1400 - Tomas Salmonson - Continuous dialogue from product ......Microsoft PowerPoint - 1400 - Tomas...

Continuous dialogue from product development Continuous dialogue from product development throughout product life cyclethroughout product life cycle

Tomas Tomas SalmonsonSalmonsonVice chair CHMPVice chair CHMP

Outline of presentation

�� The network of EMEA committees and The network of EMEA committees and working partiesworking parties

�� Statistics on SA/PAStatistics on SA/PA�� RapporteurRapporteur /Co/Co--RapporteurRapporteur AppointmentAppointment�� Interaction with Interaction with RapporteursRapporteurs�� Post authorisation dialoguePost authorisation dialogue

27 EEA Member States+ 3,000 European experts27 EEA Member States

+ 3,000 European expertsEU institutions:

Commission - ParliamentEU institutions:

Commission - Parliament

Committee for OrphanMedicinal Products

(COMP)

Committee for OrphanMedicinal Products

(COMP)

Committee for HerbalMedicinal Products

(HMPC)

Committee for HerbalMedicinal Products

(HMPC) EMEA

Secretariat

EMEA

Secretariat

Committee for VeterinaryMedicinal Products

(CVMP)

Committee for VeterinaryMedicinal Products

(CVMP)

Management BoardManagement Board

Committee for HumanMedicinal Products

(CHMP)

Committee for HumanMedicinal Products

(CHMP)

Interaction between CommitteesInteraction between Committees

Committee for Advanced Therapies

(CAT)

Committee for Advanced Therapies

(CAT)

Paediatric Committee(PDCO)

Paediatric Committee(PDCO)

Interactions Interactions betweenbetween CommitteesCommittees

•• PDCOPDCO--CHMP: CHMP: regularregular meetings of Chairs, meetings of Chairs, ""informalinformal", CHMP ", CHMP membersmembers atat PDCOPDCO

•• COMPCOMP--CHMP: CHMP: regularregular meetings of Chairs, meetings of Chairs, ""informalinformal", CHMP ", CHMP membersmembers atat COMPCOMP

•• SAWP: SAWP: membersmembers fromfrom COMP COMP •• SAWPSAWP--PDCO: PDCO: beingbeing developeddeveloped•• PDCOPDCO--otherother CHMP WP: CHMP WP: beingbeing developeddeveloped, ,

coordination on coordination on overlappingoverlapping topicstopics, joint WP, PDCO , joint WP, PDCO to to provideprovide input input intointo CHMP guidelinesCHMP guidelines

•• CATCAT--CHMP: CHMP: beingbeing developeddeveloped



�� Statistics on SA/PAStatistics on SA/PA

Scientific Advice and Protocol Assistance 2002-2008

2002 2003 2004 2005 2006 2007 2008

Total SA/PA86 97 122 194 259 288 321

Protocol Assistance 11 17 29 44 50 41 45

10%6%

5%

3%

14%

1%8%4%15%2%

3%

0%

26%

3%

J General anti-infectives forsystemic useB Blood and blood forming organs

R Respiratory system

V Various

A Alimentary tract and metabolism

H Systemic hormonal preparations,excluding sex hormonesC Cardiovascular system

M Musculo-skeletal system

N Nervous system

G Genito-urinary system and sexhormonesS Sensory organs

P Anti-parasitic products,Insecticides, RepellentsL Anti-neoplastic andimmunomodulating agentsD Dermatologicals

Scientific Advice and Protocol Assistance 2002-2008By ATC codes

SAWP ChairSAWP Chair →→ presentspresents ∼∼6 6 advicesadvices atat CHMP meetingCHMP meeting

CHMP CHMP membersmembers →→→→→→→→ ≥≥≥≥≥≥≥≥1 1 thoroughthorough peerpeer--reviewreview / / eacheach main main adviceadvice

comment comment duringduring SAWP SAWP presentationpresentation atat CHMP meetingCHMP meeting

CHMP / EWP ChairsCHMP / EWP Chairs →→ attend SAWP meeting to attend SAWP meeting to summarizesummarize CHMP CHMP decisionsdecisionswithwith ciriticalciritical impact on impact on SASA’’ss

SAWP SAWP secretariatsecretariat →→ liaiseliaise withwith PDCO for PDCO for paediaticpaediatic SASA’’ss / / PAPA’’ss

PDCO Chair or PDCO Chair or representativerepresentative →→ informsinforms CHMP of CHMP of criticalcritical PDCO PDCO decisionsdecisions

Scientific Advice

Proportion of Proportion of MAAsMAAs that received SA that received SA (by outcome year)(by outcome year)

38%

47%

56%

0%

10%

20%

30%

40%

50%

60%

2006 (n=50) 2007 (n=59) 2008 (n=70)

SA given

Does compliance with SA influence the outcome?

MAAs between 2004-2007

192 MAAs with an outcome• Positive opinion – 140 (72.9%)• Negative opinion – 10 (5.2%)• Withdrawal – 42 (21.9%)

• Non-orphans drugs – 141 (73.4%)• Orphan drugs – 51 (26.6%)

52 (27.1%)

Does compliance with SA influence the outcome?

The 72 MAA outcomes with SA (2004-2007) were assessed concerning compliance with:– Choice of primary endpoint– Choice of comparator– Statistical analyses

• Non-compliance defined as not adhering to one or more of the 3 variables

• 10 MAAs did not include questions concerning any of the 3 variables

• 62 MAA outcomes with SA analysed

SA compliance and MAA outcome

192

130

62

93

37

42

20

6

14

41

1

advice outcomecompliance

99

150

42

41

ratios

=

=

0.66

0.98

no

noyes

yes

* *

MAAs: outcome 2008 (jan – nov)

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�� Statistics on SA/PAStatistics on SA/PA�� RapporteurRapporteur /Co/Co--RapporteurRapporteur AppointmentAppointment

� Members still state relative priority� Collated by EMEA Secretariat� Proposal made by CHMP Chair

� best available scientific expertise� highly subjective judgement� experience over time

Rapporteurship appointment

� Once eligibility confirmed and if submission within 6-months, appointment of Rapporteurs and their assessment teams take place

� CHMP Secretariat sends list of products requiring Rapporteursappointment at the next CHMP meeting to all CHMP members

� Within 2 weeks CHMP members asked to express their interest and provide details regarding their proposed assessment team� Quality, non-clinical, clinical, environmental assessment,

pharmacovigilance…� Experience with similar therapeutic area, similar products� Regulatory experience

Rapporteurship appointment (2)

� EMEA internal review of the nominations received� Filter information received and propose draft outcome� No linkage/exclusion due to role as Scientific Advice

Co-ordinator� Discussion of draft outcome with CHMP Chair on Monday

CHMP week� CHMP Chair makes final proposal according to objective

criteria in line with best available scientific expertise(http://www.emea.europa.eu/pdfs/human/regaffair/12406605en.pdf)

� Adoption of Rapporteurs appointment by the Committee� Outcome letters sent to applicants during the week following

CHMP meeting

Rapporteurship appointment

Rapporteurs appointment Oct 2006 - Jan 2009

0

10

20

30

40

50

60

70

80

UK DE NL SE ES FR DK PT IE BE HU FI IT AT NO EE SL LT PL CZ GR

TotalRapporteurshipCo-Rapporteurship

Role of the Peer Reviewer

� Appointed at the same time of Rapporteurs but detail not shared with applicants

� To contribute to quality assurance of the List of Questions� Peer Review may encompass whole or part of Q / S / E� Peer Reviewer systematically address

� Extent to which scientific argumentation supports proposed LoQs� Consistency issues raised LoQs and CHMP guidelines / Scientific

Advice and similar issues seen with products same class / indication

� EMEA Peer Review Team also appointed� CHMP members also contribute to review system

��

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� !�� "#$�%��&��'%�&(

80Reports

80-100PeerReview

100Comments

107DraftLOQ

112Tele-conference

115DraftLOQ

120CHMP Adopts LOQ

Peer review appointment

Peer Review

0

10

20

30

40

50

60

DE SE FR DK EE NL PT ES IE CZ NO UK AT HU FI MT LU PL LT BE IT IC GR

Apr 05 - Sept 06Oct 06 - Jan 09Total


� The network of EMEA committees and working parties

� Statistics on SA/PA� Rapporteur /Co-Rapporteur Appointment� Interaction with Rapporteurs

Interaction with Rapporteurs

• Pre-submission• national advice• after appointment

• Day 0-120• Post Day 120 LoQ

• "clarification" meetings• pre-submission meetings

• Before OE• Post OE (after trend vote)

A few thoughts….

• when (during CHMP week?)• "clarification" meetings• advice before OE• interpretation of trend votes



�� Statistics on SA/PAStatistics on SA/PA�� RapporteurRapporteur /Co/Co--RapporteurRapporteur AppointmentAppointment�� Interaction with Interaction with RapporteursRapporteurs�� Post authorisation dialoguePost authorisation dialogue

Review and Learning Project on RMP

• Objectives

– To learn from experience to remedy problems:

• Quality/completeness of RMP

• Post-authorisation Safety Studies

• overall usefulness of RMPs

• Actions proposed to meet the objectives

– EMEA Risk Management team to take the lead for revisit of EU RMP guideline and template, to map RMP implementation in Member States, and to arrange interactive workshop with Industry.

– A joint CHMP, PhVWP, CMD(h) and EMEA drafting group to be established and to draft recommendations on procedures, best practices, training etc and on approaches for involvement of expertise, advice, etc.

– Department of Clinical Epidemiology of the Utrecht University to finalise analysis of scientific quality of the PASS in RMPs and to propose improved procedures, and to progress with a review the outcomes of RMP implementations.

– The Review and Learning project group to propose approaches to evaluate the short- and long-term overall usefulness of Risk Management, including better knowledge of life-time safety, safer/more effective use in real life and positive impact on drug related Public Health at large.

Risk minimisation Plan If additional risk minimisation activities is needed

• Should list safety concerns for which risk minimisation activities is needed

• Should include both routine and additional risk minimisation activities

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Update to the EU-RMP

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• updated throughout the lifecycle of the product• safety specification will change over time

� results from other clinical trials� results from studies in PhV Plan� spontaneous reports and literature

• PhV Plan and Risk Min Plan will also change over time

31

Evolution of Remicade (EU): Efficacy

19992000200120022003 2004 20052006RA: signs

and symptoms

FistulizingCD maintenance

AnkylosingSpondylitis

Luminal CD maintenance

Early RA

Psoriatic Arthritis

Moderate/Severe

Psoriasis

Ulcerative Colitis

RA:joint damage

Crohn’sDisease

RA: physical function

32

Dinv lettertransaminases

CHF DDL

SP commitment to CD and RA registry

German “death scare”

TB education

DDL Lymphoma

FDA panel Lymphoma

DDL Hepatotoxicity

Hepatotoxicity

Evolution of Remicade (EU): Safety

PSUR3 pancytopenia

listeriosis

1998 1999 2000 2001 2002 2003 2004 2006

TB/infectionsalert card

PSUR4 interstitial

pneumonitis/fibrosis

PSUR 6 & 7 vasculitis

PSUR 8 agranulocytosis,

pancreatitis

Severe infections

serum sickness, pericardial effusion

Malignancies

Delayed Hypersensitivity

PSUR 9 heart failure

T24 stopped

Alcoholic Hepatitis study stopped

PSUR 5 myelitis, anemia, hepatocellular damage

2005

CD: 2nd to 3rd line therapy

Label change Label change

DDL or other event DDL or other event

FU commitment FU commitment

Dinv Letter hematological AE

TB DDL

General DDL

Pneumonia

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European Network of Centres for Pharmacoepidemiology and Pharmacovigilance

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Web page: http://www.encepp.eu/

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1400 - Tomas Salmonson - Continuous dialogue from product ......Microsoft PowerPoint - 1400 - Tomas...

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