ARCHIVES HISTORIQUES
DELACOMMISSION
COLLECTION RELIEEDES
DOCUMENTS "COM"
COM(79)59
Vol.1979/0021

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COMMISSION OFTHEEUROPEAN COMMUNITIES
COM(79 )59final |
Brussels ,22February 1979
FIRST COMMISSION REPORT TOTHE COUNCIL
onthefunctioning oftheCommittee forProprietary
Medicinal Products and itsimpact onthedevelopment of
intra-Community trade
Period 1977 /1978
^-r?T rfr-
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C0M(79 >59final

FirstCommissionReportonthefunctioning
oftheCommitteeforProprietaryMedicinalProductsandits.
impactonthedevelopmentofintra-Community trade
Period1977/78
Introduction
Forthepurposeoftheprogressiveestablishment ofthecommonmedicaments
market,theCouncilhashithertoadoptedthefollowingfourDirectives :
-Directive65/65/EECof26January1965(OJof9.2.65)
-Directive75/318/EECof20May1975<0JL147of9.6.75)
-SecondDirective75/319/EECof20May1975asamendedbyDirective
78/420/EECof2May1978<0JL123of11.5.78)
-Directive78/25/EECof12December1977(OJL11of14.1.78).
Thisharmonization ofnationallawshaseliminatedmajorobstaclestothe
freemovementofproprietary medicinalproducts:
-applications formarketingauthorizations (MA)maybesubmittedtothe
competentauthorities ofthememberStatesonthebasisofthesame
particulars andthesameanalytical,toxicological,pharmacological and
clinicaltestresults;
-theproprietary medicinalproductscontrol-tested incompliancewiththe
requirements laiddownfortheMAareexemptedfromfreshcontroltests
whentheyareimportedintoanothermemberState.
However,themarketingauthorizations remaintheresponsibility ofthe
nationalauthorities andthereforethereisariskthatthedifferent
competentauthorities maytakedivergentdecisions.ThisiswhytheCommittee
forProprietaryMedicinalProductswassetup,inordertolimitthisrisk
bymeansofclosecooperation betweennationalauthorities.
TheCommitteemustgiveopinionsonmattersrelatedtotheimplementation
ofArticles5,11and20ofDirective65/65/EEC,andinparticularonthe
harmlessness,efficacyandqualityoftheproprietarymedicinalproducts.
TheCommitteedeliversopinionsinthefollowingthreeevents:

-2-
a)whenamemberStateconsidersthatitcannotgranttheMAforanapplica­
tionLodgedundertheCommunityprocedureasLaiddowninArticle9of
Directive75/319/EEC.Thisproceduremaybeemployedifthepersonconcerned
wishestoplacehisproductonthemarketsofatleastfiveothermember
States;
b)whendifferentdecisionsaretakeninrespectofthesameproprietary
medicinalproduct;
c)whenamemberState,inspecificcasesofCommunityinterest,wishesto
obtaintheCommittee'sopinionbeforetakingadecisiononanMAapplica­
tion,suspensionorrevocation.
However,theCommitteeissuesnon-bindingopinionsonlyinsuchawaythat,
inspiteofthecooperationwithintheCommittee,thesameproprietary
medicinalproductmaybeallowedonthemarketofoneormorememberStates
andrefusedonthemarketsofothermemberStates.
Itisobviousthatthissituationconstitutes anobstacletothefreemovement
ofproprietary medicinalproductsintheCommunity,whichistheobjectiveof
harmonization .ItisforthisreasonthattheCouncilhasaskedtheCommission
(Article15(2)ofDirective75/319)topresentitwithaproposalonall
appropriate measuresforeliminatingoutstandingobstaclestothefreemove­
mentofproprietary medicinalproducts,notlaterthanfouryearsafterthe
entryintoforceofthisDirective,i.e.,beforetheendof1980.
Article15ofDirective75/319alsolaysdownthattheCommissionmustreport
totheCouncileveryyearontheoperationoftheprocedureappLiedbythe
CommitteeforProprietary MedicinalProductsanditsimpactonthedevelop­
«
mentofintra-Community trade,andshalldosoforthefirsttimetwoyears
aftertheentryintoforceoftheDirective.Thisistheobjectofthepresent
document.

χ
-a-
I.Thefunctioning oftheCommitteeforProprietary Medicinal
Products
Theperiodcoveredbythereporthasbeenessentiallycharacterized bythe
setting-upoftheCommitteeandits"running-in",thanksmainlytothe
interestshowninitbythecompetentnationalauthorities.Infact,
applications fromthoseresponsibleformarketing,manufacturers orimporters
haveuptonowbeenveryfew.Accordingtotheindustrialcirclesconcerned,
thismustnotbeattributedto"atraditionalreluctancetofollownewpaths",
buttoveryprecisereasons:
-thedelayinsomememberStatesinimplementing theprovisionsofthe
Directives,renderingitimpossibletousetheCommunityprocedurein
thosecountries;
-therequirementtoapplyformarketingauthorizations foratleastfive
othermemberStates,renderingitdifficulttofollowtheprocedure
becauseproductsaregenerallyintroducedgraduallyonmarkets.
1.Thesetting-upoftheCommittee
1.1Rulesofprocedure
.TheCommitteeforProprietary MedicinalProductsdrewupitsrulesof
procedure,whichwereforwardedtotheCouncilon23December1976for
possiblecommentsaslaiddowninadeclarationincludedinthesummary
recordofthe769thmeetingofthePermanentRepresentatives Committeeon
7and12May1975.On17March1977anamendmenttothedraftruleswas
forwardedtotheCouncil,whichhadcriticizedtheprovisionsgoverningthe
languagesusedintheworkoftheCommittee;infact,theuseoflanguages
intheCommunitiesarelaiddowninCouncilRegulation No1of12April
1958*(0J17/385of6.10.58)asamendedbyAnnexItotheActconcerningthe
ConditionsofAccessionandtheAdjustmentstotheTreaties.
TherulesofprocedureoftheCommitteearesetoutinAnnexItothis
report.

-Ί-
Inadditiontothecustomaryprovisionsinsuchrules,theCommitteeisin
particularempoweredtosetuppanelsofexpertstostudymattersofcommon
interest.Thisrighthasbeenusedthreetimes,aswillbeseenlateronin
thereport.
Furthermore,itislaiddownthattheworkoftheCommitteeandofthepanels
ofexpertsandallthedocumentswhicharesubmittedtothemareconfidential
innature.Thebreachingofprofessionalsecrecyissubjectinallcasesto
penalsanctions.Thisconfidentiality isobviouslywithoutprejudicetothe
notification ofthepersonresponsibleformarketingifareasonedobjection
tothemarketingofhisproductislodgedbyamemberState,assoonasthe
Committeeisapprisedofthis.
1.2ElectionoftheChairmanandDeputyChairman
MrL£onROBERT,theLuxembourgrepresentative ,waselectedChairman,in
accordancewiththeprocedurelaiddowninArticle2oftherulesofprocedure.
MrE.L.HARRIS,theUnitedKingdomrepresentative ,waselectedDeputyChair-'
man.FollowingMrHarris'sappointmenttootherduties,ProfessorDuilio
POGGIOLINI,theItalianrepresentative,waselectedDeputyChairman.The
taskoftheelectedDeputyChairmanismainlytodeputizefortheChairman
atCommitteemeetings.
AsecondDeputyChairman,appointedbytheCommission,isprovidedfor.
HismaintaskistodeputizefortheChairmanintheperiodbetweenmeetings.
MrD.J.DEVINE,Director,wasthusappointedDeputyChairman;hewithdrew
andwasreplacedbyMrNicolaasBEL,HeadofDivision. ':':'
«
AttachedisAnnexII,whichcontainsalistofmembersoftheCommittee.'

-δ-
1.3Notifyingtradecircles
Soastodrawtheattentionofthetradecirclesconcernedtothenewpro­
cedureavailabletothemforplacingproprietarymedicinalproductsonthe
market,viatheCommittee,anoticetomanufacturers andimporterswas
publishedintheOfficialJournaloftheEuropeanCommunities NoC302of
15December1977andreprintedinthenationalofficialgazettes.
Thisnoticedescribestheconditionstobefulfilledinordertousethe
Committeeprocedure,theproceduretobefollowedandtheforceofCommittee
opinions.ThetextofthenoticecanbefoundinAnnexIII.
Meanwhile,themembersoftheCommitteeandoftheSecretariat havetaken
partinanumberoftalks,conferences,seminars,etc.,intendedtomakethe
Committeebetterknown.ItsChairmanhasbeeninvitedseveraltimes,inhis
capacityasChairman,tomostofthememberStates.
2."Running-in"oftheCommittee
2.1Developingitsworkingmethods
Fromtheoutset,theCommitteehasbeenconcernedwiththeefficacyofits
work:first,itsinternalfunctioning,bythesimplification ofprocedures;
secondly,andessentially,forthepurposeofimprovingcooperation between
thecompetentauthorities.Tothisendandsoastoavoiddivergentnational
decisionsasfaraspossible,theCommitteehasrevisedsomegeneral
standardsandhasdrawnupmorespecificprovisions.
a)ItveryquicklyemergedthatArticle9ofDirective75/319/EECwas
unsuitable.TheforwardingofdossierstotheCommitteeandthenonto
thememberStatesconcernedwasliabletocausedelaysdetrimentaltothe
manufacturers and,inthefinalanalysis,tothegoodnameoftheCommit­
tee.Onitsproposal,theCommission,afterconsultingthePharmaceutical
CommitteesetupbyCouncilDecision75/320/EEC,proposedtotheCouncil
thattheDirectivebeamendedtoprovideforthesimultaneous forwardingof
dossierstothememberStatesconcernedandtotheCommittee.Theamendment
wasadoptedbyCouncilDirectiveNo78/420/EECof2May1978(OJL123of
11May1978).
/

b)Likewise/theCommitteeexaminedanumberofproblemsraisedbyDirective
75/318/EECof20May1975(0JL147of9.6.75)withregardtoanalytical,
pharmaco-toxi cologicalandclinicalstandardsandprotocolsinrespectof
thetestingofproprietary medicinalproducts.Itputforwardanumberof
proposalsforrevisionswhichwill,ifappropriate,besubjectedtothe
proceduredescribedabovefortheamendmentoftheprocedureforforwarding
dossiers. ,
c)Soastofacilitatethetaskoftheapplicantsformarketingauthorizations
andofthecompetentauthorities,theCommitteedraftedadocumentindicating
incompliancewithDirectives 65/65/EEC,75/318/EECand75/319/EEC,the
orderinwhichitwishestohavetheparticulars insupportofapplications
forauthorization presentedtoit.(SeeattacheddocumentinAnnexIV.)
d)Moreover,theCommitteewasawarethatthegeneralnatureofthestandards
andprotocolscouldnotguaranteeeithertheuniformityoftheexperimental
workdoneinthedifferent memberStatesortheharmonization ofdecisions
takenbynationalauthorities.Itthereforedecidedtodrawupmorespecific
principlestogovernprocedureinrelationtogivenexperiments orgroups
ofmedicaments sothatthemanufacturers coulddrawtheappropriate
conclusions asregardstheirwork.InaccordancewithArticle13ofits
rulesofprocedure,theCommitteesetupthreeexpertpanelstoassistit
inthistask,namely:
-the"SafetyofDrugs"panel,chairedbyDrJ.P.GRIFFIN,SeniorPrincipal
MedicalOfficerattheDepartmentofHealthandSocialSecurity,London;
-the"EfficacyofDrugs"panel,chairedbyDrM.N.G.DUKES,Vice-President
ofthe"Collegeterbeoordeling vangeneesmiddelen "oftheNetherlands;
-the"MedicinalProductsofPLantOrigin"panel,chairedbyProfessor
B.SCHNIEDERS,DirectoroftheMedicamentsInstituteoftheBundes-
gesundheitsamt ,Berlin.

-?-
Thefollowingprocedurehasuptonowbeenusedsoastoobtainthewidest
possibleconsultations :thepanelsofexpertsdrawupscientificexplanatory
potescoveringallavailabledatathatcanbegathered.Thesenotesare
forwardedbytheCommitteetothecompetentnationalauthoritiesandtothe
tradegroupsorganizedatCommunitylevel.Thenationalauthorities send
thesenotesontothenationalgroupsconcerned.Commentsreceivedbythe
CommitteeforProprietary MedicinalProductsareexaminedbytheexpert
panelswhoamendtheexplanatorynotesaccordinglyorexplainwhytheyhave
maintainedtheirstancetotheCommittee.
Thelegalformtobeassignedtothesedocumentsdependsontheircontents.
ThePharmaceutical Committee,setupbyCouncilDecision75/320/EEC,hasbeen
askedtogiveitsopiniononthispointandthediscussions havenotyetbeen
completed.Thefollowingfivedocumentshavebeendisseminated aswidelyas
possibleandtheexpertpanelsareintheprocessofexaminingthecomments
received:
-fixedcombinationproducts,
-non-steroidal,anti-inflammatory compoundsforthetreatmentofchronic
disorders,
-reproduction studies,
-carcinogenicity testing,
-chronictoxicitystudies.
Thepanelson"SafetyandEfficacyofDrugs"aredraftingnotisinthe
followingfields:
-immunotoxicology
-mutagenicity
-pharmacokinetics
-safetypharmacology
-bioavailability
-toxicitybyinhalation
-acutetoxicity
-sub-acutetoxicity

-o-
Thesepanelsarestillworkingonthefollowingdruggroups:
-anti-epilepticdrugs
-cardiacglycosides
-anti-anginal drugs
-oralcontraceptives.
Thepanelon"MedicinalProductsofPlantOrigin"wassetuptoexaminethe
specificproblemsraisedbythistypeofproduct.Thefactisthatsubjecting
suchproductstoalltherequirements oftheMAdirectivesmightmakethem
disappearfromthemarket,whereasalargenumberoftheseproductsarestill
usedevenifonasmallscale.However,researchcapacityinthisfieldseems
fairlylimitedsincescientificmotivationislowandconsiderablefinancial
resourceswouldbeneeded.Thepanelisaccordinglytryingtoutilizethe
availablescientificdocumentation soastoassesstheefficacyandharmless­
nessoftheseproducts.
2.2Thefunctioning oftheCommittee
a)TheCommitteereceivedtwoMAapplications pursuanttoArticle9of
Directive 75/319/EEC.
Inbothcases,theinitialMAwasgrantedtotheUnitedKingdomandthe
MAapplications concernBelgium,Denmark,Italy,Luxembourg andthe
Netherlands.Theprocedureisinprogressandwillnotbecompletedby
theendoftheperiodcoveredbythepresentreport.
b)UnderArticle12ofDirective75/319/EEC,theCommitteehasnothadto
dealwithdivergentdecisionstakenbythememberStateswithrespectto
MAauthorization,suspensionorrevocation.
c)UnderArticle14oftheabove-mentioned Directive,theCommitteehasbeen
apprisedofandexaminedabouttwentymedicaments,involvingproblemsof
Communityinterest,andinparticularthefollowingproducts:
Carbamazepine -Chloroform-Practolol-Chenodesoxycholi cAcid-
Clozapine-Aprindine-Biguanides-Paracetamol-Tofenacine-Benorylate
Catalase-PipemidicAcid-Aminophenazone -Lynestrenol-Salbutamol
Allergens-Bismuthsalts.
Inaddition,ithasexaminedthefollowingspecificcases:sterilization
byethyleneoxides;asbestosfibres.

-5-
II.Development ofintra-Commumty trade
Duringthissetting-upandrunning-inperiod,itisdoubtfulwhetherthe
functioningoftheCommitteeforProprietaryMedicinalProductsprocedure
willhaveanyinfluenceonthedevelopmentofintra-Community trade.Here
too,statisticalinstruments whichwillenablethisdevelopmenttobe
followedneedtobeputintooperation.
Aworth-whileexercisemightbetotakethestatisticsgoingbackto1974,
thefirstyearforwhichdataonthenine-member Communityareavailable.
ThestatisticsaregiveninEURandinEuropeanunitsofaccount(EUA).
Table6canbeusedforconversiontonationalcurrencies.

1.Medicamentsimportsforclinicalandveterinarymedicine
Origin EUR9 DE FR **
1974'
Intra-Com.523.602 •101.40712.241 66.053
Extra-Corn.177.228 «9.967 4.24421.229
Suisse 94.969 25.834 1.804 11.821
U.S.A.*33.534"9.629*1.0614.416
1975'
Intra-Com.579.425 131,764 14.689 .65.927
Extra-Com.203.199 64.505 .3.036 25.035
i •
Suisse 114.056 33.211 57515.845
U.S.A.,,30.852 7.256 1.057 4.550
*
1976 .
Intra-Com.744.321 .160.257 17.871 82.210
Extra-Com.289.593 *98.100 3.37834.330 .
Suisse 152.872 46,318 58220.357
U.S.A.42.629 10.977 1.286 5.831
1977 '■ •
'Intra-Com.863.446 -203.934 29.645 .81.185
Extra-Com.325.549 122.190 5.403 30.607
Suisse'170.204 55.925 ■83617.197
U.S.A.•44.273 13.080 3.034 5.567IValue:i:::EUR)
m1974-1Ç75
(Value:ic:3EUA)(Chapter30.03ofthe ■\in*976-"977CommonCustomsTariff) \v
NE B-L UK IR 0A
112.583
19.552
12.125
4.402135.998
34.541
24.385
5.02545.570
29.846
11.598
7.35228.042-
2.708
1.113
75121.703
15.141
6.289
898
122.968
19.547
14.493
1.091145.021
38.799
27.479
6.61046.386
32.676
14.799
7.15929.237
3.071
1.794
68123.433
16.530
5.860
2.4480
1
174.117
24.639
17.371
1.096176.242
53.302
40.916
8.48063.573
43.633
16.433
11.11636.549
5.567
3.445
1.11433.502
22.644
7.450
2.699
182.117.'183.123 92.99647.688 -42.758
•34.79856.699'50.173.1.13624.543
25.082/0.7Ê8'21.538 -147.8.691
3.153'7.6C88.964 6242.243
Source:S0EC

ν;•)
2a)Imports&fmedicaments prepackaged forretailsale(Value :*:::EURJ
in1974-WS
(Value :1CC0EUA)
in1976-1977
Origin
1974
Intra-Com .
Extra-Com.EUR9
363.287
81.A15OE
59.258
21.623FR
9.206
2.017IT
.AA.780
13.372NE
80.891
6.370B-L
90.734
11.271UK
33.905
12.569IR
26.882
'2.6260A
17.631
12.567
1975*
Intra-Com.
Extra-Com.401.693
99.84981.080
30.3448.391
1.70245.740
15.36090.535
8.77597.302
14.42934.737
12.35128.306
3.01315.602
13.875
1976
Intra-Com.
Extra-Com."
.^
1977
Intra-Com.
Extra"Com.527.889
140.100
625.414
157.622102.099
A1.448
115.184
'63.10312.374
1.695
19.466
3.62753.860
20.886
56.719
18.623130.044
12.082
144.974
14.237122.074
18.782
125.371
14.94044.755
19.851
72.330
19.77635.067
5.133
44.491
!99227.616'
19.568
34.653
21.424
2|j)Percentage ofintra-Community importsintotalimportsofmedicaments prepackaged forretailsale
1974
1975
1976
197781X
80X
79X
80X73X
73%
71X
65%82X
83%
88X
84%77X
74X
72X
75X92X
91X
92X
89X89X
87X
87X
89X73X
74X
69%
78X917.
90X
87X
98X58%
53*
58X
.62X

-M-
2.c)Percentageofmedicaments prepackagedforretailsaleintotal
Communitymedicaments imports
In1977medicaments prepackagedforretailsalerepresented 66%
ofmedicaments importedbytheCommunity(65%in1976,64%in
1975,63%in1974).
Ifwelookatintra-Communityimportsalone,prepackaged medicaments
accountforaslightlyhigherproportionofthetotalintra-
Communitymedicaments imports:69.3%in1974and1975,71%in
1976,72.4%in1977.Thistrendmightbecomemoremarkedasa
resultofharmonization oflaws,whichmakesimportingproprietary
medicinalproductseasierthananyotherformsofmedicaments (in
bulkorincompoundedform).

Ν
,TN
V
S>3.Medicamentsexportsforclinicalandveterinarymedicine
Destination EUR9 DE fR IT
197A
Intra-Com.554.006161.099 76.59931.550
Extra-Com.1.073.959 344.232 203.415 60.918
Suisse 70.38232.924 13.836 2.626
O.S.A.*17.064 2.010 8525.673
/
1975 * 1
Intra-Com.585.925162.395 91.017 31.441
Extra-Com.1.200.476 355.310.252.999 74.808
Suisse 73.12731.524 14.905 .3.428
U.S.A.,..25.6411.480 59•12.024
1976 '
•Intra-Com."732.547197.223 106.794 46.364
Extra-Com.1.451.670 445.257'1300.203 90.982
Suisse 101.637 43.816 20.093 A.195
U.S.A..30.832 1.071-24815.241
1977
/
Intra-Com.847.668 199.574 134.041 51.746
Extra-Com.-1.703.011 508.969 338.390 120.426
Suisse 117.954 48.415 26.023 5.409
U.S.A.35.573 1.699 24218.523(Value:'CC2EUR)
in*97--^973
(Value;1C:qEUA)(Chapter30.03ofthein"976-"977CommonCustomsTariff/
NE B-L UK I* DA
61.318
60.364
3.308
6696.587
57.529
6.195
65104.623
288.834
8.351
8.1877.192
4.443
116
.9215.038
54.224
3.026
119
61.514
64.147
3.921
301112.800
58.389
7.530
30598.445
328.487
9.212
11.3519.212
6.535
220
,6919.101
59.801,
2.387£
52•
86.792
92.101
6.553
,2.461143.301
76.210
11.588
742113.913
361.196
11.964
10.88014.272
7.554
389
.12723.888
76.167
3.039
62
106.616
104.158
6.517
2.765168.659
96.929
12.404
1.378137.252
435.422
16.186
10.£3320.592
8.039
.421
10429.188
90.673
3.579
29
Source S0EC

(Value:1CCDEUR)
■in197h-1975
Aa)Exportsofmedicamentsprepackagedforretailsale (Value;10C3EUA)inl97o-"97?
Destinationfur9p£ fR IT NE8•L UK IR .DA
1974
Jntra-Comi 413.935 137.093 57.244 17.415 32.629 92.422 63.783 .3.852 9.497
Extra-Com.868.527 276.486 183.925 49.690 50.952 50.238 .207.373 2.848
**47.015
1975,
Intra-Com.439.762 135.856 67.021 19.713 29.101 106.898 61.690 •5.514 13.969
Extra-Com.990.370 291.766 229.980 61.532 54.551 53.848 244.907 3.738 51.676
1976
«ftI
Intra-Com.557.235 168.930 78.977 29.965 51.338 134.218 65.036 9.182 19.589 -C
I
Extra-Gom.1.168.131 362.169 272.880 80.759 77.546 70.650 234.047 4.144 65.936
»■
1977Τ
Intra-Com.646.974 169.777 88.852 34.070 65.768 •159.199 89.082 12.664 27.562
Extra-Com.1.408.492 421.656 ■300.616 106.489 88.056 91.742 ■107.204 5.512 82.217
LhiPercentaaeofintra-Community exportsintotalexportsofmedicaments prepackaged forretailsale
1974 32X33X 24X 26X 39X65X 24X57X 17X
1975 31X32X 23X 24X 35X67X 20X60X.21X
1976 32X32X .22X 27X40X66X 22X 69X. 23X
1977 31X29X 23X 24X43X63X 45X 70X 25X

-15-
4.c)Percentage ofmedicaments prepackaged forretailsaleintotal
Communitymedicaments exports
In1977medicaments prepackagedforretailsaleaccountedfor
80.5%ofmedicamentsexportedbytheCommunity (79%in1976,
80%in1975/79%in1974).

5Developmentoftradeinmedicamentsprepackagedforretailsale
DE- FR IT NE
Indexin1977
Imports intr&-Com.194 211..127 179
extra-Com.292 180 139 223
Exports intra-Com.124 155_196 201
extra-Com.152.•163 214 173(Index 1CC'in1974)
-I UK IR DA
138 213 165- .196
132 157 38. 170'
172 140 329 290
183 52 '193 173

6.a)ValueoftheEUR
•DE
1EUR=•••D:"FR.
1EUR=•••FF
19.74
19753,21978
3,206846,01
5,68
6.b)ValueoftheEuropeanunitofaccount (EUA)
-1EUA=...DM 1EUA=FF
1976
19772,81545
2,64832■■·.5,34486
,5,60608 ·'
6.c)Conversion rate
•1974:0,954980
■1975:0,938341IT 'HE
1EUR=•••LIT '^EUR= L
813: 3,35507,
863•'... '■3,5551)7
1EUÀ=...LITV 1EUA=...HFL
■930,150
'1006,790'-*..2,95515
2,80011 ..

B-L
1EUR=...FB/FLux.UK-IR
1EUR=...UKL/IRL
'Vι■*
197548,6572
48,65720,511
0,534
1EUA=...FB/FLux. 1EUA=...UKL/IRL
1976
1977A3,165A
4
40,88270,621578
0,653701DA,
1EUR=...DKR
7,57831
7,57831
1EUA=...DKR
6,76176
6,85568

-19'-
7.Comments
a)Inintra-Community trade,theBeneluxcountries accountforalmost
halfofprepackaged medicaments imports:
47Xin1974and1975,48Xin1976,43Xin1977.
Intra-Community exports arealsohighlyconcentrated :Germany and
Belgium-Luxembourg accountformorethanhalfofintra-Community
prepackaged medicaments exports:33.1+22.3Xin1974,30.8+
24.3Xin1975,30.3+24Xin1976,26.2+24.2%in1977.
I
I
b)ThefigureforFrenchintra-Community importsofprepackaged .
medicaments isofatokennature-2.5Xoftotalintra-Community
importsin1974,2%in1975,2.3Xin1976and3.1Xin1977.
Thisisevidence oftheobstacles totheimporting ofmedicaments .
TheresultsoftheCommission 'seffortstoeliminate theseobstacles
inconjunction withtheCouncil'seffortstoharmonize lawsarenot
yetreflected inthestatistics .
c)Since1974thepercentage ofintra-Community imports andexports
inthetotalimportsofprepackaged medicaments hasbeenstable
andthisconceals theeffectharmonization oflawshashadonintra-
Community trade.Ontheotherhand,theaccession ofnewmember
Statesseemstobemodifying thepatternoftheirtrade,increasing
thepercentage ofintra-Community imports andexports,therecord
goingtoIreland,whichin1977imported prepackaged medicaments
almostsolelyfromtheCommunity (98%).
d)Theprocedure appliedbytheCommittee forProprietary Medicinal
Products hashadpractically noimpactduringtheperiodcovered
bythereport.However,itisnodoubttoomuchtoexpectgreat
changesintradepatterns inthefuture,evenifthisprocedure
werewidelyused,whenatthepresenttime80Xofimportsof
medicaments prepackaged forretailsalealreadyderivefromimports
between memberStates.

-20
AnnexIRulesofProcedureoftheCommitteeforProprietary
MedicinalProducts
AnnexIIListofmembersoftheCommitteeforProprietary
MedicinalProducts
AnnexIIINoticetomanufacturers andimportersofproprietary
medicinalproducts
I
AnnexIVModelMAapplication 1

ANNEXI
RulesofProcédure
ofthe
Committee forProprietary Medicinal Products
THECOMMITTEE FORPROPRIETARY MEDICINAL PRODUCTS,
HavingregardtoCouncilDirective 75/319/EECof20May1975onthe
approximation ofprovisions laiddownbylaw,regulation oradministrative
actionrelating toproprietary medicinal products,andinparticular
1Article 8(3)thereof,
HASDRAWNUPITSRULESOFPROCEDURE ASFOLLOWS ;
•/«
0JNoL147,9.6.75

Article 1
1.TheCommitteeshallconsistoforerepresentative foreachMemberState
andonerepresentative oftheCommission.Onealternateshallbe
appointedforeachoftherepresentatives .
2.TheCommitteemembersandthealternatesshallbeappointedbythe
MemberStatesforthreeyearsprovidedtheycontinuetobenational
officialsresponsibleforexaminingapplications forauthorization
tomarketproprietary medicinalproducts.Theirappointments shall
*
berenewable.
3.AnalternateshallsitinthiscapacityontheCommitteeonlyifthe
fullmemberisabsentorisunabletodischargehisduties.
4.Eachrepresentative mayarrangetobeaccompaniedatCommitteemeetings
bynotmorethanthree ,.experts..
«• V
5.Evenaftertheirdutieshaveceased/,members,alternatesandexperts
shallberequirednottodiscloseinformation ofthekindcoveredby
theobligationofprofessional secrecy.
Article2
TheCommitteeshallelectitsChairman .fromamongitsmembersbyabsolute
' » •«
•» 4majorityand,secretballot.If,aftertwaballots,nobodyhasobtainedan
absolutemajorityofthevotes,thememberwhoobtainstherelativemajori
atthethirdballotshall,beelected.Intheeventofatietheoldest
candidateshallbedeclaredelected....
Article3
•■'•:.;•■,:.•-'«"t*>...:
ThetermofofficeoftheChairmanshallbethreeyears.Heshall.be
eligibleforre-election onceonly.

Article4
Assoonashetakesuphisduties,theChairmanshallceasetobea
representative andshallbereplacedinthatcapacity.:1"
ί Λ?.->,...._·
Article5
TwoDeputyChairmenshallbeappointedtoreplacetheChairmanwhen
heisabsentorunabletodischargehisduties.OneShallbeelectedby
theCommitteeandtheotherappointedbytheCommission.
TheprovisionsofArticles2and3oftheseRulesofProcedureshall
applytotheelectionandthetermofofficeoftheelectedDeputyChairman.
Article6
TheCommitteeshallbeconvenedbyitsChairman,eitheronhisowninitiative
orattherequestofamember.
Article7""." •'
TheChairmanshalldrawuptheagenda,inwhichdistinctions shallbemade
between:
(a)objectionstoapplications formarketingauthorizations submittedto
theCommitteeforanopinionunderArticle11(1)ofDirective75/319/£EC
(b)refusals,suspensionsorrevocations ofmarketingauthorizations
submittedtotheConmitteeforanopinionunderArticle12<2)of
Directive75/319/EEC;
«
(c)freshexaminations ofpreviousopinionsunderArticle13ofDirective
75/319/EEC;.
(d)specificcasessubmittedunderArticle14ofDirective75/319/EEC.

Article 8
Requests toconvene theCommittee which aremade byamember must be
drawn upinaccordance with theclassification setout intheforegoing
Article and bereasoned such that they mayconstitute theworking paper
ofthe Committee .
Article 9
1.Pursuant toArticle 9(1)ofDirective 75/319/EEC ,,theMember State
concerned shall forward totheCommittee adossier containing :
(a)acopy oftherequest forforwarding tothecompetent authorities
oftheMember States specified ;
(b)acopy ofthemarketing authorization ;
(c)theparticulars anddocuments listed inthesecond paragraph of
Article AofDirective 65/65/EEC .
There shall beforwarded asmany dossiers asthere areMember States
specified ,plusoneforthesecretariat oftheCommittee ,j
2.Pursuant toArticle 9(2)ofDirective 75/319/EEC,theCommittee shall
forthwith forward this dossier tothecompetent authorities ofthe
Member States specified .
3.The Committee shall send tothemembers ofthe Committee the documents
referred toinparagraph 1(a)and (b>above .
Article 10
/
Thedossier kept bythesecretariat oftheCommittee maybeconsulted by
anymember oftheCommittee orbytheexperts referred toinArticle 1(4)
having thewritten authority ofthemember .

Article11
1.Thenotification of-themeeting,theagendaandtheworkingpapers
shallbeforwardedbytheChairmantothemembersoftheCommittee
inaccordancewiththeprocedurelaiddowninArticle18<2>and(3).
2.ThesepapersshallbedeliveredtothePermanentRepresentatives of
theMemberStatesandtotheCommissionnotlaterthanfifteendays-
beforethedateofthemeeting.
3.Inurgentcases,theChairmanmay,attherequestofamemberofthe
Committeeor.ohhisowninitiative,shortenthisperiodofnoticeby
uptothreeclearworkingdays,statingthegroundsforhisdecision.
Article12
1.MeetingsoftheCommitteeshallbevalidlyheldifsixMemberStates
arerepresented.
2.Therepresentative of'aMemberStatemay,ifnecessary,undertakethe
representation ofoneotherMemberState.TheChairmanoftheCommittee
shallbeinformedaccordingly bythePermanentRepresentative of'the
MemberStatewishingtobesorepresented.
Article13
TheCommitteemayconvene'panelsofexpertstostudymattersofcommon
interest. .1
Article14
ThesecretarialservicesfortheCommitteeshallbeprovidedbythe
Commission,assisted,ifnecessary,byexperts.

Article15
1.TheMemberStatesconcernedshallbeinformed ,forthwithofthereasoned
opinionsdeliveredpursuanttoArticles11and12ofDirective75/319/EEC
inaccordancewiththeproceduresetoutinthefirstsubparagraph of
Article18(2).
2.Asummaryrecordshallbepreparedundertheresponsibility ofthe
Chairmanforeachmeeting;itshallbeforwardedtothemembersofthe
CommitteeinaccordancewiththeproceduresetoutinArticle18(2)
and(3).Anycommentswhichthemembersmaywishtomakeshallbe
.communicated totheChairmaninwriting.TheChairmanshallpassthem
ontotheCommittee;ifthereisdisagreement,theprbposedamendment
shallbediscussedatthefollowingmeeting.Ifdisagreementpersists,
thisamendmentshallbeappendedtotherelevantrecord."•*
Article16'
TheChairmanoftheCommitteeshallaetasproxyfortheCommitteeto
performtheformalrecordingreferredt6inArticle10(1)ofDirective
75/319/EEC.-' ••*''^...••••••••:
HeshallforthwithinformtheMemberStatesofthisformalrecordingtrt
accordancewiththeproceduresetoutinthefirstparagraphofArticle18(2).
Article17
1.ThesecretariatoftheCommitteeshallactasproxyfortheCommittee
toforwardthedossierreferredtoinArticle9(2)tothe.competent
authorities oftheMemberStatesinaccordancewiththeprocedureset
outinthefirstparagraphofArticle18(2)and,inthesameway,the
documentsreferredtoinArticle9(3).
2.Theinformation forwardedtotheCommitteeinaccordancewith;
Article11(3),Article12(4)andArticle33ofDirective75/319/EEC.
shallbebroughttotheknowledgeofthemembersoftheCommitteeby
thesecretariatinaccordancewiththeproceduresetoutinthesecond
paragraphofArticle18(2)*

-6-
Article 18
1.Correspondence ofconcern totheCommittee shall beaddressed tothe
secretariat oftheCommittee /.Directorate-General forInternal
■Market andIndustrial Affairs ,fortheattention oftheChairman .-
2.Correspondence intended fortherepresentatives oftheMember States
•shall beaddressed tothePermanent Representations .- ,
Copies ofsuch correspondence shall beaddressed directly tothe *
representati vesoftheMember States .„.
3.Correspondence intended fortherepresentative oftheCommission shall
beadressed totheCommission ,Directorate-General forInternal Market
and Industrial Affairs .
Article 19
Notwithstanding theprovisions ofArticle 214oftheTreaty ,thework of '
theCommittee and ofthepanels ofexperts andallthedocuments submitted
tothem shall betreated asconfidential .Nevertheless ,therepresentatives
oftheMember States may,inaccordance with thenational laws inforce ,
inform theperson responsible formarketing amedicinal product orproducts
of -thereasoned objection ofaMember ..State ,asreferred toinArticle 10(2 )
ofDirective 75/319/EEC .

ANNEXII
COMITEDESSPECIALITES PHARMACEUTIQUES .
COMMITTEE FORPROPRIETARY MEDICINAL PRODUCTS
Président/Chairman;
M.LéonROBERT PrésidentdelaCommissiond'Enregistrement
desMédicaments
MinistèredelaSantépublique
Luxembourg
Vice-Presidents /DeputyChairmen
1.Prof.DuilioPOGGIOLINI
2.M.Nicolaas BELDirettoreGeneraledelServizioFarmaceutico
MinisterodellaSanità
Roma
ChefdeDivisionàlaDirectiongénérale
dumarchéintérieuretdesaffaires
industrielles -CCE
a)Représentants /Représentatives :
b)Suppléants/Deputies:
BELGIQUE
a)M.BenHUYGHE
b)MmeDeniseTORFS-BRUDERInspecteurgénéral,Inspectiongénérale
delaPharmacie
MinistèredelaSantépublique
Pharmacien-Inspecteur ,Inspectiongénérale
delaPharmacie
MinistèredelaSantépublique
DANMARK
a)Mr.SteenANTONSEN
b)Mr.HansOttoANDERSENLaboratoriechef
Sundhedsstyrelsen ,Farmaceutiske
Laboratorium
Sekretariatschef
Sundhedsstyrelsen ,Farmaceutiske
Laboratorium

B.R.DEUTSCHLAND
!
a)Prof.Dr.BernhardSCHNIEDERS
b>Prof.Dr.GunterAflmannLeiterdesInstitutsfürArzneimittel
desBundesgesundheitsamtes
LeiterderAbteilung''Pharmazeutische
FragenderArzneimittelzulassung "des
InstitutsfürArzneimittel des
Bundesgesundheitsamtes
FRANCE
a)M.JeanWEBER DirecteurdelaPharmacieetduMédicament,
MinistèredelaSantépubliqueetdela
Sécuritésociale
b)M.GRECH Pharmacien-Inspecteur delaSantéau
ServiceCentraldelaPharmacieetdes<
Médicaments
MinistèredelaSantépubliqueetdela
Sécuritésociale
IRELAND
a)Dr.AleneSCOTT
b)Prof.OliverFitzGeraldMedicalDirector
NationalDrugsAdvisoryBoard
ChairmanoftheNationalDrugsAdvisory
Board
ITALIA
a)Prof.DuilioPOGGIOLINI DirettoreGeneraledelServizioFarmaceutico
MinisterodellaSanità
b)Dott.RomanoCAPASSO ConsigliereMinisteriale
MinisterodellaSanità
DirezioneGeneraledelServizioFarmaceutico
LUXEMBOURG
a)MileJosannette WEYDERT
b)MlleMarie-Thérèse STROMMENGERPharmacien,InspectiondesPharmacies
MinistèredelaSantépublique
Pharmacienattachéàl'Inspectiondes
Pharmacies
MinistèredelaSantépublique

NEDERLAND
a)Dr.C.A.TEIJGELER
b)Dr.M.N.G. DUKES
UNITED KINGDOM
a)Dr.J.P.GRIFFIN
b)Dr.P.A.FLETCHER
C.C.E./C.E.C.
a)M.N.BEL
b)M.Pierre DUPRATVoorzitter vanhetCollegeterBeoordeling
vanGeneesmiddelen
Ministerie vanVolksgezondheid
Vice-Voorzitter vanhetCollegeter
Beoordeling vanGeneesmiddelen
Ministerie vanVolksgezondheid
SeniorPrincipal MedicaiOfficer
Medicines Division
Department ofHealthandSocialSecurity
Principal MedicaiOfficer
Medicines Division
Department ofHealthandSocialSecurity
ChefdeDivision àlaDirection générale
dumarchéintérieur etdesaffaires
industrielles
Administrateur principal
Direction générale dumarchéintérieur et
desaffaires industrielles

ANNEX III
Notice tomanufacturers and importers ofProprietary Medicinal Products
I. Anewprocedure forplacing proprietary medicinal products onthe
market
Following theEuropean Community Directives adopted in1975 (Official
Journal oftheEuropean Communities NoL147of9/6/1975 )aLlmanufac­
turers ofandpersons responsible formarketing proprietary medicinal
products maynowuse anewprocedure forplacing their products onthe
markets oftheMember States :they may gothrough theCommittee for
Proprietary Medicinal Products attached totheCommission ofthe
European Communities inBrussels .
II.Conditions tobefulfilled inorder touse this procedure
(1)TheProprietary medicinal product inquestion must first have
obtained amarketing authorization (subsequently referred toas
M.A. )inoneoftheMember States ,aslaid down inDirectives
65/65/EEC,75/318/EEC and75/319/EEC .
Vaccines ,toxins andserums ,proprietary medicinal products based
onhuman blood orblood constituents ,radioactive isotopes and -
homeopathic proprietary medicinal products may notbenefit from
this procedure (Article 34ofDirective 75/319/EEC).
(2)Applications forM.A. viatheCommittee must relate toatleast
five other Member States .
Ill -Procedure tobefollowed •
(a)Documents tobesupplied tothecompetent authority oftheMember
State which hasgranted the initial M.A. :
1.Request that thedocuments beforwarded toatleast five named
Member States through theCommittee forProprietary Medicinal
Products ,
2.Information anddocuments listed inthesecond paragraph of
Article 4ofDirective 65/65/EEC,
3.Copy oftheM.A.
(b)Thenumber ofcopies ofthese documents tobesupplied isonefor
each Member State concerned plus one fortheCommittee secretariat .
(c)The languages inwhich thedocuments must bepresented :
•1.The documents referred toinitems 1-7 and9-11 ofthe se­
cond paragraph ofArticle 4must beprovided inoneoftheof­
ficial languages ofeach oftheMember States concerned .

2.Thedocuments referredtoinitem8ofthesecondparagraph
ofArticle 4may,alternatively ,bepresented for
-Germany,inEnglish
-Belgium,inEnglish
-Denmark,inGerman,EnglishorFrench
-Italy,inEnglishorFrench
-Luxembourg ,inGerman,English,ItalianorDutch
-TheNetherlands ,inGerman,EnglishorFrench..
3.ThecopyintendedfortheCommittee secretariat mustbein
EnglishorFrench.
<d)NospecialfeeispayabletotheCommittee forProprietary Medi­
cinalProducts,butnationalregistration feesremainapplicable .
IV.Consideration ofdivergent decisions
Directive 75/319/EECalsomakesprovision forconsideration bythe
Committee ofdivergent decisions takenbytheMemberStatesasregards
theauthorization ,suspension orrevocation ofanM.A.
AnyoneoftheMemberStatesconcerned mayrequestthsopinionofthe
Committee concerning thegroundsforrefusal,suspension orrevoca­
tionoftheM.A.asgivenbytheauthorities ofanother MemberState.
Within30days,theMemberStatesshalln6tifytheCommittee ofthe
actiontheyintendtotakefollowing theopinion.
V.Forceoftheopinions oftheCommittee
Theopinions oftheCommittee shallnotbebindingonMemberStates
andshallriotreplacenational decisions .
Theopinions oftheCommittee ,whichwillbebasedcninformation
contained intheapplication foranM.A.,shallnotberegarded as
M.A.inanyMemberState.
VI.Additional information
Foradditional information ,pleaseapplytotheSecretariat ,Committee
forProprietary Medicinal Products,3Rond-Point Schuman,*049Brussels
ortotheappropriate national licensing authority .
-2-

COMMISSION
OFTHE
EUROPEAN COMMUNITIES
Diroctorato-Gonorol
iniornalmarketandindustrialaffairsOrig.:F
ANNEXIV
COMMITTEE FORPROPRIETARY MEDICINAL PRODUCTS
Applicationformarketingauthorization for
■aproprietary medicinalproduct
TheCommitteeforProprietary Medicinalspecialities wishesin
respectofCouncilDirectives 65/65/EEC,75/318/EECand75/319/EEC
thattheparticulars insupportofapplications forauthorizations
toplaceproprietarymedicinalproductsonthemarketarepresented
inthefollowingwayinordertofacilitatethetaskoftheapplicants
andthecompetentauthorities .

flyleaf •••
•,•»
1.Nameorbusiness nameofapplicant formarketing authorizati
2.FullAddress ••• *>•*«..?
3(a)Nameandaddressofmanufacturer
• 1•'.
3<b)Nameandaddressofimporter '
4.Nameoftheproprietarymedicinalproduct J
* 1
> «*.#'•
5.Pharmaceutical form ■ ••
6.Methodandrouteofadministration
7.Numberofannexessuppliedinsupportoftheapplication

-2-
AnnexI:Generalinformation
Nameoftheproprietary medicinal product -
Pharmaceutical form ;
Qualitative andquantitative composition intermsofactiveprinciples
Therapeutic indications ...„
Dosage
. * ..* *
Côntra-indi cations
Warnings andprecautions (including duringpregnancy )'"'•
Side-effects I
Directions foruse(whereapplicable )
Shelflifeandstorageprecautions .•'

•3•
• «
»
Annex II;Jrifo_rma' tjonand _dqcumen tj:once rni£g^Jr! /j>Ì£0^cJie£Ì >caJL/
biologica lorjni^crobi^o^o^ljca ^_tejrts
Annex IIA;£omp_Utejqua_li ia^ij /e^ujnd^c^a^tj^t^tive composition .■_
*i »*'i' "k'i'' (' «4%• • a'tf) '*«.* »* .£•'iL# •»-Name ofproduct " ' * *' • ■ ••••
-Composition
Names ofconstituents QuantityReference to
standards
Active principles
Other constituents
I
-Container (brief description )
/

4
Annex IIB:Method of^rep^ratlort
1*Manufacturing formula
2.Manufacturing process including in-process control andthe
pharmaceutical assembly process

AnnexIIC;C_o_nt£0_l _ ,£3U
1.Activeprinciples .
(a)Activeprinciplesdescribedin3pharmacopoeia
(b)Activeprinciplesnotdescribedinapharmacopoeia

-6-
AnnexIIC:£ontroj^_of_sjta_rtj_n£ .materla.Is
2.Otherconstituents
ι
(a)Constituents describedinapharmacopoeia .
(b)Constituents notdescribedinapharmacopoeia

-7-
AnnexIID:Control,J^ests£n_in_t <er£edii3_ttG
(ifnecessary )

-8-
AnnexIIE;Cont_ro_ljtests£n_tJ]_e_fj_rn_s_hed £roduct
1.Generalcharacteristics ,otherqualitycontroltestsrequiredby
thenatureoftheproduct
(appearance,dimension,shape,colour,odour,distinguishing
features,etc.)

-9-
AnnexIIE;£ont_ro_L _te_st_s^n_tjhe_f]_n]_s_hed product
2.Identification andquantitative determination oftheactiveprinciple
orprinciples,otherqualitycontroltests,withadescription ofthe
methodsemployed(including,ifnecessary,anddependingonthenature
oftheproduct,biologicalandmicrobiological methods)

10
Annex IIE:Contro_L _test_£ ^n_t_he_fT.nJ_s_hed £.roduct
3.Identification andquantitative determination oftheother
constituents <ifnecessary )

-11-
AnnexIIF:Stabilitytests
1.ProposedshelfLife(dependingonthetypeofcontainer)
2.Informationconcerningstability,includingphysicalstability
-numberofbatchestested
-storageconditions
-methodsemployed
-description ofcontainers

-12-
Annex II F;
'»
3.Results andinterpretations

AnnexIIG:_£qnc_L_usi_ons
Certificate bytheexpertanalystontheapplication ofthemethodsand
justification ofthecontrolmethodstobeusedbythemanufacturer

14-/
AnnexIII:Tox\co^o£ij:a_Land Jtests*
(Summaryofthetasksperformedbytheexpertpharmacologist )
Thefollowinginformation mustbeprovidedinrespectofeachtest:
1.Animalsused(species,strain,sex,etc.)
2.Experimental conditionsincludingdiet
3.Results
AnnexeIIIA:Acutetoxicity
Ifuseismadeofalistofpublishedreferencespursuanttopoint8ofthesecondparagraphofArticle4ofCouncilDirective65/65/EEC
(OJNo22of9February1966),theexpertmustshowthatthisis•justified.

AnnexIII:J[ox_i_£0_l_q£Í_c a_l_arid£harn.a^oj^qc 1icaltests
AnnexIIIB:To_x_i_c .£e£eat_ed„2_dmji_nistration
1.Subacutetoxicitytnals
Vs.

-16-
G
AnnexIII:J[ox>iiiço_lq2.i£a_L _and£ha_rma_co_lq£i >ca_L.tests
s--V.'* **..v
AnnexIIIB: rege£t£d_ajdmjnj[3 _tration
i .ji•
2.Chronictoxicitytrials

-17-
AnnexIII:Tojxi£0_L_qai_ca_l _and^harr^a^co^oai^ça^t_e_st_s
AnnexIIIC:Fo£ta_l_toxj_cjt_£
(a)testsforteratogenicity (dosingduringperiod
oforganogenesis )
(b)pre-andpuv-tr.ataldosingofthemotherto
demonstrateeffects i.atepregnancy,parturition
andLactation

-18-
AnnexIII;Toxi^o^o^û^L and£hannacoJ.q2.i£aJ !i.test^,
AnnexIIIP:FertUjtx£tuches

19-
Ar.nexIII:_To_xi_ccUcci_£a_L__and_o_hsa_co_^o_£i_ca_t__tests
AnnexIIIE:_£a_rc_inog_en_i _c_i_tj£_and£j,ut_a_cenicity;*•

-20 ■;
AnnexIII:Jfo^ijrq^oj^^ça^jarid£hjar£a£oJoçj_\ça t.tests.
AnnexIIIF:Pharmacodynamics •••
1.ActionsreLevanttothe.proposedtherapeutic uses
2.Otheractionsinvestigated .,■
3.Interactions

-21-
AnnexIII;Toxi_co_l0£i_ca_lan_d£harma_co_Lo£Ìcaitests
AnnexIIIG:Pharmacoj<ine_t_i_cs .*
1.Absorption (serumlevelsofthemedicinalproduct)
2.Distribution ofthemedicinalproduct
3.Biotransformation
A.Excretionofthemedicinalproductormetabolites

AnnexIV;jTUn^CjU^tjna^js * _
(Summaryofthetasksperformed bytheexpertclinician)
AnnexIVA;Humanj3harm_acoJLo£y
U^e1Sjmaealistofpublishedreferences pursuanttopoint8of
5o!N0C02n2do?%a9Fr!Ph-0f 40fCo-<^Di^tiVe65/65/EEC
ebruary theexpertmustshowthatthisisjustified .

AnnexIV:CIinj_caL__tri_at_s
AnnexIVB:Clinicald_ata
1.Individualdata-clinicalreports

AnnexIV:Clirncaltnals
AnnexIVB;Qj/n.caL__aata
2.Summary

AnnexIV:_Cl_2_rn_ca_l_tn_a
AnnexIVB:^.^n^cal__da
3.Conclusions

-26
AnnexIV:_CMrnca.l_tr\aL_s i
AnnexIVC:Sidf£>c^s_ajid_ijnte racti_ons
Information onside-effects andinteractions observedwhenusedin
othercountries(theextentofusageintermsofnumberofprescriptions
anddurationofuseisusefulinassessingthefrequencyoftheadverse
reaction).

-27
AnnexV:_Sp_ejDa_rt_]_cjjl_a_rs
AnnexVA:Dosageform
1.Packaging
2.Label
3.Packageinsert

AnnexV;Speci_aJL£a£tj_culars
AnnexVB:SarnpJLe^

-29-
AnnexV:_SpecTaIparticula
AnnexVC:Manufacturer sauthorization

-•30-
JAnnexV:Sp^ciaJ.£a£tj_cuUrs
AnnexVD:Ma^k^ring .a.uthoMz^ti.on