Global access to vaccines is extremely important at this time, to save lives, reduce the spread of the virus and the limit development of variants. Vaccines offer a means to end the pandemic. Current demand for vaccines far outstrips supply.
FPM believes that the key stakeholders in healthcare – governments, international bodies, patient organisations and charities, academia, pharmaceutical companies and manufacturers and healthcare professionals – with the potential to ensure effective, expedient and equitable global access to vaccines have an ethical duty to do so, for the good of patients and public health as a whole.
However, the means by which global access can be achieved are complicated, and innovative solutions in supply must not come at the expense of the safety, quality and the ability to monitor the safe use of vaccines. A compromise on these could potentially lead to devastating consequences, both for patients receiving the vaccine, and for the wider community in terms of herd immunity and trust in vaccines. These consequences could reach beyond COVID-19 vaccines and affect uptake of all vaccines.
This FPM statement aims to give an overview of the key issues and the status at the time of writing, and encourages stakeholders to work together to find innovative, effective and safe solutions to the problem.
Manufacture and Supply of COVID-19 Vaccines
Manufacture of vaccines is a critical step and whilst it needs to be done as quickly as possible, this must not compromise quality and safety standards. Manufacture of vaccines is a complex set of processes (upstream, downstream, fill-and-finish) requiring skills and technical know-how, together with cutting-edge science and technologies. This means that effective manufacturing capacity expansion needs to address the need for highly specialised equipment, qualified and trained personnel, effective technology transfers, and, not least, managing complex international supply chains.1 For example, the BioNTech/Pfizer vaccine contains 280 ingredients sourced from 19 countries. All others currently in use are similarly complex.2
Additionally, there needs to be robust oversight as the manufacturing is ongoing, that requires established national regulatory systems. These systems need to check that the manufacturing facility has the right procedures in place, that the manufacturing is being done to the right quality and is also needed to help solve issues which may arise during the manufacturing. It’s also important to recognise the need for diversified supply chains so that the global vaccination effort can withstand disruption in individual countries or regions, such as future waves of COVID-19 or future zoonotic pandemic viruses.
Before COVID-19, annual global vaccine production, including seasonal flu vaccines, totalled 5 billion doses. During the pandemic, vaccine manufacturers have continue to produce those, but are adding new capacity to make more than 10 billion COVID-19 doses.2 This is to enable the world population of 8.5 billion to receive one or two separate injections.
The challenge of scaling up manufacturing was identified as early as March 2020. At this time pharmaceutical companies identified that partnerships would be needed and they made a commitment to “increase industry’s manufacturing capabilities and willingly share available capacity to ramp up production once a successful vaccine or treatment is developed”.3
Pharmaceutical companies have developed new collaborations to increase manufacturing capacity. For example, Sanofi have announced an agreement to help manufacture the Moderna COVID-19 vaccine, in addition to their commitment to provide manufacturing support for the BioNTech and Johnson & Johnson (J&J) vaccines.4 Novartis announced an agreement to support the production of the Pfizer-BioNTech COVID-19 vaccine.5 Another example is that of Lonza, a contract development and manufacturing company is partnering with Moderna to enable manufacturing in the US and Switzerland of up to 1 billion doses per year.6
As of January 2021, over 200 novel coronavirus vaccine candidates are under development, of which 64 are in clinical trials. The London School of Hygiene & Tropical Medicine has developed an interactive tool that tracks the progress of the candidate vaccines in real time. It is recommended to access it regularly to verify the status of the vaccines’ development progress, profiles and potential controlled temperature chain (CTC). Aside from the challenges posed by the different storage and transportation needs for vaccines there as specific logistic considerations:
- A robust mechanism to ensure the traceability of COVID-19 vaccines, should be in place to avoid the risk of diversion and falsification of the vaccines.
- Procedures of reverse logistics need to be strengthened or implemented to allow tracking of the vaccines during the vaccination campaigns.
- Ensure safety plans to safeguard stock at national and subnational stores and during the distribution of products.
- Establish security arrangements to ensure the integrity of COVID-19 vaccines and ancillary products throughout the supply chain; ensure availability of plans to safeguard the security of staff as well as security at the central and/or regional storage facilities and for products in transit in a situation of high demand but limited stocks.
- COVID-19 vaccination campaigns are expected to generate unusually large amounts of health care waste. Countries should ensure that a safe and effective waste management plan, budget for training, employment of waste handlers, bins and treatment technologies are in place prior to vaccine deployment, including the option of outsourcing to the private sector.7
The current bottleneck in vaccine manufacturing has been caused mainly by the shortage in raw materials, insufficient production capacity and the highly complex manufacturing processes. 8 At a meeting in March 2021, COVAX, IFPMA, the Developing Countries Vaccines Manufacturer Network and the Biotechnology Innovation Organization reviewed the situation and the supply chain challenges. All stakeholders agreed there is a need to expand capacity in a way that promotes equitable access and discussed free flow of goods and workforce; continuing technology transfer and manufacturing partnerships between innovators and manufacturers to scale up and scale out COVID19 vaccine capacity; better demand forecasting and inventory management of raw materials and critical consumables; the value of regulatory harmonization and streamlining to accelerate manufacturing capacity and supply; and better production, sustainable supplies of ingredients, demand and supply, forecast and visibility.9 In May 2021 manufacturers and biotech companies announced commitments to step up dose sharing; continue to optimise production; call out trade barriers to be eliminated; support country readiness; and drive further innovation.10
One proposed solution being discussed to increasing vaccine supply is to waive patents on COVID vaccines. IP mechanisms enable the innovation cycle by supporting investment in R&D which may or may not result in a product. IP is complex, covering many aspects of the science and manufacturing processes. Waiving IP has been proposed as a potential way to speed up manufacture of COVID vaccines and while this may offer a route to enhancing global access, it is not a simple solution. Establishing safe and reliable manufacturing capacity will take time and would need to go hand-in-hand with an appropriate regulatory and governance system. There are a number of views on this including the view from the Bill and Melinda Gates Foundation which supports a narrow waiver for COVID-19 vaccines during the pandemic but notes that an IP waiver alone is not sufficient to improve vaccine supply globally.11
Delivery and Uptake of COVID-19 Vaccines
As and when sufficient quantities of vaccines become available, there are challenges around rapid scaling up of vaccine delivery due to the urgency of the situation as well as challenges such as vaccine hesitancy, storage and transportation issues, and coordination across multiple communities. However, rapid vaccination campaigns are possible with information campaigns, setting up technology platforms, regulatory approvals, and training personnel for an efficient deployment of the vaccines.12
The question of variants
SARS-CoV-2 has been in the human population for more than a year now, causing severe disease in some and resulting in a pandemic that continues to put severe strain on economies and healthcare infrastructures worldwide. In the UK, the first three vaccines have emergency use authorisation, and a national rollout is in progress. Many other countries are also instigating large scale vaccination programmes. These vaccines express the spike glycoprotein, the major target of neutralising antibodies in a natural infection. The vaccines protect against disease, and preliminary data suggest that transmission is also decreased after vaccination.
Current vaccines are based on a version of the spike glycoprotein from the start of the outbreak, however, and central questions remain around the ability of an old version of the spike glycoprotein to generate protective antibodies against newer emerging variants. The linked paper by Challen and colleagues (doi:10.1136/bmj.n579) suggesting that variant of concern B.1.1.7 might be associated with increased mortality adds urgency to these questions.13 The B.1.617 variant is the lineage thought to be responsible for the sharp rise in coronavirus disease 2019 (COVID-19) cases and deaths in India over recent weeks.
More recently India has been hit be a further variant. A team from the German Primate Center in Göttingen, the University of Göttingen Medical Center, the Friedrich-Alexander University of Erlangen-Nürnberg and Hannover Medical School – also reports that the entry of B.1.617 into lung and intestinal cells was blocked following treatment with soluble angiotensin-converting enzyme 2 (ACE2) or the serine protease inhibitor Camostat. However, this host cell entry was not blocked by the monoclonal antibody Bamlanivimab, which has received emergency use authorization (EUA) as a COVID-19 treatment. Finally, B.1.617 also partially evaded neutralization by the antibodies induced through natural infection or immunization with the Pfizer-BioNTech BNT162b2 vaccine.
These developments indicate that adaptations will need to be made to vaccines to control later waves of variants of the virus. Rather like the influenza virus, which is endemic, a worldwide programme similar to the WHO monitoring of influenza will be needed to enable timely new vaccines to be developed.14
Learning from HIV
COVID-19 isn’t the first infectious disease where novel approaches have been needed to solve issues of access globally. Another example is HIV. This has affected countries round the globe, with severe impact in low and middle-income countries. UNAIDS, WHO, Boehringer Ingelheim, BMS, Roche, GSK and MSD partnered in the Accelerating Access initiative which applied preferential pricing to ARVs, opening the door to improving access in developing countries. Another mechanism to improve access is voluntary licensing agreements whereby a patent holder grants a license over product patents in certain countries to generic manufacturers, enabling development of generic versions in resource-limited settings. By 2006, 28% of those in need in sub-Saharan Africa received treatment, compared to just two percent in 2003; 2007 saw a 54% increase in the number of people in LMICs receiving antiretroviral therapy, but there is a need for continued progress.15
The way forward
FPM believes that new collaborations are essential to increase supply without compromising safety and quality. One example of a collaboration is COVAX, the vaccines pillar of the Access to COVID-19 Tools (ACT) Accelerator which is a global collaboration to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines. COVAX is co-led by Gavi (the Vaccine Alliance), the Coalition for Epidemic Preparedness Innovations (CEPI) and WHO.16
The aim of COVAX is to accelerate the development and manufacture of COVID-19 vaccines, and to guarantee fair and equitable access for every country in the world, aiming to have 2 billion doses available by the end of 2021, which should be enough to protect high risk and vulnerable people, as well as frontline healthcare workers. Gavi has created the COVAX Facility through which self-financing economies and funded economies can participate. This also contains a separate funding mechanism, the Gavi COVAX Advance Market Commitment (AMC), which will support access to COVID-19 vaccines for lower-income economies. Combined, these allow the participation of all countries, regardless of ability to pay.17
The need to supply vaccines urgently is a complex situation and whilst there is much attention on the role of IP, there are many factors that need to be considered. FPM urges governments, industry and regulators to collaborate to find solutions to ensure supply as soon as soon as possible. This is important not only for COVID-19 but also to protect the world against future emerging infections.
This statement has been prepared by FPM and is supported by IFAPP.
- 1. https://www.ifpma.org/resource-centre/meeting-discusses-covid-19-vaccine-manufacturing-bottlenecks-that-must-be-urgently-tackled-for-c19-vaccine-output-to-reach-its-full-potential/
- 2. https://www.ifpma.org/global-health-matters/waiving-ip-rules-will-not-deliver-more-covid-vaccines/
- 3. https://www.ifpma.org/resource-centre/global-biopharmaceutical-industry-pulling-out-all-the-stops-to-address-coronavirus-public-health-crisis/
- 4. https://www.sanofi.com/en/media-room/press-releases/2021/2021-04-26-13-00-00-2216648
- 5. https://www.novartis.com/news/media-releases/novartis-signs-initial-agreement-provide-manufacturing-capacity-pfizer-biontech-covid-19-vaccine
- 6. https://www.lonza.com/news/2020-05-01-04-50
- 7. WHO COVID-19 vaccination: supply and logistics guidance
- 8. https://www.ip.mpg.de/fileadmin/ipmpg/content/stellungnahmen/2021_05_07_Position_statement_Covid_IP_waiver.pdf
- 9. https://www.ifpma.org/resource-centre/meeting-discusses-covid-19-vaccine-manufacturing-bottlenecks-that-must-be-urgently-tackled-for-c19-vaccine-output-to-reach-its-full-potential/
- 10. https://www.abpi.org.uk/media-centre/news/2021/may/five-steps-to-urgently-advance-covid-19-vaccine-equity#d353ce23
- 11. Bill and Melinda Gates Foundation - Why we focus on vaccine equity
- 12. World Bank | How to end the COVID-19 pandemic by March 2022
- 13. https://www.bmj.com/content/372/bmj.n771
- 14. https://www.news-medical.net/news/20210506/Indian-SARS-CoV-2-variant-shows-enhanced-host-cell-entry-and-immune-evasion.aspx
- 15. https://50years.ifpma.org/in-focus/hiv-aids/
- 16. https://www.who.int/initiatives/act-accelerator/covax
- 17. https://www.gavi.org/vaccineswork/covax-explained