Critical Lessons from Development and Implementation of the Bivalent Oral Polio Vaccine Paper

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Introduction:
Polio, also known as poliomyelitis, is a viral disease that can cause paralysis, muscle weakness, and even death in severe cases. In this case study, we will explore the development of bivalent oral polio vaccine (bOPV) as a strategic tool in the Global Polio Eradication Initiative (GPEI). We will examine the key steps in the development, the programmatic impact of its introduction, the product lifecycle perspective of bOPV, and the role of the World Health Organization (WHO) in its coordination and clinical trial. We will also discuss the pricing of vaccines, especially the fair pricing of bOPV and COVID-19 vaccines, and how the lessons from vaccine development can be utilized in the current COVID-19 pandemic and other diseases.

1. In 2-3 paragraphs please explain how poliovirus is transmitted – additionally:
Poliovirus is transmitted mainly through the fecal-oral route, which means it enters the body through the mouth from contact with contaminated food, water, or surfaces. The virus can also spread through close contact with an infected person’s saliva, mucus, or feces, especially if the person is shedding the virus asymptomatically. Poliovirus can survive in the environment for several weeks, depending on the temperature and humidity, and can withstand small amounts of chlorine and other disinfectants.

a. Why was a bivalent oral polio vaccine (bOPV) chosen as a key strategic tool?
bOPV was chosen as a key strategic tool because it is effective against two types of poliovirus, type 1 and type 3, which are the most common types circulating in endemic and outbreak-prone countries. bOPV is also easier to administer than the trivalent oral polio vaccine (tOPV), which included type 2, but was also associated with rare cases of vaccine-associated paralytic polio (VAPP) caused by the live attenuated type 2 virus in the vaccine. Therefore, the decision was made to withdraw tOPV and replace it with bOPV, which is safer, more cost-effective, and can be used in combination with inactivated polio vaccine (IPV) to provide broader immunity.

b. What were the key steps in the development of bOPV?
The development of bOPV involved several key steps, including the identification of suitable strains of type 1 and type 3 poliovirus, their attenuation to reduce their virulence while retaining their immunogenicity, the selection of a suitable vaccine seed virus, the optimization of vaccine production, and the testing of safety and efficacy in preclinical and clinical trials. The key stakeholders involved in the development of bOPV were the WHO, vaccine manufacturers, national regulatory authorities, and the technical advisory groups, such as the Global Polio Laboratory Network, the Polio Eradication and Endgame Strategic Plan Committee, and the Strategic Advisory Group of Experts on Immunization.

c. Who were the key stakeholders involved in both bOPV development and implementation?
The key stakeholders involved in both bOPV development and implementation were similar but also included local health authorities, partners in the GPEI, such as UNICEF and Rotary International, and the communities and families affected by polio. The implementation of bOPV required not only the production and distribution of the vaccine but also the surveillance and response to polio cases, the coordination of vaccination campaigns and routine immunization, and the maintenance of cold chains and vaccine quality control.

2. How did the development of the bOPV align with evolving programmatic needs? What were the vaccination tools available to the Global Polio Eradication Initiative (GPEI) prior to bOPV? Why were new strategies required for the polio eradication program in remaining endemic countries? What was the programmatic impact of the bOPV introduction?
The development of bOPV aligned with the evolving programmatic needs of the GPEI, which aimed to interrupt the transmission of all types of wild poliovirus and eradicate the disease globally. Prior to bOPV, the GPEI used mainly tOPV, which was effective against all three types of poliovirus but also had some disadvantages, such as the risk of VAPP, the need for multiple doses, and the interference with other live vaccines. The GPEI also used IPV, which was safer but more expensive and less suitable for mass campaigns.

New strategies were required for the polio eradication program in remaining endemic countries because the epidemiology of polio had changed, and the challenges of reaching underserved and high-risk populations had increased. The introduction of bOPV allowed the GPEI to switch from tOPV to bOPV without compromising the coverage or quality of vaccination. Moreover, bOPV could be used in supplementary immunization activities (SIAs) and routine immunization, as well as in response to outbreaks and emergencies.

The programmatic impact of the bOPV introduction was substantial in terms of reducing the burden of polio and strengthening the immunity of vulnerable populations. According to the WHO, the global incidence of polio decreased from 416 cases in 2013 to 33 cases in 2018, and the type 2 wild poliovirus was declared eradicated in 2015, thanks to the withdrawal of tOPV and the introduction of bOPV and IPV. However, challenges remain, especially in conflict-affected and hard-to-reach areas, where surveillance and vaccination coverage are inadequate.

3. What were the key stages from a product lifecycle perspective that had to be addressed in the development of bOPV?
From a product lifecycle perspective, the development of bOPV had to address several key stages, such as research and development, preclinical testing, clinical testing, regulatory approval, production, distribution, post-marketing surveillance, and supply chain management. Each stage required different expertise, resources, and timelines, and involved various stakeholders, including scientists, clinical trial investigators, epidemiologists, statisticians, regulators, manufacturers, distributors, health workers, and communities. The lifecycle approach enabled the WHO and its partners to ensure the quality, safety, efficacy, and accessibility of bOPV, and to monitor and evaluate its impact on the polio eradication program.

4. How did the World Health Organization (WHO) coordinate the accelerated clinical trial and production of bOPV? Why was India selected as the location for the clinical trial? Why was the clinical trial able to bypass phase I and II? Why and how did the WHO engage drug manufacturers and national regulatory authorities?
The WHO coordinated the accelerated clinical trial and production of bOPV through its Prequalification Team and its Network of Quality Control Laboratories, which provided technical support and guidance to vaccine manufacturers and regulatory authorities. The clinical trial of bOPV was conducted in India, where the burden of polio was highest and the vaccine production capacity was also high. The clinical trial was able to bypass phase I and II because it was based on previous experience with OPV and bOPV, and the safety and efficacy profiles of the type 1 and type 3 components of bOPV were well established. The clinical trial focused on establishing the non-inferiority of bOPV compared to tOPV in terms of immunogenicity and safety.

The WHO engaged drug manufacturers and national regulatory authorities through its Global Advisory Committee on Vaccine Safety, which advised on the safety of vaccines, including bOPV, and its Expert Committee on Biological Standardization, which recommended the establishment of international reference materials and quality control assays for bOPV. The WHO also worked with the manufacturers and regulatory authorities to ensure the timely and affordable production, procurement, and delivery of bOPV, and to strengthen the local capacity for vaccine production and regulation.

5. Based on what you’ve learned about reimbursement in the course how would manufacturers go about determining a fair price for the vaccines mentioned in this case? How about a COVID-19 vaccine for which the benefits of utilization outweigh the potential risks from a safety perspective? If your answers are different why are they different?
Manufacturers would go about determining a fair price for the vaccines mentioned in this case by considering several factors, such as the research and development costs, the manufacturing costs, the regulatory costs, the distribution costs, the intellectual property rights, the affordability for low- and middle-income countries, the perceived value of the vaccine, the potential market size, and the competitive landscape. One method of calculating the fair price is the cost-plus approach, which adds a reasonable profit margin to the total cost of production. Another method is the market-oriented approach, which sets the price based on the willingness-to-pay of the customers and the competitive prices of similar vaccines.

In the case of a COVID-19 vaccine, for which the benefits of utilization outweigh the potential risks from a safety perspective, the determination of a fair price would require additional considerations, such as the urgency of the pandemic, the global public health implications, the equitable access for all, and the ethical principles of justice and solidarity. One approach could be the tiered pricing strategy, which sets different prices for different income groups based on their ability to pay and their burden of disease. Another approach could be the cost-effectiveness analysis, which compares the cost of the vaccine with its health and economic benefits, and determines the optimal price range that maximizes the net benefit for society.

6. What can the global health community leverage from this experience that can be utilized during the current COVID-19 pandemic? Additionally, what other diseases could benefit from the lessons learned in vaccine development from this case?
The global health community can leverage several lessons from this experience that can be utilized during the current COVID-19 pandemic, such as the importance of global cooperation and coordination, the need for evidence-based decision-making and risk communication, the role of partnerships and stakeholder engagement, the value of innovation and research, the challenges of vaccine hesitancy and misinformation, and the barriers of access and affordability. The GPEI provides a useful model for the COVID-19 response, especially in terms of surveillance, case management, risk assessment, and vaccine deployment.

Other diseases that could benefit from the lessons learned in vaccine development from this case include other vaccine-preventable diseases, such as measles, rubella, and yellow fever, as well as emerging infectious diseases, such as Ebola and Zika. The product lifecycle perspective provides a useful framework for ensuring the quality, safety, efficacy, and accessibility of vaccines, and for monitoring and evaluating their impact on the disease burden and public health outcomes. The WHO and its partners can continue to improve the vaccine research and development ecosystem by strengthening the regulatory frameworks, increasing the funding and investment, expanding the collaborations and partnerships, and enhancing the scientific and technological capacities.

Conclusion:
The development and implementation of bivalent oral polio vaccine (bOPV) as a key strategic tool in the Global Polio Eradication Initiative (GPEI) provide a valuable case study in vaccine development and programmatic impact for other vaccine-preventable diseases and emerging infectious diseases. The lifecycle approach, the global coordination, the strategic deployment, and the quality control of bOPV, as well as the fair pricing and global access of vaccines, are essential components of a successful vaccine ecosystem. The lessons from this experience can inform and guide the global health community in its efforts to combat the current COVID-19 pandemic and other public health challenges.