S Y S T E M SH A N D L I N G

Precision PFS handling made to advance your businessWhite PaPer

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it is now a fact that the worldwide market for prefilled syringes (PFS) has been growing for two decades, and will con - tinue growing at double-digit rates with the emergence of new biotech drugs. Prefilled syringes offer significant advan - tages over other traditional packaging forms such as ampoules or vials. They are much preferred by both the healthcare community and consumers of self-admin-istered drugs. They are easy to handle, provide safer conditions and are always ready for use. Regarding drug manufac-turers, PFS’s offer the possibility to differentiate generic products, improve delivery systems and save manufacturing costs thanks to their dose accuracy and fewer processing requirements. In the beginning, syringes were only delivered in bulk. The process steps such as washing, siliconisation and sterilisation, as well as filling and sealing, were then performed in-house by the pharmaceu-tical companies. Nowadays, device manu facturers are supplying prefillable syringes in a pre-sterilised and ready-to-fill form, so the pharmaceutical compa-nies are saving these manufacturing

steps. However, due to its nest-and-tub components, the irruption of such pre-processed forms has added more complexity to the logistics and handling operations. As a result, gaps have appeared in the production chain where manual handling for transferring the product from one step to another has become the common practice. Indeed, there’s a general belief that the automa-tion of such process steps is too complex and risky. The objective of this article is to introduce the Krysalid® system, a new and innova-tive solution to resolve the new problems encountered in the handling, transfer and transport of nest-and-tub configuration syringes. It is a solution that is easily integrated into existing production lines and will allow the transfer, storage and/or transport of nest-and-tub syringes in a very clean, fast and gentle way.

 

When producing drugs in prefilled syringes (PFS), pharmaceutical manufacturers usually focus their engineering efforts on the filling equipment. How ever, once the product is filled, there are several remaining process steps that also pose a big challenge from the GMP perspective.

As a matter of example, these operations are: transfer to terminal sterilisation (if applicable), transfer to inspection and labelling machines, internal transport for temporary storage, etc. These operations, typically carried out manually, are actually a bottleneck in the production area

and require a lot of human intervention, making them susceptible to the potential risks. Moreover, being an intensive manpower job, there is more need for space due to the “physical” work involved.

The benefits of automated handling and transfer operations would be significant in order to simplify the workflow and reduce the manpower, working area and use of materials. But how should we transfer, store and protect large volumes of syringes produced at a high rate without compromising revenues or quality? We will elaborate the problem and the solution in the following case study.

Figure 1. A layout showing the production area to inspect prefilled syringes including: a buffer table with conveyor (in purple), a de-nesting machine plus rejection tub and nests (yellow), the inspection machine (blue) and the Plasticomb rotation conveyor to collect the syringes after visual inspection (orange). The clear blue pallets are the empty Plasticomb units to be loaded with syringes. Many people are needed in order to cope with the production rate; additional components are needed and others rejected, so there is a complex workflow in a limited area.

the KrYSaLiD® SYSTEM

An integrated solution for the transfer and transport purposes of nested PFS s

Jordi Net, Business Development Manager. STERISYS

Eric Lepot, R&D Manager. STERISYS

Our customer, a pharmaceutical company based in France, faced many difficulties when handling the production output of prefilled syringes in various formats on two different high-speed filling ma-chines. Some of these products needed terminal sterilisation, although others did not. Those products not requiring terminal sterilisation were to be directly transferred to plastic Euro-pallet- sized containers, while the others required diversion and transfer to the loading sterilisation racks. After the sterilisation cycle was complete, the sterilised nested syringes were to be removed from the racks and transferred to the plastic Euro-pal-let-sized containers. These containers would be used to transport the products to other production areas by means of standard manual or electric pallet lifters. The final production stages such as automatic visual inspection, final packaging, storage or delivery outside the site would then be carried out.

The customer was looking for an automated solution to carry out these operations, with minimum human intervention and without the need to touch the product, so the handling and transport could be executed efficiently without posing a risk to the product.

CaSe StUDY

In summary, these were the main challenges of the project:

Improve the profitability of the product by reducing the overall handling operation costs.

Improve quality by ensuring full traceability in handling, sterilisation and sampling operations.

Keep technical risks to a minimum by allowing for easy ‘degraded mode’ processing.

And these were the technical constraints:

The customer was not only using nests of 100 or 160 syringes in different diameters and lengths, but they were also from different suppliers, which created many product combinations.

The filling lines were already installed and the workflow could not be changed.

The filling lines were also operating at different speeds simultaneously with various products and components.

The implementation of the new equipment could not impact existing production rates.

Implementing the STERISYS Auto matic Handling System for terminal sterilisation of PFS

Figure 2. A layout showing the production cells placed right after filling and terminal sterilisation. The first one will have two distinct production modes:

1) ‘Container-loading mode’, in which tubs are directed by a conveyor to a first station where the syringes are counted and marked with codes. The tub is then transferred to a station where the Combycover™ is added to protect the syringes and allow easy palletisation. The now-closed packaging is then automatically placed in the Combypal™ plastic container by the anthropomor-phic robot. This ‘containerloading mode’ results in filled nested syringes with full traceability gently arranged in a Euro-sized plastic container.

2) ‘Rack-loading mode’, in which tubs are also counted and marked with codes before being transferred to a handling station, where components are quickly separated by the robot: the tub is released onto a first station where the nested syringes are placed on a specially designed exchange station, and the robot finally picks up the tub and automatically places the now- empty package (tub + Combycover™) in the plastic container. A second anthro- pomorphic robot will simultaneously recover the nested syringes from the exchange station and firmly place a Stericover™ on it. The robot then auto- matically loads the sterilisation rack with the newly created package (nested syringes + Stericover™). These sequen- ces are similar, but in the opposite direction in the production cells after terminal sterilisation, with the purpose of picking the syringes from the steri- lisation racks and transferring them into the pallet containers.

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A. Krysalid® robots in ‘rack-loading mode’B. SteriSYS terminal sterilisation auto-claves with capacity for one Volcanorack™C. Volcanorack™ sterilisation rack with Stericover™ support traysD. Combypal™ pallet container with stacked tubs and Combycover™

implemented solution Based on our range of Krysalid® handling solutions for PFS’s, we were able to quickly offer a global solution to meet the specific requirements of the project.

Our proposal was simple and straightforward: Two robotised production cells dedicated to handling the nested filled syringes right at the exit of the existing filling equipment and right after terminal sterilisation. The first one would be designed for palletising those products not requiring terminal sterilisation or, if the product had to go through the autoclaves, for transferring (loading) the nested syringes into the sterilisation rack. The second cell, located in the unloading area of the sterilisers, would serve to unload the nested syringes from sterilisation racks and transfer them into plastic containers. Each of these operations would be performed automatically by robots.

Additionally, an embedded laser marking head placed in the first cell would provide a convenient traceability solution by identifying the nest with plain text and 2D codes. And in the second cell, a camerabased system would provide another traceability solution by identifying the nest’s 2D codes.

The Krysalid® system does not focus on a specific application for automation, but on finding a global solution for handling nest-and-tub configured products. Pre-fillable systems are usually very diffi - cult and tedious to handle manually. They are applied in multiple situations (transfer to working stations, inspection machines, terminal sterilisers, etc.) and have slightly different shapes depending on the manufacturer. The solution to all these variables is based on combining the nest-and-tub support elements with specific patented devices to facilitate the interface with both humans and robots. By using these devices, the handling operation is gentle and the products (syringes, vials) are safe from risk. Indeed, the name Krysalid® implies the idea of ‘protection while in the transformation process’.

But what are these devices and how do they work? We have listed the required components and provided a short description on the right:

Utilising all of these components as part of the production system, the Krysalid® Automatic Handling System can be easily and quickly implemented. One of the key advantages is that the customer can begin checking how production rates, product quality and employee working conditions improve in the manual mode, while determining how much more this development would improve in an automated mode. The automated handling in the case study has allowed the customer to reduce the number of employees by a third. A production line requiring 3 persons per shift can easily be reduced to 1 person for supervisory and sampling purposes only.

BUt hoW DoeS the KrYSaLiD® SYSTEM WORK?

A. Combycover™ protection lids B. Stericover™ universal nested syringes sterili-sation support tray C. Volcanorack™ designed to load nested syringes in Stericover™ sterilisation support trays D. Combycover™ allows easy stacking of tubs

Combypal™ this is a special container designed to be seated on a Euro-pallet with a capacity of 120 tubs. It is designed to enable safe, stable and reliable palletisation by stacking tubs using the Combycover™ solution.

Volcanorack™ This is a cart especially designed to enable safe, stable and reliable loading/unloading of nested syringes in Stericover™ sterilisation support trays to/from the rail guides of the cart.

Combycover™ This is a patented universal plastic cover that is placed on top of the tub, regard- less of the tub manufacturer. It serves as a lid and, thanks to its robust design, makes it possible to stack the tub-and-nest syringes. This property enables them to be easily placed into a specifi- cally designed Euro-pallet type container, conferring stability and eliminating the risk of damage. The special Combypal™ container is also described below.

Stericover™ This is a stainless steel tray, with a patented design, easily adaptable to any type of nest and tub. Its design enables easy fixation of the nest and facilitates the inverting of the nested syringes’ orientation, as well as the loading/unloading into a sterilisation rack without the risk of falling. In case of automated operation, the Volcano-Rack™ sterilisation rack is to be used.

A B C D

The investment was perceived as being low-risk and offered a quick return. It is a simple, straightforward, technical solution.

The workflow layout was easily adapted to their current installations thanks to the modular design, which is both flexible and scalable.

It was also very important for the customer to have an alternative operative mode in case of robot failure. The system offered the possibility to easily work in a ‘degraded mode’ (same operation as manual loading used before automation).

The solution did not bind them to a specific supplier of pre-fillable systems, as our solution is design-compatible for multiple formats.

The capability to enhance quality assurance with full manufacturing traceability. In the case of terminal sterilisation, this ensures the certainty that the product has gone through the sterilisation process.

We were the only company capable of offer- ing a true global turn-key solution, including handling equipment and autoclaves.

And finally, the installation was easy-to-clean and provided better product safety; no glass against glass, no need to protect the pallet container.

THE BENEFITS AND THE REASONS FOR oUr SUCCeSS

ConclusionRegardless of whether or not the project involves automation of nest-and-tub syringes, one of the biggest advantages is that the Krysalid® system can be implemented in phases, and is therefore scalable from manual to fully automatic. Moreover, you can start as a pilot plant and expand produc-tion quantity without compromising quality by adding more accessories until reaching complete robotic automation. The solution will provide a high return on investment for the growing require-ments of handling pre-fillable nest-and-tub container systems.

STERISYS Sàrl · Am Hock 2 · L-9991 WeiswampachPhone: + 352 661 190 030 · E-mail: info@sterisys.eu

STERISYS PGmbH · Gewerbestraße 38 · B-4731 EynattenPhone: +32 (0)87 74 00 78 · E-mail: info@sterisys.eu

For more information: www.sterisys.eu

Compared to other solutions, our proposal contained genuine benefits that helped convince the customer.