The pharmaceutical industry is alight with movement. We continue to witness mergers, acquisitions, clinical successes and attritions, filling pipelines, and changes in technologies. Sometimes it’s hard to see the forest for the trees when working within individual companies or therapeutic areas because of the curse of myopicity. By getting so narrowly-focused in therapeutic areas or within disciplines inside of a company, which are themselves focused on a narrow therapeutic window many recursive layers of myopicity ‘down’, seeing changes across the industry broadly is very difficult indeed.

Several of the changes we’re working on across the industry, of which you may or may not be familiar, include:

• Restrictions in travel and shipments (global logistics) which are disrupting some supply chains, but also calling for greater use of expert contractors remotely;
• Changes in cell types for biologics;
• Autologous and allogeneic cell therapy modernization, to contend with remote patients and more advanced processing methods;
• Newer approaches to bioreactor production methods;
• Greater use of CDMOs and CMOs;
• Updates to process measurements, including in-line PAT (which likely makes Contract Pharma’s Analyze This! columnist Emil Ciurczak happy); and
• AI/ML in production manufacturing decision-making, what we once called ‘Fuzzy Logic’, has now advanced to the next level to be incorporated into more advanced AI/ML algorithms.

in·no·va·tion
/ˌinəˈvāSH(ə)n/
noun
the action or process of innovating.
“innovation is crucial to the continuing success of any organization”

You may not have seen any, or many, of these above changes in the past year or two, but they are indeed advancing. It’s that it can be very difficult to observe change when it occurs very slowly, and especially in complex situations.

Glaciation and Boiling Frogs
By way of analogy, let’s think about glaciation. This is one of geology’s most-studied processes, and like many systems in geology, it occurs over v – e – r – y long timeframes. Glaciers have literally shaped the terrestrial earth that we can see, and have, along with the also incredibly-slow plate tectonics, created and shaped mountains all over the planet. But it took good measurement before early researchers even realized these monoliths of ice were moving.


Similarly, there is the fable (really, it’s an allegory) from the 19th Century about ‘boiling the frog.’ If you haven’t heard it, it goes something lie this: If you put a frog into a pot of boiling water, it will jump out* immediately (stimulus:response). The temperature delta is the key—the frog goes from thermal equilibrium to very much not. However, if you put a frog into a pot of room-temperature water and slowly add heat, the frog will slowly equilibrate with the water volume and be killed. I don’t recommend trying this, and I doubt the purveyor of the allegory tried it, either. But as a thought experiment, you see how this situation could work. Slow changes are hard to definitively ‘feel’. Sorites Paradox would have me asking you: “If I give you a pile of sand, and ask you to begin removing individual grains of sand one at a time, how long until you will no longer have something called ‘a pile’?” Or conversely, Zeno’s Paradox, which suggests that if you watch someone shoot an arrow out of a bow (owing to the era within which this paradox was devised), if you keep taking measurements at infinitesimally-small increments (zero duration) of the arrow in its trajectory, at each measurement, the arrow will in principle be standing still. So then how does it actually get to its target?
The point of covering glaciers and boiling frog allegories is that slow change, at imperceptible paces, can look like no change.

Black Swans and Climate Change
This inability of people to act or react—or perhaps their unwillingness—is what will ultimately be the arbiter of what happens with climate change. We’ve been dreadfully slow to recognize any changes, and when changes have been noted and published, there is a boiling frog metaphor somewhere to be found.

Once the global threat is critical, it may indeed be too late to mitigate it within human civilization’s time horizon. But, we live and we learn. Or, we don’t learn and we don’t live. Mother Nature doesn’t care because she would prefer that we were not here—we’re not in thermal equilibrium with the universe (it costs a lot of biological energy to not be at Temperature=0, that’s why your BMR each day is A LOT of calories).

I’m going to contrast the slow pervasive risk of climate change etching its way up the global thermometer with Nassim Nicholas Taleb’s idea of Black Swans. These are the unexpected changes, innovations and collapses that defied the ability to predict them. That’s why they’re called Black Swans. Our industry also has these punctuations over its timeline, where new technologies, therapeutic advances, delivery modalities, etc. led to paradigm shifts in how we’ve done our work. Black Swans will continue to occur, at a rate that may be suggestible by a Power Law, but largely unknowable. The COVID-19 situation was a global Black Swan for just about everyone, and dramatically impacted in mostly a negative way everything that has happened on the planet. Though the planet itself has benefitted, however briefly, from a moratorium on travel and manufacturing waste. But maybe all Black Swans aren’t totally unknowable:


Note the date. You just need to know where to look and how to listen.

In our industry, process improvements often take the place of what are called “Kaizen” events, which are quick changes with the intent being better processes and outcomes. Contrast this idea with “Kaikaku,” which are the Kaizen’s longer-timeline, bigger-outcome brother. In both cases, things keep improving over time. It is for this reason that Toyota has become so successful. By developing what would become the principles of lean at the Toyota Production System, incremental changes (kaizen) and radical changes (kaikaku) both sum and accumulate over time to produce levels of quality unlike what have ever been achieved in engineering. You can also consider those changes which are Revolutionary vs. Evolutionary in nature. Neither is better than the other, they are context-dependent, and both lead to advances in our healthcare industry. After all, small evolutionary changes are why you don’t look like a butterfly.

Where and which of these changes to production processes, measurement, data analysis, and therapy types will stick and be viable in propelling the industry forward? The answer is based in part on reproducibility and success rate, and also in regulatory favor and difficulty in implementation. There is a sort of natural selection about this, where the ‘fittest’ innovations will survive and permeate the industry, from the bleeding edge to the leading edge, to the also-rans and followers. To assess them for your organization could be quickly done using a Benefit:Effort quad chart seen in Figure 1.


In this way you identify what benefit you’d be likely to glean (production throughput, volume, velocity, quality, etc.) vs. the effort or difficulty to operationalize the changes (cost, capital intensity, resources, logistics, etc.).

Outro
What is true is that innovation doesn’t happen in a day, but more in a manner that is day-by-day. It’s only because we are often too close to it, that we don’t see its slow march to producing what separates the ‘future’ from the ‘past.’ The Second Law of Thermodynamics requires change in nonequilibrium situations (and that’s all of them, by the way). So as Heraclitus of Ephesus waxed ~2,500 years ago, “Change is the only constant.” Don’t stagnate. Your competition would love to eat your lunch. 

* The ability for the frog to escape the pot of boiling water would be based in part on the depth of the pot, distance from the outside perimeter, etc.

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Ben Locwin
Contributing Editor, COVID-19 Task Force member, Healthcare Futurist

Ben Locwin has been working on various COVID-19 vaccines since March of 2020, and development of state and national public health policy throughout the pandemic. He has frequently been called in to organizations to innovate healthcare and pharmaceutical approaches, and has been featured in various media and on podcasts focused on innovation in many industries.