Pharma Packaging Customization: Better Late Than Never

With personalized medicine and shorter product lifecycles becoming a new norm, the pharmaceutical industry faces a blend of emerging challenges and exciting opportunities. Historically, the vast majority of New Product Introductions (NPIs) necessitated large-scale production lines churning out millions of doses. However, as pharmacological science progresses and becomes more narrowly targeted, medicines are becoming far more specialized. Such next-generation drugs inevitably require next-generation manufacturing solutions. 

Amid the paradigm shift toward smaller-population drugs, there are fewer instances where bigger is better. A growing set of pharma manufacturers are finding that, when producing and packaging today’s more targeted drugs, large-scale production lines can lead to larger-scale headaches—particularly when it comes to increased machine downtime, elevated overall costs and unacceptable levels of waste. 

End-of-line processes can be especially prone to such pitfalls—including the final stages: packaging and labeling. With necessity being the mother of innovation, more pharma companies, CMOs and CPOs are employing Late-Stage Customization (LSC) techniques, enabling efficiently packaged products in a more flexible, responsive fashion that streamlines production and helps increase speed to market. 

Late-stage customization utilizes versatile digital printing and other on-demand tactics, allowing pharmaceutical companies to delay the final packaging of products until their destination—and therefore their end user audience—is determined. Rather than printing large batches of preconfigured packaging, LSC practices maintain a standardized stock whose printed assets (text as well as graphics) can be customized to meet real-time requirements. This approach helps manufacturers, CMOs and CPOs nimbly pivot to address shifting market demands, region-specific regulatory requirements and, for batches divided and distributed to various geographies, language versioning. 

Let’s look at late-stage’s latest trends, as well as its benefits, challenges and growth trajectory.

Trumpet Syndrome: Striking the Right Notes

Among the most significant bottlenecks in pharmaceutical packaging is what industry experts call “Trumpet Syndrome” (Figure 1). Setting aside any potential to hit a wrong note here and there, Trumpet Syndrome draws its name from the instrument’s shape—a reverse funnel—rather than its sound.

Trumpet Syndrome’s basic premise is that pharma manufacturing tends to start small and end large. Often, lead times for active pharmaceutical ingredients (APIs) and other drug substances are lengthy and narrow in scope. Upon receipt, the production process is both expanded and expedited, as ingredients become first bulk drug products and then precise dosages. And while supply chain complexity may be minimal at SKU level during early-stage manufacturing, complexity increases as the process moves downstream to commercial packaging operations. This is where multiple SKUs, varying regulatory requirements, a litany of languages and differing dosage forms all become commonplace. 

Managing such intricacies within short lead times is a true challenge – and one that LSC techniques are uniquely designed to solve. By postponing customization until the final phases, manufacturers can simplify bulk production while ensuring that market and even patient-specific packaging is employed whenever necessary. Production waste is reduced, costs are minimized, regulations are adhered to and, most importantly, patients are properly treated.  

Leveling Up: The Four Tiers of Late-stage Customization 

Late-stage customization can be implemented at distinct levels, per various companies’ needs, existing infrastructure and investment capabilities. Generally, these levels can be categorized into four scenarios, with each bringing unique advantages and specific considerations. 

Level 1 involves purchasing customization assets directly from a trusted printing vendor. This can be an attractive approach, as it eliminates the need for capital investment. And since digital printing is a simpler process that requires less setup compared with conventional offset printing, customized package printing usually can be executed expediently and with low minimum order quantities.  

However, companies going the direct purchase route should remember that material evaluation and stability testing may be required to ensure compatibility with a vendor’s digital printing equipment. Initiating such activities early in a launch timeline best ensures regulatory and market acceptance of various digitally printed components; if this step is not done diligently, the result can be untenable delays and reworks.  

Conversely, Level 2 customization brings the printing process in-house. This option requires investment in printing equipment, which is then integrated into one or more packaging lines. Such a DIY approach offers manufacturers, CMOs and CPOs more control over packaging operations and, by securing and storing stock rather than relying on on-demand vendor purchases, reduces component lead times. Real-time printing also mitigates waste and affords greater flexibility than buying piecemeal from vendors. 

With Level 2, implementation time is longer than with Level 1, since it requires securing equipment and completing a robust validation process. The need for precise, proper validation cannot be underestimated, as it ensures not only correctly printed graphics, data and repeatability but optimized overall line efficiency. Also, as with Level 1 material evaluation and stability requirements must be considered. 

Level 3 ups the ante on complexity: it involves the customization of both primary and secondary packaging elements. This layered approach may be best suited, for instance, to a large commercial product with several small and/or international stock-keeping units (SKUs), where it becomes beneficial to perform segregated inline customization for both primary and secondary packaging. Doing so may involve printing on any number of components, including blister lidding, labels wallets, paper trays and cartons. 

If properly integrated, Level 3 customization can substantially diminish line changeover delays – which, in turn, provides better bulk yield, since a new SKU doesn’t require a significantly reconfigured line. Among other benefits, eliminating pre-ordered components entirely and cutting dependency on external suppliers results in little to no waste, accelerates turnaround times, and enables ‘named patient’ production.

Unsurprisingly, similar considerations apply to this level vis-à-vis material evaluation, stability requirements and robust validation. And given its multi-tiered nature, Level 3 customization brings higher infrastructure investment and longer implementation times compared to the straightforward inline printing inherent in Level 2. 

Atop the LSC ladder sits Level 4, which can best be described as all-in, late-stage customization. Here, high volumes are supported by hefty investments to empower comprehensive, fully in-house component printing with maximum pivoting prowess. 

At Level 4, all components up to and including patient inserts are printed in-house. This high cost/high reward approach pairs premium investment with unsurpassed short-term flexibility and longer-term cost efficiencies. If a manufacturer, CMO or CPO is regularly involved in mission-critical rapid market launches, Level 4 likely fits the bill. 

However, in addition to the sizable infrastructure investment it entails, Level 4 requires an abundance of something else: in-house printing expertise. Past the robust validation, materials testing and evaluations required to get up and running, operating and maintaining a Level 4 customization environment also means establishing institutional knowledge of digital printing’s extensive and evolving attributes.

Reaping LSC Benefits & Overcoming Its Challenges

As demonstrated, late-stage packaging customization minimizes lead times by replacing uniformly pre-printed packaging with the ability to strategically pause prior to this final step, then print variable information on-demand. By keeping stock in its lowest common denominator form—for example, unlabeled blister lidding—manufacturers, CMOs and CPOs can nimbly react to regulatory changes, business forecasting shifts, and seasonal variability. Notably, such a setup also improves working capital profiles, since it diminishes the need for pre-printed stock to crowd busy, often inundated warehouses.  

Late-stage customization also comes in handy when time—and timing—is of the essence. For instance, LSC processes can streamline activities for drug products with relatively short shelf lives or limited stability data; with all but the final packaging step (namely, printing) pre-completed, the timeframe from a drug’s production to its shipment can be significantly reduced. These benefits apply not only to commercial products but can also help companies be strategic during clinical stages, when new indications for existing programs must be explored. 

Sustainability profiles present another attractive comparison. Conventional package printing operations often lead to ample minimum-quantity-centric waste, expired packaging stock and redundant materials. In contrast, late-stage customization mitigates material waste, improves operational efficiencies and, often lowers the overall carbon footprint associated with transportation and logistics.

Of course, implementing late-stage customization practices seldom comes without its share of challenges. As discussed, the substantial investments in infrastructure and workflow integration may by onerous to some and nearly impossible for others—especially at Levels 3 and 4. LSC also requires companies to develop and hone robust validation processes to ensure repeatability and regulatory compliance of all printed components.

Transitioning to LSC also demands skilled personnel who can operate digital printing systems and manage new packaging workflows. Importing such infrastructure also means importing the expertise to man it. Here, one overlooked yet undeniably critical aspect is integration optimization; only by aligning LSC strategies and tactics with existing supply chain elements and enterprise resource planning systems can the full benefits of late-stage packaging customization be realized. 

A Late-stage Lookahead: The Future of Packaging Customization

As pharmaceutical packaging continues to evolve, late-stage customization is poised to go from an intrepid outlier to a new industry standard. With advancements in digital printing technology and automation, manufacturers, CMOs and CPOs will enjoy greater efficiencies, reduced costs, and improved ability to course correct per market demands.

In the coming years, we can expect LSC to be further integrated with AI-driven forecasting tools, blockchain-enabled serialization, and enhanced on-demand manufacturing capabilities. The ability to personalize packaging at scale will redefine how pharmaceuticals are delivered, ensuring faster, more efficient, and more sustainable packaging solutions for global markets.

Michelle D’Angelo is VP of North American Business Development, Commercial Services for PCI Pharma Services. Paul Smallman is Senior Director, Global Technical Sales – Commercial Packaging Technology for PCI Pharma Services. PCI is a leading CDMO providing clients with integrated end-to-end drug development, manufacturing and packaging capabilities that increase their products’ speed to market and opportunities for commercial success. For more information visit www.pci.com.