PMPS spoke with David O’Connell about the technical, formulation and manufacturing considerations that developers should address to ensure a successful transition.
As demand for patient-centric drug delivery continues to grow, more biopharma companies are evaluating the transition from traditional vial presentations to pre-filled syringes (PFS). While the benefits are well understood from improved dosing accuracy and reduced administration steps to enhanced patient convenience, the development and manufacturing journey is significantly more complex than a simple container change.
PMPS: What is driving the industry’s continued shift from vials to PFS?
David O’Connell (DOC): The move towards PFS is being driven by a combination of patient expectations, healthcare efficiencies and the increasing prevalence of biologics. Today’s therapies are often intended for chronic conditions where patients are administering treatments themselves, either at home or in community settings. A PFS simplifies that process by providing a ready-touse format that reduces preparation steps and minimises the potential for dosing errors.
From a pharmaceutical perspective, manufacturers are also looking to differentiate products in increasingly competitive markets. Improving the delivery experience can be an important part of a product’s life cycle management strategy, particularly when extending the commercial value of established therapies. Although the commercial rationale is compelling, the technical implications should not be underestimated. Transitioning to a PFS introduces new challenges across formulation, container compatibility, manufacturing and regulatory strategy that are best considered early in development.
PMPS: From a formulation science perspective, what are the key considerations when transitioning a drug product from a vial to a PFS?
DOC: Transitioning from a vial to a PFS involves much more than changing the primary container. The formulation is exposed to additional materials, including silicone oil, elastomeric plunger stoppers and needle shields, all of which can influence product stability and compatibility.
For biologics, interactions with silicone oil and other contact surfaces can promote protein adsorption, aggregation and sub-visible particle formation, potentially impacting critical quality attributes. High-concentration formulations present further challenges, as increased viscosity affects syringeability, injection force and fill-finish performance, requiring careful optimisation of buffer systems and excipients.
A comprehensive assessment of extractables and leachables, container closure integrity and longterm stability is therefore essential. If the syringe will ultimately be incorporated into an auto-injector, formulation development should also consider device performance characteristics such as glide force and extrusion force early in development. Taking an integrated approach to formulation, primary packaging and process development enables developers to identify compatibility risks early and establish a robust, scalable product for clinical and commercial manufacture.
PMPS: What additional development activities should sponsors plan for when making the transition?
DOC: One of the biggest differences is the breadth of characterisation work required. Alongside conventional stability studies, developers need to evaluate container closure integrity, functionality throughout shelf life, extractables and leachables, silicone interactions and the mechanical performance of the syringe.
Process development also becomes more involved. Parameters such as fill accuracy, plunger placement, headspace control and stoppering require careful optimisation because they directly influence product quality and device performance. Another important consideration is the intended route to commercialisation.
If the syringe is likely to be integrated into an auto-injector or safety device in the future, those downstream requirements should influence development decisions from the outset. Designing with the final presentation in mind can prevent unnecessary redevelopment later in the product life cycle.
PMPS: How does sterile fill-finish become more complex with PFS?
DOC: Sterile fill-finish for syringes introduces additional process complexity compared with traditional vial filling. The equipment itself is more sophisticated, with tighter tolerances and additional process steps associated with nested syringe formats.
Maintaining container integrity throughout the filling process is critical. Needle insertion, plunger positioning and stoppering all require precise control, while particulate management becomes even more important because the finished presentation is often administered directly without further manipulation by healthcare professionals.
Manufacturers also need to ensure robust environmental monitoring and contamination control strategies, particularly as expectations under Annex 1 continue to evolve. Automated, highly contained filling technologies have become increasingly valuable in supporting consistent aseptic performance while reducing operator intervention.
Technology transfer is another area that deserves careful planning. Even where a formulation is well understood, transferring to a syringe filling line requires extensive engineering work to establish process capability and maintain product quality throughout commercial manufacture.
PMPS: What role does a development and manufacturing partner play in helping companies manage these challenges?
DOC: Increasingly, pharmaceutical companies are looking for partners that can support the entire development journey rather than individual manufacturing activities.
Early collaboration enables potential risks to be identified before they become expensive development issues. For example, selecting the most appropriate syringe platform, understanding primary packaging compatibility and establishing an effective analytical strategy can all significantly reduce later programme risk.
Integrated development also provides scientific continuity between formulation, analytical development, process optimisation, clinical manufacture and commercial production. Rather than transferring knowledge between multiple organisations, sponsors benefit from a single technical team with visibility across the entire programme.
As therapies become more complex, particularly biologics and high-value injectable products, this integrated approach can improve development timelines while reducing overall technical risk.
PMPS: Looking ahead, what trends do you expect to shape the future of PFS development?
DOC: Patient-centric design will continue to be a major driver. We’re seeing increasing demand for presentations that support self-administration, whether through standalone PFS or combination products incorporating auto-injectors, pens and wearable delivery systems.
Sustainability is also becoming an increasingly important consideration and is being reinforced by significant new legislation such as the EU Packaging and Packaging Waste Regulation, which entered into force in February 2025 and will generally apply from August 2026. While patient safety will always remain the primary priority, developers are exploring opportunities to reduce material usage, optimise packaging configurations and improve manufacturing efficiency across the product life cycle.
Perhaps the biggest and most beneficial change especially from a contract development and manufacturing organisation perspective, is that companies are involving fill-finish specialists much earlier in development than they did previously. Rather than viewing sterile manufacturing as a late-stage activity, it’s increasingly recognised as a critical element of product design.
PMPS: What advice would you give to companies beginning the transition from vial to PFS?
DOC: The most successful programmes are those that start planning early. Decisions around formulation, primary packaging, device compatibility and manufacturing strategy are all interconnected, so considering them in isolation can create unnecessary technical challenges later.
It’s also important to remember that every molecule behaves differently. There isn’t a universal road map that applies to every product, particularly for sensitive biologics or highly concentrated formulations. Comprehensive risk assessments, appropriate analytical characterisation and close collaboration between development, manufacturing and device specialists are essential.
Ultimately, transitioning to a PFS offers significant benefits for patients, healthcare providers and pharmaceutical companies alike. But achieving those benefits requires much more than changing the primary container. Success comes from understanding how formulation science, container technology and aseptic manufacturing work together to deliver a robust, commercially scalable drug product that maintains quality throughout its life cycle.