Vaccine Development: Mind the Gap

Article by Timothy Clayton CEng MIChemE

Timothy Clayton details IChemE’s Covid-19 Response Team’s work on identifying what needs to be done

VACCINES are a wonderful invention that have transformed the health of billions. Not only can an individual be protected by a vaccine but, once enough people have been vaccinated, the whole population is protected because the infection cannot spread in a sustainable way (herd immunity). If a good vaccine that can generate an immunity to the virus causing Covid-19 is developed, there will be huge benefits (see Table 1).

We are promised a vaccine at record speed but Ken Frazier, CEO of MSD notes that we must be careful not to be too bullish about the speed of development of a new vaccine. In the last 25 years only seven truly new vaccines have been developed and taken to the market. Making a new vaccine is difficult. The fastest vaccine ever brought to market was for mumps, and took four years. Normally a vaccine takes about ten years to develop and costs more than US$1bn to get to market. Consequently, there is a timeline that allows for production facilities to be built and for supplies to be ramped up. This is not the case for Covid-19; everybody wants to get back to normal and a vaccine will be invaluable – but where is the capacity to make and distribute vaccine when a good candidate is available?

Development timelines are constrained by clinical studies. Because the vaccine is given to healthy people it is essential to ensure its safety using a large number of subjects. Before vaccines can be used in the general population, tens of thousands of people need to be included in clinical studies to test safety and efficacy. A major challenge in development of a vaccine is carrying out a clinical study that will be conclusive. The clinical trial must be carried out in an area where the virus is actively infecting a large enough number of people to allow demonstration of efficacy and duration of protection. A vaccine that lasts for less than a year is not much use to anyone. At present Brazil, South Africa and the US are being chosen for trials, but if the rate of transmission drops during the trials the data may not be conclusive enough and the trial period may need to be extended and new sites opened in other countries. When conclusive data are available, everyone will want the vaccine immediately.

As part of the Covid-19 response, an IChemE volunteer team has been looking at the options to help this extraordinary effort to develop and manufacture a vaccine.

Table 1: Vaccine benefits based on present knowledge

The challenge

What process will be used? We want to know which vaccine will work, and can we make enough? Before major decisions on manufacturing capacity are made it is normal to answer three questions. Is the vaccine safe? Does it give immunity? And how long does the immunity last?

There are at least 160 candidates in development (summarised in Table 2). Many of the vaccine approaches being used have never produced a marketed vaccine.

There are significant differences in the methods used to produce different types of vaccine, so we can’t make general assumptions about what might be needed yet in terms of production capacity for drug substance or the type of filling and distribution capacity. For example, will the product be filled into multi-use bags, single or multi-use vials, pre-filled syringes or special devices, and will it be stored and transported as a liquid or lyophilised and will it be frozen, chilled or at ambient temperature?

Table 2: Vaccines in development as of 13 July (23 candidates in clinical studies, 137 in preclinical studies) Source: WHO Novel Coronavirus Landscape

Assuming that one, or several of these vaccines is successful, what strategy will be used to make it, and where? There is no clear definition of what a successful vaccine to prevent Covid-19 would look like, and questions remain. For example:

  • Is a quick and dirty initial vaccine which is not as safe as would normally be accepted likely to be registered? Apart from liability issues (who will pay compensation and how much) there is a danger of losing the trust of the general population and generating a perception that the vaccine is not worth the risk.
  • What is the acceptable response to the vaccine? (% immunised, length of immunisation, full immunisation vs partial immunisation –what if we mitigate the infection to reduce the death rate but don’t stop the spread?).
  • Will the supply of the vaccine be limited by materials or delivery system costs/availability? (simple examples are availability of disposable bioreactors, cell culture medium, RNA manufacturing components, glass vials, silicon rubber tubing and syringes and needles. Some vaccines also need an electroporation device to get the vaccine into cells after injection.)
  • How quickly will the supply need to be ramped up? We are adding a need for billions of doses of product that was not needed previously. A new vaccine plant with filling capacity will normally take 3–5 years to build and commission depending on location and capacity. We also need to continue other vaccine manufacture. Major vaccine manufacturer GSK claims to already make about 3m doses of vaccine a day. That is about 1bn doses per year – or about 1/15th of the quantity just needed for Covid-19 but not necessarily available.
  • The race today is to make a vaccine – any vaccine – and cost is not a major consideration. However, as time progresses, governments will want a cost-effective vaccine. To date Moderna is thought to be targeting US$50–60 per course (US$25–30 per dose), Biontec/Pfizer US$19.50 per dose, and AstraZeneca a few dollars per dose. To use the Moderna vaccine for 1 cycle of vaccinations in the UK would cost about US$3.4–4bn just for the vaccine. Even a few dollars a dose will be out of reach for much of the world’s population. As the memories of the economic cost of our recent shutdowns recede, there will also be significant pressure to reduce annual re-vaccination costs if they are necessary, so a second round of more cost-effective vaccines may be needed.
  • Allocation of vaccine - will there be enough to supply key populations?
  • Will we have a choice of vaccines?

Article by Timothy Clayton CEng MIChemE

CMC at Antev

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