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THE EUROPEAN MEDICINES AGENCY: STRUCTURE AND REGULATORY STRUCTURE AND REGULATORY PROCEDURES
M d l J M t Module Jean Monnet: “Regulatory networks and European governance”
5 November 2010, Milan
An agency of the European Union
Tomasz JabłońskiLegal Service - Directorate
OUTLINEOUTLINE
• STRUCTURE / TASKS OF THE EMA
- DEFINITION OF THE MEDICINAL PRODUCTDEFINITION OF THE MEDICINAL PRODUCT
• REGULATORY PROCEDURES
- STANDARD MA PROCEDURESTANDARD MA PROCEDURE
- RENEWAL PROCEDURE
- MAH TRANSFER PROCEDUREMAH TRANSFER PROCEDURE
- REFERRAL PROCEDURES
2
PHARMACEUTICAL INDUSTRY:A CORE SECTOR FOR EUROPE
635 000 employees often highly skilled~ 635.000 employees, often highly skilled
Limited number of big multinationals and
~ 2.000 biotech companies
~ 145 Billion Euro market value ex factory
205 Billi E t t il i~ 205 Billion Euro at retail prices
430 € retail expenditure for each EU citizen
~ 57 Billion Euro invested in marketing and ~ 57 Billion Euro invested in marketing and promotional expenditure each year
~ 27 Billion Euro invested in R&D each yearSource: EFPIA
3
European Union Member States
496 million users of medicinal products
States
30 EU and EEA-EFTA countries
M th 40 ti l t t More than 40 national competent
authorities
4,300 European experts
6 scientific committees
41 EUROPEAN MEDICINES AGENCY
A EUROPEAN AGENCY
The EMEA is a decentralised body of The EMEA is a decentralised body of the European Union
The EMEA has its own legal personality and it is not part of the personality and it is not part of the European Commission
The EMEA issues scientific opinions addressed to the European addressed to the European Commission
The Commission issues decisions i k ti concerning marketing
authorisations*
Opinions are not binding but h dCommission has to provide
justification if departing from the opinion
5
* Exception: Decision-making power is assigned to the EMA by Paediatric Regulation with regard to PIPs approval
The EMEA is responsible for the evaluation andfor the evaluation and
supervision of medicinal productsproducts
for human and veterinary useuse
in the European Union
6
SCOPE OF THE EMA’s RESPONSIBILITIESSCOPE OF THE EMA s RESPONSIBILITIES
Inter alia:
• Centralised procedure [Reg.(EC)726/2004]Centralised procedure [Reg.(EC)726/2004]
• Referral procedures [Reg.(EC)726/2004 and Dir.2001/83/EC]
• Paediatric medicinal products [Reg.(EC)1901/2006]
• Orphan medicinal products [Reg.(EC)141/2000]
• Advanced therapies medicinal products [Reg.(EC)1394/2007]
7
45 YEARS OF HARMONISATION
1965 - First Directive set out basic principles1965 - First Directive set out basic principles
1975 - First pharmaceutical testing Directive
1981 - Specific veterinary legislation adoptedp y g p
1985 - ‘1992 Single Market’ project launched
1993 - Council Regulation No 2309/93 adopted
1995 - EMEA officially opens and new Europeansystem comes into operation
2001 - Commission proposes ‘Review’ packagep p p g
2004 - Part of new legislation comes into force
2005 - New legislation came fully into force
2006 - New legislation on paediatrics
2007 - New legislation on advanced therapies
2008 New legislative package
8
2008 - New legislative package
A NETWORKING DECENTRALISED AGENCYA NETWORKING DECENTRALISED AGENCY
M b S h l d h i i f h i i f Member States have pooled their sovereignty for authorisation of medicines
EMEA i d i d t di t th i ti i tifi EMEA is designed to coordinate the existing scientific resources of Member States
EMEA is not intended to replace national authorities but to be a EMEA is not intended to replace national authorities, but to be a partner in the system
A ‘virtual’ agency providing an interface between all partnersA virtual agency, providing an interface between all partners
All parties linked by an IT network (EudraNet)
9
EMA AND EU INSTITUTIONSEMA AND EU INSTITUTIONS
EMA is a decentralised agency of the EU, not part of the European Commissionthe European Commission
EMA adopts opinions on basis of scientific criteria, C i i t k d i i b d th t i iCommission takes decisions based on that opinion
Commission must fully justify decision when it is not in accordance with EMA opinion
10
EMA AND EU INSTITUTIONSEMA AND EU INSTITUTIONS
European Commission (mainly DG Enterprise and DG Health and consumer protection)Health and consumer protection)
European Parliament (Environment, public health and f d f t itt )food safety committee)
Other EU agencies such as the EMCDDA (narcotics agency), ECDC, EFSA, Translation Centre, etc.
11
EMA AND NATIONAL AUTHORITIESEMA AND NATIONAL AUTHORITIES
EMA hosts CMD (human and vet) meetings and provides secretariat, which meet in parallel to CHMP and CVMP meetings , p g(11/year)
EMA participates at the Heads of Medicines Agencies’ meetings (4/year)
Regular reports between HMA and Management Board (4/year)
12
EMA AND NATIONAL AUTHORITIESEMA AND NATIONAL AUTHORITIES
European experts’ network underpins the work of the scientific p p pcommittees and working parties
European experts work for EMEA independently of their nominating authority
Scientific competence is guaranteed by their nominating authority, independence and integrity assured through public declaration of independence and integrity assured through public declaration of interests
Services provided to EMEA on basis of a contract (conditions, quality and p ( , q ypayment)
13
THE EUROPEAN SYSTEM WHY?THE EUROPEAN SYSTEM – WHY?
Complete single EU market for pharmaceuticals
Protect and promote public and animal health
Facilitate access by patients to new & better medicines
Same product information for professionals and for patients Same product information for professionals and for patients
Benefit European R&D pharmaceutical industry
Platform for discussion of public health issues at European level
14
THE EUROPEAN SYSTEM HOW?THE EUROPEAN SYSTEM – HOW?
“One European system: two procedures”
Centralised procedure
Mutual recognition and decentralised procedures
EMA is focal point of centralised procedure
Rapid and EU-wide authorisation
1 evaluation 1 authorisation 1 evaluation, 1 authorisation
No price or reimbursement issues
15
WE (HAVE TO) DIALOGUE WITH …
• European Commission• European Commission• NCAs• Council of Europe/European Pharmacopeia• Council of Europe/European Pharmacopeia• WHO• FDA• FDA• Other institutional partners (EP, EFSA, EMCDDA,
ECDC, etc.)ECDC, etc.)
regulators16
… regulators
BUT WE (HAVE TO) DIALOGUE ALSO WITH…ALSO WITH…
• Industry
• Patients
• Healthcare professionals
… stakeholders
17
… INCIDENTALLY, THERE COULD BE A SLIGHTLY DIFFERENT APPROACHSLIGHTLY DIFFERENT APPROACH
Whilst dialogue between regulators is focused on how to ensure better public health interest protection,
… dialogue with industry may be affected by the tendency of pharma companies to seek an equitable balance between general public health interest and corporate financial health interest corporate financial health interest.
18
DIALOGUE WITH REGULATORSDIALOGUE WITH REGULATORS
EUROPEAN COMMISSIONEUROPEAN COMMISSION
our major institutional partnerour major institutional partner
• Regular bilateral and teleconferenceg• Two representatives in the Management Board• Representatives from the Commission in major meetings
l / l l l• Close EMA/EC Cooperation in implementing legislation
19
DIALOGUE WITH REGULATORSDIALOGUE WITH REGULATORS
NATIONAL COMPETENT AUTHORITIESNATIONAL COMPETENT AUTHORITIES
• Heads of Medicines Agenciesg• One representative each in the
Management Board• NTA meetings• NTA meetings• CMD meetings• Flow of information concerning PhV issues g
and, more in general, safety, quality and efficacy of medicinal products
20
DIALOGUE WITH REGULATORSDIALOGUE WITH REGULATORS
COUNCIL OF EUROPECOUNCIL OF EUROPE
• EDQM - European Directorate for the Quality Q p Q yof Medicines
• European Pharmacopeia• Dialogue and cooperation in the field of • Dialogue and cooperation in the field of
inspections• EEA OMCLs network
21
DIALOGUE WITH REGULATORSDIALOGUE WITH REGULATORS
WORLD HEALTH ORGANISATIONWORLD HEALTH ORGANISATION
A i EEA b i • Assistance to non EEA member countries
• Cooperation and consultation provided for b t 58 f R l ti (EC) 726/2004by art. 58 of Regulation (EC) 726/2004
• First positive opinions released by CHMP on 17 November 200517 November 2005
22
DIALOGUE WITH REGULATORS
FOOD AND DRUG ADMINISTRATION
•Regular bilateral and teleconference•Meeting FDA/EMA/European Commission•Provision of parallel scientific advice and
exchange of information concerning Q S & exchange of information concerning Q,S & E of medicinal products + regulatory & legal issues
•Confidentiality arrangement
23
ALREADY IN THE AGENDA/FUTURE CHALLENGESFUTURE CHALLENGES
• Pre-accession dialogue = PERF, PHARE• Increase cooperation/interaction with non-p /
EU countries (i.e. Japan, Canada)• Mutual recognition agreements
… export the network model!p
Latin/South America cooperation
24
DEFINITION OF MEDICINAL PRODUCT
Definition in Article 1(2) of Directive 2001/83/EC allows a substance or combination of substances to become a medicinal
d i product in two ways:
(1) by presentation
when the substance/s is presented as having properties for treating or preventing disease in human beings;
oror
(2) by function
when the substance/s may be used in or administered with a view to when the substance/s may be used in or administered with a view to restoring, correcting or modifying physical functions by exerting a pharmacological immunological or metabolic action, or to making a medical diagnosis.
25
DEFINITION: PRESENTATION
Case 319/05 Commission v Federal Republic of Germany
A product is a medicinal product by presentation if it is expressly A product is a medicinal product by presentation if it is expressly indicated or
recommended as a product for the treatment or prevention of disease; or or
if the average well informed consumer is likely to think it is intended to prevent or treat disease.
R l t F tRelevant Factors
• Claims made for product• Appearance of product (e.g. packaging)pp p ( g p g g)• Form of product (e.g. capsule)• Method of use
26
DEFINITION: FUNCTIONDEFINITION: FUNCTION
Joined Cases C -211/03, C 299/03 and C-316/03 to C-318/03, HL Warenvertriebs GmbH (C-211/03), Orthica BV (C-299/03 and C-316/03) v Germany.
The “Function” definition has potential to (but does not) cover all substances capable of having an effect on the functioning of the body capable of having an effect on the functioning of the body.
Relevant Factors
• Composition of product
• Pharmacological properties
• Manner in which product is used
• Extent of distribution • Extent of distribution
• Familiarity to consumers
• Risks entailed by its use
27
BORDERLINE PRODUCTS
Case C-319/05 Commission v Federal Republic of Germanyp y
It can be difficult to decide whether a product is a medicinal product or some other product such as a some other product such as a
• Food• Food supplement • Medical device• Cosmetic
A product which satisfies the definition of “medicinal product” within A product which satisfies the definition of medicinal product within the meaning of Directive 2001/83/EC must be held to be a medicinal product and be made subject to the corresponding rules even if it comes within the scope of other, less stringent Community rules
28
WHEN IN DOUBTWHEN IN DOUBT…
Article 2(2) Directive 2001/83/ECArticle 2(2) Directive 2001/83/EC
“In cases of doubt, where, taking into account all its characteristics a product
may fall within the definition of a medicinal product and within the definition of a may fall within the definition of a medicinal product and within the definition of a
product covered by other Community legislation the provisions of this Directive
shall apply”
Case - 140/07 Hecht – Pharma GmbH
Rule of doubt only applies in cases where a product is covered by both the Rule of doubt only applies in cases where a product is covered by both the
definition of food (supplement), cosmetic product or medical device and the
definition of medicinal product.
29
RULES APPLICABLE TO CENTRALLY AUTHORISED PRODUCTSAUTHORISED PRODUCTS
M d t ( i N b 2004)Mandatory (since November 2004):
• Biotech plus– Medicinal products containing new active substances indicated for Medicinal products containing new active substances indicated for
the treatment of– AIDS– CancerCancer– Diabetes– Neurodegenerative diseasesh d d d l d– Orphan designated medicinal products
Mandatory (since May 2008):
» Viral diseases
30
» Viral diseases» Autoimmune diseases and other immune dysfunctions
RULES APPLICABLE TO CENTRALLY AUTHORISED PRODUCTSAUTHORISED PRODUCTS
•• Optional:Optional:
•• New active substancesNew active substances
•• Medicinal products with a significant Medicinal products with a significant therapeutic benefit scientific or technical therapeutic benefit scientific or technical therapeutic benefit, scientific or technical therapeutic benefit, scientific or technical innovation, or answering the interest of innovation, or answering the interest of patients or animal health at Community patients or animal health at Community l ll llevellevel
•• Generics of centralised productsGenerics of centralised products
31
EMA STRUCTURE
h i i h ’ l l
EMA STRUCTURE
The Executive Director is the EMA’s legal representative
The EMA is supervised by a Management Board and its scientific activities are largely carried out through its six Committees and their Working Parties
Management Board, Committees and their Working Parties are supported by the EMA secretariat
32
THE EXECUTIVE DIRECTORTHE EXECUTIVE DIRECTOR
Thomas LönngrenThomas Lönngren
Joined EMEA January 2001
Re-nominated October 2005Re nominated October 2005
Duties set out in CouncilRegulation (EC) No 726/2004
Legal representative of EMA
Ultimately responsible forall decisions of the Agencyall decisions of the Agency(budgetary, staff and scientific matters)
33
THE NEW ORGANISATIONAL CHART
34
MANAGEMENT BOARD
The Management Board is responsible for the Agency’s budget and work programme
• One representative per Member State
• Two representatives of the European Parliament
• Two representatives of the European Commission p p
• Two representatives from patients’ organisations
• One representative from doctors’ organisations • One representative from doctors’ organisations
• One representative from veterinarians’ organisations
35
• One observer per EEA-EFTA Member State
MANAGEMENT BOARD
Chairman:
Pat O’MahonyVice Chairman:
D Li Tidd E i d36
yDr Lisette Tiddens-Engwirda
Committee for Medicinal Products for Human Use
The CHMP is responsible for formulating the
(CHMP)
The CHMP is responsible for formulating the Agency’s scientific opinions on any aspect regarding medicinal products for human use
The Committee is composed of one member The Committee is composed of one member per Member State. Each Member has an alternate
Chairman
The Committee has co-opted five members to provide for additional scientific expertise
37
Dr Eric Abadie
Committee for Medicinal Products for Veterinary Use
The CVMP is responsible for formulating the
(CVMP)
The CVMP is responsible for formulating the Agency’s scientific opinions on any aspect regarding medicinal products for veterinary use
The Committee is composed of one member The Committee is composed of one member per Member State. Each Member has an alternate
ChairmanDr Gerald Moulin
The Committee has co-opted five members to provide for additional scientific expertise
38
Committee on Orphan Medicinal Products (COMP)
The COMP is responsible for reviewing applications for ‘orphan medicinal product’ pp p pdesignation, submitted by persons or companies (‘sponsors’) intending to develop medicinal products for rare develop medicinal products for rare diseases
The Committee has one member per Member State, three members from
ChairmanDr Kerstin Westermark
,patients’ organisations and three members nominated by the EMEA
39
Committee on Herbal Medicinal Products (HMPC)( )
The Committee on Herbal Medicinal Products is responsible for formulating the Agency’s responsible for formulating the Agency s scientific opinions regarding the quality, safety and efficacy of herbal medicinal products
Th C itt h b M b The Committee has one member per Member State. Each member has an alternate
The Committee can also co-opt five members Chairman
Prof. Konstantin Keller
The Committee can also co opt five members
40
Paediatric Committee (PDCO)Paediatric Committee (PDCO)Regulation (EC) No 1901/2006
The PDCO is responsible for:
• assessing the content of Paediatric • assessing the content of Paediatric Investigation Plans
formulating the Agency’s scientific • formulating the Agency’s scientific opinions on any aspect regarding medicinal products for use in the paediatric population
41
PDCO CompositionPDCO Composition
Five members of the CHMPFive members of the CHMP
One member per Member StateOne member per Member State
not yet represented by CHMP repsnot yet represented by CHMP repsnot yet represented by CHMP repsnot yet represented by CHMP reps
Three members to representThree members to represent
health professionalshealth professionalshealth professionalshealth professionals
Three members to representThree members to represent
patient associationspatient associationspatient associationspatient associations
Each Member has an alternate Each Member has an alternate
Chairman
42
Dr Daniel Brasseur
Committee for Advanced Therapies (CAT)Regulation (EC) No 1394/2007
Advanced Therapy medicinal products (ATMP)
• Gene therapy products• Somatic cell therapy products• Tissue engineered products CAT prepares a draft opinion on each ATMP application before the CAT prepares a draft opinion on each ATMP application before the CHMP adopt the final opinion
CAT provides scientific advice on classification and other ATMP related queriesrelated queries
Support to SMEs
43
CAT COMPOSITIONCAT COMPOSITION
CAT should covers the scientific areas relevant to advanced therapiesadvanced therapies, including:- Medical devices
[2+2 at least],- TissueTissue engineering,- Gene therapy, - Cell therapy,
Bi t h l- Biotechnology,- Surgery,-Pharmacovigilance,Pharmacovigilance,- Risk management and - Ethics.
44
[Recital 9 & Art.21]
EMA BUDGETEMA BUDGET
About one-third of budget is paid to national agencies for work done at request of EMA ( € 72 million in 2010 € 67 4m in 2009)million in 2010, € 67,4m in 2009)
Fees represent the major part of total revenueFees represent the major part of total revenue
EU l b id i l l t bl t b t EU general subsidy is largely stable amount but reducing in proportion of total budget
45
Budget evolution 1995-2010 (€ million)(€ million)
180
200
120
140
160
180
80
100
120
20
40
60
01995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Basic EU contribution Total fee revenue Orphan drug contributionTelematics strategy Paediatric contribution SME contribution
46
Telematics strategy Paediatric contribution SME contributionAdvanced therapies Other revenue
A DYNAMIC AND CONSTANTLY CHANGING AGENCYCHANGING AGENCYThe Agency new tasks and responsibilities:
2001 O h di i (+ itt )• 2001: Orphan medicines (+ new committee)
• 2005 & 2008: Extended mandatory scope
2005 ‘Bi i il ’ d i di i• 2005: ‘Biosimilar’ and generic medicines
• 2005: Herbal medicines (+ new committee)
2007 P di t i di i (+ itt )• 2007: Paediatric medicines (+ new committee)
• 2008/2009: Advanced therapies (+ new committee)
S h i il ( itt ) d • Soon: pharmacovigilance (+ new committee) and counterfeit medicines legislation
47
IN THE PIPELINE
The Pharma package:
• Legal proposal on “Counterfeit” medicines• Legal proposal on Information to patientsp• Legal proposal on Pharmacovigilanceg
48
PRIORITY AREAS FOR 2010PRIORITY AREAS FOR 2010
• Deliver on our core businessDeliver on our core business
• Implement new legislative tasks
• Strengthen the European medicines networkStrengthen the European medicines network
• Continue to improve safety-monitoring of medicines
• International partners and international activitiesInternational partners and international activities
• Communication, provision of information and increasing transparency
• Contribute to an environment that stimulates innovation and improved availability of medicines
49
REGULATORY PROCEDURESREGULATORY PROCEDURES
- STANDARD MA PROCEDURESTANDARD MA PROCEDURE- RENEWAL PROCEDURE- VARIATION PROCEDUREVARIATION PROCEDURE- MAH TRANSFER PROCEDURE- PAEDIATIRC INVESTIGATION PLAN PROCEDUREPAEDIATIRC INVESTIGATION PLAN PROCEDURE- ORPHAN DESIGNATION PROCEDURE- ADVANCED THERAPIES MEDICINAL PRODUCT ADVANCED THERAPIES MEDICINAL PRODUCT PROCEDURE- REFERRAL PROCEDURES
50
STANDARD MA PROCEDURE (1)STANDARD MA PROCEDURE (1)
• applications for the MA shall be submitted to the Agencyapplications for the MA shall be submitted to the Agency
• accompanied by fee payable to the Agency for the examination of the
application
• 210 days for giving CHMP opinion counted from the receipt of a valid
application in which CHMP:
- shall verify that the particulars and documents submitted comply with the
requirements of the Directive 2001/83/EC
- may request that an OMCL test the MP/its starting materials/its intermediate
products
- may request that the applicant supplement the particulars accompanying the
51
- may request that the applicant supplement the particulars accompanying the
application within a specific time period (“clock stop”)
STANDARD MA PROCEDURE (2)STANDARD MA PROCEDURE (2)
• the Agency shall inform the applicant about CHMP opinionthe Agency shall inform the applicant about CHMP opinion
• 15 days for the applicant to give written notice if intended to re-examine the opinion;
within 60 days after receipt of the opinion obligation to submit detailed grounds for the
request
• within 15 days after its adoption the Agency shall send the final opinion of the CHMP to
the EC/MSs/applicant together with assessment report
• within 15 days after receipt of the opinion the EC shall prepare a draft of the
decision; where the draft decision is not in accordance with the opinion of the Agency decision; where the draft decision is not in accordance with the opinion of the Agency,
the EC shall annex a detailed explanation of the reasons for the differences
• Standing Committee phase with MSs observations/comments
52• final EC decision within 15 days after the end of the procedure
GROUNDS FOR REFUSAL OF MAGROUNDS FOR REFUSAL OF MA
Inter alia:Inter alia:
- R-B balance is not considered to be favourable; orfavourable; or
- therapeutic efficacy is insufficiently substantiated by the applicant; orby the applicant; or
- qualitative and quantitative composition of the product is not declaredproduct is not declared
53
RENEWAL OF THE MARENEWAL OF THE MA
• The MA may be renewed after five years on the basis of a re-evaluation by the Agency of the R-B balance.
• Obligation for the MAH to provide the Agency with a consolidated version of the file in respect of Q,S,E incl. all variations at least 6 months before MA ceases to be valid
54
VARIATIONSVARIATIONS
• Possibility for the MAH to change certain elements of the MAPossibility for the MAH to change certain elements of the MA
• “on request” procedure
• Different types of variations: type IA, IB, IIDifferent types of variations: type IA, IB, II
• Commission Regulation (EC) No 1234/2008 of 24 Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products f h d t i di i l d t for human use and veterinary medicinal products
55
AIM OF NEW VARIATIONS REGULATIONAIM OF NEW VARIATIONS REGULATION
•Simpler Clearer More flexible legal framework•Simpler, Clearer, More flexible legal framework
•Reduce administrative burden
Ad t t ICH t•Adapt to ICH concepts
•Further harmonise handling of variations in EU
Same level of public and animal health Same level of public and animal health protection
56
MAIN FEATURES & SCOPEMAIN FEATURES & SCOPE
• Type IA ‘Do and tell’ (annual reporting)• Type IA Do and tell (annual reporting)
• Type IB by default & Article 5
G i (f l d d• Grouping (facilitate review & reduce administrative burden)
W k h i • Worksharing (avoid duplication of work)
• CMD referrals (increase cooperation between MSs)
• Implementation of variations by MAH
57
MAIN FEATURES & SCOPE• Classification of variations depending on level of risk to public or
MAIN FEATURES & SCOPE
animal health &
• Impact on the quality, safety and efficacy of medicinal product
concernedconcerned
Applies to:
Medicinal products authorised via MRP, DCP
-
Following a CHMP referral (full harmonisation)
58
-
Medicinal products authorised via CP
MAH TRANSFER PROCEDUREMAH TRANSFER PROCEDURE
• “special” variationspecial variation
• “transfer of a marketing authorization” means the procedure of changing the addressee of the marketing authorization decision
• 30 days procedure
• The Agency's opinion can only be unfavourable if the documents submitted in support of the application are incomplete or if it appears that the person to whom the transfer shall be granted is not established within the Communityestablished within the Community.
59
MAH TRANSFER PROCEDUREMAH TRANSFER PROCEDURE
• The transfer of the MA shall be authorised from the date of The transfer of the MA shall be authorised from the date of notification of the amendment of the Commission decision
• The date on which the transfer actually takes place shall be set by the EMA by mutual agreement with the holder of the marketing authorization and the person to whom the transfer is to be granted; EMA shall immediately inform the Commission of this dateEMA shall immediately inform the Commission of this date.
• Commission Regulation (EC) No 2141/96, of 7 November 1996, concerning the examination of an application for the transfer of a g ppmarketing authorization for a medicinal product falling within the scope of Council Regulation (EEC) No 2309/93
60
COMMUNITY REFERRALS: RA/LEGAL CONTEXT/
Di ti 2001/83/EC d d iDirective 2001/83/EC as amended i.a.:– Article 30 – “Divergent Decision Referral”– Article 31 – “Community interest Referral”– Article 31 – Community interest Referral– Article 107 – “Pharmacovigilance Urgent Measures”
Reference: Reference: Notice to Applicants, Volume 2A Notice to Applicants, Volume 2A –– Chapter 3 Community referralsChapter 3 Community referrals
6161
Notice to Applicants, Volume 2A Notice to Applicants, Volume 2A Chapter 3 Community referralsChapter 3 Community referrals
SELECTION OF PRODUCTS FOR SPC HARMONISATIONSPC HARMONISATION
Proactive harmonisation
- CMD(h) lays down list and forwards to Commission
- Commission or MS, in agreement with EMA, taking into account views f IP f th d t f bit tiof IP, may refer the product for arbitration
Criteria for selection of products
• Significant differences in Core parts of the SPC (Sections 4 1 4 4)• Significant differences in Core parts of the SPC (Sections 4.1 – 4.4)
• Exclusivity/patent expiry dates.
• Extent of the use of the product.
• Number of MS where the product is authorised.
Website: http://www hma eu/242 html
62
Website: http://www.hma.eu/242.html
FACTS AND FIGURES J l 2007 J l 2010FACTS AND FIGURES
Art 30Art 30 –– Triggering partyTriggering party
July 2007 – July 2010
Triggering party No. of procedures
Art. 30 Art. 30 Triggering partyTriggering partyMS
MAH
EC 28
MS 4
MAH 3EC
63
IMPACT ON PUBLIC HEALTHIMPACT ON PUBLIC HEALTH
• “Old” products are re-examined, streamlined and brought up to date
• Availability of harmonised package leaflets Availability of harmonised package leaflets and labelling for widely-use drugs
• Improved patient access and use for both reference and generics
6464
g
IMPACT ON COMPANIESIMPACT ON COMPANIES
MAHs obtain harmonised and updated PIs, taking into account all variations authorised nationally and into account all variations authorised nationally and all available post-marketing data.
Indications granted in few MS can be expanded to Indications granted in few MS can be expanded to all EU MS or restricted, depending on the robustness of the scientific data and supporting evidence.
EC d i i l d t MRP t t f ilit ti EC decision leads to MRP status, facilitating subsequent variations and maintenance of the product life-cycle.
Streamlining of indications is beneficial and avoids “pick and choose” of reference for generics.
6565
Benefits of harmonised EU position on Safety and Pharmacovigilance aspects
ART. 31 COMMUNITY INTEREST REFERRALREFERRAL
Interest of Community Public Healthrelated to a medicinal product which is on the market in the EU in the light of the market in the EU in the light of Quality, Safety and Efficacy data or new Pharmacovigilance informationg
Who can trigger?
- Member States
- Commission
6666
- applicant/marketing authorisation holder
FACTS AND FIGURES 1995 J l 2010FACTS AND FIGURES
Grounds for Art 31Grounds for Art 31
1995 - July 2010
Grounds for Art. 31Grounds for Art. 31Grounds for Referral
No. of procedures
Safety/
Quality
Safety + EfficacySafety/
Pharmacovigilance30
Efficacy 2
Safety Efficacy
Efficacy 2
Safety/Pharmaco-vigilance + Efficacy
11EfficacyEfficacy
Quality 1 Safety
Efficacy
67
FACTS AND FIGURESFACTS AND FIGURES
Outcome of the Art 31Outcome of the Art 31
1995 - July 2010
Procedure outcome
No. of procedures
Outcome of the Art. 31Outcome of the Art. 31Ongoing
Maintenance/
Variation32
Withdrawal
Withdrawal 4
Ongoing 8
Maintenance
In case of variation/suspension of MA conditions may apply
68
In case of variation/suspension of MA, conditions may apply e.g CTs, Post-marketing studies, change PSUR cycle
ART 31–IMPACT ON PUBLIC HEALTHART.31–IMPACT ON PUBLIC HEALTH
Same level of protection to EU patients in relation Same level of protection to EU patients in relation to specific concerns
Information widely available through various communication toolscommunication tools
Update/harmonisation of product information (full Update/harmonisation of product information (full or partial)
6969
Article 31 – Impact on MAHsArticle 31 – Impact on MAHs
EU level assessment consistency across d t i l di tit / iproducts including competitors/generics
I f i l i h i i i ll In case of revocation loosing authorisation in all EU Member States
Only one response/assessment/discussion better coordination/use of resourcesbetter coordination/use of resources
In case full harmonisation MRP status (facilitate 7070
In case full harmonisation MRP status (facilitate maintenance life-cycle of the product)
ART.107 - PHARMACOVIGILANCE URGENT MEASURESURGENT MEASURES
• Where urgent action to protect public health is necessary MS may suspend the MA
• Art 107 triggered automatically and is mandatory; the CHMP shall prepare the opinion
• Possibility to request all MSs where the product is marketed to take temporary measures immediately
MAHs to be heard (written/oral) whenever possible; could be brand leader MAHs to be heard (written/oral) whenever possible; could be brand leader
only!
No legal timeframe depends on urgency!No legal timeframe – depends on urgency!
No re-examination of Opinion!
7171
FACTS AND FIGURESFACTS AND FIGURES Since 2007
Outcome of the Art 107(2)Outcome of the Art 107(2)
MA Variation
Procedure outcome No. of procedures
Outcome of the Art. 107(2)Outcome of the Art. 107(2)
OngoingMA Variation
MA Variation 2
Withdrawal 4
WithdrawalSuspension
Suspension 2
Ongoing 3
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g g
STEPS COMMON TO ALL REFERRAL PROCEDURESPROCEDURES
o Feeso Feeso Letters of Representationo Legal timeframes (except Art 107!)
o Re-examination (except Art 107!)( p )
o Translationso Decision making p ocesso Decision-making processo Published information
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FEES AND LETTERS OF REPRESENTATIONREPRESENTATION
No fee if triggered by Member State or ECFee of 62 800 € payable for Article 30 and 31 referrals triggered by MAH.
A MAH can group with other MAHs to provide a single answer to CHMP; Letters are used to designate a contact person/groupingdesignate a contact person/groupingIf several MAHs involved possibility to group and provide one single dossier paying a single fee.p g p y g g
Reference: Explanatory note on fees payable to the
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Reference: Explanatory note on fees payable to the European Medicines Agency (EMA/649350/2009 )
STANDARD TIMETABLES (http://www.ema.europa.eu/pdfs/human/submission/Referrals_triggered
_by%20MS_and_EC.pdf)
ClockClockNotification ofNotification ofStart Start MS MS ClockClockStopStop
Notification ofNotification ofreferralreferral
Start Start of procedureof procedure EvaluationEvaluation MS MS
Implement.Implement.
D.0D.0 D.2D.2D.1D.1 D.60*D.60*D.127D.127 D.157D.157
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*May be extended by 90 days
Described in Articles 32, 33 and 34 of Directive 2001/83/EC, as amended
RE EXAMINATION OF CHMP OPINIONRE-EXAMINATION OF CHMP OPINION
Re-examination of the adopted CHMP opinion is possible (except Art 107)107)
Request for re-examination to be submitted within 15 days of the receipt of the opinion and detailed grounds submitted within 60 days
Possibility of consultation of SAGs or Ad-Hoc Expert Groups
Different Rapporteurs appointed
B d l i tifi d t il bl t i iti l i iBased only on scientific data available at initial opinion
FINAL CHMP opinion within 60 days
Ref: Guideline on Procedure for re-examination of CHMP Opinions (EMEA/CHMP/50745/2006)
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POST CHMP OPINIONPOST-CHMP OPINION
Translations of CHMP Opinion annexes to all Translations of CHMP Opinion annexes to all official EU languages (within 5 days).
T l ti f A I & III ibilit f • Translation of Annex I & III responsibility of MAH/Applicant
• Complex procedure, instructions and translation timetable must be followed, otherwise possible delays! delays!
Start of the European Commission Decision-ki P
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making Process
PUBLISHED INFORMATION
EMA website EC website
CHMP Monthly report/Press Start of procedure
y pRelease -
Press release (dedicated for safety
Opinion
referrals)-
*Special situation: Adoption of temporary measures
CHMP Monthly reporttemporary measures
Q&A (English)
EC decisionQ&A (All languages) Commission Decision (All languages)
Annexes of Opinion (All l ) Annexes of Opinion (All languages)
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languages) Annexes of Opinion (All languages)
THANK YOU!The views expressed in this presentation are those of the author and do not necessarily reflect and cannot be The views expressed in this presentation are those of the author and do not necessarily reflect and cannot be
quoted as the views of the European Medicines Agency
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