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EMVI Statutes

Articles of Agreement - Statutes

Vaccines are central in improving public health in developed and Developing Countries, and are likely to remain a publicly funded or subsidised health promoting intervention, specially benefiting the poorest segments of society. As malaria seriously impairs productivity it is a major cause and consequence of poverty in Developing Countries, particularly in Africa. Thus, the development of malaria vaccines directly contributes to the European Community’s stated priority of combating poverty.

The ultimate aim of malaria vaccine research and development is to contribute to the reduction in mortality and severe disease caused by malaria.

EMVI should serve as a mechanism complementary to National as well as European Commission supported research and development programmes addressing malaria vaccines.

The European Malaria Vaccine Initiative (EMVI) has been launched in recognition of:

the unacceptable burden of disease that malaria causes in many countries,
the contribution of vaccines as crucial tools in controlling infectious diseases,
the pressing need for accelerated research and development, including clinical trials, in the field of malaria vaccines,
the broad public health need to assure conditions in which people can be healthy, by organising commitment of national and international resources,
the need to mobilise additional funding for malaria vaccine research and development,
the fact that national/local laboratories are highly specialised and are therefore individually unable to provide the full spectrum of expertise necessary to execute all steps of malaria vaccine development.
the importance of the genuine involvement of research partners in developing countries (DC’s),
previous and current EC supported programmes in this field such as VINCOMAL and AMANET formerly AMVTN.

1. Mission

The mission of EMVI is to contribute to the global efforts to control malaria by:

providing a mechanism for accelerated development and clinical trials of malaria vaccines in Europe and Developing Countries,
promoting affordability and accessibility of malaria vaccines in Developing Countries,
engaging European and international resources committed to malaria vaccine research.

2. Mandate

EMVI provides:

a mechanism to facilitate concerted interaction between a European Commission core activity and Union Member States’ investments, and
a mechanism to accelerate the process of bringing promising research results, i.e. experimental malaria vaccines, via limited industrial production to clinical evaluation in European volunteers; and subsequent clinical evaluation in Developing Countries in close collaboration with trials networks in malaria endemic areas.

3. Objectives

3.1 General Objectives

To bridge the conceptual and operational gaps between the bench product - i.e. candidate molecules - and further validation, limited production and clinical testing, thus making further industrial development and production feasible.

3.2 Specific Objectives

to fund research and development, including clinical trials, with a supra national focus,
to create a conducive technical and financial environment in which potential malaria vaccines can be brought to clinical trials in humans, linking together research, education and training, development, manufacturing and clinical trials expertise from both developed and disease endemic countries,
to improve the flow of information between the European scientific community, partners in Developing Countries, relevant organisations/institutions, and vaccine manufacturers (private and public), in order to facilitate co-operation,
to provide a forum and networks to enhance general and political awareness of the importance of controlling malaria,
to provide a forum for the EC and EU Member States Research and Development Ministries/Agencies for consultation on the role and development of malaria vaccines in the wider context of malaria control,
to focus on vaccines targeting infants, children and primagravidae against Plasmodium falciparum, which causes most malaria mortality worldwide.

4. Scope

EMVI is not a research undertaking in the traditional sense. Upstream basic research, essential for vaccine development, is normally supported by national or international research programmes, and generally speaking does not qualify for EMVI funding.

EMVI’s scope of operation is in the niche between promising malaria vaccine candidates developed via basic science and limited industrial production allowing subsequent clinical trials. This niche is technically and legally complex and has traditionally been under financed.

EMVI will support:

The manufacture in Europe of candidate malaria vaccines according to international quality requirements (GMP).
The conduct of phase I, and in some cases, Phase II clinical trials of these vaccines in a limited number of clinical trial centres in Europe.
The conduct of Phase Ib safety and IIb limited clinical efficacy trials of candidate vaccines in field sites that will be developed by trials networks in malaria endemic areas.
The support of studies and other support measures relevant to malaria vaccine development.

These goals will be achieved by strengthening an integrated clinical trials and development platform with EMVI and its partners, such as AMANET, to coordinate the clinical trials in Europe and malaria endemic areas of candidate malaria vaccines.

Within its scope of operations and with respect to managerial and financial restraints, EMVI is prepared to assume general responsibility for the coordination of European research efforts in the area of malaria vaccine development, e.g. organisation of relevant workshops, harmonisation of protocols and standards, participation in relevant multilateral initiatives.

5. EMVI’s Structure and Governance:

EMVI is governed by:

The Board

5.1 Board

5.1.1 Composition of Board

the representative of the Contracting Institution
one representative from each of the European countries and agencies/entities that contribute or pledge financial support to EMVI
a representative from the malaria vaccine research community in a malaria endemic area (identified by the above Board members)
representative(s) from industry (identified by the above Board members)
representatives(s) from the European Commission
the SAC Chairperson (non-voting member)

The Board aims at a balanced male/female composition and the inclusion of technical, strategic as well as policy skills.

The Board elects a Chairperson and Vice Chairperson.

5.1.2 Board Tasks

to appoint a Scientific Advisory Committee (SAC) from prominent members of the scientific community
to set and adjust goals
to develop scientific policies and strategies based on advice from SAC
to evaluate progress in relation to objectives and goals
to approve and when possible to allocate available funding for research and development in accordance with recommendations made by SAC (5.3)
to approve the annual work plan of the Secretariat (5.4)
to secure funds from EU Member States and other interested parties.

5.1.3 Board Meetings

The Board meets at least twice a year, preferably in conjunction with a meeting of SAC.

Decisions are based on a broad consensus. Dissent can be incorporated in the written Minutes of the Meeting.

A quorum of 50% of Board members, including the Chairperson or Vice Chairperson and the legal representative of Statens Serum Institut, is necessary for any decision to be binding. In the event a quorum is not achieved decisions must be confirmed by written procedure.

Decisions regarding funding of proposals are taken on the basis of the text of the proposal, the written summary evaluation prepared by SAC and a budget estimate prepared by the secretariat.

Members who do not participate in or otherwise contribute to three consecutive meetings can be replaced by consensus decision of the other Board members.

5.2 Contracting Institution

European Malaria Vaccine Initiative (EMVI) is a programme registered at Statens Serum Institut, Copenhagen, Denmark, who appoint a representative to the Board. Contracts signed between EMVI and manufacturers, clinical trial centres or research institutions contain an article stating that arbitration and disputes are governed by the law of Denmark.

Contracts are only legally binding with the signature of the Administrator, or her/his mandated proxy.

The Contracting Institution, Statens Serum Institut is responsible for:

the management of funds,
establishing a secretariat for the implementation of the Board’s decisions,
financial and technical reports to DG Research/INCO programme with regard to its financial contribution to EMVI in accordance with the Model Contract, Annex II General Conditions, as well as any other legal dealings with the Commission,
financial and technical reports to contributing Member States and other contributors,
providing to the Board reports on the disbursement of financial contributions from Member States and other contributors.
day to day supervision of the secretariat.

5.3 Scientific Advisory Committee (SAC)

The independent Scientific Advisory Committee (SAC) make recommendations to the Board on scientific direction and technologies as well as on the choice of applications for funding.

A major feature of EMVI is its ability to react quickly and flexibly to new technological innovations and scientific breakthroughs in vaccine development, while remaining focused on the key objective of developing and testing malaria vaccine for use in developing countries.

5.3.1 Composition of SAC

The Board appoints seven scientists to serve as members of the Scientific Advisory Committee for a period of three years. Re-appointment for an additional three-year period is permitted. See Appendix 1 for details of SAC selection process.

The following areas of expertise should be represented in this group:
basic research and immunology, vaccine research and development, process development and clinical trials, field trials of vaccines and/or drugs in malaria endemic areas.

SAC elect a Chairperson from their midst, who is a non-voting member of the Board.

SAC can co-opt additional experts for a period of up to one year at a time, with the approval of the Board, relevant to the nature of the submitted proposals or on-going projects. Additional external experts, preferably from DC and industry, can be called on for specialist advice and evaluation of proposals.

5.3.2 Functions of SAC

SAC will advise the EMVI Board on all matters of a scientific and technical nature in relation to malaria vaccine development and clinical trials.

SAC will develop EMVI’s scientific strategies and policies for Board approval.

SAC can recommend new initiatives or re-direction of EMVI initiatives to the Board.

SAC will design the texts for EMVI Calls for Letters of Interest and/Proposals.

SAC will evaluate Letters of Interest and Project Proposals and will submit recommendations in a written consensus report for prioritised projects to the Board via the secretariat.

Each Letter of Interest/Proposal must be evaluated by at least five SAC members, or co-opted SAC members.

SAC will meet at least twice a year to arrive at a written consensus with regard to Letters of Interest/Proposals, as well as possible policy proposals. A quorum of four is required for decisions to be binding. Members who do not participate in or otherwise contribute to three consecutive meetings can be replaced, in consultation with the Board.

Unsolicited proposals received by Board members, the Secretariat or SAC will be subject to the evaluation procedures, as stated in this section 5.3.2, used for proposals/Letters of Interest received in response to calls.

SAC recommendations should normally be based on written consensus decisions. In the event of widely divergent opinions, additional expertise can be sought. Dissent can be recorded in detail in the written “consensus report”.

Each SAC member submits at the consensus meeting a written evaluation of each Letter of Interest/Proposal taking into account the scientific value and practicalities, as well as identifying possibilities for collaboration between submitted proposals.

SAC will, on request, provide scientific and technical advice to the secretariat to assist in its executive function.

SAC may evaluate the progress of on-going EMVI funded research/development.

5.4 Secretariat

The Secretariat will be staffed by experts of proven experience in the fields of malaria research, vaccine development and clinical trials and regulatory affairs

The Secretariat reports to the Contracting Institution, Statens Serum Institut, which is responsible for employment contracts and administrative supervision.

5.4.1 Composition of Secretariat

The Secretariat consists of senior experts with proven experience and expertise in vaccine R&D and clinical trials and support staff.

5.4.2 Functions of Secretariat

There are five main functions of the secretariat, the details of which are given in Appendix 2:

1) Management of Vaccine Development

2) Management of European Clinical Phase I and II Trials

3) International Collaboration with Major Players

4) Information Policy

5) Financial Planning

Appendix 1

Selection of SAC

Each Board member nominates three scientists with expertise in malaria and/or vaccine research and development to a Panel of experts. One of the nominated specialists should come from outside Board members’ own countries, and preferably from a DC. Besides a balanced geographical representation, the Board ensures a balanced representation of the vaccine discipline in the broadest sense. Conflicts of interest, i.e. where SAC members and potential recipients of EMVI support are the same or closely associated should be carefully avoided.

The panel of experts can be augmented by additional experts proposed either by Board members, SAC members or the secretariat with the approval of the Board.

The Board selects the seven members of SAC from this panel. In the event that consensus cannot be obtained, decisions are reached by simple majority.

Appendix 2

Functions of the Secretariat

1) Management of Vaccine Development
The vaccine development pipeline comprises individual steps, each with a decision point: EMVI’s mandate extends to clinical Phase I and, where appropriate, Phase II testing in Europe. Malaria is not endemic in the EU, and while limited Phase II efficacy trials are possible in Europe for pre-erythrocytic vaccines, vaccine efficacy will have to be determined in large-scale Phase II and III trials in malaria endemic areas.

GMP manufacture: The EMVI Secretariat has compiled a list of contract GMP manufacturers with capabilities in process development and/or GMP manufacture in the areas of each vaccine platform, including recombinant prokaryotic and eukaryotic expression, recombinant viruses and bacteria, synthetic peptides, and DNA vaccines. When SAC recommends a particular vaccine candidate for GMP manufacture, and subsequent to Board approval, EMVI will establish a Product Development Team (PDT) for each product, comprising a member of EMVI’s secretariat – frequently the Director for Clinical and Regulatory Affairs - as Chair, the Investigator who developed the candidate and representatives from the contract manufacturer selected for the product. This team will oversee the process development of each product. If the construct has not previously been subject to process development and upscaling in the chosen platform, a feasibility study would normally be required before a decision as to whether the construct can move into GMP manufacture is taken. The PDT will assume responsibility for GMP manufacture, including delivery of vaccine in vials, all SOP’s (Standard Operating Procedures), scientific files and other information required for preparation of the Clinical Trials Protocol and application to the IRB. Pre-clinical toxicology is usually incorporated in the GMP manufacturing contract. For pre-clinical safety and immunogenicity studies in primates, if considered essential, the PDT may include an expert from Biomedical Primate Research Centre, Rijswijk, The Netherlands, or another centre with relevant expertise.

2) Management of European Clinical Phase I and II Trials
EMVI’s Director of Clinical and Regulatory Affairs will plan, oversee and advise on all aspects of EMVI supported clinical trials, and will normally act as sponsors monitor The designated Clinical Investigator will prepare all reports for the Trial Centre’s Internal Review Board, EMVI, EU and regulatory authorities as required. All clinical trials will adhere to Good Clinical Practice (GCP) legislation, transposition of EC directives (20/2001) and the International Congress of Harmonisation (ICH) guidelines. It is anticipated that some candidate vaccines showing promising immunogenicity may have to be re-formulated with different adjuvants to optimise immunogenicity in subsequent Phase I trials, before transfer to a malaria endemic area.

A Data Safety and Monitoring Board (DSMB) will be established for all vaccine trials following initial Phase I trials.

Evaluation Procedure of Outcomes of Phase I Trials: Decision to move to clinical trials in a malaria endemic area: Past experience suggests that candidate malaria vaccines will have variable immunogenicity. Experimental challenge of volunteers immunised with pre-erythrocytic vaccines has been validated. Small Phase II trials will provide valuable information for the decision to move these vaccines to testing in malaria endemic areas. The role of challenge in blood stage vaccines trials remains more controversial, and in the absence of clinical challenge Phase II data, it will be essential to establish immunological outcomes that must be satisfied to justify progressing to testing a vaccine in malaria endemic areas. It will be the responsibility of the Director of Clinical and Regulatory Affairs in collaboration with the inventor and SAC to establish these criteria in an annex to the clinical trial protocol, in advance of the clinical trial, and to further determine whether they have been fulfilled. It is likely that a number of vaccines will fail at this stage, and these will either be abandoned, or more likely re-formulated for further clinical testing, before being re-evaluated by SAC.

3) International Collaboration with Major Players
EMVI is currently a focal point of major European malaria vaccine development efforts, endeavouring to coordinate both nationally supported and EC supported malaria vaccine efforts, as recognised by the Council of Ministers resolution adopted May 14, 2001. EMVI has established close links with the European and Developing Countries’ Clinical Trials Partnership (EDCTP), colleagues in the USA, the Gates Foundation-supported Malaria Vaccine Initiative (MVI), the US Agency for International Development (USAID) and National Institutes of Health (NIH). EMVI has further established close links with WHO/TDR, and there is a reciprocal participation in planning meetings and workshops.

4) Information Policy
EMVI will strive to act as a forum for strategic discussions and communications. Based on requests from the Board and SAC, the Secretariat will after Board-approval call meetings to address key issues in malaria vaccine development and testing. A major challenge for SAC will be to develop guidelines for the secretariats implementation of appropriately formulated multi-component and/or multi-stage malaria vaccines.
The Internet is an essential element for providing information to an international network. Position documents, protocols and results of all EMVI conducted clinical trials will be published by the secretariat on EMVI’s web site www.emvi.org, and where applicable automatically disseminated to relevant institutions/entities etc. The EMVI Secretariat will make itself available as a source of expertise on malaria vaccine research, development and clinical trials to relevant European, national and international bodies.

5) Financial Planning
The Secretariat assists the Board in raising financial support from EU Member States and other sources. The Board will approve the EMVI annual work plan and budget. A development plan including staggered budget will be elaborated for each approved project. For each malaria vaccine that has passed phase I clinical trials in Europe a full vaccine-development plan including provisional budget will be elaborated. It is the Executive Directors responsibility, assisted by the staff of the secretariat, to plan and budget for all EMVI’s activities, including Committee and Board meetings and furnish relevant documentation to the Board.

Non-Exhaustive List of Tasks of the Secretariat

to implement Board decisions (5.1),
to keep the Board informed of events, progress, relevant information etc. in order to optimise its performance (5.1),
to arrange Board meetings and draw up Minutes of Meetings (5.1),
to launch Calls for Letters for Interest/Letters of Intent/Proposals based on SAC recommendations and Board approval (5.3.2),
to convene SAC members consensus report meeting and circulate the report to the Board (5.3.2),
to negotiate contracts for GMP production and clinical trials, or to assist investigators in negotiating contracts,
to take delivery of experimental vaccines and ensure documentation for the product and release payments subject to Board approval,
to design, plan and negotiate phase I and II clinical trials in humans as well as non-human primates,
to ensure, in close co-operation with the investigator, access to the results of phase I and II clinical trials for the EMVI Network,
to assist the investigator in making the reagents, derived from the clinical trials, available to other research groups in the Network,
to maintain an interactive data base (based on SHARED),
to monitor project progress,
to organise Workshops and studies relevant to the advancement of EMVI’s mandate,
to participate in international meetings, seminars, workshops pertinent to the objectives of EMVI,
to liase with international organisations such as EDCTP, WHO, USAID, NIH, MVI, AMANET and others,
to improve communication and information between the European scientific community, partners in developing countries, like-minded organisations/institutions and vaccine manufacturers.