Global Ebola Vaccine Implementation Team (GEVIT) Regional Workshop

Transcription

1 MEETING REPORT Global Ebola Vaccine Implementation Team (GEVIT) Regional Workshop 27 to 29 October 2015, Geneva, Switzerland Rev. 1 World Health Organization All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. WHO/EVD/Meet/HIS/16.1

2 Contents Contents... 2 Abbreviations & acronyms... 3 Executive Summary... 4 Introduction... 5 Session I: External factors that affect GEVIT s work... 6 Session II: Country situation and challenges for preparedness Session III: Presentation of the GEVIT working groups work Session V: Review of GEVIT documents and materials Session VI: Agreement and next phase Annexes Annex 1: Programme Annex 2: List of Participants

3 Abbreviations & acronyms AEFI CDC CIG DPLM EPI EUAL EV EVD FDA GEVIT GMP HCW ICC ICG IDRS IDSR IFRC IPV M&E MoH MSF MVA NGO NRA PHEIC ppt R&D RED SAGE topvbopv adverse event following immunization Centers for Disease Control and Prevention (US) country implementation guide Direction de la Prévention de la Lutte contre la Maladie Expanded Programme on Immunization emergency use assessment and listing process Ebola virus Ebola virus disease US Food and Drug Administration Global Ebola Vaccine Implementation Team Good Manufacturing Practices (WHO) health-care worker immunization inter-agency coordination committee International Coordinating Group infectious disease reporting system integrated disease surveillance and response International Federation of Red Cross and Red Crescent Societies inactivated polio vaccine monitoring and evaluation Ministry of Health Médecins sans Frontières modified vaccinia-virus Ankara non-governmental organization National Regulatory Authority public-health emergency of international concern PowerPoint (presentation) research and development reaching every district Strategic Advisory Group of Experts on Immunization trivalent-bivalent oral polio vaccine UNICEF United Nations Children s Fund WG WHO working group World Health Organization 3

4 Executive Summary Between 27 and 29 October 2015, a Global Ebola Vaccine Implementation Team (GEVIT) regional workshop was convened at the World Health Organization (WHO) headquarters in Geneva with the goal of agreeing on the final steps required to complete, by December 2015, the development of a plan for future Ebola vaccine use and to define a way forward for 2016 and beyond. The focus of this workshop was on fostering technical discussions, and not issuing WHO recommendations. The meeting was an essential milestone to obtain insights on the guidance documents developed to support the planning for the potential deployment of Ebola vaccines, and to advance and integrate plans with the entire GEVIT team, including countries and essential partners. By means of plenary presentations, group discussions and a series of simulation exercises, the workshop focused on the following three objectives: 1) to discuss draft documents and tools, among GEVIT members and with country representatives, to ensure they are relevant, and to address feasible strategies to foreseen challenges to Ebola vaccine use; 2) to ensure GEVIT is addressing all important steps for vaccine use in the case of a future outbreak in the presence of a licensed product; 3) to discuss options for a way forward. The main topics covered during the three-day workshop included: external factors that affected GEVIT s work, such as clinical trials, progress and results; country situations and challenges for preparedness, including presentations from Democratic Republic of the Congo, Guinea, Liberia and Sierra Leone; presentation and review of the GEVIT working groups work, including simulation exercises to assess to what extent the different GEVIT materials would be useful and adequate, and the changes required; agreements and way forward to finalize the GEVIT documents and accompanying materials. During the course of the workshop, the following broad work priorities for GEVIT were proposed for 2016, and beyond: Global, regional and country integration of the Ebola vaccination component with the overall Ebola preparedness and response, as well as with the Expanded Programme on Immunization (EPI), considering that preparatory activities could be organized before vaccine licensure. Consolidation of the International Coordinating Group (ICG) processes and related contingency funds. Coordination of regular reassessments, and updates of the GEVIT Practical Guidance on the Use of Ebola Vaccine in an Outbreak Response and tools, as new information becomes available. Technical assistance in the post-licensure period will require GEVIT to reconvene and strategize on how to best provide cooperation to countries in light of the new information available. 4

5 Introduction Welcome address Dr Jean-Marie Okwo-Bele, Director Immunization, Vaccines and Biologicals WHO headquarters, Geneva, Switzerland. Dr Okwo-Bele opened the meeting and highlighted the milestones achieved in the drive towards the end of the exceptionally large 2014 to 2015 Ebola outbreak, including a full week without any new Ebola-confirmed cases and the very encouraging interim results of a Phase 3 trial of an Ebola vaccine which demonstrated the power of a partnership including national authorities, research institutions, donor agencies and vaccine manufacturers. He also touched on the global expectation and the critical need to be ready if and when another outbreak of Ebola strikes, commencing with the WHO s Strategic Advisory Group of Experts on Immunization (SAGE) provisional recommendations for use of Ebola vaccines and continuing with the work undertaken by GEVIT to successfully deploy and use a licensed vaccine in, eventual, affected countries. He finished by thanking partners and ministries of health of Guinea, Liberia and Sierra Leone, as well as those of the Democratic Republic of the Congo and of Uganda, for taking time away from the many important issues they are dealing with, and wished them a very productive workshop. Context and objectives of the workshop Dr Marie-Pierre Preziosi, Medical Officer, Initiative for Vaccine Research, Immunization, Vaccines and Biologicals, WHO headquarters, Geneva, Switzerland. The regional workshop was an essential milestone to gain insights on the guidance documents developed to support the planning for potential deployment of Ebola vaccines, to advance and to integrate plans together with countries, the entire GEVIT team and essential partners. The overall goal of the workshop was to agree on the final steps required to complete the development of a plan for future Ebola vaccine use, by December 2015, and to define a way forward for 2016 and beyond. By means of plenary presentations, group discussions and a series of simulation exercises, the workshop focused on the following three objectives: To discuss draft documents and tools among GEVIT members and with country representatives, to ensure they are relevant and address feasible strategies to foreseen challenges to Ebola vaccine use. To ensure GEVIT is addressing all important steps for vaccine use through a simulation exercise of a future outbreak in the presence of a licensed product. To discuss options for a way forward. 5

6 Session I: External factors that affect GEVIT s work Progress and outcomes of Ebola vaccines clinical trials Dr Ana Maria Henao-Restrepo, Medical Officer, Initiative for Vaccine Research, Immunization, Vaccines and Biologicals, WHO headquarters, Geneva, Switzerland. Presentation available electronically. No vaccine-related serious adverse events were observed to date in the Guinea trial of the rvsv ZEBOV vaccine. All vaccinated participants who went on to develop the disease, experienced an onset of symptoms within six days after vaccination, indicating that these cases were already infected before receiving the vaccine. The Ring vaccination trial has been extended to Sierra Leone, with children from six years of age and adolescents eligible to participate in the trial. This extension of age was also applied to the Guinea trial. The vaccine is currently stored at -80 C at all times. These low temperatures were kept to ensure that changes in temperature would not affect the results of the clinical trial. The scientific rigour of the study was combined with the community communication and engagement. A continuous and dynamic exchange with the community promoted community engagement and acceptance of the vaccine. Sierra Leone representatives noted that vaccine rejection in the communities frequently occurred and confirmed that more and continuous community engagement and advocacy is required to increase vaccine acceptance. They also communicated that, even though pregnant women were not eligible to participate in the clinical trial, a few did receive the vaccine inadvertently and would need to be followed up. Vaccination continues to be implemented in the context of the clinical trials, with contacts and contacts of contacts being targeted for vaccination. Survivors and their contacts are not being vaccinated however. At present, the objective is to make the vaccine available to the closest intimate partners of the survivors, but further rigorous evaluation of this strategy is required within a clinical study context. The virus lingers in some survivors and follow-up of survivors is taking place. There is limited information on how survivors become sick once again, and recent investigation could not identify an obvious chain of transmission. Research is ongoing in this regard. At present, it is not known how long vaccine protection will last, and this is an important factor to consider when planning vaccine introduction. Ebola, unlike afflictions such as measles, does not affect swathes of people in a community, but rather it affects individuals and their close contacts. The disease can be controlled and stopped, however, through effective public-health measures. Emergency-use recommendation Mr Olivier Lapujade, Scientist, Prequalification Team, Essential Medicines and Health Products, WHO headquarters, Geneva, Switzerland. Presentation available electronically. The emergency-use assessment and listing process (EUAL) is not a WHO prequalification process. It is a time-limited special circumstance procedure, where vaccines are assessed as fit for use in an emergency situation, despite the fact that not all the data usually required is available. The criteria for the use of an EUAL include a public-health emergency of international concern (PHEIC) declared by the WHO Director General. The 2014 Ebola crisis highlighted the need for such an emergency process, and similar procedures are now also available for medicines and vitro diagnostics. EUAL is not a regulatory authorization, but rather a recommendation for countries to provide guidance in their decision-making process as to whether to use the vaccine or not. The criteria required for an EUAL include: a declared PHEIC; the lack of routine marketing authorization of a vaccine for the disease in question; a vaccine manufactured in accordance with the WHO Good Manufacturing Practices (GMP) and manufactured in a country whose National Regulatory Authority (NRA) is assessed as functional according to the WHO vaccine regulatory standards, and an attestation from the producer of the intention to complete the vaccine development and apply for WHO prequalification. All the documents required for a clinical trial authorization are also needed for requesting an EUAL. These include technical documents relating to vaccine safety and performance, including documentation of the consistency of vaccine batches. 6

7 WHO may consider reviewing a candidate vaccine for EUAL that does not meet all these requirements. EUAL applications are submitted to, and reviewed by, the WHO prequalification team. As new data on vaccine quality, safety and efficacy emerge, they are submitted to WHO for re-evaluation. One condition for reviewing data for a specific vaccine is the willingness of the manufacturer. Rolling submission is accepted and the quality of the vaccine is a very important part of the assessment. The listing will generally remain valid for a period of 12 months, whereas once a vaccine has been prequalified by WHO, the information will be reviewed every 18 months. rvsv ZEBOV vaccine storage at a temperature of -80 C is not compliant with the criteria for programmatic suitability of vaccine candidates for WHO prequalification the current storage conditions were maintained strictly for the clinical trials. At present, insufficient data is available on vaccine stability for storage at -20 C or higher; however, further stability evaluation is being undertaken by the manufacturers. WHO recommends that the final decision with regard to the use of the vaccine be made within the country. Countries are required to carefully analyse the proposed interventions and to be responsible for the use and safety of the vaccine. For example, within four months, Sierra Leone received 18 expressions of interest for potential clinical trials, which represented a challenge to expertly review them. When implementing EUAL, WHO always involves the countries and ensures that training is conducted at country level. Public-health agencies are active in training and advocacy at country level, and workshops and meetings are organized for the NRAs when necessary. The risk/benefit analysis is key in the decision-making process and may vary with factors such as the disease case-fatality case rate or the availability of treatment. Countries need to make informed decisions at all levels in their preparedness to accept an EUAL vaccine. Further information can be found at (WHO public reports of EUAL assessments will be available on the WHO website). Update on SAGE draft recommendations Dr Thomas Cherian, Coordinator, Immunization, Vaccines and Biologicals, WHO headquarters, Geneva, Switzerland. Presentation available electronically. During its October 2015 meeting, SAGE concluded, based on available data, that vaccination is likely to provide added value in controlling outbreaks of Ebola virus disease (EVD) caused by Zaire ebolavirus (ZEBOV) species. Currently, there are no data to support any recommendations on vaccines against other species of Ebolavirus. However, one leading candidate vaccine has a multivalent boost component (MVA), and a bivalent ChAd3-vectored Zaire-Sudan ebolavirus vaccine is under development. SAGE noted that candidate vaccines are currently only being used in the context of clinical trials (or in exceptional circumstances in countries where no trial is ongoing) to respond to a new confirmed EVD case within the context of expanded use of an investigational vaccine. Recommendations for use as an additional publichealth tool will depend on the vaccines receiving regulatory approval (i.e. full licensure, conditional licensure or emergency-use authorization outside a clinical trial setting). In light of the emerging data on the persistence of Ebola virus in survivors of EVD and transmission of infection to sexual contacts, SAGE also noted that the expanded use of vaccines in contacts of survivors is under consideration within the context of expanded use of an investigational vaccine as one element of a study. Provisional recommendations: Based on review of current data, SAGE made provisional recommendations that are not vaccine specific and will be reviewed and revised in light of the emerging data from different Ebola vaccines. These provisional recommendations are published in the Weekly Epidemiological Record; WER. 2015:90(50): available at ( 7

8 Modelling the impact of vacination strategies Dr Rosalind Eggo, Research Fellow, London School of Hygiene and Tropical Medicine, London, The United Kingdom. Presentation available electronically. Analysis of health-care workers vaccination strategy: Health-care workers (HCW) are at very high risk, particularly at the outset of Ebola epidemics. They may also play a role in amplifying initial disease spread. Therefore, vaccination of HCW has potential populationlevel effects by limiting infection spread to the community. The proposed model showed that vaccination of HCW can prevent cases in both HCW and in the community, with the benefit that the number of vaccine doses needed is much smaller (900 doses for HCW vaccination strategy versus for the community vaccination strategy). A representative from the Guinea trial mentioned that the experience also showed a positive impact of vaccinating all HCW, prior to starting Ring vaccination in the community, as a means to set an example and demonstrate vaccine safety to the community. An important point to highlight is that, without an early start of the HCW vaccination campaign, the protection of HCW is significantly lower; even a delay of one month from the first confirmed case to vaccination of HCW diminishes the effect significantly, both in HCW and the community. Among the main limitations of the HCW model used, is the local definition of HCW, which may vary from the definition used in the model, both geographically and through time. Also, the model does not consider the depletion of HCW due to morbidity and mortality, or to HCW leaving posts, and the model assumes homogeneous mixing of HCW and community members. Finally, the duration of protection of vaccine is a key factor that is still unknown. Analysis of Ring vaccination strategy: The randomized clinical trial in Guinea gave the clearest evidence on the Ring vaccination strategy. It has shown to be least effective if the cases who escape detection have a high reproduction number. It is worth noting that the reproduction number can change over time. The strategy may have to consider the need to widen Ring, or to be supplemented with more widespread vaccination, which then has stockpile implications. The main limitations of the Ring vaccination model used include: the reliance on data from the early part of the epidemic; the fact that clustering of cases and contacts is not included in the model, and that there is no account of depletion of susceptibles in the model. Analysis of Mass vaccination strategy (district, country): Even though Ebola vaccination is not preventive but reactive, the effectiveness of a mass vaccination campaign is highly dependent on its timing and, according to this model, is only appropriate if conducted in the earliest possible timescale. Late vaccination has little impact and very high costs (in the number of doses deployed). The main limitations of the mass vaccination model include: vaccination in a district ends only when 70% coverage is reached, or at the end of the simulation (one year) so the number of doses deployed in the model is an upper limit; the importation of cases do not account for the region that imported cases are from because those data are not available, and that the model assumes homogeneous mixing within a district, again because data are not available at a lower spatial scale although the observed epidemic in West Africa did display spatial heterogeneity within districts. Similarly to the other analyses, the duration of protection is unknown. International Coordinating Group (ICG) Mr Alejandro Costa, Scientist, Control of Epidemic Diseases, Pandemic and Epidemic Diseases, WHO headquarters, Geneva, Switzerland. Presentation available electronically. The International Coordinating Group (ICG) on vaccine provision for epidemic disease control is currently managing four vaccine stockpiles, respectively, for each of the following diseases: smallpox, meningitis, yellow fever and cholera. An ICG mechanism is now under discussion for Ebola vaccine. The ICG was established in 1997 as a result of International Federation of Red Cross and Red Crescent Societies (IFRC), Médecins sans Frontières (MSF), UNICEF and WHO combined efforts to address an emergency situation in 1996, whereby, during the largest recorded outbreak of meningitis in Africa, the emergency response 8

9 exhausted international vaccine reserves. The objectives of the ICG include: ensuring rapid access to vaccines together with injection devices for countries experiencing epidemics; promoting the optimal use of these resources (especially when stock is limited), and coordinating international efforts in preparing for and responding to epidemics. The basic principles of the ICG include: timely arrival of vaccines for an effective outbreak response where most needed; fairest distribution of the vaccine, careful assessment of risks and benefits global stock is managed by an international partnership; work with manufacturers to ensure availability of an emergency stock of supplies at global level; use and promotion of epidemiological and operational criteria for vaccine release; standard operating procedures; established financial mechanisms to purchase emergency supplies and ensure sustainability. The ICG mechanism components include stock management, storage, management of applications and decision-making. The decision-making is conducted within 48 hours, based on consensus. When the organizations are in disagreement, teleconferences are convened to reach consensus. The ICG decision can be either approval, partial approval, more information needed, or no approval. The conditions to release the vaccine for procurement and shipping include: evidence of an ongoing outbreak laboratory confirmation of the pathogen responsible feasibility of conducting a vaccination campaign (security, partners in the field) adequate storage conditions and resources plan of action for mass vaccination. The target date for vaccine arrival onsite is seven days from request approval, which includes the vaccine to be ready in 48 hours, plus five days for shipping it to the affected country. The ICG has strategies in place to minimize the chances of a vaccine shortage in case of an outbreak. For example, with meningitis, yellow fever and cholera, close collaboration with the manufacturers was maintained over the years, instead of only interacting with them during the procurement process. The ICG also encourages other manufacturers to produce vaccine so there are more options to produce extra vaccines quickly if needed. With regard to efforts to shorten the ICG process for Ebola, it is important to note that the main cause of delays is the time required to collect the necessary evidence. Countries may take one month to submit an application and, when the vaccines arrive in country, it may result in an additional delay of one month to initiate the vaccination campaign. The ICG partners have the responsibility to ensure that the vaccines are deployed in such a way that they will yield the greatest impact. The ICG will always require an application and the minimum information required, so an outline of the plan of action will not suffice. Once the application is received and all the necessary information has been completed, the ICG can make a decision within two hours. With regard to thermostability, at present there is insufficient stability data available from the manufacturers. Minimal capacity for the most affected countries, including Democratic Republic of the Congo and Uganda, is being planned on a global level by the GEVIT cold-chain and logistics team. 9

10 Session II: Country situation and challenges for preparedness Epidemiological situation and preparedness to the introduction of Ebola vaccine in Guinea Dr Samah Yombouno, Chief of Vaccine Logistics, and Dr James Richard, Chief of Surveillance Section, Ministry of Health, Conakry, Guinea. Presentation available electronically. Given the magnitude of the current Ebola outbreak in Guinea, the country has been preparing for the introduction of the Ebola vaccine. There are several management and coordination bodies currently in the country, including an immunization inter-agency coordination committee (ICC), a crisis management committee and a piloting committee at the central level, as well as support from non-governmental organizations (NGOs) and other entities (including media) at peripheral levels. The Guinea vaccine trial has strengthened the technical and operational capacities and infrastructure of the country. Communication strategies have also been enhanced through the trial, with advocacy efforts and commitment of authorities at all levels. There are several surveillance systems in place in the country, including a routine surveillance system for specific diseases within the Direction de la Prévention de la Lutte contre la Maladie (DPLM), an EPI surveillance system for EPI target diseases and a daily surveillance system for Ebola virus disease (EVD) with a total of 38 national and international WHO experts teams. Additionally, a dedicated epidemiological team investigates suspected cases and analyses the situation. In spite of this, surveillance remains a challenge in Guinea. Guinea has developed a plan to strengthen surveillance, but currently there are insufficient funds to implement it. One of the greatest negative factors for Ebola surveillance has been contacts that flee to a neighbouring country; however, now there is a strategy to share information about contacts between countries. A green (free) phone line 115 offers a solution for surveillance and communication issues in the Ebola response. Surveillance systems are being strengthened for Ebola, including immediate notification of new cases to the national level. Guinea will use this experience to strengthen all future surveillance systems including adverse events following immunization (AEFIs). Forms are defined for each reporting level; district, regional and national. With regard to EPI communication activities, the priority for all communication activities in 2014 and 2015 has focused on the Ebola epidemic. Messages focused heavily on resistance related to prevention, and control measures, in relation to the Ebola epidemic. Guinea is currently trying to integrate EPI messages into general communication strategies, for which a national communication plan, that includes Ebola and EPI, is being developed and will be finalized soon. Ebola surveillance overview in Sierra Leone Dr Dennis Marke, EPI Programme Manager, and Mr Roland Conteh, National Surveillance Programme Manager, Disease Prevention and Control (DPC), Ministry of Health and Sanitation, Freetown, Sierra Leone. Presentation available electronically. The Ebola response in Sierra Leone has been coordinated by a military-led command and control structure, with strong political commitment. The implementation of a quarantine strategy has been very useful, i.e. by keeping contacts in quarantined areas the country was able to contain transmission. Food supplies and psychosocial support was provided, and social mobilization pillars were involved. The outbreak revealed the need to strengthen the surveillance system, with incomplete or poor-quality data in some areas, staff payment issues and insufficient personnel trained in disease surveillance. Other challenges identified include slow behavioural change regarding disease perception, burial and other practices, and weak coordination among response partners. Some strengths of the current system include a strong cold-chain infrastructure, processes available for AEFI case reporting and data-collection tools and investigation forms at all levels, among others. Some weaknesses include insufficient legislation, trained personnel and budget for pharmacovigilance, and weak policy, guidelines and standard procedures for AEFI activities. Community engagement also needs to be improved to address the issue of people moving between countries. 10

11 Ebola has improved the country s surveillance capacity, and it is now in the process of reorienting the surveillance officers to focus on all vaccine-preventable diseases. Sierra Leone is in the middle of their 42- day countdown to being declared Ebola-free. The focus is now on maintaining a sensitive surveillance system, with integrated disease surveillance and response (IDSR) training being completed and focused on community-based surveillance to identify cases. The country will move into new surveillance systems at zero plus 90 days, with a focus on cross-border collaboration. Liberia presentation Mr Adolphus Clarke, Deputy EPI Manager, Ministry of Health and Social Welfare, Monrovia, Liberia. Presentation available electronically. The country has many vaccination challenges coming up in 2016; campaigns, inactivated polio vaccine (IPV) introduction, trivalent to bivalent oral polio vaccine (topv-bopv) switch and rebuilding the EPI programme, among others. The introduction of Ebola vaccine will be possible, but the country does not have capacity for a -80 C cold chain. A great lesson learned from the Ebola epidemic is that surveillance is not a stand-alone activity. The surveillance system is moving towards a One Health approach with an integrated system within the infectious disease reporting system (IDRS) for pharmacovigilance, vaccine-preventable diseases and Ebola. A strong surveillance system will be crucial to quickly implement vaccination after detection of the first confirmed case. Regarding social mobilization related to survivors, the country uses the reaching every district (RED) strategy with the psychosocial support pillar to improve community ownership, working with traditional healers and teachers, etc. Survivors were also part of this effort. After being declared Ebola-free, Liberia had a new confirmed case, hence the EPI recovery plan is important. The country will need to use the lessons learned from Ebola to move forward. There is a need to move away from vertical towards integrated programmes. Four decades of Ebola outbreaks experience in Democratic Republic of the Congo Professor Jean-Jacques Muyembe Tamfum, Director of the National Institute of Biomedical Research (INRB), Kinshasa, Democratic Republic of the Congo. Presentation available electronically. Democratic Republic of the Congo has suffered Ebola outbreaks since 1976, and these are increasingly frequent due to a range of factors such as a better surveillance system and the habits for consumption and handling of bush meats. The national strategy to implement public-health interventions for Ebola outbreak control has evolved to include social mobilization, community engagement and dialogue, case management, safe burials, psychosocial support, clean water, hygiene and sanitation, mobile laboratories, associated research and epidemiological surveillance. In Democratic Republic of the Congo, Ebola outbreaks are localized without significant expansion and may be kept under control using simple public-health control measures based on a community approach. The community approach aims at early community engagement and early ownership for implementing Ebola prevention and control measures. The message to the community is particularly important, and it is imperative to avoid any contradictions. At the outset, the messaging to the population was very challenging but currently there is more clarity. The message needs to be in the local language, to be very precise and detailed, and there is a particular need to explain why a person needs to go to the hospital when falling ill, even though there is no treatment available. Counting on an adequate social mobilization to overcome the socio-cultural aspects of EVD outbreak remains a challenge. Others include giving a safe and dignified burial, the logistical challenge to reach the epicentre of the outbreak and challenges in the management of cases. 11

12 Session III: Presentation of the GEVIT working groups work GEVIT Country Implementation Working Group Dr Gavin Grant, Medical Officer, Accelerated Disease Control and Vaccine Preventable Diseases Surveillance Branch/ Global Immunization Division, US Centers for Disease and Control Prevention, Atlanta, USA. Presentation available electronically. The main task of the working group (WG) has been to develop guidance for Ebola vaccine (EV) use among the identified target groups. Countries will use the plans and materials that are familiar to national staff, adapting them to EV activities, and the guidance will focus on EV specific issues. The process to develop guides and tools included face-to-face discussions, regular conference calls, experience-sharing from other campaigns and country visits. The WG has developed ideal plans for EV use, focusing on areas that are unique to EV implementation. For instance, one of the criteria to mobilize vaccine from the hub to the country is laboratory confirmation and, depending on the country, its capability to confirm a diagnosis will vary. However, how the confirmation itself will be carried out is not included in this guide, rather there is reference to the existing guidance and enhancement of the need for coordination with the overall Ebola outbreak response. GEVIT Surveillance, Monitoring & Impact Evaluation Working Group Dr Jason Mwenda Mathiu, Coordinator, Routine Immunization and New Vaccines, Immunization, Vaccines and Emergencies, Brazzaville, Congo. Presentation available electronically. Country preparedness for Ebola vaccine use will require increased robustness of the general health-care capabilities; the country should be able to respond as soon as possible, human resource capacity is key and health systems in the most affected countries may be weak, but an EVD outbreak may represent an opportunity for an improvement. There seems to be some confusion as to the proposed integration of Ebola vaccine within other vaccination programmes within countries, as opposed to a vertical Ebola-specific programme. Additionally, vaccination activities should be linked in the overall Ebola Response Plan. To this end, the WG developed the following draft guidelines: Subgroup 1: a monitoring plan during vaccine delivery, and an assessment plan after vaccine delivery. Subgroup 2: a range of proposals for field study designs for Ebola vaccine effectiveness, and changes to the Ebola surveillance systems to incorporate use of vaccines in outbreak response. Subgroup 3: case definitions for AEFI and guidelines to strengthen AEFI and vaccine safety surveillance. The choice of the vaccination strategy to be implemented needs to be made in the light of the local context. The choice of a vaccination strategy should be an operational decision based on the epidemiology of the outbreak, and countries can combine different strategies depending on the number of cases and funding available to purchase the vaccine. Strong political will at country level is imperative. An active communication system needs to be established that provides accurate information in order to gain trust. Since the vaccines are still in clinical trials, there is resistance to vaccination and this needs to be managed. For vaccine introduction, countries should initiate the campaign from a communication perspective, i.e. preparing people with clear communication messages regarding the type of vaccination strategy and the objectives prior to the vaccination campaign, not after the campaign has started. Community engagement and involvement should start two weeks prior to a vaccination campaign as it takes time to prepare the community. At present, this is the last action on the list. Vaccination brings hope and the benefits of vaccine can build trust; therefore, the community needs to understand what the benefits of the vaccine are. The pros and cons of vaccination strategies, e.g. mass (geographic) vaccination versus Ring vaccination, are discussed in the guide based on the knowledge currently available and consistent with SAGE s provisional recommendations. 12

13 Session IV: A blueprint for research & development, and simulation exercises A blueprint for research and development Dr Marie-Paule Kieny, Assistant Director General, Health Systems and Innovation, WHO headquarters, Geneva, Switzerland. Presentation available electronically. Everything discussed so far is hypothetical since no vaccine is, to date, actually licensed. There is extensive ongoing discussion and consultation with SAGE regarding policies and with regulators, in particular with the US Food and Drug Administration (FDA), to see what kind of regulatory framework they could propose for the immediate potential use of Ebola vaccine, but none of the strategies discussed here will be implemented unless a vaccine is licensed. There are several options currently on the table for the use of an unlicensed vaccine in specific circumstances; specifically for the use of the rvsv vaccine, because for this vaccine there are interim efficacy data and the largest safety data information available, due to the large number of people vaccinated. However, the rvsv clinical trial has NOT yet shown statistically significant efficacy. The options referred to include: Use of a vaccine in a clinical trial setting. This means adherence to a protocol and requirement of written informed consent from all vaccinees, as is currently happening in Guinea and Sierra Leone. The authorization for a trial is given in weeks to months and clinical trials are covered by insurance if any adverse events occur. There is a protocol for a clinical trial among intimate and sexual partners of survivors currently in discussion for Guinea at WHO, and this could be envisaged in other countries. Use of the vaccine under expanded use. This is still a study, not a mass vaccination or a vaccination campaign. The current requirements are to precisely define a target population and to obtain written informed consent from all vaccinees. The United Kingdom requested an expanded use (not a clinical trial) authorization from an ethics committee and all volunteers signed the informed consent forms, while the United Kingdom government took full liability for any AEFI that could occur in these volunteers, whereas in case of a trial, this is covered by the trial insurance. This expanded-use access was implemented in Scotland to vaccinate around 25 contacts of an ill nurse and this process took a few days; however, governments need to take the juridical responsibility for this. Emergency use authorization (WHO has something similar called emergency use listing). Once a country has authorization, written informed consent may not be needed but there is still clear need for insurance. Receiving the authorization could take months and all aspects (preclinical, clinical, safety, immunogenicity, etc.) need to be reviewed by regulators. Use after full vaccine licensure. The process could take at least 18 months, with licensure after full review in the country of manufacture, and then from the national authorities in the most affected countries. GEVIT is working on the introduction of a registered vaccine. The blueprint for research and development (R&D) aims to reduce the time lag between the declaration of an international public-health emergency and the availability of effective medical technologies that can be used to save lives and avert a crisis. The blueprint will encourage research to generate safety data from Phase 1 studies in man, for the most promising experimental products for priority infectious diseases, before the outset of an outbreak. The R&D blueprint aims to map existing knowledge and good practices and to identify gaps and establish a roadmap for R&D preparedness. Through an enabling environment in affected countries, WHO and international partners are poised to address the challenge of developing and implementing the R&D blueprint. The R&D blueprint has five work-streams: 1) prioritization of pathogens focus on global need; 2) identification of research priorities what is already available; 3) coordination of stakeholders and expansion of capacity; 4) assessment of preparedness and impact of intervention; 5) innovative financing options. 13

14 EVD outbreak Scenario A country in West Africa Scenarios A available electronically. Notes have been collected by the coordinating rapporteur and summarized in the following: EBOLA VACCINE DEPLOYMENT TABLE-TOP EXERCISE, Scenario A country in West Africa (ppt presentation). EVD outbreak Scenario B Democratic Republic of the Congo Scenario B available electronically. Notes have been collected by the coordinating rapporteur and summarized in the following: EBOLA VACCINE DEPLOYMENT TABLE-TOP EXERCISE, Scenario B DRC (ppt presentation). AEFI for Scenario A and for Scenario B AEFI for Scenario A and for Scenario B available electronically. Notes have been collected by the coordinating rapporteur and summarized in the following: AEFI MONITORING AND RESPONSE TABLE-TOP EXERCISE, Scenario A and Scenario B (ppt presentation). 14

15 Session V: Review of GEVIT documents and materials Country Implementation Working Group documents The document has some placeholders and areas that require further discussion and additional work, including the definition of Ring vaccination, the clarification of criteria governing the choice of vaccine strategy and improvement of the vaccination forecasting tools to be consistent with the ICG requirements. The document also requires further editing to improve the flow for better clarity, especially around the preparation for deployment, decision-making and implementation sections. It would also benefit from more checklists and figures and it will finally need to be translated into French. Monitoring and Evaluation (M&E) Working Group documents A robust surveillance system is needed; for the Ring vaccination the rapid response teams identify the contacts and so need the corresponding reporting tools and mobility capacity to follow the contacts. A functional laboratory is needed for confirmation of cases within 24-hours. The AEFI strategy should be prepared well in advance, adapting guidance to allow for existing systems. The flow of information needs to be coordinated and it is advisable to have one focal point from the Ministry of Health (MoH) to coordinate with and inform the international organizations and partner agencies. In addition, the documents would need to be shortened to improve their user-friendliness, and titles could be discussed as they do not include mention of deployment or use of the vaccine. A decision needs to be made regarding whether these documents will remain high level, be general guidance materials, or whether they will be made country-specific. Finally, a preparedness checklist should be developed (the team taking the lead to work with other groups). 15

16 Session VI: Agreement and next phase Proposed way forward for GEVIT in 2016 and beyond Dr Marie-Pierre Preziosi, Medical Officer, Initiative for Vaccine Research, Immunization, Vaccines and Biologicals, WHO headquarters, Geneva, Switzerland. The focus of this workshop was on fostering technical discussions, and NOT on issuing WHO recommendations. Both the regulatory context (with no licensed vaccine) and the policy context are challenging. SAGE has provided provisional guidance but this is a highly evolving context, as extensively discussed throughout the workshop. Additional feedback on the Country Implementation Guide (CIG) is requested by 10 November Participants can provide feedback on sections relevant to their areas of expertise or on the entire document. The next version of the CIG will be drafted by the end of the year. As per countries request, all documents will then be translated into French. In terms of the distribution of tasks for revision of documents, it is agreed that the WHO Secretariat will compile all comments and then focus on revising the main guide document (CIG) and that each WG will focus on revising the corresponding appendices. The following broad work priorities are proposed for 2016 and beyond, along the lines discussed among countries and partners during the workshop. Global, regional and country integration of the Ebola vaccination component with the overall Ebola preparedness and response, as well as with EPI. For example, some focused activities could be organized in priority countries, and countries with past Ebola outbreak response experience could provide assistance to less experienced countries. Preparatory activities could be organized before rather than after vaccine licensure. Consolidation of the ICG processes and related contingency funds. Coordination of regular reassessments and updates of the CIG and tools. For instance: when new information becomes available; e.g. SAGE guidance, trial data, vaccine stability data, additional lessons learned or EVD expert group inputs: or when new comments are submitted, e.g. following other countries, partners and manufacturers reviews; or when deemed necessary, e.g. when a licensed product will be available. With regard to the documents, GEVIT volunteers will review the next version. Additional reviews could be conducted by other countries, and other partners will also be invited to review. With regard to integration and technical support, the first step will be to identify the priority countries at high risk, as well as the countries with significant experience with Ebola. For overall and country preparedness, financial support information and training materials will need to be developed. A method also needs to be identified for integrating the guides into the overall Ebola response at global and national level. Initial ad hoc country meetings could be organized to provide comments on the document through in-country committees. At the coordinating level, WHO has many Ebola subject-matter experts, and some of them could be involved in the review to ensure integration in the overall response. With regard to ICG contingency funds, it was mentioned that some extra resources for preparedness might be needed. Sierra Leone clarified that contingency funds would be needed and would be most valuable at country level for preparedness, i.e. to be able to do the needed work ahead of time to achieve faster, more effective implementation and avoidance of the inherent delays in authorizations for use of regular funds. Technical assistance in the post-licensure period would require GEVIT to reconvene and work on the documents in light of new information available. It would be valuable to provide a schedule for updating the document as new trial information becomes available and in case licensure takes a long time. GEVIT could work on updates to the document every six months and then when licensure happens there could be a comprehensive update. The document to be finalized by early 2016 would still be in draft form and be posted on the WHO website for comments. A release as version 0 might be needed before any licensure. 16

17 Annex 1: Programme Background As part of a comprehensive Ebola Research and Development effort, a multi-partner Global Ebola Vaccine Implementation Team (GEVIT), created under WHO leadership, is actively working on the collaborative planning for the potential introduction of Ebola vaccines. GEVIT currently associates countries most affected by the current Ebola virus disease (EVD) outbreak (Guinea, Liberia and Sierra Leone) and key partners, including the Bill & Melinda Gates Foundation, Gavi the Vaccine Alliance, UNICEF, the U.S. Centers for Disease Control and Prevention, the United States Agency for International Development and WHO. GEVIT is led by a Steering Group (SG) with a structure consisting of three Working Groups (WG): (1) Vaccine Supply, Allocation and Procurement; (2) Country Implementation; and (3) Monitoring, Surveillance and Impact Evaluation. The scope of work of GEVIT is to support affected countries in their efforts to plan for the potential deployment of Ebola vaccines, in accordance with WHO recommendations, with the following two main objectives: 1. To support development and dissemination of tools and guidelines, synthesis of evidence to inform strategies and policies, including community engagement strategies; and 2. To provide capacity and work with Ministries of Health and partners to develop and implement their country plans, and to enable and facilitate in-country planning, management, and coordination mechanisms. The GEVIT working groups are progressing steadily. The regional workshop will be an essential milestone to advance and integrate plans together with countries, the entire GEVIT team and essential partners. The workshop will focus on integrating country inputs into planning materials, using plenary presentations, small group discussions and simulation exercises with various epidemiological scenarios. Goal and objectives The goal of the workshop is to agree on final steps required to complete the development of a plan for future Ebola vaccine introduction by December 2015 and to define a way forward for 2016 and beyond. The three main objectives of the workshop are: 1. To discuss draft documents and tools among GEVIT members and with country representatives, to ensure they are relevant and address feasible strategies to foreseen challenges to Ebola vaccine introduction; 2. To ensure GEVIT is addressing all important steps for vaccine introduction through a simulation exercise of a future outbreak in the presence of a licensed product; 3. To discuss options for a way forward. 17