Injecta Series Aseptic Processing

Whereas conventional attempts to use robots are typically confined to just one step of production, i.e. simply for moving vials from station to station or for removing the cover from a tub of nested containers, INJECTA uses the full potential of its robots.

INJECTA uses the full potential of its robots.

The use of advanced robotically driven manipulations throughout all production operations, from outer/inner bag opening to the stoppering station, allows for a very smooth production process, drastically reducing human interventions and cross-contamination risks; all issues are solved through robot interactions. INJECTA is designed as a whole, exploiting all robotic capabilities in an integrated system. Kawasaki’s seven-axis robot arms are designed for the lowest particle shedding. They are resistant to positive/negative and high pressures and fully compatible for decontamination using H₂O₂ vapour.

INJECTA’s specialised robots not only provide precise, consistent handling activities, but also offer a high level of flexibility: they are completely digitally controlled with Industry 4.0 capability.

INJECTA is designed to be flexible in aseptic processing. It can easily combine and perform a fully robotized 100% check-weighing for:

• in-nest configuration
• de-nesting configuration.

INJECTA accurately and efficiently fills and closes RTU components in a nest or with de-nesting.

As a de-nesting solution, INJECTA’s flexible handling units allow for precise removal of components. Individual components are filled, check-weighed, stoppered and then replaced into the nest, in the case of syringes and cartridges, or transferred by a conveyor belt to complete the process.

De-nesting operations are available for high-level quality control, with individual component handling by a robot.

All processed RTU components are individually check-weighed (in the case of de-nesting) or check-weighed all together while in nest, with single rejection of each individual non-conformity, safeguarding the nest.

All the operating units are located in a remote position from the product path with easier access to filling and stoppering areas from both sides of the machine.

INJECTA uses the same supports and transfer devices for all types of RTU components with a unique robotic pincer for material pick&place procedures. This means built-in scalability, high flexibility, simplicity and adaptability in product handling.

Design standardisation helps INJECTA conserve its agility.

Design standardisation helps INJECTA conserve its agility when switching from one container type to another (in nest or with de-nesting), overcoming the complexity and the difficulties of performing aseptic processing with high sterility assurance. INJECTA’s container handling system provides consistency and repeatability, simplifying set up and material transfer without any glass-to-glass contact.

INJECTA’s robotic multi-format filling system design meets multiple requirements, ranging from small-scale clinical trial batches up to medium-high production levels. Its unique production platform, which implements any number of filling pumps between one and ten, performs the same identical filling, check-weighing and stoppering operations avoiding re-qualification of the production process.

INJECTA, performing the same operations without process re-qualification, enhances your production efficiency.

The filling system implemented on INJECTA relies upon a unique driving system for volumetric and peristaltic pumps and a filling nozzle approved for integration in single-use package forms. Similarly, its 100% check-weighing system can count upon the same HW components for the weighing cells, the same change over parts  and the same SW process.

When handling syringes, stoppering operations are performed with the same deep tube and vacuum insertion. In the case of vial stoppering, all operational sequences are identical for both lyo & non-lyo stoppers. When it comes to handling the new integrated rubber & plastic caps, recently introduced on the market, INJECTA handles them in the same way.

The INJECTA family in all configurations ensures unique, standardised sterilisation, filling and stoppering performance, leading to improved product quality and superior manufacturing efficiency.

INJECTA allows the optimisation of space design for new parenteral manufacturing and/or for newly designed plants.

Furthermore, in the case of existing plants, thanks to its superior adaptability, INJECTA perfectly fits into an unlimited number of layout configurations with upstream de-pyrogenating tunnel and downstream alu-capping, external washing, up to freeze-drying and complete high potent lines under isolation. In addition, the RTU containers can be accurately and efficiently filled and closed  in a nest or with de-nesting. By implementing a modular approach, INJECTA models itself to any kind of production context requirement. 

INJECTA can achieve unlimited best-in-class modular layout solutions.
Here are some examples of possible layout configurations:

• Customised solutions to process RTU components (syringes, vials and cartridges) pre-arranged in nest and tub;
• Dedicated solutions to process RTU vials from bulk with de-nesting;
• Dedicated solutions to process RTU vials upside down from trays with de-nesting;
• Dedicated solutions to process RTU vials lyophilised in a nest;
• Dedicated solutions for handling plastic press-fit vial closures (snap caps) for lyo vials.

To help them reduce costs emanating from their supply chain, today’s innovative pharma and biotech companies retain flexibility and have the agility to react quickly to changing circumstances within the development, manufacturing and packaging process. The final aim is to combine intelligent facility layout, cutting-edge technologies and innovative processes.

Facilities should allow for flexibility in terms of process development and technical equipment, while maintaining high quality standards. INJECTA helps enhance space flexibility thanks to its own unique intrinsic modular approach. 

Controlled barriers, containment measures of pressure differentials and protective airflow applied together with advanced robotic handling all help preserve the sterility of the tub (and its components) during outer bag opening procedures. To meet the regulatory requirements, the whole tub-opening unit is completely robotized and under containment. Bag opening is performed in a way that minimises contamination risks, at a point where airflow and pressure difference between two sections ensure the tub remains sterile. After cutting the bag overwrapped around the tub, the primary package is instantly transferred by an internal transfer port to the isolated, processing area.

INJECTA’s robotic technology is a key contribution to preserving tub sterility.

To preserve the sterility of the tub, the bag flaps are opened by suction cups, only when the tub is physically transferred to the isolated area. This innovative pass-through solution helps minimize the exposure of tub and relevant components in less restrictive areas to particles originating from primary packaging materials and/or other routes of particle introduction, improving process quality.

INJECTA’s robotic system provides flexibility, ease of use, and sterility assurance enabling a real-time fill-weight check and ensuring the greatest quality result by a single-component rejection system.

INJECTA can easily combine fully robotized 100% check-weighing, while ensuring top-notch machine performance.

All processed RTU components are individually check-weighed (in case of de-nesting) or check-weighed all together while in nest, with single rejection of each individual non-conformity, safeguarding the nest.

INJECTA ensures single rejection both from the nest or with de-nesting.

A patented device used to eliminate the electrostatic charge in the nest is the first step towards accurate weighing, handled by a system designed to minimise interference in weighing accuracy caused by airflow. As a de-nesting solution, INJECTA’s flexible handling units allow for precise removal of the components from the nest. Individual components (1 or 2, or 5-6 at a time) are filled, check-weighed, immediately stoppered, meaning the sterile drug product is subject to much shorter exposure times within the aseptic environment. The design of the 5/6 weigh-cell block also allows for the tolerance required to manage different RTU component formats.

Smaller batches, high potency products such as biologics or conjugates and therapies, involving genes and cells to combat cancer indications, involve the implementation of proper cleansing procedures to avoid or isolate contamination from process areas. INJECTA’s design allows for easy pass-through and cleansing procedures, which are mandatory when handling potent compounds, ensuring the safety and the integrity of the products.

Equipment design, also featuring a massive presence of robots, facilitates protection of open containers thanks to unidirectional airflow.

The overwhelming presence of robots entails the total absence of conventional transfer combs or conveyor belts, facilitating unidirectional airflow (avoiding barriers). Furthermore, INJECTA’s concept design supports proper wash-in-place (WIP) cleansing processes, removing internal surface contaminants from the machine. Surface design facilitates more effective cleaning procedures. Ensuring potential contamination is kept to a strict minimum means greater protection for the product, the equipment itself and the staff operating the equipment or attending to cleaning procedures.

Thanks to the extreme flexibility of INJECTA, at IMA Life we create the best suited layout configurations according to each customer need and check its ergonomics and design during final review phases.  All the activities performed on the line (e.g. assembly of disposable systems, etc.) are tested by a wooden mock-up of the complete filling line and the related isolator, made to 1:1 scale.

INJECTA’s mock-up testing procedure is performed to check INJECTA’s upstream and downstream interactions.

A similar testing procedure is performed to check the interaction between INJECTA and the other units upstream and downstream of the line (e.g. CLU, LUAT etc.), also made of wood and full scale.

Once the mock-up of INJECTA is implemented, the positioning of the utilities inside the isolator (e.g. water, nitrogen, compressed air and steam) is also defined which, thanks to the single block design, do not need to be connected/disconnected during production. The positions of the utilities will therefore be set so as not to affect the ergonomics of the line.

Communication between INJECTA and the isolator requires no changes in the transition from one filling configuration to another, since disconnecting and reconnecting is not necessary in the size changeover phase.

The electronic and electrical connections, just like for the utilities, are defined in the design phase of the machine and tested during the line mock-up phase.

The unidirectional air flow (UDAF) air in Grade A filling environments suppresses any release of contaminant to a lower level zone, which is contained by the barrier boundary filtration and it is possible to decontaminate in place. The containment barrier is automatically closed for WIP (Washing In Place) cycle which ensures removal of surface contaminants, preventing and neutralizing possible contamination. The improved design of the isolator on a single machine as well as the use of easily cleanable robots capable of moving independently and facilitating the UDAF allows the WIP (Washing In Place) cycle to be optimized.  Consequently, considering the worst case filling scenario, it will be adequate to validate a single washing cycle.

INJECTA safeguards a dedicated VPHP bio-decontamination cycle for a single line (INJECTA + isolator).

During the filling line set-up phase, by analysing specific customer production requirements, such as multiple filling processes and production parallelism, it is possible to develop a single decontamination cycle with VPHP. The specific set-points for the decontamination process, once validated, do not require modification or re-testing since it is a dedicated cycle for a single line (INJECTA + isolator).

Developing and validating a single VPHP cycle, for all the possible configurations of INJECTA, results in time saving both for the first validation and for periodic re-validations.

In the pharmaceutical industry, aseptic processing is monitored—in accordance with regulatory requirements—to prove the environment surrounding a process does not negatively impact product quality and, ultimately, patient safety. Environmental parameters monitored include temperature, relative humidity, differential pressure, and airborne particles. Annex 1, FDA and cGMP’s guidance on Aseptic Processing give special attention to ongoing routine monitoring with regards to the design of systems and setting of action limits alert levels for viable and non-viable environmental and process monitoring. Compliance to these regulatory guidelines, which require continuous monitoring of airborne particle cleanliness, has been a driver for pharmaceutical companies to install facility monitoring systems.

Optical particle counters have historically been the only way of monitoring the cleanliness of the air in real time in pharmaceutical applications. These instruments are installed, based on the principles of quality risk management (QRM) in locations where there is the greatest risk of airborne particle contamination to the process. These instruments could not determine particle viability; they can only count and size particles in real-time.

Recently, the commercialisation of a new technology based on Laser Induced Fluorescence (LIF) has made it possible to look at airborne viable microbial counts in real time. Real-time alarms notify facility operators of alert limits to enable an immediate response to an unwanted event or excursion. Real-time viable particle counters not only offer the potential to monitor these very clean and controlled environments, but can also provide continuous data when integrated into a facility monitoring systems FMS System. 

Approval of this technology will result from discussions between the pharmaceutical companies and the authorising bodies. IMA Life is carefully evaluating applying the technology to the current machines, whereas it will be part of the design criteria for all pipeline projects.

The potential to instantly respond to an airborne microbiological event when it happens is exciting – and beneficial: it improves process understanding and enhances process knowledge. Result is an increase in product quality, a safer product, and risk reduction.