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Warp speed is amazoning pharma practices and protocols.
The pandemic cast new light on the importance and vulnerabilities of the distributed nature of the pharmaceutical industry’s specialized supply and shipping infrastructure. Pharmaceutical scale permits, like those for semiconductor or surgical hospital consortiums, lower barriers to entry for otherwise fantastically complicated or fit-for-one-purpose-only technologies to gain traction. Scale also enables designs dedicated to eking out the last precious microns of performance or purity, which can determine the usefulness or failure of an approach. But specialization at this scale also proliferates nesting doll dependency. Each successive layered network of interlocking manufacture depends on an exact product or design specification to feed it. Shortfalls in one seemingly survivable area cascade like crashing waves onto the following layer, and so on throughout the system. Subcontractors focused narrowly to a single design task are reliant on yet more specialized subcontractors. By intention, all are equally synchronized in configuration, tolerance, and material conformation. Seeking alternatives is not simple, easy, or at times even possible. It was a growing source of pride to become so finely tuned that pharmaceutical manufacturing migrated to a just-in-time (JIT) mode to maximize these benefits, but this also exacerbated interdependencies.
Multiple industry contacts recently emphasized better outcomes these past two years from having increased frequency and depth of dialogue. At the 2021 AAPS, PharmSci 360 event in Philadelphia, Gabe Longoria, chief commercial officer at Astrea Bioseparations, encapsulated this well, saying, “I think supply chain challenges have forced a lot of organizations to actually align their overall focus on what they are trying to achieve. And because of these challenges, we’ve had to identify better ways of doing things, such as intelligent standardization protocols. And these same challenges have required finding better ways to provide resources not just to our customers but B2B as well. I think it’s important to recognize and note down those challenges, a lot of which we’ll continue to see in the next 9–12 months, and even after we come out of COVID, we’ll need to continue to look to better align resources toward goals. We’ve been forced to help one another, and we’ve been talking with our competitors to make sure we can do the right thing for our customers. Which has been intensely interesting. The end point is asking, what does the customer experience look like? And all organizations are looking to achieve success in this regard.” Direct and frequent conversation became the norm rather than a luxurious exception, driven by dire need more than anything else.
From a logistics and innovation perspective, the pandemic can be considered a smaller scale version of World War II. Development and deployment of radar is a parallel for vaccines in that metaphor. In each case they had been around for many decades, both had to be suddenly optimized and brought to scale in an abbreviated timeline. Each required highly skilled operators working in intensively coordinated interlocking systems. But both were only a key part of the overall response, not the sole basis for defense. Historians and analysts will grasp onto vaccine production when writing accounts of what happened during the pandemic response—just as they did with radar for the Second World War. But that falls short of telling the full story. Calls currently abound for a global commitment to a fully coordinated response next time around. Hence, the need to dig into the details, so that lessons learned are not so easily lost. The obvious is also worth pointing out.Pandemic pressures have transformed pharmaceutical manufacturing in a similar way that Amazon next day delivery became an inviolate rule for the shipping industry, dragging everyone in shipping to deliver at the same accelerated pace. However, vulnerabilities and downsides of JIT manufacturing and specialization were widely recognized well before the pandemic. FDA and the National Institute for Standard and Technology (NIST) came together to draw up plans to implement advanced manufacturing for medical supplies. Other groups became involved. A new manufacturing institute, BioMADE, supported by both industry and the defense department, began to organize.
And then COVID-19 hit.
Kevin Nepveux, vice president, Pfizer Global Supply, recalled, “Development and launch of the Pfizer-BioNTech COVID-19 vaccine was unlike anything I have experienced in my career in Pharma Manufacturing—and without a doubt the highlight. Multiple mRNA vaccine constructs were manufactured and tested in the clinic in parallel versus the normal sequential approach, and the selected strain was immediately scaled, both up and out, to begin manufacturing launch supplies before the pivotal efficacy study even started. In manufacturing alone, Pfizer/BioNTech committed over $1B in CapEx and OpEx before the first sign of efficacy.”
Pfizer went all in, coming out the other side having a changed perspective, as Kevin observes. “Learnings from the vaccine will be enduring, including streamlined internal governance, bringing on multiple supply chains simultaneously compared to normal post-approval expansion, and simplified regulatory engagement.”
Which brings us nicely to FDA, which might otherwise unfairly drop to a footnote to the vaccine success. FDA created a dialogue framework for COVID-19 vaccines to be developed at warp speed. Communication was excellent. In November 2021, FDA updated its resiliency roadmap, pointing out that since April 1, 2021, FDA conducted more than 600 domestic and more than 200 foreign remote regulatory assessments, which included review of records submitted upon request under section 704(a)(4) authority, as well as review of documents and other information voluntarily submitted upon request … more than 100 human and animal food firms participated in voluntary remote regulatory assessments (1).
While these assessments cannot be used to meet FDA Food Safety and Modernization Act (FSMA) mandated surveillance inspections, the assessments provided critical oversight to FDA during the pandemic. Dr. Elizabeth Miller, assistant commissioner for the Office of Regulatory Affairs (ORA) Office of Medical Products and Tobacco Operations, commented, “Throughout the course of this pandemic ORA has had to adjust and change how we work.We have been more agile than ever before.Our regulatory agility is an important cornerstone to delivering the oversight and consumer protection the public deserves from ORA and FDA.”FDA continued with mission critical inspections when they paused routine surveillance. They also developed a new process to assess facilities submitting Emergency Use Authorizations. These investigational activities allow the agency to directly observe operations at manufacturers of COVID-19 therapeutics and assess whether the firm has proper controls in place to ensure the safety, purity, and potency of the COVID-19 product.
It was FDA’s open and frequent communications that helped keep everything rolling forward as smoothly as possible. FDA made strong efforts at transparency in their Resiliency Roadmap, and have energetic plans to continue this as they inaugurate an Inspection Affairs Council to update inspection procedures. This new body within FDA will be headed up by Dr. Judy McMeekin, associate commissioner for regulatory affairs. It is a transformative solution born in part by the elevated contacts and cooperation during the pandemic.
Other lines of defense also needed bolstering, and these are the success stories hidden by the glare of vaccine successes. Hovione CEO Guy Villax said at the 2021 CPhI Worldwide conference in Milan, “In the early days of the pandemic, there were hiccups and delays, but that we didn’t see huge problems points to the resilience of the industry … the industry stepped up to the challenge. Gilead’s remdesivir has a critical excipient which only Hovione manufactures, we massively scaled up to produce a years’ production in only a month. CDMOs [contract development and manufacturing organizations] were doing heavy lifting to support the needs brought on suddenly by COVID-19.”
Susan Darling, senior director of capillary electrophoresis and biopharma product management and marketing at SCIEX, echoes the sentiment but also emphasizes the knock-on effects of increased calls for speed (see page 32 in this issue of BioPharm International). Darling comments, “Companies are looking to get development times down to 1000 days; they want to develop everything at pandemic speed, even when they have diverse portfolios that include highly complex next-generation products such as multispecifics, gene and cell therapies, and RNA-based treatments, all of which require new and different analytical capabilities.” So the trend line is becoming obvious. More complex molecules at faster speeds for development equals an opportunity for analytical tool makers to sell into a growing unmet need. Manufacturers must adapt quickly to new types of technologies more quickly because their competitors are already doing so. This will also have a knock on effect for products for purification and separations in both upstream and downstream processes, such as novel chromatography materials or quicker acting buffers and solvents, and so on. It is a defining moment for future planning requirements. “The industry is really driving to be creative, not just in terms of analytical solutions, but in how they manage data and pull it together to knock the inefficiencies out of every step,” Darling concludes. “Our customers are challenging us to develop new analytical techniques that provide more information more quickly, and when we bring them new solutions, they are adopting them at a much faster rate than could ever be imagined even a decade ago,” Darling says.
Corning Incorporated also stepped up to the challenge during the pandemic, in part supported by the Department of Defense (DOD), in coordination with Department of Health and Human Services (HHS), who awarded a $15 million Firm Fixed Price contract to Corning Incorporated to expand domestic production of pipette tips for robotic liquid handling instruments (2). But more well known was the Biomedical Advanced Research and Development Authority agreement to give $204 million to expand manufacturing capacity for glass vials to store potential vaccines for COVID-19 (3). Valor Glass vials, first introduced in 2017 and made from aluminosilicate glass, were of great strategic significance. “Velocity Vials” are now being introduced. And what more could a marketing department tell us about the business importance of “Amazoning”, than to use velocity in the product name. Velocity Vials are borosilicate externally coated with Corning’s proprietary technology, to eliminate bottlenecks and speed the delivery of life-saving treatments. These vials have demonstrated a 20–50% improvement in efficiency, up to a 96% reduction in glass particulates, and a 3x reduction in the likelihood of damage that leads to cracks and breaks, according to the marketing materials (4).
Other than the headline vaccines, much of great importance went on or evolved behind the scenes to manufacture excellence out of adversity in the fight against COVID-19. Landmark efforts in communications and cooperation kept the conveyer belts moving. Agilent’s digital solutions group “ramped up to meet the needs of customers by offering cloud-based software for remote instrument access and asset utilization monitoring (to) pulls together advanced IoT sensor technology and data analytics to enable lab-wide visibility,” according to Shane Elliott, vice president, Global Laboratory Solutions Marketing, Agilent.This effort was broad based across multiple vendor platforms, again in a concerted effort to increase and improve manufacturing communications. It was a near universal practice over the past two years. Production line pace is set to accelerate rather than slow down. Pharma production has been industrious in the good old-fashioned sense of the word. Ingenuity and hard work manufactured positive results out of adverse conditions. When serious global policies begin to become clear for the next pandemic planning groups, industrious effort, ingenuity, and improved communications will be the seed crystals for successful outcomes.
1. FDA, Resiliency Roadmap for FDA Inspectional Oversight (November 2021), FDA.gov.
2. DoD, “DOD Awards $15 Million Firm Fixed Price Contract to Corning Incorporated to Increase Domestic Production Capacity of Robotic Pipette Tips,” Press Release, Dec. 23, 2020.
3. BioPharm International Editors, “Corning Expands Glass Vial Capacity,” BioPharmInternational.com, June 17, 2020.
4. Corning, Velocity Vials, Corning.com, accessed Dec. 14, 2021.
Vol. 35, No. 1
When referring to this article, please cite it as C. Spivey, “Industrious Pharmaceuticals,” BioPharm International 35 (1) 10–13 (2022).