While we await the end of the pandemic phase of COVID-19 and to begin the new normal, we recognize the rapid development and deployment of vaccines as one of the biggest success of science, technology, regulatory flexibility. That and the rapid and effective role played by governments in many parts of the world as highlights of what we as a society can do to rise to serious challenges. These accomplishments would have been decade long process in the past or minimally a multi-year process.

As with the other posts of ‘HiBrow Perspectives’ – we highlight salient and some not obvious aspects of some of these huge successes in biomedical and technological innovations, business strategy, regulatory and governance aspects that have impacted the society positively in major ways as well as some stark disappointments.

The resistance to COVID vaccine and masks from a section of our society and the constitutional right facet

Given the time-sensitive importance, we start with the topic of vaccine resistance vaccine and masks that have impact on other parts of the society and can prove to be a major cause for avoidable delay in our quest to end the pandemic phase of COVID-19. We start with this topic before other business and innovation related thoughts.

There is no denying of the fact that for ending the pandemic phase of COVID-19, the use of vaccines and masks at the societal level are key needs. However, significant section of our society resisting these protective measures citing infringement of their constitutional rights, and mounting challenges to mandates in its current form in courts and through other channels are big deterrents. Getting to the other side of the pandemic requires compliance and participation of almost everyone and over one in five people in the USA have not received a single shot of the vaccine to prevent COVID-19. In this context, in the earlier post “Crushing COVID-19: Masks, Messaging and Creating the Moment” I highlighted the equivalence of seatbelts and airbags in automobiles to masks and social distancing, and suggested that fact should help us create (time-limited) mandates. I restate that solution proposed there (in brown letters below) with modifications that accommodate interim developments including availability of multiple approved vaccines, the (conditional) mandate issued by the current government and mounting legal challenges to void the mandate.

Masks, social distancing and vaccines being protective to the individual and for others and the equivalence and precedence of seatbelts and airbags should help enforce mandates (as a time-bound legislation) and overcome legal challenges that cite infringement on constitutional rights and individual liberty, as was protested when seat belt law was introduced. Refusing to comply with the mandate (or the inability to enforce the mandate) puts those who do not comply as well as others to dangers that include risk of death and significant burden on our hospital and public support systems, in addition to significantly higher short and long term negative social consequences. We should rightfully expect protection from those risks as our constitutional rights, as well as our duty to protect ourselves from known danger posed by such non-compliance. Certainly, that does not spare the responsibility of the government to continue making good decisions and messaging with suitable, well supported and socially acceptable reasons (and providing compensations when appropriate).

In the USA, the Biden government has so far taken some steps on vaccine mandates that have had some success but are legally on a slippery slope, but not yet irreparable. Are steps we had to take such as shutting down businesses, lockdowns etc. ‘legal’ from the same perspective as claimed for the resistance to vaccine mandates?   Would we want to go back to the shutdowns that cause major loss of productivity and mental turmoil? Instead, if we use the realistic reasoning and precedent of seat belts and airbags, we should be able to get legal clearance and enforce time-limited mandates.  Our collective goal as a society to start settling into and to reshape the ‘new normal post COVID-19 pandemic’, we have all be looking forward to, can be achieved in a significantly shorter timeframe with the mandate (that enables cooperation and compliance of society as a whole) than otherwise.

We can also spend time and resources to understand and thwart or prepare to effectively tackle aspects that are beyond our control such as the evolution of the COVID-19 causing virus evolving variants with increased transmission and disease causing ability, and the recent recognition of deer population harboring the virus (thus acting as a reservoir and potentially serve as a medium for the virus to mutate and evolve further).

I hope we find the best way to respect and tap the diversity of human behavior and variety of opinions, that often tend to add originality and provide the opportunity to see many sides of problems or decisions that has positive impact on wider society.

Despite the importance of equitable access of vaccines (if possible at all) not only within the societies of rich countries but also to other parts of the world is a responsible and humane thing to do, and might prove an important need in ending the pandemic phase as well as curbing resurgence, we avoid that topic in this post.

Innovation and speed of vaccine generation

Even people who do not have strong science and technology background would have learnt from the media that two of the most widely used vaccines were derived using a novel biomedical innovation ‘mRNA delivery based approach’ as opposed to traditional use of protein based agents to elicit immunity to the COVID-19 causing virus.

The two major mRNA vaccines were from Moderna and Pfizer-BioNTech, both of whom were (and are) at different stages as businesses. Some claim that mRNA based approach is going to be make it non-bespoke technological module like approach that is going to transform the way we create medicines. With the ‘buzz’, the investment that comes with it, and the way it is projected I am certain we will have lot of success from this approach, with the cost of mRNA medicines also likely be high (far higher than it should be) as the investors have to get their return on investment (ROI). However transformational mRNA delivery based approach is, it is not significantly more modular or cost-effective in the overall context of developing medicines (or vaccines) than other approaches as it being touted. Other aspects of development, accumulating evidence for regulatory approval, manufacturing and delivery of medicines need change for the costs of development to get lower.

A continued and major failure of another biomedical innovation even in time of such need

We cannot ignore a major failure of one scientific innovation that SHOULD HAVE SUCCEEDED AND THAT ALSO HAD A GREAT POTENTIAL KEPT THE COST OF VACCINES MUCH LOWER, which is an important factor for a worldwide need at this time. The discovery/invention of RNA interference “RNAi” (that act through microRNA “miRNA” as one of the components) that also got a Nobel Prize in the year 2006. Among playing other important roles, the citation of the Nobel Committee included role of RNAi in viral immunity. Later use of RNAi even paved way to discover novel RNA viruses (for context: COVID-19 is caused by a RNA virus).  Please look up the post in this series Why I am indifferent to the effects of sequestration on research funding where I highlighted the case of identifying novel viruses, and in the post during the time of SARS-CoV time: Just in time (JIT) vaccines and cures for Ebola and other sporadically emerging (and devastating) global infectious diseases, that covered the cost aspect in using that approach. However, despite the invention linked in a major way with viruses, and in contrast to recent trend of Nobel Prize winning biomedical innovation having paved immediate impact on practical biomedical uses for the society, the miRNA companies or community not delivering at this time for this major need (either as a vaccine or a therapeutic) of the society stands out as a stark failure. Unlike the business leadership examples highlighted in the next section, it is possible that the leaders of the miRNA companies though of COVID-19 vaccines as a low revenue opportunity (wrongly, I would guess).

Business of vaccines – contrasting two business strategies

I focus on the mRNA approach to discuss the business of vaccines (despite the fact that J&J & Astrazeneca took different approaches to get vaccines to the society) as the former covers important aspects of business strategy and contrasting approach taken by the leaders of the two major mRNA vaccine manufacturers –  Pfizer and Moderna.

To give a simplistic background, Moderna focuses primarily on the mRNA delivery based approach for drug development. Their CEO Stephan Bancel has been extremely good in filling their coffers with lots of money, tout the promise of the new approach, and continue to be secretive of what they were doing. Stephan (Bancel), under his leadership as the CEO of Moderna, had garnered capital and partnerships worth 2.7 billion dollars before they went public in 2018 (an example article). In fact, it has been a puzzle for many that they were touting so much but not brought a single medicine to advance phases of clinical trial phase. Even in the case of COVID-19 vaccine, Moderna made sure to get a billion dollars for trying to develop and initial commitment worth $ 1.5 billion to buy the vaccines once they succeed in developing and the vaccine gets approved – consistent with the approach of their CEO. They also had the support of (and collaboration with) the nation’s top research agencies that are also significant financial sources that bankrolled the development of the science even before this pandemic.

Here we contrast the strategy taken by Moderna with that of the other mRNA COVID Vaccine commercial effort (Pfizr- BioNTech).  The company BioNTech, made a smart choice to collaborate with the Big Pharma Pfizer. BioNTech could have been secretive and decided to go alone with the possibility of not having contributed this way to the society or their business goals with such major exposure with the success of delivering on COVID-19 vaccine. From the other side, Pfizer could have rejected the deal – but to the credit of their leader Albert Bourla (CEO), Pfizer acted swiftly to leverage their capabilities in science, technology and logistics in the medicines business. Further, in contrast to Moderna, they decided to deliver on outcomes (in this case deliver on a major societal need) and then rely again on government as a major buyer of the end product, than try to get money for trying irrespective of success as a safeguard. That demonstrated confidence in the capabilities of their enterprise, despite the risk, and at the same time recognizing the opportunity (and of not failing) not conflicting with their for-profit mandate. Of course, this approach has many other benefits – including not getting burdened with reporting needs that come with public money and control over existing and new intellectual property. Their business leadership got their scientific leaders, and whole enterprise motivated to act with the requisite urgency and acumen. With the end result known, we should laud not only the business acumen of their leader but the capabilities of biomedical and other teams and delivering on their capabilities. Pfizer had continued to act on that leadership in COVID-19 vaccine at every phase since the first success of getting emergency use authorization (EUA) to extend that to the next age group, and now to pediatric population. Importantly, I would also think they instigated Moderna to deliver a product to the market. Moderna has been a close follower on the successes at each stage.

The biggest qualm I (and many in the society) would have on the Pfizer-BioNTech vaccine is the need for -80^oC storage – and they did not overcome that need subsequently as well. With an active agent like mRNA (not a proteinaceous agent that inherently tends to be labile) I will consider that a failure of sorts that probably highlights the lack of capability in some front in their organization that they should evaluate.

Yet another troublesome fact is the relatively short-lived immunity triggered by this generation of vaccines that is currently attributed to the inherent characteristics of this COVID causing virus and dynamics of immunity, as mentioned above. That fact also indicates the need for the continued search for approaches to trigger immunity that lasts longer and will work against variety of mutations that the virus is likely to accumulate and some of which could cause reemergence.

Kudos to the efforts of governments and regulatory agencies in a time like this where speed is of essence

Finally, we should applaud the excellent and rapid responses of our regulatory agencies (e.g., USFDA , CDC in the USA) and the governments of many countries besides the USA in acting swiftly and getting the vaccine into the arms of people (or trying to do so), and continuing to implement a variety of other measures during this time of major disruption with so many facets that need to be addressed in parallel.

Consistent with the goals of ‘HiBrow Perspectives’ I am certain that this post helped stimulate thoughts on some important aspects that fall at the interface of innovation, regulation and business and have major societal impact. Please share your thoughts ideally as an open forum here (instructions at the end of this web page) – or continue to do so as personal communications as several of you have been doing in the past.

*Post-publication edit: A statement on the number of drugs based on RNAi that slipped edit was removed - about 2 hours post publication