Before the pandemic, scientists around the world fought for media space to communicate the latest findings from their research. Few could imagine that the new decade would eradicate this fight by putting scientists at the center of attention.
As two experts working in different fields but interconnected disciplines within the same industry, we see the arrival of vaccines as a scientific triumph. But, this situation brings to the surface some fundamental questions. How will manufacturing be scaled-up (increased) to supply vaccines for the entire world? What have we learned about the monitoring and safety processes after the start of widespread vaccination? And what are the challenges that emerge from the simplifications made by public opinion about complicated scientific issues?
As seen by CMC (Chemistry, Manufacturing, and Controls), every medicinal product faces challenges during the development process. Typically, the biggest challenge is increasing the size of the production, because each manufacturing process has to consistently deliver quality products and guarantee sustainable global supply. Each production step should be developed in such a way that it does not compromise the quality and safety of the medicinal product.
This is exactly why each of the approved vaccines so far in Europe — Pfizer/BioNTech, AstraZeneca, Moderna, and Janssen — have lower production than expected: Because vaccines are extremely complex products for mass production.
We have safe and efficacious vaccines from a clinical perspective, but the same cannot be said in relation to the efficiency of the manufacturing.
Every vaccine batch must meet the criteria and specifications that have been set during the development process. However, the ability of a particular batch to meet the manufacturing criteria is directly linked with the time taken to optimize the manufacturing process. The need for vaccines to reach patients quickly has led to a situation where manufacturing parameters are sufficiently developed to produce high quality vaccines; but this has not left room for developing highly efficient processes that minimize waste during manufacture.
In other words, we have safe and efficacious vaccines from a clinical perspective, but the same cannot be said in relation to the efficiency of the manufacturing.
The rapid discovery of anti-COVID vaccines is a scientific triumph
In pharmaceutical terminology, each manufacturing process has a rate-determining step that defines how fast the process can be completed. In producing vaccines containing the virus’ genetic information, mRNA, the rate-determining step is the encapsulation of mRNA with lipid nanoparticles — four of which are found in the Pfizer/BioNTech vaccine.
The encapsulation of mRNA with lipids serves as a protective shield from degradation and facilitates the mRNA to be transported across the body. Even the slightest difference in the shape and composition of the lipids can change the properties and, consequently, lead to a change in their permeability, which affects vaccine efficacy. The requirement to carry out the encapsulation process with high precision is a delicate step that slows down vaccine production — this is why some manufacturers have produced fewer vaccines than expected.
In another vaccine production technology, that of viral vectors, the main challenge is growing cells where the adenovirus proliferates as the active ingredient of the vaccine.This is the reason why AstraZeneca has run into problems with the supply of its doses.
In fact, the active substance obtained at the end of cell growth, a process lasting almost 10 days, has a different yield from batch to batch — that directly impacts the number of doses that can be produced. After this step, the adenovirus is added, which proliferates for a few days and leads to the creation of the active substance of the vaccine. It is precisely the unpredictability of the cell growth process that causes delays in vaccine supply.
Post-authorization monitoring is paramount to continually review that the benefits of the vaccines continue to outweigh the risks.
Notwithstanding the pressures of the pandemic, the assessment process of anti-COVID-19 vaccines by national regulators was conducted in accordance with the same quality, safety , and efficacy requirements as for all other medicinal products.
The European Medicines Agency (EMA); the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA); and the United States’s Food and Drugs Administration (FDA) review the documentation submitted by pharmaceutical companies to their respective countries. If they assess that the benefits of a medicinal product outweigh the risks, then marketing authorization is granted and the product can be released for use.
In parallel to the documentation review by regulators, pharmaceutical companies, and certain divisions within the regulators, actively work in drafting plans to monitor the safety and efficacy of the medicinal product while it is being used in the community. This is done because the clinical studies have a limited number of subjects, who may not show all the possible adverse effects, especially those that are rare.
In fact, post-authorization monitoring is paramount to continually review that the benefits of the vaccines continue to outweigh the risks. If the balance shifts in favor of risk, then the pharmaceutical company is forced to recall the vaccine from the market.
In contrast to “classical” medicinal products, where the number of users is limited depending on the number of those affected by a certain disease; the urgency of the COVID-19 disease has exposed a large number of people to the vaccine over a short time span. The rapidly changing news landscape around vaccines has erroneously placed the focus on the adverse effects that come from vaccines — casting a shadow on the actual benefits that emerge from them.
But, how effective are the safety monitoring systems, and what are their positive and negative sides, especially when we are dealing with a pandemic that has been present for over a year?
Safety monitoring and a skeptical public
Developed countries have robust systems of reporting adverse effects, be it by medical personnel or directly by patients. With the start of vaccinations, the number of reports is increasing, bringing to the fore the adverse effects and complications that have not been previously documented in clinical trials. Thus far, two COVID-19 vaccines — AstraZeneca and Janssen — have been put under scrutiny by regulators and respective vaccination authorities, which, in itself, is a strong indicator of the robustness of these monitoring systems.
The serious adverse effects, which have emerged in a limited number of vaccinated people, carry another side effect: Increased skepticism and fear toward vaccines.
When there is a platform for scientific collaboration, the result is directly contributing to saving lives.
All the media and public noise around the pandemic is being further complicated by the panic created by those with limited knowledge of life and medical sciences. When non-experts give unfounded opinions on the virus and vaccines, they should be ignored. When their opinions lead to an increase in skepticism and fear of vaccines, they should be fought. The pandemic and infodemic are defeated only through science and facts.
At a time when the number of infected people in the world has broken new records, laypeople’s interventions are dangerous because they tend to ignore the context of the pandemic. This puts us in a dangerous situation, because the adverse effects or the complications shown in a relatively small number of vaccinated people, are putting at risk the vast majority of the population — who remain unprotected from COVID-19.
In this context, we face an ethical dilemma: Is it right that during a pandemic we stop using effective and safe vaccines, because of adverse effects that are rarely fatal? While at the same time we risk the lives of hundreds of thousands of people that remain unvaccinated?
The COVID-19 pandemic has brought a fundamental shift to the drug development, commercialization, and review of medical products. At the start of 2020, none of us would have predicted that within a few months we could develop vaccines that usually take over a decade to produce and in most cases are not successful.
What we have learned from this experience is that when there is a platform for scientific collaboration, the result is directly contributing to saving lives. In addition, the fragility of the situation is so significant, that the successes of vaccine development may be shadowed by the infodemic where fake and unproven news infects society and risks the triumph of science.
Owing to the pandemic, we have learned that medicinal products can be developed and studied with a speed that is proportional to the public health crisis. But the blinkered focus on the shortcomings of the process, while ignoring the benefits, seems to be the next challenge where the robustness of science collides with simplifications created by society.
Cover Image: CC0.
The authors’ points of view are personal based on their professional experience and do not represent the stances of any pharmaceutical company.