Corona Daily 146: Bottlenecks

On the fifth of March, my parents got their first shot of Oxford/AstraZeneca vaccine (called Covishield in India). They were told to get the second shot four weeks later. Today, the Indian government asked the states to increase the gap between doses to 6-8 weeks. Reportedly, the Oxford vaccine will henceforth be given only as a second dose. Anyone coming for the first dose will be given Covaxin, a locally developed vaccine by Bharat Biotech.

The Serum Institute of India, the world’s largest vaccine producer, has informed several countries of possible delays in supply. The European Union, embarrassingly lagging in vaccination, is considering banning export of vaccines. UK’s ambitious plans have suddenly hit a roadblock.

Why are the vaccine shipments getting delayed everywhere?

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Anyone who has worked in the manufacturing industry knows how complicated supply chains can be. The i-phone, the size of our palm, is assembled in China with components coming from over 27 countries. Each product has suppliers for equipment and raw materials, and the suppliers in turn have other suppliers. The logistics of this entire pyramid must work as planned. Even in our personal lives, we know the wide variance between our plans, our desires, and reality.

Industries get close to their targets after decades of trial. But covid vaccine production is an infant.  A year ago, the USA invested billions of dollars to develop the vaccines, but not enough attention was paid to the supply of the raw materials.

The raw material suppliers had full sets of orders from pharma companies for items totally unrelated to covid. Now suddenly, they have been asked to set everything aside, expand their capacities, build new equipment, employ skilled workers, and refuse supplying to their earlier customers.

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A new production facility for a vaccine like Oxford can take six to nine months. The biggest issue, unrelated to raw materials, is with yields. Yields depend on the health of the underlying cell culture. Quality control issues, such as those relating to temperature, humidity or compromised sterility, lead to less vaccine at the end of the process. Surprisingly, at two identical facilities, the yields can vary by a as much as an order of three. Human nature, particularly in an emergency, tends to take the best-case scenario. Even running three shifts doesn’t help when the output can vary wildly.

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A shortage of any critical item results in irreplaceable shortage of vaccines. Pfizer, Moderna and Novavax vaccines use bioreactor tanks. If it was a restaurant kitchen, you could call them containers for vaccine soup. The bioreactor tanks need giant disposable plastic bags as sterile liners. Without them the vaccine may get contaminated. In EU and some other countries, this has emerged as a production bottleneck. The sterile plastic bags are produced by a small number of suppliers, and vaccine producers have struggled to source them. Merck has now announced expansion plans to address this issue.

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Or take the case of vials. The liquid vaccine has to be put into vials before it can be distributed. Pfizer and Moderna vaccines require ultra-cold temperatures to preserve them. Normal glass vials would break in the super-freezers. Just a single damaged vial can ruin an entire batch of doses and stop the production line. Corning, the US manufacturer, was asked to supply special super strong Pharma grade glass called Valor.

Most vials need rubber stoppers. In autumn 2020, tropical storms in Thailand, Vietnam and India led to rubber shortages.

United States of America is now hoarding rubber. Both Trump and Biden used a 1950 act from the Korean war times called “the defence production act”. This allows US presidents to order a private company to divert manufacturing to what the State needs. A year ago, for example, General motors was ordered to produce ventilators. Biden is likely to use this act to use the scarce rubber for vaccine needs.

Rubber gloves are recommended to administer a vaccine. Except the USA, all other nations are likely to face shortages of rubber.

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More on the bottlenecks tomorrow.

Ravi