2013_07_HMA_Annual_Report_2012_2013_webfile

2012–2013Annual Report of the HMA Strategy

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Postal address: Heads of Medicines Agencies Permanent Secretariat, c/o Irish Medicines Board, Earlsfort Centre, Earlsfort Terrace, Dublin 2, IrelandWebsite: http://www.hma.eu/E-mail: [email protected]

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Contents

Chairman’s Introduction ...................................................................... 4

The European Regulatory Network .................................................... 5

The HMA Strategy 2011–2015 .............................................................. 7

Strategy Implementation Plan ............................................................ 9

Specific Objectives of the HMA Strategy ........................................... 10

Safeguarding Public and Animal Health: Theme overview .............. 13

Strengthened Surveillance .................................................................. 15

Quality of Medicines and Inspections ................................................ 17

Supporting Innovation: Theme overview ........................................... 19

Emerging Issues, New Technology .................................................... 20

Clinical Trials ........................................................................................ 21

Further Improving the Efficiency of DCP/MRP: Theme overview ...... 22

Best Practice ......................................................................................... 24

Streamlining and Harmonisation ........................................................ 25

Good Communication .......................................................................... 26

Information Technology ...................................................................... 28

Progress Reports on Specific Objectives of Strategy ...................... 29

Further Information .............................................................................. 46

Glossary ................................................................................................ 50

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A.A.W Kalis Chair of the HMA Management Group Executive Director of the Medicines Evaluation Board (MEB), theNetherlands

It is my pleasure to introduce to you the 2012/2013 Annual Report of the HMA Strategy, the second such report in the new five year strategy cycle. Since work first started on the new Strategy in 2009, the HMA was keen to see that the strategy document has a forward focus bearing in mind the fulfilment of all objecti-ves. In this year’s Annual Report, a lot of progress has been made in the second year and also the potential for further achievement in the future.

Since its inception in 1995, the HMA has demonstrated how effective and productive an informal, voluntary network of National Competent Authorities can be. The the-mes of the 2011-2015 Strategy are firmly rooted in the shared interests and values of all National Competent Authorities that have made this partnership a success. High on the agenda is patient safety and the implementation of the pharmacovigilance legislation that gave a new dimension to the cooperation among National Competent Authorities and European Medicines Agency (EMA). The theme Safeguarding Public and Animal Health underlies our core mission which unites all our agencies, to safeguard public and animal health. The theme Supporting Innovation reflects the commitment of the HMA to support innovation within Europe, in a rapidly changing landscape of medicine pro-duction and development. Currently the Clinical Trial Regulation is under discussion and will include major changes for the National Competent Authorities (NCAs) in the near future. The third theme Further Improving the Operational Efficiency of Medicines Authorisation by the Decentralised and Mutual Recognition Procedures illustrates the national challenge of the HMA in maintaining connections between NCAs to ensure an effective decentralised and mutual recognition for the market authorisation of both human and veterinary medicines, running complementary and in cooperation with the centralised system maintained by the EMA. In a more coordinated approach we would like to underline that the Common EU Submissions Platform (CESP) is operating as a fully-developed system. Much work of the last year has been undertaken in readiness for the implementation of the falsified medicines legislation and the API importation. There has been progress done by the Taskforce on Falsified Medicines in international exchanges of information on third country inspections, in cooperation both with the European Commission and EMA and also with the industry. The summaries from the work area leads and updates from the individual working groups compiled in this Report reveal how well the HMA has responded to the year’s challenges. Making the 2011-2015 Strategy a reality has involved much hard work from a number of individuals in the Network. I would like to thank Pat O’Mahony and his team from the IMB for their work in preparing this document. Special thanks are also due to the HMA Permanent Secretariat and Management Group, and all Chairs of working groups, for coordinating the strategy work going forward. I would also like to particularly note the work achieved by the Cypriot and Irish Presidencies during 2012 and at the same time to wish the incoming Presidencies of Lithuania and Greece success. The year 2013 will be another important year for medicines regulation. We will see the implementation of the delegated acts of the Falsified Medicines Directive and on-going revision of the European legislation on clinical trials, medical devices, fees for pharmaco-vigilance activities and veterinary medicines. In endorsing this Report to you, I am con-fident that the Heads of Medicines Agencies and the wider European Medicines Regula-tory Network will meet the future challenges and continue to grow as a Network.

Chairman’s Introduction

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The European Medicines Regulatory NetworkThe European Medicines Regulatory Network (EMRN, ‘the Network’) is composed of the National Competent Authorities (NCAs) for human and veterinary medicines regula-tion, the European Medicines Agency (EMA) and the European Commission. There are 45 national agencies from the 27 European Union (EU) member states and the three countries from the European Economic Area – Iceland, Liechtenstein and Norway. Of the 45 NCAs, 14 have responsibility only for human medicines; 14 are purely veterinary agencies; 17 are joint veterinary and human agencies; and some veterinary agencies are integrated with their respective national food safety agencies. Some have responsibility for pricing and reimbursement of human medicines. 22 have joint responsibility for medicines and medical devices. All are accountable to their national governments. The EMA is a key part of the Network and all 45 NCAs work closely with it. Yet in ad-dition to their role in supporting centralised EU processes, NCAs also have major responsi-bilities for the functioning and efficiency of national and decentralised activities. Established in 1995, the Heads of Medicines Agencies (HMA) is a network of the Heads of the National Competent Authorities whose organisations are responsible for the regulation of medicinal products for human and veterinary use in the European Economic Area.

Mission of the Heads of Medicines Agencies The HMA works to foster an effective and efficient European medicines regulatory system.

Main activities• AddresseskeystrategicissuesfortheNetwork,suchastheexchangeofinformation,IT

developments and sharing of best practice;• Focusesonthedevelopment,co-ordinationandconsistencyoftheEuropeanmedicines

regulatory system;• Ensuresthemosteffectiveandefficientuseofresourcesacrossthenetwork.Thisinclu-

des developing and overseeing arrangements for work-sharing;• Co-ordinatesthemutualrecognition(MRP)anddecentralisedprocedures(DCP);• Member agencies support the network by providing high-quality professional and

scientific resources to all areas of medicines regulation including centralised, MRP, DCP and national procedures.

The initial focus of the HMA was on the smooth functioning of non-Centralised regu-latory applications, through regular meetings and working groups, such as the Co-ordina-tion Group for Mutual Recognition and Centralised Procedures for human and veterinary medicines (CMDh and CMDv). Over the years, HMA has extended its coordination activities to encompass clinical trials authorisation; worksharing of periodic safety update reports (PSURs) and paediatric indications; interpretation of legal provisions; inspection and enforcement operations; and product testing. New European pharmacovigilance law will further endow CMDh with decision- making powers. Common initiatives to strengthen the system have resulted in Europe-wide projects concerning information technology (IT) infrastructure, communication policy, training programs, audit, benchmarking and more. 70 per cent of the NCAs for human medicines within the HMA also have authority for human medical device regulation, and the HMA works closely with its counterpart in medical devices, the Competent Authority for Medical Devices and Central Management Committee (CAMD, CMC).

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Photo: Shutterstock.

Governance of the HMA The Heads of Medicines Agencies is supported by working groups covering specific areas of responsibility. Most of these groups are specific to the HMA, others are legally separate but share joint mandates for activity (such as CMDh, CMDv and the Pharmacovigilance Working Parties (h and v). The HMA Management Group (HMA MG) has as its main objective the co-ordination and facilitation of the operation of the HMA, and the supervision and management of the HMA Permanent Secretariat (HMA PS). The Permanent Secretariat facilitates and supports the work of HMA, HMA MG and the EU Presidency by ensuring co-ordination, consistency and continuity of their work and activities and providing the collective memory of HMA.

Meetings

The HMA usually meets in full session twice during each Presidency of the Council of the EU (i.e. four times per year). After each HMA meeting a stakeholders information document is published on the HMA website. The working groups also meet several times per year, physically and by teleconference.

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The HMA Strategy 2011–2015In July 2009, the HMA commissioned a new five year Strategy for its activities within the Network, covering the period 2011–2015. This is intended to build upon the work of the first Strategy (2006–2010) and also complement the European Medicines Agency’s Roadmap to 2015. The aim of the Strategy is to identify the key challenges which face the Network and how the HMA can best respond to these challenges for the benefit of the European population. The new Strategy recognises that there have been significant political, economic, social and legislative developments since the first Strategy was published. These include the glo-bal economic downturn, influenza virus pandemics and changes within the pharmaceutical industry with increasing use of third countries for production and innovation. While the Strategy covers the diverse activities of the HMA’s contribution to the EMRN, three key themes also emerged where the HMA believes it can make a real difference in the next five years:

(1) Safeguarding Public and Animal Health

The HMA is dedicated to strengthening surveillance of the benefits and risks of medi-cines in the European population, including: improving spontaneous reporting systems toenableearlydetectionofrisks;strengtheningmonitoringofthequalityofmedicines(including risk-based inspections); and targeted action against falsified medicines.

(2) Supporting Innovation

The HMA will continue to support the efficient and proportionate regulation of new medicines, and clinical trials in humans, through initiatives such as the new Voluntary Harmonisation Procedure (VHP) and through the provision of excellent scientific and regulatory advice.

(3) Further Improving the Operational Efficiency of Medicines Authorisation by the Decentralised and Mutual Recognition Procedures (DCP/MRP)

The HMA is dedicated to excellence in the operation of the DCP/MRP. This will be achieved through the promotion of risk-based proportionate regulation; the harmonisa-tion of assessment; work-sharing; the best use of information technology; dialogue with industry on operational matters, such as streamlining validation procedures; the harmoni-sation of training; and the promotion of good communication channels.

Legislative ChangesThe Strategy also identified a number of key changes in European legislation that the HMA will need to respond to during 2011–2015. These include the impact on NCAs, healthcare and industry of the Pharmacovigilance Directive and Falsified Medicines Di-rective; an expected recast of the medical devices legislation; an expected revision the Clinical Trials Directive; and reviews and updates to veterinary legislation.

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Emerging IssuesThe Strategy identified a number of key emerging issues for medicines regulation in the next five years. These include changing patterns of disease e.g. emerging antibiotic resistance in both humans and animals and new pathogens and viral strains. In addition, innovation of medicines will lead to more advanced therapies for humans and animals, as well as personalised medicines, medicine/medical device combinations and further deve-lopment of new technologies such as nanotechnology. Regulatory science will continue to develop, with advances for example in risk-benefit modelling. More Member States are increasing their use of Health Technology Assessment (HTA) to estimate clinical effecti-veness and cost-effectiveness of health care interventions. Finally, there is a call for greater transparency in the processes of regulation.

Trade and industry The European Commission has expressed concerns about the rising cost and apparent declining productivity of pharmaceutical innovation in Europe. In addition, the effects of globalisation have created new needs for quality assurance of medicines and Active Pharmaceutical Ingredients (APIs) sourced from one or more third countries, as well as the need for robust measures against counterfeit medicines. Furthermore, the Strategy needs to be mindful of the financial constraints, in public organisations and private companies, currently experienced across the member states of the regulatory Network.

Looking forwardThe Strategy outlines the direction of travel the HMA wishes to take in the next five years. However, it is not possible to predict with certainty what may happen over 2011–2015 and how priorities might change. Through the regular meetings of the HMA and its working groups, and its annual reviews of the progress of the Strategy, the HMA retains the ability to adapt to and meet the challenges of the future.

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Strategy Implementation PlanThe HMA formally adopted the HMA Strategy at its October 2010 meeting in Antwerp. A strategy implementation plan was agreed in February 2011 at the following meeting in Budapest. The purpose of the implementation plan is to ensure that the efforts of the HMA remain focused on the key goals of the Strategy throughout its lifetime. The key elements of the strategy implementation plan are as follows:

(1) Use of Working Groups

An analysis of the Strategy document revealed 50 specific objectives for HMA activity during 2011–2015. These objectives were assigned to the existing working groups of the HMA, who would carry responsibility for the practical implementation of these objectives.

(2) Creation of Work Area Leads

To help coordinate and support the efforts of the working groups, eight ‘work areas’ were created, subserving the three main themes of the Strategy. Each work area has been allo-cated a “work area lead” drawn from the heads of European NCAs. The work areas leads liaise with the chairs of the respective working groups, as well as the HMA Management Group, to ensure that necessary progress is being made and to provide high-level support whenrequired.

(3) Targets and Deliverables

A further role of the work area leads and working groups is to identify key targets and priority areas where success can be measured on an annual basis. Several such targets are identified in this document.

(4) Annual Review

For the Strategy 2011–2015, there will be a yearly review process to assess progress. This will take place at the first HMA meeting of each year. This annual report forms a key part of the 2012–2013 review process.

(5) Embed Strategy into Joint Sessions of HMA Meetings

The joint (human and veterinary) sessions of HMA meetings are now organised themati-cally, so that each of the three themes are now considered in turn. It is intended that this way each theme and work area of the Strategy will be given the necessary attention and resource. The July 2011 meeting in Warsaw was the first meeting to adopt this thematic approach which has been used ever since.

Strengthened Surveillance

EmergingIssuesNew

Technology

ClinicalTrials

Qualityof

Medicinesand

Inspections

BestPractice

Streamliningand

Harmonisation

GoodCommunication

InformationTechnology

SafeguardingPublicand

AnimalHealth

SupportingInnovation

FurtherImproving

theOperationalEfficiency ofDCP/MRP

Theme

WorkArea

Heads of

Medicines Agencies

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Specific Objectives of the HMA Strategy

No Specific objective PrincipalWorking Group(s) Work Area

1 Improve on variations between Member States on spontaneous reporting of Adverse Drug Reactions(ADRs); through education, motivation, facilitation, promotion and forthcoming pharmacovigilance (PhV) legislation

PhVWP(h/v)ERMS FG

Strengthened surveillance

2 Improve safety profile of vaccines and antivirals and implementation of real-time signal detection

PhVWP (h)ERMS FG


3 Good pharmacovigilance practice and sys-tems efficiency, data quality (metrics)

PhVWP (h)ERMS FGWGQM


4 Integration of new methodologies into PhV systems, raise standards of PhV across Network to complement further develop-ment of Eudravigilance by EMA

PhVWP (h)ERMSFG


5 Benefit/risk communication, transparency and patient engagement

PhVWP (h)ERMS FGHMA/EMA WG TWGCP


6 Influencing development of revised EU legislation on veterinary PhV to ensure that a PhV master file system is introduced

PhVWP(v)ESS WG, TFIVL


7 Strengthening regulatory sanctions to en-sure that veterinary Marketing Authorisation Holders (MAHs) meet vigilance responsi-bilities for their products, using guidance, regulatory powers and pharmacovigilance inspections

PhVWP (v)ESS WG


8 Raising ADR reporting levels by veterinarians and farmers

PhVWP (v)ESS WG


9 Simplifying veterinary reporting process; taking forward development of EudraVigilance (EV) Vet and systems for electronic ADR reporting

PhVWP (v)ESS WG


10 Releasing resources by increasing the flexibility of Perioidic Safety Update Reports (PSUR) submissions

PhVWP (v)ESS WG, TFIVL


11 Protect public health through inspections and laboratory control of all sta-ges of pharmaceutical supply chain, human and veterinary

WGPTGMP/GDP IWG

Quality and Inspections

12 Develop co-ordinated response to risk of counterfeit medicines; cooperation within Network, industry and other agencies to share intelligence and inspection data; cooperation between NCAs, authorities, police, customs

WGEO Quality andInspections

13 Risk-based redeployment of inspections leading to greater focus on third country manufacturers

GMP/GDP IWG Quality andInspections

14 Enhanced legal powers against falsified medicines

WGEOGDP/GMP IWGEMACOLEX

Quality andInspections

15 Use of EudraGMP and EDQM database for product testing to share intelligence within Network

WGPTGDP/GMP IWG

Quality andInspections

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16 Efficiency of use of Official Medicines Control Laboratories for sample testing

WGPT Quality andInspections

17 Emerging areas of regulation – new technology (including medical devices, advanced therapy medicinal products, tissues and cells, novel foods, cosmetics)

ERMS FGTFIVLEMACOLEX

Emerging IssuesNew Technology

18 Best linkage between regulation and HTA – consultation with stakeholders

Polish presidency (in 2011)


19 Closer engagement of HMA Group in considering medical devices strategy

HMA/CAMD/CMC Steering Group


20 Availability of medicines issues – human and veterinary – including possible new legislation

AMWGTFIVL(EMACOLEX)


21 Publication of Summary of Product Characteristics (SPCs) for authorised products on national agency websites and/or Eudrapharm

NCAs, EMATSG

Streamlining and Harmonisation

22 Devising better risk based, proportionate, efficient regulation which maintains public confidence

EMACOLEXTFIVL, HMP WGEMA/HMA WG T

Emerging Issues /New Technology

23 Developing work-sharing across NCAs in regulation

WGQMHMP WG

Best Practice/ Streamlining and Harmonisation

24 Harmonisation of clinical trials procedures and processes; creating an efficient and unified regulatory environment for clinical trials in Europe that encourages innovation and high quality research

CTFG Clinical Trials

25 Implementation of revised Clinical Trials Directive

CTFGEMACOLEX

Clinical Trials

26 Work sharing approaches to assessment of clinical trials


27 Cooperation with EMA and Commission on common clinical trials regulatory environ-ment, and its promotion/communication


28 Voluntary Harmonization Procedure – implementation and streamlining


29 Regulation of veterinary medicines, including consideration of the extent to which human and veterinary medicines legislation should diverge and active participation of HMA in modification of veterinary legislation (including medicated feeds)

TFIVLCMDv

StreamliningandHarmonisation

30 Strengthen collaboration with international agencies and resources applicable to veterinary medicines; align with European Technology Platform for Animal Health, OIE, Codex Alimentarius

ESS WG Good Communication

31 To take steps to help reduce the develop-ment of antimicrobial resistance and help communicate policies on responsible use to healthcare workers

vAMR TFPhVWP(h/v)TFIVL

Emerging Issues/ New Technology

32 To consider whether a collaborative and proportionate arrangement for control clinical trials in food producing species is necessary

CMDvTFIVL


33 To gather information on unregulated areas for products used in animals and borderline areas and explore the need for proportionate regulation and co-operation in the network

CMDvTFIVL



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34 Influence the development of revised legislation for feedingstuffs to ensure that it is risk based and addresses specific challenges of antimicrobials

TFIVLvAMR TF


35 Build and strengthen regular communications with HMA stakeholders; ensure efficient interaction with pharmaceutical industry

WGCP Good Communication

36 Developing the HMA web presence WGCP Good Communication

37 Crisis communication links – interactions between regulators

WGCP Good Communication

38 Optimum utilisation of resources, including financial

TF R in DCP Best Practice

39 Making decentralized processes work better CMDh/vTF R in DCP


40 Extending new EU variation regulation provisions to national variations

CMDh/v Streamlining and Harmonisation

41 Supporting new functionality bestowed on CMDh by strengthened pharmacovigilance legislation

CMDh

TF R in DCP


42 Providing more authorised medicines for children and implementation of paediatric regulation provisions

CMDh

TF R in DCP


43 Promoting work sharing and principle of fair distribution of work across the Network

CMDh/vTF R in DCP


44 HMA Common Portal for MRP/DCP applicants

TSG Information Technology

45 Promoting inter-operability of NCA systems with best use of telematics


46 Communications plan to ensure that stakeholders are provided with up-to-date information on telematics


47 Support of internal communications platforms for each working group of HMA

TSGWGCP

Information Technology

48 Further development for benchmarking European medicines agencies (BEMA) programme

BEMA SGWGQM

Best Practice

49 Implementation of harmonized training strategy across network to improve quality and consistency, including harmonized interpretation of guidelines

OTSG Steamlining and Harmonisation

50 Providing basic and specialized training to all staff members of competent authorities

OTSG Streamlining and Harmonisation


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Safeguarding Public and Animal HealthTheme Overview

This theme encompasses the cooperative efforts of the European Medicines Regulatory Network to maintain and improve European pharmacovigilance for human and veterinary medicines as well as ensuring that the supply chain of medicines remains of the highest quality.Therearetwoworkareaswithinthistheme:(1)StrengthenedSurveillanceand(2) Quality of Medicines and Inspections. The Strengthened Surveillance work area was led by Jytte Lyngvig of the DKMA (DK) until June 2012 when she retired from the agency; the area is now led by Aginus Kalis of the MEB (NL). The work was supported by the Pharmacovigilance Working Party, human (PhVWPh) until a new legal committee was installed. In July 2012, this new com-mittee, the Pharmacovigilance Risk Assessment Committee (PRAC) was mandated to cover all aspects of the risk management of the use of medicinal products, including the detection, assessment, minimisation and communication of adverse reactions. The European Risk Management Strategy Facilitation Group (ERMS FG) aims to develop a European Strategy for risk management, built on the NCA’s resources and expertise, and incorporating the EMA’s role in the coordination and the supervision of products authorised through the Community. The European Surveillance Strategy Working Group (ESS WG) is the initiative for a closer cooperation of EU member states and EMA in a pro-active approach to veterinary pharmacovigilance. This includes setting up strategies for continuous monitoring of pro-ducts, further development of harmonised risk management strategies, risk communica-tion, work sharing and resource optimisation.

Pharmaco-vigilance

Working Party(human)

June Raine

Pharmaco-vigilance

Working Party(veterinary)

Peter Ekström

European Risk Management

Strategy Facilitation

GroupAginus Kalis

European Surveillance

Strategy Working Group

Cornelia Ibrahim

GDP/GMP Inspectors

Working Group

David Cockburn

Working Group of

Product Testing

Miguel Bley

Working Group of

Enforcement Officers

Kim Helleberg Madsen

Quality of Medicines and

InspectionsKent Woods

MHRA

Strengthened SurveillanceJytte Lyngvig

DKMA/ Aginus Kalis

MEB

SafeguardingPublicand

AnimalHealth

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The Quality of Medicines and Inspections work area is led by Kent Woods of the MHRA (UK). The work area includes the work of the Working Group of Enforcement Officers (WGEO), which ensures adherence to the regulation of the manufacturing and distribu-tion chains of medicinal products, the disruption of illegal activities and the sharing of information relevant to enforcement operations. The Working Group of Product Testing(WGPT)ismandatedbytheHMAforqualityand control product testing of MRP and DCP products. Major elements of its endeavours are the rational use of resources and a risk based approach to defining which medicinal products should be tested for the benefit of patients. The Good Manufacturing Practice/Good Distribution Practice Inspectors Working Group (GMP/GDP IWG) provides input and recommendations on all matters relating directly or indirectly to GMP or GDP, irrespective of the marketing authorisation procedure, through different reporting lines to the European Commission, the EMA and the HMA. For the HMA, the GMP/GDP IWG takes responsibility for overseeing the Joint Audit Programme (JAP) as well as liaison and cooperation with the WGEO.

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Jytte Lyngvig /Aginus KallisWork area lead for Strengthened SurveillanceDirector of the Danish Medicines Agency (DKMA)Chief Executive of the Medicines Evaluation Board (MEB), the Netherlands

The work area of Strengthened Surveillance covers both medicinal products for human use and veterinary medicinal products.

Medicinal Products for Human UseIn the area of medicinal products for human use, the core priority of the work was the implementation of the new pharmacovigilance legislation. Members of the PhVWPh and the new PRAC, the ERMS FG and the WGCP all contri-buted to the on-going implementation of the new pharmacovigilance legislation, through the six project teams established, and also with representatives from EMA, the Committee for Medicinal Products for Human Use (CHMP), CMDh and Member States. Much progress was made throughout 2012. The Pharmacovigilance Working Party was superseded by the Pharmacovigilance Risk assessment Committee which met for the first time in July 2012. June Raine of the Medicines and Healthcare products Regulatory Authority (UK) was elected chair at the first meeting with Almath Spooner of the Irish Medicines Board (IE) as vice-chair. The committee met 4 times during the remainder of the year, during which it adopted its Rules of Procedure and advised on the ‘black symbol’ for identification of medicinal products subject to additional monitoring. The committee’s remit includes the analysis and prioritisation of safety signals and this will enable a more consistent approach across Europe to signal detection in order for timely action to be taken in response to emerging safety issues. An important focus is ensuring that the committee’s work is transparent to the public and its agendas and minutes are publically available and communications on the key recommendations are issued after each meeting.

Medicinal Products for Veterinary UseIn the area of veterinary medicinal products, the Pharmacovigilance Working Party PhVWP(v) supports the EVVet datawarehouse which is currently used for signal detec-tion of centrally-authorised products. Good progress was made to develop the recommen-dation on pharmacovigilance surveillance and signal detection of veterinary medicinal products. An update to the guidance on harmonising the approach to causality assess-ment for adverse events was initiated for consistency with Volume 9B. Support to the VICH Electronic Standards Implementation Expert Working Group was given. An important new point is the reflection paper under development in 2012–2013 on pharmacovigilance communication to the public on safety concerns arising from veteri-nary pharmacovigilance data with a view to a harmonized approach in Member States.

Strengthened SurveillanceWork Area Lead Update

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Specific objectives (6) and (10) on respectively a PhV master file and flexibility of PSURs submissions were fulfilled for the time being by their inclusion in an updated reflection paper on the improvement of veterinary pharmaceutical legislation that was sent to the European Commission. The increased flexibility in PSUR submissions is also expressed in the PSUR work-share project of the ESS group. The “consolidation phase” of the PSUR work-share project ended in 2012. In 2012 a new phase with improved conditions was agreed by HMA and started with active participa-tion of nearly all Member States as decided by written agreement of the HMA(v). The successful continuation of the PSUR work-share project was the top priority of the ESS group in 2012.

Priorities for 2013Medicinal products for human useThe ERMS FG will oversee further implementation of the legislation within the Member States (including implementation of Directive 2012/26/EU and Regulation 1027/2012). The group will consider and agree technical contributions to delegated acts, good vigilance practice (GVP) modules and any reflection papers, as well as overseeing key performance measures of the legislation and the European pharmacovigilance and risk management system.

Medicinal products for veterinary useSpecific objective (8) on raising ADR reporting levels by veterinarians and farmers is a prio-rity area of strengthened surveillance in regard to veterinary medicinal products. Actions to implement the objective are included in the European Surveillance Strategy Action Plan. Further discussion on the implementation of this priority action will take place at the ESS WG throughout 2013. The TFVIL will make proposals to the HMA on EC draft proposal on revision of VMP legislation and medicated feeding stuff regulation including the specific objectives (6) and (10) on respectively a PhV master file and flexibility of PSURs submissions.

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Sir Kent Woods,Work area lead for Quality and InspectionsChief Executive of MHRA, UKChairman of the EMA Management Board

The Quality of Medicines and Inspections work area covers a range of regulatory activity from the risk based deployment of inspections, the efficiency of product testing, to the de-tection of counterfeit medicines.

EnforcementOperation PANGEA V forms the reporting highlight for 2012 in the continuing campaign to combat the illegal online supply of unlicensed and falsified medicines. This year’s in-ternational week of action was the largest to date involving 100 countries of which 30 WGEO member countries were represented (including EEA countries and Switzerland). The operation led to the global seizure of over 4.1m doses of medicines being supplied illegally spanning 35 therapeutic categories and worth approximately €8.1m. PANGEA V also led to the taking down of over 18,100 websites selling medicines illegally. WGEO workstreams continue to support the five year WGEO strategy through sharing experience and best practice between medicines regulators, police and customs to effec-tively combat falsified medicines and similar crimes that impact public health as well as animal health and welfare. Much of this work is in support of the enhanced legal powers in the EU Directive on Falsified Medicines and the Council of Europe (CoE) Medicrime Convention.

Product TestingNew product testing guidance was rolled out in 2012. A pilot (endorsed by the HMA in Budapest in 2011) on risk-based selection of medicinal products for laboratory testing byqualityassessorsinMRP/DCPsupportedtheharmonizationofthisapproachforallproducts authorized and marketed in the EU. The pilot suggests that an assessment of the current risk-based approach used for CAP should be conducted for MRP/DCP as thishasthepotentialtoimprovequalitysurveillanceofmedicinalproductsforhumanand veterinary use on the EU market. The pilot also recognised the need for good communicationbetweenassessment,GMPinspection,andtestingforeffectivequalitysurveillance.

Inspections The Work Plan for the GMP / GDP Inspectors Working Group (IWG) for the year con-tained a large workload with significant activities across the full range of the IWG’s remit. In GMP, the revision of several Chapters (1, 2, and 7) and Annex 2 were completed, while the revision of several other Chapters (3, 5, 6, 8) were progressed and the revision of An-nexes 15 and 17 were initiated. In GDP the revision of the current (1994) Guide was completed by IWG and taken to the Commission for final review and publication. The publication of the Falsified Medicines Directive in 2011 resulted in approximately 30 actions for delivery by the IWG, these actions were prioritised into one of three levels in conjunction with the European Commission and rapporteurs and contributing members states were identified. Delivery of several of these priority actions has been completed.

Quality of Medicines and Inspections Work Area Lead Update

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Moving to cooperation with international partners, in May an Addendum to the exis-ting cooperation arrangements between IWG and PIC/S was signed to ensure closer exchange of information and harmonisation of GMP Guide and related documents. The GMP inspection cooperation between the EU and US FDA continued resulting in the waiving of the routine re-inspection of some US manufacturers of centrally authorised products. In addition the work to include active substances into the HMA’s Joint Audit Programme Checklist in conjunction with the PIC/S Joint Reassessment Programme was also completed.

Priorities for 2012The priorities for WGEO in 2013 are to support the broader implementation of the EU FalsifiedMedicinesDirective,especiallytherequirementsforimportationofactivephar-maceutical ingredients from 2 July 2013 and to facilitate a WGEO presence on the HMA website. The future of the Working Group on Product Testing will be discussed at a future HMA plenary.TherollingWorkPlanwhichidentifiesactionfor2013showsanequallybusyyearahead.This will be particularly challenging given increasingly stretched resources and undersco-res the increasing importance and benefits of international regulatory collaboration. 2013 seestheimplementationdatesofthemajorityoftherequirementsoftheFalsifiedMedi-cines Directive with the key dates being January and then in July for the new rules on the importation of active substances. The extension of EudraGMP to include a third country inspection planning module will start to realise coordination benefits and the launch of the new GDP section will see this database being re-named as EudraGMDP. Several of the on-going GMP Chapter revisions are due for completion and the revision of a key section of GMP, Annex 1 on the manufacture of sterile medicinal products, will commence. There are further work areas and cooperation with groups such as HMA and with international regulators, such as the extension of the inspection waiver programme with US FDA for non-centrally authorised products and the continuation of the collaboration and joint in-spections on active substances and finished products.


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Supporting InnovationTheme Overview

The Supporting Innovation theme considers the work of the HMA to ensure that Europe provides the best regulatory environment for the development of new treatments for humans and animals. The theme consists of two work areas: (1) Emerging Issues, New Technology and (2) Clinical Trials. The Emerging Issues, New Technology work area is led by Aginus Kalis, CBG-MEB (NL). The European Medicines Agencies Cooperation on Legal and Legislative Issues (EMACOLEX) enhances knowledge, trust and confidence between legal staff and others involved in legal matters to ensure the best legal assistance to the EMRN and the indivi-dual national competent authorities. The Task Force for Improvement in Veterinary Legislation (TFIVL) works on all the HMA Strategy objectives relevant for a modification of the EU legislation regard-ing pharmacovigilance, availability, emerging issues, antimicrobial resistance, marketing authorisation and consideration of legislation in the human side. The main objective for the near future will be to identify the possible improvements of the revised veterinary legislation and if the impact assessment reflects the role/work for the National Competent Authorities that will be published in 2013. For the long run to the revised legal proposal should be in more detail look into; and to flag other areas where a revision may be needed in the near future. The HMA veterinary Antimicrobial Resistance Task Force (vAMR TF) has been established to develop and then progress an action plan designed to deliver the HMA’s veterinary strategy on antimicrobial issues. The HMA/EMA Working Group on Transparency works to achieve greater harmonisation, consistency and efficiency of National Competent Authorities on issues related to transparency.The HMA/CAMD/CMC Steering Group, formed in 2011, seeks to improve the cooperation between HMA and the European devices regulatory network. The Clinical Trials work area is led by Xavier de Cuyper, FAMHP (BE). The Clinical Trials Facilitation Group (CTFG) aims to foster a common approach to the regulation of clinical trials conducted in the EU. To this end, the CTFG establishes and improves com-munication channels within the EMRN and develops and promotes common processes and procedures relating to clinical trials within the scope and duties of the National Competent Authorities.

EMACOLEX

Chaired by Presidency

HMA/CAMDDevices

Steering Group

Pat O´Mahony

EMA/HMA Working Group

on TransparencyTruus Janse de

Hoog/Emer Cooke

Task Force on Improvement in Veterinary LegislationJean-Pierre

Orand

Antimicrobial Task Force

Peter Borriello

Clinical Trials Facilitation

GroupChantal

Berlorgey

Clinical Trials

Xavier de Cuyper

Emerging Issues

New Technology

Aginus Kalis

Supporting Innovation

Aginus KalisWork area lead for Emerging Issues, New TechnologyChair of the HMA Management Group Executive Director of the Medicines Evaluation Board (MEB), the Netherlands

The Emerging Issues, New Technology work area covers a wide variety of topics regarding both human and veterinary medicinal products. The overall objective is to achieve more harmonisation and consistency among the Network in new areas of regulation and to use the resources and staff of the National Competent Authorities more efficiently.

Progress in 2012TheprocedurebetweenNCAsintheEUwhenthirdpartiesrequestaccesstoassessmentreports has been agreed between the joint HMA/EMA working group and endorsed by the HMA after discussion in the CMDh. The Steering Group on Devices involves and works in close collaboration with both the HMA and the Competent Authority for Medical Devices (CAMD) and devices Central Management Committee (CMC) The Task Force on improvement on veterinary legislation (TFIL) sent, following adop-tion by HMA Veterinary, a Reflection position paper to the European Commission. Anti-microbial resistance is part of the strategic proposal. Availability of veterinary products and the improvement of the strategic plan regarding antimicrobial resistance are part of the strategic proposals. The Task Force on improve-ment on veterinary legislation has produced a Reflection position paper to the European Commission. Antimicrobial resistance is under serious consideration by the Commission, including for forthcoming legal proposals. Through the work of the HMA Veterinary Task Force on Antimicrobial issues, the HMA agreed definitions for the terms antimicrobials and antibiotics and these terms have also been accepted by a number of international bodies including International Federation for Animal Health-Europe (IFAH-Europe), the Federation of Veterinarians in Europe (FVE) and the World Health Organisation (WHO).

Priorities in 2013A joint meeting of the HMA and the Competent Authority for Medical Devices (CAMD) will be held in Dublin January 2013. This will be an historic occasion which will lay the foundation for future collaboration across the high-level management groups of the two competent authority networks. The lack of specific legislation on veterinary medical devices could be considered an omis-sion. TFVIL will reflect on these possible extensions of legislation and address this deve-lopment in the new legislation, including the link needed to rules on medicated feedstuffs and the need for a more prominent role for diagnostics within veterinary and “feeding stuff” legislation. The impact of the new legislation on the availability of antibiotics for use in animals will also be examined closely. The HMA will contribute to the evidence base in the important area of antibiotic prescri-bing for animals through the publication of the results of a survey of EU veterinarians.

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Emerging Issues, New TechnologyWork Area Lead Update

21

Xavier de CuyperChief Executive of FAHMP, Belgium Work area lead for Clinical Trials

The Clinical Trials Facilitation Group is progressively achieving regulatory consistency in the European Union by developing a harmonised view on the interpretation of the legislation and a harmonised position on the future legis-lation on Clinical Trials in the EU. In addition, scientific consistency in the EU is being achieved through the de-velopment and enhancement of VHP and development of safety data worksharing.

Progress in 2012Publication of updated Q&A documents e.g. on follow-up of patients after clinical trials, DSUR reporting. Enlargement of the Voluntary Harmonisation Procedure in the number of ini-tial applications, substantial amendments and distribution of Sponsors (worldwide: EU; USA, Canada, Australia, Singapore). Liaising between the EMA, CHMP and CTFG on specific topics where the decision on a marketing authorisation has an impact on clinical trials in Europe. Continuation of work sharing e.g. DSUR, exchange of opinions or assessment on critical topics/ national Clinical Trial Applications. Supporting the EU-Commission in writing the draft regulation on clinical trials and coordinating proposals for improvement of this draft.

Clinical TrialsWork Area Lead Update

150

100

50

0 2009 2010 2011 2012

15 26

85

124

No. of VHPs per submission year

Priorities for 2013The topics pursued in 2012 will be continued. In addition, electronic portals for the voluntary harmonised procedure will be prepared as well as the DSUR work-sharing to save resources at the Member States and the co-ordinator for the harmonisation procedure.Contributing to the negotiations on the draft regulation on clinical trials:

Practical implications of the draft regulation on the future assessment/approval of •CT at the NCA.Concept and functions of the EU-Portal for clinical trials. •

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Further Improving the Operational Efficiency of MRP/DCPTheme Overview

This theme is dedicated to ensuring the smooth functioning and commitment to best practice of the decentralised and mutual recognition procedures. The theme has four work areas: (1) Best Practice, (2) Streamlining and Harmonisation, (3) Good Communication and (4) Information Technology. The Best Practice work area is led by Pat O’Mahony, IMB (IE). The Benchmarking of European Medicines Agencies Steering Group (BEMA SG) works to develop and agree on a number of high level indicators, supported by specific performance indicators, to ac-hieve the best practice standards; to define procedures and methodology for self assessment and assessment; to coordinate information gathering activity; to validate outcomes through peerreview;andtomakerecommendationstoHMAforanapproachtocontinuousqualityimprovement, and EU wide implementation in the future. The HMA Working Group of Quality Managers (WGQM) provides guidance related toqualitymanagementandbestpracticebenchmarking,andoperatestoimprovetheex-changeofqualitymanagementexpertise. The Streamlining and Harmonisation work area is led by Gro Wesenberg, Statens le-gemiddelverk (NO). The Coordination Group for Mutual Recognition and Decentra-lised Procedures (human and veterinary) (CMDh, CMDv) considers points of disagree-ment raised by Member States during Mutual Recognition and Decentralised procedures, in relation to the assessment report, Summary of Product Characteristics (SPC), labelling and package leaflet of a medicinal product (human or veterinary), as related to new applica-tions, variations and renewals.

BEMA

Pat O´MahonyKlaus Cichutek

Working Group of Quality

ManagersBrigitte

Mauel-Walbrol

CMDh

Peter Bechmann

CMDv

Esther Werner

Task Force on Resources

in DCPMartina Cvelbar

Best Practice

Pat O´Mahony

GoodCommunication

Jytte Lyngvig

Streamlining and

HarmonisationGro

Wesenberg

FurtherImproving

theOperationalEfficiency ofMRP/DCP

InformationTechnology

Marcus Müllner

Office of Training

Gro Wesenberg

HMA Homeopathic

Medicinal Products

Working GroupLaurence

Girod

Working Group of

Communication ProfessionalsDiane Leakey

Telematics Support GroupMarcus Müllner

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The Task Force on Resources in DCP was established with the aim of analysing the availability of resources in National Competent Authorities for acting as Reference Mem-ber State (RMS) in MRP and DCP procedures. This initiative was due to the difficulties for NCAs in providing industry with slot times, mainly in the DCP, a fact which had been heavily criticised by pharmaceutical companies and trade associations. The Task Force was to identify the problem areas and prepare recommendations. The Joint HMA/EMA Office of Training Steering Group (OTSG) is a group of experienced assessors and regulatory experts from HMA and EMA, mandated to provide harmonised,highqualitytrainingandtomanagethecreationoftheEUOfficeofTrain-ing,aswellasprovidingstrategicguidancetoitssubsequentoperation. The HMA Homeopathic Medicinal Products Working Group (HMP WG) is a forum for the exchange of regulatory and scientific expertise regarding the assessment of thequalityandsafetyofhomeopathicmedicinalproductsintheMemberStates. The Good Communication work area was led by Jytte Lyngvig, DKMA (DK) and then by Pat O’Mahony IMB (IE). The HMA Working Group of Communication Professionals (WGCP) is set up to promote best practice and to improve communica-tions across the Network and its stakeholders (e.g. patients, doctors, veterinarians, the pharmaceutical industry) and the general public (including the media). The Information Technology work area is led by Marcus Müllner, AGES PharmMed (AU). The HMA Telematics Support Group (TSG) facilitates communication between European and national IT systems and gives advice on other IT activities undertaken by the EMRN.

Photo: Bruno Ehrs

Pat O’MahonyWork area lead for Best PracticeChief Executive of Irish Medicines Board

BEMA III, the third benchmarking cycle, has been deve-loped to assist in sharing best practices among medicines agencies and provide assurance that they are developing in line with the HMA Strategy, and making a contribution relative to their size and stage of development. The work of the Working Group of Quality Managers (WGQM) involvessharingexperiencesandbestpracticesforqualitymanagement systems.

Progress in 2012Following on from the end of the second cycle of benchmarking visits in 2011, the BEMA Steering Group drafted the final report on the BEMA II cycle. The report outlined the development of the second cycle, gave an overview of the benchmarking visits and sum-marised the results. In addition, a number of recommendations were made to HMA for improvement of the network. The report was approved by HMA in its September meeting. The results of the benchmarking cycle show an overall mature level of systems and proce-dures across the regulatory network but with some variation in maturity across individual agencies and specific indicators. Thequestionnaireandratingschemeforthethirdcyclehasbeensignificantlydevelo-pedfromthatusedinBEMAIIduring2011.Thefinalquestionnaireandratingmaturitystatements were approved by HMA at their February meeting. Assessors and agency ‘self-assessors’ were trained in March and April. A draft schedule of visits, covering all national competent authorities and the EMA over a three year period, was created. Benchmarking visits began in September and are scheduled to continue to Q2 2014. An improved data-base is being developed to allow better stratification and searching of visit results. The Working Group of Quality Managers (WGQM) is now constituted as a subgroup of the BEMA SG, thereby bringing together the two HMA groups relevant to the topic of‘bestpractice’.Itisenvisagedthatthiscloserco-operationwillenablethequalityma-nagers’ group to function more effectively. During 2012, the group focussed significantly ontherequirementsinthenewpharmaceuticallegislationforinternalauditsofagencies’pharmacovigilancesystems,preparingsupportingdocumentstoassistqualitymanagersinimplementingthequalitysystemaccordingtothenewrequirements. HMA approved the mandate of a new subgroup of the BEMA SG, the Pharmaco-vigilance Audit Facilitation Group. The creation of this group was envisaged by the Guideline on good pharmacovigilance practices, Module IV - Pharmacovigilance Audits. The subgroup has been established to support the agencies in their compliance with the legislativeandregulatoryrequirements,throughestablishingcommonmethodologiesand formats for reporting, facilitating training and sharing best practices.

Progress for 2013The anonymised results from the first four BEMA visits and the agency and assessor eva-luations will be reviewed and any necessary adjustments made to the programme. At least one seminar for BEMA assessors will be held, for feedback on the initial visits and training of new assessors. The recommendations in the BEMA II final report for improvement of specific areas will be progressed. Regular updates from the WGQM to HMA will be made on the implementation of the qualitymanagers’workplan. A functioning Pharmacovigilance Audit Facilitation Group will be established, and a work plan developed. Support will be provided to agencies, especially for the period up to September 2013 when the agencies’ first audit reports are to be sent to the European Commission. 24

Best PracticeWork Area Lead Update

25

Gro WesenbergWork area lead for Streamlining and HarmonisationChief Executive of Statens legemiddelverk, Norway

The Streamlining and Harmonisation work area focuses on improving the ability of the Network to operate the decentralised and mutual recognition procedures, through optimisation of processes, consistency of approach, best use of resources and the provision of excellent training.

Progress in 2012The task force on DCP/MRP has completed its mission (on improving the transparency of available DCP slots to help reduce cancellations and to reduce the time for validation of applications (including technical validation of e-submissions). The CMDh is continuously working on streamlining of the MRP/DCP. The main focus is with regard to the critical parameters validation and start of the procedures, restart after clock-stop and granting of a marketing authorisation. As part of the programme, focused meeting with stakeholders are carried out in parallel to the established stakeholder meet-ings. The continuous implementation of legislation (e.g. Pharmacovigilance Legislation, Variation Regulation) into practical work by guidance and procedures is one of the main priorities. Taking this into account, the need and possibilities for further administrative simplification and worksharing will be explored within, but also outside, the EU/EEA. The CMD(v) set up a working group to specifically review the operation of the decen-tralisedprocedure,includingarationalisationofnationalvalidationrequirements,thepossible use of a single point of validation etc. The group also finalised the EMA-QRD/CMDv harmonisation exercise to revise the veterinary product information templates, resulting in one common template to be used for centralised, MRP and DCP.

TrainingPrioritylistoftrainingtopicshasbeenestablished(bioequivalence,clinicaltrials,phar-macovigilance and basic regulatory training) and a competence framework for assessors workingonqualityofmedicines.

Priorities for 2013Harmonise and simplify the validation process as a crucial part during MRP/DCP of veterinary applications and develop a common approach on the validation process and a standard validation check list. Survey NCA and publish lists of Training Plans for 2013. Starting work on a web-based training platform containing variety of training tools (video-on-demand, webinar, e learning etc) Create and maintain a list of contact points in National Competent Authorities for training. Build links with international partners (e.g. Health Canada) (at an early stage).

Streamlining and HarmonisationWork Area Lead Update

26

Jytte Lyngvig/Pat O’MahonyWork area lead for Good CommunicationDirector of the Danish Medicines Agency (DKMA)/ Chief Executive of the Irish Medicines Board (IE)

In order for the HMA to deliver its Strategy it must communicate effectively both with its internal and external stakeholders.

Communication is by its very nature a two-way process and when delivered effectively it helps ensure that:

The HMA’s Strategy evolves and continually improves following feedback from its •stakeholders;Stakeholders understand the HMA’s objectives and are in a position to help deliver •these.

Progress in 2012A HMA Communications Strategy 2012-2015 to support the implementation of the HMA Strategy was developed and agreed by the HMA in June 2012. The Strategy acknowledges that the HMA has a number of diverse stakeholders, and particularly highlights the need to establish two-way communication and effective rela-tionships with industry and other regulators. This has to be sustained to build trust and a shared commitment to work together to protect and promote public and animal health. It is acknowledged that communications with industry will be handled via the relevant industry associations as it is recognised they are an excellent channel to individual member states. A list of priority stakeholders was also agreed. As well as this focus on communications with industry and other stakeholders it was agreed the HMA web presence needs to be enhanced. There are also a number of other im-portant areas where communication needs to be co-ordinated between national agencies. Forexample, thenewpharmacovigilance legislationrequiresaconsistencyofhigh levelmessages across the European network, and also offers the opportunity for sharing com-munications resources and best practice. This work is mostly targeted at healthcare profes-sionals, together with patients and the public. In addition, the licensing decisions made inonecountrycanimpactveryquicklyanddynamicallyonotherMemberStates,becauseof the way in which the media operates on a Pan-European and often global basis and the speed with which news stories develop. It is therefore essential that robust communication channels are in place to help disseminate information across the network, including me-dia handling approaches, where issues arise or in crisis situations. This will not only help consistency in messaging across Member States; help prevent mixed messages or media confusion; and ultimately help build credibility and trust for the regulatory system. Therefore, under the HMA strategic theme of communications, three priorities were confirmed:

Communicating and interacting with industry and stakeholders;•Website enhancement; and•Crisis communication links between regulators.•

Good CommunicationWork Area Lead Update

27

Work started on improving the HMA website through an audit and update of all the cur-rent information held. Users were surveyed both within the HMA group of regulators and external stakeholders on their needs for the future design of this web site. The direction the HMA wished to take was also established and a final concept paper was prepared fol-lowing the findings arising from the survey. Work was also conducted on developing a proposal to submit to the HMA on how to better manage crisis communications across the HMA, particularly focussing on media relations and some very practical aspects of delivery. It will also cover the management of issues. Work was conducted on helping the more effective sharing of information across the HMA network, particularly focusing on pharmacovigilance and the new arrangements under PRAC was also started. A stakeholder action plan was drawn up with the commitment to review this on a regular basis.

Priorities for 2013Priorities for the coming year are seen as refining the HMA Communications Strategy to ensure it continues to support the network as this develops its future ways of working. The results from the survey on the website will be used to help redefine the future structure,scopeandrequirementsfortheHMAwebsite.Amodularplanwillbeprepared,including the resources and costs needed to launch such a new HMA website. Another priority will be ensuring the delivery of the actions following agreement of the stakeholder action plan.


Marcus MüllnerWork area lead for Information TechnologyChief Executive of AGES PharmMed (Austria)

Progress in 2012ICT plays a key role in supporting the regulatory activities of the HMA network. In 2012 the Telematics Support Group (TSG) focussed considerable effort on the introduction of new and improved mechanisms to deliver data securely and efficiently across the network. This work was principally in the area of testing and implementing the Common European Submission Portal (CESP).

A small working group of the TSG worked closely to identify potential benefits and models over an 18 month period. These operational and costing models were presented to the HMA at various meetings throughout 2012, and will culminate in a final proposal for adoption at the January 2013 HMA in Dublin. As with the CTS solution, the CESP initiative highlights the value of NCAs collabo-rating to deliver added value to the network. CESP represents the second successful IT solution delivered by the HMA network since its inception, CTS being the first technology introduced for the network. Industry stakeholders have welcomed CESP as providing a very practical solution, and removingtherequirementtosubmitinformationthroughmultiplenationalsystems. The TSG also considered proposals for a roadmap for electronic submissions and the potential to mandate for such applications over the coming 3 year period. These proposals have been presented to the HMA during 2012 and will become more important as NCAs seek to introduce automation and new technology solutions over the coming years. The TSG also participated in the ERMS-FG focussed on the implementation of the pharmacovilgance legislation. EMA invited representation from HMA following discus-sions on the potential impact of the new legislation on the broader regulatory network. The HMA is also active on the EMA Management Board Telematics Committee. As EMA has worked to develop a new model for EU telematics governance, HMA has enga-ged and provided feedback through its representation on this Committee. HMA has sup-ported proposals for improved prioritisation and project management in the new model. Active role in governance of IT-projects and maintenance:

Implementation of CESP according to plan; serious proposal for a funding model for •CESP.MBTC governance study•Revision of costs implementing EU-telematics•

Supporting the implementation of new legislation (mainly pharmacovigilance).

Priorities for 2013Further implementation and development and roll-out of CESP.•E-submission roadmap.•Preparing the implementation of an EU Database for Veterinary Medicinal Products.•Support implementation of the new legislative changes (falsified medicines).•Continue with active role in governance of IT-projects and maintenance, particularly •in relation to a new EMA-HMA governance structure.Pilot on central repository together with EMA.•

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Information TechnologyWork Area Lead Update

29

Progress Reports on Specific Objectives of Strategy

Strategy Objective Achievements 2012 Priorities 2013

(1) Improve on variations between Member States on spontaneous reporting of adverse drug reactions (ADRs); through education, motivation, facilitation, promotion and forthcoming pharmacovigilance legislation.

Proposed and endorsed transitional arrang-• ements in relation to ADR reporting and is developing a Reflection Paper on revised definition of an ADR.

(ERMS FG)

A Signal Management Drafting Group • reporting to the PhVWP was set-up.

The PhVWP set-up an ad hoc drafting group-reporting to the plenary - on GVP module VI Adverse Drug Reactions Management and Reporting in the margins of the meetings focussing on the refinement of ADR reporting from PASS and ADR reporting from non- EU clinical trials.

(PhVWP)

ERMS will oversee completion • and implementation of the legislation within the Member States (including implementation of Directive 2012-26-EU and Regulation 1027/2012).

(2) Improve safety profile of vaccines and antivirals and implementation of real-time signal detection.

The PhVWP contributed to the activities • of the EMA Pandemic Task Force (ETF) relating to the pharmacovigilance related to the swine-origin Influenza A (H1N1) virus in humans.

(PhVWP)

ERMS will consider and agree • technical contributions to delegated acts, Good Vigilance Practice (GVP) modules and any reflection papers - including updated guidance on vaccine vigilance.(ERMS FG)

(3) Good pharmaco-vigilance practice and systems efficiency, data quality (metrics).

Agreed Good Vigilance Practice (GVP) • modules(ERMS FG)

Drafted a checklist for implementation of • the quality system for pharmacovigilance.

Contributed to the GVP modules on quality • systems and pharmaco-vigilance audits, and to the template for reporting on audits to the European Commission.

(WGQM)

The PhVWP(h) has contributed to all the • Good Vigilance Practice modules drafted under the new pharmacovigilance legislation and in particular Module I on pharmacovigilance Systems and their Quality Systems and Module II on Pharmacovigilance System Master File (PSMF)

ERMS will consider and agree • Good Vigilance Practice (GVP) modules.

ERMS will oversee performance • of the European Pharmaco- vigilance system particularly in light of the new legal provisions.

(ERMS FG)

Review pharmacovigilance • system requirement for the implementation of the new legislation and the integration in the existing quality management systems.

(WGQM)

Ensure the work of facilitating • pharmacovigilance audits is undertaken under the auspices of the BEMA Steering Group.

(BEMA SG)

30


(4) Integration of new metho-dologies into pharmacovigilance systems; raise stan-dards of pharmacovigilance across Net-work to complement further development of Eudravigilance by EMA.

The PhVWP(h) adopted the “Progress • report on the pilot for signal management the EU” covering the first phase of the pilot and inputted in the draft GVP module IX on signal management to capture the lessons learnt from first pilot phase.

Discussed improvements to the European • Pharmacovigilance Issues Tracking Tool (EPITT) - (tracking systems for implemen-tation of safety-related regulatory action in EU and other communication tools for the PhVWP) in relation to various aspects on signal management and exchange of infor-mation between MSs.

Agreed a proposal for a new eRMR (elec-• tronic Reaction Monitoring Reports) format which should facilitate the detection of safety signals using EudraVigilance data for active substances included in nationally authorised products (PhVWP)

Acted as Project Oversight Committee for • implementation of new pharmacovigilance legislation.

Received progress updates from the Project • Co-ordination Group and overseen tracking of major items.

Agreed draft technical contributions to • Implementing Measures and Reflection Papers.

Proactive planning to ensure HMA and sta-• keholders kept up to date on progress.

Supported the HMA strategy and ensured • key objectives taken forward by Project Teams.

Oversight of EU Regulatory Network Inci-• dent Management Plan implementation.

(ERMS FG)

ERMS will oversee • performance of the European Pharmacovigilance system particularly in light of the new legal provisions.

To oversee completion and • implementation of the legislation within the Member States (including implementa-tion of Directive 2012-26-EU and Regulation 1027/2012).(ERMS FG)

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(5) Benefit/risk communication, trans-parency and patient engagement.

The PhVWP(h) has continued to published • regular monthly reports of its safety reviews of nationally authorised products. A dedicated drafting group has received all Direct Health-care Professional Communications, and communication plans have been prepared for key items in accordance with a specific template to ensure consistency. Patient observers weare present at all meetings.

The PhVWP agree a Communication Plan • template for distribution of DHPCs.

The PhVWP inputted in the GVP Module • XV on Safety. Communication structure and content, and the PhVWP(h) has consulted the Patient and Consumer Working Party on particular communications for patients.

(PhVWP)

Contributed to ERMS FG project implemen-• tation on the communications and trans-parency elements of the new pharmacovigi-lance legislation including requirements for national website.

(WGCP)

Patient representatives invited to attend the • human medicines stakeholder meeting. This was the first such attendance.

(The HMA)

ERMS will consider and agree • Good Vigilance Practice guidelines.(ERMS)

Provide communication support • to roll-out concept of “black triangle” at a national level.(WGCP)

HMA/EMA working group on • transparency will provide input to the transparency discussions in context of new Pharmaco-vigilance legislation.

Patient representatives to be • invited to the human medicines stakeholder meeting organized by the Irish Presidency.(The HMA)

(6) Influencing deve-lopment of revised EU legislation on veterinary pharmacovigilance to ensure that a pharmaco-vigilance master file system is introduced.

The proposal on the review of veterinary • legislation, in particular which elements from the new human pharmaco-vigilance legislation which would suit veterinary legislation, was adopted by the HMA and described in the HMA letter to European Commission on June 2011. In 2012, no draft was delivered from the Commission on the new regulation.(TFVIL)

Produce a position paper on the • draft regulation provided by the Commission (draft announced for Q3/4 2013).(TFIVL)

(7) Strengthening regulatory sanctions to ensure that veterinary Marketing Authorisation Holders (MAHs) meet vigilance responsibi-lities for their pro-ducts, using guidance, regulatory powers and pharmacovigilance inspections.

Efforts continued to be made to strengthen • communication between the PhVWP(v) and PhV Inspectors working group to prepare for pharmacovigilance inspections and a training session was held for pharmaco-vigilance assessors and inspectors in relation to this.(PhVWP(v))

Further input and proposals • will be given in 2013 after draft proposal of Commission for New Veterinary Legislation is available.(ESS WG)

(8) Raising adverse drug reaction (ADR) reporting levels by veterinarians and farmers.

Developed a reflection paper on pharmaco-vigilance communi-cation concerning veterinary medicinal products (EMA/CVMP/PhVWP/536313/2011).PhVWP(v))

Further discussion on the • implementation of this priority action to raise ADR reporting levels by veterinarians and farmers will take place meetings throughout 2013.(ESS WG)

Continue the development of • the reflection paper on pharmaco-vigilance communication.(PhVWP(v))

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(9) Simplifying veterinary reporting process; taking forward development of EudraVigilance (EV) Vet and systems for electronic ADR reporting.

Provided advice to the Joint Implementation • Group (JIG) for the continued development of EVVet 3 via the EVVet Vet JIG technical advisory group.

Undertook the annual review of the fourth • revision of the Combined VeDDRA List of Clinical Terms for Reporting Suspected Adverse Reactions in Animals and Humans to Veterinary Medicinal Products (EMA/CVMP/10418/2009).

Good progress was made to develop the • concepts for a risk/pharmaco vigilance based approach and signal detection met-hods for surveillance of veterinary medicinal products.

Discussed and responded to requests for • advice from CVMP and from Member States, on a variety of topics; including further updates on Pregsure BVD and bovine neonatal pancytopenia.

Promote and develop the use • of EudraVigilance Veteri-nary (EVVet) and the EVVet DataWarehouse in case of non-urgent safety reports and rapid alerts and for the systematic surveillance of adverse events in particular for non-centrally authorised products.

Continue to elaborate the • principles for a risk/pharmaco-vigilance based approach to, and signal detection for, surveillance of veterinary medicinal products, for the update of the CVMP recommendation for the basic surveillance of EVVet data.

Continue supporting EMA in • the development of EV VET3 together with the EVVet Joint Implementation Group.(PhVWP(v))

(10) Releasing resour-ces by increasing the flexibility of periodic safety update reports (PSUR) submission.

Meetings in 2012 dedicated to the PSUR • work share project.(ESS WG)

Proposal on the issue was adopted by the • HMA and described in the HMA letter to EC on June 2011. In 2012, as no draft was delivered from EC on the new regulation the TFVIL remained on standby on this particular point.(TFVIL)

Proposed to HMA to continue • with the PSUR work share with improved conditions.

Training of assessors is • planned for the end of May 2013 for a harmonised way of work on the assessment. The assessment is substance based on the originator product, In addition the data lock points of substances will be actively synchronised by competent authorities in the future.

Vaccines are no longer part • of the workshare based on experience from the pilot and consolidation phase.(ESS WG)

33


(11) Protect public health through inspec-tions and laboratory control of all stages of the pharmaceutical supply chain, human and veterinary.

GDP for medicinal products was revised, • including requirements for brokers, draft principles of GDP for active substances and the development of a range of harmoni-sed procedures and documents related to inspections of wholesale distributors.(GMP/GDP Inspectors Working Group)

A pilot test of risk-based selection of DCP • medicinal products for human and veterinary use for laboratory testing has been completed.(WGPT)

Revision of the Community • procedure for triggers for active substance inspections to take account of the FMD and inspections of active substance manufacturers in third countries to avoid the risk of shortages caused by the implementation of FMD.(GMP/GDP Inspectors Working Group)

Present the outcomes of the • pilot test underpinning the added value of the risk-based approach to product testing.

Re-evaluation of the current • approach for the selection of CAP for sampling and labora-tory testing.

Seek HMA endorsement for the • implementation a harmonised European guidance for risk based selection of medicinal products for laboratory testing for all European procedures.(WGPT)

(12) Develop a coordinated response to the risk of counterfeit medicines; cooperation within Network, industry and other agencies to share intelligence and inspection data; cooperation between National Competent Authorities, other authorities, police, customs etc.

Operation PANGEA V forms the reporting • highlight for 2012 in the continuing campaign to combat the illegal online supply of unlicensed and falsified medi-cines. This year's international week of action was the largest to date involving 100 countries of which 30 WGEO member countries were represented (including EEA countries and Switzerland). The operation led to the global seizure of over 4.1m doses of medicines being supplied illegally span-ning 35 therapeutic categories and worth approximately €8.1m. PANGEA V also led to the taking down of over 18,100 websites selling medicines illegally.

WGEO tabled its 5-year Strategy in April • 2012. This includes a number of work-streams centred on sharing experience and best practices for protecting the licensed, regulated supply chain for human and veterinary medicines; safeguarding against the supply of medicines through illicit supply chains, specifically the internet; in order to protect public health as well as animal health and welfare.

Three training sessions were held during • the WGEO meetings hosted in Cyprus and Ireland, covering the following topics: media handling; advanced internet training; scenario-based enforcement training culminating in a simulated ‘raid’. An Enforcement field investigation manual was also issued during the year.

The WGEO Rapid Alert System to alert • WGEO members of threat products disco-vered in the illicit supply chain in the EU/EEA was used 51 times in 2012.(WGEO)

Support the broader • implementation of the EU Falsified Medicines Directive (see also Objective 14) and to facilitate a WGEO presence on the HMA website.(WGEO)

34


(13) Risk-based redeployment of inspec-tions leading to greater focus on third country manufacturers.

The inspection planning module for 3rd • country inspections was developed on EudraGMDP, to come into operation during 2013. This module allows sharing of inspe-ction plans amongst the various agencies to avoid duplication of effort and better use of inspection resources for third country inspections.(GMP/GDP Inspectors Working Group)

A harmonised procedure for risk • based inspection planning has been developed and is under-going adoption by the European Commission. The procedure obliges MS inspectorates to focus inspection resources based on risk and to use inspection information from “trusted” international authorities to inform the risk management process and where appropriate to defer third inspections based on such information.(GMP/GDP Inspectors Working Group)

(14) Enhanced legal powers against falsified medicines.

Identified all areas of the FMD that impact • GMP and GDP inspection activities, developed a work plan and is on target with the work plan.(GMP/GDP Inspectors Working Group)

Supported the HMA Task Force on Falsified • Medicines Directive by providing an enforcement perspective on FMD implementation.(WGEO)

Continue with the work plan • and facilitate implementation by the MS.(GMP/GDP Inspectors Working Group)

Support the broader • implementation of the EU Falsified Medicines Directive (see also Objective 12).(WGEO)

(15) Use of EudraGMP and European Directorate for the Quality of Medicines & Healthcare (EDQM) database for product testing to share intelligence within Network.

Incorporated the future development of a • product testing platform into the IT work plan.(TSG)

The HMA to mandate the TSG • for identification of requirments for evolution of CTS, in order to support the implementation of risk-based selection of medicinal products, together with EDQM in relation to MRP/DCP Database. Follow up the development of EudraGMP and integrate relevant information to the Product Testing risk based platform.(WGPT)

(16) Efficiency of use of Official Medicines Control Laboratories (OMCLs).

Completed a pilot on risk-based selection • of medicinal products for laboratory testing in support of risk identification by quality assessors as part of the quality assessment report for Marketing Authorisation for MRP/DCP medicinal products. (WGPT)

Mandate CMDh and CMDv to • draft and adopt guidance for risk identification by quality assessors as part of the quality assessment report of MRP/DCP products using the outcome of the HMA WGPT pilot together with EMA for a harmonised approach to CAP.

Mandate the TSG for • identification of requirements for evolution of CTS, in order to support the implementa-tion of risk-based selection of medicinal products, together with EDQM in relation to MRP/DCP Database. Follow up the development of EudraGMP and integrate relevant information to the Product Testing risk based platform.

Consider termination of the • activity of HMA WGPT.(WGPT)

35


(17) Emerging areas of regulation – new technology (including medical devices, advanced therapy medicinal products, tissues and cells, novel foods, cosmetics).

In relation to medical devices see below, • objective (19).

Advanced therapy medicinal products:• New guidance for advanced therapy medicinal products and revised EU GMP Annex 2 guidance on the full range of biological medicinal products, drawn up by the GMP/GDP Inspectors Working Group (IWG) was published by the Com-mission and due to come into effect on 1 January 2013.

Proposal on the issue was adopted by the HMA and described in the HMA letter to EC on June 2011. In 2012, no draft was delivered from EC on the new regulation.

(TFVIL)

Produce a position paper for • the Commission on the draft regulation provided by the Commission (draft announced for Q3/4 2013).(TFVIL)

(18) Best linkage between regulation and HTA, including consultation with stake-holders.

During the meeting which was held in Janu-• ary 2011 in Warsaw the topic concerning the identification of the linkage between regulatory assessment and HTA was chosen as leading discussion topics for the following Polish and Danish Presidencies. The Polish Presidency held two sessions on "Defining the linkage between Regulatory Assessment (RA) and Health Technology Assessment (HTA)" at both the HMA meetings in Warsaw in July and in Sopot in November 2011.

During the HMA meeting under Danish • Presidency in June 2012 it was discussed on the interactions between Risk Assessment and HTA in view of the new Pharmaco- vigilance legislation and the potential of using new regulatory instruments for the objectives of the HTA.

–

36


(19) Closer engage-ment of HMA Group in considering medical devices strategy.

Agreed and planned for the first formal joint • meeting of the HMA and CAMD plenary to take place during the Irish Presidency in Q1 2013.

Held two workshops on the current and • possible future mechanisms for funding and resourcing the regulatory system for medical devices. These workshops allowed for exchange of information on the different models used in competent authorities for devices across Europe. Representatives from medical device industry and notified body associations also attended for part of one of the workshops to discuss the possibilities for developing alternative fun-ding models. The importance of seeking fee-based funding models was recognised in the European Commission’s Proposals for Regulations on Medical Devices, published in September 2012, in which specific provisions are made for national medical device competent authorities to charge fees to recover costs of all of their medical device regulatory activities.

Held workshop in Lisbon to discuss clinical • research. This workshop allowed for useful and constructive of clinical research, in particular research of drug-device combination products, experiences with work-sharing and voluntary harmonisation for clinical trials (and applicability of similar schemes to medical devices), and the use of EUDRACT and the EUDAMED systems for tracking clinical research. The workshop also allowed for discussion on the Clinical Trial Regulation and, in particular those elements which may have relevance to the discussions on the Proposals for Regulations to revise the medical device legislation.

The outcome of the HMA-CAMD • questionnaire on how competent authorities currently deal with drug-device combination products and potential areas for develop-ment of their assessment was presented to the CAMD and the HMA.

Received periodic updates on the activities • and developments in HMA-CAMD cooperation.(HMA-CAMD steering group)

Hold the first formal joint • meeting on the HMA and CAMD in Dublin in January 2013.

Further develop the discussion • on cooperation and key topics of mutual interest. Key detailed aspects of the cooperation, structural development and support are all for further discussion and agreement.

Review the existing structures • for the HMA and CAMD net-works to establish how these operate most effectively and examine options for revision of these structures if necessary and assess means of establishing structures to facilitate HMA-CAMD cooperation.

Further progress discussions • and develop proposals on alter-native mechanisms for funding and ways of optimising the use of resources in medical devices regulatory network.

Promote further discussion on • topics of mutual interest, such as companion diagnostics.

Progress and develop topics • identified during the clinical research workshop, possibly through formation of a small group to identify key work items, develop common under-standings, guidance and best practice documents.

Further examine the pos-• sibilities to progress relevant topics relating to drug-device combination products and their assessment by competent authorities.(HMA-CAMD steering group)

(20) Availability of medicines issues – human and veterinary – including possible new legislation

Work completed in 2011 by task force • (human medicines).

Proposal on the issue was adopted by the • HMA and described in the HMA letter to EC on June 2011. In 2012, no draft was delive-red from EC on the new regulation. (TFVIL)

Produce a position paper for • the Commission on the draft regulation provided by the Commission (draft announced for Q3/4 2013).(TFVIL)

(21) Publication of SPCs for authorised products on national agency websites and/or Eudrapharm.

NCAs continued to publish SPCs on their • websites.

NCAs continued to publish SPCs • on their websites.

37


(22) Devising better risk based, proportio-nate, efficient regulation which maintains public confidence.

HMA/EMA WG on Transparency met twice • in 2012, of which once for a training work-shop based on case studies on the hand-ling of requests from the Cochrane Institute. The guidance paper on identification of Commercial Confidential Information (CCI) and Protection of Personal Data (PPD) in Marketing Authorisation applications was finalised following the February 2012 HMA meeting and published in March 2012.

The responses on comments received • during the consultation were also published.

The HMA stakeholder meeting in June • 2012 provided an opportunity for additional feedback with interested parties to explain the Guidance document.

Preliminary discussion in ICH and HL7 • has taken place and concluded that it is possible to create an international standard to tag data fields as confidential or non-confidential.

Certain aspects of the MA dossier (risk • management plans and description of the pharmacovigilance system) are being addressed by the transparency subgroup in the context of new Pharmacovigilance legislation.

The CMDv started to work on applying the • principles to general guidance on veterinary dossiers.(HMA/EMA WG on Transparency)

Adopted a list of terms used in homeopathy.•

Conducted a public consultation on the • first safe dilutions of several homeopathic stocks.(HMPWG)

Editorial review of Guidance • Document on the identification of CCI and PPD in MA application”.

Meeting of WG to discuss • experience with implementation of guidance.

Discussion in ICH and HL7 • on possibilities to create a standard for the identification of confidential information and on the localization of such information.

Finalisation of veterinary • guidance.

Exploring greater transparency • of national compassionate use programmes.(HMA/EMA WG on Transparency)

Follow up on its consultation on • first safe dilutions.

Conduct a public consultation • on the list of stocks for which homeopathic use is justified and of the list of terms used in homeopathy.

Update the document on • ‘Points to Consider on safety of homeopathic medicinal products from Biological origin’.

Review the legislation on • veterinary homeopathic medicinal products.(HMPWG)

(23) Developing work-sharing in risk-based regulation.

See above. See above.

(24) Harmonization of clinical trials procedures and processes; creating an efficient and unified regulatory environment for clinical trials in Eu-rope that encourages innovation and high quality research.

Published and updated Q&A papers on • clinical trials and DSUR on HMA web site. (CTFG)

Held workshops to facilitate • the harmonisation of assess-ments between Member States (e.g. nonclinical and quality Assessors.(CTFG)

(25) Implementation of revised Clinical Trials Directive.

Developed harmonised positions on a • number of key areas for negotiation on the draft Clinical trial Regulation(CTFG)

Assist the revision of the EU • legislation on clinical trial i.e. draft regulation on clinical trial and impact of these changes.(CTFG)

(26) Work sharing approaches to assess-ment of clinical trials.

Piloted work sharing in the assessment of • annual safety reports and DSUR.(CTFG)

Assist the revision of the EU • legislation on clinical trial i.e. draft regulation on clinical trial and impact of these changes.(CTFG)

38


(27) Cooperation with EMA and Commission on common clinical trials regulatory environment.

Used procedure for liaising between the • EMA, the CHMP and the CTFG on the potential CHMP negative opinion, pre-opinion or post-authorisation with-drawal, suspension or revocation of a Marketing Authorisation with impact on EU clinical trials for actions on clinical trials e.g. Aliskiren and the Atmosphere trial (2012/13).(CTFG)

Improve and extend actions • on clinical trial when several Member States are involved e.g. according SOP/INSP/2033 or comparable cases.

Improve information systems • to facilitate work-sharing and simplify processes e.g. IT requi-rements for safety assessment and surveillance as support (European Database on SUSARs the Eudravigilance Clinical Trial Module (EV-CTM); further support the integration or link of EV-DAS, EV-MPD and EudraCT-DWH including interim solutions; Safety database DSUR.(CTFG)

(28) Voluntary Harmonization Procedure – implementation and streamlining.

Assessed more than 10% (125) of all • multinational clinical trial in Europe though the Voluntary Harmonisation Procedure.

Unanimously agreed more than 95 % of the • procedures between Member States.

The introduction of a Reference-NCA and • the preparation of a consolidated assess-ment report led to a work load reduction of the concerned Member States.(CTFG)

Enlarge and improve the • Voluntary Harmonisation Procedure i.e. update the sponsor guidance on second waves, conditions and substantial amendment.

Introduce a web based data-• base with access of all Member States to administer the VHP to reduce administrative burden.(CTFG)

(29) Regulation of veterinary medicines, including consideration of the extent to which human and veterinary medicines legislation should diverge and active participation of HMA in modification of veterinary legislation (including medicated feeds).

The TFIVL proposal on the issue was • adopted by the HMA and described in the HMA letter to EC on June 2012. This paper makes proposals on SPC harmonisation and the marketing authorisation procedures. (TFIVL)

Provided proposals to the EC for • consideration during the drafting of the new legislation on the following areas:

simplification of labelling & packaging requirements, which could be barriers to availability of VMPs;

simplification of the authorisation proce-dures that provides both applicants and competent authorities with greater clarity and predictability;

management of generics to have legis-lation that is transparent and supports the generics industry whilst protecting and encouraging a thriving innovator sector;

application of the generic concept to biological and immunological VMPs;

harmonisation of existing products, environmental risk assessment, duplicate application, authorisation of antimicrobials etc.

(CMDv)

Produce a position paper on • the draft regulation provided by the Commission, and a position paper on the draft of medicated feed regulation (draft announced for Q3/4 2013).(TFVIL)

Review the veterinary legisla-• tion – discussing and providing comments on any amendments or drafts proposed by the European Commission to the veterinary legislation.(CMDv)

39


(30) Strengthen collaboration with inter-national agencies and resources applicable to veterinary medicines; align with European Technology Platform for Animal Health, OIE, Codex Alimentarius.

On-going cooperation with FDA/ CVM and • Health Canada is maintained by EMA and some NCAs who have a bilateral memorandum of understanding.

In February 2013 several MS • PHV experts (UK, ES, PT, FR, DE) will attend the International Workshop on Veterinary Pharmacovigilance for Global Food Security at Madras Veterinary College in Chennai, India. Possible cooperation contracts between NCAs and the University in Chennai related to pharmacovigilance will be further explored.

(31) To take steps to help reduce the development of antimicrobial resistance and help communicate policies on responsible use to healthcare workers.

Agreement on definition of antimicrobials • and antibiotics for use by HMA. Terms also adopted by a number of other bodies.

Joint survey conducted with FVE on EU • veterinarian antibiotic prescribing habits and factors influencing these. (Veterinary Antimicrobial Resistance taskforce)

Publication of the paper on the • antibiotic prescribing survey.

Continued co-ordination of work • to facilitate national action to deal with products containing a fluoroquinolone in combination with colistin and to advice as necessary on the need for a referral.(Veterinary Antimicrobial Resistance taskforce)

(32) To consider whether a collabora-tive and proportionate arrangement for control clinical trials in food producing species is necessary.

–

Begin work in collection infor-• mation on how clinical trials are undertaken across the network.(CMDv)

(33) To gather informa-tion on unregulated areas for products used in animals and borderline areas and explore the need for proportionate regulation and cooperation in the Network.

Compiled a comprehensive list of relevant • legislation and court rulings in a single document.

Established and published a list of border-• line contacts across the network.

Provided a forum for discussion on • candidate products, with majority view reports issued in relation to five products. (CMDv)

Continue to provide • recommendations for classification.

Identify the different areas of • borderline products.

Agree on common • understandings.

Move from a case-by-case • product-based approach towards a consistent decision based on general principles.(CMDv)

(34) Influence the development of revised legislation for feeding stuffs to ensure that it is risk based and addresses the specific challenges of antimicrobials.

Proposal on the issue was adopted by the • HMA and described in the HMA letter to EC on June 2011. In 2012, no draft was delivered from EC on revised legislation for feeding stuffs.(TFIVL)

Consider the proposals from • the Commission on the revised legislation for medicated feed, expected in 2013, and produce a position paper.(TFIVL and AMR TF)

40


(35) Build and strengthen regular communications with HMA stakeholders; ensure efficient interaction with pharma-ceutical industry.

Prepared a leaflet describing the work of • the HMA with the intention for it to be used on Member State’s websites.

Ensured that the HMA brochure and Annual • Report 2012 were consistent in terms of editing and design, and organised the production of the Annual Report 2012.(WGCP)

Approve the HMA leaflet and • produce templates so that all NCAs can publish this leaflet on their websites.

Prepare text for a Wikipedia • entry for the HMA.

Develop a PowerPoint template • for use by the HMA.

Revise the stakeholder pages • on the HMA website to update them with more relevant infor-mation.(WGCP)

(36) Developing the HMA web presence.

Surveyed users, both within the HMA group • of regulators and external stakeholders, about their needs and desires for the future design of the HMA website.

Prepared a final concept paper following • the findings arising from the survey about the development of the HMA website, for approval by HMA at their January 2013 meeting in Dublin.(WGCP)

Prepare a detailed set of • proposals for the development of the HMA website to present to the HMA at their April 2013 meeting.

Once approved, implement • the agreed development of the HMA website.(WGCP)

(37) Crisis communica-tion links – interactions between regulators.

Developed processes and working • procedures for communicating across the HMA network in a crisis. This included clarifying the conditions that members understand what a crisis is and how such an issue would be handled across the network.(WGCP)

Embed and test the agreed • communication procedures across the network. (WGCP)

(38) Optimum utilization of resources.

The work of the Task Force on Resources • in DCP was successfully concluded and the tasks transferred to the CMDh.(Task Force on Resources in DCP )

The inspection planning module for 3rd • country inspections was developed on EudraGMDP, to come into operation during 2013. This module allows sharing of inspe-ction plans amongst the various agencies to avoid duplication of effort and better use of inspection resources for third country inspections.(GMP/GDP Inspectors Working Group)

In order to avoid referrals or • difficult legal situation after a negative outcome for a DCP, a procedure will be set up to for early identification and discussion of the item in the CMDh.

Further discussion on and • implementation of IT-tools to save resources at the level of RMS and CMS. Further empowerment of the RMS in the validation phase of procedures for new application, renewal and variations.

Use CTS as a communication • tool whenever possible and to avoid the sending of emails.

Start a pilot on the work-sharing • of the assessment of ASMF.(CMDh)

41


(39) Making decentra-lized processes work better.

The BPG for new marketing authorizations, • renewals and variations have been continuously updated.

Chapter 7 of the NtA was substantially • updated and the relevant information transferred to the CMDh-website.

The work item on better access of non-• prescription medicinal products to the MRP/DCP was finalized and the outcome published. A BPG was agreed and is in place. (CMDh)

Completed the voluntary pilot procedure • for harmonisation of summary of product characteristics (SPC) and review of lessons learned. Procedures to implement the harmonised SPC and standardised Part II of the dossier as well as for transfer of the marketing authorisations (MAs) involved to MRP were finalised.

Updated information regarding VMPs • authorised nationally (purely national/ MRP/DCP) on national matters/requirements previously maintained within Chapter 7 of Volume 6A of the European Commission’s NtA and transfer to the CMDv website.

Set up working group to specifically review • the operation of the decentralised procedure, including a rationalisation of national validation requirements, the possible use of a single point of validation etc.

Finalised the EMA-QRD/CMDv • harmonisation exercise to revise the veterinary product information templates, resulting in one common template to be used for centralised, MRP and DCP.(CMDv)

Further streamlining of the • procedure validation taking into account the further reduction of national requirements, the empowerment of the RMS to start procedures and to use IT-tools to streamline the process. Start of a pilot concerning the technical validation of eCTD submissions by the RMS.

Critical reevaluation of the DCP • process (including timelines) in light of the current experience and taking into account the opinion of the stakeholders. Targeted meetings with the European Trade Associations will continue. The process will be led by the WG on the Future of the CMDh.

Complete the implementation of • the variation regulation and to adapt the BPG to the changed legislation. Transfer the Guidance on the annual update of human influenza vaccines from the European Commission website and to integrate the updated version in the BPG on Variations.

Continue the discussion on the • accessibility of non-prescription medicinal products and traditional herbal medicinal products for the MRP/DCP. CMDh will take active part in a planned Workshop of the non-prescription pharmaceutical industry.(CMDh)

Harmonise and simplify the • validation process as a crucial part during MRP/DCP –develop a common approach on the validation process and a standard validation check list.

Finalise the HMA/EMA • guidance on the identification of commercially confidential information (CCI) and personal data (PPI) within the structure of the marketing authorisation (MA) dossier for veterinary medicinal products - release of information after granting of a marketing authorisation document.(CMDv)

42


(40) Extending new EU variation regulation provisions to national variations.

Contributed to the update of the Variations • Regulation to incorporate variations to purely national marketing authorisations and also contributed to the update of the associated guidelines.

Amended the CMDh best practice guide to • take into account the updated regulation and associated guidelines.

Updated the published list of Member • States who have agreed to apply the Variations Regulation to purely nationally authorised products on a voluntary basis ahead of the official implementation date.(CMDh)

Continued work on improvement of the • handling of variations work-sharing procedures, revision of the Best Practice Guides on work-sharing and unforeseen variations.(CMDv)

Continue work on implementa-• tion of the variations Regulation (1234/2008), particularly with regard to the extension of this Regulation to variations for purely nationally authorised products (scheduled on 4 Aug 2013).

Further revision of the CMDh • best practice guide mand rele-vant Q&A to provide guidance for stakeholders and ensure successful implementation of provisions of regulation for purely nationally authorised products.(CMDh)

Continue work on implementa-• tion of the variations Regulation (1234/2008), particularly with regard to the extension of this Regulation to nationally authorised products – revision of the Variations Best Practice Guides.(CMDv)

(41) Supporting new functionality bestowed on CMDh by strengthe-ned pharmacovigilance legislation.

Prepared for the new tasks of the CMDh • proposed in the legislative proposals on Pharmacovigilance.

Actively participated in and contributed to • the discussions on the new Pharmaco-vigilance legislation, in the various project teams, PCG and ERMS FG.

Developed a procedure for the CMDh • handling of PRAC recommendations, in relation to referrals, PASS and the outcome of single EU PSUR assessment (not yet in place for nationally authorised products).

Commenced implementation of the new • Pharmacovigilance legislation at the September 2012 CMDh meeting.

Commenced the publication of CMDh • agendas and minutes related to Pharmaco-vigilance discussions, on the CMDh website as of September 2012.(CMDh)

Further implement the Pharma-• covigilance procedures.

Further develop a procedure for • implementing the Pharmacovi-gilance legislation for nationally authorised products.

Fully integrate the PSUR WS in • the CMDh work.

Actively participate and contri-• bute in the new Pharmacovigi-lance governance structure.(CMDh)

43


(42) Providing more authorized medicines for children and imple-mentation of paediatric regulation provisions.

Five meetings of the joint CMDh/EMA • working party on the Paediatric Regulation were convened in 2012. This group discussed work-sharing for the assessment of paediatric studies submitted according to Article 45 & 46 and issues arising in relation to the Paediatric Regulation.

Four new waves of the work-sharing for the • assessment of paediatric studies submitted according to Article 45 were commenced in 2012.

Introduced a formal review process for • public assessment reports, prior to their publication on the CMDh website.

Published lists of active substances subject • to work-sharing and CMDh adopted public assessment reports on the CMDh website.

Participated in the public consultation on • the Paediatric Regulation, for the prepara-tion of the Commission report.

Organised a workshop in close collabora-• tion with the EMA for assessors, the aim of which was to bridge assessments of new applications, PIPs and work-sharing procedures.(CMDh)

Develop a process for the prio-• ritisation of active substances on the Article 45 work-sharing list.Plan to hold a further EMA/• CMDh workshop for assessors.(CMDh)

(43) Promoting work sharing and principle of fair distribution of work across the Network.

Worksharing procedure for Active • Substance Master File (ASMF) assess-ment drafted by Working Group on ASMF Procedures.

Responsibility for PSUR Worksharing • assumed by CMDh pending the implementation of the single assessment procedure for nationally authorised products.

(CMDh)

Worksharing procedure for Active Sub-• stance Master File (ASMF) assessment drafted by the Joint Working Group on ASMF Procedures:Revision of the existing ASMF guideline (new and revised Annexes - basis for the ASMF worksharing)

Practical guideline of administrative nature particular for ASMF holder, in order to fascilitate filling in of the Annexes.

Guideline on the EU-numbering system for ASMF (will start in 2013 with the Pilot project).

Guideline on how to run the ASMF Worksharing Pilot Project.

Development of the database: CTS - ASMF AR repository.

Q&As are published (Joint WG on ASMF procedures)

Start a pilot for ASMF • worksharing.

Continue and streamline the • PSUR-Worksharing for purely national marketing authorisations until the single PSUR assessment is in place.(CMDh)

Finalisation of the CTS - ASMF • AR repository (essential for the WS-project) - mid 2013.

Start of the Pilot project "ASMF • worksharing" - including EU numbering system (proposed starting date 1 Oct 2013).

Organisation of training of the • responisble colleagues in the NCAs (July - Sept 2013 - repository has to be finalised and tested prior the training).

Information and training of • industry:

Meeting with IPs;

Q&A published.(Joint WG on ASMF procedures)

(44) HMA Common Portal for MRP/DCP applicants

Common European Submission Portal • completed and operational.(TSG)

Ensure proposals for adop-• tion of electronic submissions and ramifications, e.g., AF, are understood and progressed.(TSG)

44


(45) Promoting inter-operability of NCA systems with best use of telematics.

Interoperability of IT systems is the • foundation of all IT endeavours in common projects, such as the Common European Submission Portal, roadmap to electronic submissions, the electronic application form, the controlled terminology project. Above all interoperability is supported and ensured in the best possible way by participation in the implementation of the new pharmacovigilance legislation, implementation of the falsified medicines directive and devising and implementing the new EU telematics governance structure.(TSG)

Continue to contribute to IT • solutions in implementation of falsified medicines directive.

Address possibility of EU • portals, such as one for clinical trials and medical devices.(TSG)

(46) Communications plan to ensure that sta-keholders are provided with up-to-date information on telematics.

IT is a regular agenda point at every HMA • meeting and in addition a horizontal topic touching many other agenda points. External stakeholders are routinely involved, e.g. when devising the Common European Submission Portal and e-submis-sion roadmap. The IT section on the HMA website has been updated.(TSG)

Continue to communicate with • external stakeholders on developments in EU telematics.

Regular training and stake-• holder sessions for CESP(TSG)

(47) Support of internal communications platforms for each working group of HMA.

Agreed that common technical standards • and interoperability are supported; no specific system recommended.(TSG)

No further work required.•

(48) Further develop-ment for benchmarking European medicines agencies (BEMA) programme.

Finalised questionnaire and supporting • documents for BEMA III cycle, including a process for follow up to visits.

Completed training of 49 assessors and 13 • agency staff.

Scheduled all BEMA III visits between Q3 • 2012 and Q2 2014; dates for visits in 2012 and 2013 were agreed.

Began BEMA III visits in October.•

Finalised the report on the BEMA II cycle.• (BEMA SG)

Ensured that quality managers were kept-• up-to-date with new procedures for BEMA III cycle.(WGQM)

Manage the scheduling of • BEMA visits, ensuring receipt of reports into the database and evaluations of visits by both assessors and agencies.

Deploy the database for • Secretariat to upload visit reports.

Conduct any necessary training • of assessors.

Hold a seminar in September • for feedback to assessors on visits conducted so far.

Make proposals for HMA • concerning the fourth cycle of BEMA visits, especially concerning the length of the cycle, composition of the Steering Group and secretariat.(BEMA SG)

Revise the practical steps to • prepare for the BEMA self-assessment and the BEMA visit as necessary following experience of BEMA III visits.(WGQM)

45


(49) Implementation of harmonized training strategy across Network to improve quality and consistency, including harmonized interpretation of guidelines.

A Competence Framework for Quality • Assessors was published on the HMA and EMA websites.

This serves as a model of the way in which • the OTSG can promote the creation and use of competence frameworks as a key element in harmonising training across the network.

The OTSG has identified bioequivalence, pharmaco-vigilance and basic regulatory competence as areas of priority for the OTSG in 2013.

(50) Providing basic and specialized training to all staff members of competent authorities.

A network of training contacts has been established with a nominated contact person in each Agency.

Opportunities for improving dissemination of training material through using existing or enhanced ICT tools will be explored.

The outcome of a survey on training available within the network will be sent to the list of training contacts.

46

Further Information

Useful DocumentsHMA Strategy 2011-15 http://www.hma.eu/74.html

EMA Roadmap to 2015 http://www.ema.europa.eu/

Falsified Medicines Legislation - http://ec.europa.eu/health/human-use/falsified_medicines/index_en.htm

Pharmacovigilance Legislation - http://ec.europa.eu/health/human-use/pharmacovigilance/

Useful WebsitesHeads of Medicine Agencies website – http://www.hma.eu/

European Medicines Agency – http://www.ema.europa.eu

European Commission – http://ec.europa.eu

Regulators outside the European Union – http://www.ema.europa.eu

Pharmaceutical Inspection Co-operation Scheme – http://www.picscheme.org/

World Health Organization website – www.who.in

World Organisation for Animal Health – http://www.oie.int/

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Austria AGES-PharmMed LCM www.ages.at

Belgium Federal Agency for Medicines and Health Products www.fagg-afmps.be

Bulgaria Bulgarian Drug Agency www.bda.bg

National Veterinary Service www.nvms.government.bg

Cyprus Ministry of Health – Pharmaceutical Services www.moh.gov.cy

Veterinary Services-Ministry of Agriculture, Natural Resources and Environment www.moa.gov.cy/moa/vs/vs.nsf

Czech Republic State Institute for Drug Control www.sukl.cz

Institute for State Control of Veterinary Biologicals and Medicaments www.uskvbl.cz

Denmark Danish Medicines Agency www.dkma.dk

Estonia State Agency of Medicines www.ravimiamet.ee

Finland Finnish Medicines Agency www.fimea.fi

France Agence française de sécurité sanitaire des produits de santé www.afssaps.sante.fr

ANMV – Agence nationale du Médicament Vétérinaire www.anmv.anses.fr

Germany BfArM www.bfarm.de

Paul-Ehrlich Institut www.pei.de

Bundesamt für Verbraucherschutz und Lebensmittelsicherheit www.bvl.bund.de

Greece National Organization for Medicines www.eof.gr

The National Competent Authorities

Country National Competent Authority Website

www.ages.at

www.fagg-afmps.be

www.bda.bg

www.nvms.government.bg

www.moh.gov.cy

www.moa.gov.cy/moa/vs/vs.nsf

www.sukl.cz

www.uskvbl.cz

www.dkma.dk

www.ravimiamet.ee

www.fimea.fi

www.afssaps.sante.fr

www.anmv.anses.fr

www.bfarm.de

www.pei.de

www.bvl.bund.de

www.eof.gr

48

Hungary National Institute of Pharmacy www.ogyi.hu

Institute for Veterinary Medicinal Products www.ivmp.gov.hu

Iceland Icelandic Medicines Control Agency www.imca.is

Ireland Irish Medicines Board www.imb.ie

Italy Agenzia Italiana del Farmaco www.agenziafarmaco.it

Ministero della Salute, Direzione Generale della Sanità Pubblica Veterinaria, la nutrizione e la Sicurezza degli alimenti, Direzione Generale della Sanità Animale e del Farmaco Veterinario www.salute.gov.it

Latvia State Agency of medicines www.zva.gov.lv

Food and Veterinary Service www.pvd.gov.lv

Liechtenstein Office of Health/Dpt. of Pharmaceuticals www.llv.li

Lithuania State Medicines Control Agency www.vvkt.lt

State Food and Veterinary Service www.vet.lt

Lithuanian State Inspection on Veterinary Preparations

Luxembourg Direction de la Santé Villa Louvigny Division de la Pharmacie et des Medicaments www.ms.etat.lu

Malta Medicines Authority www.medicinesauthority.gov.mt

Veterinary Medicines Unit, Food & Veternary Regulatory Division http://vafd.gov.mt/home

Netherlands College ter Beoordeling van Geneesmiddelen Medicines Evaluation Board www.cbg-meb.nl

Norway The Norwegian Medicines Agency www.legemiddelverket.no


www.ogyi.hu

www.ivmp.gov.hu

www.imca.is

www.imb.ie

www.agenziafarmaco.it

www.salute.gov.it

www.zva.gov.lv

www.pvd.gov.lv

www.llv.li

www.vvkt.lt

www.vet.lt

www.ms.etat.lu

www.medicinesauthority.gov.mt

http://vafd.gov.mt/home

www.cbg-meb.nl

www.legemiddelverket.no

49

Poland Office for Registration of Medicinal Products, Medical Devices and Biocidal Products www.urpl.gov.pl

Portugal INFARMED – Autoridade Nacional do Medicamento e Produtos de Saúde, I.P. www.infarmed.pt

DGV – Direcção Geral de Veterinária, Divisão de Meios de Defesa da Saúde Animal

Direcção Geral de Veterinária

Romania National Medicines Agency www.anm.ro

Institutul pentru Controlul Prodeselor Biologice si Medicamentelor de Uz Veterinar www.icbmv.ro

Slovakia State Institute for Drug Control www.sukl.sk

Institute for State Control of Veterinary Biologicals and Medicaments www.uskvbl.sk

Slovenia Agencija za zdravila in medicinske pripomocke www.jazmp.si

Spain Agencia Española de Medicamentos y Productos Sanitarios www.aemps.gob.es

Sweden Medical Products Agency www.lakemedelsverket.se

United Kingdom Medicines and Healthcare products Regulatory Agency www.mhra.gov.uk

VMD – Veterinary Medicines Directorate www.vmd.gov.uk


www.urpl.gov.pl

www.infarmed.pt

www.anm.ro

www.icbmv.ro

www.sukl.sk

www.uskvbl.sk

www.jazmp.si

www.aemps.gob.es

www.lakemedelsverket.se

www.mhra.gov.uk

www.vmd.gov.uk

50

Glossary

ADR Adverse Drug Reaction

AMR TF Antimicrobial Resistance Task Force (veterinary)

AMWG Availability of Medicines Working Group (2008-2011)

BEMA Benchmarking of European Medicines Agencies

BEMA SG Benchmarking of European Medicines Agencies Steering Group

CAMD Competent Authority for Medical Devices

CHMP Committee for Medicinal Products in Human use

CMC Central Management Committee for medical devices

CMDh/v Coordination Group for Mutual Recognition and Decentralised Procedures – human and veterinary

CVMP Committee for Medicinal Products for Veterinary Use

CTFG Clinical Trials Facilitation Group

DCP Decentralised Procedure

DKMA Danish Medicines Agency

EDQM European Directorate for the Quality of Medicines & HealthCare

EEA European Economic Area

EudraGMP Community database on manufacturing and import authorisations and Good Manufacturing Practice

EMA European Medicines Agency

HMA/EMA WGT HMA/EMA Working Group on Transparency

EMACOLEX European Medicines Agencies Cooperation on Legal and Legislative Issues

EMRN European Medicines Regulatory Network

ERMS FG European Risk Management Strategy Facilitation Group

51

ESS WG European Surveillance Strategy Working Group

GMP/GDP IWG GMP/GDP Inspectors Working Group

HMA Heads of Medicines Agencies

HMA MG HMA Management Group

HMA PS HMA Permanent Secretariat

HMP WG Homeopathic Medicinal Products Working Group

HTA Health Technology Assessment

MRP Mutual Recognition Procedure

NCA National Competent Authority

OTSG Office of Training Steering Group

PhV Pharmacovigilance

PIC/S Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme

PRAC Pharmacovigilance risk assessment committee

PSUR Periodic Safety Update Report

PhVWP Pharmacovigilance Working Party – human and veterinary

SPC Summary of Product Characteristics

TFIVL Task Force for Improvement in Veterinary Legislation

TFR DCP Task Force on Resources in MRP/DCP

TSG Telematics Support Group

VHP Voluntary Harmonisation Procedure for clinical trials

WGCP Working Group of Communications Professionals

WGEO Working Group of Enforcement Officers

WGPT Working Group on Product Testing

http://www.hma.eu/Postal address:Heads of Medicines Agencies Permanent Secretariat, c/o Irish Medicines Board, Earlsfort Centre, Earlsfort Terrace, Dublin 2, Ireland

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