Four Lessons To Improve Your Supply Chain Reliability

By Life Science Connect Editorial Staff

Can you name a more anxiety-inducing phrase for biopharma executives than supply chain delays? Over the last several years, long lead times, unreliable suppliers, and costly aborted runs have increasingly become top concerns across the industry. Though supply chain risk mitigation has long been a key function of successful drug development, companies new to the space might be wondering, “What does risk mitigation look like in practice?” In a recent Outsourced Pharma Live event, Chief Editor Louis Garguilo sat down with four industry experts to discuss best practices to bolster your supply chain. The panel comprised Biogen’s Director of External Network Strategy Joseph Graskemper; Sonnet BioTherapeutics' Chief Technical Officer Susan Dexter; Stoke Therapeutics' Director of CMC Project Management Tony Sampognaro; and CARGO Therapeutics' Head of External Manufacturing Adam Haskett. To improve your supply chain robustness, check out said panel’s hard-won lessons.

1. Establish Transparent Communication with All of Your Partners

Graskemper has found that being up front and honest about your game plan with all stakeholders is critical: “Companies sometimes keep CDMOs in the dark, which isn’t a great approach. They’ll find out regardless and you’re closing doors for yourself on optionality.” During his time in small molecule manufacturing, one scenario emphasized this for him.

A pharma company had purchased a filter dryer at a CDMO for a Phase 3 manufacturing campaign. The team was under tight timelines and immense pressure for the equipment to work, yet there were concerns about the equipment not being right. The sponsor opted to work with two CDMOs to mitigate risk, initially leveraging the manufacturer with the filter dryer as the primary supplier and the other as the secondary supplier. Once they reached the process performance qualification (PPQ) campaign, the primary CDMO was facing difficulties with the filter dryer that would require resources that were detrimental to the product’s timeline. Thanks to up-front communication from the sponsor about the risks and contingencies, both CDMOs were aware that at any time the secondary CDMO may need to pivot to being the primary, which is ultimately what happened.

Thanks to this transparency, the secondary supplier was already set up in parallel to accommodate this scenario. Since the rate limiting step was the GMP starting material, both CDMOs had enough material to execute a PPQ campaign at any time, which made sense in terms of business risk.

2. Maintain a Strategic Backup Inventory

Dexter’s company, Sonnet BioTherapeutics, needed to mitigate supply chain risks for both drug substance and drug product to ensure they could start clinical studies on time. To start, Sonnet assessed the relevant technologies and raw materials in terms of inventory and lead times. From there, they collaborated with a CDMO to find vendors for critical raw materials and determine their lead times. For raw materials with a lead time longer than four months, Dexter opted to order enough material for a backup run, for which the CDMO would manage inventory – thus, they maintained excess inventory to guarantee coverage. Per Dexter, “It worked out remarkably well. We got a handle on what would expire, what the lead times were, if we could use these products in the future, and how to implement first in, first out (FIFO). The amount we paid was nothing compared to the consequences of not doing it.”

3. Ensure that Your CMC Team Accounts for Supply Chain Delays

Sampognaro’s lesson has both a happy and unhappy ending. His team was moving into pediatric trials to treat a respiratory virus via a suspension in an oral syringe. Early in the process, a specific syringe was selected. Later, the clinical group decided to send caregivers home with prefilled syringes to minimize travel and limit the chance of missed dosing. However, when the clinical team changed their plan, the CMC team didn’t catch it, and the syringe had only been qualified for immediate use. After running into delays for extractables and leachables testing, they opted to source and qualify a new syringe from scratch. This was amid the height of the pandemic when syringes were hard to come by and suppliers were difficult to get in touch with.

Since the illness starts in November and peaks in late December, a brief delay could have forced the clinical team to wait another year before starting. Luckily, they were able to identify an oral syringe that fulfilled all the requirements and was qualified for more than immediate use. Per Sampognaro, “That's the happy ending. The unhappy part is that the CMC team had zero room to maneuver. It created a lot of stress, tension, and bad blood, which contributed to the weakening of the CMC function at this company. The lesson here is that those of us in CMC often don't pay enough attention to the supply chain. We're so focused on the drug substance and drug product that we forget it’s a part of a larger kit that's supplied to the pharmacies.”

4. Build Risk and Change Management into the Business Model

Haskett’s learning experience concerns navigating supply chain constraints for manufacturing viral vectors. Analytical tests at a CDMO showed high invalid rates and reagent supply issues, creating a backlog for the material. Furthermore, the CDMO had an aborted run and was facing other manufacturing difficulties. The potential impact included a failure to supply the market and maximize patient outcomes, which might have led to regulatory discussions, damaged reputations, and lower revenue. A mitigation plan was crucial and would need to accommodate change management protocols across multiple jurisdictions.

A team of analytics, IT, and manufacturing SMEs created a proactive risk mitigation plan that ranked steps by impact and ease of implementation while defining workstreams. Haskett’s team sought both external and internal buy-in, opting to gather vendor insights on their plans. Per Haskett, “It took about six months of mitigations to relieve the supply constraint and release enough safety stock of the vector. It was a win in that we didn't stock out and were able to serve patients, but it also has a silver lining. Many of these mitigations served as long-term corrective actions that enhanced robustness or highlighted the need and prioritization for further next-gen solutions.”

The Bottom Line

Successful supply chain management requires a proactive approach from both external and internal partners. Though it may seem daunting to always look 10 steps ahead, ultimately, this planning and risk mitigation process can save your budget and help ensure on-time delivery to patients.