War and IPs

Joe Biden’s administration came to power with a pledge to take Covid-19 seriously, and a promise to deliver 100 million vaccine doses in its first 100 days. In the end, it managed twice that. Still, in the President’s words, “the war is far from won”. The key rate-limiting factor there is rhetoric: pandemics are not wars – they’re not even elections – but over the past year, taking Covid-19 seriously has got tangled up in taking its most pervasive metaphors literally.

Though, thankfully, Biden isn’t declaring victory, he has, like Trump before him, made extensive use of the Defense Production Act – a law passed to mobilise the US for the Korean War in 1950 (and thus targeted at the spread of communism, rather than coronavirus) – to prevent the export of raw materials for vaccine manufacturing. The US, and a select few other countries, are well on their way to herd immunity; much of the rest of the world fears it is being left behind.

Logistically, this looks a bit like a reversal of what happened in the early months of 2020, when disruptions to PPE and API supplies that relied on China and India drove calls for European and North American countries, which quickly became the contagion’s epicentre, to shorten and reshore their supply chains. When it comes to vaccine manufacturing, however – and particularly for the more innovative vaccine platforms – many of the most important raw materials and critical input components actually come from the most economically developed nations.

Through March and April 2021, Adar Poonawalla – the CEO of the world’s largest vaccine manufacturer, the Serum Institute of India, where the Oxford-AstraZeneca (AZ) vaccine and Novavax candidate are being made – repeatedly requested that the US lift the DPA export ban on materials like filters, bioreactor bags and single-use systems, so established manufacturers in the rest of the world could ramp up production. Unsurprisingly, a law enacted to help the most powerful country on the planet fight a war is having an adverse impact elsewhere. In spring 2020, the bodies were piling up outside New York’s graveyards; at the time of writing, the people of New Delhi are cremating their suffocated dead by roadsides and in empty lots.

On 25th April 2021, that devastation finally prompted the US to reconsider its use of the DPA. Two days earlier, multiple speakers at the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) vaccine manufacturing media briefing had fingered the Act as one of the biggest threats to the global effort to stop the pandemic. Michelle McMurry-Heath, president and CEO of the US-based Biotechnology Innovation Organisation (BIO) contrasted the impact of the DPA with the “positive steps” the Biden administration took in re-engaging with WHO and committing to Covax, which has so far delivered just over 40 million doses to low and middle-income countries.

“The Defense Production Act, which was really designed to withhold capacity, expertise, doses and raw materials to the US customer base, was wellintentioned but somewhat misguided at this stage,” she said. “We need to get those raw materials out to the limited manufacturing capacity that exists around the globe and now is the time to act on that. The rate-limiting step is not intellectual property, the rate-limiting step is manufacturing know-how and capacity, and we need to make sure that in every corner of the world that has this great capacity... they have the ability and the means to manufacture as many doses as possible.”

Sai Prasad, executive director for quality operations at Bharat Biotech, makers of Covaxin, an inactivated virus vaccine approved for use in India, and the president of the Developing Countries Vaccine Manufacturing Network (DCVMN), echoed McMurry’s point, listing Europe and China alongside the US as important suppliers of raw materials and production tools. “There is no way that we could get that technology manufactured anywhere else,” he stressed. “We really have to depend on these companies that we have established long-term partnerships with, and [on] countries to enable the free flow of goods between where the manufacturing of these materials is happening and where the vaccine manufacturing is happening.” Crucially, around 55% of the world’s vaccine manufacturing capacity is in East Asia.

Prasad linked the risks of misjudged protectionism to those of variants like the multiple strains currently ravaging India. “I don’t think any country... can just protect their population by these kinds of concepts or laws and not expect the virus to come back again, and I think we are seeing this in the waves and waves of the pandemic,” he said. “Policymakers around the world need to think about this. I would request [that] better and cooler heads prevail.”

Cool, calm and collective

The US government’s willingness to reconsider its export restrictions is a start, as is the recently announced Covax manufacturing task force, but there are far more examples of missteps. Frustrated by the slow delivery of doses through Covax, a majority of WTO members are now pushing for the Covid vaccine IP waiver proposal initially submitted by India and South Africa in October 2020. Prasad couldn’t offer a view for the DCVMN as a whole but, with the other speakers at the IFPMA conference, cautioned that a focus on sharing IP is no way to solve the more pressing shortages of materials and expertise. It could worsen the situation.

“All our IP is on the internet,” pointed out Moderna CEO Stephane Bancel. Any interested party can download instructions and ingredients lists but, as Prasad put it, you can’t manufacture vaccines from USBs. The resources that companies like Moderna or Bharat Biotech use for technology transfers, which take six months to a year, are the same they use to make drugs. If they can’t be sure that they’re working with a partner that has the expertise to make vaccines, it’s a dangerous waste of time. The IFPMA has recorded 214 such agreements involving Covid-19 vaccines so far, but every additional manufacturer puts more strain on the raw material supply chain, potentially diverting resources from sites approved to provide doses today. After a certain point, there’s a choice between scaling up and scaling out, between inoculating people now or later.

“Trying to diffuse the limited raw materials that we have right now across many more manufacturers that perhaps don’t have experience manufacturing vaccines, could jeopardise the progress we’re on track to make,” explained McMurry-Heath, a former FDA official. “We need to recognise that there are only a handful of manufacturers across the globe who have that expertise at hand, and we need to focus on getting them the materials they need to produce as many doses as quickly as possible.”

Technology transfers are difficult enough within single countries and companies. McMurry-Heath alluded to a contract manufacturing site in Baltimore, where a mix-up of AZ and Johnson & Johnson vaccine ingredients resulted in the loss of 15 million doses, while issues at AZ production plants in Europe have caused similar breakdowns in the continent’s politics, negatively impacting both the global supply of numerous different vaccines and overall vaccine confidence. Citing lower than expected yields and difficulties moving materials through different territories, AZ only delivered 30 million of the 80–120 million doses the EU expected by the end of March 2021, and projects that it will deliver less than 100 million of the 260–300 million ordered by June. In response, the EU has blamed its slower than expected vaccine rollout “solely” on the company, limited vaccine exports from the bloc (though it remains one of the globe’s biggest vaccine exporters, sharing more than it distributed internally between the end of January and mid-April 2021) and taken legal action against AZ. It also attempted to buy ten million doses of the AZ vaccine from the Serum Institute, which was originally only supposed to make vaccines for low and middle-income countries and has pledged 1.1 billion doses to Covax. Fearing for its supply of the Pfizer/BioNTech vaccine from EU manufacturing plants, the UK also put pressure on the Serum Institute to fast-track a delivery of another five million AZ doses.

Both were scuppered by the Indian government’s decision to pause all vaccine exports and prioritise its own vaccination campaign. Essentially, a host of rich European nations ended up competing to buy vaccines from a poor country in the middle of a surge, despite the fact one of them is producing its own doses at a high rate and many of the others had gone out of their way to disparage the product. The US, meanwhile, has a stock of 30 million AZ vaccines – which it has suggested it may never approve for use domestically – sat in one plant in Ohio. Its attitudes have left its territory more easily. In line with the established pattern, India’s rise in cases followed quickly on from Prime Minister Narendra Modi’s declaration of victory in the war against the coronavirus. The country’s surge has months left to run and will hamstring Covax for much of the year.

So much for Prasad’s better heads. Any material shortages can always be supplemented with intrigue and suspicion, and every success is liable to spread complacency. Similar formulations of poor communication, manufacturing inexperience, yield variability and politics will continue to sow discord and uncertainty in the months ahead.

Vaccine diplomacy

But it’s wrong to suggest IP isn’t a contributing factor. After such a publicised development race, there’s no way it couldn’t be. Most starkly, instead of using political tools to accelerate the use of its cheap and effective Sputnik V vaccine (another Cold War callback) domestically, Russia has focused on using the IP as a political tool for improving its international standing. While importing doses to support its own vaccine rollout, it has capitalised on the perceived failures of European and North American governments to support equitable distribution by signing (relatively small) manufacturing and export agreements with countries across the world, all while trumpeting the fact that Russia has produced ‘a vaccine for all mankind’.

That focus on the politics of the pandemic is giving it opportunities to become even more deadly. It’s presenting a particular image internationally, but Russia’s efforts to vaccinate its own population have been compromised by low stocks, poor distribution and governmental insistence that Covid-19 is not a problem for the country. China has far greater production capacity, but its success in stopping the spread of the virus has also resulted in a sort of vaccine apathy among its populace. These conditions mirror India’s earlier in the year.

The most impressive rollout of a Chinese vaccine might be in Chile, which has administered 12 million Sinovac doses (along with two million from Pfizer/ BioNTech) to its 18 million people. Troublingly, that makes the South American country a geographical outlier. As the southern hemisphere enters its second Covid-19 winter, even advanced economies like Australia and New Zealand have struggled to source raw materials and completed vaccines, while Brazil, where the US and Russia have both tried to exert influence over vaccine imports, has manufacturing capacity and very little supply. Bancel finds this particularly concerning. “The last six months have been really horrific in terms of what’s happened across the northern hemisphere,” he told the IFPMA panel. “Especially with such a large immunocompromised population [south of the equator], a lot of people that are unfortunately HIV-positive, I worry deeply, on the guidance of my epidemiologists, that we should be seeing many more variants.”

When compared with the HIV/AIDS pandemic, which had continued for close to ten years before antivirals reached patients in Sub-Saharan Africa, the global response to Covid-19 should be appreciated as an impressive step forward. IFPMA director general Thomas Cueni believes there’s a realistic chance to produce ten billion Covid-19 vaccine doses this year, a staggering achievement that would mean tripling the pre-pandemic vaccine output. The only issue is that half of those doses are going to high-income countries, freeing them to vaccinate their populations twice over and leaving the rest of the world with much less than 50% coverage. If the excess doses aren’t distributed quickly and fairly, that leaves plenty of room for variants. “Until everyone is safe,” warned Cueni, “no one is safe.” To stop the virus, leaders will need bigger ideas than they can fit in old metaphors.