PART III: Finish off Covid19. Hurry.
How do we manufacture vaccines for 7.8 billion people?
This is the third part of the Cosmopolitan Globalists’ blueprint for ending the pandemic. We argue that the United States must immediately lead the democratic world in a program to eradicate Covid19 globally.
We believe it feasible to vaccinate the entire planet by the end of 2021, if the US has the will to do it. It will be costly. But the cost is a fraction, and very likely only a small fraction, of the cost of allowing the disease to spread uncontrolled. Even if the United States assumed the entire cost of vaccinating the world—and clearly this would not be necessary—the cost would amount to a rounding error in the proposed USD 1.9 trillion coronavirus relief plan.
We urge President Biden personally to take charge of this. This is a global emergency with implications far beyond the Americans’ health. Controlling the pandemic is essential to rescuing the global economy, which is essential to American national security and the security of American allies. The excessively cautious and dilatory FDA can’t be expected to have this perspective. But the President can. The FDA and other American bureaucracies must not be allowed to plod along at their typical, risk-averse pace. The President must take charge of the global pandemic response. This, not a speech at the Munich Security Conference, is the test of whether “America is back.” To be a global leader, Americans must lead the globe.
In Part I, we reviewed the strengths and weaknesses of available vaccines and therapies. In Part II, we argued that fast tests, and every vaccine with a tolerable safety profile, must be approved immediately.
Today, we explain how to manufacture enough doses of vaccine for everyone on the planet.
We encourage you to share this blueprint with your elected representatives.
By Owen Lewis and the Cosmopolitan Globalists
How many doses do we need?
We’ve solved the problem of designing a safe and effective vaccine against Covid19 and done so in record time. Now, all 7.8 billion of us need at least one, and often two, injections.
Wealthier and more-developed countries can manufacture or buy their own vaccines. But many poorer and less-developed countries can’t. Some have significant manufacturing capacity. India, for example, is a pharmaceutical powerhouse; it is already the source of more than half of the global vaccine supply. But many countries have no domestic vaccine manufacturing capacity at all, nor can they afford to buy them in the quantity they need.
Some wealthy countries have already reserved doses far in excess of their populations. The UK, for example, has ordered five doses for every citizen. In part, this is because governments haven’t known which vaccine candidates would prove safest and most effective and so they hedged their bets.
Most wealthy countries have reserved at least as many doses as they need to ensure all of their citizens are vaccinated. But poorer countries have been unable to do anything of the sort. Most countries in Africa, the Middle East, Southeast Asia, and South America have reserved less than half the amount of vaccine they need. Many countries have reserved less than five percent.
World map of vaccine contracts, from Bloomberg
A reserved vaccine is not the same thing as a manufactured vaccine, however. Manufacturing will have to be ramped up significantly just to meet the wealthy countries’ targets. To meet the target of vaccinating the whole world by the end of 2021, manufacturing must be ramped up very significantly.
Our goal is global herd immunity. We reach herd immunity when enough of the population is immune, through vaccination or prior exposure, that the disease can no longer spread. How many doses of vaccines must the world make to achieve this by the end of 2021? Pick a number between 50 and 100 percent of the total global population, and (depending on the vaccine in question), double it. (Since the most effective vaccines we’ve so far devised require two injections, we’ve run the numbers assuming a two-injection scenario.)
The number is imprecise because we don’t yet know it. The threshold number is an empirical statistic, not a guess; we will only know it when we have more experience. The threshold for polio is about 80 percent; for measles, 95 percent. Given the infectiousness of Covid19, the number is probably on the higher end. Because we don’t know, we’ve based our calculations on a goal of 100 percent coverage. The closer we are to 100 percent, the better our chances of conquering the disease and forestalling mutations.
Remember that no vaccine is 100 percent effective. The threshold for herd immunity may be 80 percent, but this doesn’t mean herd immunity is achieved when 80 percent of the population is vaccinated. It’s achieved when 80 percent of the population is immune. Depending on the efficacy of the vaccine—and on levels of immunity already present in the population—it may not be necessary to vaccinate 80 percent of the public. Or it may be necessary to vaccinate more of it.
The world’s population, by the end of 2021, will be 7.95 billion. So we must manufacture nearly 16 billion injections, even though herd immunity might well be achieved at 80 percent coverage or less. We should be preparing, now, for the worst-case scenario, not the best.
How close are we to doing this, given current production schedules? The good news is we’re not all that far off.
The production schedule
Pfizer, Sanofi, and Moderna, will produce 3.1 billion doses of mRNA vaccine in 2021, enough to vaccinate 1.55 billion people. Novartis has just signed an agreement to produce Pfizer’s mRNA vaccine. We don’t yet have production estimates, but we reckon they can probably produce as many doses as Sanofi: about 0.1 billion. All together, they will produce 3.2 billion doses of mRNA vaccine, enough for 1.6 billion people.
Pfizer’s mRNA vaccine must be stored at a very low temperature, which is a severe logistical constraint. Failure to observe temperature specifications at any part of the cold chain renders the vaccine useless. Generally, vaccines must be transported between 2-8°C. Pharmaceutical companies are accustomed to dealing with this requirement, though it’s not a simple matter. The mRNA vaccine is much more challenging. The key molecule is extremely fragile. Pfizer’s vaccine must be stored at -70°C. Moderna vaccine’s is slightly less demanding, but still needs to be transported at -20°C. Pfizer has developed special packaging that allows the vaccine to be stored for ten days on dry ice. It’s carrying out tests to evaluate the vaccine’s stability at the more traditional temperatures of 2-8°C, and it’s exploring methods for transporting it at room temperature. The results of this research will be critical.
Wherever electricity is unstable, as Texas recently discovered, the vaccines spoil. Barring an innovation that solves this problem, we believe it is only suitable for use in the rich world and in urban areas of poor countries. According to our back-of-the-envelope calculation, 1.5 billion people live in the rich world. Another 3.3 billion live in urban areas of the poor world. If mRNA vaccines are used wherever they can be—and because they are more effective, they should be—our projected supply of vaccines is 6.4 billion doses short.
But other vaccines can make up the shortfall. The AstraZeneca/Oxford vaccine is 82.4 percent protective, and it can be stored at refrigerator temperature. It’s the vaccine of choice wherever there’s a shortage of stable electricity and ultra-cold freezers. Its efficacy makes it a good choice everywhere, though: We expect it to be used broadly in rich and poor countries alike. AstraZeneca/Oxford predicts it will make 3 billion doses this year, enough to protect 1.5 billion people.
Trial data published in The Lancet suggests, to our surprise, that Russia’s Sputnik V vaccine works extremely well, with a 91.6 percent efficacy rate. Russia says it will produce 1.4 billion doses in 2021, enough to vaccinate .7 billion people. Like Moderna’s vaccine, the Sputnik V must be kept very cold. It is poorly suited to undeveloped rural areas. But some 30 countries around the world have ordered it anyway, including Turkey, which will manufacture it; Mexico; and much of Central and South America.
China expects to produce 1.1 billion doses of its Sinopharm vaccine by the end of this year, enough to cover .55 billion people. Its estimated efficacy is 79.3 percent, which means it can render .44 billion people immune. Sinovac is quickly adding production capacity with a goal of producing a billion doses in 2021, enough to vaccinate half a billion people. But the news from Brazil is not encouraging. Its efficacy may be low as 50.4 percent. Reducing vulnerability to the disease by half is better than nothing, but obviously, most people would prefer to receive a more effective vaccination.
The single-shot CanSino vaccine hasn’t yet received full approval from the Chinese government. Initial data, not yet peer reviewed, suggests an efficacy rate of 65.7 percent, on par with the still-unapproved Johnson & Johnson vaccine based on the same technology. We don’t yet know how much will be produced, but early estimates suggest between 0.1 and 0.2 billion doses in 2021. All three of China’s vaccines may be stored at refrigerator temperature.
Even though India’s Covaxin is in wide use as part of India’s national vaccination campaign, we’re still unsure how well it works. It’s stable at refrigerator temperature, so it’s apt to be a favorite. African countries, in particular, are keen to purchase it. Manufacturers expect to make .7 billion doses this year, enough to vaccinate .35 billion people.
Novavax and Johnson & Johnson have both applied for the approval of their vaccines in countries around the world. If all goes well, these vaccines too may soon contribute to the global effort. Both can be stored in normal refrigerators. Johnson & Johnson’s vaccine is 66 percent effective in preventing moderate to severe disease. There is no data yet about whether it prevents asymptomatic illness. As expected for an adenovirus vector vaccine, its efficacy was slightly higher in the United States than in poorer countries. Despite production delays, the company expects to produce a billion doses by the end of the year. It’s a single-shot vaccine, so that means a billion more people vaccinated, even if the protection it offers is not as complete.
The Novavax vaccine’s efficacy is much better, at 89.3 percent, bringing it close to Moderna’s and Pfizer’s. With its manufacturing partners, including the Serum Institute of India, Novavax should be able to produce a billion doses in 2021, enough to vaccinate half a billion people.
How close are we to having the number of injections we need? If everything goes without a hitch, 6.8 billion people can be vaccinated by the end of 2021. If all of these vaccines make it into our arms, and if the threshold for herd immunity is on the lower end of the scale—and if the world remains diligent about masks, hygiene, social distancing, testing, and contact tracing—this should be enough to end the nightmare.
But it isn’t realistic to assume everything will go without a hitch. What’s more, none of these vaccines are 100 percent effective, and the threshold for herd immunity might easily be higher. So we must manufacture more.
Encourage collaboration
Meeting this demand will require collaboration among manufacturers. The WHO initially encouraged manufacturers voluntarily to share their data and intellectual property in the Covid19 Technology Access Pool, but the pharmaceutical industry wasn’t keen: Their knowhow, after all, is the result of considerable investment.
As the pressure on manufacturing pipelines grows, however, it has become obvious that their secrecy is an obstacle. Some companies have voluntarily begun sharing their information. The Department of Justice recently gave six biopharma companies permission under antitrust law to share their research on monoclonal antibody candidates. We want to encourage vaccine companies to do the same, and we should make it easy for them to do so. The Biden Administration should facilitate and encourage this at every turn, making federal funding contingent upon it. Knowledge of manufacturing obstacles—and techniques for solving them—should likewise be pooled to the greatest extent possible.
It would be particularly useful for the Biden Administration to create an international platform to coordinate contracts among vaccine manufacturers, contractors, distributors, governments, and donors. If governments and donors agree to allocate funding only to companies that use the platform, it would result in significant efficiencies. Companies that used the platform would benefit from a guarantee that their capacity will be used and a clear timeline of commitments. If their vaccine candidate fails, they could be enrolled automatically as a licensed manufacturer of a successful vaccine. Governments, in turn, would benefit from spreading the risk among vaccine candidates: If one fails, there will be others to take its place.
Appropriate the IP
There are two obvious ways to ramp up production. The first is through second-source agreements, in which a company with a viable vaccine contracts with another company to produce it. Breaking the production bottleneck and expanding manufacturing capacity will require widespread technology transfer. Companies must share their knowledge, technology, and data with domestic manufacturers.
Some vaccine developers have agreements to this effect already: AstraZeneca and Novavax have agreements with the Serum Institute of India, Johnson & Johnson has one with Aspen Pharmacare in South Africa. The US government can make closer collaboration a condition of its contracts with vaccine manufacturers: It can insist, for example, that companies conduct engineering and stability studies jointly to save resources and time.
The second, obvious, way to ramp up production is to make vaccine technology public domain. This would allow companies around the world to manufacture and distribute them without paying royalties to their creators. The original companies could still make and sell their vaccines, but public domain designation would allow production to proceed at much greater scale than any single company, even with second source agreements, could manage. This would also help to remove production bottlenecks and lower the unit cost of the vaccine.
The obvious candidates are the smaller companies that received money through Operation Warp Speed, such as Moderna and Novavax. The legal argument is straightforward. When the US government signs R&D contracts, it includes a clause reserving the right to make use of the intellectual property if it chooses. Typically, the clause is never exercised; it’s there so that in a national emergency, such as war, the government can make as much of the technology as it needs at an acceptable price. This is precisely such a situation. Moderna has eagerly volunteered its vaccine for this purpose, so in this case, there’s no obstacle. The technology should be made public domain, now.
Pfizer conducted its research on its own dime. But we propose that Pfizer’s intellectual property be appropriated, too.
We hear gasps from our readers. That’s theft. You can’t do that to Big Pharma!
Our readers are right to be alarmed by this idea—and if they aren’t, they’re foolish. Appropriating intellectual property without compensation would hobble future efforts to develop essential medications and vaccines. This will not be the last pandemic; indeed, for a number of environmental reasons, we should expect them to occur more frequently in the coming century. Big Pharma’s hunger for profit is the only reason we have any hope of eradicating this pandemic in 2021. We can’t just appropriate their IP. That would kill the golden goose.
So we propose appropriating their IP while compensating them so handsomely that they’re positively eager to do it again. We suspect six billion dollars in cash would keep them sweet, but this is no time to be stingy. Ask them what they want. Don’t say, “Our bottom line is whatever you ask.” But that should, in fact, be your bottom line.
Even though the US government isn’t legally required to compensate Moderna, it should do it anyway. We need to preserve the incentive to produce these kinds of vaccines. Four billion dollars, we think, would make for a handsome incentive. If the UK and Sweden do the same for the Oxford/AstraZeneca vaccine, production could be ramped up rapidly.
We should not object if China wishes to manufacture these vaccines. It’s not a zero-sum game. To the contrary, the faster the world is vaccinated—and the more effective the vaccination—the better off everyone will be.
Predictable obstacles
Manufacturing setbacks must be expected. Consider how many have happened already happened. Pfizer’s shipments were delayed, in January, because it had to retool its plant in Belgium. Canada was hard hit; shipments were reduced by 50 percent. Production is expected to return to normal soon. Pfizer maintains the improvements will allow them to raise production from 1.3 billion to 2 billion doses this year.
Moderna’s vaccine has also been delayed owing to the challenge, the manufacturers say, of ramping up their plant in Switzerland. Shipments have been reduced to parts of Europe and Canada. AstraZeneca has suffered manufacturing glitches so severe that in the first quarter, its Belgian facility was unable to provide 60 percent of the contracted doses to the EU. This prompted the EU to mutter about banning the export of vaccines—all vaccines. Manufacturing in the UK and India is so far on schedule, despite a fire at the Serum Institute in January.
Russia has so far had difficulty producing enough of the second shot of their Sputnik V vaccine. The manufacturer claims this will not be an obstacle to future production and delivery. No delays have been reported, so far, with India’s Covaxin or the three Chinese vaccines.
Johnson & Johnson has had to revise its initial estimate. Its early production goals will not be met until April. Novavax has not recently issued an update, but given the difficulties other manufacturers have faced in scaling up production, it wouldn’t be surprising if there were delays.
The choke points are predictable: raw materials, glass vials, cell cultures, and enzymes must be sourced; new plants and equipment must be built. If any component in the chain is missing or delayed, the vaccine will be, too. For example: Vaccination has been held up for lack of low dead-space syringes, which minimize the amount of vaccine wasted in the needle. By using these syringes, a sixth dose can be extracted from what is usually a five-dose bottle. This would augment Pfizer’s 2.2 billion doses by .44 billion, which means another .22 billion people protected. Until now, these syringes were typically used only for extremely expensive medications, so manufacturing capacity for them is limited. More must be built.
The Biden Administration plans to use the Defense Production Act to increase syringe supply, which is exactly what it should do. It should be possible to extract extra doses from Moderna’s vaccine this way, too. These contain ten doses to the vial. Obtaining an eleventh dose would boost supply by 0.1 billion doses in 2021—and this may be true of other vaccines, as well.
Solve these problems now, not later
All of this should have been considered last year, not now. The manufacturing and logistical problems we will face in the coming year should be solved now, not when they inevitably arise.
The Biden Administration should be working in close cooperation with the pharmaceutical and logistics industry, now, to anticipate every manufacturing challenge that may arise as a result of increasing manufacturing scale. Wherever it would expedite vaccine production and shipment, Biden should invoke the Defense Production Act. BARDA, DARPA, and CEPI can all be mobilized to support the effort.
This means planning supply chains actively, not passively, and identifying every possible risk and disruption to the manufacturing process now, not at the last minute. The top two US manufacturers of vials, for example, can produce 280 million vials per year. These can hold 2.8 billion doses. That’s not enough. The suppliers of niche chemical and biological vaccine components are spread around the world. Everyone is competing for their products. The number of US companies capable of loading mRNA into lipid nanoparticles and purifying the vaccines at the scale we need is inadequate. There is no way we can do this without extensive international collaboration.
What component materials does Pfizer need for its special packaging? Now’s the time to make sure there will be enough. The US and Canada together manufacture between 30,000 and 35,000 tons of dry ice annually. That’s definitely not enough. What if Pfizer is successful in developing a method for transporting its vaccine at traditional temperatures? We need to reserve enough of every component material it might use to do this, now. (And the Biden Administration should fund Pfizer’s research, too—and anyone else who’s doing research that might help to crack this problem. It’s as important to solve it as it was to develop the vaccine in the first place. Operation Warp Speed should be the model for funding the research. This will also allow the government to make the technology open source, if it’s successful.)
Redundancies need to be built into the supply chain, now. Every warehouse with an ultracold freezer needs a store of dry ice should the freezer fail. If in six months’ time the Cosmopolitan Globalists read that a shipment of vaccines has perished because a warehouse freezer suffered a power outage, we will be apoplectic. This is a predictable and preventable problem. There will be no excuse for it.
The vaccines, whatever their market price, are more precious than diamonds. This means they will be stolen. As we saw at the beginning of the pandemic, when PPE was heisted around the world, they will be particularly tempting targets. Organized crime groups are looking for ways to steal these vaccines, now—so we must be looking for ways to ensure they don’t.
Similarly, we should expect large-scale cyber-attacks aimed at disrupting vaccine production and transport. The usual culprits will be involved. We must establish a platform, now, for sharing threat intelligence among governments and manufacturers. This will provide better warning of impending attacks. It will also raise awareness of the threat among those whose carelessness creates vulnerabilities.
What about IT? Can our logistics companies handle the necessary exchange of data? If not, this must be solved, now. Supply chains usually link many different companies and subcontractors, each of which handles a leg on the route. Now is the time for an inventory of every company and stage—manufacturers, air cargo carriers, airports, ground handling agents, freight forwarders, transport companies, warehouse operators, vaccination centers, medical staff—to assess their capacity. What do they lack? What might they lack? Every step of the journey should be modeled and simulated, now, including every potential disruption—from fluctuations in vaccine to sites taken down by power outages. We do not want to discover at the last minute which airports lack temporary air storage capacity. The time to build it is now.
What raw materials need to be reserved to build cold-chain storage facilities? Reserve them, now. What about sensors to monitor temperatures? Build them, now. A central IT platform to track receipt of these measurements? Now. Blockchain technologies might prove their value here: They were practically designed for such a situation. But a project of this scale won’t happen on its own; the Biden Administration should take charge of it—now.
Now, not later, is the time for manufacturers to reserve enough raw materials to ensure redundancies across the supply chain. The Biden Administration can help to finance this. In exchange, manufacturers should obey guidelines ensuring a diversity of global suppliers, so that none will be made hostage to diplomacy or misfortune. Contracts with manufacturers should include incentives for companies to invest, now, in scaling production and stockpiling goods. The operative principle should be exactly the opposite of the just-in-time ethos management has spent decades cultivating. If it is done correctly, there will be waste.
Contracts should specify, too, that producers must be transparent about their inventory: They should reevaluate, now, the risk of shortages of key raw materials.
Nor are the manufacturing challenges limited to Covid19 vaccines. It is not just the United States that needs rapid testing, but the world. Antibody drugs used to treat the disease are complex to produce. All of the above arguments apply to these drugs and therapies, too.
We must also plan, now, for the possibility of mutations that render our vaccines ineffective. Most are highly effective against the UK variant, but evidence is coming in that they are not as effective against the South African variant. The AstraZeneca vaccine prevents severe disease, hospitalization, and death; it seems nearly useless against mild and moderate cases of the disease. Moderna is already working on a booster shot aimed at the South African strain, which doesn’t appear to be more deadly, but does spread more easily.
Mutations are inevitable. That’s what viruses do. This is another reason vastly to ramp up manufacturing capacity—today. It’s all but certain we’ll need it.
So hurry.
In the next two installments in this series, we will discuss the remaining big problems to be solved. First, the logistical challenge of shipping and administering these vaccines is enormous.
Second, the anti-vaccination movement must be comprehensively defeated.