Across the world, the COVID-19 pandemic has touched every continent except Antarctica. With approximately 380,000 deaths worldwide attributed to COVID-19, countries, organizations and companies have come together in an unprecedented manner to develop globally accessible therapeutics and vaccines. With experts citing the need to vaccinate between 50 to 80% of the world’s 7.8 billion people to control the pandemic, creating around six billion doses of any successful vaccine candidate poses some unique challenges.

 

At the time of writing, there were approximately 140 vaccine candidates in development for SARS-CoV2, with 14 of those already in human clinical trials.* Historically, there’s only around a 6% chance that any individual vaccine under clinical investigation will make it to the market. Combined with the often transient nature of epidemics, which makes evaluating vaccines challenging due to unpredictable patient volumes, developing safe and effective vaccines can be a high-risk venture. To encourage development and pave the way to widespread production and access, public and private groups often partner or make investments in vaccines. In this edition of our COVID-19 vaccine series, we will highlight the key manufacturing and distribution partnerships that have been forged for the leading vaccines under clinical investigation.

 

Manufacturing partnerships and contracting for global demand

 

To meet the global demand for rapid and widespread vaccine access, sponsors must consider how to scale up commercial manufacturing. To address this, many of the leading COVID-19 vaccine developers have partnered for manufacturing scale up at risk, even before they know if their candidate might succeed. Sponsors may seek different types of manufacturing partners based on their needs: They may choose to contract specialized manufacturing organizations to expand commercial factory capacity or to gain direct access to supply chains needed to produce a finished product, or they may pair up with more established life sciences companies that might have a breadth of expertise and resources to contribute, including manufacturing.

 

With financial support from the U.S. Biomedical Advanced Research and Development Authority (BARDA), Moderna is aiming to create capacity for producing a billion doses of its candidate (mRNA-1273) per year. They partnered with Lonza, a contract development and manufacturing organization (CDMO), and initial manufacturing sites will be in the U.S. and Switzerland, with later expansion to other parts of the world with Lonza facilities.

 

In a more broad partnership, Oxford University has teamed up with AstraZeneca for the global development, manufacturing and distribution of their lead vaccine candidate, known as AZD1222 (formerly ChAdOx1 nCoV-19). Shortly thereafter, they announced they had secured capacity for manufacturing one billion doses of their candidate, and agreed to provide BARDA with 300 million of the first 400 million doses in exchange for $1.2 billion. With BARDA securing three-quarters of the first doses produced for the U.S., the “U.K. government secured the other 100 million doses by agreeing to pay AstraZeneca £65.5 million ($80 million).” However, across other vaccine programs in both the U.S. and the EU, the ramifications of government funding to prioritized domestic or widespread global access is not always as explicit. Each public investment may or may not come with strings attached, but in the U.S., BARDA has historically invested with the understanding that they will have the option to be the first purchaser of the vaccine, according to  former BARDA director, Dr. Robin Robinson, during a recent webinar on the COVID vaccine landscape.

 

In India, Oxford also partnered with the Serum Institute, the world's largest vaccine manufacturer, which stated that doses of the vaccine manufactured there will be prioritized for distribution to the local market first. And while AstraZeneca has stated that its goal is to ramp up to producing a billion doses of the vaccine, it remains to be seen who may get access to the remaining doses.

Similarly, funded by a $384 million grant from the Coalition for Epidemic Preparedness Innovations (CEPI), Novavax purchased Praha Vaccines and forged a partnership with the Serum Institute to increase its vaccine candidate manufacturing capacity to above one billion doses by 2021.

When vaccines begin to attain regulatory approval, and as manufacturing scales up to meet global demand, many challenges will remain regarding the global distribution of doses. As we learned from H1N1, even after a suitable vaccine is found, widespread distribution during a pandemic poses unique challenges. There are a multitude of logistical and legal considerations, with experts already citing concerns that wealthy nations will continue to compete amongst themselves for priority access to COVID-19 vaccines, while poorer nations will have to wait “at the back of the queue.” Additionally, we previously shared that many countries recently clamped down on exports of protective medical equipment and drugs needed to fight the virus, which has inspired calls for coordinated and evidenced-based allocation of vaccines.

 

Notably, in China state-owned firms make up about two-fifths of the country’s vaccine industry, 12 of which may have implications for how vaccine distribution may be prioritized to meet local versus global demand. And while China recently pledged to make any coronavirus vaccine universally available, foreign regulators may ask for more transparency regarding the clinical development or manufacturing practices before approving their use outside of China. Private companies in China such as CanSino Biologics and Sinovac have also received government funding for their vaccine programs, but the implications of this to downstream distribution abroad remains unclear. 

 

As the precedents show, when demand is high for a medical product, manufacturing countries may restrict exports. To better understand how doses of potential vaccines may be distributed, we can consider how sponsors may meet demand in their countries and in the countries of their manufacturing sites. Setting aside the two candidates from China with currently modest manufacturing goals, in figure 2 we considered two illustrative scenarios (assuming each vaccine is effective in one dose [no booster]):

  1. Could we meet global vaccine demand if all the lead candidates succeeded in clinical trials and all pooled supply?
  2. What supply would remain if sponsors first met demand in the country of their headquarters and in the countries where they have manufacturing sites?

In scenario No. 1, we have assumed that the four clinical candidates with large manufacturing targets succeed, meet manufacturing goals and pool doses to meet global demand. However, even this may only provide enough vaccine for about 40% of the world’s population. By this estimate, it would take over three years to produce enough pooled doses to vaccinate the world’s population.

 

In scenario No. 2, we have instead assumed that sponsors supply their own countries and manufacturing countries first, and any remaining doses are pooled for global demand. In this scenario, countries with multiple vaccines sponsored or manufactured in their borders may have a surplus. (For example, in this illustration the U.S. has 315% of the doses needed to vaccinate the population by the end of 2021.) But this means less may remain for global demand, and in this scenario only about 17% of the doses needed for the rest of the world’s population may be available for global distribution. However, companies may need to account for risk by having over-supply to consider development failures.

To date, only Oxford/AstraZeneca has disclosed specific distribution commitments, but fulfilling these commitments will be contingent on successfully exporting and distributing the vaccine. To avoid export restrictions, widespread and distributed manufacturing footprints may be key.

Clearly, meeting global demand for a COVID-19 vaccine is a huge undertaking. Even considering the incredible pooling of resources from both the public and private sectors, the current projections of the lead candidates could create potential competition for doses. The pressure will be on any candidates with promising data to continue to ramp up potential supply.

 

To this end, vaccine sponsors are taking on risk by ramping up partnerships and manufacturing capacity now to stockpile doses of yet-to-be proven vaccines, still in the earliest phases of clinical development. While typically these efforts are sequentially gated, under these unusual circumstances sponsors are investing in these development and manufacturing efforts in parallel. These risks are essential, however, and additional partnerships will be key to ensuring vaccines that succeed in clinical trials can be manufactured and distributed to the world. In our next post, we will highlight some of the key financial and technological and clinical development partnerships that have been created to accelerate COVID-19 vaccines.

 

For additional information about the evolving COVID-19 pipeline, study results and milestones, please visit our visual COVID-19 vaccine and treatment pipeline tracker. Check back weekly as we provide an updated view of the clinical development landscape and advancements in the search for safe and effective tools to fight the COVID-19 pandemic.