Urgent need for a vaccine

The COVID-19 pandemic is having a devasting effect internationally and in South Africa. With approximately 770,000 known cases and almost 21,000 deaths as of 24th November 2020, combined with the contraction of the South African economy and a fall of over 16% in the Gross domestic product (GDP) between the first and second quarters of 2020, and the associated job losses, it is urgent to find a more permanent solution to the crises. The development and roll-out of an effective vaccine are one of the main tools against COVID-19.

Since the detection of the novel SARS-COV-2 coronavirus in Wuhan, China in December 2019, the genetic sequence of COVID-19 was published on 11 January 2020. This triggered an urgent international response to prepare for the outbreak and accelerate the development of a preventative vaccine. A number of companies initiated their vaccine R&D efforts from March/ April and in most cases built on already existing platform technologies. The vaccine effort is being prioritised for speed of clinical evaluation for safety and efficacy, financing, and planning to manufacture billions of doses, and eventual worldwide deployment and equitable access among developed and developing countries.

Vaccine development usually takes more than 10 years, as the development of a safe and effective vaccine is a highly complex process. A large share of vaccine candidates fails in pre-clinical development or during clinical trials. Currently there about 260[1]  vaccines against COVID-19 in development, with 58 COVID vaccines in the clinical evaluation phase and an additional 203 in pre-clinical development. South Africa is participating in several clinical trials across phase I to phase III.

It is envisaged that the first successful vaccines will be delivered early in 2021.  However, the upscaling of the manufacturing pipeline for hundreds of millions, or even billions of doses will also require serious collaboration and needs to be done in such a way that it will not compromise the production of other essential vaccines.

In order for South Africa to be able to secure early access to and delivery of, safe and effective COVID-19 vaccines as soon as they become available, the development and implementation of a comprehensive COVID-19 Vaccine Strategy is essential.

Outcomes

The COVID-19 Vaccine Strategy aims to contribute to the following outcomes:

  • Sufficient supply and adequate access to a safe and effective vaccine to achieve population immunity to COVID-19;
  • Protection of vulnerable population groups from acquiring COVID-19;
  • Contribute to South Africa’s social and economic recovery following the negative impact of COVID-19;
  • Enhance South Africa’s preparedness for response to future disease outbreaks; and
  • Development of a comprehensive communication programme developed with civil society and the media, to address vaccine hesitancy and increase vaccine confidence.

Elements of South Africa’s COVID-19 Vaccine Strategy

The COVID-19 Vaccine Strategy comprises of the following areas:

  1. Research and Development
  2. Purchase agreements
  3. Support for local manufacturing
  4. Regulatory approvals
  5. Immunisation administration and monitoring
  6. Selection criteria for vaccines

 

1.    Research and development

South Africa has world-class clinical, sociological, epidemiological, and laboratory research expertise, and this has been the basis of the development of a wide-ranging research agenda for COVID-19 including vaccine development. The South African government is supporting the efforts of South African research institutions and vaccine manufacturing sites to conduct and contribute to research to accelerate the development and manufacture of promising COVID-19 vaccines and treatments. In addition, research institutions and manufacturing sites have partnered with international vaccine manufacturers and research allowing the country to make significant contributions to vaccine development efforts.

An amount of approximately R95million has been allocated by the South African Government to help develop COVID-19 vaccines, treatments, therapeutics, and diagnostics. The South African Medical Research Council is managing the funding of research activities targetting the clinical evaluation of potential treatments and vaccines against COVID-19; development of antiviral therapies for COVID-19; and the improvement of the health system’s response to COVID-19 and future pandemics.

The research and development support includes funding to include certain high priority vulnerable groups in South Africa in the clinical trials being conducted in South Africa, as well as the enhancement of the community engagement activities around the vaccine trials. This will ensure that the vaccines tested in South Africa do address some of the main concerns around the appropriateness of the vaccines for the South African situation.

Further research around the implementation and roll-out of the vaccines also needs to be supported, including guided communication plans.

2.    Purchase agreements

2.1.  COVAX facility

The Global COVID-19 Pledging Conference of 4 May 2020, culminated in the creation of the Access to COVID-19 Tools Accelerator (ACT-A), a global collaboration to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines. President Ramaphosa, of South Africa, was elected as co-Chair of ACT-A Facilitation Council during the meeting held on 10 September 2020.

COVAX is the vaccines pillar of the ACT-A and is co-led by the Global Alliance for Vaccines and Immunisation (Gavi), the Coalition for Epidemic Preparedness Innovations (CEPI), and WHO. It aims to accelerate the development and manufacture of COVID-19 vaccines and to guarantee fair and equitable access for every country in the world.  https://www.who.int/publications/m/item/the-covax-facility.

The COVAX pillar aims to offer advance purchase agreements for vaccine candidates meeting technical threshold criteria.  COVAX aims to procure a cumulative 2 billion doses by the end of 2021 including an emergency buffer (10% of doses). The aim is to ensure that participating countries receive allocations of a vaccine as quickly as possible by procuring the highest possible volume of vaccine from each manufacturer at economically efficient prices tiered for countries according to GDP. This will allow globally fair and equitable allocation of vaccines.  Gavi is managing the activities around access to vaccines.

Gavi has created the COVAX Facility through which self-financing economies and funded economies can both participate. Within this, a funding mechanism, the Gavi COVAX Advance Market Commitment (AMC), will support access to COVID-19 vaccines for 92 lower-income economies. The COVAX Facility will negotiate for and provide all participating countries access to the same vaccine as and when they become available, based on the participant’s selected quantity. Gavi approached the Department of Health with an offer to participate in this investment opportunity to ensure access to vaccines against COVID-19. On 31 August 2020, the Director-General of the National Department of Health submitted a non-binding expression of interest in the COVAX Facility.

The COVAX Facility is offering Self-financing countries two different options to participate in. (1) In the “Committed Purchase” option, participating countries make a lower upfront payment, but need to make firm guarantees to procure doses from the Facility without the option to opt-out of specific candidates.  (2) In the “Optional Purchase” option, participating countries make a larger upfront payment, but can opt-out of vaccine allocations while they still reserve the option for later vaccines.

In order to gain access to vaccines rapidly, South Africa agreed to participate in the Committed Purchase option of the COVAX to vaccinate at least 10% of South Africa’s population. Initially, the supply of vaccines will be constrained and specific criteria need to be applied to prioritise those who should be eligible for vaccination.  For example, those at high risk of exposure such as our frontline health care workers and the medically vulnerable.

It is expected that South Africa will receive the first batch of vaccines in quarter two of 2021.

2.2.  Advance Purchasing agreements with individual vaccine producers

Whilst the COVAX facility is the favoured option South Africa also needs to explore all options to ensure that the process of rolling out vaccines is safe and cost-effective, by engaging with vaccine producers. Mechanisms such as advance purchase agreements, direct purchase agreements, and open tender procedures need to be explored, to secure sufficient supplies of the appropriate vaccines to provide herd immunity in South Africa.  It is also envisaged that it might be necessary to obtain more than one kind of vaccine to cover the needs and requirements of different groupings.

3.    Supporting local manufacturing

With limited vaccine manufacturing capacity around the world, individual countries will have to prioritise their own requirements in the interest of securing access to the vaccine as a matter of national security.

An opportunity exists as a result of the COVID-19 pandemic, for South Africa to expand its scope of production in response to the need for more global capacity for COVID vaccine manufacturing. It, therefore, becomes imperative that South Africa harnesses and stimulates its own capability for local production while serving as a primary vaccine and health product supplier to the rest of Africa in response to this and future pandemics.

3.1.  Vaccine manufacturing capability in South Africa

Sub-Saharan Africa has only four vaccine manufacturers with limited and specific manufacturing potential. In South Africa, Biovac is a specialist vaccine company with product development, formulation, and filling capability designed specifically for vaccines. It is licensed to formulate, fill (in vials and prefilled syringes), pack, and label vaccines. The country has other sterile manufacturing capacities in the form of intravenous bags, vials, and ampoules. The companies that have these installed capacities are Adcock Ingram, Aspen Pharmacare, Fresenius Kabi, and PharmaQ. These companies have licensed sterile manufacturing capability mainly dedicated to injectable intravenous pharmaceuticals i.e small molecules.

All of the above manufacturers need to receive the active pharmaceutical ingredient (also known as drug substance) from suppliers outside South Africa, with the blending/formulation taking place locally as well as the filling in the right primary container i.e vial or ampoules.

Two companies are currently involved in setting up to do the drug product manufacturing for COVID-19 vaccines, using the active pharmaceutical ingredients from vaccine developers and manufacturers outside South Africa.  The ability to locally formulate, fill and finish vaccines will assist in the reduction in the trade balance, provide high skilled employment, and in the long run, ensure the security of supply of vaccines. These companies are:

Biovac

Biovac was originally formed as a Public-Private Partnership with the South African government. It currently takes responsibility for approximately 70 percent of South Africa’s vaccine needs and was in the process of expanding its manufacturing efforts before the pandemic.

Biovac’s current activities are limited to the development of bacterial vaccines, sterile formulation and filling as well as labeling, packaging and cold chain distribution.

Concerning the COVID-19 vaccine, it is engaged in both bilateral discussions as well as with the Coalition for Epidemic Preparedness Initiative (CEPI)  for the formulation, fill-finish activities.

Aspen

Aspen is a South African-based pharmaceutical company with a global footprint. They have recently expanded their sterile capability mainly for sterile pharmaceutical products i.e small molecules.

Aspen Pharmacare and Johnson & Johnson (J&J) have made an announcement wherein Aspen will dedicate some of its vial manufacturing capacity to manufacture (fill-finish) for J&J  its candidate COVID-19 vaccine. This presents additional fill-finish capacity and vaccine access for the country to leverage.

3.2.  Sustainability for future pandemics

Large vaccine manufacturing capability is critical in response to the current COVID pandemic and for future pandemics. This capability, however, needs to be sustained through the manufacture of routine vaccines. In order for the country to have the pandemic-readiness capability for future pandemics, local manufacture of routine vaccines must be encouraged and supported in-between pandemics.

4.    Regulation and safety approvals

In order to ensure safe and timeous approval of any COVID-19 vaccine candidates, it will be necessary to put several measures in place to ensure regulatory approvals of safe vaccines. These measures include:

4.1.  Early engagement with the South African Health Products Regulatory Authority (SAHPRA)

Any vaccines that will be made available in SA will require authorisation by the national regulator, SAHPRA.  SAHPRA is a member of the WHO Collaborative Registration Procedure (CRP) and uses this process of reliance during the registration of medicines. This continues to be an option including for the COVID-19 Vaccine reviews. Furthermore, the WHO HQ is working with WHO AFRO through the African Vaccine Regulatory Forum (AVAREF) to identify countries to participate in the global joint assessment of COVID-19 vaccines for registration.  SAHPRA has expressed interest in participating in the joint reviews.

In terms of section 2B of the Medicines Act, SAHPRA has entered into MOUs with EMA, USFDA, MHRA, and TGA and will be able to use their assessment reports as a reliance approach to reduce timelines in the evaluation process.

4.2.  Accelerated procedure for authorisation

SAHPRA has adopted a priority review approach for all COVID-19 vaccine applications since the onset of the pandemic. Thus, the process of expedited review will apply to any COVID-19 vaccine registration application. SAHPRA has a dedicated team, the COVID-19 Vaccine registration Working Group (CVr WG), who will not only provide the necessary guidance to applicants at pre-submission but will also engage in expedited reviews taking into account available reliance and review approaches such as rolling reviews, to facilitate quicker registration without compromising on quality, safety, and efficacy. Vaccines containing newer technologies are anticipated to take longer for approval despite the process of expedited review. In addition, if a new COVID-19 vaccine is required urgently before the necessary data for full registration is available, a Section 21 application could be awarded which will permit the emergency use of a vaccine.

4.3.  Flexibility in relation to labeling and packaging requirements

SAHPRA will effect Section 36 of the Medicines Act (exemption of medicines by the Minister of Health from certain requirements of the Medicines Act) for specific labeling requirement exemptions noting that the labeling would have to be available at least in English. Matters relating to storage conditions and in-use stability will be handled on a case by case basis based on available data.

4.4.  Legislation on genetically modified organisms

The Department of Agriculture oversees the enactment of the Genetically Modified Organisms (GMO) Act of 1997 and the establishment of the GMO Council that oversees any application that involves the use of GMOs. SAHPRA is a council member and also provides evaluators to the GMO review committees. To date, the GMO Council has been involved in endorsing vaccines intended for COVID-19 vaccine clinical trials in South Africa. Generally, these vaccines once reviewed do not need to be re-reviewed by GMO Council unless there have been reports that require further investigation and review. It is not anticipated that the GMO Council review will delay vaccine access.

5.    Immunisation roll-out, administration, and monitoring

Efficacy results from the Phase 3 COVID-19 vaccine trials are becoming available and more are expected in late 2020 / early 2021 and beyond. To date, four vaccine trials have reported preliminary efficacy data ranging from 62-95%. In addition, the data suggest that these vaccines are generally regarded as being safe. Assuming that one or more of these vaccines are approved by SAHPRA,  it is unlikely that there will be sufficient vaccines available for use beyond specific high-risk groups in the country before the third quarter of 2021 and even then it is likely that only limited quantities of the vaccine will be available. Vaccine allocation will thus have to be based on a framework of prioritisation and need.  The principles underpinning this framework emphasises an evidence-based approach and an ethical and moral perspective, in particular from an African indigenous values context.

The framework will serve as a guide and will have to be adapted as new scientific information becomes available e.g. information about specific characteristics of available vaccine/s, the benefit-risk assessment for different population sub-groups, the amount and pace of vaccine supply, the epidemiology at the time of vaccine introduction, clinical management, public health response, and economic and social impact of the pandemic.

The framework is presented in four sections:

 

5.1.  Fair allocation guided by African indigenous values of interdependence, interrelatedness, and mutually respectful discussion and dialogue giving rise to the following four principles:

 

  1. Affirming the humanity of others: Allocation decisions must promote the common good while respecting human dignity. Every person is considered and treated as having equal dignity, worth, and value when promoting public health and economic and social wellbeing, both in the short and long terms. Societal benefit is broadly understood in this context as the public’s health and socioeconomic well-being. Allocation decisions should be non-discriminatory in design and impact. In line with section 9 of the South African Bill of Rights, there are to be no exclusions based solely on characteristics such as religion, race, ethnicity, national origin, disabilities, etc.
  2. Survival of the community: Allocation decisions are to be evidence-based. Vaccination phases, specifying who receives the vaccine and when, should be based on the best available scientific evidence regarding the risk of infection and transmission, disease severity, and societal impact. Those who provide essential services and contribute towards the advancement of prevention and treatments of the disease could be considered essential for the survival of the communities. In addition, vulnerable groups and those at greatest risk of severe illness and death could be included in priority groups. In this way, benefits will be maximized and the risks of severe morbidity and mortality caused by transmission due to SARS-CoV-2 reduced.
  3. Social Solidarity: The moral right to equal concern requires allocation of vaccine to proceed impartially according to fair criteria. People are to be treated fairly and equally. Backgrounds and inequities amongst socially vulnerable and disadvantaged groups require consideration. That vulnerability increases, or may emerge for the first time during pandemics, is to be taken into account.
  4. Meaningful community engagement: This will allow for the promotion of legitimacy, trust, and ownership of the allocation decisions. Community involvement will be required for both allocation decision-making and addressing vaccine hesitancy. Faced with the challenge of maintaining public trust while simultaneously stemming the pandemic through various control measures, decision-makers need to be trustworthy by ensuring early engagement with stakeholders and that decision-making processes are ethical and transparent. For this, integrity, which reflects the need to act with honesty, reliability, and fairness, and a willingness to be held accountable to explain one’s actions, is critical.

 

5.2.  Identification, classification, and prioritization of risk groups based on the above values:

 

These include:

  1. Health Care workers: Health professionals, nurses, general health workers, care home workers, selected laboratory workers, and traditional healers.
  2. Persons with co-morbidities and at risk for morbidity and mortality: These include persons 60 years and older, persons living with HIV, tuberculosis, diabetics, chronic lung disease, cardiovascular disease, renal disease, obesity, etc.
  3. Persons in congregate or overcrowded settings: This group includes persons in prison, detention centres, shelters, and care homes. In addition people working in the hospitality and tourism industry, and educational institutions are also at risk.
  4. Essential workers: This group includes police officers, miners, and workers in the security, retail food, funeral, travel, banking, and essential municipal and home affairs services.

 

5.3.  Programmatic implications including Monitoring and Evaluation

The introduction of a new vaccine into the immunisation programme provides an opportunity for health system strengthening and integration of health services. A National Technical Working Group for COVID-19 vaccine introduction has been established to plan and coordinate the vaccine introduction inline with the strategic objectives of the National Department of Health.

Standard operating procedures are currently being developed to ensure that the vaccine rollout programme is effectively managed and implemented. These include:

  1. Development of vaccine guidelines: This needs to be completed for each vaccine and provide guidance around eligibility, application, dosage, and storage.
  2. Vaccine supply management: This includes the ordering and distribution of and the safe storage and handling of vaccines to maintain potency.
  3. Health care worker training: Staff will be trained on how to counsel recipients on the benefits and risks of the vaccines and delivery of the vaccines.
  4. Adverse events following immunization surveillance: This is a standard component of the current national Expanded programme on Immunization (EPI) and is being adapted for COVID-19 vaccine rollout as well.
  5. Monitoring and evaluation (M&E): The EPI M&E tools currently in use are being adapted for the COVID-19 vaccine rollout. This should include registration and tracing mechanisms, especially in the event of the requirement for more than one dose per person.
  6. Development of vaccination certification tools: This should be aligned to International Health Regulation if there are any requirements. These can be paper-based or electronic.
  7. Disease surveillance: While COVID-19 surveillance is currently ongoing in the country, the surveillance should be adjusted after COVID-19 vaccines are introduced to understand the impact of vaccination
  8. Service delivery: To ensure access to the COVID-19 vaccines various service delivery platforms should be considered including healthcare centres, hospitals, outreach services, and community pharmacies in the private sector. COVID-19 vaccination delivery will be tailored based on the vaccine characteristics, the priority groups, the service delivery platform, and the amount and pace of vaccine supply.

 

5.4.  Communication and social mobilization

There is an urgent need to put in place a multi-sectoral communications strategy to support the work of government and civil society to ensure that the investment made into COVID-19 related scientific research and the eventual rollout is not jeopardized but protected through the provision of scientifically sound, evidence-based communications and a critical mass of community support.

The development of a COVID-19 vaccine communication strategy should be a joint effort by government agencies and civil society and will ensure that all stakeholders have clear guidelines within which to communicate scientifically sound, evidence-based messages to the public. The strategy should take into account global research, whilst articulating the need for South African research into the national context.

The issues around science denialism, anti-vax sentiments, and vaccine hesitancy in South Africa should be addressed through an understanding of the main drivers of the hesitancy and the development of effective local responses.

The COVID-19 vaccine communication strategy should be informed by the communication strategies developed for other South African Health programmes (HIV, TB, Diabetes, etc), but it is of importance that the impact of the COVID-19 pandemic on the national psyche should also be taken into account. Engagement with representatives of community groups affected by the COVID-19 pandemic will be essential.

The communication strategy should include the use of online social media platforms (WhatsApp, Facebook, Twitter, etc), as well as traditional media (print, community radio, etc.) as critical platforms for engagements.

6.    Selection criteria for vaccine candidates

In negotiating with different vaccine producers, it is essential that selection criteria are developed and should take into account the following aspects:

  1. Evidence of quality, safety, and efficacy in different groups generated from clinical trials.
  2. Review of vaccine technology and potential risks associated with different technologies e.g. established platform, new platform, viral vector, live attenuated virus, adjuvants, etc.
  3. Epidemiology at the time of vaccine introduction i.e. no cases, clusters of cases, community transmission.
  4. The ability to secure vaccine in 2021 and possible amounts of a vaccine available over time.
  5. Cost of the vaccine, the amount of financing requested, the schedule, and conditions of the related payments.
  6. Liability attached to specific vaccines.
  7. Capacity to supply through the development of production capacity.
  8. Vaccine presentation and suitability for the South African market.
  9. Local registration is a requirement.
  10. Ease of introduction into programmes including cold chain requirements, single or multidose vials, risk of wastage, storage space requirements, etc.

 

[1] https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/