Manufacturing

What the manufacturing landscape can tell us now

j.harris — Sat, 15 May 2021 00:08:40 +0000

What the manufacturing landscape can tell us now j.harris Sat, 05/15/2021 - 00:08

INSIGHTS

What the manufacturing landscape can tell us now

Author: Andrea Taylor

Manufacturing projections for Covid-19 vaccines seem to shift on a near-weekly basis. We are not even halfway into 2021 and already we have seen adjustments, both up and down, across all vaccine makers.

2021 projections differ by vaccine platform

Overall, we see 2021 projections increasing for mRNA vaccines Pfizer-BioNTech and Moderna, while decreasing for viral vector vaccines Oxford-AstraZeneca and Janssen (J&J). AstraZeneca, in particular, has faced significant manufacturing issues throughout its global production network. In addition to the well-covered constraints slowing down manufacturing in Europe and the Serum Institute of India, partners in Mexico, Brazil, and elsewhere have struggled to get production started or sustained.

Janssen’s vaccine has also experienced setbacks, including the temporary closure of the Emergent BioSolutions plant in the US after up to 15 million doses were discarded due to an error in production. Merk is signed up to help with production but not until September at the earliest. White House officials told state governors this week that there were no available doses of J&J vaccine to order. The CEO recently punted when asked if the company could still meet its 2021 goal of 1 billion doses, saying only that they would be able to meet their current contractual obligations.

Novavax, using a protein subunity platform, has also experienced delay after delay in their 2021 production. Like AstraZeneca, the company lacked in-house manufacturing and had to build a global network of manufacturing partners. Scaling these partners has been slowed by the global shortage of supplies needed for production, such as filters and bioreactor bags. This week, Novavax announced further delays to their manufacturing projections, now expecting to reach 150 million doses per month by the end of the year.

*Platform*	*Vaccine*	*2021 Projections*			*2022 Projections*
		January	March	May
*mRNA*	Pfizer-BioNTech	1,300,000,000	2,500,000,000	3,000,000,000	4,000,000,000
	Moderna	600,000,000	700,000,000	800,000,000	3,000,000,000
	CureVac	300,000,000	300,000,000	300,000,000	1,000,000,000
*Viral vector*	Oxford-AstraZeneca	3,000,000,000	2,100,000,000	2,100,000,000	2,000,000,000
	Janssen (J&J)	1,000,000,000	1,000,000,000	1,000,000,000	2,500,000,000
	CanSino	200,000,000	500,000,000	500,000,000	500,000,000
*Inactivated virus*	Bharat Biotech	unknown	150,000,000	494,200,000	700,000,000
	Sinopharm-Beijing	1,000,000,000	1,000,000,000	1,000,000,000	1,000,000,000
	Sinovac (CoronaVac)	1,000,000,000	1,000,000,000	1,750,000,000	2,000,000,000
*Protein Subunit*	Novavax	1,500,000,000	1,500,000,000	580,000,000	2,000,000,000
*TOTAL*				11,524,200,000	18,700,000,000

Looking at the projection trendlines, it appears that mRNA vaccines will be able to scale faster and more reliably this year. That is likely due to a few factors. The mRNA vaccines were the first to the global market and thus had a jump start on other Covid-19 vaccines in working through teething problems as they expanded production.

The mRNA vaccine makers have also used a more centralized production approach, likely out of necessity as there are very few manufacturing partners with mRNA capabilities. This may also have given them an early advantage in reaching scale. The production networks for Pfizer-BioNTech and Moderna are tightly centered in the US and Europe and largely kept in-house. They did not have to invest time into getting 10 or 15 technology transfers off the ground, like AstraZeneca or Novavax.

The production process for mRNA vaccine is also faster than for traditional vaccine platforms. Pfizer-BioNTech’s mRNA vaccine can be produced from start to finish in about 2 months. By contrast, each batch of viral vector, inactivated virus, and protein subunit vaccines can take more than 3 months to produce if all goes perfectly. Yields for the drug substance for these vaccines are somewhat unpredictable and batch issues can set the process back by months. So although mRNA vaccine makers faced challenges with new technology and a dearth of partners, they appear to have the advantage this year.

2022 is looking good for vaccine production all around

The projections for 2022 are astounding. Western-based Covid-19 vaccines project 14.5 billion doses in 2022 (representing 8.5 billion people who can be vaccinated, given that J&J is one dose). We anticipate that there will be bumps along the way and these numbers (just as in 2021) will shift. Some discounting is probably wise, given the 2021 experience so far. But we have more confidence in these numbers than we did in the early 2021 projections.

We do not yet have credible projections for Russia-made vaccine manufacturing in 2022 but Chinese and Indian vaccine makers expect to produce another 4.2 billion doses next year, for a possible global total of 18.7 billion doses in 2022.

Since much of the world will still be waiting for vaccinations by 2022, this is definitely good news. It also indicates that there will be room for annual booster production without compromising access to first-round vaccinations globally. The key questions will be whether we can prevent devastating surges while we wait, make sure doses actually get to every country, and adequately address vaccine hesitancy.

INTERESTING TRENDS

Significant updates, news, and trends we saw last week:

The US FDA expanded emergency use authorization for the Pfizer-BioNTech vaccine to include children ages 12 and older.

US supply appears to be outpacing demand, with states reducing orders from the federal government and turning to lottery models to further increase vaccination rates.

As the US vaccine drive slows down, the EU rollout is finally speeding up.

Europe and Australia, having initially bet heavily on Oxford-AstraZeneca, are now swinging away and working to replace it with other vaccines for national supply.

The Independent Panel for Pandemic Preparedness and Response released their findings and recommendations this week, which include our data and analysis.

Serious questions were raised in the Lancet this week about the Sputnik V Phase 1/2 trial data, as well as availability of data from the Phase 3 trials and the trial protocols.

WHO labeled the Indian variant “of global concern” this week. It is too early yet to assess how it responds to current vaccines.

Seychelles has the highest rate of vaccinations in the world but is now seeing high rates of infection, including among the vaccinated.

Novavax has delayed plans to complete applications for regulatory approval in the US, UK, and Europe until end of September.

For more information on our research on Covid-19 vaccine supply, please see https://launchandscalefaster.org/COVID-19.

Weekly COVID Vaccine Research Update

Vaccines

Manufacturing

High-income country confirmed dose total:	5.9 billion
Upper-middle-income country total:	1.7 billion
Lower-middle-income country total:	933 million
Low-income country total:	270 million
COVAX total:	2.7 billion
Total worldwide confirmed purchases of Covid-19 vaccines:	11.6 billion doses

Can the TRIPS waiver save the world?

j.harris — Fri, 07 May 2021 19:05:36 +0000

Can the TRIPS waiver save the world? j.harris Fri, 05/07/2021 - 19:05

INSIGHTS

Can the TRIPS waiver save the world?

Author: Andrea Taylor

The US threw its weight into the ring on the side of the TRIPS waiver this week, surprising many. There is still a long road ahead for the waiver, which much be agreed through discussion and consensus. With vocal opponents (including Germany), this is unlikely to happen before December. But if it does go through and intellectual property (IP) protections are waived, will it make a difference?

The short answer is maybe, but not this year. The TRIPS waiver is important because of what it stands for; it is a concrete action for which people can advocate, on behalf of global equity. And it is safe to say that the record profits recently reported by several Covid-19 vaccine makers have undercut industry’s opposition. But the need is most acute in the next six months and the waiver is unlikely to help.

This is not lost on US leaders and this decision may be more about optics than impact. But it also signals that the US has decided to be a global leader on vaccine equity and could mean that the administration will support dose sharing and accelerate exports to poorer countries from US manufacturers, both of which would be more meaningful actions in the short-term.

The TRIPS waiver in brief

The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) was launched in 1995, in order to protect IP in global trade, including copyrights, trademarks, patents, and trade secrets across all industries (not just pharma). It integrated and added to earlier agreements and set out minimum standards for intellectual property protection among World Trade Organization (WTO) member countries. TRIPS-related disputes are subject to WTO’s dispute settlement procedures.

The proposed waiver, supported by more than 100 countries, would temporarily remove global protection of intellectual property for innovations that address Covid-19 infection. The goal is to increase manufacturing, making it possible for drug makers around the world to start churning out doses of Covid-19 vaccines without having to negotiate technology transfer and licensure deals with vaccine developers.

We are not optimizing the capacity we already have

Calls for the TRIPS waiver are based on the assumption that IP is holding up global production. Our review of the evidence, however, does not support this.

Our data on vaccine manufacturing show that most Covid-19 vaccines using traditional platforms, such as viral vector and inactivated virus, did use tech transfer deals to set up global manufacturing networks. AstraZeneca has agreements in place to manufacture Covid-19 vaccine in 16 countries, Novavax and Sputnik V in 11 countries, Sinovac in 6 countries. But many of these manufacturing partners (particularly those in middle-income countries) are delayed in starting or operating at only partial capacity because knowledge transfer is difficult and raw materials are in short supply.

For mRNA vaccines, like Moderna and Pfizer-BioNTech, the picture is even more complicated. Very few manufacturers (and none in LMICs) are equipped to manufacture mRNA vaccine, with or without access to intellectual property.

Setting up manufacturing takes longer than we think

Starting from scratch to set up new manufacturing through access to IP is not an immediate fix. And right now, we need to be focused on an immediate fix. Retrofitting or building new plants takes a long time. Running test batches, quality checks, audits and regulatory approval of manufacturing sites also takes a long time. Starting that process now is not likely to produce more doses this year, when they are most needed.

The capacity gap is more than IP

Patents and written trade secrets alone do not provide the information, expertise, or equipment needed to produce vaccines. It would be significantly more difficult to force the sharing of specialized expertise required to apply the information. Without investment in knowledge exchange and skill development, as well as physical equipment, the intellectual property in written form cannot cover the capacity gap. To succeed, any waiver of IP must be embedded within a larger transfer of know-how and infrastructure development, which is unlikely without bringing pharmaceutical companies along as willing partners.

The world is on fire

When the pharma industry says the waiver will “undermine our global response to the pandemic,” most of us can agree that yes, that is precisely the point. Our analysis of vaccine data indicate that response has not been particularly successful and a pivot is certainly indicated.

But it is the next six months that are most critical. Right now, the immediate need is to increase the production of equipment and raw materials needed to fuel existing technology transfer deals so that manufacturers who have already spent months learning the recipes and gaining the expertise can get to work.

There is a real risk that this discussion about patents and IP is distracting us from focusing on the crisis at hand. We are essentially arguing over who is allowed to make fire engines while we watch the world burn. Right now, we need to make sure we can get water flowing through every hose we have.

In the medium- to long-term, we do need to develop regional manufacturing hubs, with capacity to make drug substance as well as fill-finish, across Africa, Latin America, and South and Southeast Asia, so that we do not end up in the same place next time. An IP waiver may or may not help this effort. But right now, we need to focus on goals with immediate impact: maximizing production where it is ready to go, dose sharing, and funding Covid-19 response (including vaccine purchase) for lower-income countries.

INTERESTING TRENDS

Significant updates, news, and trends we saw last week:

The US changed course, announcing support for the TRIPS waiver, which would allow a temporary waiver of intellectual property for Covid-19 related drugs and vaccines (see above for our take on this).

WHO approves Sinopharm for emergency use listing (EUL), making it eligible for COVAX supply.

Numbers for low-income country vaccine purchases dropped significantly this week, reflecting the decision by the African Union to cancel its order of Oxford-AstraZeneca vaccine from the Serum Institute. Given the supply constraints facing COVAX, the AU decided to purchase from other makers, rather than compete with COVAX for the SII-AstraZeneca doses.

Moderna agrees to supply COVAX with 500 million doses, including 34 million in late 2021.

Novavax finalized their deal with COVAX for 350 million doses, with delivery scheduled to begin in Q3 of 2021 (these doses were already counted in COVAX supply forecasts but had not yet been finalized)

Canada became the first country to approve use of Pfizer-BioNTech vaccine in children, ages 12-15. A decision on the same is expected by the US early next week.

Pfizer-BioNTech increased their 2021 manufacturing projection to nearly 3 billion doses.

Janssen (J&J) vaccine starting to ship from South African firm Aspen Pharmacare. Aspen has an annual capacity of 200 million doses. Half of the doses will go to the African Union, 31 million doses will stay in South Africa, and the remainder will be exported outside of Africa.

The EU is negotiating the largest Covid-19 vaccine deal yet, for 1.8 billion doses from Pfizer-BioNTech.

Pfizer-BioNTech will donate doses to Olympic delegations to ensure immunity prior to the opening ceremony on July 23.

For more information on our research on Covid-19 vaccine supply, please see https://launchandscalefaster.org/COVID-19.

Weekly COVID Vaccine Research Update

TRIPS waiver

Vaccines

Manufacturing

High-income country confirmed dose total:	4.9 billion
Upper-middle-income country total:	1.5 billion
Lower-middle-income country total:	718 million
Low-income country total:	270 million
COVAX total:	1.62 billion
Total worldwide confirmed purchases of Covid-19 vaccines:	9.1 billion doses

What have we learned in one year of COVAX?

j.harris — Fri, 23 Apr 2021 21:56:33 +0000

What have we learned in one year of COVAX? j.harris Fri, 04/23/2021 - 21:56

INSIGHTS

What have we learned in one year of COVAX?

Author: Andrea Taylor

Launched as a global cross-organization collaboration only one month after the pandemic was declared, COVAX was built to facilitate global equity in the pandemic response. As COVAX passes the one-year mark this month, there are some early lessons and insights that can inform its further development and help us prepare for future crises.

In terms of numbers, COVAX is short of the mark. Photo ops of government officials on the tarmac to meet planes full of doses and declarations of the numbers of countries reached can paint an optimistic picture. But the truth is that COVAX has delivered 43 million doses to 119 countries. This is only 2% of the way towards the 2 billion dose goal for 2021 and about 70 COVAX-participating countries have not yet received any doses (though some of these countries have waived their doses).

As Dr. Tedros wrote in the New York Times this week, we are nowhere near the 20% mark, and with significant supply constraints set to continue through the second quarter of 2021, this is not likely to change soon. COVAX is also However, it is not all bad news. COVAX has supported manufacturing deals and bulk purchases that would not have been feasible without its pooled procurement approach. And while distribution of vaccines is coming in more of a trickle than a wave, it is still getting doses to some of the most remote and poorest regions of the world. One year in, we can look back and begin to see what has worked and what needs rethinking.

Iterating in the midst of a crisis is difficult

COVAX was pulled together by a group of people who foresaw the dangers of inequitable access to vaccines in a pandemic, part of the ACT Accelerator that also focused on access to diagnostics and therapeutics. But at the time it was launched, the shape and timeline of the pandemic were unknown, the symptoms and impact of Covid-19 were still not well understood, and no one yet knew if or which vaccine would work. There was not the luxury of time to wait for these answers before designing and market testing an equity solution.

It is a difficult thing to build the car while you are driving it. The designers of COVAX and the partners who have steered its implementation have had to iterate as they go along, adding this, removing that. They have navigated the same dynamic landscape as national leaders, responding to changes in disease patterns, infection rates, vaccine trial results, manufacturing supply. But they’ve had to do all of this while keeping the world’s leaders engaged, maintaining a vision and strategy that would hold both wealthy and poor countries and everyone in between. It is worth keeping in mind the sheer difficulty of this task. To large degree, COVAX was down to grit and persistence.

Nationalism will win, so let’s plan for it

COVAX was premised on an all-for-one-and-one-for-all approach to defeating the pandemic. It was a way to invest together in a portfolio of vaccines and therapeutics and then ensure that the successful ones were shared out equally, regardless of country wealth or geopolitics. We know from economic and epidemiolocal modeling that this would have led to the best outcomes for everyone and was our best hope for ending the pandemic quickly. But we also know from experience that the world doesn’t really work this way. And COVAX used a traditional donor-aid model to drive an all-in-this-together program, leading to, as the Lancet put it this week, “a funding shortfall and a system not based on solidarity but rather one that reinforces inequities.”

Vaccine purchase decisions are made (for the most part) by national leaders, whose primary responsibility is to protect their own population. If leaders have the opportunity to control the purchase (and production) of vaccines for their country, they will. If they have the opportunity to prioritize their population over others, they will. This is their job.

For future iterations of COVAX, nationalism must be baked into the design from the beginning. COVAX needs to assume that government leaders will prioritize their own, and work with that. Perhaps vaccine makers could commit that 20% of every batch produced goes to supply COVAX, while 80% can go to the wealthy countries first in line. The important thing is to bake it in from the beginning so that it not a choice of “giving up” doses that leaders have to explain to their voting population.

Messaging matters

COVAX can be described in many ways but transparent is not one of them. The risk-averse partnership has consistently kept its cards close to its chest, providing information only in broad strokes and only when absolutely necessary. While we can understand why, we also think this may be a strategic error.

When COVAX does share information, the tone tends to be defensive and protective and the data shared is difficult to parse. The risks and dangers inherent in the COVAX design are not lost on the watching world and simply choosing not to talk about them doesn’t make them disappear. Rather, clear messaging about the benefits of vaccine equity (which are well documented by others), what is needed to get there, and the potential pitfalls on the way could allow COVAX to drive and shape the story. Unfortunately, opaque supply updates built on data that cannot be externally validated undermine, rather than build, confidence.

COVAX is the largest purchaser in the Covid-19 vaccine market and could use its platform and purchasing power to push for more transparency and accountability in Covid-19 vaccine purchases and manufacturing. Making its supply deals public, including prices and delivery schedules, and clearly communicating about the gaps, could drive urgency and more transparency across the board.

Equitable distribution must begin with equitable manufacturing

The location of manufacturing matters and countries with domestic manufacturing of Covid-19 vaccines are better able to ensure supply. While COVAX was quick to secure manufacturing capacity, this is less relevant in the context of export controls. COVAX does not have a country or government and is unable to use policy levers to commandeer manufacturing when the going gets tough.

Ensuring equitable access to vaccines globally means that manufacturing must be global. There are a very limited number of manufacturing partners who could provide the scale of vaccine needed for COVAX and this led to an overreliance on Serum Institute of India (SII). When a second wave of Covid-19 infections hit India and sent it into crisis, export controls cut short the COVAX supply. There was no Plan B and no clear options for making up the shortage in production for countries counting on COVAX.

The world needs more regional manufacturing hubs that can produce vaccine independently and do not require drug substance to be imported from other regions. There is a particularly acute need in Latin America, the African continent, South East Asia, and the Pacific. With more equitably distributed manufacturing, COVAX or a similar future effort could draw on a broad network of manufacturing partners to supply the world and lower-income regions could control their own supply.

The world is better off with COVAX than without it. But one year in, we can see how far we are from the goal and the factors that have prevented success. One of the strengths of COVAX is its ability to iterate and it will continue to do so in a continually changing environment. And importantly, we now have something on which to build and improve for future global crises.

INTERESTING TRENDS

Significant updates, news, and trends we saw last week:

India’s health systems are collapsing from the pressure of a near-vertical rise in infections. With more than 330,000 new cases on Friday, India set a world record for the second day in a row.

In response, India is opening up vaccine eligibility to all adults aged 18 and older, starting May 1. The country is facing a significant vaccine shortage, however, and has declared that domestic manufacturers must sell 50% of their doses to the government but can sell the other 50% on the private market within India. Prices for the private market can be different than the government rate but must be transparent and set in advance.

The European Medicines Agency (EMA) found a possible link between a very rare blood clotting disorder and the Janssen (J&J) vaccine, similar to that identified with the Oxford-AstraZeneca vaccine, but stressed that “the vaccine’s benefits in preventing Covid-19 outweigh the risks of these very rare side effects.”

Dr Tedros offered a scathing indictment of the choices wealthy countries have made in the pandemic in a NYT opinion article, and called on rich countries to support COVAX financially, to donate vaccine doses, and to share manufacturing expertise to allow production to scale up globally.

Japan will host the next fundraising summit for COVAX in June, bringing together leaders from the US, Japan, and European countries.

New Zealand, France, and Spain announced plans this week to donate excess vaccine doses through the COVAX Facility.

The ACT Accelerator released a report in honor of its first anniversary: ACT Now, ACT Together: 2021 Impact Report.

For more information on our research on Covid-19 vaccine supply, please see https://launchandscalefaster.org/COVID-19.

Weekly COVID Vaccine Research Update

High-income country confirmed dose total:	4.7 billion
Upper-middle-income country total:	1.5 billion
Lower-middle-income country total:	732 million
Low-income country total:	770 million
COVAX total:	1.12 billion
Total worldwide confirmed purchases of Covid-19 vaccines:	8.9 billion doses

Will chicken eggs change the Covid-19 vaccine landscape?

j.harris — Fri, 09 Apr 2021 20:42:07 +0000

Will chicken eggs change the Covid-19 vaccine landscape? j.harris Fri, 04/09/2021 - 20:42

WEEKLY INSIGHTS

Will chicken eggs change the Covid-19 vaccine landscape?

Author: Andrea Taylor

A promising new vaccine candidate is getting a flurry of attention this week, even in a very crowded landscape that includes 11 vaccines on the market and 50+ more in Phase 2 or 3 trials. The newcomer NDV-HXP-S vaccine, developed through collaborations between researchers at University of Texas at Austin, PATH, and Mount Sinai, among others, is a mouthful to say but the name captures the two reasons people are excited about it.

NDV refers to the Newcastle Disease Virus, a disease that effects birds but does not harm people. Using NDV as a viral vector for vaccines means the vaccine can be developed in chicken eggs, as is commonly done for the flu vaccine. NDV has also been used as a vector for vaccines against SARS 1, RSV, and Ebola.

HXP stands for HexaPro, a spike protein developed by researchers in the US that is stronger than the protein used by the vaccines currently on the market. This means it can work well in difficult climates. Several of our current Covid-19 vaccines (we’re looking at you, mRNA) are divas – extremely difficult to manufacture and difficult to transport. The HexaPro protein was designed to be rugged and easy to make without falling apart, intentionally created with lower-income markets in mind.

The NDV-HXP-S vaccine candidate is being eyed as a potential gamechanger for several reasons:

Manufacturing: Many low- and middle-income countries (LMICs) already have expertise in making flu vaccines using chicken eggs and could apply this to making Covid-19 vaccine. And manufacturers in 80 LMICs can use HexaPro without paying royalties, thanks to a licensing agreement with University of Texas. This means countries such as Brazil and Thailand could own the manufacturing of this vaccine from start to finish.
Cost: Experts estimate that it could be produced for as little as $0.50 to $1 per dose, which would make it the cheapest Covid-19 vaccine by far.
Scale: Production can be scaled up very quickly, using existing infrastructure. The vaccine is so potent, that each egg can provide enough for 5 to 10 doses (typically flu vaccine gets 1 to 2 doses per egg).

This is not going to be a quick fix, however. The vaccine candidate is just beginning Phase 1/2 clinical trials in Brazil, Thailand, Vietnam, and Mexico (all of which also have the capacity to make it). If all goes well, it could potentially enter Phase 3 trials by late summer and, if effective and safe, start production by end of 2021 at earliest.

But most of the world will still be waiting for vaccines at the end of this year so this may still come in time to supply LMICs. It could also put us a much better position for global equity if boosters are needed.

To serve LMICs, a vaccine needs to be effective, affordable, available, and easy to transport. This vaccine looks like it can tick three of those boxes so far. We will have to wait on clinical trial results to see if it can tick all four.

INTERESTING TRENDS

Significant updates, news, and trends we saw last week:

We’ve posted a new visualization on our procurement webpage this week that shows how many doses per person have been purchased by each country, differentiated by country income category. (Note that to allow an apples-to-apples comparison, we doubled the single-dose vaccines Janssen and CanSino for this visualization.)

Indian manufacturer Panacea Biotech has signed up to manufacture the Sputnik V vaccine for global supply, with capacity to make 100 million doses per year.

The University of Oxford has launched a Phase 1 trial to test the Oxford-AstraZeneca vaccine delivered as a nasal spray, rather than injection.

The European Medicines Agency (EMA) is investigating reports of blood clots stemming from the Janssen (J&J) vaccine.

Pfizer and BioNTech filed for EUA expansion to include adolescents (12-15 years old) in the US. The companies plan to request expansion approvals across the world in the near future.

Many countries are restricting use of the Oxford-AstraZeneca vaccine in younger people, as a potential connection with rare blood clots (and now a bleeding disorder) are further investigated. In Europe, Italy, Spain, Belgium, Germany, the Netherlands, France, Finland, Sweden and the UK have required or recommended that the shot be used only for older age groups. Canada, Australia, and the Philippines have followed suit.

Supply of the Janssen (J&J) vaccine in the US is expected to drop by 80% this week, though the reasons are unclear. The company says it is still on target to deliver 100 million doses to the US by midyear.

The Biden administration in the US has appointed Gayle Smith to a new State Department role leading the US response to Covid-19 globally. Ms. Smith is the CEO of the ONE campaign and previously served as USAID administrator; she has advocated for vaccine donations and a more coordinated international response to support lower-income countries.

However, an article this week in Vanity Fair explores how and why the US may be contractually restricted from sharing surplus doses with other countries.

Last week, we noted that the Emergent BioSolutions facility in Baltimore accidentally mixed ingredients for the Oxford-AstraZeneca and Janssen (J&J) vaccines, invalidating a batch of Janssen vaccine. Emergent’s facility will now only manufacture Janssen and the manufacture of Oxford-AstraZeneca will be relocated.

Serum Institute of India (SII) asked the government of India for $400 million to help increase production to relieve its “very stressed” capacity. SII is the primary supplier of doses for COVAX and many LMIC markets but India’s recent export controls have delayed shipments out of the country.

Despite the stress on SII’s production capacity and resulting delays to COVAX and LMIC supply, the EU asked if they could possibly get 10 million doses of Oxford-AstraZenca vaccine from SII to make up for the shortfall from European manufacturers. The UK made a similar request earlier this year and received half of their order from SII.

African Union and Africa CDC are hosting a two-day conference on “Expanding Africa’s Vaccine Manufacturing,” April 12 and 13.

The US will host a (virtual) event on April 15 bringing together private- and public-sector leaders to make the case for additional investment in the COVAX AMC to support access to Covid-19 vaccines for lower-income countries.

For more information on our research on Covid-19 vaccine supply, please see https://launchandscalefaster.org/COVID-19.

Weekly COVID Vaccine Research Update

High-income country confirmed dose total:	4.6 billion
Upper-middle-income country total:	1.5 billion
Lower-middle-income country total:	721 million
Low-income country total:	770 million
COVAX total:	1.12 billion
Total worldwide confirmed purchases of Covid-19 vaccines:	8.8 billion doses

The curious case of upper-middle income countries

j.harris — Fri, 02 Apr 2021 20:57:15 +0000

The curious case of upper-middle income countries j.harris Fri, 04/02/2021 - 20:57

Weekly Insights and Interesting Trends

The curious case of upper-middle income countries

Author: Andrea Taylor

The global imbalance in Covid-19 vaccines is often framed in terms of wealthy versus poor countries. While it can be summed that way (wealthy countries do have the majority of doses, while low-income countries have almost none), this overlooks the experience of upper-middle income countries (UMICs), such as Brazil, Indonesia, and China.

The challenges faced by UMICs are different than those faced by lower-middle and low-income countries. They do not lack public funding to make vaccine purchases; countries like Mexico and Brazil can finance large purchases. But UMICs were less willing to make these purchases at risk, when there was no indication that any of the vaccines would work. While high-income countries (HICs) purchased from multiple vaccine makers in the summer of 2020, before any efficacy data were released, UMICs tended to wait until there was some indication of efficacy before negotiating a deal.

This put them behind the large orders from HICs for vaccines like Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca and meant their delivery dates were generally later. This issue is compounded by the location of manufacturing capacity for vaccines that have come to market. Most of the doses that have received authorization from stringent regulatory authorities are currently manufactured in HICs, many of which leveraged early investment in manufacturing (and sometimes export controls) to guarantee priority delivery.

So while UMICs have purchased a combined 1.5 billion doses so far, few of these vaccines have been delivered. This translates into low vaccination rates. About a third of UMICs have covered less than 1% of their population with a first dose. Another third have covered between 1% and 5% of their populations, and one-third have covered more than 5% of their population with first doses (according to data on vaccine administration as of March 31, 2021 from Our World in Data).

What is particularly curious about the experience of UMICs is that many of these countries have manufacturing capacity and contracts to produce Covid-19 vaccines, but this isn’t leading to national supply. Brazil, Indonesia, Mexico, and Thailand (among others) have manufacturing contracts in place for a variety of Covid-19 vaccines but actual production has been slow to get going. Russia, which funded the development, testing, and manufacture of domestically produced vaccines, is so limited by domestic bottlenecks in production that it is relying on manufacturing partners in other countries. China, another UMIC with domestically developed vaccines, has far more manufacturing capacity but is still struggling to meet projections for domestic and global production.

The production delays in UMICs have significant epidemiological consequences. In Brazil, for example, the health system is overwhelmed; shortages of hospital beds and oxygen mean acute cases go untreated. The country now accounts for a quarter of daily Covid-19 deaths globally and the death rate among even younger adults is rising rapidly. There are many factors contributing to the unchecked spread of Covid-19 in Brazil, including a chaotic response from the national government, contradictory public health messages, and rampant misinformation. But another crucial factor has been the slow rollout of vaccines.

Brazilian firms have technology transfer agreements in place to manufacture Oxford-AstraZeneca, Sputnik V, and Sinovac’s Coronavac, for domestic and regional distribution. But the doses are not materializing and only 2% of Brazil’s population have been fully vaccinated (9% have received a first dose). If we are going to address equitable access to vaccines, we need to better understand why production in Brazil and other UMICs is so far behind. Clarity on the causes of bottlenecks and delays for UMIC manufacturing will improve decisions about the manufacturing investments and policy changes needed to increase regional production.

Interesting Trends

Significant updates, news, and trends we saw last week:

WHO expects to have a decision on emergency use listing (EUL) for Sinopharm-Beijing and Sinovac’s Coronavac vaccines by end of April. Receiving EUL status would ease the path to regulatory approval in many countries around the world and make the vaccines eligible for use in COVAX.

Sinovac reported that, with a third plant up and running, their annual capacity is now 2 billion doses.

UAE tech company Group 42 announced plans to manufacture Sinopharm’s Beijing-based vaccine, with capacity to produce 200 million doses a year

However, Group 42, which currently distributes the Sinopharm-Beijing vaccine in the UAE, also reported that some people may need a third dose, due to low immune response.

CanSino’s single-dose vaccine may also need a booster, six months after the first shot, in order to maintain efficacy.

A new Covid-19 variation was discovered in Tanzania, with the most mutations yet seen. Tanzanian’s recently deceased president claimed that there was no Covid-19 in Tanzania, which has not officially reported any cases since the spring of 2020.

The US FDA said that, with the right syringes and needles, providers can extract 11 doses (instead of 10) from Moderna vials. They also gave approval for Moderna to fill vials with up to 15 doses, which may speed the pace of delivery.

New data show that efficacy of the Pfizer-BioNTech remains high six months after vaccination, with a small drop to 91.3% protection from symptomatic cases.

Pfizer-BioNTech also reported very positive results in their trial with children ages 12-15, demonstrating 100% efficacy.

BioNTech said that, together with Pfizer, they will increase 2021 manufacturing capacity to 2.5 billion doses globally.

In response to recent reports of possible increased risk of blood clots for women under 50 receiving the Oxford-AstraZeneca vaccine, Canada has said they will only use the vaccine in people over the age of 55 while Germany restricted it to people over age 60.

Manufacturing partner Emergent reported contamination of the drug substance for up to 15 million doses of Janssen (J&J) vaccine, due to human error.

Brazil health regulator Anvisa declined to approve the Covid-19 vaccine made by Bharat Biotech in India, saying that it did not meet manufacturing standards. The government of Brazil has ordered 20 million doses. Bharat plans to appeal the decision.

For more information on our research on Covid-19 vaccine supply, please see https://launchandscalefaster.org/COVID-19.

Weekly COVID Vaccine Research Update

High-income country confirmed dose total:	4.6 billion
Upper-middle-income country total:	1.5 billion
Lower-middle-income country total:	691 million
Low-income country total:	670 million
COVAX total:	1.12 billion
Total worldwide confirmed purchases of Covid-19 vaccines:	8.6 billion doses

COVID-19 vaccines are flowing into the private sector. What does this mean for equity?

j.harris — Tue, 09 Mar 2021 04:46:06 +0000

COVID-19 vaccines are flowing into the private sector. What does this mean for equity? j.harris Tue, 03/09/2021 - 04:46

Weekly Insights and Interesting Trends

COVID-19 vaccines are flowing into the private sector. What does this mean for equity?

While the vast majority of Covid-19 purchases have been through the public sector, we have also seen some private sector deals. This appears to be increasing recently, as governments are partnering with private sector health providers to widen the reach of their vaccine rollouts.

Back in 2020, the Russian Direct Investment Fund (RDIF) was selling Sputnik V to private companies and setting up private distributers in countries including Egypt, India, and Mexico. At the time, there was very little private sector involvement with any other vaccine and most developers pledged that they would work only with governments during the pandemic.

We are seeing an uptick of private sector involvement now, often at the invitation of governments, as countries struggle to ensure both supply and distribution. This makes sense particularly in countries where a large proportion of health care is provided in the private sector. Private sector involvement is a wide tent, however, and there are at least three key variables:

Who purchases the vaccine – private company or government?
Who pays for the vaccine – purchaser or end user? and
Who decides the priority groups and schedule for recipients?

The third variable holds the most risk of inequity at the country level.

For example, private companies could deliver government-purchased vaccine following the government’s priority schedule. This is a pragmatic move, leveraging all available health care providers and locations and is happening in many countries, both rich and poor, as vaccines are rolled out through local pharmacies and private care providers.

Or private companies could purchase their own vaccine and provide it to end users willing to pay. Where vaccines are sold directly to the public through private sector pharmacy chains or provided by employers, it can reduce the cost burden for governments that have not been able yet to purchase enough vaccine for their population. This may be on balance a positive trend in countries such as India, that have wide income disparity, where a large wealthy population can (and will) pay for a vaccine, ensuring that limited government funds support those in most need.

As in the case of India and Indonesia, private employers could purchase the vaccine and provide it to their employees free of charge. (In Indonesia, these doses must be acquired through the government and also be separate from the doses intended for the public sector campaign.) In the Philippines, more than 30 companies came together to purchase vaccine doses and promised to donate half to the government, while using half to cover their employees.

All of these options can relieve pressure on overburdened public health systems. But if people willing to pay are able to get vaccinated ahead of the priority schedule set by the government, countries risk creating a two-track vaccine rollout. Rich people will be vaccinated before poor people and may have access to different vaccines. It may also drive up prices for vaccines as a commercial product, tempt manufacturers to prioritize higher-paying private sector purchasers, and lead to an increase in fraud and black market activity.

While there is a critical and positive role for the private sector in the equitable distribution of vaccines at the national level in many countries, the key risk is when these companies work outside of the government priority schedule. Vulnerable populations around the world need to receive the vaccine on the same timescale to ensure the best results for everyone; the same is true at the country level. Public health priorities should continue to guide vaccine rollout, regardless of which sector administers the doses.

Interesting Trends

Significant updates, news, and trends we saw last week:

COVAX has delivered more than 12 million doses to 21 countries over the past two weeks: Ghana, Ivory Coast, South Korea, Nigeria, Angola, Cambodia, Democratic Republic of the Congo, the Gambia, Rwanda, Kenya, Senegal, Lesotho, Sudan, the Philippines, Indonesia, Fiji, Moldova, Uganda, Mali, Malawi, and Afghanistan. COVAX also this week published projected allocations by country through May.

Bharat Biotech released interim Phase 3 results, demonstrating 81% efficacy.

Sinovac’s vaccine (Coronavac) demonstrated 83% efficacy in phase 3 trials in Turkey. This data release follows phase 3 data announcements from Sinopharm (Wuhan) and CanSino last week.

Good news in real world data from the UK suggesting that the first dose of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines prevents symptomatic cases among the elderly.

The European Medicines Agency has begun a rolling review of the Sputnik V vaccine. The vaccine has racked up a slate of approvals recently, including in Democratic Republic of the Congo, Iraq, and Sri Lanka.

Novartis will manufacture drug substance for CureVac’s mRNA vaccine in their Austrian facility. Novartis is also helping to produce the Pfizer-BioNTech vaccine in their Switzerland facility.

Merck will partner with J&J to produce the Janssen vaccine in the US.

Canada approved the Janssen (J&J) vaccine but may not receive its ordered doses before September.

The US government projects it will have enough doses in hand by May to cover the adult population.

France and Germany have only distributed a fraction of their Oxford-AstraZeneca doses. Meanwhile, the EU is offering an additional 100,000 vaccine doses each to Austria, Czech Republic, and Slovakia to combat rising Covid-19 cases. Italy and Germany are following in France and Spain’s footsteps, hoping to conserve vaccine by giving only a single dose to people confirmed to have already had Covid-19.

Italy invoked the EU export controls to block shipment of 250,000 doses of the Oxford-AstraZeneca vaccine to Australia, highlighting the vulnerability of global supply contracts. Australia is domestically manufacturing the vast majority of its Oxford-AstraZeneca order, however, so the export block is more of a diplomatic than supply issue.

On the topic of export controls, the CEO of the Serum Institute of India said this week that US export controls on raw materials such as bags and filters are a limiting factor for global manufacture of Covid-19 vaccines.

Pfizer’s opaque distribution strategy is motivated by order size, timing of deal, relationship between country and company leaders, data sharing agreements, and profit opportunity according to in-depth article in Bloomberg this week.

Chile donated 20,000 doses to Ecuador in one of the first donations we’ve seen among Latin American countries.

For more information on our research on Covid-19 vaccine supply, please see https://launchandscalefaster.org/COVID-19.

Weekly COVID Vaccine Research Update

Data Updates

High-income country confirmed dose total:	4.6 billion
Upper-middle-income country total:	1.3 billion
Lower-middle-income country total:	608 million
Low-income country total:	670 million
COVAX total:	1.12 billion
Total worldwide confirmed purchases of Covid-19 vaccines:	8.3 billion doses*

*Change from March 9, 2021 reported total of 14.7 billion, which included potential dose purchases

What are the latest developments with vaccines developed in Russia and China?

rwatkins — Mon, 14 Dec 2020 13:00:00 +0000

What are the latest developments with vaccines developed in Russia and China? rwatkins Mon, 12/14/2020 - 13:00

Weekly Insights and Interesting Trends

What are the latest developments with vaccines developed in Russia and China?

We are frequently asked why some data about vaccines purchased by Russia and China appear to be missing from our data. The answer is because both countries control largely state-owned vaccine development and manufacturing chains, and, in part because of this, are notably less transparent than some other countries about advance purchases for domestic use as well as exports.

Our dataset includes publicly announced purchases of vaccine candidates. For nearly all countries, purchases of vaccines (even those developed within the purchasing country) are announced through press releases and global media channels. For example, if the US government wants Moderna's vaccine, it still has to negotiate a purchase agreement, even though the vaccine is developed (and manufactured) in the US.

Russia (with Sputnik V) and China (with Sinopharm's Beijing-based and Wuhan-based vaccines) appear to be relying primarily on vaccines developed and manufactured through state-owned resources; these may not require a formal or public ‘purchase' by the country in order to ensure domestic supply. And even where they might (CanSino and Sinovac are private companies headquartered in China), domestic purchases may not be registered through a public announcement.

Though they are not yet shown in our data of vaccine purchases, it is likely that both Russia and China have large domestic supplies of vaccine candidates. China announced that it has already vaccinated hundreds of thousands of people with (one of) the state-owned Sinopharm vaccines. Sinovac has vaccinated nearly all of its employees and is selling its CoronvaVac to the public (at $60 USD for two doses) in at least one Chinese city.

Russia announced a mass immunization campaign this week, after more than 100,000 people in the country have already received the Sputnik V vaccination. (This vaccine candidate has received emergency use authorization in Russia but has not completed Phase III trials and robust efficacy data have not yet been shared.) There are questions, however, about whether this campaign will be met with demand from the Russian public.

Both Russia and China have launched aggressive sales campaigns to other countries. Sinopharm's vaccine was famously provided to UAE Prime Minister Mohammed Bin Rashid Al Maktoum and both UAE and Bahrain have since approved general use of the vaccine. Countries in Latin America, South East Asia, and the Middle East have finalized purchases with Chinese vaccines.

Russia has inked deals selling Sputnik V to countries in Eastern Europe, Latin America, South East Asia, North Africa, and the Middle East. Interestingly, Russia's Sputnik V is selling to both private sector pharmacy chains as well as direct to governments, with support from the Russian Direct Investment Fund, the national sovereign wealth fund.

The deals coming out of Russia and China, however, often lack detail and clarity about quantity and expected timing of delivery. We reached out to the Russian Direct Investment Fund for clarity on their claim of 2.4 billion doses (to vaccinate 1.2 billion people) sold worldwide and a representative responded to us by saying that many of these purchases have not been made public.

China (and possibly Russia) may also be looking to import foreign vaccines, though we haven't seen any official purchases yet. At least two leading vaccine candidates, Oxford-AstraZeneca and Pfizer-BioNTech, have partnered with Chinese manufacturers and (if regulatory approval is obtained) will presumably then sell their product directly to China's population through the private sector.

Finally, it is important to recognize the highly dynamic situation with vaccine purchases and deliveries globally, including with China and Russia. We will continue to aggregate publicly available data, augmented with additional private data where accessible, to provide clarity and transparency. Please reach out to us with questions or suggestions on how to continue to improve our efforts.

Interesting Trends

Significant updates, changes, and trends we are seeing this week:

In encouraging news for global equity, the Asian Development Bank launched a $9 billion effort to help low- and middle-income countries in Asia with vaccine procurement and distribution. This funding will include investment in vaccine infrastructure, such as cold-chain storage, surveillance, and outreach.

Pfizer/BioNTech had a big week, receiving emergency use authorization in the UK (where vaccination began on Dec 8), the US (vaccinations set to begin on Dec 14), and Canada.

Mix and match trials: the UK will trial a combination of one dose of the Pfizer vaccine and one dose of the Oxford-AstraZeneca vaccine, while Russia has announced that they will test a combination of Sputnik V with Oxford-AstraZeneca. The Oxford-AstraZeneca vaccine published its Phase III results in the Lancet this week.

The University of Queensland-CSL vaccine candidate will not move forward, after recipients were found to have antibodies that could interfere with HIV testing. Australia responded by canceling their order and swiftly moving to increase their Oxford-AZ and Novavax orders.

This week we saw a number of increased orders: In addition to Australia's mentioned above, the US and Switzerland increased their purchased doses with Moderna.

In the past two weeks, smaller economies have begun to make more purchases, including South Korea, Israel, and Lebanon. The early positive results from leading candidates may have sufficiently de-risked the Covid-19 vaccine landscape, allowing these countries to jump in.

For more information on this research and our findings, please go to
https://launchandscalefaster.org/COVID-19.

Weekly COVID Vaccine Research Update

COVID

Manufacturing

Vaccines

Data Updates

High-income country confirmed dose total:	3.9 billion
Upper-middle-income country total:	1 billion
Lower-middle-income country total:	1.8 billion
Low-income country total:	0
COVAX total:	700 million
Total worldwide confirmed purchases of Covid-19 vaccines:	7.4 billion doses