#34 Veterinary pharmacovigilance, Part I – James Mount - Drug Safety Matters

Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Fredrik Brounéus (00:15):
Welcome to Drug Safety Matters, a podcast
by Uppsala Monitoring Center,where we explore current issues
in pharmacovigilance and patientsafety.
I'm Fredrik Brouneus and todayI'm looking forward to learning
more about veterinarypharmacovigilance, including its
differences and similarities tothe human side.
Human and veterinarypharmacovigilance share many

(00:36):
goals, challenges and approaches, but there are also significant
differences, such as thenumerous species and breeds that
need to be considered inveterinary pharmacovigilance.
In this two-part episode, Iwill be joined in the studio by
James Mount, veterinarypharmacovigilance assessor at
the Swedish Medical ProductsAgency and EU-elected chair of

(00:58):
the Pharmacovigilance WorkingParty for Veterinary medicinal
products.
Hi, James, and welcome to theDrug Safety Matters studio.

James Mount (01:16):
Thank you very much .
Thank you for the invitation.

So, veterinary pharmacovigilance; this is
something that's quite new to meand I was hoping we could start
off with sort of the broaderpicture here, James.
How similar would you say thatveterinary pharmacovigilance is
to human pharmacovigilance?

Well, I would say they're very similar, but before
I develop that point further,I'd just like to say that the
views that I express in thispodcast will be the ones of my
role as veterinarian andpharmacovigilance assessor at
the Swedish Medical ProductsAgency and are not an EU view or
opinion, despite my currentrole as elected chair of the

(01:57):
European Union's VeterinaryPharmacovigilance Working Party.
But if we go back to yourquestion now, actually there is
an enormous amount of similarityand crossover between human and
veterinary pharmacovigilance,and I would say, above all, we
share the same goal, which is tomaintain the supply of safe and
effective medicines for use,and obviously this
simultaneously sort of maintainsanimal and public health and

(02:20):
also even protects ourenvironment as well.
In terms terms of challenges,we share the same ones there,
with trying to encouragehealthcare professionals, and
this is whether they're vets orhuman healthcare professionals
and even the general public, toactually report suspected
adverse events when they occur.
After all, these reports areactually the fundamental source
of information that we use bothfor human and veterinary

(02:43):
pharmacovigilance, and I wouldsay that the basic approaches,
even for surveillance and signaldetection, are very similar,
although we do have differentdigital systems, of course, and
also we have quite differentvolumes of data available to us.
But then also there's anincreasing use on the veterinary
side with polypharmacy andthat's the use of multiple drugs

(03:03):
in an individual, or"multimodal treatment, you might
call them and human andveterinary pharmacovigilance
share more and more now the samechallenges in relation to
trying to establish a causalrelationship when many drugs are
used at the same time, and alsotrying to establish any product
association with any potentialinteraction if you suspect one.
There's also an increase in thenumber of advanced therapies as

(03:26):
well, and many of these arealready available on the human
side, but they are beingintroduced on the veterinary
side and if we take someexamples that we've got a number
of stem cell therapies on theveterinary side, now there's
quite a number of monoclonalantibody therapies marketed as
well, and then gene therapiesare coming along as well, and
all these pose their own uniquechallenges which I think the

(03:48):
human side really are familiarwith in terms of
pharmacovigilance

So very similar would perhaps sum it up
then.
I mean, mean at least withregards to the bigger picture of
aims and goals and challengesthat we are talking about here.

Yeah, very much similar, and I know that we're
focusing on similarities here,but I think I should mention one
significant regulatorydifference within Europe, and
that's been implemented in thenew veterinary medicines
regulation, which actually onlycame into force in January 2022,
which is relatively recently,and that is that the traditional
PSURs, or the periodic safetyupdate reports that you still

(04:27):
have on the human side, andthese are when the marketing
authorization holder submits anevaluation of their benefit risk
balance on defined time points,and these are usually every
three years or so, or evenlonger, on the human side as
well.
But now on the veterinary side,these have been replaced with a
more continuous signalmanagement process, as we've
called it, now and here.

(04:48):
Now, these marketingauthorization holders, which are
the responsible pharmaceuticalcompanies, should notify any
competent authority of anychanges in the benefit risk
balance of their product, or, ifthey see any new risks emerge,
they should report these within30 days, so it becomes more of a
continuous process, and thenalso, these responsible

(05:12):
companies should be providing aconclusion of their general
benefit risk balance assessmenton an annual basis instead.

But then this annual report or conclusion
would be less comprehensive thanthe PSUR?

Yes, it is definitely much less
comprehensive, but theveterinary side now has really
instead become more focused ontrying to identify new risks
when they emerge and thenquickly establishing any
mitigating measures in a timelyfashion, and the overall aim of
the veterinary medicinesregulation in terms of
pharmacovigilance is to reducethe administrative burden for

(05:52):
all concerned parties and thenmake us more efficient and
focused, which I think it does.
Obviously, the implementationof this new process moving away
from those traditional PSURs isstill ongoing in Europe, despite
being implemented in 2022.
And there have been obviouschallenges, mainly because it's
quite a different approachtraditionally, and also we've

(06:13):
had to make some significantadjustments to our IT systems,
which does take some time.

Now you mentioned both animal and public
health.
Could you perhaps go a littlebit deeper into how animal
health is connected to publichealth, because there is a quite
intimate connection, isn'tthere?

There is a significant interconnection as
animal health does impact publichealth in many ways and even I
should say that even impacts ourenvironment together.
And I think this interaction isquite well recognized in this
establishment of the One Healthconcept, which is well
established globally and thattries to integrate approaches to
contribute to better human,animal and environmental health

(06:55):
simultaneously, and I shouldalso mention it also tries to
improve our food safety.

Yes, I must say that One Health is an
intriguing concept and I thinkwe will need to have a separate
episode on that on the pod nextyear, but in the meantime, we
will add a link to the shownotes for those who want to find
out more.

And then, in relation to this interconnection
with animal and public health,one ongoing focus is to reduce
the need for antibiotics totreat animals, and also
minimizing the emergence ofresistance through alternative
methods such as efficientdisease control, and this is
through either use of morevaccination or applying better

(07:40):
farm management and animalhusbandry, or even improving
biosecurity, which isparticularly important in in
terms of trying to preventinfections from coming in in the
first place.
Apart from the changes topharmacovigilance, another goal
of the veterinary medicinesregulation is actually to reduce
the development ofantimicrobial resistance.
For example, there's been a banon the prophylactic use of

(08:02):
antibiotics introduced, and thenalso there's a clear
restriction being introduced toreserve certain antibiotics for
only human use, and this hascaused a generation of a list of
reserved antimicrobials forhuman use, and the overall aim
of that list is that it reducesthe risk of developmental
resistance because you'relimiting the use of it, and that

(08:26):
means that effectiveantibiotics will be available
for humans when they're reallyneeded.
And also, on top of this, allmember states now are obliged to
actually report sales and useof antimicrobials in their
member states, so that thisinformation can then be compiled
centrally within Europe andthen that means that we can

(08:46):
closely monitor the situationand take action when necessary.
And if I may, there are otherinitiatives as well.
I'd like to mention one fromthe European Medicines Agency
where they've introduced aranking scheme of antibiotics as
well to support thedecision-making of vets, and
that considers what level ofrisk their use of a certain

(09:07):
product in animals has on thepublic health through the
possible development ofantimicrobial resistance.
And they also actually considerthe absolute necessity to use
these antibiotics in veterinarymedicine as well.
And they've introduced aclassification scheme with four
categories, and there'santibiotics to absolutely avoid
in animals, restrictive use,cautious use and then the

(09:30):
prudent use category as well.
This advice from the EuropeanMedicines Agency also indicates
that the route of administrationin animals should be considered
, because, if you take theexample of group medication in
feed and drinking water, whichis quite commonplace in large
animal species, also calledmetaphylaxis, this has been

(09:51):
shown to be a considerabledriver of resistance and this
type of treatment should only beconsidered if it's really fully
justified in those cases.

So in human medicine, some side effects can
be clinically discovered orobserved from the outside, so to
say, such as skin rashes, heartpalpitations or impaired liver
or kidney function, whereas thediscovery of other effects are
dependent on patientsexperiencing and describing them

(10:23):
, such as headaches, nausea,blurred vision.
In veterinary medicine, we areonly dealing with side effects
that can be observed from theoutside by a human, so I was
wondering, could this mean thatanimals plausibly experience
side effects that are neveractually discovered?

(10:45):
Reported?

I think this is quite a relevant reflection on
many levels, as in if we takethe level of adverse event
reporting first, human andveterinary pharmacovigilance
share a significant level ofunderreporting generally and
it's estimated that around 90percent of our adverse events
that occur are not reported, andthat's documented both on the
vet and human side.

(11:07):
And I should mention here, infact, that there has been
actually a recent study at theUniversity of Liverpool in the
United Kingdom that actually hasconfirmed this degree of
underreporting on the vet side.
And they actually did thisthrough a new sort of tool that
they've established wherethey've identified and
quantified the mention ofunreported adverse events in the
free text within veterinarymedical record systems, and

(11:31):
they've analysed data that theyextract from these veterinary
medical record systems throughthe Small Animal Veterinary
Surveillance Network, and that'salso known as SAVSNET, and it
collects data from a proportionof small animal veterinary
practices in the UK and it's apromising system really.
But if we go back to the aspectof your question regarding

(11:53):
adverse events goingundiscovered, if you take
companion animal species andhere we're talking about dogs,
cats, rabbits and horses theseindividual animals tend to live
relatively close, in closecontact with their animal owners
and I would say then that theadverse events are normally
observed quite readily, althoughthere are some species of
domestic animals, such as catsparticularly, which often tend

(12:16):
to hide systemic clinicaldisease quite well, probably due
to their survival instinct, Iwould have thought.

So as not to show signs of weakness or
vulnerability to possibleenemies.

Yes, exactly, that would be the case and I think
it's an evolutionary sort ofholdover from their sort of wild
ancestry that they have.
But generally speaking, thesigns of illness and injury in
cats is generally quite subtleand often overlooked if you're
not careful.
But despite cats and thoseother companion animals, adverse
events can also go undiscoveredin production animal species,

(12:49):
and here we're talking aboutcattle, pigs, poultry, mink and
even aquaculture.
So that's fish we're talkingthere.
So it's quite diverse, andthese animals are often kept and
treated in very large groupsand the daily contact with an
animal owner is relativelylimited, although it does occur
– that's a legal requirement, infact.
But adverse events can then gounnoticed in these species

(13:12):
unless the adverse events arereally severe, or they're fatal,
obviously, or they affect manyanimals in the group, so it's
very, very obvious that there isa an issue.
And the other aspect, apartfrom adverse events not being
really detected, it can also bethe case that the known adverse
events are not reported.
And here when I when I sayknown adverse events, these are

(13:33):
those adverse events that arealready listed in the product
information and it's assumedthat many vets and animal owners
don't realize that they can, oreven in fact should, report
these known adverse events inorder to help us, both as
regulators and also industry, tofacilitate the monitoring of
the overall safety of medicines.
And it's often the case thatanimal owners particularly tend

(13:56):
to report suspected adverseevents through their vets, and
then unfortunately the vetsdon't have time to complete that
task.

Right.
Just roughly during a normalyear in Sweden, how many or how
big a proportion of the incomingreports are from pet owners and
how many are from professionals, say, you know, veterinarians?

Well, I can say on an average, as in during a
normal year, um, we receiveroughly 70 to 80 percent of our
adverse event reports fromveterinarians in Sweden, and the
rest come from animal owners,but we also get a few from
veterinary nurses andpharmacists.
To give you an idea of theentire volume in Sweden of
reports, this year so far we'vereceived 1,140 adverse event

(14:45):
reports totally, and just over50 percent have been handled by
the Swedish Medical ProductsAgency and the rest have come
via the marketing authorizationholders.

Okay.
Going back to what you saidabout production animals and
side effects often being harderto detect in those larger
populations, could that meanthat the level of underreporting
could be even higher than the90 percent that you mentioned
that were found in the Liverpoolstudy, as those unnoticed

(15:20):
events among production animalswouldn't appear in the medical
records?

Absolutely I would agree with you, but I would say
that the Liverpool study didonly use data from small
companion animals.
But there are similar systemsto SAVSNET and actually
Liverpool own them, for dataextraction from both equine and
production animal systems aswell.
These are the record systems,but they're not as well
developed at this moment in time, but they're coming along.

(15:46):
And apart from the fact thatthese adverse events in
production animals go unnoticed,potentially due to this limited
contact with their animal owner, there can be other potential
reasons for the limited degreeof adverse event reporting, and
these could vary from a generallack of awareness, which we try
to increase.
There can be time limitations,both from the animal owners

(16:06):
themselves as, particularlyfarmers, they're particularly
busy and vets themselves, andeven there can be an instance
where there's a potentialreluctance to report, and this
could be the scenario when aproduct is potentially sort of
used off label in some scenarios.

Well, underreporting is a quite a challenge
, isn't it?
So are there, or have there been, initiatives or innovations to
stimulate more reporting on theveterinary side?

Yeah, numerous.
Within the European Union,which I can only really speak
for, there are many initiativesin place to both encourage and
then also to try to facilitatethe adverse event reporting, and
this is mainly done at a memberstate level.
But of course, when you'retalking about these initiatives,
it really is highly dependenton the budgets available and

(16:54):
then also the resources atmember state level.
So there is quite a diversity ofoptions available within member
states, and I should mentionhere that there have been
several surveys performedamongst the veterinary health
care professionals in order totry to elucidate the main
hinders or the issues that theyhave with adverse event
reporting, and from surveysconducted by the FVE, which is

(17:18):
the Federation of Veterinariansof Europe, and even the Swedish
Medical Products Agency, therehave been a number of factors
that have been identified, andthis includes that, potentially,
vets have a limited time toreport.
As I said, they are very busyindividuals and they have to
prioritize other activities, andalso the presence of some of
the inefficient methods ofreporting that we have doesn't

(17:40):
really help them.
And there's also a need forfurther or continued educational
interventions to keep the levelof awareness up, of course, and
then also we need to try toencourage other veterinary
healthcare professionals, suchas veterinary nurses, to even
report.
In the new veterinary medicinesregulation, which I've

(18:00):
mentioned a number of times now,it's possible for national
competent authorities to imposespecific legal requirements on
vets and other veterinaryhealthcare professionals to
report suspected adverse events.
And if you look at Europe, mostreporting is still voluntary,
but in a few member states,including Sweden, it is
obligatory for veterinarians toactually report.

So when did it become mandatory and did it
increase the level of reporting?

Well, this mandatory option is not a new
thing, and the ability to imposethis specific requirement on
vets to report was available inthe previous EU directive
related to medicinal productsfrom 2001.
And this requirement has beenimposed on vets since then, such
as 2001 and obviously thenadopted in our national
legislation, of course, butwhether it's had an impact on

(18:50):
reporting rates is difficult todetermine, but I would say that
Swedish vets appear to be veryaware of this obligation, and I
would also say that evenreminding vets of this
obligation can be a useful toolin generally raising awareness.
We have actually considered, inSweden, to expand the obligation
of reporting adverse events toinclude even qualified

(19:11):
veterinary nurses, and this isbased on evidence we saw in our
survey that veterinary nursestend to have more contact time
with animals in the clinic.
They also have more contacttime with animal owners as well
to actually receive informationon adverse events.
And if you do apply thisspecific requirement to nurses,
it will signal to them that theycan actually report themselves

(19:32):
and they don't have to gothrough their vets, which they
tend to do at the moment.
And also I think that,potentially, nurses may have
more time to actually report orcomplete the task.
And if you look at the humanside, in some of the studies
that have been done and I thinksome of them have actually been
done in Sweden they have shownthat if you encourage nursing
staff to actually report, therecan be quite a significant

(19:53):
improvement in reporting rates,so that's something to take into
account.
Other initiatives to raiseawareness have been run by the
European Medicines Agency, andI'd just like to say here that,
like in recent years, they'vetried to hold regular veterinary
focus groups in order todiscuss adverse event reporting

(20:14):
with veterinarians from specificveterinary sectors.
e recently they've targetedpoultry and aquaculture sectors,
and these are quite substantialsectors on their own.
And these kinds of forums thatthey've had have generally been
welcomed by all parties involvedand they form a basis to raise
awareness and also to try tounderstand the hurdles more and

(20:36):
to have generally just an activedialogue with vets in the
field, really, and the EuropeanMedicines Agency plan to hold
these next year as well withother sectors – it's not yet
known which ones.
But as a spinoff, I'd just liketo say that a spinoff to this
is that the European MedicinesAgency has discussed and
indicated that they potentiallywill establish a yearly campaign

(20:59):
which is very similar to theUppsala Monitoring Centre's #Med
Safety Week, in order to try topromote and raise awareness.

Nice! As part of the #Med Safety Week planning
team, I'm very happy to hearthat.

Good, and we'll probably get some tips from you
going forward.
But if we go back to the EU,some national competent
authorities have invested quitesubstantially in trying to
improve their electronicreporting forms.
Some of them have developedmobile apps to cater for the
vets that are out in the fieldmore than they are in the clinic
.
And then also there are anumber of member states that are

(21:34):
quite active in engaging witheducational initiatives and
specifically targeting evenveterinary students and
veterinary nursing students aswell, and obviously this then
means that they ingrain theimportance of adverse event
reporting early on in the career.
And I also should mention here,otherwise I might get into
trouble, that even the SwedishMedical Products Agency has

(21:56):
recently launched an onlinereporting form, and this should
hopefully, not hopefully, but itwill, as in, facilitate the
reporting by vets and animalowners in Sweden okay, so it's.

It's one form for both pet owners and and
veterinaries, and you find thisform via the agency's website

Yeah, absolutely, it's up and running.
And yeah, it's one form, butthere are different sorts of
ways in, if you're an animalowner or a vet, but it's
relatively straightforward andit's all up and running, and
it's been popular.
Actually, most of our reportsnow are coming in through that
online reporting form, which isencouraging, and some of the

(22:40):
advantages of this reportingform is that particularly the
veterinary products that areconcerned can be searched for
within our national productregister, and this means that
then some of the information canbe auto-populated in the form
for you which then obviouslyfacilitates and reduces the time
to report.
But while we're on reportingforms, if we consider the new

(23:00):
initiatives or new innovationsaround, one of the most
significant innovations aroundtrying to facilitate adverse
event reporting is thegeneration of a so-called
adverse event reporting button,which is in the SAVSNET system,
which I've already mentioned,the SAVSNET data collection
system, and here this buttonallows veterinarians to send

(23:25):
information about an adverseevent directly from their
medical record system to thenational competent authority.
In this case, because thesystem's in the UK, this is the
Veterinary Medicines Directorateand this method has actually
anecdotally cut down reportingtimes to as little as five
minutes in the the mostuncomplicated of cases, and
there's still ongoingrefinements to improve this and
I've had engagement withindustry around it and there's

(23:47):
also ongoing investigation tosee if reports can actually be
extracted more passively fromthis vast array of information
in the veterinary medicinerecord systems.

That's a very interesting approach to
integrate the reporting buttoninto the medical record system.
I was also wondering aboutthis: when you say passively, do
you mean by some kind ofautomated process like data
mining and so on?

Yeah, that's correct, but it's very much in
its infancy within this system.
But I would say that in factthere are numerous studies on
the human side which have useddifferent methods of data mining
, including regular expressionand regression techniques, to
try to identify adverse eventsin electronic health records, as
you call them, within the humanhealthcare service, and they've

(24:36):
been quite promising.
In fact, with those studies,and here, to promote the Swedish
Medical Products Agency again,as in, we've actively engaged
with providers of theseveterinary medical record
systems in Sweden to try todiscuss the potential
development of adverse eventreporting tools which could be
integrated within the veterinarymedical record systems and
there seems to be a demand forthat from the vets in the field

(24:59):
and currently, uniquely, I think, there are only two providers
that dominate the market inSweden and we're quite
interested in continuing thesediscussions in the near future
with those with those parties.

So, taking a small step back here perhaps in
the discussion, going back tothe side effects experienced by
animals; are we in generaltolerating more side effects
from veterinary medicaltreatments than we do for human

(25:33):
medical treatments?
Is there a difference in thebenefit-risk balance?

That's an interesting reflection and
question.
But generally speaking, whenveterinary medicinal products
are authorized, the benefitsmust always outweigh the risks
following the use of thatproduct in a particular target
species.
And that is the case withauthorisation of human medicines
as well, that the benefitsshould always outweigh the risks
.
In some instances there might bea degree of tolerance for some

(26:00):
types of adverse events, andthese are normally restricted to
the non-serious adverse eventswhen you're using these
veterinary medicinal products.
But I think that a tolerance ofadverse events is also seen
within human medicine and candepend heavily on the indication
of that medicine, both forhuman and veterinary use.
So, regardless of whetheryou're talking about a human or

(26:22):
veterinary medicine, itfundamentally depends on the
situation or the indication ofthat medicine which dictates how
much risk is allowed tooutweigh the benefit.
And if you take one of theextreme examples of chemotherapy
treatment, which we do use inanimals and is available for
human use, these treatmentsoften cause quite significant
adverse events that we all knowabout, which are tolerated as

(26:44):
the substantial benefit of thetreatment is considered to
outweigh the risk of theseadverse events occurring.
I
guess it's the the question ofbalance is both on the
regulatory side and on the sideof the individual patient.
so I mean, what risks or sideeffects are acceptable to the
system and to me also as thepatient, given sort of the

(27:08):
prospect of a certain benefit?
And the same for animals, ofcourse.
But here the decision alwaysneeds to be made by the owner,
and in a way I think this alsotouches on the question of
animal protection regulations,as they can also be quite
different in different parts ofthe world.
Are are these differencesreflected in the veterinary

(27:32):
pharmacovigilance practices aswell?
Yeah no, think so.
I don't think I have a concreteanswer, but animal protection
regulations are quite differentaround the globe.
If you take the case of theEuropean Union, which I'm most
familiar with, we do havesubstantial animal welfare
legislation and there's beenrecent updates to that regarding
transportation of animals thatI'm aware of and also breeding

(27:54):
of dogs and cats.
But all the welfare regulationthat's around is based on the
five freedoms, which is thefreedom from hunger and thirst,
freedom from discomfort, painand injury, freedom for disease
and freedom to express normalbehavior, and also freedom from
fear and distress.
And, and although people aroundthe world are heavily reliant
on their animals for theirsurvival and I do generally

(28:16):
believe that they care foranimal welfare, it's often the
case that it's the economic andsocial cultural differences
which cause countries to kind ofvary on their animal-related
values.
And if you bring this into thecontext of pharmacovigilance,
this would potentially have animpact on any veterinary
pharmacovigilance system,assuming a country has an

(28:37):
established system in place onthe veterinary side, which very
few have, potentially, theimpact being that there'll be
potentially reduced awareness,even reduced funding, and also a
decreased motivation of thegeneral public to actually
report adverse events.
But I don't think it would be amajor challenge and it wouldn't
be totally impossible to kindof overcome these economic and

(28:58):
social cultural differences inthese countries to establish a
fully functional veterinarypharmacophysic system.

Okay, so let's talk a bit about that system
aspect now that you mentioned it.
How and where are veterinaryreports collected and stored?
Locally, internationally,managed by whom, and so on?
How big is the veterinarydatabase?
If we could sort of startpulling the threads out of that

(29:25):
sort of snake's nest ofquestions .
.
.

Yeah absolutely, and I'm going to mainly focus on
the european situation becausethat's the one I'm most familiar
with.
But before we delve into thedetails, I'd just like to sort
of clarify again thatveterinarians have the right to
use and prescribe humanmedicines as well as veterinary
medicines, and as long as it'spossible to guarantee that it's
safe for the consumer whenyou're actually treating food-

(29:50):
producing animals, so that meansthat, both veterinary and human
medicines can be used to treatanimals.
That's something to considerand that's quite unique to our
side.

Yeah, I'm sorry, but I need need to insert

another question (30:01):
does this include any and all human
medicines?

No, not all human medicines are allowed to be used
in in animals.
Of course, as I said earlierthat there is a list of
antimicrobials that are onlyreserved for human use, and then
I'm also aware of some otheractive substances, such as these
antiviral medicines which arerestricted for human use and
shouldn't be used in animals.
However, I should probably saynow that, before human products

(30:29):
are actually used in animals,vets should always follow what
we call the cascade, which is arisk-based decision tree, which
has been actually set out in theveterinary medicines regulation
and that should always beapplied on a case-by-case basis.
Now, I'll try to summarize thecascade.
There are different scenarioswhere it's implemented, but the

(30:49):
idea is that the first treatmentchoice of a vet should always
be a veterinary medicinalproduct which is authorized in a
member state, so here we'retalking about the EU mainly, and
it should be for a specificindication in that specific
target species.
And if that first choice is notavailable, then a vet can then
use, potentially on license, aveterinary medicinal product

(31:12):
authorized in another EU memberstate for use in that same
species, or it could be anotherspecies, and ideally it should
be for the same indication, butyou could also choose a product
that has a slightly differentindication, but in the absence
of any of those veterinarymedicinal products that are
authorized, then you can thenconsider a medical product for
human use.

(31:32):
But this summary is quitesimplistic and I wouldn't take
it as formal guidance for me.

Apologies again
further away from the originalquestion on the system, but I
have to ask.
The reason for human productsnot being authorized for animal
use when they are apparentlybeing used in veterinary
medicine, is that because themarket authorization holders

(31:59):
have no incentive to seekveterinary approval, so to say?

Yeah, it's mainly the economic and practical
reasons really, I think, whichexplain that there are some
products that are not availablefor veterinary use, and it's
down to the fact that theveterinary sector is simply just
not a big enough market and themargins are just so small that
it makes it really veryuncertain for companies to
invest in the development ofveterinary medicines.

(32:24):
And I would say even that oftenyou find that there's a
practice or a routineestablished around the use of
human medicines in veterinaryclinics and thus then it
conceivably makes it unnecessaryto spend large amounts of money
or invest large amounts ofmoney and time in applying for
the approval of medicines for aspecific veterinary use.

(32:45):
And in some cases, when you'retalking about specialist
treatments for the use ofunusual conditions, so it's a
very few individuals involved,it can be very challenging even
to actually design and carry outstudies or relevant studies in
those target species to actuallyeven justify or support that.
And actually, I would say herethat the new veterinary
medicines regulation has beenquite good in fact, by

(33:08):
introducing specificauthorization routes for
medicines which are intended forthese kinds of limited markets
on the veterinary side and forsort of these special
circumstances or exceptionalcircumstances as they call them
in the legislation, and that theaim here is to try to further
stimulate the development ofveterinary medicinal products
for these small markets andmainly to focus on increasing

(33:30):
the availability of treatmentsfor really these serious and
life-threatening diseases butalso focus on these other unmet
needs from the veterinary side.
And this means these aspectsthat are stipulated in the
legislation means that medicinescan actually be approved with
less comprehensive data thannormal, so the process is more

(33:50):
straightforward.
The other reasons potentiallyfor the use of human medicines
in animals can also be due tothe problem of availability of
veterinary medicines.
Some anesthetics for animalsare also authorized for human
use and that can sometimes causea level of competition for
supply, and I would say thatthis was most notable during our

(34:14):
COVID pandemic that we had,when vets then were encouraged
to identify alternatives to someanesthetics that they commonly
use, and one of these that'smost commonly used is propofol.
And it was there during theCOVID pandemic, it was critical
to ensure that there was asteady supply of propofol
specifically to human patientsand obviously in this scenario,

(34:34):
with the reliance on some humanmedicines in veterinary clinics,
then a reduced availability ofhuman medicines can have quite
an impact on the veterinary side.
And I should mention here,actually, we have a live example
in place here where there is anongoing availability issue
related to a human inhaler whichcontains a form of cortisone,

(34:56):
and this inhaler is primarilyused to treat asthma in very
small children, but this samesubstance is also used on
license in cats and horses and,due to the ongoing availability
issue and the very importantfact that there are very few
alternatives to treat thesesmall children, the Swedish
Medical Products Agency has nowappealed to vets to limit the

(35:17):
use of this product in animalsfor the time being.

ctually actually read about that in the
paper – the shortage of themedicine, but I didn't see any
mention of the use in veterinarymedicine.

This crossover is quite significant occasionally,
and all these examples thatwe've talked about now really do
emphasize that.
There is a need to have anefficient communication strategy
that crosses over between theveterinary and human medical
disciplines so that we canconsider both supply and
availability of medicines, wecan mutually sort of raise each
other's awareness and, in termsof pharmacovigilance, we should

(35:50):
be together minimizing the riskof adverse events that occur
from any medicinal product,whether it's used in animals or
humans, or even both.

Yeah, communication is key, as is
often the case, perhaps.
Well, now let's turn the shiparound and go back to that
original question on thereporting infrastructure.
Sorry James, so let's startagain.
How and where are veterinaryadverse drug reactions reported,
collected, stored and so on?

Well, first of all, I'd just like to stress the
point that the suspected adverseevents are reported both for
veterinary and human medicineswhen they're used in animals,
and within Europe, which I canonly have the picture of, really
, these suspected adverse eventsare mostly reported by
veterinarians or animal owners,with the reports being submitted

(36:43):
either to the national comptentauthority within that EU member
state or to the marketingauthorization holder themselves
and, as I said, these are theresponsible pharmaceutical
companies for their particularproducts.
And, in accordance with the newveterinary medicines regulation
, these adverse events should berecorded within 30 days now,
which is a slight change frompreviously, and they should be

(37:06):
recorded in the UnionPharmacovigilance Database, and
this is also known asEudraVigilance Veterinary, or
EVVet for short, and this systemis maintained and managed by
the European Medicines Agency inAmsterdam, and within this
database there are even reportsfrom countries outside of the EU
, in fact.
So this does provide, in someway, a very broad data set for

(37:29):
signal detection.

So, does that mean that you could report side
effects from anywhere in theworld to the EVVet database?

No, not really, as in the EV Vet system is not a
global veterinarypharmacovigilance database,
although I should say that wepotentially do need one soon and
perhaps a UMC or a similarorganization might want to help
us here.
But the only national competentauthorities within the EU and
the pharmaceutical companieswhich have a marketing

(38:01):
authorization or productsmarketed within the EU have
access to EVVet, and this meansthat they then have the ability
to register their adverse eventreports and also perform some
form of signal detection in thedashboards that are available
there.
The reports that I mentioned,that come from outside of the

(38:25):
EU, are actually recorded by theMAHs within Europe which have
the same veterinary medicinalproducts marketed or and
authorized in countries, ormaybe several countries, outside
of the EU, so it comes fromtheir global sales and use.
But while we're touching on thedatabase, I could give you an
idea of the size of the EUdatabase and currently, when I

(38:45):
last looked, there was roughly950,000 reports or cases in the
database.
And that's in total, whichobviously is significantly
dwarfed by the volume of casesin the human equivalent database
, and from what I've heardthey've got around 12 million
cases there.
But if you consider the casesthat we have on the vet side,

(39:08):
the 950,000 within the EUdatabase, currently, these
contain about 300 millionanimals that have experienced an
adverse event.
And that's if the data iscorrect, but it roughly is, and
this is because more than oneanimal can be reported per case.
And if you talk aboutproduction animals and these
large facilities that holdanimals on a production scale,

(39:30):
like pigs and poultry and mink,these are the extreme ones,
where you can have thousands ofindividuals reacting to a
medicine and can be reported inone single case.
I don't know what the record is, but I've seen cases of 5,000
individuals reported.
And this is where you'veperformed large-scale
vaccination in these individualsor some form of large-scale

(39:51):
treatment.
But I also should mention that,like with the UMC system, where
part of it is publiclyavailable, I should mention here
that there is a public portalavailable in the European Union
pharmacovigilance database andthat's open to anyone to go in
there if anyone's interested.

Right, so well , 300 million animals.
So if we're comparing numbersof individuals instead of
reports in the databases, theveterinary side is in a league
of its own, really.
Is there a difference inreporting due to the quantities
of veterinary medicines that areused when it comes to treating

(40:28):
individuals versus masses, if Imean, for example, a companion
animal versus the mass treatmentof livestock, poultry,
aquaculture and so on?

Yes, I would say so .
And we do have a diverse arrayof animals that are treated in
different ways.
And just to emphasize the pointthat I've already made, is that
most of the events in companionanimals and here we're talking
about pets and horses, these arereported on an individual basis
or a small group.
But, as we've just mentioned,when you're talking about pigs,
poultry, mink and aquacultureand here I should even mention

(41:04):
beehive owners, there can belike thousands of individuals
that are treated and this couldbe either through drinking water
, mass vaccination campaign,waterborne medicines for the
aquaculture, and even we do havespecific beehive treatments.
And in these scenarios, as Imentioned, it's quite difficult
to observe the adverse eventsunless a large number of animals

(41:27):
are affected, and this meansthat there may be a significant
number that die potentially andyou normally have to take this
in consideration to the normalfatality rate within that
population.
But the differences in what isreported on the vet side is also
due to different types ofhandling that we have within
veterinary medicine compared tohuman medicine and, as you've

(41:50):
alluded to, there is largequantities of medicine that can
be administrated in veterinarypractice and in quite different
ways to human medicine,Which can lead, if you consider
the environment and exposure tothe environment, when
environmental exposure doesoccur, and if you compare
veterinary and human side,different compartments of the

(42:12):
environment tend to be exposed.
With veterinary medicines,which are used in production
animals, these medicines tend toend up in the soil through the
manure, whereas with humanmedicine, they tend to end up
most always in the wastewaterinstead.

We'll get back to that eco aspect of
pharmacovigilance in a littlewhile.
But first, how does theEudraVigilance veterinary
database compare to otherveterinary pharmacovigilance
databases around the world?
You mentioned that there's noglobal database as of yet, but

(42:49):
are there similar systems inplace in other regions?

Well, I don't have a complete picture of all the
systems that are availablearound the world, but those that
I am aware of are very similarto the European Union's
pharmacovigilance database.
And here I'm talking aboutdatabases that are used by both
regulators and industry, becausesometimes they have separate
systems, and the similarity withthem is that mainly through the

(43:13):
adherence to the sameelectronic standards to transfer
data and here it's called theVICH standard that we use
globally, or most of us useglobally, and, if I may, that
VICH stands for theInternational Cooperation on
Harmonization of TechnicalRequirements for Registration of
Veterinary Medicinal Products.

(43:35):
It's a rather long-winded titleso it's often easier to refer to
VICH, but it's very muchcomparable with the ICH standard
on the the human side, and herethere are VICH guidelines that
cover all the different areas.
For example, you've gotstandards on the construction of
a single electronic message,the management of adverse events

(43:57):
generally, and also onespecific unique aspect is these
controlled lists of terms thatwe have on the vet side, which
include the global species listand the global breeds list and
also other veterinarypharmacovigilance databases
similar to the EU.
One also use what we callVeDDRA terminology to code the

(44:18):
clinical signs which aredescribed in adverse event
reports and to define VeDDRA asin that stands for the
Veterinary Dictionary for DrugRelated Affairs, and here it's
very much similar to the MeDDRAterminology which you use on the
human side, although there arequite some significant

(44:40):
differences.
Most notably is the totalnumber of terms available.
On the vet side, we haveroughly 2,900 lower level terms,
as we call them, or LLTs, andthese are mainly the terms that
describe the clinical signs thatyou report in an adverse event
report.
And if you compare this to thehuman side, in MeDDRA they have
currently 88,000.
So there's a lot more there.

(45:02):
And also MeDDRA is a bit more ofa complex list, being
multi-axial, so there's severalinterconnections within the list
, whereas VeDDRA is just astraightforward, simple Excel
list.

Thank you very much, James.
That concludes the first partof this two-part episode on
veterinary pharmacovigilance,and next time we will talk about
differences in types of adverseevents reported on the
veterinary and human sides,methods and new technology,
including AI, being used inveterinary pharmacovigilance,
and user safety in veterinarymedicine.

(45:35):
As a veterinarian, I know youhave some hands-on experience of
so-called self-injection, James.

Unfortunately, yes.
Working as a vet, our patientstend to be not so compliant at
times.
Often we're working with movingtargets, which can add an
element of risk.

Yes, I look forward to hearing more about
that.
Until next time.
And if you'd like to learn moreabout differences and
similarities between human andveterinary pharmacovigilance,
James has put together a list oflinks for you in the episode

(46:15):
show notes.
Apart from these conversationswith experts, we offer a series
of audio stories from UppsalaMonitoring Centre's
pharmacovigilance news sitecalled Uppsala Reports Long
Reads, so why not check that outtoo?
That's all for now, but we'll beback soon with the second part
of the VeterinaryPharmacovigilance episode.
In the meantime, please feelfree to reach out on Facebook,

(46:38):
LinkedIn and X, send comments orsuggestions for the show or
questions for our guests, andvisit our website to learn more
about what we do to promotesafer use of medicines and
vaccines for everyone,everywhere.
If you like the podcast, pleasesubscribe to make sure you won't
miss an episode.
And spread the word so otherlisteners can find us too.

(47:00):
For Drug Safety Matters.
I'm Fredrik Brouneus.
Thanks for listening.
Thankyou
.

All Episodes

#34 Veterinary pharmacovigilance, Part I – James Mount

Episode Transcript

Popular Podcasts

Stuff You Should Know

24/7 News: The Latest

Crime Junkie

.css-15opob5{left:0;position:absolute;top:0.8rem;} All Episodes

.css-14f5ked{margin:0;word-break:break-word;display:-webkit-box;-webkit-box-orient:vertical;box-orient:vertical;-webkit-line-clamp:2;overflow:hidden;}#34 Veterinary pharmacovigilance, Part I – James Mount