Overcoming Challenges in Prefilled Syringe Manufacturing

Injectable drug products often consist of a vial and syringe product. However, these drugs can also be delivered via a prefilled syringe combination product, which present specific challenges for visual inspection. PharmTech spoke with Deborah Smook, co-founder and co-owner of TurboFil Packaging Machines, to find out about some of the complications involved in prefilled syringe manufacturing.

PharmTech: How does the viscosity of liquids complicate the filling of prefilled syringes? How does it impact traditional vial/syringe delivery?

Smook: Viscosity tends to complicate a variety of filling and delivery parameters. Depending on the particular viscosity, different methods of filling are necessary—and specific obstacles may arise. These include drips, stringiness, and air bubbles, the latter of which concerns how various viscosities differ in the ways they trap air.

In addition to filling methodologies, viscosity also may necessitate fine-tuning of both equipment and processes. For example, if a product is not only viscous but compressible, the product may ooze from the tip after the syringe and nozzle are separated, requiring pulling back on the plunger to prevent this untenable outcome. A low-viscosity product is more susceptible to leaks during the fill cycle; for that reason, an operator may want to alternate between pumps when switching between low- and high-viscosity liquid products.

Notably, syringes may require additional force at the start of activation—a phenomenon known as breakaway force. This is another reason why exercising the plunger may be recommended at the inception of the filling process.

Which parts of the filling processes are best suited to the addition of artificial intelligence (AI) into automated filling steps?

Obviously, the primary benefit of AI-enabled systems is an abundance of data. But it’s what is done with this depth and breadth of information that is critical.

For equipment operators, AI can pay huge dividends when it comes to predictive maintenance. Increasingly, AI-enabled systems can track not only the quality of products being produced, but also the overall health of the line itself. The goal is to understand not only how and when production goes out of spec, but when an individual production process is trending toward becoming out of spec. This allows for real-time, continuous adjustments that keep product flowing and machines running.

Batch data and changeover assistance are two other areas where AI can bring substantial value. With batch data, it is not a simple matter of ‘the more info the better.’ Rather, it is in choosing from and curating the troves of data systems can generate that make it far easier to identify key performance indicators of not only successive batches but individual items, providing unprecedented actionable insight for engineers and operators alike.

In terms of changeover assistance, one AI-relevant area that is steadily gaining steam is virtual reality-enabled changeover guidance. Such tools amount to interactive instruction manuals that clearly and expediently guide operators through the complicated task of switching between batches and components. This is especially valuable since downtime is frequently the result of human error. A properly executed AI-enabled setup brings the potential to mitigate or eliminate mistakes, optimally tune machines and, ideally, minimize costly machine downtime.

How do supply chain complications impact filling lines (eg, glass and stopper materials, plastics, suspension and other media)?

Prefilled syringes can be composed of exceptionally complicated mechanisms, comprising dozens of individual components. When the reliable supply of any one of these components is threatened or compromised, the result is a ‘weakest link’ scenario that adversely affects the sum of its parts.

For example, there was a recent shortage of pharma-grade glass tubing that created substantial challenges surrounding its procurement. This was a reminder that the issues that thankfully ebbed following the COVID-caused shipping crisis can still resurface at times.

Concerningly, when a manufacturer is planning a new filling line, it may have requirements for specific components that are appropriate in the near-term but unsustainable over the long-term, due to a risk of supply chain delay or disruption. Avoiding such tenuous scenarios requires manufacturers to carefully consider their syringe components from conception, to best ensure those parts are readily and reliably available in an increasingly volatile global trade market.

How do aseptic/sterile manufacturing requirements impact the number of prefilled syringes that can be produced at one time?

Given their reliable revenue streams and comparably robust resources, major manufacturers are accustomed to producing high volumes of prefilled syringes without sacrificing quality control or overlooking aseptic guidelines. It’s the small and medium-sized producers that may experience pitfalls when attempting to maintain output under increasingly stringent sterility requirements.

One issue can become batch size limitations, since routine batch size production for commercial settings must align with the sizes submitted for validation. Here, a smaller manufacturer may not have the initial discretionary capital to invest in sterility solutions like isolators for larger batches. This dearth of resources can inadvertently paint manufacturers into a corner through validated batch sizes that are smaller than they could be. This sort of ‘limitation from conception’ may become more frequent in the short term, as heightened sterility gradually becomes the new norm.

About the Interviewee

Deborah Smook is the co-founder and co-owner of TurboFil Packaging Machines, where she oversees all commercial and operational aspects of the business, including sales, marketing, strategic planning and business development. Smook works closely with customers to define practical, compliant solutions for aseptic filling and containment, helping bridge technical requirements with real-world manufacturing and regulatory considerations.

In total, Smook has more than 35 years of experience across the life sciences industry, including leadership roles at True North Partners, Pfizer, and The Wilkerson Group. She earned a bachelor’s degree in electrical engineering from Tufts University, and an MBA from The Wharton School.

TurboFil is dedicated solely to the design and development of liquid filling and assembly machines for the pharmaceutical and medical device segments. The company specializes in designing and constructing bespoke production solutions for challenging applications. It aims to set new benchmarks for filling precision and operational simplicity.