On April 24, 2020, I decided to call Life Science Leader emeritus editorial advisory board member Andy Skibo, an icon in biomanufacturing circles. I don’t normally call executives unannounced, even one supposedly “retired,” but Skibo and I have continued to stay in touch ever since we developed the May 2014 cover feature on how he applied a risk-based approach to manufacturing capacity planning.
While the phone was still ringing, I got a text stating, “Sorry, I can’t talk right now.” So, I left a message saying I was just calling to check in. I soon learned that he had been meaning to reach out to me. Turns out he had committed to giving a Fireside Chat at the 2020 American Biomanufacturing Summit (Bioman) on July 22, and wondered if I’d be interested in moderating, despite it having now gone virtual. When we finally connected, though, his Bioman presentation wasn’t our first topic of discussion.
Family And COVID-19 Always Come First
Ever since COVID-19 caused the unprecedented use of the word “unprecedented,” I feel compelled to ask how people and their families are doing whenever getting on a phone call. Such was the case with Skibo. Learning that all was well on the home front, we transitioned to how he was managing working remotely. Because despite being “retired,” he still spends about 25 percent of his time helping AstraZeneca, another 50 percent working as chief manufacturing officer for FluGen, with the remaining 25 percent split between family, consulting and board of directors’ work, and hobbies. “I was working from home anyway, so the only change was not traveling, which sure as hell didn't bother me much,” he relays. We talk about family some more, and before you know it were into the unavoidable topic of COVID-19. “With all my work on ongoing influenza programs, which are informed by a continuing flow of WHO, CDC and other inputs on circulating virus strains, I had an early view into the coronavirus data,” he elaborates. According to Skibo, it was clear in early December that the coronavirus was going to get ugly. “Though we didn't realize how infectious it was going to be, the data was telling you it was never going to stay in China, not when you have tens of thousands of people infected in a city with a major airport.” Skibo speculates that the reason China didn’t initially take the coronavirus outbreak very seriously, is Wuhan, despite its size, is considered more of a backwater city when compared to China’s other technology innovation hubs (i.e., Shanghai, Beijing, Hong Kong SAR and Shenzhen).
The conversation wound through how the coronavirus impacts people differently. “For some, It trashes the inside of your body with major impact on vital organs,” he exclaims. For some, it’s respiratory with a significant impact on the lungs, while for others it attacks the kidneys, liver, brain, or spinal cord. “Most other viruses have a specific focus of attack. COVID-19 seems to have multiple routes of attack, with no current predictors of why those specific routes of attack occur for a given patient. It can cause multiple blood clots, and it depends on the individual as to where those will occur.” There’s the skin rash that’s been showing up in old people and kids that sometimes goes away, and sometimes turn septic, resulting in amputation. Then there’s discussion on how environmental temperature might impact the coronavirus, as experience with seasonal influenza, and the coronaviruses that cause the common cold, has shown that virus outbreaks/spreading traditionally declines in warmer summer months. “With a totally naïve population, that seasonal affect may not be in play during the first season or two of a new pandemic.” That is what happened with the “Spanish Flu” pandemic in 1918. We see it now in China. “China is having resurgence in cases right now, and these are in southern China, where it is hot and humid,” Skibo adds. That argues that summer isn’t likely going to calm things down. “The significant, current spikes of occurrence in Florida and Texas are giving us this, “will it go away in the summer,” answer right now.”
Skibo and I talked about COVID-19 testing, or the lack thereof in the U.S., along with viral shedding. “There's pretty strong data that people are viral shedding for up to six weeks after being symptom free from having had COVID-19.” Factor in another five days when viral shedding can occur prior to showing symptoms, along with how ever long someone is considered “sick,” and you can understand why so much of the economy was initially shut down. “We can’t shut the country down for an entire year, but we also can’t pretend it isn’t out there or we’ll end up killing a million or more people. The whipsaw effect on our economy of opening too soon or too much, and then having to re-close in the face of a large recurrence of the disease might be worse that a more cautious approach to opening in the first place.”
In total, Skibo and I spent roughly 22 minutes of our first planning call talking about stuff related to COVID-19, and not in a way related to his manufacturing area of expertise. But we soon got into that. For example, we talked about how many companies are working on COVID-19 treatments and vaccines (115+), along with Moderna’s promising data. And even if some company miraculously gets a vaccine developed before the end of December, how do you get a few hundred million doses manufactured? “It isn’t just the physical manufacturing capacity for drug substance and drug product, it is all the supplies and support logistics like testing, that go into a large manufacturing program. Simple things: where/how do you obtain hundreds of millions of units of pharmaceutical glass (vials, syringes), on top of industry’s normal ongoing demands? There are limited suppliers. And they don’t maintain a 50 percent unused capacity in this day and age of lean, just in time, lowest possible cost, manufacturing? “There’re two major suppliers of pharmaceutical glass in the western world, Becton Dickinson (BD) and Schott AG over in Germany,” Skibo shares. Now, imagine if all of the companies working on a vaccine are trying to order a few hundred million units of glass, when not all will end up getting across the finish line. “This is where the absence of a strong federal government program oversight is not helping.” Skibo believes that we should have some sort of managed strategic glass reserve or allocation system in place, or such that whoever gets the vaccine first actually gets the glass. The only question is, who would oversee this system? “But because this system doesn’t exist, and because glass is cheap, and you can't administer the vaccine if you don't have glass, companies are more than willing to write $30 million checks to purchase and proceed full steam ahead.” Skibo uses glass as an example of critical supplies, but the same concern applies to all necessary, critical supplies needed for vaccine manufacture.
Assuming a vaccine is successfully developed, manufacturing then becomes a question. “Some of the of what is being developed is live virus, which means you won’t want to manufacture in a plant actively producing other products, unless you are willing to take those offline.” Another issue is that many of the coronavirus candidates are in development at very small companies, meaning, manufacturing will require CMOs. And while coronavirus vaccine R&D teams have been getting most of the press for their vaccine development efforts, rightfully so, Skibo says it will be those responsible for manufacturing and those companies supplying of media, resins, glass, testing, and all the other necessary materials that will determine whether or not biopharma is able to deliver hundreds of millions of units should a COVID-19 vaccine prove promising.
We also talked about the risks associated with both the compressed timelines being proposed for the COVID-19 programs in development, and the risks added by all the publicity and hype associated with some of the major programs. We’ll save those discussions for our fireside chat.
Preparing For The New Biomanufacturing Frontier
Back when Skibo was first asked to give his planned Bioman talk, it was months before COVID-19 had burst on the scene. As such, Skibo planned to discuss preparing for the new biomanufacturing frontier, which included his thoughts on the challenges around cell and gene therapy production, along with manufacturing platforms and capacity requirements for personalized medicine. “The science has determined that we can make these products, but the manufacturing and supply chain necessary to execute is half bio and half Amazon,” Skibo explains. The clarity of what is necessary to successful manufacture cell and gene therapies and other personalized medicines came to him this past December. “For the first time in my life, I actually had time to watch what happens when I order a book from Amazon,” he begins. “Once you’ve ordered, if you want, you can go online and watch the book leave a warehouse somewhere and begin its journey through places like Des Moines and Louisville.” You can watch the process right up to the exact time when the book will arrive at your doorstep. Skibo says the manufacture of personalized medicine needs to function the same way, and companies need to start hiring experts in this field, as part of their supply chain team. “Many companies think it is all about the bio and science,” he begins. “We need to be confident that we can track a vile of fluid extracted from patient number 23 through the cold chain to a plant in less than 24 hours. We then need to track it through the whole manufacturing and QC process as it is converted into the intended medicine for that specific patient, and then back through the entire cold chain and delivered to patient 23.” According to Skibo, the regulations for managing such a process haven’t even been invented yet. Then there’s the regulation (or lack thereof) of plasmids and other critical raw materials. “The question of what is a raw material vs. what is a ‘co-product’ needs to be answered.” What about CMOs becoming major players for CAR-T?
These, and more, were planned points for Skibo’s original Bioman talk. But as you can see, based on how many phone conversations tend to go nowadays, as COVID-19 is impacting so many aspects of daily life, people are compelled to talk about it. They might not want to watch the news about it, but most need to talk about COVID-19 at some length. Plus, given the important role to be played by biomanufacturing and the supply chain in eventually bringing a COVID-19 vaccine to market, not talking about the coronavirus in Skibo’s upcoming fireside chat would be avoiding the proverbial pink elephant in the room. So, while Skibo and I plan to cover everything promised on the American Biomanufacturing Summit agenda, we’ve decided to first talk about biomanufacturing, regulations, the supply chain, CMOs, and other aspects around COVID-19 this audience should find valuable. We hope you will join us on July 22, 2020, 11:05 – 11:40 AM ET for our fireside chat, and connect in person via the “live chat” Zoom feature. See you then — albeit virtually.