Continuous dialogue from product development Continuous dialogue - - PowerPoint PPT Presentation

Continuous dialogue from product development Continuous dialogue from product development throughout product life cycle throughout product life cycle Tomas Tomas Salmonson Salmonson Vice chair CHMP Vice chair CHMP

Outline of presentation

• The network of EMEA committees and

The network of EMEA committees and working parties working parties

• Statistics on SA/PA

Statistics on SA/PA

• Rapporteur

Rapporteur /Co /Co-

• Rapporteur

Rapporteur Appointment Appointment

• Interaction with

Interaction with Rapporteurs Rapporteurs

• Post authorisation dialogue

Post authorisation dialogue

Outline of presentation

• The network of EMEA committees and

The network of EMEA committees and working parties working parties

27 EEA Member States + 3,000 European experts 27 EEA Member States + 3,000 European experts EU institutions: Commission - Parliament EU institutions: Commission - Parliament

Committee for Orphan Medicinal Products (COMP) Committee for Orphan Medicinal Products (COMP) Committee for Herbal Medicinal Products (HMPC) Committee for Herbal Medicinal Products (HMPC)

EMEA Secretariat EMEA Secretariat

Committee for Veterinary Medicinal Products (CVMP) Committee for Veterinary Medicinal Products (CVMP) Management Board Management Board Committee for Human Medicinal Products (CHMP) Committee for Human Medicinal Products (CHMP)

Interaction between Committees Interaction between Committees

Committee for Advanced Therapies (CAT) Committee for Advanced Therapies (CAT) Paediatric Committee (PDCO) Paediatric Committee (PDCO)

Interactions Interactions between between Committees Committees

• PDCO

PDCO-

• CHMP:

CHMP: regular regular meetings of Chairs, meetings of Chairs, " "informal informal", CHMP ", CHMP members members at at PDCO PDCO

• COMP

COMP-

• CHMP:

CHMP: regular regular meetings of Chairs, meetings of Chairs, " "informal informal", CHMP ", CHMP members members at at COMP COMP

• SAWP:

SAWP: members members from from COMP COMP

• SAWP

SAWP-

• PDCO:

PDCO: being being developed developed

• PDCO

PDCO-

• other
• ther CHMP WP:

CHMP WP: being being developed developed, , coordination on coordination on overlapping

• verlapping topics

topics, joint WP, PDCO , joint WP, PDCO to to provide provide input input into into CHMP guidelines CHMP guidelines

• CAT

CAT-

• CHMP:

CHMP: being being developed developed

Outline of presentation

• The network of EMEA committees and

The network of EMEA committees and working parties working parties

• Statistics on SA/PA

Statistics on SA/PA

Scientific Advice and Protocol Assistance 2002-2008

2002 2003 2004 2005 2006 2007 2008 Total SA/PA 86 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 for systemic use B Blood and blood forming organs R Respiratory system V Various A Alimentary tract and metabolism H Systemic hormonal preparations, excluding sex hormones C Cardiovascular system M Musculo-skeletal system N Nervous system G Genito-urinary system and sex hormones S Sensory organs P Anti-parasitic products, Insecticides, Repellents L Anti-neoplastic and immunomodulating agents D Dermatologicals

Scientific Advice and Protocol Assistance 2002-2008 By ATC codes

SAWP Chair SAWP Chair → → presents presents ∼ ∼6 6 advices advices at at CHMP meeting CHMP meeting CHMP CHMP members members → → → → → → → → ≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥1 1 thorough thorough peer peer-

• review

review / / each each main main advice advice comment comment during during SAWP SAWP presentation presentation at at CHMP meeting CHMP meeting CHMP / EWP Chairs CHMP / EWP Chairs → → attend SAWP meeting to attend SAWP meeting to summarize summarize CHMP CHMP decisions decisions with with ciritical ciritical impact on impact on SA SA’ ’s s SAWP SAWP secretariat secretariat → → liaise liaise with with PDCO for PDCO for paediatic paediatic SA SA’ ’s s / / PA PA’ ’s s PDCO Chair or PDCO Chair or representative representative → → informs informs CHMP of CHMP of critical critical PDCO PDCO decisions decisions

Scientific Advice

Proportion of Proportion of MAAs MAAs 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

• utcome

compliance 99 150 42 41 ratios = = 0.66 0.98 no no yes yes * *

MAAs: outcome 2008 (jan – nov)

Outline of presentation

• The network of EMEA committees and

The network of EMEA committees and working parties working parties

• Statistics on SA/PA

Statistics on SA/PA

• Rapporteur

Rapporteur /Co /Co-

• Rapporteur

Rapporteur Appointment Appointment

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 Rapporteurs appointment 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

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

Total Rapporteurship Co-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

• !"#$%&'%&(

80 Reports 80-100 Peer Review 100 Comments 107 Draft LOQ 112 Tele- conference 115 Draft LOQ 120 CHMP Adopts LOQ

Peer review appointment

Peer Review

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 06 Oct 06 - Jan 09 Total

Outline of presentation

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

Outline of presentation

• The network of EMEA committees and

The network of EMEA committees and working parties working parties

• Statistics on SA/PA

Statistics on SA/PA

• Rapporteur

Rapporteur /Co /Co-

• Rapporteur

Rapporteur Appointment Appointment

• Interaction with

Interaction with Rapporteurs Rapporteurs

• Post authorisation dialogue

Post 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
• bjectives

– 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

• n 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

• verall 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

Update to the EU-RMP

• 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 20052006

RA: signs and symptoms Fistulizing CD maintenance Ankylosing Spondylitis Luminal CD maintenance Early RA Psoriatic Arthritis Moderate/ Severe Psoriasis Ulcerative Colitis RA: joint damage Crohn’s Disease RA: physical function

32

Dinv letter transaminases 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/infections alert 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, hepato cellular 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

European Network of Centres for Pharmacoepidemiology and Pharmacovigilance

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European Network of Centres for Pharmacoepidemiology and Pharmacovigilance Web page: http://www.encepp.eu/

Thank you for your attention