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Workshop on Expanded Access to experimental Ebola vaccines during outbreaks
Workshop on Expanded Access to experimental Ebola vaccines during outbreaks
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© World Health Organization 2017 WHO/Reference number
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This publication contains the report of the Workshop on Expanded Access to experimental Ebola vaccines during outbreaks and does not necessarily represent the decisions or policies of the World Health Organization.
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Acronyms
AEFI Adverse events following immunization
AVAREF African Vaccine Regulatory Forum
CEPI Coalition for Epidemic Preparedness and Innovation
DRC Democratic Republic of the Congo
EMA European Medicines Agency
EPI Expanded programme on immunization
EUAL Emergency Use Assessment and Listing
EVD Ebola virus disease
US-FDA United States Food and Drug Administration
GAVI Global Alliance for Vaccination and Immunization
GCP Good Clinical Practice
IHR International Health Regulations
IVD In vitro diagnostic
MOH Ministry of Health
MoU Memorandum of Understanding
MSF Médecins Sans Frontières
SAGE Strategic Advisory Group of Experts on Immunization
SOPs Standard operating procedures
UNICEF United Nations Children’s Fund
US CDC United States Centers for Disease Control and Prevention
WFP World Food Programme
WHO World Health Organization
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Contents
Introduction ............................................................................................................ 6
1. Opening session ............................................................................................. 8
2. Before the Outbreak ........................................................................................ 9 2.1 Ring vaccination: the basics ........................................................................................................ 9
2.2 Expanded Access: MSF rVSV contingency plan ......................................................................... 9
2.3 MSD V920 vaccine .................................................................................................................... 10
2.4 Regulation of medicines and other health technologies ............................................................. 10
2.5 ‘Expanded Access’ framework to access to experimental Ebola vaccines in the context of outbreaks ................................................................................................................................... 11
2.6 Good Clinical Practice and Standard Operating Procedures training of field staff for ring vaccination ................................................................................................................................. 11
2.7 Discussion .................................................................................................................................. 11
3. During the Outbreak ..................................................................................... 14 3.1 Overview of key preparatory and implementation steps ............................................................ 14
3.2 Lessons learned: Likati, Bas Uélé, DRC 2017 Ebola outbreak .................................................. 14
3.3 Preparing for ring vaccination in the DRC during Likati outbreak (2017) ................................... 15
4. During the outbreak: Feedback from Working Group discussions .......... 16 4.1 Coordination and communication with stakeholders .................................................................. 16
4.2 Access to vaccines (including regulatory and ethical considerations) ........................................ 16
4.3 Logistics and cold chain ............................................................................................................. 17
4.4 Engaging communities for the use of experimental vaccines and interventions ........................ 18
4.5 Ring definition and identification of contacts .............................................................................. 19
4.6 Discussion .................................................................................................................................. 19
5. Ongoing global preparedness efforts for the use of experimental Ebola vaccines under an ‘Expanded Access’ framework ........................................... 21
5.1 Liability, indemnification and compensation for the use of investigational products during outbreaks ................................................................................................................................... 21
5.2 Regulatory preparedness for medical countermeasures ........................................................... 22
5.3 Ethical considerations for using vaccines under an Expanded Access Framework and how to involve ethics committees ...................................................................................................... 22
5.4 GAVI’s engagement in epidemic response ................................................................................ 22
5.5 Discussion .................................................................................................................................. 23
6. Improving preparedness: Feedback from Working Group discussions ... 24 6.1 Decisions to use experimental Ebola vaccines .......................................................................... 24
6.2 Partnership at field level ............................................................................................................. 24
6.3 Additional tools and guidelines .................................................................................................. 24
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7. Closing session ............................................................................................ 25 7.1 Next steps .................................................................................................................................. 25
7.2 Closing comments ..................................................................................................................... 25
Annexes Annex 1: List of Participants ............................................................................................................... 26
Annex 2: Agenda ................................................................................................................................ 28
Annex 3: During the outbreak: Working Groups and participants ....................................................... 30
Annex 4: Improving preparedness: Working Groups and participants ............................................... 32
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Introduction
Background
The 2014-16 outbreak of Ebola virus disease (EVD) in West Africa highlighted the lack of a licensed vaccine to combat the virus. The urgency to develop and license a vaccine has been amplified since then, with twelve candidate vaccines currently at various stages of development.
In April 2017, the Strategic Advisory Group of Experts (SAGE) on Immunization noted that “Should an Ebola disease outbreak occur before the candidate vaccine is licensed, SAGE recommend[s] that the rVSVΔG-ZEBOV-GP vaccine be promptly deployed under the Expanded Access framework, with informed consent and in compliance with Good Clinical Practice. If the outbreak is caused by an Ebola virus species other than Zaire, consideration should be given to the use of other candidate vaccines that target the putative viral species.
Ring vaccination, as used in the Phase 3 study in Guinea, is the recommended delivery strategy. This should be adapted to the social and geographic conditions of the outbreak areas and include people at risk including but not limited to: (i) contacts and contacts of contacts; (ii) local and international health-care and front-line workers in the affected areas and (iii) health-care and front-line workers in areas at risk of expansion of the outbreak.
The Expanded Access study protocol, which is being discussed with Member States by Medecins Sans Frontieres (MSF), the vaccine developer, and partners, should be implemented promptly after the confirmation of a case of Ebola, in coordination with the current control interventions. It should be used as an opportunity to accumulate additional information on vaccine safety, efficacy and effectiveness”.1
On 11 May 2017, the Ministry of Health of the Democratic Republic of the Congo (DRC) informed the World Health Organization (WHO) of a laboratory confirmed case of EVD. The outbreak occurred in the Likati Health Zone – a remote area with limited access to transport and communication infrastructure. The outbreak was declared over on 2 July 2017 with a total of five confirmed and three probable cases, with four deaths and four survivors.
The outbreak was controlled through existing well-defined EVD response interventions including:
surveillance, case investigation and contact tracing;
case management and infection prevention and control;
safe and dignified burials;
community engagement and social mobilization;
coordination and operations support.
1 World Health Organization. Meeting of the Strategic Advisory Group of Experts on immunization, April
2017 – conclusions and recommendations. Weekly Epidemiological Record. 2017; 92(22): 301-320. http://apps.who.int/iris/bitstream/10665/255611/1/WER9222.pdf (accessed 22 September 2017).
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In addition, as done previously during the Ebola outbreak in Guinea and Sierra Leone2, a candidate EVD vaccine (rVSVΔG-ZEBOV-GP) was available under an Expanded Access framework as recommended by SAGE. The Government of the DRC, together with MSF and WHO, were ready to deploy the vaccine should its use be indicated. Although the vaccine was ultimately not deployed, important lessons were learned in the preparations undertaken by all partners.
Objectives
The objectives of the workshop were to:
identify strengths and weaknesses of the response implemented in DRC, with a specific focus on the use of experimental vaccine in a ring vaccination strategy, under an Expanded Access framework;
identify gaps and lessons learned; and
identify key actions to guide the future use of experimental EVD vaccine under an Expanded Access framework.
Methodology
WHO convened a workshop with 54 participants from the Ministries of Health of DRC, Guinea and Sierra Leone, representatives from major partners in the DRC EVD response and stakeholders likely to provide support in future EVD outbreaks.
The meeting was structured into plenary sessions followed by discussion, and two working-group sessions.
2 Gsell, Pierre-Stéphane et al. Ring vaccination with rVSV-ZEBOV under expanded access in response to
an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report. The Lancet Infectious Diseases. Published online October 9, 2017 http://dx.doi.org/10.1016/S1473-3099(17)30541-8.
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1. Opening session
Dr Mike Ryan welcomed the participants and reiterated the purpose of the workshop to discuss the implementation of SAGE recommendations on the use experimental EVD vaccines during outbreaks. Dr Ryan noted the promising potential of these vaccines, and the opportunity provided by the workshop to meet with different partners to discuss how to ensure prompt access to experimental vaccines for people at risk of EVD. Vaccination with experimental EVD vaccines is not a straightforward proposition. Deploying experimental vaccines effectively and ethically requires careful planning in accordance with regulatory requirements and international guidelines.
Steps were taken to prepare for the deployment of experimental vaccine during the recent outbreak of EVD in May 2017 in the DRC. A number of challenges were identified during this experience, which will be discussed during this workshop and used to develop a clear process to ensure timely access to candidate vaccines in future EVD outbreaks.
Dr Ryan also referred to the new WHO Health Emergencies Programme operating across WHO. The Programme represents a true collaboration across WHO departments, offices, regions and partners globally. The diverse representation from partner organisations to this workshop was testimony to this approach.
Dr Jean-Jacques Muyembe Tamfum provided his personal perspective regarding EVD management in the DRC. In 1996, EVD was considered an orphaned disease which could not be diagnosed or treated and for which there was no vaccine. Now, twenty years later, candidate anti-viral treatments and vaccines are available. This once neglected disease may become more common in the future, but real steps are now being taken toward its control and management.
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2. Before the Outbreak 2.1 Ring vaccination: the basics
Ana Maria Henao-Restrepo, Immunization Vaccines and Biologicals, WHO
Ring vaccination was a key strategy used to eradicate smallpox in Africa, Asia and South America in the 1970s3. It works by creating a circle of immune people around each new case to prevent further spread of the infection. This is done by identifying new laboratory confirmed EVD cases and offering vaccination to a ‘ring’ of individuals around each case who are his/her contacts and contacts of contacts, including residents temporarily absent at the time of enumeration. Contacts are defined as individuals who lived in the same household, visited or were visited by the index case after the onset of symptoms, provided him or her with unprotected care, or prepared the body for a funeral ceremony. High-risk contacts are defined as individuals who were in close physical contact with the case’s body or body fluids, linen, or clothes. Contacts of contacts are the neighbors of the index case to the nearest appropriate geographical boundary, plus household members of any high-risk contacts living away from the index case’s residence.4
Twelve candidate EVD vaccines are currently at different stages of clinical evaluation. After licensure regular vaccine deployment processes can be used. However as recommended by SAGE, if an EVD outbreak occurs before one or more vaccine are licensed a candidate vaccine should be considered for deployment in a ring vaccination strategy under an Expanded Access Framework, with informed consent and in compliance with Good Clinical Practice (GCP).
Delivering an experimental vaccine is a specific strategy that must be conducted following a study protocol established in compliance with international research standards and approved by national ethics committees and regulatory authorities. It must be implemented under GCP conditions by trained staff, with assessment of eligibility, documentation of informed consent, safety monitoring and follow-up. It also necessitates addressing issues related to compensation and liability. It is a very different strategy to mass vaccination using a licensed vaccine, with significant distinctions in community and social strategies. Logistical issues must also be addressed – for example the candidate vaccine considered during the 2017 DRC outbreak required specialized equipment to maintain specific cold chain conditions (e.g. storage and transport ≤ -60°C).
2.2 Expanded Access: MSF rVSV contingency plan Micaela Serafini, MSF
The MSF study protocol and contingency plan for the rVSV ZEBOV candidate vaccine addresses the use of the vaccine as an investigational product under a cohort study protocol. The candidate vaccine can only be exported and used under an Expanded Access Framework using a study protocol. The study protocol was based on the ring trial experience in Guinea, and adjusted in collaboration with the vaccine producer Merck and the MSF ethics board. MSF
3 “Fenner F, Henderson DA, Arita L, Jezek Z, Ladnyi ID Smallpox and its eradication. Geneva: World
Health Organization; 1988” Excerpt From: “Ring Vaccination and Smallpox Control.” iBooks. 4 Henao-Restrepo, Ana Maria et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing
Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!)The Lancet , Volume 389 , Issue 10068 , 505 – 518.
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is approaching twelve at-risk African countries to present the protocol, discuss possibility of its implementation in partnership with the MOH or local research institutions, and is seeking approval from national ethics boards and regulatory bodies. An international MSF mobile team to implement the protocol is being established together with standard operating procedures, GCP training and information materials and equipment.
Currently the protocol has been approved in four countries (DRC, Mali, Niger and Uganda). After the experience of the DRC outbreak, additional cold chain preparations are being made, and MSF has made provisions to address liability issues. It was noted that implementer(s) of the study protocol (Sponsor(s)) will be legally responsible and liable. The Sponsors are being defined after interactions with each country authority. In some countries this will be MSF, in partnership with the MOH.
2.3 MSD V920 vaccine Beth-Ann Coller, Merck
V920 (rVSVΔG-ZEBOV-GP) is the candidate EVD vaccine developed by Merck. It has been studied in thirteen clinical trials in Africa, Europe and North America involving over 18,000 participants, including four Phase II/III trials conducted in the context of the West Africa EVD outbreak. Preliminary data suggests an acceptable safety profile and positive benefit-risk ratio. Safety and immunogenicity in human immunodeficiency virus (HIV) positive individuals and children is being further studied. The rVSVΔG-ZEBOV-GP candidate vaccine was granted access to the Priority Medicine (PRIME) scheme by the EMA, and Breakthrough Therapy designation by the US-FDA.
Merck intends to seek marketing authorization and is actively discussing the requirements for licensure with both the European Medicines Agency (EMA) and United States Food and Drug Administration (US-FDA). Merck also intends to seek WHO Prequalification and pursue registration in several African countries. In addition it is providing data to WHO in support of an EUAL. V920 is therefore an investigational product and can only be used in the context of an established regulatory framework to ensure patient safety (e.g. clinical trial protocol, expanded access or emergency use). Additional data on thermostability is becoming available. This would facilitate implementation (e.g. stability data for storage and transportation). Prior to licensure and in the context of a new EVD outbreak, Merck stands ready to work with partners to make the candidate vaccine available under the above mentioned conditions.
2.4 Regulation of medicines and other health technologies Olivier Lapujade, Essential Medicines and Health Products, WHO
WHO provides regulatory technical advice in the context of EVD response to: 1) support Member States to review clinical trials of EVD vaccines and collaborate with national regulatory agencies and ethics committees through the African Vaccine Regulatory Forum (AVAREF); 2) support pharmacovigilance preparedness; 3) develop guidelines and standards; and 4) develop EUAL procedures for in vitro diagnostics (IVDs), pharmaceuticals and vaccines in the context of a public health emergency of international concern 5 . WHO also supports communication, stakeholder engagement, and partner coordination, and has developed mechanisms for the surveillance of adverse events following immunisation (AEFI).
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As defined in the International Health Regulations (IHR) 2005.
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2.5 ‘Expanded Access’ framework to access to experimental Ebola vaccines in the context of outbreaks Alejandro Costa, Infectious Hazard Management, WHO
In this context “Expanded Access” (also called “Compassionate Use”), refers to the use of an investigational vaccine outside of clinical trials to prevent or treat a serious disease or condition for which there are no comparable or satisfactory approved therapy options available. It therefore provides a regulatory approval for individuals or groups of people at risk of EVD to gain access to investigational vaccines.
WHO is actively working with partners including at risk countries, MSF, Merck and other partners involved in EVD response to prepare and plan for the use of experimental vaccines. The primary objective of the Expanded Access Framework is to ensure preparedness for the use of an experimental EVD vaccine in an outbreak scenario. Secondary objectives are to collect additional data to complement information on the safety and effectiveness of the vaccine (generally derived from clinical trials) and to provide the basis for more generic approaches for the use of experimental vaccines and therapeutics for other priority pathogens. These objectives are met through the development of generic cohort protocols and standard operating procedures (SOPs) to ensure minimum GCP standards. As part of a collaborative effort, international and national field teams are established and trained in the use of experimental vaccines, ring vaccination implementation and GCP standards. Decision-making procedures and prioritization criteria are being established to ensure equitable access to vaccination, and logistic plans and community engagement strategies are being prepared. Lastly, generic agreements for collaboration, legal conditions, compensation and insurance mechanisms are put in place, as well as protocols for the vaccination of health care and front-line workers.
2.6 Good Clinical Practice and Standard Operating Procedures training of field staff for ring vaccination Godwin Enwere, Essential Medicines and Health Products, WHO
GCP is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, recording, analysis and reporting of clinical trials. Well trained trial staff on GCP will ensure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial subjects are respected and protected. An understanding of GCP principles is crucial in the context of an Expanded Access Framework to ensure that the rights of participants are protected and that generated data are valid.
GCP training should be offered to regulatory authorities, ethics committees, the agency taking on responsibility for the vaccination strategy (Sponsor) and must be provided to individuals involved in implementing and monitoring vaccination. Training should cover ethics; the rights, safety and confidentiality of participants; voluntary informed consent; approving and following protocols; medical decisions and care; data collection and management; vaccine handling and storage; and quality assurance. Team members should also be trained in the use of relevant SOPs for their role. Training should be documented and done in advance of vaccination deployment.
2.7 Discussion
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Communication: It is critical to ensure that language and communication are clear. People very often associate vaccination with mass vaccination campaigns, and have preconceived expectations about what this means, their potential role and who is vaccinated. Ring vaccination will happen in the context of an outbreak, thus it is critical to get key partners involved quickly to ensure that correct and coordinated messages are given to stakeholders and communities. Communicating who needs to be vaccinated and why must be made absolutely clear. Concerns must be addressed at community level for people who are getting vaccinated, and for people who are not.
Communicators must be re-trained on how to communicate uncertainty and risk, the difference between experimental and licensed vaccines, who is eligible and why, and the differences between ring and mass vaccination strategies and objectives.
Ring vaccination in support of other strategies: Ring vaccination should be perceived as an additional response tool to control outbreaks. Epidemiological data and evidence of sustained human-to-human transmission are important factors when deciding to implement ring vaccination.
Allocating vaccine: A prioritization mechanism and criteria to allocate supply of an experimental Ebola vaccine may be required. This will be done within the WHO R&D Blueprint (e.g. mapping manufacturers, stocks, vaccine types) and the Global Coordinating Mechanism for Research, SAGE or other advisory groups.
Vaccine quantities for ring vaccination: Ring vaccination requires far less people to be vaccinated than mass vaccination, as it only targets people at risk of infection (i.e. contacts of cases, and contacts of contacts). For example, during an EVD outbreak in Guinea Forestière in 2016 there were 13 cases, resulting in the vaccination of approximately 1,500 people in a ring vaccination strategy including eligible health care and frontline workers6.
Stockpiles and ICG: After a vaccine becomes licensed, a mechanism such as the International Coordinating Group (ICG) on Vaccine Provision or similar may be established to manage a vaccine stockpile.
Generic protocols: A generic protocol will be developed and pre-agreed by ethics committees and national regulatory authorities as a template to be used across all countries. Where necessary, the generic protocol can be adapted to a country’s specific circumstances by the Sponsor(s) and the vaccine manufacturer following the advice of national regulatory authorities and ethics committees. Regulatory approval and labelling: Experimental or unlicensed vaccines cannot be imported without regulatory approval (export and import permits) and approved vial labelling. To avoid delays, national regulatory authorities should ideally receive requests to approve protocols and labels between outbreaks, so that during an outbreak these requests can be approved promptly. In some countries, regulatory review is a slow process and may create bottle-necks that should be proactively addressed.
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Gsell, P-S et al. Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report, The Lancet Infectious Diseases, 2017 dx.doi.org/10.1016/S1473-3099(17)30541-8.
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Research/core capacity strengthening: It is important to build country capacities to implement an Expanded Access Framework in the context of EVD outbreaks. Such capabilities can also be used to deploy other experimental vaccines and therapeutics against priority pathogens included in the WHO R&D Blueprint. Maintaining research capacity and preparedness during and between outbreaks is a real challenge. During the recent DRC outbreak, MSF staff paired with Ministry of Health colleagues to work and share knowledge. Similar strategies could be developed to improve knowledge transfer in the future.
Exercises and simulations: Exercises and simulations could be conducted to help countries assess their preparedness to authorize and deploy experimental vaccine quickly, e.g. table-top exercises with an unlicensed vaccine scenario. Training: Training on basic GCP concepts is required to implement a research protocol meeting international standards. More time is generally required when training people with little or no research experience. Staff already in service could be trained as ring vaccination team members, as well as people working in other disease areas where these skills can be applied. After training on GCP, staff can be assigned to different tasks and trained in the use of specific SOPs.
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3. During the Outbreak 3.1 Overview of key preparatory and implementation steps
William Perea, Infectious Hazard Management, WHO
A number of key global initiatives have been initiated to prepare for the deployment of a licensed EVD vaccine. In 2015 the multi-partner Global Ebola Vaccine Implementation Team (GEVIT) was established to support collaboration and planning for the deployment of an EVD vaccine after licensure (marketing authorization). GEVIT has met several times and developed guidelines to request, deploy and use licensed EVD vaccines in response to outbreaks.
As no Ebola vaccine is yet licensed, the SAGE recommended in April 2017 that an experimental vaccine be used during an EVD outbreak, delivered in a ring vaccination strategy and under an Expanded Access Framework. Recently MSF has initiated discussions with Merck to develop a memorandum of understanding (MOU) and ring vaccination protocol to prepare for new EVD outbreaks in Africa. In support, WHO has contacted national authorities in twelve at-risk countries and invited them to consider this protocol.
In the May 2017 EVD outbreak, discussions on the use of experimental vaccine were initiated between the DRC Ministry of Health, WHO and MSF soon after the first cases were confirmed. A WHO/Global Outbreak Alert and Response Network (GOARN) team and an MSF Ebola vaccine team were deployed to support implementation. Communication between Merck, MSF and WHO was fluid and frequent during the outbreak.
Two steps strategy was put in place to provide access to ultralow cold chain equipment:
A loan by the Ministry of Health Guinea of -60°C -90°C freezer. It was packed and ready to be shipped in 48h.
Procurement of new equipment by WHO for vaccine in country transportation, stored in Geneva, packed ready to be shipped in 48h.
Although the vaccine and the cold chain equipment were not finally deployed, limited experience in deploying experimental vaccines made communications efforts complex and uncertain. The experience highlighted challenges in coordination, regulatory and ethical approval process, logistic and procurement preparations, vaccination strategy, community engagement. Identifying and communicating the roles and responsibilities of partners was challenging and contributed to confusion. Limited experience in deploying experimental vaccines made communications efforts complex and confusing.
3.2 Lessons learned: Likati, Bas Uélé, DRC 2017 Ebola outbreak Luis Encinas, MSF
MSF has been the primary medical non-government organisation (NGO) supporting communities to address outbreaks of viral haemorrhagic fevers since 1995, and was also the reference medical emergency organization in the field prior to 2014. The May 2017 DRC EVD outbreak was the first since that in West Africa in 2014-16, and presented an opportunity to combine case management with a cohort study protocol using a candidate Ebola vaccine under an Expanded Access Framework. As the outbreak evolved, MSF and WHO defined three potential scenarios with epidemiological criteria to justify the
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use of a candidate vaccine. Although the situation led to preparations to deploy vaccine, the criteria to initiate a ring vaccination strategy were not met. The epidemiological criteria for ring vaccination is:
evidence of sustained human to human transmission expressed as new probable/suspected/ confirmed cases, with or without new clusters
Overall the experience demonstrated a high level of interest from donors, laboratories and the public, as well as strong commitment and collaboration between partners including DRC health authorities and WHO. The MSF Epicentre unit provided epidemiological input. Local and international staff deployed were experienced in EVD outbreak management, and a task-force to mobilise additional medical and logistic capacity was quickly assembled. However, a number of areas for improvement also became apparent. Key documents were discussed but not officially approved in advance by national authorities, including the study protocol and a MOU between MSF and the Ministry of Health. There was not enough experienced national staff to follow-up and manage a cohort study. The ring vaccination cohort study was commonly confused with a mass vaccination campaign.
3.3 Preparing for ring vaccination in the DRC during Likati outbreak (2017) Jean-Jacques Muyembe-Tamfum, Ministère de la Santé Publique, DRC
The DRC is a large country of 70 million people, surrounded by countries affected by Ebola and Marburg viruses. It has experienced eight EVD outbreaks since 1976 and has subsequently developed experience and knowledge in EVD control. Two strains of Ebola virus are in circulation (Ebola Zaire and Ebola Bundibugyo), with the majority of cases from the Zaire strain. The time taken to launch an outbreak response has decreased over time, and identification and diagnosis of EVD are now more rapid than ever.
On 11 May 2017 an outbreak of EVD was confirmed in Likati, northern DRC. A central level response team was mobilized by 14 May, and international teams by 17 May. The outbreak involved eight cases (five confirmed and three probable), of which four died. 583 contacts of these cases were identified before the outbreak was declared over on 2 July 2017. During this time the use of experimental EVD vaccine in a ring strategy was considered with the agreement from the Minister of Health, national ethics committee and the affected population. After a risk/benefit analysis considering low risk of transmission, it was ultimately decided that vaccination was not necessary, as standard public health response measures seemed to be effective with no new community cases or hospital infections to justify vaccination.
The experience highlighted a number of challenges, including achieving consensus on inclusion criteria for vaccination, accessing very remote villages, transport and ensuring cold chain resources for shipping and storage. Staff required training to use experimental Ebola vaccine and there was a need to establish an effective system to monitor and manage adverse events. Many of these challenges could be addressed by strengthening local capacity to implement an Expanded Access protocol with well trained staff in GCP .
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4. During the outbreak: Feedback from Working Group discussions
4.1 Coordination and communication with stakeholders
Defining roles, responsibilities, accountability and lines of communication between government and partners is essential to avoid frustration and tension. Roles should be defined in a signed MOU between the Ministry of Health (lead) and the Sponsor of the study. Some stakeholders can be kept informed even if they do not need to be directly involved. Staff from routine Expanded Programme on Immunization (EPI) units may have no or limited roles in implementation, but could be kept informed to build capacity for future outbreaks with a licensed vaccine. Epidemiological criteria should be clarified and clearly communicated to ensure that all stakeholders understand the risk/benefit analysis and decision-making processes, and to decrease the likelihood of political influence on decisions. Simulation exercises should be held to test roles and lines of communication.
The Working Group suggested the following actions:
Define and communicate roles, responsibilities and accountability mechanisms for key stakeholders in advance.
Negotiate MOUs between governments and sponsors in advance.
Conduct simulation exercises to practice and test roles, responsibilities and communication.
Finalize and communicate decision-making criteria and processes for the use of experimental vaccine.
Improve transparency: – Share information on Expanded Access, experimental EVD vaccines
and ring vaccination strategies (e.g. websites, printed materials, links to WHO materials).
– Communicate lessons learned from Guinea ring vaccination.
Start communication with the media early. Develop in advance communication tools (fact sheets, Q&A)
4.2 Access to vaccines (including regulatory and ethical considerations)
Twelve candidate vaccines (including monovalent, bivalent and multivalent candidates) have undergone or are currently undergoing clinical development. The Phase III trial for an rVSV-vectored candidate vaccine (rVSVΔG-ZEBOV-GP), undertaken in Guinea, is the only study that has reported clinical efficacy and effectiveness for any candidate EVD vaccine. The rVSVΔG-ZEBOV-GP candidate vaccine and a prime/boost candidate vaccine based on Ad26- and MVA-vectored components (Ad26.ZEBOV/MVA-BN-Filo) have been submitted to WHO EUAL.
It is critical that protocols are reviewed and pre-approved by national regulatory authorities and ethics committees, and that agreements between manufactures and Sponsors are in place in advance of an outbreak. These preparations will facilitate the rapid adjustment of the protocol (if needed) and approval during an outbreak. Some countries may require support to develop legal instruments and
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regulatory frameworks. Insurance provisions to address compensation and liability for AEFI should also be in place in advance.
The Working Group suggested the following actions:
Hold regular consultations to review clinical data, safety, and efficacy of EVD candidate vaccines, protocols and to establish minimum approval procedures under Expanded Access. Include at-risk countries and AVAREF network as appropriate. Consider joint review of clinical data, protocols by regulatory authorities and ethics committees in Africa.
Adjust a simplified generic protocol and synopsis to assist pre-approval by national regulatory authorities and ethics committees.
Consider developing a centralized online documentation system (restricted access) for supporting documents, guidelines, SOPs and instructions to implement ring vaccination under an Expanded Access Framework.
Support ongoing mapping of regulatory capacities and regulations of each target country and identify those that may need support.
Support national regulatory authorities and ethics committees to conduct risk/benefit assessments of the use of a given experimental vaccine.
Support national authorities to communicate on the use of experimental vaccines and develop arguments to facilitate social acceptance.
4.3 Logistics and cold chain
A number of logistical challenges were highlighted in the 2017 DRC experience. Ttransport was extremely difficult, with large distances and barely passable or non-existent road infrastructure. The need to maintain temperatures of -60°C for vaccine transport and storage required the procurement of specialised cold chain equipment and expertise. As the vaccine involved a genetically modified organism, waste management and destruction of unused vaccine required strict control following SOPs. Coordination of the multiple logistics actors was demanding, as was ensuring support to the large field-based vaccination team.
The Working Group suggested the following actions:
Pre-define roles and responsibilities of each logistic actor with respect to the protocol, GCP training and training to implement SOPs. Clearly indicate the responsibilities assumed and potential liability issues.
Define coordination mechanisms for logistics and launch coordination early.
Develop an operational and logistics management framework (e.g. concept of operations or plan of action) to manage tasks, time frame and budget if not already defined and covered by the Sponsor(s).
Sponsor(s) to prepare kits of equipment for deployment (e.g. passive and active cold chain, energy, vaccination equipment, administration module, IT for data management and reporting). Develop standard reporting tools to strictly monitor and report on temperature and vaccine inventory. Nominate focal points at each level.
Conduct trainings and simulations to test logistic preparedness.
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4.4 Engaging communities for the use of experimental vaccines and interventions
Despite communication efforts, stakeholders and communities can easily confuse ring vaccination with mass vaccination campaigns. Research protocols are complex to communicate, as is explaining who gets vaccine and why. High demand for and resistance against the vaccine can both occur if stakeholders do not use the same agreed approaches and messages. In the experience of Sierra Leone, multiple candidate vaccines and multiple clinical trials contributed to further confusion in target populations. In Guinea good strategies for community engagement led to high levels of participation (see Gsell P. et al). Coordination of community engagement (CE) and social mobilization actors is challenging, and activities must adapt over time as demand and dynamics change. Capacities for CE on experimental products must be built, as most experts are only familiar with mass mobilization and information dissemination methods. Communication and engagement must be initiated early to build trust in stakeholders, implementers and the government, and to limit misinformation and rumours. Public concerns and fears (on vaccination, disruption to livelihoods, stigmatization etc.) should be listened to and addressed, including perceptions that participants are used as ‘guinea pigs’.
The Working Group suggested the following actions:
Community engagement coordination – Leverage existing CE networks and social mobilization teams – Define roles and responsibilities of partners in risk communication
(RC), CE and social mobilization. – Include CE in coordination platforms and deployed teams.
Assessing community perception, beliefs and concerns – Integrate social science approaches (e.g. anthropology, sociology,
psychology) into interventions. – Conduct operational research to better assess people’s beliefs and
practices, and to measure effectiveness of interventions. – Pre-identify trusted influencers and preferred channels/modes (oral,
visual, written) of information of target populations. – Communicate regularly throughout the event, adapt as needed, and
maintain communication between emergencies to avoid gaps.
Standard approaches and tools for community engagement (noting that delivering information on the vaccine to eligible people and informed consent is the responsibility of the Sponsor) – Ensure materials, tools and guidelines are available in local and official
languages, with visual and oral aids. – Develop materials and key messages to communicate uncertainty,
consent, adverse effects, ring vs. mass vaccination, and how decisions to vaccinate are made.
– Develop SOPs for CE. – Develop specific approaches and tools for frontline workers.
Community engagement human resources and capacity building – Draw on global and regional pools of trained RC/CE experts. – Include CE in national planning, capacity building and training. – Sensitize experts from other disciplines to CE. – Develop online training resources for CE and ring vaccination. – Map communication platforms and means of reaching populations, and
partners in priority countries. – Document CE knowledge and lessons learnt.
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4.5 Ring definition and identification of contacts
Discrepancies have been noted between the lists of contacts developed by surveillance contact tracing team and the ring vaccination team involved in the study protocol. This could be due to a number of reasons, including use of different definitions, the negative perception of surveillance teams (associated with confinement measures) by communities, or different training and supervision approaches. Surveillance contact tracers were mostly volunteers while the ring vaccination teams received specific GCP training and were closely supervised. Training and supervision is needed for all parties, including training on how to develop trust and interpersonal skills. Another difference is the need to maintain confidentiality (as per GCP and ICH requirements) has also meant that ring vaccination teams were not able to share detailed personal information about the individuals they have identified for vaccination. In some countries, access to confidential patient information may be exceptionally permitted during public health emergencies if authorized by the national regulatory authority and ethics review committee, this patient information will help to address important public health issues, however these special procedures should be authorized in advance. Many partners who have implemented contact tracing in the past have developed toolkits and best practices that can be shared with affected countries to adapt SOPs relevant for their context. To maintain this in country workforce should also be addressed since trained staff may leave or no longer be available for the next public health emergency.
The Working Group suggested the following actions:
Consider de-duplicating the roles of surveillance and contact tracing to improve quality and human resource capacity.
Review international and national regulations regarding patient confidentiality during an outbreak. Consider updating national regulation if appropriate.
Review available and make accessible contact tracing and ring vaccination guidance/tools.
Address issues of human resource sustainability (e.g. draw on surveillance/contact tracing staff from other disease areas, or train staff in generic skills that can be applied in other settings).
Consider using electronic data collection methods (e.g. tablets, smartphones, mobilephones) to facilitate contact identification data collection and comparing contact lists between ring definition teams and contact tracing teams when is authorized.
4.6 Discussion Country leadership: It is critical for country leadership to be clear and visible. Pre-approval of protocol, regulatory requirements and other documentation: Access to experimental vaccine during an outbreak is dependent on the protocol being in place and approved by the national regulatory authority and ethics committee. The study protocol and regulatory requirements (e.g. labelling, packing inserts, handling instructions, storage) should be pre-approved so that vaccine can be immediately released by the manufacturer and shipped when a request from the government is made. Legal
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documents, MOUs, insurance and other authorizations must also be discussed and agreed in advance with national authorities to prevent delays. Protocol simplification: Any changes to the protocol must be agreed to by the Sponsor(s) and manufacturer and approved by the national regulatory authority in the producing country before a vaccine can be released, in order to meet regulatory requirements. Including vulnerable populations may be challenging due to a lack of safety data available at this time. Exercises: Exercises should be held regularly for countries to practice and test the protocol and processes needed to deploy experimental vaccine. If this is only tested during an outbreak, decisions will likely be influenced by opinion and politics, rather than verified processes and experience. Involving EPI: EPI is normally responsible for vaccination campaigns using licensed products. They will have limited or no role in Expanded Access. However, efforts should be made to brief them about the study protocol and why this must be implemented by researchers with specific training (e.g. GCP, AEFIs, ultralow cold chain expertise). Regular EPI practices cannot be used, thus EPI staff can only participate if trained in GCP and SOPs of the protocol and if agreed by the Sponsor(s). Equipment and waste removal/disposal: The use of experimental vaccines may require bringing in unique equipment and kits (e.g. cold chain) and provisions to dispose of potentially bio-hazardous waste. Plans should be made to recover the cold chain and other equipment and safely dispose of waste. Communications: The research protocol team should include communication specialists to communicate clear messages around informed consent, assent and the research study. There should be a coordination between the communicators informing about general activities related to the outbreak and the response; and the communicators informing about the study and ring vaccination to avoid conflicting messages. Communication specialists can help develop messages for stakeholders, people who will potentially benefit from the vaccine and the general population. The right language and terminology must be chosen to avoid creating misunderstandings and resistance in communities. Language must be clear, consistent and accurate, but also sensitive to local customs and communities.
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5. Ongoing global preparedness efforts for the use of experimental Ebola vaccines under an ‘Expanded Access’ framework
5.1 Liability, indemnification and compensation for the use of
experimental products during outbreaks Anne Mazur, Principal Legal Officer, WHO
During the 2014-2016 EVD outbreak in West Africa, concerns were raised about potential liability risks arising from the occurrence of serious AEFI in individuals vaccinated with an experimental Ebola vaccine that had not yet been fully tested. While the manufacturer agreed to assume liability arising from failure to manufacture the vaccine in accordance with current Good Manufacturing Practices (cGMP) and agreed specifications, this did not extend to other risks arising from the use of their experimental product. Hence, governments were required to indemnify the manufacturer, donors and WHO.
WHO is currently developing a proposal to address liability for the use of experimental vaccines and compensation for individuals who suffer from serious AEFI. As part of this proposal, WHO is exploring an insurance solution to cover serious adverse events following the large scale use of experimental vaccines, i.e. where it is not possible to cover these risks by means of a clinical trial liability or similar insurance.
This would particularly be the case where WHO supplies experimental vaccines to governments for use in their country:
(i) following an Emergency Use Assessment Listing (EUAL) of the product; or
(ii) in cases where WHO deems the public health situation to be critical and a group of external experts considers the large scale deployment of the product to be warranted.
The ultimate objective of this special insurance product is to facilitate emergency response action and timely deployment of experimental vaccines in the event of infectious disease outbreaks for which no licensed vaccine exists.
While manufacturers of experimental vaccines will be required to assume liability arising from failure to manufacture their product in accordance with current Good Manufacturing Practices and agreed specifications, recipient countries will (as was the case during the 2014-2016 Ebola outbreak) as a condition for receiving experimental vaccine be required to assume liability and indemnify WHO, donors and manufacturers for other risks arising out of the use of the product. At the same time, WHO would obtain insurance coverage for the benefit of recipient countries, to provide compensation to individuals who suffer from serious AEFI.
The insurance would have two levels:
(i) a first level based on an annual premium, to keep the insurance open over time; and
(ii) a second level of insurance to be obtained when an outbreak occurs, with a premium based on agreed criteria (vaccine safety profile, Gross Domestic Product of the country where the experimental product would be used and the number of people that would receive the product).
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The insurance could also include a certain coverage for manufacturers, i.e. in case an individual refuses to accept the compensation offered under the insurance and wishes to pursue a liability claim against the manufacturer in a court of law (or any similar forum).
Next steps include further discussions with insurance brokers and consultations with stakeholders.
5.2 Regulatory preparedness for medical countermeasures Olivier Lapujade, Essential Medicines and Health Products, WHO
To support regulatory preparedness before an emergency WHO has published guidance on the assessment of medical countermeasures for public health emergencies, guidelines for the expedited review of clinical trials in public health emergencies7, and is developing guidelines on the quality, safety and efficacy of EVD vaccines8. A pre-EUAL process is being developed to facilitate informed decision-making, including defined minimum criteria and a vaccine assessment tool. Support is also being provided to national regulatory authorities and ethics committees to assess medical countermeasures and strengthen capacities for emergency response.
WHO is revising the EUAL procedure used during public health emergencies of international concern and is developing additional tools for assessment and decision-making. The Organization is also providing assistance to Member States to implement surveillance mechanisms to monitor the safety of medical countermeasures deployed during public health emergencies.
5.3 Ethical considerations for using vaccines under an Expanded Access Framework and how to involve ethics committees Abha Saxena, Information, Evidence and Research, WHO
The protocol for using an unlicensed vaccine in the context of a public health emergency must be clearly identified as either a ‘treatment’ protocol or a research cohort protocol. Even though collecting safety and efficacy data is an ethical requirement, it is not the primary purpose of the protocol under an Expanded Access Framework. This has important implications for the consent process required, as participants must be asked to consent to accepting the vaccine as well as to providing data for safety and efficacy studies.
Ethical criteria that must be considered include transparency, fairness, informed consent, freedom of choice, confidentiality, respect for the person, preservation of dignity, involvement of the community and risk-benefit assessment. The protocol must be accompanied by clear messaging and community engagement. Plans to ensure fair and equitable sharing of vaccine doses should be developed, and hard-to-access and vulnerable populations (including pregnant women and children) included where possible to ensure fairness. Ethics committees should be involved early on in order to fully understand and advise on the issues involved.
5.4 GAVI’s engagement in epidemic response Melissa Malhame, GAVI
7 May 2017 WHO Informal Consultation on options to improve regulatory preparedness to address public
health emergencies report: http://www.who.int/medicines/news/2017/PHEmeeting-reportIK-EG16_Nov_2017.pdf 8 ECBS 2017 Guidelines on the quality, safety and efficacy of Ebola
vaccines http://www.who.int/biologicals/Ebola_GL_22_Nov_2017_ZHOU.pdf?ua=1
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GAVI has made an Advance Procurement Agreement with Merck which includes making 300,000 doses available in advance of licensure. Currently 100,000 doses are in finished product and 200,000 doses in bulk. The vaccines are stored by Merck and since the vaccine is not yet licensed can only be accessed under an ‘Expanded Access’ framework. GAVI will provide funds to procure vaccine if and when it is licensed, prequalified and recommended to be stockpiled. The size and choice of vaccine for the stockpile will be aligned to WHO recommendations, and access will be through the ICG mechanism.
5.5 Discussion
Insurance: Consideration should be made to assess if the insurance options being considered can be extended to cover Sponsors and others designated in the protocol. Some countries may prefer to work with WHO over NGOs to fulfil this role. Only people who are vaccinated under the protocol will be covered.
Language: Many terms are being used and suggested for the type of protocol being proposed (e.g. research, treatment, cohort, response research), as well as the type of use it is being put towards (e.g. expanded access, compassionate use). Different audiences interpret these terms differently. Work needs to be done to develop a defined and standardized language so that all stakeholders have the same understanding.
Importance of standard regulatory process: Even though the use of unlicensed vaccine is being considered for public health emergencies, it is important not to lose sight of the need to complete the clinical evaluation and regulatory process. It is always important to base the decision to use an unlicensed vaccine on a careful risk/benefit analysis, and not to give the impression that ‘short cuts’ are being used.
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6. Improving preparedness: Feedback from Working Group discussions
6.1 Decisions to use experimental Ebola vaccines
Further clarification on the SAGE recommendations are needed regarding the epidemiological and operational criteria that would trigger the use of experimental vaccine, and the timing of when to start a vaccination strategy. If an outbreak is caused by a strain other than Zaire-strain Ebola virus, criteria should be available to guide decisions on which candidate vaccine should be used. Clarification is also needed on vaccination criteria for ‘at risk’ groups such as health care and front line workers. The Working Group suggested preparing an operational guideline to help countries understand and implement the SAGE recommendations, and to make complementary documents available online to communicate the SAGE recommendations to partners and stakeholders.
6.2 Partnership at field level
Coordination (via a national emergency operations or coordination centre) is essential to successfully integrate vaccination into overall response activities. Ring vaccination should eventually be added to the traditional pillars of EVD response of: surveillance, case investigation and contact tracing; case management and infection prevention and control; safe and dignified burial; community engagement and social mobilization; and coordination and operations support. Simulations are strongly recommended to test all aspects of the response, and may involve multiple countries. Vaccination preparation activities should be designed to strengthen research capacities that can also be used to manage other public health emergencies. Engagement with communities to enable education and preparedness should be conducted in advance. National regulatory authorities should review and pre-approve the generic protocol, with further review when more data or other vaccine candidates are available. Implementing the protocol will require the preparation and exercise of SOPs, roles and responsibilities, logistics and communication mechanisms. Existing surveillance, research, response, regulation and communication structures should be strengthened, and coordination pathways established or reinforced.
6.3 Additional tools and guidelines
Simplified tools are needed to help partners and countries implement approved guidelines. Many tools already exist on ring vaccination clinical trials, good participatory practices guidelines9, communication during outbreaks and from experiences in past EVD outbreaks. These should be pooled and made available to countries and Sponsors. Guidance should also be developed to improve coordination between contact tracing teams and vaccinators. Training modules can be developed to strengthen the use of these tools, and access to this training should be made available to all countries at risk of EVD and to partners interested in supporting the use of experimental EVD vaccines.
9 WHO. Good participatory practice guidelines for trials of emerging (and re-emerging) pathogens that are
likely to cause severe outbreaks in the near future and for which few or no medical countermeasures exist (GPP-EP). Outcome document of the consultative process. 2016 available at http://www.who.int/blueprint/what/norms-standards/GPP-EPP-December2016.pdf?ua=1.
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7. Closing session
7.1 Next steps Ana Maria Henao-Restrepo, Immunization Vaccines and Biologicals, WHO
Many issues were identified during the workshop that will require collective effort to resolve. The benefits of deploying experimental EVD vaccine in the context of a research protocol were discussed, as well as suggestions on how to integrate vaccination into existing EVD response interventions. It was also clear from discussions and recent experience that timely and transparent communication with partners, stakeholders and communities is critical.
Immediate steps to take before the next outbreak include:
Adjust existing protocols and pre-approve ring vaccination research protocols;
Adjust existing ring vaccination SOPs and guidelines to implement ring vaccination;
Continue work with national regulatory authorities and ethics committees to build capacity to review requests in advance or during public heath emergencies for clinical studies and/or Expanded Access to experimental Ebola vaccines;
Develop guidelines to establish, communicate and coordinate roles and responsibilities for each partner involved in an experimental vaccine deployment;
If the country will implement the Expanded Access study protocol (be the Sponsor), strengthen country capacities for experimental vaccination deployment including GCP, monitoring and oversight, logistics and cold chain will need to be provided.
Simulations to test capacities, SOPs and coordination mechanisms;
Further discussions with partners and manufacturers on how to manage an EVD outbreak caused by non-Zaire strain;
A WHO secretariat will compile these activities and develop an action plan. This will be circulated to workshop participants for verification, and to assign responsibilities and support for each area of work.
7.2 Closing comments Mike Ryan, Deputy Executive Director, WHO Health Emergencies Programme
Dr Ryan thanked the participants for their work over the past days to develop a common language and understanding of the issues around the use of experimental EVD vaccine. This is a collective opportunity and responsibility to add an important intervention to efforts to control EVD. Enabling factors must be amplified and barriers removed to make a vaccine deployment happen, if and when it is needed. Open collaboration and communication among partners should be continued and stakeholders held self-accountable to plans and timelines to move these issues forward. This is a transformative opportunity to bring a ground-breaking intervention to the people and communities facing the threat of EVD.
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Annex 1
List of Participants
EXTERNAL PARTICIPANTS
Tony BYAMUNGU UNICEF Country Office Democratic Republic of the Congo
Gail CARSON International Severe Acute Respiratory and Emerging Infection Consortium United Kingdom
Rosalind CARTER WERTHEIM US Centers for Disease Control and Prevention United States of America
Beth-Ann COLLER Merck United States of America
Heather DEEHAN United Nations Children’s Fund Denmark
Rene EKPINI UNICEF West and Central Africa Regional Office Senegal
Luis ENCINAS Médecins Sans Frontières Switzerland
Libby HIGGS US National Institutes for Health United States of America
Pierre HONNORAT World Food Programme Italy
Halimatou KEITA Ministère de la Santé Guinea
Coralie LECHELLE Médecins Sans Frontières Switzerland
Nicki LURIE Coalition for Epidemic Preparedness and Innovation Norway
Emilie MACHER Médecins Sans Frontières Switzerland
Frank MAHONEY International Federation of the Red Cross and Red Crescent Societies Switzerland
Melissa MALHAME Global Alliance for Vaccination and Immunization (GAVI) Switzerland
Marion MENOZZI-ARNAUD Global Alliance for Vaccination and Immunization Switzerland
Roberto MILIOTI Médecins Sans Frontières Switzerland
Jules MILOGO Merck United States of America
Jean-Jacques MUYEMBE TAMFUM Ministère de la Santé Publique Democratic Republic of the Congo
Gunnstein NORHEIM Coalition for Epidemic Preparedness and Innovation Norway
Pierre ROLLIN US Centers for Disease Control and Prevention United States of America
James RUSSELL Ministry of Health and Sanitation Sierra Leone
Micaela SERAFINI Médecins Sans Frontières Switzerland
Stephen SOSLER Global Alliance for Vaccination and Immunization Switzerland
Esther STERK Médecins Sans Frontières Switzerland
Facinet YATTARA Ministère de la Santé Guinea
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WORLD HEALTH ORGANIZATION
COUNTRY REPRESENTATIVE OFFICES
Ernest DABIRE WHO Representative Office in Democratic Republic of the Congo
Vital MONDONGE WHO Representative Office in Democratic Republic of the Congo
Robert MUSOKE WHO Representative Office in Sierra Leone WHO HEADQUARTERS
Virginia BENASSI Immunization Vaccines and Biologicals, Family Women's and Children's Health
Aphaluck BHATIASEVI Infectious Hazard Management, WHO Health Emergencies Programme
Alejandro COSTA Infectious Hazard Management, WHO Health Emergencies Programme
Pat DRURY Infectious Hazard Management, WHO Health Emergencies Programme
Godwin ENWERE Essential Medicines and Health Products, Health Systems and Innovation
Pierre FORMENTY Infectious Hazard Management, WHO Health Emergencies Programme
Mara FRIGO Infectious Hazard Management, WHO Health Emergencies Programme
Gaya GAMEWHAGE Infectious Hazard Management, WHO Health Emergencies Programme
Pierre GSELL Immunization Vaccines and Biologicals, Family Women's and Children's Health
Ana Maria HENAO-RESTREPO Immunization Vaccines and Biologicals, Family Women's and Children's Health
Sophie IOOS Infectious Hazard Management, WHO Health Emergencies Programme
Bertand JACQUET Emergency Operations, WHO Health Emergencies Programme
Qiu Yi KHUT Infectious Hazard Management, WHO Health Emergencies Programme
Souleymane KONE Immunization Vaccines and Biologicals, Family Women's and Children's Health
Rafael LA ROTTA Finance, General Management
Olivier LAPUJADE Essential Medicines and Health Products, Health Systems and Innovation
Anaïs LEGAND Infectious Hazard Management, WHO Health Emergencies Programme
Ira LONGINI Immunization Vaccines and Biologicals, Family Women's and Children's Health
Anne MAZUR Principal Legal Officer, Director General’s Office
Bernadette MURGUE WHO Health Emergencies Programme
Tim NGUYEN Infectious Hazard Management, WHO Health Emergencies Programme
William PEREA Infectious Hazard Management, WHO Health Emergencies Programme
Isis PLUUT Essential Medicines and Health Products, Health Systems and Innovation
Marie-Pierre PREZIOSI Immunization Vaccines and Biologicals, Family Women's and Children's Health
Guillaume QUEYRAS Emergency Operations, WHO Health Emergencies Programme
Ximena RIVERAS BALTA Immunization Vaccines and Biologicals, Family Women's and Children's Health
Alex ROSEWELL Emergency Operations, WHO Health Emergencies Programme
Mike RYAN Deputy Executive Director, WHO Health Emergencies Programme
Jordi SACRISTAN LLOBET Emergency Operations, WHO Health Emergencies Programme
Abha SAXENA Information, Evidence and Research, Health Systems and Innovation
Annex 2
Agenda
Monday, 18 September 2017
Time Session Topics
9:00 – 9:30 Session 1: Opening Opening remarks Objectives and methodology of the workshop
9:30 – 10:45 Session 2: Before the outbreak
Ring vaccination: The basics Expanded Access: MSF rVSV Contingency Plan MSD V920 vaccine
10:45 – 11:15 Coffee break
11:15 – 12:30 Session 2: (cont.) Regulation of medicines and other health technologies
Expanded Access Framework to access experimental Ebola vaccines in the context of outbreaks
GCP and SOP training of field staff for ring vaccination
Discussion
12:30 – 13:30 Lunch
13:30 – 14:30 Session 3: During the outbreak: the experience in DRC
Overview of key preparatory and implementation steps
Lessons learned: Likati, Bas Uélé, DRC 2017 Ebola outbreak
Preparing for ring vaccination in the DRC during Likati outbreak (2017)
Discussion
14:30 - 14:45 Session 4: During the outbreak: Working Group discussions
Introduction to Working Group methodology Working Group discussions
15:45 – 16:15 Coffee break
16:15 – 17:30 Session 4: (cont.) Working Group discussions
17:30 Wrap up
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Tuesday, 19 September 2017
Time Session Topics
9:00 – 10:40 Session 4: (cont.) Feedback from Working Group discussions
10:40 – 11:10 Coffee break
11:10 – 12:30 Session 5: Global efforts to improve preparedness for the use of experimental Ebola vaccines under an ‘Expanded Access’ framework
Liability, indemnification and compensation for the use of investigational products during outbreaks
Regulatory preparedness for medical countermeasures
Ethical considerations for using vaccines under an Expanded Access framework and how to involve ethics committees
GAVI’s engagement in epidemic response Discussion
12:30 – 13:30 Lunch
13:30 – 15:00 Session 6: Recommendations and tools to improve preparedness: Working Group discussions
Working Group discussions
15:00 – 15:30 Coffee break
15:30 – 17:00 Session 6: (cont.) Feedback from Working Group discussions
17:00 – 17:30 Session 7: Closing Wrap up Conclusions and Next Steps Meeting close
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Annex 3
During the outbreak: Working Groups and participants
1. COORDINATION AND COMMUNICATION WITH STAKEHOLDERS
Gail CARSON
Rosalind CARTER WERTHEIM
Beth-Ann COLLER
Pat DRURY
Luis ENCINAS
Pierre FORMENTY
Halimatou KEITA
Melissa MALHAME
Vital MONDONGE
Jean-Jacques MUYEMBE TAMFUM
William PEREA
Alex ROSEWELL
2. ACCESS TO VACCINES Alejandro COSTA
Rafael LA ROTTA
Olivier LAPUJADE
Anaïs LEGAND
Ira LONGINI
Emilie MACHER
Marion MENOZZI-ARNAUD
Tim NGUYEN
Gunnstein NORHEIM
Micaela SERAFINI
Facinet YATTARA
3. LOGISTICS AND COLD CHAIN Virginia BENASSI
Heather DEEHAN
Pierre HONNORAT
Bertand JACQUET
Souleymane KONE
Roberto MILIOTI
Jules MILOGO
Robert MUSOKE
Guillaume QUEYRAS
Jordi SACRISTAN LLOBET
4. COMMUNITY ENGAGEMENT AND COMMUNICATION
Aphaluck BHATIASEVI
Tony BYAMUNGU
Ernest DABIRE
Rene EKPINI
Mara FRIGO
Gaya GAMEWHAGE
Frank MAHONEY
Coralie LECHELLE
Isis PLUUT
James RUSSELL
5. RING DEFINITION AND IDENTIFICATION OF CONTACTS
Godwin ENWERE
Pierre GSELL
Ana Maria HENAO-RESTREPO
Libby HIGGS
Sophie IOOS
Nicki LURIE
Ximena RIVERAS BALTA
Pierre ROLLIN
Stephen SOSLER
Esther STERK
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Annex 4
Improving preparedness: Working Groups and participants
1. DECISIONS TO USE EXPERIMENTAL EBOLA VACCINES
Virginia BENASSI
Beth-Ann COLLER
Alejandro COSTA
Rene EKPINI
Mara FRIGO
Ana Maria HENAO-RESTREPO
Rafael LA ROTTA
Marion MENOZZI-ARNAUD
Roberto MILIOTI
Robert MUSOKE
Tim NGUYEN
Guillaume QUEYRAS
James RUSSELL
Jordi SACRISTAN LLOBET
2. PARTNERSHIPS AT FIELD LEVEL Gail CARSON
Rosalind CARTER WERTHEIM
Pat DRURY
Luis ENCINAS
Godwin ENWERE
Pierre FORMENTY
Libby HIGGS
Pierre HONNORAT
Halimatou KEITA
Souleymane KONE
Nicki LURIE
Jules MILOGO
William PEREA
Alex ROSEWELL
Marie-Pierre PREZIOSI
Ximena RIVERAS BALTA
Stephen SOSLER
3. ADDITIONAL TOOLS AND GUIDELINES Aphaluck BHATIASEVI
Ernest DABIRE
Heather DEEHAN
Pierre GSELL
Sophie IOOS
Bertand JACQUET
Olivier LAPUJADE
Emilie MACHER
Melissa MALHAME
Vital MONDONGE
Jean-Jacques MUYEMBE TAMFUM
Gunnstein NORHEIM
Isis PLUUT
Pierre ROLLIN
Esther STERK
Facinet YATTARA
