Vaccine safety and pharmacovigilance in the WHO African Region
Bartholomew D Akanmori,i Mutale Mumba,ii Madhav Balakrishnan,iii Isabelle Sahinovic,iii Richard Mihigoi
Corresponding author: Bartholomew D Akanmori; e-mail: email@example.com
i WHO Regional Office for Africa, Brazzaville, Congo, Immunization Vaccines and Emergencies, Routine Immunization and New Vaccines
ii Routine Immunization, WHO-AFRO Intercountry Support Team
iii Safety and Vigilance Team, EMP, WHO, Geneva
Every vaccine has a lifecycle, which starts with discovery, to clinical evaluation, licensure and eventual introduction and use in routine immunization programmes. During clinical trials of new candidate vaccines all adverse events associated with vaccination are monitored. Clinical trials are, however, limited in their ability to detect rare and late occurring adverse events associated with vaccination due to smaller sample size and limited participant follow-up time.1,2,3 Careful, systematic and regular monitoring for possible infrequent but serious adverse events following immunization is thus desirable during the post-marketing, widespread use of any vaccine. An adverse event following immunization (AEFI) is defined as any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. The adverse event may be any unfavourable or unintended sign, abnormal laboratory finding, symptom or disease.4
Vaccine safety and pharmacovigilance has, therefore, assumed more significance in the WHO African Region which has also seen a growth in clinical development of new vaccines as well as their introduction into the national immunization programmes in many countries. Some of the vaccines being introduced include pneumococcal conjugate, conjugate meningococcal A meningitis, human papilloma virus, rotavirus and rubella. For the first time a vaccine against malaria, RTS,S/AS01, is in phase 3 clinical trial in seven countries in the Region, which if licensed and pre-qualified could be added to the list.
Participants at a workshop for the development of national plans for vaccine safety and pharmacovigilance, Accra, Ghana
Recognizing the critical need for vaccine safety and pharmacovigilance, WHO has been supporting individual and institutional capacity building for the countries of the Region to implement the Global Vaccine Safety Blueprint, a strategic framework for strengthening the monitoring and response to AEFIs.5
Pharmacovigilance is one of the six required regulatory functions of national regulatory authorities (NRAs) for vaccines. In this context, WHO has developed an assessment tool to support institutional capacity building of NRAs, consisting of seven indicators and 28 sub-indicators. This tool allows countries to prepare development plans that guide institutional building efforts and to identify technical support needs for all areas of regulation of medicines, including vaccines.
Why vaccine safety?
Annually, vaccines prevent more than 2.5 million child deaths globally and it is projected that an additional 2 million child deaths could be prevented through immunization with currently available vaccines. Most vaccines are very safe and prevent disease or infection altogether. Vaccines have the special advantage of promoting health, having an expansive reach, significant impact (eradication of smallpox, elimination of polio and reduction in measles-related deaths) and saving lives and resources which would have been spent on managing diseases.
Vaccines are prepared with different types of antigens, using different scientific methods, which include attenuation, inactivation and recombination DNA technology. In addition, some vaccines have components to enhance immune response, such as adjuvants, while for others protein conjugation to polysaccharide (conjugate vaccines) allows for a stronger immune response.
Vaccines can also contain antibiotics, stabilizers and preservatives to reduce contamination during the manufacturing process and to maintain their effectiveness during transport and storage. Because of this variety of excipients regulatory authorities must therefore ensure that all vaccine components, singly and in combination, do not compromise vaccine safety.
Public trust is critical to the success of immunization programmes. In recent years, a number of newspapers, publications and websites have provided unbalanced, inaccurate, misleading and alarming information about vaccine safety, making it more difficult to identify and access reliable sources of information about vaccines. This could adversely erode the significant gains made by immunization programmes in the African Region and slow the progress towards control, elimination and eradication of vaccine-preventable diseases. For these and other reasons it is important for countries to have in place appropriate safety monitoring systems for reporting, analysis, causality assessment and communication of any AEFIs. This will reinforce the confidence in vaccines and immunization programmes.
Requirements of a functional vaccine safety and pharmacovigilance system
The Global Vaccine Safety Blueprint defines the requirements for a functional vaccine safety and pharmacovigilance system. This requires collaboration between the national expanded programme on immunization (EPI), national regulatory authority, national pharmacovigilance centres (NPCs), AEFI review committee and other groups (interagency coordinating committee, national immunization technical advisory group, health professional associations etc.). The system should capture AEFI reports, investigate AEFIs, analyse the data, conduct causality assessment, define corrective actions and follow up the AEFIs and clearly communicate on AEFIs (see Figure 1).
This cycle depicts the steps for an effective AEFI surveillance system, from identification, to notification, reporting, investigation, analysis, causality assessment, feedback and corrective action.
WHO Global Vaccine Safety Blueprint
Recognizing the need to strengthen capacity for vaccine safety especially in low- and middle-income countries, which lack this capacity, WHO and partners developed a strategic framework document on vaccine safety called the Global Vaccine Safety Blueprint, in 2011.6 The document sets out key indicators that aim to ensure that all countries have at least a minimal capacity to ensure vaccine safety. The Blueprint defines a strategy for strengthening safety activities globally.
The primary focus is to establish national capacity for vaccine safety in countries lacking this capacity through the coordinated efforts of all major stakeholders. The development of the document was achieved through consultations of experts globally and clearly defines its mission, vision and goals.
The Blueprint proposes three priority objectives:
- Establishing minimum capacity for vaccine safety and pharmacovigilance in each country;
- Enhanced approach in special situations; and
- Development of a global technical support network.
The eight strategic objectives of the Blueprint, which are being implemented by countries with the support of WHO are:
- Detection of AEFI;
- Adequate investigation of safety signals;
- Adequate communication of vaccine safety issues;
- Use of appropriate tools and methods;
- Ensuring a regulatory framework is in place;
- Technical support and training;
- Global analysis and response; and
- Public-private information exchange.
While the first four objectives relate directly to the components of vaccine pharmacovigilance systems, the last four address the supporting elements or prerequisites that must be in place for the vaccine safety system to function effectively. This Blueprint represents an excellent framework which if properly implemented can significantly strengthen vaccine pharmacovigilance in countries lacking the capacity, especially those of the African Region.
WHO capacity building efforts for vaccine safety and pharmacovigilance
Through workshops organized by WHO and bringing together national immunization staff, NRAs and pharmacovigilence centres, WHO has supported countries to develop work plans for vaccine safety and pharmacovigilance, which address their needs and are being implemented. These plans were developed in consultation with all stakeholders, WHO and partners in each country. The activities are defined, with timelines, defined roles and responsibilities and clear monitoring and evaluation plans.
The workshops evolved around a template for the development of work plans. The template defines the areas of activity, the baseline or current status, specific plans to fill gaps, estimated cost of achieving the results, source of funding, responsible person(s), partners and stakeholders, and a monitoring and evaluation framework to track progress made. The template is presented as Table 1.
WHO is also training the national AEFI committees for countries, who will in turn train provincial/regional and district committees. WHO has developed tools for causality assessment, training on vaccine safety and pharmacovigilence by countries.
Status of vaccine safety and pharmacovigilance in the WHO African Region
Eight anglophone countries (Ethiopia, Ghana, Kenya, Malawi, Nigeria, Uganda, United Republic of Tanzania and Zambia) and seven francophone countries (Burundi, Côte d’Ivoire, Cameroon, Democratic Republic of the Congo, Guinea, Madagascar and Togo) have been supported to develop work plans for 2014 and 2015. The countries have started implementation of their plans. This includes establishment or training of national expert committees, establishment of mechanisms for collaboration between stakeholders, collection, analysis and reporting of AEFIs. Evaluation of the status of implementation, and support where required, is ongoing through teleconferences and e-mail exchanges.
Participants at a workshop for the development of national plans for vaccine safety and pharmacovigilance, Grand Bassam, Côte d’Ivoire
The national expert committee for AEFIs of the United Republic of Tanzania was trained in the use of the new WHO causality assessment tool by a panel of international experts. In addition, six international participants from Ethiopia, Ghana, Kenya, Malawi, Nigeria and Zimbabwe attended the meeting. Similar workshops will be conducted in their respective countries as part of a regional effort to strengthen national capacity for vaccine safety.
- Ellenberg SS, Foulkes MA, Midthun K, Goldenthal KL. Evaluating the Safety of New Vaccines: Summary of a Workshop. Am J Pub Health 2005; 95(5):800–807.
- CDC. Surveillance for Adverse Events Following Immunization Using the Vaccine Adverse Event Reporting System (VAERS). Chapter 21 in: Vaccine-Preventable Diseases Surveillance Manual, 5th edition. CDC: 2011. Available: http://www.cdc.gov/vaccines/pubs/surv-manual/chpt21-surv-adverse-events.html [accessed 9 January 2015].
- Global Advisory Committee on Vaccine Safety (GACVS) and WHO Secretariat. Global safety of vaccines: Strengthening systems for monitoring, management and the role of GACVS. Expert Review. Vaccine 2009; 8(6):705–716.
- Council for International Organizations of Medical Sciences. 2013. For further details see: www.cioms.ch/index.php/vaccine-pharmacovigilance [accessed 14 January 2015].
- Amarasinghe A, Black S, Bonhoeffer J, Carvalho DSM, Dodoo A, et al. Effective vaccine safety systems in all countries: A challenge for more equitable access to immunization. Vaccine 2013; 31 Supplement 2:B108–14.
- Global Vaccine Safety Blueprint. World Health Organization 2011. Available: http://www.who.int/vaccine_safety/initiative/en/ [accessed 9 January 2015].
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