High quality resins manufacturing during a pandemic and beyond

MAY 27, 2022
By Jeanene Swanson, Senior Marketing Writer, Cytiva

Since 2021, there have been significant supply chain challenges across the world. Whether it’s lumber, car parts, or grocery deliveries, every good and service supplier seems to have been impacted by the current supply chain crisis.¹ And, that includes suppliers to the biopharmaceutical industry like Cytiva, which offers both instruments and consumables for bioprocessing.

According to the Global Biopharma Resilience Index (which comes out of a 2021 report by Cytiva and the Financial Times’ research arm, Longitude),² the biopharmaceutical industry as a whole has become more dependent on a global manufacturing and distribution supply chain over time, which has made things less expensive while at the same time increased vulnerability to bottlenecks in supply. During the COVID-19 pandemic, this vulnerability led to supply chain shortages due to increased demand, in tandem with raw material supply bottlenecks.

A key consumable in downstream bioprocessing, the chromatography resin, is one material that has been impacted by increased demand. However, as a long-term industry stalwart supplier of resins, Cytiva is dedicated to ensuring not only the highest quality resin product, but also security of supply. At Cytiva, the Security of Supply team helps ensure that manufacturers can rely on us to get the resins they need to fill their drug development and manufacturing pipeline when they need them. In this article, we provide an overview of the resin manufacturing process, then describe how Cytiva is helping alleviate supply chain issues through its reliable product discontinuation policy, commitment to business continuity management (BCM), and capacity expansion plans.

Chromatography resins: quality takes time

Chromatography resins are the cornerstone of many downstream processes. Cytiva has been manufacturing resins for many years, adhering to the highest quality standards, and is now considered an industry leader. “Historically, the oldest product we have is more than 60 years old,” Camilla Lindgren, Security of Supply Program Leader, says. “We have done this a long time, [and we’re] known for our quality of products.”

In addition, she acknowledges that the pandemic has significantly disrupted the resins supply chain. “Demand has increased to levels that we could never have foreseen, due to COVID.” While there are material shortages due to supply chain issues, the main issue for resins is that “we don’t have enough capacity for this demand that the pandemic has created.”

Producing resins is a complex and time-consuming process that involves one of three main starting materials: agarose, sugar, or polystyrene. Specific types of chromatography—for instance, gel filtration, affinity, and ion exchange—use an agarose gel matrix, in which the agarose is not used as a continuous gel but is formed into porous beads. Agarose and sugar are polysaccharides that come from seaweed and sugar beets, respectively; they are made into a white powder, which is dissolved in water to form a gel. Beads composed of polystyrene, a synthetic polymer made from a liquid petrochemical, are used to create a gel-based matrix. Optionally, different ligands can be bound to these bead matrices to form a variety of types of resins for different separation processes required for different types of therapeutics.

“When we create beads, we produce the base matrix,” Camilla says. “Those different base matrices are different in size and porosity, and they create the basis for [many] products.” In fact, she says, Cytiva has between 27 to 30 matrices that form the basis of more than 1700 products. The entire process of resin production can take from six to 12 weeks. “In some processes, we still use manual steps, using microscopes to understand what happens in the process, whereas in other processes, the inline controls are further developed and processes are more automated. Regardless of process setup, the manufacturing processes follow a strict protocol, carried out by skilled and experienced operators to ensure high quality products at all times.”

With organizations around the globe quickly acting to evaluate, develop, and produce a vaccine over the past two years, increased demand for resins has caused industry-wide shortages. To help maintain security of supply, as an example Cytiva uses more than one supplier to source the key raw material agarose. Manufacturing using biological materials introduces variability in the processes; however, Cytiva aims to minimize this factor through intensive supplier risk management and raw material studies, to safeguard customers’ product quality.

To summarize, the imperative of high quality production processes and skilled labor as well as current scarcity of supply of raw materials add to the complexity behind the resin manufacturing process at Cytiva.

Business continuity management helps ensure security of supply

Cytiva continues to alleviate supply chain issues through a combination of its reliable product discontinuation policy and its commitment to business continuity management (BCM). Cytiva’s Business Continuity Management system is certified to ISO 22301 across bioprocessing sites. One BCM strategy employed by Cytiva is having a strategic reserve of resins as a means for futureproofing production of approved human therapeutics. In other words, Cytiva has backup reserves that can be used in the unlikely event of an incident occurring at one of its manufacturing sites. The company is looking to enhance this even further in the future.

“Business continuity is one of the pillars of security of supply,” Amanda Thomson, Global BCM Leader, says. “It is about having a plan B. If we have a disruption or a crisis event, we have business continuity plans in place with detailed recovery strategies.” The company’s Uppsala, Sweden, site became ISO certified in business continuity management in 2015, making it among the first of its kind to achieve that type of certification. “We continue to work to create awareness of BCM, sharing the importance of conducting business impact analysis, risk assessments, and contingency planning.”

Another way that Cytiva demonstrates its dedication to customers is through its product discontinuation policy. Essentially, the policy says that Cytiva will not discontinue the manufacture of a product that is part of any registered process for manufacturing a biopharmaceutical product (e.g., drug or vaccine). As stated in the policy: “Cytiva is committed to continuing supplies of each of its BioProcess and Cell and Gene Therapy products for as long as Cytiva is aware that such products are being used in an approved, registered process for the manufacture of human biopharmaceuticals and vaccines.”

Capacity expansions help alleviate supply chain disruptions

Importantly, Cytiva has plans in place for multiple global capacity expansions, which will be applied to an “in-region, for-region” long-term strategy to help ensure that products get to customers faster. In July 2021, Cytiva and Pall Corporation announced that they would invest 1.5 billion USD over two years to meet the growing demand for biotechnology solutions.³ The investment is in addition to Cytiva’s continuing capacity investments estimated at 500 million USD through 2022.

As part of the 1.5 billion USD, the companies are investing 600+ million USD in chromatography resins by establishing a new manufacturing site in the US. They are also investing 300+ million USD in single-use technologies, which include bioreactor bags for growing cells used to make personalized medicines and syringe filters for scientific research. There are plans to expand operations in the US and the UK, as well as build out a new facility in Cardiff, Wales. In March 2022, Cytiva announced that it had begun to make mixer bags, flow kits, and tubing assemblies at the new Cardiff site.⁴

In conclusion, while resins manufacturing is a complex and time-consuming process—and, one that has been impacted by the pandemic-related supply chain crisis and high global demand—Cytiva is committed to securing supply through a variety of means, including maintaining the highest production standards, mitigating supply chain risks, business continuity management, and increasing production capacity through site enhancements and global expansions.

For more information, visit Cytiva’s Security of Supply web page.