By Matthew Pillar, Editor, Bioprocess Online
I was in Boston and Cambridge last week to record a few Business of Biotech podcasts and take in a few sessions at the BioProcess International conference. Against the advice of my friends there, I rented a car to get around. I’ll never do that again. Thankfully, no one was injured.
The show was representative of post-pandemic (is it acceptable to say that yet?) conferences. Well attended – show organizers say it was the best attended BPI on record (of course they do) – though I didn’t experience any lines at registration, bottlenecks on the show floor, crowds, or standing room only sessions. The booths occupied by the industry’s big suppliers were relatively demure by pre-pandemic standards.
One of the discussion sessions I enjoyed most offered a street-level view of the manufacturing capacity crunch, and I enjoyed it particularly because the panelists didn’t do what I expected them to – spend an hour lamenting a problem we’re all familiar with. Instead, they offered some insight into the root causes of the problem and connected the dots to the strategies they’re employing to address them.
Those strategies aren’t all heroic and rosy, mind you. For many biopharmas, it’s boiling down to sacrifice and prioritization. Pipelines are shrinking as early-stage candidates get pushed to shelves and backburners because capital’s at a premium, inflation’s high, and supply of raw materials and consumables is slim. While biopharma manufacturing square footage is growing at an incredible clip, those three aforementioned problems are limiting manufacturers’ ability to put all that square footage to good use. The stark reality is that innovation is suffering as a result. Here’s part one of a two-part recap of the discussion.
How Real Is The Capacity Crunch?
The panel began as most do, at a high level. Moderator Anthony Davies, Ph.D., Founder & CEO at Darkhorse Consulting, asked each panelist if they were actually experiencing the symptoms of the capacity crunch that’s been so well-covered in the trade press.
Those panelists represented comprehensive perspectives. From the research and CDMO side, the group featured Kelly O’Hare, SVP of Operations at Lykan Bioscience and Larry Lockwood, VP of Sales at Aldevron Company. The sponsor angle was represented by Kumar Dhineeshaan, SVP of Technical Operations at Renovacor and Ken Green, Ph.D., Sr. Dir. Of MSAT-Commercial Manufacturing and Supply Chain at Vertex. For good measure, Brian Taylor, EVP of Biopharma Solutions at SmartLabs joined as the voice of the growing outsourced research laboratory community.
To a one, the panelists agreed that they’ve all been feeling the impact of capacity constraints over the past 24 months, and that the most acutely affected are early-stage developers of biologics and cell and gene therapies. Lykan’s O’Hare says that’s due to the large volume of drugs in early-stage development requiring manufacturing capacity for first in-human trial, adding that she anticipates the problem expanding to the commercial space when and if a glut of these drugs reach approval.
Physical Capacity Expansion, Supply Chain Constraint
The conversation quickly shifted when Dhanasekharan added that, for emerging biopharmas in particular, manufacturing capacity challenges have been exacerbated by supply chain disruptions. Because raw materials needed for manufacturing were often impossible to secure in a timely manner, many contracted sponsor companies had to postpone their manufacturing engagements by three or four months. Their CDMOs suddenly found themselves with last-minute, short-term production capacity. But, when those scarce raw materials were once again available, albeit in fits and starts, demand began to outweigh supply. That remains the case, and Dhanasekharan says that’s made it very difficult for new clients to engage in outsourced manufacturing arrangements.
The “whys” behind ongoing COVID-related supply shortages are many. People couldn’t go to work in manufacturing plants for a long time. In China, where many raw materials and consumable supplies are manufactured, widespread lockdowns remain commonplace even today. Raw material and consumables manufacturing facilities that remained online were largely, or in some cases solely, dedicated to supplying COVID vaccines and therapeutics developers. For perspective on that, Darkhorse’s Davies points out that to meet the commercial product demand for two doses of an mRNA vaccines—in the United States alone—the glass vials required would stretch from London to San Francisco and halfway back when lined up side-by-side. That’s a lot of glass vials, the production of which depends on silicon dioxide, which itself is in short supply. Supply chains are just that—chains—and there are many weak links in this one.
Aldevron’s Lockwood acknowledges those problems. He says outsourcers struggled with material sourcing across the spectrum, and that even when capacity became available, basic necessary supplies did not. That means simple things, like final filling operations, were often undoable. He says the company has tried to address the aspects of the issue it has control over—accelerating the adoption of technology that will (eventually) enable continuous manufacturing methods, for instance—to make more efficient use of limited supplies. The pandemic, he says, gave Aldevron cause to reevaluate operations team execution. Those tech and process refinements, he says, contributed to a 50 percent reduction in batch cycle times, effectively enabling more capacity without a capital facilities investment.
Lykan’s O’Hare says the ongoing supply shortage creates a mounting problem as demand for manufacturing surges. Biopharmas — many of them at once, in fact — are eagerly ramping up COVID-delayed clinical trials, but supply constraints remain, particularly in primary equipment and materials including incubators and cell stacks. That, she says, makes it difficult for Lykan to help sponsors schedule production. Like Lockwood, she says the best an outsourcer can do is lean into process optimization (and, in her words, re-optimization) in pursuit of time and material efficiencies.
Sole Sourcing Is Now A Sin
You want loyalty, go buy a dog, the old saying goes. Same story in the modern era of biopharma supplier management. Dhanasekharan, referencing the fact that a dearth in the availability of consumables as basic as filters can create manufacturing challenges, says it’s been key at Renovacor to create optionality by designing component interchangeability into its manufacturing processes. Evaluating multiple filters from different vendors withing a specific process and, ultimately, sourcing from multiple of those vendors allows the company to better manage supply lead times. It’s a clean and simple concept, albeit sullied and complicated the by the heavily regulated industry we’re in.
Indeed, O’Hare reminds us that multi-sourcing isn’t merely a function of procurement—it’s very much a function of QA as well. Moving away from sole-sourcing, she says, is incredibly important, but it’s also a good time to assess surrounding functions for efficiency. She recommends asking questions like, how can you qualify your vendors more quickly? How can you add to your pool of vendors, and how should you handle comparability of substitute materials? She also suggests monitoring the markets to proactively head off supplies that could go into shortage.
Perhaps that’s why, as Dhanasekharan admits, few biopharma manufacturers proactively considered multiple suppliers of a single product or consumable in pre pandemic times.
We’ll pick up in part two with panelist’s perceptions of how long these supply chain constrictions and capacity crunches will last, and what it’s going to take to beat them.