Container Closure – How do we seal products to keep the safe?

Edition 8, October 2024.

I’m back at it with a new edition of The Aseptic Quarterback.? This time I’ll cover the basics of container closure.

Immediately after the filling process the containers must be closed prior to moving out of the Grade A – Aseptic area. Each container type requires a different closure type.? Many parenteral products are being filled into vials, syringes or cartridges.? The vial typically utilizes a polymer stopper and an aluminum cap.? Syringes have a needle or luer lok at one end, and a polymer plunger at the other.? A cartridge blends the vial and cartridge closures – at one end it uses a plunger, at the other it uses an integrated polymer stopper and aluminum cap.

Container Closures

Vials have a two-step closure process.? A polymer stopper is placed into the vial opening immediately after filling. This is completed in a few different ways depending on the equipment speed and overall operation.? This can be a pick and place system, or a stoppering wheel.? The system must ensure the stopper is moved into the correct position into the vial, with the correct force and hold time to make sure the stopper does not pop back out.?

Lyophilized products are a special case with a specific stopper. These have two positions in the vial and a vent to allow the air & liquid in the vial to move out during the lyophilization process.? The stopper is first placed at the higher position which allows for ventilation to the aseptic area and lyophilizer.? Once inside the lyophilizer, and the freeze-drying process is complete, the equipment closed the vial by using the shelves to push the stopper into its lowest position.

Stoppered vials are then ushered to the capping station. The cap is placed onto the vial, then the vial is captured by the machine on the top and bottom. Pressure is applied to ensure a proper downward force on the seal during the crimp process while the vial is rotated.? The crimp process uses a freely rotating wheel with a specific profile to curl the aluminum under the vial top towards the neck.

Syringes enter the filling system with the needle or luer lock already closed when they’re delivered as Ready to Use (RTU) commodities.? The syringe is filled through the back. After filling a plunger is inserted into the back of the syringes.? There are two typical plunger insertion methods: mechanical, or vacuum stoppering.? The plungers are delivered through a sorting and feeding system, then using fixed automation the plunger fixture is moved from the feeding system to place the plungers directly over the opening of the syringe.? The mechanical stoppering method compresses the stopper on the sides, then a rod presses the plunger into the syringe to predetermined depth.? In vacuum stoppering, a seal is created around the syringe opening, then a vacuum is created inside the syringe.? The plunger is then pressed into the syringe. The vacuum allows the plunger to get closer to the liquid product, reducing the air bubble in the syringes.? This is especially important for oxygen sensitive products, or syringes being assembled into autoinjectors.

Cartridges come in two configurations; bulk cartridges have no closures when they enter filler, Ready to Use cartridge come with a pre-placed stopper/cap.?

Bulk cartridges must first receive the plunger – this is placed mechanically from underneath the cartridge. Placement must be precise for the delivery mechanism in the plunger to work properly.? After filling through the small opening of the cartridge, the stopper/cap combination is placed and sealed just like the vial crimp cap.

Ready to use cartridges must be filled through the larger end in a similar fashion to a syringes.? The plunger is placed above the opening after filling, and vacuum stoppering is used to place the plunger into the cartridge.? This method does not result in the same precision of the plunger placement location as a bulk process.

Just to add a quick note on glass ampoules, these are flame sealed and formed into a rounded end.? Flame or heat-sealed products (ampoules, IV bags, etc.) require 100% leak detection prior to batch release. Glass ampoules have had a long run in pharmaceutical manufacturing but are phasing out in North America.

In the Rearview…

August and September were two very different months.? I took a few weeks off in August to relax on the beach and build sandcastles with my son. ?September snapped back into full steam just after Labor Day.?

I spent a week in Germany with a group from Ohio for a Mockup study.? This is a critical step in the design phase of a large isolator line. It’s the best way to get hands on to run through the equipment setup and operation.? It’s a great chance for fine tuning for placement of environmental monitoring systems, glove ports, and planning out interventions on the line.

A few weeks ago I was in Boston at the ISPE Boston Chapter Product Show.? This was a great event with huge attendance and a great venue.

Looking Ahead

I’m working on a handful of proposals for visual inspection and fill/finish lines. Many companies are planning their capital budgets for 2025.

The next big event we’re preparing for is Pack Expo in Chicago November 3rd - 6th. ??We’ll be in the Healthcare wing, booth #W-16099. ?I hope to see you there!

-Mike Kerbaugh