We have often talked about the importance of NPIs (Nonpharmaceutical Interventions) like flu hygiene, school closures, and social distancing in the opening months of any pandemic because the creation, mass production, and distribution of an emergency vaccine is a difficult, uncertain, and time consuming endeavor.
We were lucky in 2009, in that the pandemic virus required a relatively simple `strain change’, and it did not require – as first feared – two shots spaced a month apart to produce immunity.
Even so, the first batches of the emergency vaccine arrived after the peak of the pandemic, and in much smaller quantities than predicted. Fortunately, the novel H1N1 virus proved to be relatively mild compared to past pandemics.
Last May, in Manufacturing Pandemic Flu Vaccines: Easier Said Than Done, we looked at a Japanese pharmaceutical manufacturer (Daiichi Sankyo Company, Limited) – which in 2011 received a Japanese government contract to supply H5N1 vaccines for 40 million people in the time frame allotted (6 months) – having to formally apologize for being unable to fulfill the terms of the contract.
Illustrating that gearing up to produce a pandemic flu vaccine in quantity, and in a timely manner – even when we are not hampered by an active pandemic – is a tall order.
While novel influenza is – at least based on recent history – the most likely cause of the next pandemic, it isn’t the only possibility. And non-influenza vaccines are often harder to create.
Despite 16 years of research, there is still no commercially available SARS vaccine. Seven years after MERS emerged in the Middle East, a vaccine remains elusive (see Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism), and twenty years after its discovery, a Nipah vaccine is still in the works.
None of this is meant to diminish the importance of developing, and distributing, a safe and effective pandemic vaccine in the shortest time frame possible. Even if it isn’t made available for the first wave, once it arrives, it could still save millions of lives.
But for that to happen, governments and vaccine manufacturers will have to work together, share information and virus strains, and agree to how (and where) the first vaccines available are allocated.
The World Health Organization has been working for years to develop a global framework for emergency pandemic vaccine production, and has recently published the results of their Third WHO Informal Consultation, which was held in Geneva, Switzerland, in June of 2017.
This 37-page PDF file outlines the anticipated obstacles and bottlenecks to emergency vaccine production, which includes not only scientific and logistical problems, but political ones as well.
From the Executive Summary:
This meeting report provides an overview of discussions and outcomes from the third WHO informal consultation on influenza vaccine response during the start of a pandemic, held in June 2017. The aim of the meeting was to address challenges and bottlenecks in vaccine response at the start of an influenza pandemic, including issues associated with the decision to start the pandemic vaccine production which might entail the switch from seasonal to pandemic vaccine production.
The first WHO informal consultation on this topic, which took place in 2015, analysed the complexities of vaccine response at the start of an influenza pandemic and provided clarity and understanding among key players on roles and responsibilities of the response. The 2 nd WHO informal consultation in 2016 furthered the discussion to developing principles and processes of decision making of the start of pandemic vaccine production and addressing bottlenecks surrounding the switch. Based on the outcome from the two consultations, the 2013 interim WHO pandemic guidance WHO Pandemic Risk Management Framework (PIRM) was finalized in 2017.
The third informal consultation developed operationalization of the outcomes from the previous two consultations jointly with influenza experts, public health officials, and other stakeholders to address vaccine response at the start of an influenza pandemic, in particular, issues surrounding the potential switch from seasonal to pandemic vaccine production. In addition, the specific challenges for low- and middle-income countries were discussed.
During the consultation, participants drafted an operational framework for pandemic vaccine response, developed a common understanding of an effective pandemic vaccine response, and identified key challenges and potential bottlenecks that would interfere with switching from seasonal to pandemic vaccine production.
Guiding principles of technical, ethical and political aspects involved in making the decision to start pandemic vaccine production were also elaborated.
Key outcomes from the third informal consultation included the following:
- A clear, transparent and integrated approach to initiating pandemic vaccine production was proposed; this proposed approach will be further developed by WHO working groups.
- At the start of a pandemic, WHO will issue recommendations on pandemic vaccine composition and use which will be based on a variety of criteria clearly communicated to all stakeholders involved in the pandemics vaccine response.
- Such criteria will be based on risk assessment and to be developed by
WHO working groups. These will inform the vaccine production decisions.
Solutions to potential bottlenecks in the pandemic vaccine response at the start of a pandemic should be further prioritized, addressed or operationalized through WHO working groups
- Communication to clarify the critical responses – including the declaration of a public health emergency of international concern (PHEIC), the declaration of an influenza pandemic, the recommendation to start pandemic vaccine production and subsequent availability of pandemic vaccines should be comprehensively incorporated into global and national pandemic preparedness planning.
These informal consultations clarified critical complexities at national, regional and global levels, and the need for WHO coordinated global response especially the decision to commence the start of pandemic vaccine production based on risk assessment.
The entire document is well worth reviewing, as many of the barriers to developing and distributing an emergency vaccine are not immediately obvious, nor easily solved.
As the chart below illustrates, their 6-months to the first vaccine availability timeline is based on everything going right.
The following timelines represent ideal circumstances, when all staff, facilities, reagents, equipment and process stages are in place and function optimally. If some activities do not go well, they may take longer and this is indicated by the hatched areas of the chart. Due to the interrelatedness of many of the activities, a delay in one activity would delay others in the timeline.
The reality is, even under the best of circumstances, most of the world would not see a pandemic vaccine for a year, maybe longer. Lesser developed countries, particularly those without domestic vaccine production capabilities, would likely find themselves at the back of the line.
But no one is guaranteed that they’ll see a vaccine in a pandemic.
Last year Johns Hopkins presented a day-long pandemic table top exercise (see CLADE X: Archived Video & Recap), where a vaccine was expected `within 6 months’, but turned out to be a failure.
If you don’t have the time to watch the (highly recommended) entire 8 hour exercise, I would urge you to at least view the 5 minute wrap up video. It will give you some idea of the possible impact of a severe – but not necessarily`worst case’ – pandemic.
While telling people to wash their hands, cover their coughs, avoid crowds, and stay home while sick may seem like an inadequate response to a pandemic – they and other more disruptive measures like school closures, cancellation of public events, etc. – will almost certainly be our most powerful weapons until a pandemic vaccine becomes widely available.