Resiliency is not a decision.

Without question, the SARS-CoV-2 pandemic has negatively affected supply chains around the globe. While some businesses have reported a positive impact—an increase in customer demand, or bringing new products to market, for example, 72% of supply chain executives interviewed in late 2020 reported a negative effect.¹ Contract development and manufacturing organizations (CDMOs) recognized early in the pandemic the need to re-evaluate and shore-up supply chains, as weaknesses in supply were brought to the surface.² When your business model is built on the ability to deliver high quality results on time, in a hugely competitive marketplace, disruptions are an unwelcome guest. Some CDMO suppliers have fared better than others, continuing to supply specialty chemicals and consumables as and when needed—even keeping one step ahead of unprecedented demand (the development and manufacture of sufficient vaccines and therapeutics for the whole world, anyone?).

Supplier resilience is not something that can be switched on or off. Resilience is about the application of experience and knowledge in the face of uncertainty and adversity. It’s about businesses identifying and mitigating risks before situations escalate. It’s about knowing every step of their supply chain, to be able to provide uninterrupted supply to their customers. 

CDMOs – The powerhouses of the pandemic
Full-service CDMOs hire highly talented scientists to guide vaccines and therapeutics through the development and manufacturing processes. You might say they have played the understudy to the pharmaceutical industry’s spotlight performance for many years, but the pandemic has allowed them to step into the spotlight too. There has been a shift from a somewhat transactional based approach, to the development of strategic partnerships. Those who have assessed their own risk and weaknesses, as well as those of their suppliers and their clients, are well positioned to continue to benefit from the power shift long after the pandemic subsides.³

Scientists within CDMOs are tasked with the responsibility of developing analytical procedures to identify and quantify active pharmaceutical ingredients (APIs), impurities and excipients, and then validate the analytical methods to demonstrate their suitability for the intended purpose. (i.e. – ensure they know exactly what is in that vaccine before allowing someone to inject into an arm). Validation of the analytical procedures are part of the medicines registration process and must lay out the specificity, linearity, range, accuracy, precision, detection limit, quantitation limit and robustness of the methods. Such information is also a requirement of emergency use authorizations.

At the heart of every CDMO, high performance liquid chromatography (HPLC) systems work tirelessly, turning samples into results—generating analytical data to allow decisions to be made. How pure is the API? Are the impurities below the acceptable limit? Has any degradation occurred? The engine of every HPLC system is a small, typically stainless-steel column, packed with sub-two-micron to 10-micron particles which separate sample molecules based on their affinity for the contents of the tube, and the liquid mobile phase flowing through it. Some say it is where the magic happens.

Method developers are adept at assessing the variables and parameters that result in good quality data and locking down methods that give them the maximum confidence in their results. They are likely to evaluate chromatography columns from different batches. The regulatory guidelines also suggest the evaluation of columns from different vendors to test method robustness.⁴

Decisions made during the development of analytical procedures can have a long-lasting and significant impact on the viability of an analytical method designed to accompany a pharmaceutical product throughout its market lifecycle, which can stretch for decades. The use of “consumables” like the chromatographic column are written into Standard Operating Procedures (SOPs), as they are a critical piece of the workflow and require periodic replenishing lest laboratory operations come to a halt. When a critical piece of the workflow fails to arrive to the laboratory on time, or a consumable needed in a validated method becomes unavailable, even the calmest scientist can get a little hot under the lab coat collar. 

Agility in supply is not heroism
As a result of the pharmaceutical industry accelerating vaccine and therapeutics through their pipeline and into clinical trials at never-before-seen speeds, the pandemic resulted in an avalanche of demand for CDMO services far beyond that predicted prior to 2019. The shockwaves were far-reaching and are still rippling through the community of vendors who support the pharmaceutical industries and CDMOs to this day. Some have been able to act with agility—adjusting forecasts, increasing product safety stock, placing inventory in local warehouses and distribution centers. Some have struggled, resulting in long lead times, or inability to supply certain consumables.⁵ Indeed, the increased demand for certain raw materials in general has resulted in challenges across multiple market sectors. Consider all the reagents and consumable materials required for millions of PCR tests and being the supplier who must decide who will have their orders fulfilled, and who will be kept waiting.

Agility in supply is not just down to good luck. Those who have continued to keep up with supply and demand did not simply put on a cape and fly into superhero mode. Their business analysts, planners, production and procurement teams have been scrutinizing the facts, and responding to the data long before the pandemic arrived. It’s part of the DNA of a supplier who takes accountability for meeting the needs of their customers. When the pandemic took hold, they mobilized business continuity plans, worked closely with their suppliers to mitigate risks and expedite orders. They maintained close relationships with transportation providers to minimize disruption to their distribution networks—and most importantly, they kept their customers informed.⁶

Experience surpasses price
While research and development are underpinned by creativity and thinking outside of the box, when it comes to supplier choice, there is something to be said for longevity and experience. Methods used to generate data which support the authorization and approval of pharmaceuticals need to withstand the test of time, and the development and manufacturing teams must have the foresight to embed consumables that will last throughout the product lifecycle. Some CDMOs enter partnerships to support products through the entire product lifecycle.

In a session on, “Navigating the CDMO Market: Hurdles, Transformation & Opportunities,” presented at the last CPhI Discovery,⁷ Kevin Sharp, head of alliance management at Samsung Biologics, pointed out that securing the supply networks in CDMOs is key to contractual planning. When negotiating commercial supply agreements, a crucial element under evaluation is the ability to ensure the long-term availability of the required capacity necessary to keep up the commercial volume.⁸ One way to understand the commitment to supply is to look at the investment suppliers make to ensure they can continue to supply items critical to sample analysis for pharmaceutical, biopharmaceutical, clinical and biomedical research applications.⁹

As a CDMO procurement specialist or manager, are you sure the vendors that you purchase from, or partner with, are as committed to their own future as you are to yours? Are they making the same columns today that were specified into methods 10 years ago? 20 years ago? 30 years ago? Your prospective clients will almost certainly visit and inspect your facilities before entering a contract. Have you considered asking to see behind the doors of your critical suppliers too?

• What processes do they have in place to guarantee supply?
• Do they have business continuity plans in the event of major disruption?
• What quality management systems do they adhere to?
• What is their track record in audits?
• Are they a primary manufacturer or are they resellers?
• How do they manage their logistics, distribution and support networks globally and locally?

Behind the scenes of a chromatography column manufacturer
If you were to take a tour of a manufacturer of chromatography columns, you would see that columns are largely comprised of two main components—the stainless-steel housing, and the particles packed within. The steel tubes are engineered to strict dimensional tolerances, which require precision milling, passivation and fabrication. They are designed to operate at high pressures and must form perfect seals to deliver chromatographic separations.

Steel is a fundamental building block of our modern lives, yet it’s availability and price can be heavily influenced by global events. The financial crash of the late 2000s saw steel production in Europe, Japan and America fall by over a quarter.¹⁰ Indeed, the coronavirus pandemic continues to rock the global steel industry.¹¹ Resiliency is built by ensuring orders for the steel are placed well in advance. One company buys in great lengths of steel to support the production of several months of chromatographic columns. In fact, if their weekly consumption for columns was placed end to end, it would shadow the world’s tallest building. At an average of 15cm a column, that’s a lot of magic happening.

The particles within the columns come in many different shapes, sizes and chemistries. The most common type of particles consists of a high purity silica, or hybrid particles, such as the bridged ethylene hybrid (BEH) particle, which is formed following the emulsification and condensation of two high-purity organosiloxane monomers. Ligands are bonded onto the silica or hybrid particles. The particles and ligands provide the surface which enables separation of molecules and require synthesis and sorting to ensure the particles have the correct chemical properties and are homogenous in size. Those who manage or manufacture in accordance with small batch principles—rather than synthesizing larger batches at less frequent intervals can act quickly when a manufacturing process goes awry. Indeed, having batches prepared and ready to be packed, batches in the synthesis stages, and batches in the planning phase allow for flexibility to increase or decrease production according to the market requirements.

A suite of quality control tests is required to ensure intra and inter batch column reproducibility, and to prevent any sub-optimal product being placed on the market. A scientist should never be in a position where they feel they must request a certain batch to get a “good” one, nor should they be unable to request columns from multiple batches to validate a method in accordance with the ICH guidelines. In addition, each column should be accompanied by a certificate of analysis, detailing the QC test conditions and results obtained by the manufacturer.

When auditing your column suppliers, consider asking what contingency plans they have in place, should their manufacturing facilities experience a flood or fire. Do they have back-up production lines, or facilities in other locations they could bring online quickly?

Mitigating risk through distribution management
When the ocean-going freighter, the Ever Given obstructed The Suez Canal in March 2021, the precariousness of supply was again thrust into the spotlight. It brought into question the just-in-time system or inventory and ordering.¹³ If it, or any of the ships behind it had been carrying laboratory reagents, solvents or analytical columns instead of household goods, electronics and footwear, imagine the impact on a CDMO ready to sign off a batch of vaccines, only to find they could not complete the tests as a vital piece of the workflow is sitting on a ship. To mitigate risk, consider how your suppliers manage and distribute their stock. Do they build products to order? Do they distribute from a single location? Or do they manage geographical distribution hubs, maintaining inventory in multiple locations, with a guaranteed level of high priority stock ready to fulfil orders as soon as they are placed?

Commitment to turn samples into results
With the pharmaceutical CDMO market projected to continue to grow at an accelerated pace because of the pandemic,¹⁴ those looking to reap the biggest gains must partner with those suppliers who have demonstrated resiliency and agility—and question those suppliers who have struggled to navigate the gauntlet thrown down by SARS-CoV-2. Talk to your suppliers. Evaluate their ability to mitigate risk. Ask to see behind the doors. Ensure your suppliers are as committed to turning samples into results as you are. 

References

1. https://www.ey.com/en_gl/supply-chain/how-covid-19-impacted-supply-chains-and-what-comes-next
2. https://www.outsourcing-pharma.com/Article/2020/08/05/Minakem-collaboration-could-elevate-pharma-supply-chain
3. https://www.bcg.com/en-es/publications/2021/the-four-critical-steps-for-cdmos-post-covid-19
4. https://database.ich.org/sites/default/files/Q2%28R1%29%20Guideline.pdf
5. https://www.nature.com/articles/d41586-021-00613-y
6. https://www.waters.com/nextgen/us/en/c/announcement/coronavirus.html
7. https://www.cphi.com/discover/en/home.html
8. https://www.europeanpharmaceuticalreview.com/news/154678/cdmo-sector-are-the-big-winner-of-the-pandemic-state-experts/
9. https://ir.waters.com/newsroom/press-release-details/2018/Waters-Corporation-to-Invest-215-Million-in-Precision-Chemistry-Manufacturing-in-Massachusetts/default.aspx
10. https://www.visualcapitalist.com/visualizing-50-years-of-global-steel-production/
11. https://www.eurofer.eu/press-releases/ongoing-covid-pandemic-piles-pressure-on-steel-sector-in-mid-2020/
12. https://www.chromatographyonline.com/view/synthesis-and-applications-beh-particles-liquid-chromatography-0
13. https://blockheadtechnologies.com/rethinking-just-in-time-supply-chains-what-the-suez-canal/
14. https://www.globenewswire.com/news-release/2021/04/19/2212263/0/en/The-Global-Pharmaceutical-CDMO-Market-was-valued-USD-160-12-billion-in-2020-and-it-is-expected-to-reach-USD-236-61-billion-by-2026-registering-a-CAGR-of-6-5-during-the-period-of-fo.html

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Dr. Hazel Dickson, Marketing Manager Europe, Chemistry Group at Waters Corporation, specializes in enabling businesses to turn samples into results. With a PhD in analytical
chemistry and over a decade of experience in the specialty measurement industry, her passion is understanding how chromatography and mass spectrometry play a role in improving human health and well-being.