Issue link: https://www.e-digitaleditions.com/i/1375981
30 BioPharm International eBook May 2021 www.biopharminternational.com The larger f inancia l investment sy nony mous w it h developing a nd manufacturing biologics makes the existence of waste and inefficiency in the supply chain commercially unvi- able. This puts pressure on sponsors to optimize supply and minimize waste. This pressure is magnif ied by the lower product yields associated with biologics. This is largely attributable to the complex manufacturing process, which involves liv ing systems that are sensitive to very minor deviations in the manufacturing process. Short expiration dates are also typical for complex biologics. A lack of stability data means biologics can easily become unstable if not maintained at precise temperature ranges through the pro- cess of development to patient delivery. When combined with the standard study-based challenges of operating global clinical trials—from mid-study protocol amendments or unplanned delays, to navigating multiple coun- try-specif ic regulatory requirements, to managing bulk drug availabilit y and enrollment changes—the condi- tions for a perfect storm are evident. To mitigate these risks to better ser ve patients and enhance perfor- mance, it is necessary to re-examine the approach to and management of the clinical supply chain. As the indus- try evolves, sponsors should prioritize exploring new ways of conducting and managing clinical supplies geared more toward biologics and personal- ized medicines. Clinical packaging strategy is a good place to start. PLANNING CONSIDERATIONS For supply chains to be f lexible and viable, clinical packaging should be planned with the complexities of bio- logics products in mind, and at the earliest opportunity. There are several critical factors that must be considered to inform a fit-for-purpose packaging strategy that can respond effectively to the complex challenges associated with biologics and personalized medicines. F i rst, t he proposed depots a nd sites should be checked to establish capacity to appropriately store mate- rials during the last leg of the cold chain. Shipping conditions and pro- cesses a lso need to be scr utiniz ed to ensure product integrit y can be upheld. Shipping requirements are often overlooked, yet failure to obtain a f irm grasp of the average quantity of material sponsors plan to ship at a time can lead to disr uption and delay, while heightening the risk of waste and negative patient impact. At this point, sponsors should con- sider development of kit designs that will fit within the core of cold-chain shippers. When dealing with high- value biologics, separating products into multiple shipments may increase overhead but mitigates the risk of loss, should temperature be compromised during distribution. Another crucial factor is assessment of the material-handling capabilities of each step of the process and party involved. This will ensure processes are in place or can be implemented to effectively and safely handle biologics material within the required storage conditions, while prioritizing end-to- end patient safety and product integrity. Packaging design, materials, and processing options are inf luenced by a number of product, study, and spon- sor-specific requirements. Perhaps the most obvious is clinical trial timelines. If timelines are short, typically it will be harder to use booklet labels and may necessitate use of a previous kit design. Contrastingly, if enough time is pro- vided, a bespoke packaging solution can be designed that meets unique kit requirements and decisions made based on what is best, not what is possible. It's also important that sponsors define all packaging and distribution requirements prior to finalizing pack- aging design, as last-minute changes have the potential to delay the start of a clinical trial. Although not unique to biologics, blinding can impact packaging strat- eg y and is a prime example of why developing adaptive supply chains is important. For example, when using commercia l compa rators w it h in a blinded study, the commercial pack- aging may change throughout the life of the study. Strategies designed to adapt to evolving program require- ments will enable sponsors to take add it iona l steps to ensu re proper blindness is maintained. Unexpected comparator changes can also have a domino effect on costs, which can be especially detrimental to the perfor- mance of programs that involve high- value, low-yield products. The amount of label text sponsors require can also present challenges when labeling small vials and prefilled sy ringes. As most biolog ics-based products are stored within vials, the fragility of the packaging can increase the risk of breakage and require the addition of a bag or pouch into the design of the final unit for shipment or storage. Not only are glass vials more susceptible to breakage during distribution, but the thaw-and-freeze Partnerships for Outsourcing Operations As the industry evolves, sponsors should prioritize exploring new ways of conducting and managing clinical supplies geared more toward biologics and personalized medicines.