1beapp pharma.be, brussels nov 23 12 be (pharmaco)vigilant! important changes in the pv-legislation...

1BeAPP pharma.be, Brussels Nov 23 12

Be (pharmaco)vigilant!Important changes in the

PV-legislation

23-11-2012

Does a safe environment guaranty safety?

M.Sangeleer, MDMedical Affairs Manager, Eli Lilly Benelux

Lecturer at the Free University of Brussels (ULB)

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The Pharmacovigilance legislation after 2012

BeAPP pharma.be, Brussels Nov 23 12

09/12/10: BeAPP Cultural event:

BeAPP pharma.be, Brussels Nov 23 12 3


Johan Braeckman: « Evolutionism & creationism »

http://www.google.be/imgres?imgurl=http://www.galamountaintours.com/imagenes/originofspeciesxq5.gif&imgrefurl=http://www.galamountaintours.com/charles_darwin.html&usg=__N-f38Prjq5-jAdw-hjM3QxlICcM=&h=475&w=322&sz=171&hl=en&start=2&zoom=1&tbnid=cVUs-L18ZwSG1M:&tbnh=129&tbnw=87&ei=nDuQUKT6K8u4hAfky4H4Aw&prev=/search?q=darwin+origin+of+species&um=1&hl=en&safe=active&gbv=2&tbm=isch&um=1&itbs=1


1.There is always variation

2.There are more organisms that are born that the amount which can survive (struggle for life)

3.The one who survive are the fitests

4.There is natural + sexual selection

5.The process is repetitive from generation to generation (positive feed-back)

6.At the end, adaptations arise


http://www.google.be/imgres?imgurl=http://challenge2.files.wordpress.com/2011/03/evolution.jpg&imgrefurl=http://challenge2.wordpress.com/2011/03/24/another-move-to-make-evolution-mandatory/&usg=__Zk_NWg1zyBdGzlezzThQbh4L1ZQ=&h=421&w=914&sz=26&hl=en&start=3&zoom=1&tbnid=vnz5GKLmZ96DXM:&tbnh=68&tbnw=147&ei=-VdoULmmF8nusgaOr4DABw&prev=/search?q=mankind+evolution+darwin&um=1&hl=en&safe=active&sa=N&gbv=2&tbm=isch&um=1&itbs=1

Pharmacovigilance evolution

5

Computerised systemInternationalisation

Proactive approach

EU reg 1235:risk based regulation

Thalidomide

Collection of AR

1962- 1995

•Signal detection•Worldwide databases MAH•Collaboration between states (WHO,…)

20001990- 2000 2012

•Risk Management systems/plans•Embryo of EU worksharing

•Ad hoc surveillance& risk management plans•Involvement of all staleholders•Improvement collaboration


http://www.google.be/imgres?imgurl=http://challenge2.files.wordpress.com/2011/03/evolution.jpg&imgrefurl=http://challenge2.wordpress.com/2011/03/24/another-move-to-make-evolution-mandatory/&usg=__Zk_NWg1zyBdGzlezzThQbh4L1ZQ=&h=421&w=914&sz=26&hl=en&start=3&zoom=1&tbnid=vnz5GKLmZ96DXM:&tbnh=68&tbnw=147&ei=-VdoULmmF8nusgaOr4DABw&prev=/search?q=mankind+evolution+darwin&um=1&hl=en&safe=active&sa=N&gbv=2&tbm=isch&um=1&itbs=1

Objectives and Key measures of the new PV law

1. Reinforcement and modernisation of current system (more rapid decisions): Additional Monitoring - ↗signal detection Pro-active Risk Management Plan for all products = CONDITION for registration Harmonisation of decisions and work sharing: reduction of redundancy Harmonisation of post –marketing, non- interventional studies for safety and

efficacy (PAES/PASS) Reinforce the link between safety evaluations and regulatory actions

2. Reinforcement of patient protection &engagement - increase the communication and transparency Direct reporting to the Agencies (web portals) Information Available on the webportal of Agencies

3. Introduction of impact of drugs on the environment


More actors

ICH CIOMS EC NCAs

EMA HCPs MAHs


Quality? (faster, better, perceived

severity, final outcomes, impact on QOL, motivation?)- Role of Advocacy

groups

Patients: Awareness and engagement – reporting, acting on information

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Adverse event reportingExpedited reporting of ICSR

Periodic reporting

Labels updates (4.8)

Proactive surveillance

Risk management plan

Risk assessment

Risk minimisation plan

Risk minimisation activities

Studies: PASS- PAES


MAH operational pharmacovigilance tasks

BeAPP pharmabe, Brussels Nov 23 12

«OLD» LEGISLATION «NEW» LEGISLATIONPatient reporting: no legal basis

Electronic reporting:no legal basis

Definition of ADR: « under normal conditions »

SERIOUS ADRs to EV- 15 days

Patient reporting: legal basis

Electronic reporting legal basis

Definition of ADR: also in case of off label use, misuse,…

SERIOUS ADRs to EV- 15 daysNON SERIOUS ADRs to EV: 90 daysNo expectedness

Legislation main changes for the MAH AE expedited reporting


Consequences for MAH

Volumeo Electronic transmission (E2B)-o signal detectiono Different timelines

Identification and « medical validation » of patient reportso Assessing causality?o Perform follow-up with patients? o What about precription medicines? Effect on treating HCP, if more administration is required? Duplicate reports?

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Which AE?

Resources, Training, adaptations of rules and procedures


Which AE?

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Periodic reporting




Risk assessment



Studies: PASS- PAES




«OLD» LEGISLATION «NEW» LEGISLATION

PSUR

PSURs for all MAs

PSUR Worksharing on voluntary basis

NO central filing

Periodic Benefit Risk Evaluation Report

submission +cycle in function of risks

Worksharing: legal basis

Central repository

Legislation main changes for the MAH

Periodic reporting


MORE EXPLICIT EVALUATIONS OF B/R

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Ad hoc periodicity according to riskclose link with RMPScientific evaluation > dataTabulations> line listingsCumulative data starting +new information of this periodSummaries of studies incl in unauthorised indications Extensive chapters on signal detection; benefit/risk evaluation

Therefore , MAH is granted

10 extra days for 6 or 12 monthly reports after the datalock point30 days for reports of a longer frequency after the datalock point

On the grounds: more pragmatic approach


PSUR-PBRER: worksharing & simplifications

• Unique List of Union Reference Dates & frequencies: EURD list

• Single assessment (variation, suspension, revocation all over EU)

• Repository for submission of PSURs (Common European Submission Platform)

• No PSUR anymore for generics and « well established use » medications

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Less work thanks to worksharing?


On the format

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Periodic reporting




Risk assessment



Studies: PASS- PAES





Eudrapharm not used- few transparency

Transparency: SPC,PIL to be published

EudraPharm (EVPMD) to be populated and up to date

SPC,PIL and summary of SPC (lay public) +PAR (summary for the public, condition of MA)

Legislation main changes

Transparency


Scope and timelines

Timelines broken down into steps:

July 2, 2012 : MAH submit information on ALL medicinal products in EVPDM

2 July 2012 : variations/suspensions/revocations within 15 calendar days

>1 Jan 2015 : MAH can submit using the new standard (IDMP )

>31 Dec 2015: All product information must be resubmitted according to ID MP.


ISO IDMP standards, a set of internationally harmonised specifications for the unique identification of medicines

Consequences for MAH

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Resources to hold timelinesQuestions from patients?Volume of events ?

Risk of induced effects?

They state reading the label

might harm the eyes


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Periodic reporting




Risk assessment



Studies: PASS- PAES





RMP if required

RMP not evaluated

PASS/PAES: no legal basis

Additional monitoring: no legal basis

RMP for all applications (proportionate to risks)

Legal basis for evaluation of the RMP-RMAactivities

PASS/PAES legal basis

Additional monitoring: legal basis

Legislation main changes for the MAH: Proactive PV


Consequences of RMP provisions

Public summary on the European Web Portal – Readibility for lay reader– Linked with list of products with additional

monitoring

Art 23 regulation

cost + burden for HCP


Compulsory assessement of impact: studies, surveys,...

MEDIA ATTENTION

Media consequences

Media trained Resources –Crisis and communication management


RMP in Belgium: Introduction of timelines…..

• PAES-PASS: – Written approval/denial given by belgian authorities/PRAC after 60 days– MAH has 30 days to express its wish to react to PASS/PAES requirement– Need to report on the progress reports ( timing to be agreed)

Risk minimisation activities local approval process: 2 months if no Medicines Commission 4 months if Medicines Commission and external expert Clock stops and timelines for MAH too

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Enough staff needed : reactivity



Detailled Description Pharmacovigilance System

Renewal submission 6 month before expiration of validity

Signal detection: no legal basis

POST MA inspections

Free of charges

Pharmacovigilance system master file


Signal detection: legal basis (at least once monthly)

PRE and POST MA inspections and more focus on sharing information between CA

Fees to be payed at EU and natonial level

Legislation main changes for the MAH : Organisation


Contributions in Belgium??

• Funding for PV resources/staffing at the AFMPS/FAGG:

– 58€/registration-All products– 0,0118€/sold pack / National-MRP products– 650€/DSUR for IMPs

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program law published 06/04/12 (entry into force 17/04/12)Circulars 588- 589RD 16 jul 2012 on DSURs payments: (effective 18 oct 12)

Conclusions: Does a safe environnement guaranty safety?

Maximising benefit, minimising risk of medicines, so focus on benefit/risk More pragmatic , risk-based approach

Focus on transparency Volume of events – balanced by more efficient signal detection-

duplicates? Effect of increased patients/media interactions ?

New formats & cycles Processes & workload: will increase at first Simplification/harmonisation: reduce duplicate work at long term

Timelines: more dynamic system reactivity will be needed (on demand PASS, PBRER, RMAs)

Fees?: will they put staffing at risk? (SME)



Basic principle remains unchanged


….There is always variation…

It is still no rocket science:…

There is a human factor

Conditions for a safer PV?:

Awareness & education of all stakeholders including patients, patients associations and HCP- (manage duplicates)

Resources to hold timelines at both MAH/NCA/…PRAC? Sufficient skilled users of signal detection tools Multidisciplinary teams (RMPs) Learn to cope with media


Learn to cope with « variation »= Mitigating the « Human Factor »



Maybe we shouldn’t disturb the medical community for

such a minor manifestation?

Probably,… a fitest pharmacovigilance,…..adapted to the variation

Does a safe legal environment guaranty safety? An industry perspective.Impact on SME’s

Bart De Greef, pharma.beKatleen Vandeweyer, Biocodex Benelux

Stability pact

31 10/04/23

Stability pact

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Major challenges for SMEs • SMEs oriented towards Rx, OTC medicines, MD, food,

cosmetics….– Less complaints – We take our responsibility!

• Requirements on– Update EUDRAPharm: (European medicines database)

• Submitting product data =>mandatory from 2 July 2012 • EXtended EudraVigilance Medicinal Product Dictionary

(XEVMPD) specific tool for SME foreseen in EVWEB– PSMF (audits/inspections, patients support programs,

subcontracts,…)– RMP-RMA-PASS/PAES – Patients/public management=>who will manage media

reactions?

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IMPACT FOR SMEs• Guidance from NCAs - has there been enough and oriented

for SMEs?• Complying with the Electronic transmission

As an SME, I cannot afford to spend tens of thousands of Euro on a PV database and a gateway:

–EVWeb: one off-training course, free tool–Contract it out: Stakeholder roles and responsibilities =>importance of well defined contract (detailed description of delegated tasks, data exchange, agreed timelines, definitions,…)

• MAH retains full responsibility• MAH need to ensure an effective quality system =>Evaluate risk/benefit

• Impact on competitiveness and business profit

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Costs for a SME?

•Workload…will it be reduced or augmented?•Software tools and technology costs?

– MEdDRA terms is free to use in EVWEB for Small & micro-sized but not for medium sized

•Human Resources and training needs – what impact will these have on SME business?•Insourcing vs. outsourcing?•Fees: EU vs Belgium as NCA•Special fee for inspections ?

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Agence fédérale des médicaments et des produits de santé

Before and after 1235: legislation reviewPharma.be/BEAPP

Thierry ROISIN – 23/11/2012

Pharma.beafmps/DG Post/Division Vigilance

23/11/2012

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Plan

New legal framework as regards pharmacovigilance of medicinal

products for human use

GVPs

Legislation : main changes

PRAC

Union-wide assessment of phvig issues

Strengthened transparency and communication

Impact for SME


23/11/2012

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New legal framework as regards pharmacovigilance of medicinal products for human use

Regulation (EU) No 1235/2010 of the European Parliament and of theCouncil of 15 December 2010 amending, as regards

Pharmacovigilance of medicinal products for human use, Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, and Regulation (EC) No 1394/2007 on advanced therapy medicinal products (specific provisions on centrally authorised products and EMA tasks)

Directive 2010/84/EU of the European Parliament and of the Council of 15December 2010 amending, as regards pharmacovigilance, Directive2001/83/EC on the Community code relating to medicinal products for human use (nationally authorised products and common provisions)

Adopted by both Council and EU parliament and publication on 31 Dec 2010 Most of the provisions came into force in July 2012


23/11/2012

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GVPs


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GVPs


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GVPs


23/11/2012

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Legislation : main changes«OLD» LEGISLATION «NEW» LEGISLATION

DDPS

RMP if required

Definition of ADR: under normal conditions

SERIOUS ADRs to EV

Patient reporting: no legal basis

PSURs for all MAs

PSUR WS on voluntary basis

Pharmacovigilance system master file

RMP for all applications (proportionate to risks)

Definition of ADR: also in case of off label use, misuse,…

SERIOUS and NON SERIOUS ADRs to EV

Patient reporting: legal basis

PSURs submission in function of risks

PSUR WS: legal basis


23/11/2012

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Legislation : main changes«OLD» LEGISLATION «NEW» LEGISLATION


Signal detection: no legal basis

PASS: no legal basis

PAES: no legal basis

Additional monitoring: no legal basis

PhVWP


Signal detection: legal basis

PASS: legal basis

PAES: legal basis

Additional monitoring: legal basis

PRAC

New urgent union procedure

More transparency…


23/11/2012

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PRAC

New scientific committee within the AgencyPharmacovigilance Risk Assessment Committee - Reg art. 56(1)(aa)

Mandate – Reg. art. 61a §6

“ All the aspects of the risk management of medicines … having due regard to the therapeutic effect of the medicinal product …”:

Recommendations to CHMP and CMD(h) on Phvig issues Role in agreement and monitoring of RMPs Prioritisation and review of emerging safety signalsReview of PSUR assessments Evaluation of protocols and results of PASS Decision on products under additional monitoring…


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PRAC - composition

Appointed by each Member State:

Appointed by the European Commission following a public call

for expressions of interest:

1 member + alternate

27 + EEA countries non voting members 1 patient organisations rep + alternate

1 healthcare professionals rep + alternate

6 members to ensure relevant expertise available


23/11/2012

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PRAC – activities

Activity Involvement

Risk Management SystemsAgreement on RMPs + monitoring their effectiveness

Periodic Safety Update ReportsPSURs

List of harmonised submission frequencies and substances, assessment + recommendation

Eudravigilance + Periodic Safety Update Reports repository

Functional specifications, any substantial changes

Signal DetectionInitial analysis + prioritisationassessment + recommendations

Medicines subject to additional monitoring

Addition to/removal from list, extension of timeframe, symbol


23/11/2012

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PRAC – activities

Activity Involvement

Urgent Safety Proceduresfor the EU

Assessment, public hearings, recommendations

Post Authorisation Safety Studies

Consultations on requests (pre and post MA), assessment of protocols (incl. amendments) + recommendations, assessment of results + recommendations

Safety announcements Advice

Literature Adverse Drug Reactions monitoring

Consultation on list of active substances and medical literature subject to monitoring?


23/11/2012

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PRAC

•Interaction with CHMP and CMD(h)

PRAC provides recommendations to CHMP and CMD(h) – Reg. art. 56(1)(aa)

CHMP / CMD(h) shall rely on the scientific assessment and recommendations of PRAC for the fulfilment of its phvig tasks, including the approval of risk management systems and monitoring their effectiveness – Reg. art. 5(2) / Dir. art. 27

Explanation on the scientific grounds for differences if opinion / agreement is not in accordance with PRAC recommendation


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PRAC Decision-making process

PSUR PASS Union procedures (art. 31, 107i)

PRAC recommendation: regulatory action

CMD(h) (no CAP) CHMP (at least 1 CAP)

Position = maint., var., susp., revoc.

Opinion = maint., var., susp., revoc.

If consensus: agreement

NO consensus: position majority

COMMISSION

Decision modifying MA

(CAP)Decision

addressed to MS

MS: adopt measures

MAH: submit variation


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Union-wide assessment of phvig issues

Two procedures for Union-wide post-authorisation assessment of PhVig issues

Dir. art. 107i-l = urgent union procedure (revision current art. 107) Dir. art. 31 in other cases Dir. art. 36 deleted

PRAC should always give its recommendation when the reason for taking action is based on PhVig data (regardless of whether centralised or non centralised procedures, urgent or normal procedure) – Dir. Cons (25a)

Procedures laid down in Directive 2001/83/EC to be followed, also for centrally authorised products – Reg. cons. (9a)


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Union-wide assessment of phvig issuesUrgent Union ProcedureTriggers - Dir. art. 107i

Urgent action necessary, as a result of the evaluation of phvig data. MS / Commission:

• considers suspending or revoking a MA;• considers prohibiting the supply of a medicinal product;• considers refusing the renewal of a MA;• is informed by the MAH that, on the basis of safety

concerns, he has interrupted the placing on the market of a medicinal product or withdrawn a MA, or that he intends to do so;

• considers that new contraindications, a reduction in the recommended dose, or a restriction to the indications is necessary;


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Strengthened transparency and communicationEuropean and national (safety) web portals

National medicines web-portal – Dir. art. 106:

summaries of RMP (national MA) list of medicinal products referred to in Article 23 of Reg. information on the different ways for reporting suspected

ADRs, including the web-based structured forms (Reg. art. 25) ..

European medicines web-portal – Reg. art. 26:

agendas and minutes from each meeting of the CHMP and PRAC and the CMD(h) as regards phvig activities

summary of the RMP (CEP authorised products) Assessment conclusions, recommendations, opinions,

agreements and decisions (for PSURs, urgent union procedure, PASS) taken by CHMP, PRAC, Commission, NCA and CMD(h)

…


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Strengthened transparency and communication


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• all the provisions of the phv legal framework (obligations for MAHs) are also applicable for SME

• Consequently, each MA must have a pharmacovigilance system

• possibility to subcontract certain activities to another organisation or person (cfr I.C.1.5. module I GVP)

Impact for SME


23/11/2012

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56

• In case of subcontract, the MA retains full responsibility for the completeness and accuracy of the PSMF

• The ultimate responsibility for the fulfilment of all phv tasks and responsibilities and the quality and integrity of the phv system always remains with the MAH

• The MAH shall ensure that an effective quality system is applied in relation to the subcontracted tasks

Impact for SME


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Thank You


23/11/2012

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Agence fédérale des médicaments et des produits de santé - afmps

Place Victor Horta 40/40 1060 Bruxelles

tél. 0032 2 524 80 00fax 0032 2 524 80 01

e-mail [email protected]

www.afmps.be

Contact

mailto:[email protected]

http://www.afmps.be/

Vos médicaments et produits de santé, notre préoccupation

Federal agency for medicines and health products

New pharmacovigilance legislation:

How to smoothen the transition period? EU and Belgian bridging measures

Goethals Sophie, famhp, vigilance department 23 November 2012

BeappFamhp/DG Post/Vigilance Department-Pharmacovigilance

23 November 201261

In this presentation …

1. What has been achieved? What to come? How to smoothen the transition period?

EU level Belgium

2. Specific topics where smooth implementation is necessary

Additional monitoring and implementation of ▼ and standardised statements in SmPC and leaflet

Post-authorisation safety studies


23 November 201262

Background

2010 Legislation: key achievements / challenges

Clear tasks and responsibilities for all parties Improved EU decision-making procedures Proactive and proportionate risk management Higher quality of safety data Stronger link between safety assessments and regulatory action Strengthened transparency, communication and patient involvement


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What has been achieved? What to come? How to smoothen the transition period? EU level

1. What has been achieved?


23 November 201264


2. What to come? Oct 2013

2014 ?

Jan 2013

Beyond 2013

June 2013


23 November 201265


2. What to come?GVP second wave modules

Module III – Inspections Publication Dec 2012

Module IV – Pharmacovigilance Audits Publication Dec 2012

Module XV - Safety communication Publication Dec 2012

Module X - Additional monitoring Publication Q1/Q2 2013

Module XI - Public participation Public consultation Q2 2013

Module XII - Continuous pharmacovigilance Public consultation Q1 2013

Module XIII - Incident management Under discussion

Module XIV - International collaboration Public consultation Q2 2013

Module XVI - Risk minimisation measures Public consultation Dec 2012 / Q1 2013


23 November 201266


2. What to come?The 2012 legislation: Pharmacovigilance II

Background: ‘Stress test’ of the 2010 legislation detected certain areas where legislation could be further strengthened

25 October 2012 new amending legislation adopted: – Directive 2012/26/EU of 25 October 2012 amending Directive

2001/83/EC as regards pharmacovigilance; Applicable from 28 October 2013

– Regulation No 1027/2012 of 25 October 2012 amending Regulation No 726/2004 as regards pharmacovigilance; Applicable from 4 Dec 2012 / 5 Jun 2013

Filling gaps:– Clarification of scope of ‘referral’ procedures and events that will lead to

the initiation of the procedures (especially Urgent Union procedure) – Modified Union interest procedure will allow Member States to take

provisional measures – Voluntary withdrawal – MAH to state reasons – Increased transparency: List of products subject to additional monitoring


23 November 201267


3. How to smoothen the transition period?

EC’s Q&A on transitional arrangements http://ec.europa.eu/health/files/pharmacovigilance/2012_02_qa_phv.pdf

EMA/ NCA Q&A on practical transitional measures – November updated awaited

http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2012/05/WC500127658.pdf

CMDh Q&A http://www.hma.eu/310.html

List of nationally approved substances for which PSURs are required for generic medicinal products during the transitional period

http://www.hma.eu/310.html

Reporting requirements of ICSRs applicable to MAHs during the interim period


NCAs requirements for PSUR submission during the transitional period


To come: Q&A on EURD list?


23 November 201268

What has been achieved? What to come? How to smoothen the transition period? Belgium

1. Achievements: programmawet van 29 maart 2012: herziening retributies wet dd. 3 augustus 2012 tot wijziging van de wet van 25 maart 1964 op

de geneesmiddelen, gepubliceerd op 11 september 2012 in Belgisch Staatsblad

Safety board, patient reporting, ..

2. Expected soon: ontwerp KB tot wijziging KB 14 dec 2006 -> advies Raad van State circulaire -> consultatie met industrie 20 nov 2012

3. Transition period: MAHs can apply European new legislation, guidelines, transitional

measures, although new directive has not been fully transposed into national law [http://www.fagg-afmps.be/nl/geneesmiddelenbewaking/]

a combination of ‘old’ and ‘new’ legislation shall not be accepted. [email protected]


23 November 201269


Patient reporting in Belgium


23 November 201270


Patient reporting in EU


23 November 201271


1. Background

[Reg 726/2004 whereas clause 17]

… some medicinal products are authorised subject to additional monitoring. This includes all medicinal products with a new active substance and biological medicinal products, including biosimilars, which are priorities for pharmacovigilance. Competent authorities may also require additional monitoring for specific medicinal products that are subject to the obligation to conduct a post-authorisation safety study or to conditions or restrictions with regard to the safe and effective use of the medicinal product. Medicinal products subject to additional monitoring should be identified as such by a black symbol and an appropriate standardised explanatory sentence in the summary of product characteristics and in the package leaflet. A publicly available list of medicinal products subject to additional monitoring should be kept up to date by the European Medicines Agency ……


23 November 201272


1. Background

Mandatory scope [Article 23 (1) of the Regulation]

Two categories of medicinal products shall be automatically included in the list :

a) “Medicinal products authorised in the Union that contain a new active substance which, on 1 January 2011, was not contained in any medicinal product authorised in the Union”;

b) “Any biological medicinal product not covered by point (a) that was authorised after 1 January 2011”.

New regulation 1027/2012 amending Reg. 726/2004:extends mandatory scopeproducts subject to specific conditions will be included under mandatory scope cfr. red text on next slide


23 November 201273


1. Background

Optional scope [Article 23 (2) of the Regulation]

There is also the possibility to include in the list medicinal products subject toconditions, not falling under the mandatory scope. This can be done at the

request of

the EC or the NCA, as appropriate, following consultation with the PRAC.

conditions or restrictions with regard to the safe and effective use [Reg Art 9(4)(c), Dir Art 21a(d)];

to take certain measures for ensuring the safe use of the medicinal product to be included in the risk management system [Reg Art 9(4)(ca), Dir Art 21a(a)];

to conduct post-authorisation safety studies (PASS) / post-authorisation efficacy study (PAES) [Reg Art 9(4)(cb) (cc) and Art 10(a), Dir Art 21a(b)(f) and Art 22a];

stricter reporting of ADRs [Reg Art 9(4)(cb), Dir Art 21a(c)];

conditional approval, i.e. authorisation is granted subject to certain specific obligations (e.g. the performance of further studies), to be reviewed annually by EMA [Reg Art 14(7)];

marketing authorisation under exceptional circumstances [REG Art 14(8), DIR Art 22];

the existence of an adequate pharmacovigilance system [DIR Art 21a(e)].

when a competent authority imposes an obligation on a marketing authorisation holder to operate a risk management system for a medicinal product approved before 2 July 2012 [REG Art 21(2)] or 21 July 2012 [DIR Art 104a].


23 November 201274


2. Creating and maintaining the list of product under additional monitoring

EMA and NCAs will be responsible for (automatic) inclusion of substances on the list

products will normally remain on the list for 5 years – for mandatory scope products removal will be tied to the renewal

procedure – for optional scope products removal will be tied to fulfillment of

conditions List to be published on EMA + NCA web portals: Q1 2013?

→ publication of list to be aligned with EC’s selection of black symbol (2 July 2013)

? Will MAHs know in advance of publication of their products? ? Will national schemes co-exist?


23 November 201275


3. Implementation of ▼ and standardised statements in SmPC and leaflet

The SmPC and the package leaflet shall include the statement “This medicinal product is subject to additional monitoring”. That statement shall be preceded by a black symbol which shall be selected by the Commission following a recommendation of the PRAC by 2 July 2013*[Reg.

2012/xx to be published], and shall be followed by an appropriate standardised explanatory sentence [Art. 11 and 59 of Directive 2001/83/EC and Art. 23(5) of Regulation (EC) No 726/2004].

a. Selection of black symbol: PRAC recommendation (Oct 2012): inverted black triangle (▼) Commission Decision (before 2 July 2013): Q1 2013 ?

EC public consultation on phasing-in launched 21 Nov 2012- till 10 Jan 2013 [http://ec.europa.eu/health/files/pharmacovigilance/2012_11_09_pb__black.pdf]

b. Standardised statements for SmPC and leaflet: CHMP endorsement of the QRD template / translation / .. Implementation plan Publication by March / April 2013 (once black symbol is selected by

EC)


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4. Wording of standardised statements for additional monitoring

SmPC

Package Leaflet


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5. Wording of standardised statements - encouragement ADR reporting for all medicinal products

SmPC (end of section 4.8)

Package Leaflet (end of section 4.)


23 November 201278

Non-interventional post-authorisation safety studies (PASS)

1. Scope of dir. 2001/83, chapter 4 “supervision of PASS”

a post-authorisation study should be classified as a PASS, when the study includes one of the following objectives [GVP, VIII.B.3]:

to quantify potential or identified risks to evaluate risks of a medicinal product used in patient populations

for which safety information is limited or missing (eg pregnant women, specific age groups, patients with renal or hepatic impairment)

to provide evidence about the absence of a risk to assess patterns of drug utilisation that add knowledge on the

safety of the medicinal product (eg indications, dosage, co-medication, medication errors)

to measure the effectiveness of a risk minimisation activity.

PASS initiated, managed or financed by a MAH non-interventional

If a PASS is a clinical trial: dir. 2001/20/EC and Vol. 10 of Eudralex shall be followed


23 November 201279

2. … voluntarily or pursuant to obligations

non-interventional PASS;initiated, managed or financed by MAH

applicable legislation

Pursuant to an obligation imposed by a competent authority:condition to the MA [Dir. art. 21a and art. 22a / Reg. art. 10 and art. 10a]exceptional circumstances MA [Dir. Art. 22 / Reg. art. 14, §8]

Dir. 2001/83 art. 107 m:cfr. infra

Dir. 2001/83 art. 107 n-q:regulatory supervision by competent authority (protocol and final study report)

Implementing Reg. 520/2012 , art. 36-38format of protocol, abstract and final study report

Voluntarily:studies required in RMPany other PASS

Dir. 2001/83 art. 107 m: no promotional character, payments to HCP restricted to compensation of time and expenses incurredprotocol and progress reports: may be requested by MS in which the study is conductedfinal report to MS where study conducted, monitor data and impact on BR

GVP: legal requirements applicable to studies conducted pursuant to obligation are recommended, where appropriate, to studies conducted voluntarily [GPV, VIII.B.1]



23 November 201280

Management of study (PASS with MAH involvement )

Imposed as an obligation Conducted voluntarily

no promotional character payment to HCP restricted …

[Dir. Art. 107m]

Legal obligation Legal obligation

Monitor data generated in the study with consideration to benefit-risk of product concerned [Dir. Art. 107m]


Use of standard formats for protocol and study report [Reg. 520/2012] Template for protocol

[http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/10/WC500133174.pdf]

Legal obligation (10 Jan 2013)

GVP recommendation

Prior protocol approval [Dir. Art. 107n-q]

regulatory supervision and assessment of study results [Dir. Art. 107n-q]

Legal obligation:PRAC supervisionNational supervision for PASS imposed after authorisation by 1 MS, and conducted only in that MS

(if in RMP)

Registration in EU PAS register Legal obligation GVP recommendation

Quality system Legal obligation GVP recommendation



23 November 201281

Reporting of study information (PASS with MAH involvement )

Imposed as an obligation

Conducted voluntarily

Any new information which might influence the evaluation of B/R balance to be reported to NCAs of MS where the product is authorised [Dir. Art. 107m]


Protocol to be submitted upon request to NCA of MS where study is conducted [Dir. Art. 107m + art. 107 n (3)]

Legal obligation cfr. Annex to GVP module VIII

Progress reports to be submitted upon request to NCA of MS where study is conducted [Dir. Art. 107m]

cfr. Annex to GVP module VIII

cfr. Annex to GVP module VIII

Final report to be sent to the NCA of the MS where the study is conducted, within 12 months of the end of data collection [Dir. Art. 107m]


Reporting of suspected ADRs in studies with primary data collection with 15 days (serious ADRs) or 90 days (non-serious ADRs) [See interim and final arrangements in GVP Module VI, C.4 ]


Final manuscript of article to be transmitted to NCAs of MS where product is authorised within 15 days after acceptance [GVP]

recommended recommended



23 November 201282

3. Annex to GVP module VIII: MS' requirements for transmission of information on non-interventional PASS with PRAC oversight

→ Belgium: famhp, vigilance department, [email protected]



23 November 201283

4. Annex to GVP module VIII –Member States' requirements for transmission of information on non-interventional PASS, conducted voluntarily



23 November 201284

5. famhp requirements for transmission of information on non-interventional PASS with famhp oversight

Protocol (CD-rom), progress reports and final study report incl. abstract to be submitted to famhp, R&D



23 November 201285

6. EU PAS Register

EU electronic register of post-authorisation studies [GVP, VIII.B.4] repository of all non-interventional PAS conducted in the EU, irrespective

of the source of funding and status of investigators (MAH, academia, regulatory or public health authorities, …)

will be developed as upgrade of ENCePP study registry transitional period: ENCePP study registry to be used

supports EMA to fulfil its obligation to make public protocols and results of PASS imposed as an obligation [Reg. art. 26 (h)]

For imposed studies: will not replace regulatory submission For studies conducted voluntarily: accepted by MS (and Belgium) as

means for submitting study information (Annex 1 of GVP Module VIII)



23 November 201286

6. EU PAS Registerhttp://www.encepp.eu/encepp_studies/indexRegister.shtml



23 November 201287

ICSR reporting requirements for MAH during interim period

1. Serious EU ICSRs

[http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2012/05/WC500127657.pdf]


23 November 201288


2. Serious non-EU ICSRs and non-serious EU ICSRs


23 November 201289


2. Serious non-EU ICSRs and non-serious EU ICSRs


23 November 201290

PSURs: List of Union reference dates and PSUR frequency

Comprehensive list of active substances and combinations of active substances, authorised in more than one member state, for which PSURs shall be submitted as determined

Harmonisation of DLPs and frequency of submission of PSUR for products subject to different marketing authorisations –> enable single assessment based on substances

EURD list used to control PSUR submission for generics; grounds for requesting PSURs for generics: concerns based on phvig data / lack of data

Agreed by the CHMP/CMDh after consultation of the PRAC [DIR Article 107c (paragraphs 4 and 7), and REG Article 26(g)]

Publication on EMA website on 1 October 2012: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/09/news_detail_001616.jsp&mid=WC0b01ac058004d5c1

Legally binding as of April 2013 [DIR Article 107c (7)]. Until then, follow currently agreed PSUR submission frequency and DLP.

The list overrules the “routine” submission schedule and any condition laid down in the MA of the products concerned.


23 November 201291

PSURs: List of Union reference dates and PSUR frequency

15/05/2012 FAMHP/Vigilance/gss 92

PSURs: overview

Old legislation New legislation Transitional provisions?

Situation since July 2012

PSUR requirement: for all MAs

Derogation: no routine PSUR for generics, WEU, THMP, homeopathic registration

No derogation for routine PSURs applicable

PSUR frequency: routine PSUR cycle for most MAs

1) Risk based PSUR cycle, through comprehensive URD List

2) Condition to MA

3) Routine PSUR cycle

No 1) List URD legally binding 6 months after publication (publication Oct. 2012 -> April 2013)

2) July 2012

3) July 2012

Timelines for submission:

Within 60 days > DLP

Within 70 or 90 days > DLP (GVP)

No Irrespective of old / new PSUR format: 70 or 90 days > DLP

PSUR submission:

to MS / EMA (centralised) [Annex 6.2 of Vol. 9 A]

E-submission to EMA PSUR repository

From 12 months after repository is operational

PSUR submission to MS / EMA (centralised)

15/05/2012 FAMHP/Vigilance/gss 93

PSUR: overview

Old legislation New legislation Transitional provisions?

Situation since July 2012

Assessment:

centralised procedure

informal PSUR work sharing

MRP

Purely national procedures

Clear legal basis for:

Assessment of single centrally authorised medicinal product

Single EU assessment

Purely national procedure

No Assessment of centralised products following new procedure (PRAC)

Informal PSUR work sharing

Mutual Recognition Procedures

Purely national procedures

Content:

Focus on presentation of safety data

Structured risk evaluation

Benefit evaluation

Integrated benefit risk evaluation module

Transitional period of 6 months in Implementing Measures - draft

Between July 2012 and

January 2013 old and new

formats will co-exist


23 November 201294

PRAC phasing-in

For complete new MAAs for CAPs starting as of December 2012:

– 1 Status-quo with current situation– 2 X = open to all PRAC delegates, the selection criteria being the best possible scientific expertise and, where

possible, from a different MS compared to the CHMP Rapporteur (A) and CHMP Co-Rapporteur (B)

For new MAAs for CAPs under CHMP review or procedures starting in Aug / Sept /

Oct / Nov 2012: PRAC Rapp/Co-Rapp stays aligned with CHMP Rapp/Co-Rapp Member States

• For generics, the PRAC Rap is from the same delegation as the• CHMP Rap of the reference medicinal product

I nitial Authorisation Phase

Post-authorisation Phase

New MAAs as of September 2012

CHMP Rapporteur A1 A1

CHMP Co-Rapporteur B1 B1

PRAC Rapporteur X2 X2

PRAC Co-Rapporteur A1 A1


23 November 201295

PRAC phasing-in

For “Legacy” centrally authorized medicines (= authorised and on-going), while awaiting formal reappointment from Q1 2013 onwards and if PRAC needs to be consulted: PRAC Rapp/Co-Rapp stays aligned with CHMP Rapp/Co-Rapp Member States

Referrals (only non-CAPs involved): Co-Rapporteur: Member State triggering the referral. Rapporteur: open to all other Member States, and criterion of best

possible and available expertise to be taken into account.

Referrals (mixture of CAPs and non-CAPs): Rapporteur: PRAC Rapporteur for the CAP(s). Co-Rapporteur: Member State triggering the referral (whereby also the

involvement of the PRAC Co-Rapporteur for the CAP(s) needs to be considered).


23 November 201296

Back up slides

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23 November 201297

Back up slides

–


23 November 201298

Back up slides

–


23 November 201299

Back up slides

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23 November 2012100

Federal agency for medicines and health products - famhp


tel. 0032 2 524 80 00fax 0032 2 524 80 01


www.afmps.be

Contact



Your medicines and health products,our concern


How to qualify for quality in the near future and be audit ready

Nele Matthijs- 23.11.2012

How to qualify for quality in the near future and be audit ready? famhp/DG Inspection/Division Industry

Date103

-What do we expect from industry in relation to safety reporting of drugs. How to be prepared for an inspection ?

- How to ensure the effectiveness and correctness of our pharmacovigilance system



Date104

A journey of quality


Date105

Journey of PhV Legislation

Good Vigilance Practices

Implementing Measure

Regulation & Directive

Incr

easi

ng le

vel o

f de

tail


Date106

GVP : Good Pharmacovigilance Practice

• Apply to marketing-authorisation holders, the Agency and medicines regulatory authorities in EU Member States

• Cover both centrally authorised and nationally authorised medicines

• Comprise 16 modules, each of which covers one major process in pharmacovigilance


Date107

Just a flavour of the changes

•Pharmacovigilance System Master File (PSMF)

•Expedited reporting (new requirements!)

•PSUR and the new format (to submit or not to submit?)

•Risk Management Plans required for all products- effectiveness of risk minimization activities needs to be assessed

•Inspections and the role of the Supervisory Authority

•Inspections of contractors


Date108


- Quality – Quality systems GVP Module I

- Inspections GVP Module III

-Audits GVP Module IV

- Written for a broad public : basic principles specific details- take out what you need / implement where needed- Risk-based approach


Date109

Module I: Pharmacovigilance systems and their quality systems

-Legal requirement for quality systems introduced by Directive 2010/84/EU and Regulation (EU) No 1235/2010

-The minimum requirements of these quality systems are set out in the Commission Implementing Regulation (EU) No 520/2012 on the Performance of Pharmacovigilance Activities

- Consistent with the general principles of the ISO 9000 Standards on good quality management practices,

Guidance for the establishment and maintenance of quality assured pharmacovigilance systems for MAHs, CAs of MSs and

the EMA


Date110

• Quality cycle: planning, QC, QA, improvements

• Responsibilities of the MAH regarding EU-QPPV - EU-QPPV qualification – ensure he has acquired adequate theoretical and practical knowledge for the performance of PhV activities - EU-QPPV role and responsibilities : oversight over the functioning of the system in all relevant aspects, including its quality system - Each PhV system can have only one QPPV. 1 QPPV can work for more than 1 MAH for shared of separate PhV systems or act as QPPV for more than 1 PhV system of the same MAH, provided that the QPPV is able to fulfil all obligations.



Date111

•Training

•Facilities and equipment

•Compliance management

•Record management

•Documentation of the quality system

•Monitoring performance & effectiveness of the PV system & its quality system



Date112

To ensure that all PhV processes are controlled :

•Case translation : in which time period, correct translate?

•Does MAH check when sending a case to global, there is always an acknowledgment of receipt sent to local?

•Does the MAH verify the timelines of compliance for transmission

of ICSRs, PSURs,..?

• Check internal timelines for reporting SPC updates

• RMP compliance and effectiveness :

- monitoring compliance and effectiveness of RMP and RMA

- is the compliance monitoring performed at regular basis

Why and how perform quality control

• Are SOPs up-to-date ?


Date113

-In many cases, error is made to implement QC only at the end of the implementation of a whole of processes

RISK that an error is made at basic level (f.e. : translation (local level), Meddra coding (global level))

A MAH may have a perfect functioning system on signal detection and PSUR evaluation, but when an error occurs at first level or case processing big impact on the whole process

Start QC at each stage as soon possible and for each individual sub process.

Why and how perform quality control


Date114

There is broad support for quality systems for pharmacovigilance, but also some concern over the burden to implement them, in particular for smaller marketing authorisation holders or for medicinal products with low risks to patients and public health.

every risk, low or high, is a risk quality is needed

implement step by step risk-based planning



Date115

- Module provides transparency to the inspection process and gives MAH and NCA guidance on the expectations during inspections

- Public consultation finished

- Final Module III publication in December 2012

Module III : Pharmacovigilance inspections


Date116

• New concepts in addition to the elements included in vol. 9A:

•Supervisory Authority •PSMF location

• Pre-authorization inspections

• Information sharing on inspections planned and conducted

• Communication of non-compliance



Date117

• Contact person for pharmacovigilance issues at national level : National nominated persons should report to the QPPV. Reporting in this context relates to pharmacovigilance tasks and responsibilities and not necessarily to line management

- Availability 24/24 and 7/7 - Employed in Belgium- Dispose the appropriate qualifications for the performance his responsibilities as also have the linguistic properties to talk with his interlocutors in the national language of his choice

- Circular 520/544/545 related to PhV local QPPV 1 new circular related to the local contact person



Date118

- Publication December 2012

- Provides clear guidance on planning and conducting audits which will help promote standards and harmonisation throughout the European network.

- Welcome the development of the risk-based approach requested in the Implementing Measures

Module IV : Audits


Date119

• INDEPENDENCE ( legal requirement, see auditing standards)

• TRAINING AND QUALIFICATIONS ( In line with Module I- I.B.7 )

• EVALUATION OF AUDIT WORK (quality assessment of the auditors work is a professional requirement)

Module IV : Audits


Date120

Why Perform Pharmacovigilance System Audits?•To ensure compliance with company procedures and local / global regulatory requirements•To ensure company regulatory obligations / commitments are met•Increasing Regulatory Inspections –Internal detection of risk is essential•To identify process / quality deficiencies and improvements

MOST IMPORTANTLY, PHARMACOVIGILANCE AUDITS ACT AS ONE MECHANISM TO ENSURE THE SAFETY OF PATIENTS IS MAINTAINED

MOST IMPORTANTLY, PHARMACOVIGILANCE AUDITS ACT AS ONE MECHANISM TO ENSURE THE SAFETY OF PATIENTS IS MAINTAINED

Module IV : Audits


Date121

Types of Pharmacovigilance System Audits

•Global Pharmacovigilance (QPPV – Global Systems and processes)

•Company Affiliates (i.e., Country Office, Local Operating Company, Marketing Company)

•Marketing (Licensing) Partners

Module IV : Audits


Date122

Global Pharmacovigilance System Audits

QPPV : qualification, availability, 24u/7, back-up procedures, training

Focus on central Pharmacovigilance processes–Safety Case Processing–Expedited Reporting–Signal Detection / Safety Surveillance–Aggregate Reports (e.g., PSUR, etc.)–Literature Search–Office of the QPPV responsibilities

Module IV : Audits


Date123

Assess compliance with company procedures and global Pharmacovigilance regulations

Sample of products across therapeutic areas and a defined timeframe (vehicle to assess the system / process)

Systems approach focused on processes

Global Pharmacovigilance System Audits


Date124

Company Affiliates• Primary focus on local contact person (qualifications// job description,

availability – back up procedure, training,..

• local Pharmacovigilance responsibilities

• Assess compliance with local and global company procedures and regulatory requirements (as applicable)

• Evaluate the flow of safety information (from all applicable sources) from initial receipt to reporting to external parties : AE collection

• Involves many functional groups that impact the Pharmacovigilance system-Pharmacovigilance -Sales-Regulatory Affairs -Product Quality-Medical/Clinical -Information Technology-Marketing -Medical Information

• Not just an audit of local affiliate but also of global processes to support local affiliates


Date125

• Reconciliation with Product Quality Complaint handling and medical questions

• Local quality systems (including compliance monitoring)

• Regulatory functions (e.g., Aggregate reports submission, Labeling, Regulatory Authority query management, etc.)

• Contracts and Agreements (Marketing Partners, CROs, consultancy, etc.) :

e.g. to verify if resources are sufficient for the required activities as described in the contract (internal/external audit)

• Promotional Material

Company Affiliates


Date126

• Standard Operating Procedures (SOPs)

• Training

• Verification of respect of RMAs and their tracking

• Management of PSP (contracts, collect and management of AEs/ARs,…)

• Document Retention / Archive

• Electronic systems used to support the Pharmacovigilance system

• Business Continuity / Disaster Recovery

Company Affiliates


Date127

Marketing (Licensing) Partner Audits

•Includes in-licensed and out-licensed product agreements

•Focus on compliance with Marketing Partner agreement –Ensure Pharmacovigilance roles and responsibilities are defined and performed –Ensure appropriate exchange of safety information

•Assess compliance with local and global company procedures and regulatory requirements (as applicable)

•May be performed independently by company, as a joint audit between companies, or by an agreed upon consultant


Date128

Global Pharmacovigilance Inspection Trends


Date129

Examples of deficiencies related to the quality system

• Lack of quality control in key processes (local as global processes) - lack in FU of cases : has it been performed, how, when,..

- no control on translation, reporting from sales reps- literature reporting : has it been performed, when, how

• Missing or incomplete SOPs in key processes - back-up procedure, - quality control, - business continuity)

• No or incomplete job descriptions - reflection of Management - defines necessary skills and training


Date130

Examples of deficiencies related to the quality system• Deficiency on the performance of audits (local affiliates/ global activities) - risk-based approach

- audits of contract companies - skills auditors

• Lack in interaction between departments - reconciliation of PhV data (medical and quality department) - regulatory affairs : update SPCs, variations, PSURs, implementation

of referrals (MRP/DCP/NAT) - interaction global / local : awareness of safety issues / RMP / …

• Lack in responsibilities of the QPPV - incomplete overview - insufficient back-up system


Date131

5 Steps You Can Take to Help Ensure Quality in the near future

-1 Define the impact of the new legislation on the processes and

process documents / database / …

-2 Update processes / documents (SOPs, guidance, working

instructions, …) / tools as appropriate risk-based planning

-3 Get the concerned people trained in time

-4 Perform quality control on the : - training

- the performance on PhV activities

- the correctness/efficacy of the PhV activity

-5 Performance of audits on global and local activities


Date132

A journey of improved quality


Date133



tel. 0032 2 524 80 00fax 0032 2 524 80 01


www.afmps.be

Contact




The Belgian consensus on Risk Minimisation ActivitiesNew process

M.L.Bouffioux - 23th November 2012

RMA New processfamhp/DG Post/Division Proper use of medicine

Date136

Reminder

• Legal basis: Article 6 § 1stocties of the law of 25th March 1964 on medicines, as amended by the law of 3rd August 2012 (MB 11th September 2012)

• Some marketing authorisations are granted on condition that the MA

holder develops additional risk minimization activities (RMA). Justified if essential for the safe and effective use of the medicinal

product

• The need for such possible measures belongs to the risk management plan (RMP) now mandatory in marketing authorization applications.

• These RMA activities often require that the marketing of the medicinal product is accompanied by materials, educational or informative programmes or services for healthcare professionals and / or patients.


Date137

Prior Approval

• Educational and informational materials, programmes or services shall be subject to the prior approval of the Minister or his delegate (CEO of the FAMHP)

- National MAs, DCP, MRP- Centralized marketing authorization- Modification of the RMA without modification of the terms of the

marketing authorizations- Variation of the MA-> with new RMA conditions

-> with modification of the RMA conditions • Implementation should be no later than at the time of the marketing of

the medicinal product or, if conditions change, within the time allowed if specified in the MA.


Date138

Approval procedure

• Working group with industry -> consensus on a proposal for an approval procedure which should be implemented in a modification of the Royal Decree of 14th December 2006 (future Article 65 quater)


Date139

Introduction of the approval application

• Contents of the file:- Standard application form (already available on the FAMHP website)- 2 copies- Copy of the MA and any annexes (conditions – key elements of RMA)- SPC, leaflet (latest approved version)- Copy and / or complete description of the material, programme or service- Copy of the part of the RMP justifying the implementation of the RMA- Terms of implementation – circulation plan- Possibly, in the case of modification, termination terms or removal

procedures of the old material


Date140

Application validation

• Within 15 days the FAMHP checks if the file is complete • If OK -> acknowledgment • If not OK -> the MA holder is informed by the FAMHP -> 15 days to complete the file • If file not complete after 15 days -> application unacceptable -> MA holder informed


Date141

Application assessment

• Within 45 days from the date of validation of the file the FAMHP sends the applicant the results of its assessment.

• The FAMHP can consult the Commission for medicines for human use (cfr current circular 532 bis to be adapted) . The delay is then extended to 90 days.

• In exceptional circumstances (e.g. to consult an external expert) the delay period may be extended by 15 additional days

• The MAH is informed.


Date142

Assessed items

• Compliance with the SPC, leaflet, approved items within the MA

• fulfilled conditions – key elements

• Necessary, sufficient, appropriate materials, programmes or services to promote the safe and effective use of medicine: - evaluation of the appropriate design and form, of the content, of rules of implementation (adapted to the health care system in place in Belgium) • Lack of promotional aspects. Information should be clearly focused on

the risk minimisation goals


Date143

Conclusions of the assessment

• 1. Positive conclusions -> intention of RMA approval

• 2. Unfavourable provisional advice Reasons:

- Objections to envisaged materials, programmes or services - Request to modify the form and / or content and / or procedures for implementation- Request to complete the fileTiming suspended:- The holder responds within a maximum of 60 days- If> 60 days: request deniedConclusions:- intention of (modified )RMA approval - Refusal (to reintroduce an application)


Date144

Introduction of the final material

• Within 60 days of the letter of intended approval the applicant shall submit a copy of:- The final presentation of the approved version- Translations with a declaration of conformity of these translations


Date145

Approval decision

• Within 5 days of receipt of the final material and translations the FAMHP- Verifies that the documents are complete- Sends the letter with the decision of approval


Date146

Implementation

• at the time of the marketing- maximum 90 days after approval - if imposed after MA

- if modified unless the Minister determines a different timing • The MA holder is responsible for the implementation of the RMA and

its consistency with the approved dossier


Date147

References

www.afmps.be -> Usage humain->Médicaments -> Bon Usage -> Additional RMAwww.fagg.be-> Menselijk gebruik -> Geneesmiddelen -> Goed gebruik -> Additional RMA

• Circular 532 bis will be adapted to the new procedure• Standard Form of application• EMA Guideline on good pharmacovigilance practices – Module V – Risk

management systems (V.B11.2 ) – further extensive guidance on additional risk minimisation measures will be provided in Module XVI

• 10 focus points published on the FAMHP website• Guidelines for the content and form published on the FAMHP website• Need for on-going dialogue during the procedure between the file manager

and the applicant, in particular to avoid having to appear several times before the medicines commission

• Keep in mind the goal of public health



Date148



tel. 0032 2 524 80 00fax 0032 2 524 80 01


www.afmps.be

Contact



Does CT-3 provide more operational transparency ?

An industry perspective

J. Van Rampelbergh Head of Clinical Study Unit

sanofi-aventis Belgium

Info session: Be (pharmaco) Vigilant - 23/11/2012

What’ s CT-3?

Circular letter 586 - National Application of the Revised CT-3 guidance

• To implement revised CT-3 in national practice

• Replaces Circular Letter 460 and provides short term improvement and updated information on management of adverse event/reaction reports arising from Clinical Trials

• Aim – Brightening – Clearing – Clarifying

152

Definitions (1)

• IMP

• NIMP

• In the scope but…..

• “an untoward or unintended response to a non-IMP which does

not result from a possible interaction with an IMP is, by definition,

NOT A SUSAR”

• Circ Letter 586: only a definition of NIMP.

153

Definitions (2)

• SUSAR– Suspected unexpected serious adverse reaction

• Reference Safety Information (RSI)– If SmPC available: most appropriate (with reference to subject safety)

version should be selected– Otherwise most recent version of RSI (mostly in the Investigator’s

Brochure) – Will serve to determine and report SUSARs– An update/change of the RSI will influence the number of adverse

reactions that are reported as SUSAR

154

Application (1)

– Interventional clinical trials with Investigational Medical Products or with nonIMP

– Post marketing Pharmacovigilance rules are not applicable, even if marketed drugs are used in the clinical trial

– Non-interventional trials – Compassionate Use and Medical Need Programs follow post-marketing PV rules

• But CUP are conducted with medicinal products without marketing authorization

155

Application (2)

– Non-commercial trials • Instructions for electronic or paper submission ? • Deadline for mandatory reporting through EudraVigilance ?

– Investigator Sponsored Trials • Avoid double reporting by sponsor and investigator? • Recommended: Technical agreement in order to delegate to

pharma company or an external consultant to perform safety reporting for the investigator without being considered as the sponsor.

• Quid: non-EudraCT studies ?

156

SUSAR ReportingSponsor to CA (1)

• All unblinded SUSARs occurring in clinical trials – Authorized in the EU or by the FAMPH– Performed exclusively in a third country or another Member State

when the active substance was authorized in the EU

• Timelines– unchanged – 7 days vs 15 days

• Reporting obligation ends with treatment completion all subjects enrolled in that MS

157

SUSAR ReportingSponsor to CA (2)

• Format – Indirect reporting through EMA EudraVigilance DB (ICHE2B format)

• Belgian Affiliate or Corporate PV• Local studies: Agreement with delegation of power

(audits) • Double reporting to avoid

– Direct reporting: Non-Commercial trials

• Individual case safety reports (ICSR) by paper with waiver

• Direct reporting possible in Belgium until when ?

SUSAR ReportingSponsor to LEC

• Sponsor of a clinical trial conducted in Belgium should send Belgian SUSAR report to LEC

• No 6-monthly line listings to LEC needed

• Format– Not specified– Electronic if accepted by LEC – Email + CIOMS in attachment = unprotected – Encourage secured company portal system?

159

SUSAR Reporting Sponsor to investigators (1)

• Sponsor should also inform all other investigators by means of periodical line listing of SUSARs together with an updated safety profile of the IMP– No timelines – To be specified by sponsor depending on type of trial ? – Drivers to define periodicity ? – All SUSARs vs only Belgian cases to LEC? Confusing for investigators

and EC – Standardize by sponsor in procedure or in protocol (audit)– Do investigators need to receive individual cases ?

160

SUSAR ReportingSponsor to investigators (2)

– Scientific, medical value and transparency of line-listing of all SUSARs to investigators and no longer to (L)EC ?

• SUSARs with no (direct) consequence on Risk/Benefit – no timelines?

• SUSAR with change of Risk/Benefit – reporting by Urgent Safety Notification to all parties?

161

Unblinding - GENERAL (1)

– CA• Belgian unblinded cases through EudraVigilance

– LEC• Belgian unblinded cases – format not specified

– Why unblinded to LEC ?

– Guarantee investigators will receive unblinded information ?

162

Unblinding - GENERAL (2)

• Investigators– Should only receive blinded information unless unblinding necessary

for safety reasons

– Blinded individual SUSARs or line-listing

– Format not specified

– Periodicity: not specified or standardized

– Use of abbreviated DSUR?

Unblinding (2)

• After unblinding by the sponsor

– Case is unexpected = SUSAR – Report according to specified rules

– Case is expected or placebo related = No SUSAR

– Comparators

• Sponsor to report SUSAR through EudraVigilance

• Information towards MAH?

• How to define a SUSAR with a comparator? RSI? SmPC?

164

DSUR reporting (1)

Format – Reference ICH E2F, DSUR (previous ASR)– To be prepared after first authorization of a clinical trial in Europe

Reference Safety Information– RSI applicable at the start of reporting periods and to be attached in

appendix– RSI serves as reference during reporting period

RSI changes/updates– Substantial amendment to LEC and CA – Alignment of DSUR, Investigator’s Brochure and/or RSI update =

alignment reporting period and reference doc

165

DSUR reporting (2)

Content • Listing all SUSARs (yearly basis) and Safety Summary

• To LEC and CA. Quid non LEC ?

Start of DSUR submission to CA

• After first authorization by CA of a clinical trial with this IMP – Most recent DSUR to submit with initial CTA dossier, if study start in Belgium is

later than first authorization

– Line listing unblinded SUSARs to fill possible gap?

End of reporting • Until LVLP in Belgium = End of exposure

• Or until End of Trial criteria as specified in the protocol

DSUR reporting (3)

• No DSUR required for trials < 1 year

• The Clinical Trial Report (CSR), as a part of the End of Trial notification, will serve as DSUR in this case – CSR is not a part of the EOT notification – CSR issued max. 1 year later after worldwide EOT – No local EOT, only worldwide EOT

• Recommended to submit DSUR if more short studies < 1 year with same IMP – Recommendation or obligation ?

167

Operational Transparency ?

Conclusion

Questions ?

Ideas ?

168


The Belgian implementation of CT3 (circ. 586 & 593)Kristof Bonnarens – 23/11/2012

The Belgina implementation of CT3famhp/DGPRE/ R&D

Date170

Revision of CT-3 guidance

• Revised detailed guidance on the collection, verfication and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use (‘CT-3’) was published in the ‘Official Journal’ on 11/06/2011

• Replaces ‘old’ guidance documents CT3 and CT4 (Detailed guidance on the European database of SUSARs – Eudravigilance /Clinical Trial Module)

• Aimed to provide short term improvements and clarifications for safety reporting, awaiting the revision of the current Clinical Trial Directive 2001/20/EC


Date171

• SUSAR =

SUSPECTED

UNEXPECTED

SERIOUS

ADVERSE

REACTION

CT3 revision and circular letter 586 (2)


Date172

• SUSAR =

SUSPECTED

UNEXPECTED

SERIOUS

ADVERSE

REACTION

Causality between event and IMP

«reasonable causal relationship»

Definitions (1)


Date173

• SUSAR =

SUSPECTED

UNEXPECTED

SERIOUS

ADVERSE

REACTION

• it results in death• it is life-threatening• it requires hospitalisation or prolongation of existing hospitalisation• it results in persistent or significant disability or incapacity• it is a congenital anomaly or birth defect

An important medical event is also ‘serious’ if it jeopardises the clinical trial participant or requires an intervention to prevent a serious outcome

Definitions (1)


Date174

• SUSAR =

SUSPECTED

UNEXPECTED

SERIOUS

ADVERSE

REACTION

Adverse reactions should be considered as unexpected if the nature OR severity

of the reaction(s) is not consistent with the reference information for the IMP.

Definitions (1)


Date175

• RSI: Reference Safety Information

The expectedness of an adverse reaction is determined in the reference safety information (‘RSI’). This should be done from the perspective of events previously observed, not on the basis of what might be anticipated from the pharmacological properties of a medicinal product

The RSI is contained in the Summary of product characteristics (‘SmPC’) or the Investigators Brochure

Absence of the RSI is the most frequent validation question in 2012

Definitions (2)


Date176

Scope

• Scope CT-3 : Interventional clinical trials falling under Directive 2001/20/EC

• Responsibilities regarding safety reporting determined only by Directive 2001/20/EC:

Whether IMP has a marketing authorisation or not

Provisions on pharmacovigilance as set out in Directive 2001/83/EC and Regulation (EC) No 726/2004 are not applicable, even for NIMPs


Date177

SAE reporting by the investigator

• Investigator should report all serious adverse events immediately to the sponsor except those specified in the reference safety information

• Timelines: Immediate reporting <24h Non immediate: ‘appropriate’ time Other critical safety issues: as specified in protocol

• Causality and seriousness are assessed by the investigator

• Expectedness assessment by sponsor


Date178

• Sponsor should report all SUSARs Occuring in a clinical trial authorised in the EU Occuring in trials performed exclusively in a third

country or another Member State when the active substance was authorised in the EU

• Timelines: Fatal or life-threatening: initial report within 7 days +

follow-report within additional 8 days Other SUSARs: initial report within 15 days

• Format Indirect reporting: through EV-CTM Direct reporting: individual case safety report (ICSR –

ICH E2B)

SUSAR reporting by the sponsor (1)


Date179

• Sponsor should equally send the SUSAR report to the EC that issued the single opinion in the memberstate where it occurred

• No line listings to Ethics Committees needed

• Sponsor should inform all other investigators by means of a periodical line listing together with an updated safety profile of the IMP

SUSAR reporting by the sponsor (2)


Date180

Annual Safety Report (1)

• Should be prepared after the first authorisation of a clinical trial worldwide

• Development International Birth Date – DIBD: First authorisation of a clinical trial worldwide with

this IMP DIBD = International Birth Date for authorised drugs:

date of the first marketing authorisation in any country worldwide

• Data lock point – DLP: last day before the anniversary of the DIBD

• Covered reporting period: 1 year or shorter for aligning purposes


Date181

Annual Safety Report (2)

• Content and format of the annual safety report should be in line with ICH guideline E2F: Note for guidance on development safety update reports (DSUR)

• Common standard for periodic reporting on drugs under development among the ICH regions (EU, USA, Canada and Japan)

• A DSUR should present a comprehensive annual review and evaluation of pertinent safety information related to an IMP, whether it is marketed or not


Date182

Implementation of CT-3 revision in Belgium

• Circular letter 586: Submission of SUSAR reports and annual safety

reports

• Circular letter 593: Submission fee for annual safety reports


Date183

Circular 586: SUSAR reporting in Belgium

• SUSARs to be reported to FAMHP: Occuring in a clinical trial authorised by the FAMHP Occuring in trials performed exclusively in a third

country or another Member State when the active substance was authorised by the FAMHP

• Only unblinded SUSARs

• Indirect reporting through EVCTM

• Reporting obligation ends with the last visit of the last patient (LPLV) in Belgium


Date184

Circular 586: SUSAR reporting in Belgium

• SUSARs to be reported to Ethics committee All SUSARs occurring in Belgium for the clinical trials

authorised by the Ethics Committee

• Should not be submitted: 6 monthly SUSAR line listings


Date185

Circular 586: submission of ASR

• Start of ASR submission to FAMHP after first authorisation of a clinical trial by FAMHP with this IMP

• An ASR should be submitted until the last visit of the last patient in Belgium or until the End of Trial criteria in the protocol are met for the last ongoing trial with this IMP in Belgium

• No ASR submission required for trials shorter than 1 year

• In unprotected pdf format (allowing search and copy/paste functionality) on CDrom with cover letter


Date186

Circular XXX : guidance on ASR submission

• Royal Decree on ASR submission fee published on 08/10/2012 – entry into force on the 18th of October

• Practical instructions in the circular letter that will be drafted asap

• Revision and evaluation of the process after 6 months with stakeholders.

• Goal = better follow-up of the safety in clinical trials by a risk-appropriate evaluation of the annual safety report (in the DSUR format).


Date187



tel. 0032 2 524 80 00fax 0032 2 524 80 01


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Contact




How to qualify for quality in IMP safety in the near future

Sarah T’Kindt – 23/11/2012

Subjectfamhp/entity/Division-Unit-Cell

Date190

Presentation topics

• Overview of a GCP inspection

• Why is it important to focus on reports from clinical trials?

• Overview of safety topics during a GCP inspection at the sponsor site

• Safety findings from previous GCP inspections

• Legislation


Date191

Overview of a GCP inspection

• Topics to be discussed during a systemic GCP inspection at the sponsor site:

The organization & personnel : qualification and training Outsourcing & contract management Project / trial management The IMP Data management Sample management Safety reporting & evaluation Statistics & study reporting Quality management


Date192

Why is it important to focus on reports from clinical trials?

• For some products, a high proportion of adverse event reports and other safety information comes from clinical trials

• Reports and other safety information from clinical trials are (usually) high quality data

• Relevant additional information can be easily obtained (medical history, other AE’s, lab values, etc.)

• Information can be retrieved in more controlled settings


Date193

Overview of safety topics during a GCP inspection at the sponsor site

• Preceding a sponsor site inspection there is usually an investigator site inspection of a specific trial from the sponsor to be inspected: The training on site of the study persons concerning

the safety reporting process

Reconciliation of data between the source, the CRF and the (serious) adverse events that are reported

Delegated safety aspects mentioned on the delegation duty log

The quality of the monitoring on site

The up to date safety information on site


Date194

Overview of safety topics during a GCP inspection at the sponsor site (cont.)

Follow up information Information on concomitant medication Evaluation of the SAE form Update of safety information leads to an update of

the informed consent form (ICF) The update of the ICF is signed in time by the

subjects Confirmation of receipt from the sponsor for the

reported information

Findings from the investigator site inspection will be further discussed during the sponsor site inspection.


Date195


• The set-up of the trial: A clear description of the safety reporting process in

the protocol A non confusion definition of the severity grade A defined time period for reporting

• Expedited reporting according to the requirements

• The reference safety information (RSI): To indicate the expectedness Usually in the Investigator Brochure (IB) Reference information allocated and updated as per

regulation requirements


Date196


• The DSMB (Data Safety Monitoring Board) The discision making process for the need of a DSMB Documentation of the discisions of the DSMB The written reports of the DSMB

• Safety procedures: Clear overview of the timelines and the

responsibilities for the safety reporting from collection to reporting

Flow of distribution of safety information to the concerned investigators: IB – DIL

Emergencies The writing of the DSUR The writing of the CSR …


Date197


• Minutes of the safety management team meetings

• Communication between the safety (PhVig) department and the Clinical trial unit and involvement of the PhVig department in critical trial processes/document review: Confirmation of the expedited reporting Protocol Case Report Form Clinical Study Report The trial statistician should be

a member of the team responsible for the clinical study report, and should approve the clinical report.


Date198


• Compliance of the information in the safety database and the safety information in the DSUR and the CSR

• Reconciliation of the information in the CT database and the safety database

• The database(s) used for the storage of safety information A risk level QC of the safety database A documented validation of the database(s) Database ready for demonstration and search of

specific topics during inspection


Date199


• The blinding and unblinding process Clear unblinding rules for SUSAR’s An independant safety monitor ISM for blinded trials

for which the IMP’s are manipulated in the hospital pharmacy

• Adequate safety training of the monitors Training and revision training of the safety

procedures Training on the discision management of issues and

protocol deviations Training of new important information during the trial


Date200


• The use of a common adverse event dictionary

• The role of the local affiliates in the safety process and the communication with global. Is there a local database? Are the procedures in line with the global ones?

• Qualified employees for the review of the events and the medical writing


Date201

Safety findings from previous GCP inspections

• No confirmation of receipt from the sponsor of the reported SAE from the investigator site

• No prove of attendance of the concerned study staff on the site initiation visit and/or the investigator meeting

• Not all adverse events are recorded, only those that the investigator classifies as clinical significant, although the protocol describes that all adverse events must be recorded


Date202

Safety findings from previous GCP inspections (cont.)

• SAE’s that are reported long after the first aknowledge by the PI and no note to file from the monitor.

• The procedures are not complete of the way of working doesn’t fit with the procedures Day ‘zero’ not clear from the SOP No identification of the responsible persons during

the safety flow Only the safety reporting on paper is explained, while

the reporting is now done via E2B

• No quality control of the information mentioned in the DSUR and CSR


Date203

Safety findings from previous GCP inspections (cont.)

• The subject identification at the sponsor site contains the name of the subject

• AE’s that are crossed out on the AE list without any further explanation or indication of the person responsible for this cross out

• No audit of the CRO who’s responsible for the safety reporting

• Very poor documented monitoring reports

• The use of a non-validated local safety database


Date204

Legislation

• Safety reporting falls either under Directive 2001/20/Ec or under the provisions on PhVig as set out in Directive 2001/83/EC and Regulation (EC) No 726/2004.

AE’s may not be reported under both regimes!

• Law of 07 May 2004: Art. 27 en 28 & the implementing orders

• Directive 2001/20/EC

• Directive 2005/28/EC: The IB shall be validated and updated by the sponsor at

least once a year

• Detailed Guidance CT-3: Note: the PhVig rules laid down in Directive 2001/83/EC and

Regulation (EC) No 726/2004 do not apply to IMP’s and non-IMP’s.


Date205

Legislation

• ICH E6: Note for Guidance for Good Clinical Practice CPMP/ICH/135/95

• ICH E3: Note for Guidance on Structure and Content of Clinical Study Report CPMP/ICH/137/95

• ICH E2A: Note for Guidance on Clinical Safety Data Management CPMP/ICH/377/95: Definitions and standards for expedited reporting

• ICH E2F: Note for Guidance on Development safety Update Reports


Date206



tel. 0032 2 524 80 00fax 0032 2 524 80 01


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Contact



Agence fédérale des médicaments et des produits de santé

PRIORITIES OF THE DGs FOR THE NEAR FUTURE AND TAKE AWAY MESSAGES

Pharma.be/BEAPP

Vanessa BINAME, Director General DG Post – 23/11/2012

Priorities of the DGs for the near future and take away messages

afmps/DG Post

23/11/2012

209

RECOGNITION AT NATIONAL, EUROPEAN AND INTERNATIONAL LEVEL

• Active participation in:– QRD WG, Variations WG and European Council meetings– Recast medical devices and European WG (MDEG, CIE, …)

• National coordination medical devices (MD)

• Development network safety experts


afmps/DG Post

23/11/2012

210

DEVELOPING PARTNERSHIPS WITH THE HEALTHCARE SECTOR

• To improve communication with stakeholders (i.a. industry via WG)

• Human phv/MD : to develop network with HCPs

• Veterinary phv: to improve feed-back

• SAM and active participation to the eHealth roadmap 2013-2018

• Publication withdrawn MA


afmps/DG Post

23/11/2012

211

PERFORMING CORE TASKS IN A PROFESSIONAL MANNER

• Monitor of the timelines and deadlines for DG POST processes

• SOPs (TQM) and corrective actions based on BEMA III

• MD: plan

• Capacity planning

• RMA


afmps/DG Post

23/11/2012

212

INFORMING THE PUBLIC OPTIMALY

• Publication SPC/PIL

• Website FAHMP

• Campaign concerning proper use medicines for children

• To develop information concerning MD

• Information for patients


afmps/DG Post

23/11/2012

213

DEVELOPING TRANSVERSALITY

intra and inter DG, i.a. between Vigilance division and DG PRE/DG Inspection


afmps/DG Post

23/11/2012

214

EALISING AND ESTABLISHING A LEARNING ORGANIZATION CULTURE

• Development cycles

• Knowledge management

• Quality system for pharmacovigilance

• CAF


afmps/DG Post

23/11/2012

215

• To improve quality of services

• Transparency and communication

IMPORTANT MESSAGE DG POST 2013


afmps/DG Post

23/11/2012

216

Agence fédérale des médicaments et des produits de santé - afmps


tél. 0032 2 524 80 00fax 0032 2 524 80 01


www.afmps.be

Contact



Vos médicaments et produits de santé, notre préoccupation


DG PRE Priorities Greet Musch – 23/11/2012


Date219

EU Strategy • Clinical Trial Regulation • Equal and Early Access ( availability of drugs )• Public Health Needs

– early authorisation in restricted population– elderly people– cooperation with HTA – bodies in early stage of

drug/device development

• Anti-Microbial Resistance ( Human and Veterinary)• Better Regulation ( Veterinary )• Selection/Reconfirmation of

“ Centres of Excellence “ • Funding • IT


Date220

• Regulatory expertise • Scientific expertise

• Strengthen the basic layers

- Focus on Clinical expertise - B/R methodology ( Clinical trials , Unmet need , Marketing authorisations , Self Care ,

Medical Devices : Clinical Investigations and Evaluations

- Coördination and integration of EU Scientific Committees (COMP-SAWP-CAT-CHMP-

PDCO and PRAC )within the FAMHP …

• Introducing the concept of “ TAC’s “ Therapeutic Area Coördinators

UNEXPECTED

SERIOUS

ADVERSE

REACTION

Expertise


Date221

• With National Institutions ( RIZIV , KCE, HGR , FOD VVVL ( WIV-CODA ), FAVV …)

• Within the FAMHP • With DG Post

- B/R : Clinical assessors and Vigilance assessors - VHB Pre and VHB Post - CI and CE of medical devices ; combined products…

• With DG Inspection- Triggers for Inspection - Outcome of Findings : impact ?

- Ad Hoc dossiers : Veterinary division , Traditional Use , ATMP’s HE, Active Pharmaceutical Ingredients …

UNEXPECTED

SERIOUS

ADVERSE

REACTION

Interfaces


Date222

• Per process and intra process • Review of role and responsabilities of the

Commission for medicinal products for human and veterinary use

• Although dreaming of ancient times …

QA of the decision making process


Date223


Date224

• Optimisation of platforms

- ad hoc for existing platforms - sufficient ? compilation ?

• Opportunities for improvement ?

• Your Priorities ?

• Future views (i.e. Role of Be as RMS for human and veterinary medicinal products ? )

Stakeholders


Date225



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Contact




Priorities of DG Inspection in the near future and take away messages

Josiane Van der ElstDirector General

Organisation chart

Directorate General Inspection 2013: Autocontrol becoming a reality

229229

The Switch to Make

AS IS: Gothic TO BE: Art Nouveau

Authority – only driven Authority – driven “supra”control in combination

direct linear control with sector – driven “delegated” autocontrol of

which selfevaluation can be part

co-regulation

Vertical link Curvilinear, Linkage with environment

Cartesian, dissection of system into parts Holistic, treating systems as a whole

Limited interface with operators, one –one interaction Strong Interface with operators

Mainly rules Rules and guides

Ressources “boxed”, strictly dedicated to one task More rational use of capacity

Low trust High trust

Authority keeps right of final decision and power of sanction

http://en.wikipedia.org/wiki/File:HortaELWI.jpg

Co-regulation Showing the relationship to a central idea

Emphasizes both information in the center circle and how information in the outer ring of circles contributes to the

central idea

Develop further the concept

AND Develop one concrete model to start with:

Medical Devices is an opportunity to develop a model and put it to the test

AND Work in parallel in different other domains of inspection

where concrete actions are foreseeable and feasible already

Publicity

Certification of persons: f.i. QPPV, oxygenotherapy

AND Design Coordinator (s) at DG Inspection

Action Plan Autocontrol / Co-regulation

Directorate General 2013: The Veterinary Experience

Veterinary issues coming up

• Fight against antimicrobial resistance is high on the agenda in view of an

holistic approach

• « The Depot »

• Lacunes in legislation

• Good Veterinary Practices to be introduced

• Better Transversal Coordination needed within FAMHP

• Autocontrol/co-regulation: first steps to be considered

• Invite stakeholders at our FAMHP house

Directorate General 2013: The New Structure

235

DG Inspection: current structure

235

236

DG Inspection: new structure to be in line with new vision

236

Autocontrol / co-regulation as a new style of inspection is

going to the test

Veterinary inspection will take up its rightfull place and

leave the position of « underdog » for the benefit of public

health

A new style structure, a new structure

The new structure of DG Inspection sticks with the new

vision on inspection

Take Away Messages for 2013

238

28 days to gotill 21 12 2012

http://nl.wikipedia.org/wiki/Bestand:Calendario_maya.jpg

1beapp pharma.be, brussels nov 23 12 be (pharmaco)vigilant! important changes in the pv-legislation...

Documents

information slide

mah periodic reporting

engagement reporting

days patient reporting

procedures beapp

mah ae expedited reporting

beapp cultural event

risk close link