Blow-fill-seal (BFS) has long been an important manufacturing platform for sterile topical ophthalmic products, particularly small-volume liquid, unit-dose and preservative-free presentations. This is the primary scope of this series.
But what is it about ophthalmic manufacturing that makes BFS such a natural fit?
The fit goes beyond the ability to form, fill and seal a container within one automated process. Topical ophthalmic products bring together demanding requirements for sterility assurance, limited intervention, container integrity, dose delivery and primary packaging design, all areas in which a well-designed BFS process can offer important advantages.
Aseptic Processing with Reduced Intervention
Contamination control is central to ophthalmic manufacturing.
FDA’s December 2023 draft guidance, Quality Considerations for Topical Ophthalmic Drug Products, identifies product sterility as a critical quality attribute. Current sterile-manufacturing expectations also place strong emphasis on minimising unnecessary interventions within critical processing areas.
This is one of the fundamental strengths of BFS.
The highly automated process reduces the handling associated with separately manufactured primary containers and can limit operator interaction during critical stages of production.
For ophthalmic manufacturers, where relatively small quantities of sterile liquid may be produced at significant volumes, that combination of automation and contamination control is particularly valuable.
Not every BFS architecture protects the critical process in the same way. Under current EU GMP Annex 1, shuttle-type equipment used for aseptic filling has an open parison; the critical extrusion, blow-moulding and sealing zones, and the filling environment, therefore must meet Grade A conditions. In rotary or closed-parison equipment, the formed parison is generally closed to the room, but the filling environment within the parison must still be designed and maintained to meet Grade A conditions.
Across both architectures, BFS does not itself guarantee sterility or regulatory compliance. The equipment, process, facility and contamination control strategy still need to be appropriately designed, qualified, validated, monitored and controlled. Annex 1 also expects aseptic BFS equipment to be installed in at least a Grade C environment, together with the applicable gowning and microbiological monitoring controls.
Small-Volume Production at Scale
Ophthalmic applications are also well aligned with the production characteristics of BFS.
Multi-cavity moulds allow large quantities of small-volume containers to be produced efficiently, while the container geometry can be designed specifically around the application.
For ophthalmics, this can include unit-dose presentations incorporating twist-off closures, dispensing features and containers produced individually or in connected blocks.
The relationship between the mould, number of cavities, cycle time and fill volume therefore allows a BFS system to be configured around both the product presentation and required production output.
This is an important distinction when evaluating BFS equipment. Machine model alone does not determine production capability. The configuration of the machine and tooling can have a significant impact on what a system is capable of producing.
The Container Is Part of the Delivery System
Perhaps one of the most interesting aspects of ophthalmic BFS is that the primary container is not simply there to hold the formulation.
Its design can directly affect how the product is opened, dispensed and administered.
Container geometry, tip design, opening characteristics, polymer selection and dose delivery therefore become part of the overall product development strategy.
This is particularly relevant for BFS because these characteristics are incorporated directly into the moulded container.
As a result, the relationship between the formulation, polymer, tooling and finished container needs to be considered as part of the overall product system rather than as separate decisions.
Preservative-Free and Unit-Dose Applications
BFS also has an established role within preservative-free ophthalmics.
Single-use containers provide one approach to delivering preservative-free formulations by keeping each presentation sealed until the point of use.
BFS is well suited to producing these small, individually sealed presentations at scale.
However, BFS should not automatically be viewed as the solution for every ophthalmic product.
Formulation characteristics, polymer compatibility, barrier requirements, filling conditions, required container performance and the wider manufacturing strategy all need to be considered.
More Than Simply a Filling Technology
Ultimately, the relationship between BFS and topical ophthalmics is about more than filling sterile liquid into a small plastic container.
It is the combination of aseptic processing, reduced intervention, container design flexibility, small-volume capability and high-volume automated production that has made BFS such an established platform for ophthalmic manufacturing.
Perhaps most importantly, BFS brings the manufacturing process and primary container together in a way that is particularly relevant to ophthalmics, where the performance of the container can be just as important as the process used to fill it.
Next, we’ll take a closer look at one of the most recognisable BFS applications: unit-dose ophthalmics.