COMMISSION REGULATION(EC)No1234/2008
of24November2008
concerning the examination of variations to the terms of marketing authorisations for medicinal products for human u and veterinary medicinal products
(Text with EEA relevance)
THE COMMISSION OF THE EUROPEAN COMMUNITIES,
Having regard to the Treaty establishing the European Community,
Having regard to Directive2001/82/EC of the European Parliament and of the Council of6November2001on the Community code relating to veterinary medicinal products(1), and in particular Article39(1)thereof,
Having regard to Directive2001/83/EC of the European Parliament and of the Council of6November2001on the Community code relating to medicinal products for human u(2),and in particular Article35(1)thereof,
Having regard to Regulation(EC)No726/2004of the European Parliament and of the Council of31March2004laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary u and establishing a European Medicines Agency(3),and in particular of Article16(4)and Article41(6)thereof,
Whereas:
(1)The Community legal framework regarding variations to
the terms of marketing authorisations is laid down in
Commission Regulation(EC)No1084/2003of3June
2003concerning the examination of variations to the
terms of a marketing authorisation for medicinal
products for human u and veterinary medicinal
products granted by a competent authority of a
Member State(4)and Commission Regulation(EC)No
1085/2003of3June2003concerning the examination
of variations to the terms of a marketing authorisation
for medicinal products for human u and veterinary
medicinal products falling within the scope of Council
Regulation(EEC)No2309/93(5).In the light of practical
experience in the application of tho two Regulations,it
is appropriate to proceed to their review in order to
establish a simpler,clearer and more flexible legal
framework,while guaranteeing the same level of public
and animal health protection.
(2)The procedures laid down in Regulations(EC)No
高泽冶
1084/2003and(EC)No1085/2003should therefore
be adjusted,without departing from the general prin
ciples on which tho procedures are bad.For
reasons of proportionality,homeopathic and traditional
herbal medicinal products which have not been granted a
marketing authorisation but are subject to a simplified
registration procedure should remain excluded from the
scope of the Regulation.
(3)Variations to medicinal products can be classified in
different categories,depending on the level of risk to
public or animal health and the impact on the quality,
safety and efficacy of the medicinal product concerned.
Definitions for each of tho categories should therefore
be laid down.In order to bring further predictability,高血压健康宣教
guidelines on the details of the various categories of
variations should be established and regularly updated
in the light of scientific and technical progress,taking
in particular account of developments regarding inter
national harmonisation.The European Medicines
遣怀杜牧Agency(hereinafter the Agency)and the Member States
should also be empowered to give recommendations on
the classification of unforeen variations.
(4)It should be clarified that certain changes which have the
highest potential impact on the quality,safety or efficacy
of medicinal products require a complete scientific
asssment,in the same way as for the evaluation of
new marketing authorisation applications.
(5)In order to further reduce the overall number of
variations procedures and to enable competent auth
orities to focus on tho variations that have a genuine
impact on quality,safety or efficacy,an annual reporting
system should be introduced for certain minor variations.
Such variations should not require any prior approval
and should be notified within12months following im
plementation.However,other types of minor variations
who immediate reporting is necessary for the
continuous supervision of the medicinal product
concerned should not be subject to the annual
reporting system.
(1)OJ L311,28.11.2001,p.1.
(2)OJ L311,28.11.2001,p.67.
(3)OJ L136,30.4.2004,p.1.
(4)OJ L159,27.6.2003,p.1.
(5)OJ L159,27.6.2003,p.24.
(6)Each variation should require a parate submission.
Grouping of variations should nevertheless be allowed
in certain cas,in order to facilitate the review of the
variations and reduce the administrative burden.
Grouping of variations to the terms of veral
marketing authorisations from the same marketing auth
orisation holder should be allowed only insofar as all
士组词concerned marketing authorisations are affected by the
exact same group of variations.
(7)In order to avoid duplication of work in the evaluation
of variations to the terms of veral marketing authoris
ations,a worksharing procedure should be established
under which one authority,chon amongst the
competent authorities of the Member States and the
Agency,should examine the variation on behalf of the
other concerned authorities.
(8)Provisions should be established reflecting tho laid
down in Directive2001/82/EC and Directive
2001/83/EC as regards the role of the coordination
groups established under Article31of Directive
2001/82/EC and Article27of Directive2001/83/EC,
to increa cooperation between Member States and
allow for the ttlement of disagreements in the
evaluation of certain variations.
(9)This Regulation should clarify when the holder of a
marketing authorisation is allowed to implement a
given variation as such clarification is esntial for
economic operators.
(10)A transitional period should be established in order to
give all interested parties,in particular Member States
authorities and the industry,time to adapt to the new
legal framework.
(11)The measures provided for in this Regulation are in
accordance with the opinions of the Standing
Committee on Medicinal Products for Human U and
the Standing Committee on Veterinary Medicinal
Products,
HAS ADOPTED THIS REGULATION:
黄山猴子观海CHAPTER I
GENERAL PROVISIONS
Article1
Subject matter and scope
1.This Regulation lays down provisions concerning the examination of variations to the terms of the f
ollowing marketing authorisations for medicinal products for human u and veterinary medicinal products:
(a)authorisations granted in accordance with Council Directive
87/22/EEC(1),Articles32and33of Directive2001/82/EC, Articles28and29of Directive2001/83/EC and Regulation (EC)No726/2004;
(b)authorisations granted following a referral,as provided for
in Articles36,37and38of Directive2001/82/EC or Articles32,33and34of Directive2001/83/EC,which has led to complete harmonisation.
2.This Regulation shall not apply to transfers of a marketing authorisation from one marketing authorisation holder(hereinafter holder)to another.
3.Chapter II shall apply only to variations to the terms of marketing authorisations granted in accordance with Directive 87/22/EEC,Chapter4of Directive2001/82/EC or Chapter4of Directive2001/83/EC.
4.Chapter III shall apply only to variations to the terms of marketing authorisations granted in accordance with Regulation (EC)No726/2004(hereinafter centralid marketing authorisations).
Article2
Definitions
For the purpos of this Regulation,the following definitions shall apply:
1.‘Variation to the terms of a marketing authorisation’or ‘variation’means an amendment to the contents of the particulars and documents referred to in:
(a)Articles12(3),13,13a,13b,13c,13d and14of
Directive2001/82/EC and Annex I thereto,and
Article31(2)of Regulation(EC)No726/2004in the
ca of veterinary medicinal products;
(b)Articles8(3),9,10,10a,10b,10c and11of Directive
2001/83/EC and Annex I thereto,Article6(2)of Regu
鲸山别墅lation(EC)No726/2004,point(a)of Article7(1)and
Article34(1)of Regulation(EC)No1901/2006of the
European Parliament and of the Council(2)and Articles7
and14(1)of Regulation(EC)No1394/2007of the
European Parliament and of the Council(3)in the ca
of medicinal products for human u;
(1)OJ L15,17.1.1987,p.38.
(2)OJ L378,27.12.2006,p.1.
(3)OJ L324,10.12.2007,p.121.
2.‘Minor variation of type IA’means a variation which has
only a minimal impact,or no impact at all,on the quality, safety or efficacy of the medicinal product concerned;
3.‘Major variation of type II’means a variation which is not an
extension and which may have a significant impact on the quality,safety or efficacy of the medicinal product concerned;
4.‘Extension of a marketing authorisation’or‘extension’means
a variation which is listed in Annex I and fulfils the
conditions laid down therein;
5.‘Minor variation of type IB’means a variation which is
neither a minor variation of type IA nor a major variation of type II nor an extension;
6.‘Member State concerned’means a Member State who
competent authority has granted a marketing authorisation for the medicinal product in question;
7.‘Relevant authority’means:
(a)the competent authority of each Member State
concerned;
(b)in the ca of centralid marketing authorisations,the
Agency;
8.‘Urgent safety restriction’means an interim change to the
product information due to new information having a bearing on the safe u of the medicinal product,concerning in particular one or more of the following items in the summary of product characteristics:therapeutic indications, posology,contra-indications,warnings,target species and withdrawal periods.
Article3
Classification of variations
1.In relation to any variation which is not an extension the classification laid down in Annex II shall apply.
2.A variation which is not an extension and who classification is undetermined after application of the rules provided for in this Regulation,taking into account the guidelines referred to in point(a)of Article4(1)and,where relevant, any recommendations delivered pursuant to Article5,shall by default be considered a minor variation of type IB.
3.By way of derogation from paragraph2,a variation which is not an extension and who classification is undetermined after application of the rules provided for in this Regulation shall be considered a major variation of type II in the following cas:
(a)upon request from the holder when submitting the
春天的四字词语variation;
(b)where the competent authority of the reference Member
State as referred to in Article32of Directive2001/82/EC and Article28of Directive2001/83/EC(hereinafter the reference Member State),in consultation with the other Member
States concerned or,in the ca of a centralid marketing authorisation,the Agency concludes,following the asssment of validity of a notification in accordance with Article9(1)or Article15(1)and taking into account the recommendations delivered pursuant to Article5,that the variation may have a significant impact on the quality, safety or efficacy of the medicinal product concerned.
Article4
Guidelines
罗曼绮1.The Commission shall,after consulting the Member States, the Agency and interested parties,draw up:
(a)guidelines on the details of the various categories of
variations;
(b)guidelines on the operation of the procedures laid down in
Chapters II,III and IV of this Regulation as well as on the documentation to be submitted pursuant to the procedures.
2.Guidelines referred to in point(a)of paragraph1shall be drawn up by the date referred to in the cond subparagraph of Article28and shall be regularly updated,taking into account the recommendations delivered in accordance with Article5as well as scientific and technical progress.
Article5
Recommendation on unforeen variations
1.Prior to submission or examination of a variation who classification is not provided for in this Regulation,a holder or a competent authority of a Member State may request the coordination group referred to in Article31of Directive 2001/82/EC or in Article27of Directive2001/83/EC(hereinafter the coordination group)or,in the ca of a variation to the terms of a centralid marketing authorisation,the Agency to provide a recommendation on the classification of the variation.
The recommendation referred to in the first subparagraph shall be consistent with the guidelines referred to in point(a)of Article4(1).It shall be delivered within45days following receipt of the request and nt to the holder,the Agency and the competent authorities of all Member States.
2.The Agency and the two coordination groups referred to in paragraph1shall cooperate to ensure th
e coherence of the recommendations delivered in accordance with that paragraph and publish tho recommendations after deletion of all information of commercial confidential nature.
Article6
Variations leading to the revision of product information Where a variation leads to the revision of the summary of product characteristics,labelling or package leaflet,this revision shall be considered as part of that variation.
Article7
Grouping of variations
1.Where veral variations are notified or applied for,a parate notification or application as laid down in Chapters II,III and IV shall be submitted in respect of each variation sought.
2.By way of derogation from paragraph1,the following shall apply:
(a)where the same minor variations of type IA to the terms of
one or veral marketing authorisations owned by the same holder are notified at the same time to the same relevant authority,a single notification as referred to in Articles8 and14may cover all such variations;(b)where veral variations to the terms of the same marketing
authorisation are submitted at the same time,a single submission may cover all such variations provided that the variations concerned fall within one of the cas listed in Annex III or,if they do not fall within one of tho cas, provided that the competent authority of the reference Member State in consultation with the other Member States concerned or,in the ca of a centralid marketing authorisation,the Agency agrees to subject tho variations to the same procedure.
The submission referred to in point(b)of the first subparagraph shall be made by means of the following:
—a single notification as referred to in Articles9and15 where at least one of the variations is a minor variation of type IB and all variations are minor variations;
—a single application as referred to in Articles10and16 where at least one of the variations is a major variation of type II and none of the variations is an extension;
—a single application as referred to in Article19where at least one of the variations is an extension.
CHAPTER II
VARIATIONS TO MARKETING AUTHORISATIONS GRANTED IN ACCORDANCE WITH DIRECTIVE87/22/EEC,CHAPTER4OF DIRECTIVE2001/82/EC OR CHAPTER4OF DIRECTIVE
2001/83/EC
Article8
Notification procedure for minor variations of type IA 1.Where a minor variation of type IA is made,the holder shall submit simultaneously to all relevant authorities a notification containing the elements listed in Annex IV.This notification shall be submitted within12months following the implementation of the variation.
However,the notification shall be submitted immediately after the implementation of the variation in the ca of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned.
2.Within30days following receipt of the notification,the measures provided for in Article11shall be taken.
Article9
Notification procedure for minor variations of type IB 1.The holder shall submit simultaneously to all relevant authorities a notification containing the elements listed in Annex IV.
If the notification fulfils the requirement laid down in the first subparagraph,the competent authority of the reference Member State shall,after consulting the other Member States concerned, acknowledge receipt of a valid notification.
2.If within30days following the acknowledgement of receipt of a valid notification,the competent authority of the reference Member State has not nt the holder an unfavourable opinion,the notification shall be deemed accepted by all relevant authorities.
Where the notification is accepted by the competent authority of the reference Member State,the measures provided for in Article11shall be taken.
3.Where the competent authority of the reference Member State is of the opinion that the notification cannot be accepted, it shall inform the holder and the other relevant authorities, stating the grounds on which its unfavourable opinion is bad.
Within30days following the receipt of the unfavourable opinion,the holder may submit to all relevant authorities an amended notification in order to take due account of the grounds laid down in that opinion.
If the holder does not amend the notification in accordance with the cond subparagraph,the notification shall be deemed rejected by all relevant authorities and the measures provided for in Article11shall be taken.
4.Where an amended notification has been submitted,the competent authority of the reference Member State shall asss it within30days following its receipt and the measures provided for in Article11shall be taken.
Article10
‘Prior Approval’procedure for major variations of type II 1.The holder shall submit simultaneously to all relevant authorities an application containing the elements listed in Annex IV.If the application fulfils the requirements laid down in the first subparagraph,the competent authority of the reference Member State shall acknowledge receipt of a valid application and inform the holder and the other relevant authorities that the procedure starts from the date of such acknowledgement.
2.Within60days following the acknowledgement of receipt of a valid application,the competent authority of the reference Member State shall prepare an asssment report and a decision on the application,which shall be communicated to the other relevant authorities.
The competent authority of the reference Member State may reduce the period referred to in the first subparagraph,having regard to the urgency of the matter,or extend it to90days for variations listed in Part1of Annex V.
The period referred to in the first subparagraph shall be90days for variations listed in Part2of Annex V.
3.Within the period referred to in paragraph2,the competent authority of the reference Member State may request the holder to provide supplementary information within a time limit t by that competent authority.In this ca:
(a)the competent authority of the reference Member State shall
inform the other competent authorities concerned of its request for supplementary information;
(b)the procedure shall be suspended until such supplementary
information has been provided;
(c)the competent authority of the reference Member State may
extend the period referred to in paragraph2.
4.Without prejudice to Article13and within30days following receipt of the decision and of the asssment report referred to in paragraph2,the relevant authorities shall recogni the decision and inform the competent authority of the reference Member State accordingly.
If,within the period referred to in the first subparagraph,a relevant authority has not expresd its disagreement in accordance with Article13,the decision shall be deemed recognid by that relevant authority.
