By Patricio V Marquez

February 17, 2023

 

“Society usually makes progress out of necessity”

Sir Jeremy Farrar 

former director of the Wellcome Trust and current chief scientist at the World Health Organization (WHO)

 

As lucidly argued in a recent book by Prof. William D. Nordhaus, a Nobel Prize–winning pioneer in environmental economics, humans are vulnerable, but not helpless in the face of societal catastrophes, such as a pandemic.  

In scenarios where a deadly virus, such as SARS-CoV-2 that causes the COVID-19 disease, is making all people vulnerable to contagion and infection, governments have a central role to play.  Further, as shown by the recent COVID-19 experience, unless political leaders at the highest levels of government actively shape public opinion and adopt appropriate policies, scientific expertise cannot by itself stop it. 

Operation Warp Speed (OWS) in the United States offers an example of the bold and decisive actions that are required from governments to mitigate the health, social, and economic impacts of sudden and extreme shocks, or acute disturbances, such as the COVID-19 pandemic.  OWS was established in 2020 as an interagency partnership between the U.S. Department of Health and Human Services (HHS) and the U.S. Department of Defense (DOD) to coordinate the federal government’s efforts, in partnership with private companies, to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.  OWS also included as collaborating HHS agencies the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the Biomedical Advanced Research and Development Authority (BARDA). 

OWS exemplifies the critical role that governments can play in the development of public goods in a country in the face of a public health crisis. During the COVID-19 emergency, the most devastating pandemic in a century, vaccines, as public goods, benefited all members of society and were provided for free to individuals, financed by public taxation.

The “scientific miracle” of COVID-19 vaccines

COVID-19 clearly showed that the effective control of highly infectious pathogens and communicable diseases requires pharmaceutical interventions, including the development and use of new vaccines and therapies, as well as the repurposing of existing medicines.

Vaccine development, like drug development, is generally a long and expensive process. History  shows that in some cases it took decades of work to develop vaccines.  For example, the eradication of smallpox through a vaccine--one of the biggest achievements in public health history —took several centuries.  After a decade of work, Max Theiler developed the first safe and effective yellow fever vaccine in 1937, for which he receive the Nobel Prize for Medicine in 1951.  Similarly, it took years of research to understand the complexities of the influenza virus, before the first vaccine was approved for use in the United States in 1945. 

No vaccines in history, however, have been developed and authorized as quickly as the COVID-19 vaccines. The frontrunner COVID-19 vaccines developed by Pfizer/BioNTech and Moderna use a new technology that had never before been approved for human use.  Both use a synthetic version of coronavirus genetic material, called mRNA, to program a person’s cells to churn out many copies of a fragment of the virus. That fragment sets off alarms in the immune system and stimulates it to attack as if the person were exposed to the real virus. It is important to note, however, as observed in an article by Jeffrey Sachs, key scientific breakthroughs of mRNA vaccines were achieved before by two researchers working under NIH grants at the University of Pennsylvania in the 1990s and early 2000s, and their pioneering work relied on a network of academic researchers funded by the US NIH.

The critical role played by OWS

To accelerate development, OWS subsidies were large and were given early to participating private companies, mainly for vaccine development.  Other measures implemented by OWS included supporting increased manufacturing capacity for some of the vaccine candidates while they were still in testing, rather than waiting until testing was complete to scale up production—an “at-risk” investment whereby the federal government paid to develop or manufacture vaccine candidates that may not prove to be safe or effective. 

By March 1, 2021, vaccinate candidates that received federal government support under contracts for both the development of vaccines and the purchase of doses included Moderna ($4.94B for 300 million doses and $954M for development), Janssen Pharmaceuticals ($456M for development), Sanofi/GSK ($2.04B for 100 million doses and $30.8M for development), and Merck/IAVI ($38M for development).  In the case of Pfizer/BioNTech ($5.97B for 300 million doses), AstraZeneca/Oxford University ($1.2B for 300 million doses), Johnson & Johnson ($1B, for 100 million doses), and Novavax ($1.6B, for 100 million doses), candidates participated in OWS through federal purchase of doses only. By the end of January 2021, in about 12months or less, five of the six OWS vaccine candidates had entered phase 3 clinical trials, two of which—Moderna's and Pfizer/BioNTech's vaccines—had received an emergency use authorization (EUA) from the Food and Drug Administration (FDA) in December 2020.   Because OWS had purchased these vaccines, all doses were federally owned and provided at no cost to the US population.

The efforts under OWS helped achieve a “scientific miracle” in a relatively short period of time, that allowed the United States to manufacture more doses earlier than other vaccine-producing countries.  Indeed, as highlighted by Chad P. Bown, of the Peterson Institute for International Economics (PIIE), in testimony delivered at a hearing at the European Parliament, “US plants delivered 103 million vaccine doses by the end of February 2021.  In contrast, India provided 40 million doses and the EU only 27 million. By the end of March, the United States supplied nearly 200 million doses, compared with 117 million for India and 140 million for the EU. While the EU and India produced hundreds of millions of more doses than the United States overall—by the end of 2021—the United States was relatively more successful at producing hundreds of millions of early doses.”

Some of lessons from the OWS experience

First, as documented in a study done by the U.S. Government Accountability Office (GAO), in the race against the novel coronavirus, OWS, by selecting vaccine candidates that used different mechanisms to stimulate an immune response, showed the “importance of product diversification”.   More specifically, as argued by Chad P. Bown of the PIIE, the importance of this decision was shown by the fact that out of the seven different vaccine candidates that received funding from the U.S. Government in early 2020, only three-- the vaccines from Pfizer-BioNTech, Moderna, and Johnson & Johnson-- made it through clinical trials and succeeded. Brown also observed that diversification also mattered when there were subsequent and highly publicized manufacturing problems for the Johnson & Johnson vaccine at its main production facility in the United States.

Second, an incentive arrangement was adopted to stimulate vaccine manufacturers to deliver more quickly the contracted doses. According to Chad P. Bown’s testimony, these arrangements had additional price benefits for early doses delivered, as shown from what is publicly known about the contract with Moderna, that included an additional incentive of $3.00 per dose to meet an emergency-use authorization deadline of January 31, 2021.

Third, the GAO study also illustrates in detail how the effective workings of the public-private partnership arrangements established under OWS helped accelerate technology readiness levels and overcome manufacturing challenges along the way in a proactive and flexible manner to develop the COVID-19 vaccines.  Key findings of the GAO study in these two areas, which offer some valuable lessons for future crises, are summarized below:    

Accelerating technology readiness

• Originally developed by NASA in the 1970s for space exploration technologies, technology readiness level (TRL) measures the maturity level of a technology throughout its research, development, and deployment phase progression. With early and guaranteed funding under OWS, the pharmaceutical companies had a strong financial backing to assume vaccine-specific investment risks—de facto, the financial risk of a failed Phase 3 trial was shifted from the companies onto the government.
• The OWS vaccine candidates' TRL showed that COVID-19 vaccine development under OWS generally followed traditional practices, with some adaptations. FDA issued specific guidance to help accelerate vaccine development during the pandemic. For vaccine companies the primary difference from a non-pandemic environment was the compressed timelines.
• To meet OWS timelines, some vaccine companies relied on data from other vaccines using the same platforms, where available, or conducted certain animal studies at the same time as clinical trials. However, as is done in a non-pandemic environment, all vaccine companies gathered initial safety and antibody response data with a small number of participants before proceeding into large-scale human studies (e.g., phase 3 clinical trials). The two EUAs issued in December 2020 were based on analyses of clinical trial participants and showed about 95 percent efficacy for each vaccine. These analyses included assessments of efficacy after individuals were given two doses of vaccine and after they were monitored for about two months for adverse events. 

Overcoming Manufacturing Obstacles

As of January 31, 2021, companies under contract with OWS had released 63.7 million doses—about 32 percent of the 200 million doses that, according to OWS, companies with EUAs have been contracted to provide by March 31, 2021. Vaccine companies faced a number of challenges in scaling up manufacturing to produce hundreds of millions of doses under OWS's accelerated timelines. DOD and HHS worked with vaccine companies to help mitigate manufacturing challenges, including:

• Dealing with limited manufacturing capacity: A shortage of facilities with capacity to handle the vaccine manufacturing needs can lead to production bottlenecks. Vaccine companies worked in partnership with OWS to expand production capacity. For example, HHS's Biomedical Advanced Research and Development Authority helped one facility to identify an additional manufacturing partner to increase production. Additionally, the U.S. Army Corps of Engineers oversaw construction projects to expand capacity at vaccine manufacturing facilities.
• Confronting disruptions to manufacturing supply chains: Vaccine manufacturing supply chains had been strained by the global demand for certain goods and workforce disruptions caused by the pandemic. For example, one facility manufacturing COVID-19 vaccines experienced challenges obtaining materials, including reagents and certain chemicals. Also, due to global demand, the facility waited 4 to 12 weeks for items that before the pandemic were typically available for shipment within one week. Vaccine companies and DOD and HHS undertook several efforts to address possible manufacturing disruptions and mitigate supply chain challenges. These efforts included federal assistance to (1) expedite procurement and delivery of critical manufacturing equipment, (2) develop a list of critical supplies that were common across the OWS vaccine candidates, and (3) expedite the delivery of necessary equipment and goods coming into the United States. Additionally, DOD and HHS, by December 2020, placed prioritized ratings on 18 supply contracts for vaccine companies under the Defense Production Act, which allows federal agencies with delegated authority to require contractors to prioritize contracts for supplies needed for vaccine production.
• Addressing gaps in the available workforce: Hiring and training personnel with the specialized skills needed to run vaccine manufacturing processes can be challenging. OWS officials worked with the Department of State to expedite visa approval for key technical personnel, including technicians and engineers to assist with installing, testing, and certifying critical equipment manufactured overseas. OWS officials requested that DOD personnel be detailed to serve as quality control staff at two vaccine manufacturing sites until the organizations could hire the required personnel.

Vaccines are necessary but not sufficient; vaccination is equally important

While the role of OWS in the development of new vaccines was important, equally important has been the effort of the U.S. Government to administer shots in the arms of an anxious and often agnostic population.  Indeed, as argued in a study in Health Affairs, when it comes to cutting down on COVID-19 infections, hospitalizations, and deaths, a well-coordinated and timely deployment of vaccines has mattered just as much as their efficacy. So, preparation for the massive deployment of the vaccines and their administration has been another “public goods” role of the U.S. Government.   

COVID-19 vaccination has required unprecedented, scaled-up efforts to be mounted in health systems across the world to support the administration of vaccines, requiring the strengthening of key core activity areas, from planning and management, supply and distribution, and program delivery to systems and infrastructure, including the establishment of mass vaccination sites. The vaccination effort has also required building public confidence through public education campaigns, community mobilization and involvement, and on-the-ground, grassroots outreach efforts.  And the reality of isolated cases of adverse effects in recipients of COVID-19 vaccines cannot be discounted.  They highlight the importance of pharmacovigilance or the monitoring of vaccine safety, to support the rolling out of vaccination programs in order to address hesitancy and mistrust of some people to getting vaccinated, by ensuring that the benefits of vaccines outweigh the risks.

In the United States, the role played by the federal government via the Federal Emergency Management Agency (FEMA) and other federal and state agencies, supported COVID-19 vaccination sites by providing expedited financial assistance, providing federal equipment and supplies, and deploying federal personnel to states, tribes, territories, and other eligible applicants for vaccination efforts in accordance with the White House National COVID-19 Preparedness Plan.

No country is an island in a pandemic: the imperative of collaboration and solidarity

During the pandemic, countries such as the United States and those in the European Union had early access to sufficient quantities of vaccine doses.  But, a common challenge faced by most countries in the world, particularly in 2021, was the stark inequity in accessing, deploying, and administering COVID-19 vaccines, that left the poorest regions behind along with vulnerable population groups within rich and poor countries alike. 

This has been a very visible and worrisome problem during COVID-19 that demands priority global action going forward to avoid repeating it again in the future.  To this end, an urgent measure is securing the continuation of support for scaling up vaccine manufacture and supply.  If done, this will help ease supply shortages as faced during COVID-19, that disproportionately affected lower income countries, risking a prolongation of the pandemic.  Having more countries across the world manufacturing more vaccines and other medicines potentially will help move the needle in the future towards a more resilient and safer world, assuming that capacity is already in place or developed in countries and access to critical raw materials and other related supplies is not hindered by trade bottlenecks and political conflicts. 

Besides mechanisms that facilitate timely and equitable access to vaccines and related supplies, expanding vaccination coverage will depend on the strength of well-structured, resourced, and adequately funded health systems that offer universal coverage to the population.  Again, most countries in the world are still lagging behind the implementation of their commitments in this critical area, and concerted action is urgently required at the international level as a national and global security imperative.  After all, the human and economic cost of the COVID-19 pandemic has been extreme, erasing in some areas decades of achieved progress.

Take-aways

Typically, the development of new vaccines has required years or even decades of research and testing before being deployed. In the case of the new COVID-19 vaccines, scientists raced to produce a safe and effective vaccine in record time.  In a historical feat, the trials of some of the vaccines took less than a year. In some cases, such as with the mRNA vaccines, the development was accelerated building upon existing platforms and processes already under way. 

As evidenced by Operation Warp Speed in the United States during the COVID-19 pandemic, and previous government investments that supported scientific breakthroughs of mRNA vaccines, the “public goods” role of governments to foster and coordinate public-private partnerships for the development of the COVID-19 vaccines was critical.  It was also critical for the deployment and the scaling up of the vaccination effort.

Extrapolating from the US experience, a key lesson for the future is that national governments, by enforcing regulation and taxation, can mobilize resources to provide public goods at the country level to realize the full societal benefit of public health actions and investments in pandemic preparedness and response capacities. 

Likewise, for some global public goods, whose benefits affect all citizens of the world--especially for those for which the exclusion of nonpayers is not feasible—as in the case of new vaccines, medicines, and therapies to prevent and control the spread of infectious pathogens that put all across the world at risk, a public sector push is needed or else the good will not be financed.  At the global level, there are existing mechanisms in international organizations, such as the World Bank Group, to collect and manage contributions from member countries to underwrite international public goods.  Examples of the these mechanisms are the Pandemic Fund, recently-established to provide a dedicated stream of additional, long-term financing to strengthen pandemic prevention, preparedness, and response capabilities and address critical gaps in low- and middle-income countries through investments and technical support at the national, regional, and global levels; the Global Financing Facility (GFF), is a country-led global partnership anchored at the World Bank Group committed to ensuring all women, children and adolescents can survive and thrive; or more broadly, the International Development Association (IDA), a member of the World Bank Group, that provides interest-free loans – called credits – and grants to governments of the poorest countries for supporting development efforts across sectors.   

 

Source of Image:  Stock Photo ID: 1697873311.  "Development and creation of a coronavirus vaccine COVID-19".