Flexibility and technology at the service of the pharmaceutical industry

One reason for the success of INJECTA, our latest-generation fill-finish machine for RTU components, lies in the strategic use of advanced robotic technologies.  When developing the machine, we turned to Tiesse Robot based in Visano (Brescia), whose long-standing experience with Kawasaki robots made all the difference.

Read the article explaining how many of the benefits behind INJECTA are directly related to the advanced robotic technologies. For example, the superior flexibility of the solution as well as the no-touch-transfer capabilities.

The demand for greater flexibility, speed, precision and quality in the filling and sealing (fill-finish) process for injectable products to be packaged in Ready-To-Use containers such as bottles, syringes and cartridges has always been a feature of the medical product market. A trend accelerated, in recent years, by new pharmaceutical products and by the growing pressure from regulatory bodies.

To keep pace, pharmaceutical companies and Contract Development Manufacturing Organizations (CDMOs) must be able to handle a wide variety of container types and packaging formats.

The use of robotics in operator-less or glove-less systems, designed to do without human operators in critical activities such as placement of sterile material or manipulation of tools using gloves, is fundamentally important and has been strongly advised by international authorities to avoid risks of contamination from human intervention, the possibility of human error and failure to comply with operating procedures.

IMA and the INJECTA solution.

The INJECTA series developed by the Bologna-based IMA Spa Life Division is the result of six years of design and development work, carried out by a team of business experts, and the first such product built around a fully robotic concept. Conventional attempts to use robots are typically limited to a single production step, e.g. moving bottles or syringes from one station to the next or removing tyvek from a tub or tray.

INJECTA, however, is designed to make the most of the potential of its robots. Thanks to its integrated robotic technology, it offers countless advantages: first of all, the reduction of the system footprint, thanks to system configurability allowing a single machine to be used for different filling techniques, formats and processes. Therefore, different solutions are possible to feed pre-sterilised containers placed in Tubs/Trays (bottles, syringes, cartridges) via “no-touch” methods or, in the case of bottles, in bulk from depyrogenation tunnels. Other benefits are shorter change-over times, as the high flexibility for multi-product and multi-format manipulation allows for fast switching between different pharmaceutical products and primary packagings; the possibility of automatic decontamination with vaporized hydrogen peroxide at the start of production, and automated washing and de-activation procedures at the end of the campaign – in the event of toxic or biologically active products. Manual operations are thus minimised – avoiding contamination of the clean room and ensuring perfect control of process trajectories, which minimises the risk of going through critical areas. We can also offer configurability of all the fill-finish process phases, through recipes selectable via the control panel, with minimal mechanical adjustment requirements. Finally, accurate control of product handling in critical phases can be achieved, such as container positioning on weighing units for process IPC or during the filling phases.

The solutions integrated with INJECTA consist of several modules, each equipped with one or more robots capable of automating the entire production process and suitable for being configured so as to create layouts according to production needs and required protocols. The initial bag opening module is the inlet point for wrapped tubs or trays, coming from the conveyor loaded by the operator in the clean room. The robotic arm picks up the package by means of a gripper gripping the bag flaps; an automatic cutter opens the package along the edge, while the robot gripper keeps it closed, preserving the sterile interior from contamination. The robot then carries the bag to the next chamber, where a “docking station” system transfers the tub/tray with a “no-touch transfer” or NTT approach, without having to implement decontamination processes or compromising the internal container and the area classification.

The bag opening module is integrated into an Open RABS (Restricted Access Barrier System) which limits particulate and microbiological contamination and, depending on the package (single or double bag), pushes the tub/tray into the next chamber. Downstream, in the first chamber under aseptic conditions, i.e. isolated and decontaminated in order to achieve the pharmaceutical Grade A, the tub/tray is opened by removing the top tyvek and the internal lid.

This operation is performed by a robotic arm equipped with grippers and suction cups, which follows special trajectories to avoid going over the exposed area, maximising the container washing action with the laminar flow in the isolator.

Finally, the system moves on to the denesting module where the containers will be removed for filling and stoppering (fill-finish); this step is 100% controlled by weighing units positioned under the product distribution point in each bottle or syringe. INJECTA can carry out “in-nest” filling, i.e. filling containers without removing them from their feeding nest, or denesting, i.e. filling every single container by removing it from its nest/tray. The next operation involves capping the bottle or inserting a plug into the syringe/cartridge. In the case of freeze-dried products, the line is connected to loading/unloading systems to/from the freeze dryers; conversely, the bottles are conveyed towards the capping area where an aluminium cap will be applied and the container finally sealed.

The Kawasaki MC004-V robot.

INJECTA was developed with an integrated approach as regards three fundamental components: machine, isolator and robot. As far as robots are concerned, IMA Life identified a strategic partner to supervise all the development phases by offering innovative solutions for the pharmaceutical sector. Kawasaki MC004-V robots were supplied by Tiesse Robot based in Visano (Brescia), a leader in industrial automation and a historical partner of Kawasaki Robotics. The model features 6 degrees of freedom, VPHP resistant coating, 4 kg payload, grade IP65, hollow wrist with fully integrated wiring and piping. The IMA Life-Kawasaki team experts have appointed Fraunhofer Ipa to perform all the lab tests aimed at validating the use of the MC004-V robot in aseptic areas – from the hygienic design of the mechanics and external components to the evaluation of effectiveness of manual and automated washing, with methods based on visible contrast liquid residues with UV (riboflavin), while for decontamination aspects, resistance to vaporized hydrogen peroxide was tested, as well as the impact on the logarithmic reduction of the microbiological load over time (D-value). As regards the robot profile from an aerodynamic point of view, smoke tests were carried out under laminar flow.

One of the main difficulties in the development of the INJECTA machine was finding a reliable partner, willing to follow IMA Life in the development of a robot with characteristics and finishes suitable for an aseptic environment, in compliance with the stringent regulations for the production of injectables. At European level, the main reference guideline is the cGMP Annex 1 – Manufacture Of Sterile Medicinal Products, which has its North American counterpart in the FDA. Having robots suitable for integration in Grade A area, where critical pharmaceutical processes are carried out, such as filling and capping, implies requirements that often have a radical impact on the mechanical design and performance of the anthropomorphic system.

Flexibility and straightforwardness in control and programming are not a secondary aspect, since it is necessary to create parameterized trajectories such as to achieve the objectives of cycle time, accuracy and repeatability. It is important for the robot to become interfaced with different types of interchangeable tools, grippers and suction cups. To avoid exposed pipes and cables in the aseptic area, a solution was identified that provides for routing them inside the body of the robot. The use of advanced robotic manipulation during all production operations, from the opening of the external/internal bag all the way to the capping station, allows a very smooth production process to be obtained, dramatically reducing the risk of cross-contamination.