Unit-dose ophthalmic containers are among the most recognisable applications of blow-fill-seal technology.

Small fill volumes, high production requirements and the need for a practical dispensing system create an interesting manufacturing challenge and one that aligns particularly well with BFS.

But producing a successful unit-dose ophthalmic presentation involves more than simply creating a small container. The interaction between the formulation, fill volume, polymer, container geometry, opening mechanism and dispensing performance all needs to be considered.

Container Design Becomes Critical

In ophthalmics, the primary container has a direct relationship with the patient.

It must protect the formulation throughout shelf life, but it must also allow the product to be opened and administered appropriately.

For unit-dose BFS products, the mould can incorporate features such as:

• Twist-off openings 
• Integrated dispensing tips 
• Different neck and tip geometries 
• Individual or connected containers 
• Different wall profiles and container shapes 

This makes tooling an important part of the overall manufacturing strategy. Changing the mold does not simply change what the package looks like. It can change how the finished pharmaceutical product is ultimately presented and used.

Unit-Dose Design Goes Beyond Fill Volume

For ophthalmic applications, nominal fill volume is only one part of the container design.

The finished presentation also needs to perform appropriately when it reaches the patient. Factors such as container flexibility, opening characteristics, tip geometry and the relationship between the product and container can all influence dispensing behaviour.

Manufacturers may therefore need to consider aspects such as:

• The quantity of product required for the intended use 
• Dispensing behaviour 
• Drop formation and delivery 
• Residual product remaining within the container 
• Opening characteristics 
• Ease of handling 
• Container flexibility 
• Patient usability 

These considerations demonstrate why developing an ophthalmic BFS container is not simply a packaging exercise.

Regulatory expectations can also influence the presentation. FDA’s December 2023 draft guidance recommends that a nonpreserved unit-dose solution, emulsion or suspension contain no more than 0.5 mL and that the unit-dose container should not be capable of being recapped. These are draft US recommendations, but they illustrate why fill volume and opening design need to be defined early.

The container becomes part of the delivery system itself.

Small Volumes, Large Quantities

Ophthalmic unit doses may contain a relatively small quantity of product, but manufacturers can require very significant production volumes. This is where mould configuration becomes particularly important. A multi-cavity BFS mould allows several containers to be produced during each cycle, with overall output influenced by factors including cavity count, container geometry, fill volume, product characteristics and cycle time.

Manufacturers therefore need to consider the relationship between container design and production output, rather than treating the two independently.

Increasing the number of cavities may appear to provide a straightforward route to greater output, but the complete process needs to be considered. Container dimensions, mould layout, filling requirements and machine capability all influence the practical production rate achievable for a particular format.

The Importance of Dispensing Performance

The performance of an ophthalmic container does not end when it successfully passes through the BFS machine.

Opening characteristics and dispensing behaviour are also important. Tip geometry, polymer characteristics and container design can influence the way in which product is delivered.

This is particularly important for ophthalmics because relatively small changes to the container can potentially affect how the patient interacts with the finished product.

This is also why regulatory consideration of ophthalmic container closure systems extends beyond their ability to protect the formulation and includes their delivery and dispensing characteristics.

Tooling Becomes Part of the Product Strategy

For BFS manufacturers, this makes mould and tooling selection particularly important.

A BFS machine may be capable of operating across a range of applications, but the installed tooling defines the container actually being produced.

When assessing either new or existing BFS equipment for an ophthalmic project, manufacturers therefore need to look closely at the relationship between:

Machine + Mould + Fill System + Polymer + Product + Required Output

rather than focusing on the machine model alone.

This becomes especially important when considering existing equipment, where understanding the installed moulds and previous container formats can help determine how closely the system aligns with a proposed new application.

Why Unit-Dose Remains an Important BFS Application

Unit-dose ophthalmics demonstrate one of the fundamental strengths of BFS particularly well. The technology allows the primary container to be designed around the pharmaceutical application and then manufactured, filled and sealed within the same automated process.

For ophthalmics, that brings together several requirements:

Sterility + Small Fill Volume + Container Design + Dispensing + Production Scale

within a single manufacturing platform.

The result is an application where the capabilities of the BFS process and the requirements of the finished product are particularly well aligned. And when preservatives are removed from the formulation, the relationship between the manufacturing process and primary container becomes even more important.

Next, we’ll explore how removing preservatives changes the microbiological and packaging strategy.