Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, Dublin 2, Ireland
T: +353 1 676 4971 E: [email protected] www.hpra.ie
January 2021 – April 2021
HPRA MEDICINAL PRODUCTS
ISSUE
68
NEWSLETTER
Human Medicines
• ApprovalDatesforPackageLeaets
• Nitrosamine Impurities
• Article 31 Referral for Sartan Medicines – Reminder
• Preparation of Labelling for Joint IE/UK (NI) Packs
• AuditsofTypeIANotications:2019/2020Review
• Reference Medicinal Products – Updated CMDh
Brexit Guidance
• Clinical Trial Regulation Progress
Veterinary Medicines
• HPRA Appearance before Oireachtas Committee on
Agriculture and the Marine
• HPRAVeterinaryMedicinesInformationDay2021
• Submission of Variations to Change MAH’s Local
Representative for MR Products
• Veterinary Medicinal Products and Labelling-related
Revisions
• Update on Implementation of HPRA Report on
the Method of Supply of Antiparasitic Veterinary
Medicinal Products Intended for use in Food-
producing Animals
• UpdateonImplementationofRegulation2019/6and
NewNationalLegislationtoReplaceSINo786of
2007
• PharmacovigilanceChangesArisingfromtheNew
VeterinaryRegulation(EU)2019/6
• QPPV Data Requirement for the Union Product
Database
• Uploading of Product Data to the EMA’s Union
Product Database
• Change to VPO and VPO-1 Category of Supply
• Revision of National Legislation on Veterinary Clinical
Field Trials
• Update on Irish Language Case
Compliance
• AuthenticityVericationofAuthorisationsand
CerticatesissuedbytheHPRA
• CerticatesofFreeSaleforDevicesApprovedunder
theNewMedicalDevicesRegulation2017/745
• EU And UK Trade and Cooperation Agreement
Summary of Annex on Technical Barriers to Trade
(TBT)2-MedicinalProducts
In this Issue
Human
Medicines
Approval Dates for Package
Leaets
Nitrosamine Impurities
TheapprovaldateforaPackageLeaet(PL)isthedatethatthe
caseimplementingoramendingthePLwasclosedbytheHPRA.
ReplacementofaPLontheHPRAwebsiteonlyoccurswhere
thePLtextismateriallychangedduringacase.Whereonlythe
revisiondatehasbeenupdated,thePLtextisnotreplaced.
‘Call for review’ on nitrosamine impurities –
deadline for submission of responses
InlinewiththeCHMPArticle5(3)ScienticOpinion‘callforreview’
process, marketing authorisation holders of human medicinal
productswhichcontainchemicallysynthesisedorbiologically
derivedactivesubstancesarerequiredtoreviewtheirmedicinal
products to determine the risk for the presence of nitrosamines,
andtocompletetherequiredriskevaluation.Whereany risk for
thepresenceofnitrosaminesisidentied,conrmatorytesting
must be performed, and a suitable control strategy implemented
asrequired.Thestepsrequiredbythe‘callforreview’processand
relevantdeadlinesaresummarisedasfollows:
Step Number Chemical Medicinal
Products Deadline
Biological Medicinal
Products Deadline
Step 1 – Risk Evaluation 31March2021 01July2021
Step2–Conrmatory
Testing
26September2022 01July2023
Step 3 – Submission of
relevant variations
26September2022 01July2023
Note that the deadlines differ
betweenchemicalandbiological
medicinalproducts.
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue682
The HPRA reminds marketing
authorisation holders (MAHs) that the
deadlinehasnowpassedforsubmission
of step 1 risk evaluations for medicinal
products containing chemically
synthesisedactivesubstance.MAHs
that have not submitted the step 1 risk
evaluations for these medicines must
complywiththeconclusionsofthe
CHMPScienticOpinionandprovide
a response to step 1 as a matter of
priority.MAHsareremindedoftheir
responsibility to ensure the quality and
safetyoftheirmedicines.
MAHs are also reminded of the
approaching timeline for submitting
step 1 risk evaluations for biological
medicinalproducts,whichis1July
2021.
Furtherpracticalandscienticguidance
on the preparation and submission
of these responses is available on the
CMDhwebsiteunderAdvice from
CMDh -> Nitrosamine impurities.
Article 31 Referral
for Sartan Medicines
– Reminder
TheCHMPinitiallyconcludedareview
of a class of medicines called sartans
(angiotensin II receptor antagonists) in
January2019.Thisreviewexamined
the potential presence of certain
nitrosamine impurities in sartan-
containingmedicinalproducts.In
October2020,theCHMPconcluded
that the outcome of the Article 31
referral on angiotensin II receptor
antagonists (sartans) containing a
tetrazolegroup(EMEA/H/A-31/1471)
shouldbealignedwiththeoutcome
oftheArticle5(3)assessmenton
nitrosamines(EMEA/H/A-5(3)/1490)–
seeDecision(2021)1309of19February
2021.Themainchangeconcernsthe
limitsfornitrosamines,whichpreviously
applied to the active ingredients but
nowapplyinsteadtothenished
products.Marketingauthorisation
holders (MAHs) of sartan medicines
(candesartan, irbesartan, losartan,
olmesartan, valsartan) are advised
to refer to the relevant European
Commission implementing decision
for the revised list of conditions to the
marketing authorisations that must be
compliedwith.
Further guidance on the practicalities
of submitting responses is available on
theCMDhwebsiteunder‘Advice from
CMDh -> Q&A on the implementation
oftheoutcomeoftheArt.31referral
on angiotensin-II-receptor antagonists
(sartans) containing a tetrazole group’.
Inparticular,Question4highlights
the condition categories, implications
andduedatesofthenewCommission
Decision.TheMAHmustensure
that the manufacturing processes
of the active substances used for
theirnishedproductsarereviewed
for the potential risk of formation
of n-nitrosamines and changed as
necessary to minimise nitrosamine
contamination as much as possible, in
linewiththerecommendationsadopted
byCHMPon25June2020(article5(3)
procedure).Theduedateforthisaction
was17April2021.By30June2021,
theMAHmustintroducespecications
forNDMAandNDEAintothenished
productspecication,asappropriate.
Question7outlineswhichvariations
must be submitted to lift the conditions
on the risk assessment and control
strategy for the active substance and
nishedproduct.MAHsformedicinal
products are required to familiarise
themselveswiththerequirements,
ensure compliance and submit the
appropriate variations by the required
timelines.
Whensubmittingthesevariations,
please clearly indicate in the cover
letterand‘scopeandbackground’
section of the variation application form
that the variation is being submitted
to lift the conditions on the MA of
tetrazolesartansandstatewhich
conditionitrelatesto(A,B,C,D).
Preparation of
Labelling for Joint
IE/UK (NI) Packs
The HPRA has received a number of
queries on the approach that marketing
authorisation holders (MAHs) should
takewhenpreparingjointIE/UK(NI)
packsformedicinalproducts.Wewould
liketohighlighttheexibilityalready
available in the HPRA Guide to Labels
andLeaets.Section10.3oftheguide
details some minor amendments to
thelabellingandpackagingleaetthat
donotrequirepriornoticationtothe
HPRA, as long as there are no changes
to the livery layout, design or font size
result.Theseinclude:
– Addition, deletion or change in
foreign MA numbers and/or foreign
MAholderdetails,whichdoesnot
affect any other aspects of the livery
layoutandfontsize.
– Addition, deletion or change in the
administrative information for an EU
MSortheUKplacedwithinthe‘blue
box’,whichdoesnotaffectanyother
aspects of the livery layout and font
size.
– Change to the details for reporting of
side effects in other Member States
not affecting the details for reporting
ofsideeffectsinIreland(jointcountry
packageleaets).
– Change/deletion of a product name
in another Member State in section
6ofthepatientinformationleaet
(MRPproductsonly).
– Change in the details of a distributor/
wholesaler/localrepresentative.
A designated blue box is not required
for the inclusion of such information for
nationalorMR/DCPauthorisations.
Applicants should carefully evaluate
whetherthisexibilitycouldapply
totheirproposedchanges.Insuch
instances, the revised labels or patient
leaetshouldbesubmittedtothe
HPRA at the next regulatory activity
involving a change in the product
information.However,wherechanges
to livery layout design or font size
result,anArticle61.3noticationshould
besubmittedinadvanceasusual.
For MR/DCP procedures, no
divergences of the PL, SmPC or of the
labelling requirements from those in
theEUcommontemplatewouldbe
envisaged, and the name must be the
same for IE and UK (NI) to avoid any
confusion.
Applicantswhowishtodiscussthis
possibility further may submit their
query to [email protected].
TheHPRAwouldalsoliketohighlight
the guidance included in the HPRA
GuidetoLabelsandLeaets on the
development of multilingual packaging
(section5.3oftheguide).
Audits of Type
IA Notications:
2019/2020 Review
The HPRA performs regular audits
ofTypeIAnoticationsinorderto
verify that submissions have been
appropriately categorised; the relevant
conditionsfullledandnecessary
documents submitted; and to ensure a
consistent approach in the processing
of these variations both by marketing
authorisationholdersandtheHPRA.
RecentauditsofTypeIAnotications
haveidentiedanumberofdeciencies,
someofwhichrequiredcorrective
actionsfromtheapplicants.Themost
commondecienciesidentiedwere:
–‘ECClassicationGuideline’pagenot
submitted;
– Missing or incomplete
documentation;
– Conditions relevant to the chosen
TypeIAcategorynotfullled;
–TypeIAINnoticationsnotsubmitted
immediately after the implementation
of the change in the quality system of
the marketing authorisation holder;
–IncorrectclassicationofTypeIA
noticationswherethewrongTypeIA
noticationsubcategorywasselected
orwhereachangewasincorrectly
classiedasaTypeIAnotication
whenaTypeIBvariationwasrequired.
As a result, and in order to reduce
the number of incorrect Type IA
submissions,theHPRAwouldliketo
remindapplicantsofthefollowing:
–AllchangeswhichfallundertheType
IAclassicationareoutlinedinthe‘EC
ClassicationGuideline’,accompanied
by a list of conditions and
documentation requirements for each
category.Inorderforthevariationto
beclassiedasaTypeIA,allofthe
conditions outlined in the guideline for
therelevantcategorymustbefullled
and all of the required documentation
shouldbeprovided.Otherwise,the
variation should be submitted as a
Type IB (default category) or a Type
II variation (if the proposed change
mayhaveasignicanteffectonthe
overallquality,safetyorefcacyofthe
nishedproduct).Applicantsshould
carefully consider the list of conditions
of the relevant category to make
certain the variation is appropriately
classiedasTypeIA.Theauditsfor
2019/2020(Q4andQ1)and2020
(Q2andQ3)foundthatanumber
of submissions did not meet the
conditionsofaTypeIAclassication
andtherefore,theseapplicantswere
requested to resubmit the applications
as Type IB variations, for example,
‘unchangedadditionalspecications
forimpurities’,‘minorchangeinthe
manufacturing process of the active
substance’.
–Therelevantpage(s)ofthe‘EC
ClassicationGuideline’including
conrmationofcompliance
withallrelevantconditionsand
documentation requirements must be
submitted for each change applied
forunderagroupedvariation.
Conditionswillonlybeconsideredto
befulllediftheyhavebeenticked
onthesubmittedguidelinepage.
–TypeIAINnoticationsmustbe
submitted immediately after the
implementation of the change in
the quality system of the marketing
authorisation holder and Type IA
noticationsmustbesubmitted
within12monthsofimplementation.
The date of implementation of each
change should be stated in the
applicationform.
– All of the documentation requirements
should be adhered to, for example, the
details of changes should be outlined
in the present and proposed sections
of the application form and amended
relevant section(s) of the dossier, GMP
certicates,QPdeclarations,etc.,as
applicable, to each variation category
shouldbeprovided.Updatedlabelling
and/orleaettextmustbesubmitted
withthevariationwherethechange
results in changes to the label and/or
leaettext.
– Minor issues, for example,
submission of an incorrect or
incomplete application form, are
also communicated to applicants
viaanemailoutliningthedeciency.
Although no corrective action may
berequiredforthesedecienciesat
the time, if applicants do not address
theseissuesandsuchdeciencies
continuetoarise,theHPRAwill
consider requesting that applications
areresubmitted.
Finally,theHPRAwouldliketoremind
applicants that the EMA has published
a ‘Pre-noticationchecklistforType
IA variations’ intended to support the
submission of complete and accurate
TypeIAnotications.Applicantsare
advisedtoreviewthischecklistpriorto
submissionofTypeIAnotications.
Reference
Medicinal Products
– Updated CMDh
Brexit Guidance
A generic or hybrid application, in
accordancewithArticle10ofDirective
2001/83/EC,referstoinformation
that is contained in the dossier of a
reference medicinal product (RefMP)
that is or has been authorised in
theUnion.AstheBrexittransition
periodhasnowended,theCMDhhas
published updated guidance on RefMPs
in the latest version of the Practical
guidance for procedures related to
Brexit for medicinal products for human
useapprovedviaMRP/DCP(Feb2021).
Specically,forMAHsofgeneric
productstheHPRAwishestodrawyour
attention to the responses to Question
34and39oftheguidancedocument.
Forgeneric,hybridandbiosimilarnew
applications, applicants are advised to
carefullyconsidertheadviceinQ34for
theuseoftheUKRefMP,whichvaries
dependingonwhichsubsectionofthe
applicationform(1.4.2or1.4.3)isunder
consideration.Thesuitabilityforuse
dependsonwhentheUKreference
authorisationwasgranted,whenthe
authorisation for the generic/hybrid
willbegranted,andthetimingof
completionofthenalstudyreportfor
pivotalstudies.
GuidanceondealingwithnewDCPs,
and variations that are cross-referring to
UK marketing authorisations for product
information alignment, is addressed in
theresponsetoQ39andalsoincluded
in Section4.1oftheCMDhminutes,
January2021.
Fornewmarketingauthorisation
applications (MAAs) a European
referenceproduct(ERP)shouldnow
be used unless the exceptional case
outlinedinQ34oftheCMDhBrexit
guidancearises.However,forongoing
genericnewapplications,whilethe
UK ERP may be kept as being the
RefMP of the original application, the
applicant should align the product
informationtoasuitableRefMPwithin
the global marketing authorisation
(GMA).Forvariations,whileitisnot
possible to change the RefMP of the
original application, another EEA RefMP
product from the same GMA should
be used for the purposes of product
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue683
information, or adaptation to a different
EEAproductcouldbeconsidered.
The CMDh minutes provide details of
variationclassicationsandhighlight
the need to keep product information
uptodate.
Pleasenotethatifthenewreference
product (from the same GMA) is not
harmonisedwiththeUKreference
product, a variation needs to be
submitted as a type II variation under
C.I.2.btoaligntheproductinformation
withthisnewreferenceproduct.
In case no other product from the
same GMA is available, adaptation
to a different product, not being the
reference product might be possible by
atypeIIvariationC.I.4.Intheabsence
of another reference product from
thesameGMA,orwheretheMAH
doesnotwishtoadapttoadifferent
product, MAHs are reminded of their
legal obligation to keep their product
informationuptodate.Oftensafety
updates of the product information are
linked to recommendations by PRAC
or CMDh and can be implemented
viatypeIA/IBvariations.Bibliographic
reviewsshouldalsobeperformed,
whererelevant,tosupportanupdate.
Finally, MAHs of generic medicinal
products in such situations are
requested to clearly highlight in the
cover letter for variations the reference
medicinal product used, and further
substantiatetheirchoicee.g.in‘notes
forreviewers’.
The choice of RefMP is the
responsibility of the applicant/MAH,
andHPRAcannotprovidespecic
advice.Generalreferencemedicinal
product related queries can be
submittedto:[email protected].
Clinical Trial
Regulation Progress
On24April2021,theEMA’s
ManagementBoardconrmed
that the introduction of the Clinical
Trial Regulation (Regulation (EU)
No536/2014)wasontracktobe
introducedon31January2022.
Theintroductionofthenewregulation
willseeasignicantchangeinhow
trials are processed across Europe,
withamorestreamlinedapproach
beingadopted.Undertheregulation,
sponsorsofclinicaltrialswillbeable
to submit one application to numerous
Member States across the EU using
an online portal and database called
the Clinical Trial Information System
(CTIS).InIreland,theimplementationof
theregulationwillresultinclinicaltrial
applicationsbeingreviewedintandem
by both the HPRA and the National
Research Ethics Committee for Clinical
Trials(NREC-CT),withasinglenational
decisionbeingissued.Theintroduction
of a more harmonised submission
and assessment process under the
regulationwillalsoresultinincreased
transparency in the area of trials across
Europewhilealsoincreasingefciency
intheapprovalprocess,whichwill
benetIrishpatients.
To ensure national preparedness
in advance of the regulation being
introduced,theHPRAisworkingclosely
withboththeDepartmentofHealth
andtheNationalOfceforResearch
Ethics Committees (nrecofce.ie)aswell
ascontributingtoanumberofworking
groupsatEMAlevel.Furthermore,the
HPRA has created a dedicated page on
itsclinicaltrialsectionofthewebsite
to keep stakeholders informed of all
the latest developments regarding
thelaunchoftheregulation:hpra.ie/
CTR.Thewebsitenotonlyinforms
stakeholders of the latest guidance
in relation to the regulation but also
provides a number of links to key
presentations delivered by both the
EMA and other European organisations
thatdealwithawiderangeoftopics
from the introduction of CTIS to the
submission and assessment of trials
undertheregulation.
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue684
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue685
National Ofce for Research
Ethics Committees
TheHPRAwouldliketotakethis
opportunitytoofciallywelcomethe
NationalOfceforResearchEthics
Committees (nrecofce.ie)whose
memberswereformallyappointed
by the Minister for Health Stephen
Donnellyon6May2021.Themembers
willsitonthreeNationalResearch
EthicsCommittees(NRECs),twoof
whichareintheareaofClinicalTrials
of Investigational Medicinal Products
(NREC-CT)whilethethirdisinthearea
of Clinical Investigations of Medical
Devices(NREC-MD).Theformationof
theseCommitteesmarksasignicant
step on the road to applications
receiving a single national ethics
opinion that is respected nationally,
whilealsoensuringthecontinued
protection of Irish patient safety and
dignity.TheHPRAlooksforwardto
collaboratingcloselywiththeNational
OfceforResearchEthicsCommittees
in the future in the advancement
of clinical trials in Ireland for both
medicinesandmedicaldevices.
Clinical Trial Regulation-
National Collaboration
Project
TheHPRA,intandemwiththeNational
Research Ethics Committee for Clinical
Trials of Investigational Medicinal
Products (NREC-CT), are pleased to
announce the creation of the Clinical
Trial Regulation-National Collaboration
Project(CTR-NCP).TheCTR-NCP
representsjustoneofthewaysinwhich
Ireland is actively preparing nationally
for the introduction of the Clinical Trial
Regulation.TheCTR-NCPwillmimic
thejointassessmentandapproval
model set out under the regulation in
thatapplicationssubmittedwillreceive,
ineffect,asinglenationaldecision.
TheCTR-NCPwillrununtilDecember
2021andSponsorsareencouraged
to contact either clinicaltrials@hpra.
ie or [email protected] for further
information regarding submitting under
thisjointproject.
Clinical Trial Regulation
Information Sessions 2021
The HPRA is planning to host a
number of information sessions on
the upcoming Clinical Trial Regulation
inNovember2021.Theinformation
sessionswillbedeliveredremotelyby
theHPRAandwillprovideattendees
withaninsightintothepractical
application of the regulation, and the
accompanying Clinical Trial Information
System (CTIS), including requirements
forsponsorsaheadofitsintroduction.
Themeetingwillbeofinterestto
those involved in the submission and
managementofclinicaltrialsinIreland.
ColleaguesfromtheNationalOfce
for Research Ethics Committee and
theDepartmentofHealthwillalso
attend.Shouldyouhavesuggested
areasyouwouldliketoseediscussed,
please feel free to email these to
[email protected], quoting Clinical
Trial Regulation Info Day 2021 in the
subjectheading.Interestedpartiesare
encouraged to monitor the Newsand
EventssectionoftheHPRAwebsite for
additional information and instructions
regardingconrmedagendatopicsand
registrationclosertotheplanneddate.
Veterinary Medicines
The HPRA appeared before the
Oireachtas Committee on Agriculture
andtheMarineon27April2021
to discuss the regulation of
veterinary medicines, including the
implementationofRegulation2019/6.
A recording of the event and the HPRA’s
opening statement to the committee
areavailable.
Applicants are reminded that a variation
to change a MAH’s local representative,
as listed in the product labelling, need
only be submitted to the RMS and
totheCMS(s)wherethechangeis
beingapplied.Thechangeshouldbe
classiedasaType1AC.II.6.avariation.
This information is taken from the
January2018meeting minutes of
the Co-ordination Group for Mutual
Recognition and Decentralised
Procedures – Veterinary and Interested
Parties.
The HPRA expects to host an
Information Day for marketing
authorisation holders and
manufacturers of veterinary medicines
ontheimplementationofthenew
requirementsduringQ42021.
Thefocusofthiseventwillbetoassist
stakeholdersinunderstandingthenew
requirementsandtheirimplications.
For more details on this event going
forward,pleaseconsulttheHPRA
websiteforup-to-datenews.Itisthe
preference of the HPRA to host a
physical meeting, rather than a virtual
event,ifpossible.
HPRA Appearance
before Oireachtas
Committee on
Agriculture and the
Marine
Submission of
Variations to
Change MAH’s Local
Representative for
MR Products
HPRA Veterinary
Medicines
Information Day
2021
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue686
Veterinary
Medicinal Products
and Labelling-related
Revisions
Whilstthereviewofmock-upsduring
the various regulatory procedures
remains a valuable activity, the HPRA
continually strives to reduce the
administrative burden associated
withthistaskforbothapplicantsand
regulators.Tothisend,anumber
of HPRA labelling-related guidance
documents and requirements have
been revised to ensure a clear and
efcientprocessforallinvolved.
1. Joint Labelling document
Followingthewithdrawalofthe
UK from the EU, the HPRA remain
committedtosupportingthejoint
labellingprocedure.Theprocedure
involves the coordination of approval of
nalcolourmock-upsbetweenIreland
and the UK for veterinary medicines and
enables marketing authorisation holders
(MAHs) to create one set of mock-ups
forwhichevermarketstheMAHwishes
to combine; IE and GB, IE and UK (NI)
orIEandUK(whichincludesbothGB
andNI).ToaddresstheseBrexit-related
procedural changes, applicants are
advised that the previous guidance
document “HPRA/VMD Joint-labelling
ofproductliteraturebetweenUKand
Ireland”hasnowbeenreplacedwith
the HPRA Guide to Joint Labelling
for veterinary medicinal products for
use in Ireland and the UK.Thisrevised
guidance document sets out the steps
tobothachieveandmaintainjoint
labellingbetweenIEandtheUK.
2. Product literature standard
The HPRA Guide to Product Literature
Standard (PLS) for Veterinary Medicinal
Products(previouslyajointdocument
withtheVMD)hasbeentransformed
into a more compact, user-friendly
document,whichaimstoassist
applicants in the creation of mock-
upsforassessment.There-vamped
document focusses on both general
labellingrequirements,whichwillassist
applicantswiththelayoutanddesign
of their mock-ups and national HPRA
requirements related to method of sale
etc.AppendixIofthisGuideincludesa
practical checklist for consultation prior
tomock-upsubmission.Forjointlabels,
applicants are advised to also consult
the UK’s Product Literature Standard as
publishedbytheVMD.
3. Submission of mock-ups for
variations
Recent updates have been made to the
HPRA Guide to Submission of Mock-
ups for Variations.Theupdatesresultin
the list of variation categories no longer
requiring routine mock-up submission
beingexpanded.Applicantsshould
note,however,thatthesubmissionof
mock-ups may be requested by the
HPRA for any variation category on a
case-by-casebasiswhereareviewis
deemednecessary.
4. Labelling notication
requirements
Historically, changes to mock-ups that
did not affect the font size, layout or
legibilityrequirednoticationbyway
ofemailtotheHPRA.Inaneffortto
reduce administration burden for both
MAHs and the competent authority, the
HPRAnolongerrequiresnotication
ofsuchminorchangesanditwillbe
assumed that the labelling remains
essentiallyaspreviouslyapproved.A
non-exhaustivelistofwhatconstitutes
a minor change can be found on the
HPRAwebsite.Ifthecriteriaofaminor
change is not met and formal approval
of the labelling is requested, please
submitaTypeIB(C.II.6.b)variation
withacoverletterandrevisedmock-
ups.Ifyouareindoubtaboutwhether
a variation is needed, please contact
[email protected].
Update on
Implementation of
HPRA Report on the
Method of Supply
of Antiparasitic
Veterinary Medicinal
Products Intended for
use in Food-producing
Animals
The HPRA is actively engaged in
implementing the change of labelling
process for changing products from
Licensed Merchant (LM) to Prescription
OnlyMedicines(POM)currently.All
newantiparasiticveterinarymedicinal
products for food-producing species
thathavebeenauthorisedsince30
April2021bearaprescriptionmedicine
supplycategory,whilevariation
applications to change existing
productsarebeingprocessedcurrently.
The HPRA hopes to approve all
productsconcernedby28July2021.
TheHPRAwillfollowthepolicy
outlined in the HPRA Guide to
Implementation of Packaging Changes
to Authorised Veterinary Medicinal
Products in implementing the changes
tothelabelling(speciedas‘other
safetyrestrictions–item3.2ofthat
policy).ThismeansthatMarketing
AuthorisationHoldersshould:
• Coordinate the supply/importation
of stock to ensure the introduction
of the amended product labelling
and literature as soon as possible
andinanycase,withinsixmonths
oftheapprovalofthevariation.
Products in old livery containing the
LM supply designation should not be
QP released after six months from the
dateofapprovalofthevariation(i.e.
the labelling of all products released
for the Irish market must be compliant
withtheprescriptionrequirementat
thelatestby28January2022).
• Plan to avoid having large quantities
of product in old livery in the
marketplace in the second half
of2021.Wheretheyexist,MAHs
should place notices in the farming
pressand/orprofessionaljournals
as appropriate, alerting users to the
changes.
•Informretailersofthechanges.
TheHPRAisworkingwiththe
Department of Agriculture, Food and
theMarinetoraiseawarenessofthis
changewithstakeholders.
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue687
Update on
Implementation of
Regulation 2019/6
and New National
Legislation to Replace
SI No 786 of 2007
TheHPRAismid-waythroughaproject
to implement the requirements of
Regulation2019/6ontheauthorisation
and monitoring of veterinary medicinal
products.Thisproject,whichisbeing
led by Ms Elaine Hynes, HPRA Planning
and Authorisation Manager, has a
numberofdifferentobjectives:
• the HPRA’s authorisation and
monitoring processes operate in
compliancewiththenewlegislation;
• the HPRA authorisation and
monitoring processes provide
maximumefciency;
• the HPRA authorisation and
monitoring systems interface correctly
withtheexternalenvironment(e.g.
the EMA’s Union Product Database
and pharmacovigilance systems);
•theHPRAcanpositivelyinuencethe
newnationallegislationthatisbeing
elaborated by the Department of
Agriculture, Food and the Marine;
• the HPRA’s suite of guidelines,
application forms, internal procedures
and other documents are updated;
• stakeholders are provided
withregularandappropriate
communications on developments;
• the HPRA’s personnel are trained on
developments;
• any implications for the HPRA’s
business planning and model is fully
understood.
The HPRA provides a monthly update
on progressonourwebsite.Wewould
encourage marketing authorisation
holderstoreviewtheirownoperational
processes too, to ensure that they are
inlinewithanynewrequirements.
If you have queries relating to the
implementationofthenewlegislation,
please email [email protected].
Pharmacovigilance
Changes Arising from
the New Veterinary
Regulation (EU)
2019/6
TheHPRAwishestohighlightthefact
that Periodic Safety Update Reports
(PSURs)willnolongerberequired
underthenewveterinaryregulation.
Instead,MAHswillberequiredtocarry
out a signal management process for
their veterinary medicinal products, the
outcomeofwhichmustberecorded
on the European Medicines Agency’s
(EMA) Union Pharmacovigilance
database(currentlybeingdeveloped).
InaccordancewithArticle76.2of
theregulation,from28January
2022MAHswillneedtouploadall
suspected adverse event reports that
are reported to them to the Union
Pharmacovigilancedatabasewithin30
daysofreceiptofthereports.
As submission and assessment of PSURs
after28January2022isnotforeseenin
the regulation, only PSURs submitted to
theHPRApriorto28January2022will
beassessed,i.e.thosesubmittedafter
28January2022willnotbeassessed.
Consequently, holders of marketing
authorisationswithaPSURdatalock
point(DLP)of27November2021
orearlierwillneedtosubmitthose
PSURsforassessmentpriorto28
January2022.Marketingauthorisations
withaPSURDLPfallingbetween28
November2021and27January2022
mayalsobesubmittedpriorto28
January2022forassessment.
TheHPRAisawarethatforanumberof
marketing authorisations currently on
a 3-year PSUR submission cycle, and
forwhichtheDLPforthenextPSUR
submissionfallsonorafter28January
2022,thosenon-seriousadverseevent
reportsthatwouldnormallybereported
inaPSURwillnotbeavailablefor
reviewbytheHPRAwithinthecontext
ofaPSURassessment.However,itis
expected that those adverse event
reportswillbeincludedwithintherst
signal management process to be
conducted by marketing authorisation
holdersinaccordancewithArticle81of
theregulation.
Guidance on signal management is
currently being drafted by the EMA and
willbepublishedontheirwebsitein
duecourse.
In the meantime, further information
onthenewveterinaryregulationis
available from the dedicated section
ontheHPRA’swebsite:hpra.ie/
NewVetReg.
QPPV Data
Requirement for
the Union Product
Database
Article55(1)oftheNewVeterinary
Regulation(EU)2019/6requires
the Agency to establish and, in
collaborationwiththeMember
States, maintain a Union database on
veterinary medicinal products, also
referred to as the “product database”,
“UnionProductDatabase”,or“UPD”.
The Commission Implementing Act (EU)
2021/16of8January2021laysdown
the necessary measures and practical
arrangements for the UPD and details
thespecicationstoimplementin
ordertofulltherequirementsofthe
Regulation.
Informationonthequaliedperson
for pharmacovigilance (the QPPV)
is required for upload to the UPD
inrespectof‘legacy’productdata.
‘Legacy’dataisdenedasanydata
on a veterinary medicinal product
authorisedinaMemberStatewitha
marketing authorisation or registration
validonorbefore28January2022.
In order to meet this requirement,
theHPRAwillwritetomarketing
authorisation holders shortly to request
specicQPPVinformation.Wewill
specifywhatisrequiredandthe
deadlineforprovidingthisinformation.
Itisimportantwereceivethisdata
andhavetimetoupdateoursystems.
Wewillbeunabletocompletethe
submission of our product data to the
UPDwithoutthesedetails.
If you have any queries, please do not
hesitate to contact us at newvetreg@
hpra.ie.
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue688
Uploading of Product
Data to the EMA’s
Union Product
Database
TheUnionProductDatabase(UPD)will
contain information on all veterinary
medicinal products that are authorised
intheEU,whenitgoeslivetothe
publicon28January2022.Thiswill
beasignicantstepinimproving
transparency in respect of veterinary
medicines in the EU, as it is expected
to provide information on more than
30,000individualmedicines,once
uploaded by Member States, in due
course.Thedatabasewillinclude
extensive and searchable information
on products, including Summaries of
Product Characteristics and package
leaets.InaccordancewiththeEMA’s
implementation guide,theHPRAwill
commence uploading information
on veterinary products authorised
nationally using the decentralised or
mutual recognition procedures in the
periodupto30September2021.
Data in respect of the other nationally
authorisedveterinaryproductswillbe
uploadedinasecondphase,withthe
upload of all data to be completed by
28January2022.
TheHPRAintendstomaintainitsown
national listing of authorised veterinary
medicinal products on the HPRA
websiteatleastuntiltheendof2022,
butwillreconsiderthepositionatthat
point in the light of experience gained
withtheUPD.
Change to VPO and
VPO-1 Category of
Supply
InaccordancewithArticle34of
Regulation2019/6,theUnionProduct
Database(UPD)willrecordveterinary
medicinal products as either being
‘subjecttoveterinaryprescription’or
‘notsubjecttoveterinaryprescription’.
All nationally authorised veterinary
medicinal products that are currently
authorisedwithaVPOorVPO-1
categoryofsupplywillbemapped
intheUPDassubjecttoveterinary
prescription.TheHPRAisindiscussion
withtheDepartmentofAgriculture,
Food and the Marine and expects that
the use of VPO and VPO-1 categories
ofsupplywillbediscontinuedin
Ireland,andwillinsteadbereplaced
byprescriptionsupply.However,any
warningsandrestrictionsforuseby
veterinarypractitionerswillbestatedin
the Summary of Product Characteristics
(SPC) and product literature, in
accordancewiththerequirementsof
Article35(1)(xi)ofRegulation2019/6.
Theneteffectwillbethatthewords
‘forusebyveterinarysurgeonsonly’
willbestatedintheSPCandproduct
literature,whiletheVPOandVPO-1
symbolswillnolongerappearonthe
productlabelling.TheHPRAexpects
that the QRD template,whichis
currentlybeingupdated,willprovide
additionalexplanationofthispoint.
The HPRA understands that the DAFM
plans to continue current national
supply categories in respect of products
thatarenotsubjecttoveterinary
prescription(i.e.POM(E),PS,LMand
CAM),inaccordancewithArticle103of
theRegulation.
Revision of National
Legislation on
Veterinary Clinical
Field Trials
Veterinaryclinicaleldtrialswill
besubjecttonewcontrolsunder
Regulation2019/6from28January
2022.Theexistingnationalcontrols
speciedbySI.No.786of2007,
asamended,willberevisedbythe
Department of Agriculture, Food
and the Marine to ensure that they
complementRegulation2019/6and
arenotinconictwithit.TheHPRA
understands that the overall process for
submitting and processing applications
forclinicaleldtrialswillremainlargely
similartothatinoperationcurrently.
Applicants are requested to keep in
touchwithdevelopments,whichwillbe
reportedontheHPRAwebsite(hpra.
ie/NewVetReg).Thenewnational
legislation is not expected to be
availableuntiltheendof2021.
Update on Irish
Language Case
In respect of proceedings relating to
the provision of bilingual packaging of
veterinary medicines in the Irish and
English languages brought against
the Department of Agriculture, Food
andtheMarine(DAFM)in2016,the
European Court of Justice (ECJ) gave
itsrulingon17March2021.TheEU
CourtsaidthattheDirective2001/82/
EC language requirement for the
labelling of veterinary medicines had
been incorrectly transposed into Irish
nationallaw.Italsofoundthatthefact
thatRegulation2019/6,whichapplies
from28January2022andprovides
that Member States can choose the
language of the text to be used in the
packageleaetandlabelling,cannot
justifydisregardingtheobligationinthe
directive.ItstatedthattheHighCourt
is required to uphold the application
for a declaration that Ireland is under
an obligation to remedy the incorrect
transpositionofthedirective.
Thejudgmentisexpectedtobe
returned to the High Court in Dublin to
decideonwhattodonext.TheHPRA
willcontinuetomonitordevelopments
inthiscase.
HPRAMedicinalProductsNewsletter–January2021toApril2021–Issue689
Compliance
Authenticity
Verication of
Authorisations and
Certicates issued
by the HPRA
Since1September2020,theHPRAhas
issuedelectronicauthorisationswith
e-signatures and no longer routinely
issues hard copies of Manufacturing
Authorisations/Licences,Wholesale
Distribution Authorisations and Active
SubstanceRegistrations.Authenticity
of electronic authorisations issued
bytheHPRAmaybeveriedonthe
EudraGMDP database or, alternatively,
enquiries can be submitted to the
compliance mailbox (compliance@hpra.
ie).
GMPandGDPcerticateswillbe
uploaded to the EudraGMDP database
upon receipt of responses to the
decienciesandpointsforclarication
outlinedintheinspectionreport,which
havebeendeemedacceptable.The
HPRAwillnotroutinelyissuehard
copiesofGMP/GDPcerticatesand
theirauthenticitymaybeveriedon
theEudraGMDPdatabase.Hardcopies
ofGMP/GDPcerticatesmaybe
requestedviatheexportcertication
process,detailsofwhichcanbe
accessed on the ExportCertication
webpageoftheHPRAwebsite.
Certicates of
Free Sale for
Devices Approved
under the New
Medical Devices
Regulation
2017/745
Asof26May2021,theHPRAaccepts
applicationsforcerticatesoffree
saleunderthenewMedicalDevices
Regulation2017/745,whichbecame
fullyapplicableonthatdate.Anew
application form and a revised guidance
document have been published on
ourwebsite.Completedapplications
should be submitted to exportcerts@
hpra.ie.Allqueriesinrelationto
certicatesoffreesalecanalsobe
emailed to [email protected].
EU and UK Trade
and Cooperation
Agreement Summary
of Annex on Technical
Barriers to Trade
(TBT) 2 – Medicinal
Products
The EU and UK Trade and Cooperation
Agreement(TCA)waspublishedon
24December2020.TheTCAincludes
an Annex for human and veterinary
medicinalproducts,whichsetsout
the conditions for the recognition of
Good Manufacturing Practice (GMP)
inspectionsbetweenregulatory
authorities in EU Member States and
theUnitedKingdom.
Belowaresomekeysummarypoints
fromAnnexTBT–2onmedicinal
products:
•TheUKandtheEUwillrecognise
GMP inspections at manufacturing
sites carried out by either party
intheirjurisdictionsandinthird
countries.
•FollowingarequestforGMP
documentation, each party shall
endeavour to transmit the document
within30calendardaysofthedateof
therequest.
•Underspeciccircumstances,each
partymayoptnottoacceptanofcial
GMP document issued by the other
party’sauthority.
• Each party has the right to conduct
itsowninspectionofmanufacturing
facilitiesthathavebeencertiedas
compliantbytheotherparty.
• Each party shall notify the other party
atleast60daysbeforeadoptingany
newmeasuresorchangesrelatingto
GMP, concerning any of the relevant
laws,regulationsandtechnical
guidelines.
•Asaresultofanyofthenew
measures or changes, a party can
consider that it can no longer
recognise inspections or accept
ofcialGMPdocumentsissuedbythe
other party and the parties shall enter
intoconsultationswithintheworking
grouponmedicinalproducts.
• Each party has the right to suspend
totally or partially the recognition of
inspections of the other party for all
orsomeoftheproducts.
•Thepartiesshallcooperatewitha
viewtostrengthening,developing
and promoting the adoption and
implementation of internationally
agreedscienticortechnical
guidelines.
•Theworkinggrouponmedicinal
products shall assist the Trade
Specialised Committee on Technical
Barriers to Trade in monitoring and
reviewingtheimplementationand
ensuring the proper functioning of
thisAnnex.