internal medicine So im opinionated!

00:40:20: So just wait in say oh thats not really inappropriate use.

00:40:24: And we do put warnings, you know.

00:40:28: You're doing extra label use of a drug that's considered high importance in human medicine and for the last number years We've been doing prudent new seminars That are free and we advertise to our stakeholders here from people who were doing research In that area.

00:40:47: Right No like he said it is such an important issue you know, both the human side and the animal health side.

00:40:56: It is something where we don't want to lose our... You know as a veterinarian or right-to-prescribe extra label because as you've said multiple times today it's something where We don't have a label that covers every disease condition That were going to deal with.

00:41:12: so we need that flexibility To prescribe extra label but we need to do it in an prudent fashion without especially you know, when we talk about antimicrobial use?

00:41:23: Absolutely.

00:41:25: Extra-label drug abuse is a privilege and we have a responsibility to do it right.

00:41:30: Exactly!

00:41:31: We're gonna pause our discussion here.

00:41:33: thanks to Tricia for joining us for this episode of the HerdHealth podcast.

00:41:37: be sure to come back and listen to part two where Tricia and I discuss interesting requests in cases that CGFARID has received including discussion on extra label use products.

00:41:46: Tricia's also going share some stories the concept of zero and what that means in different situations.

00:41:52: And we'll be talking about maximum residue levels, how they affect requests about vaccines.

00:41:58: I want to thank you for listening today's episode.

00:42:00: Please consider leaving a review subscribing our show.

00:42:03: See ya next time!

00:42:13: Bowringer Engelheim cannot recommend the use of products outside of Canadian product approved labeling.

00:42:19: Find more episodes on Spotify, Apple Podcasts or wherever you get your podcasts from!

00:42:25: Thanks again for listening.