Any drug manufacturing facility handling the next generation of highly active/highly potent compounds targeted for smaller patient populations (HPAPI’s, ADCs) must be equipped with the appropriate methods, controls, and expertise to ensure the safety of its employees and the integrity of its product. Establishing which safety precautions need to be in place to successfully and safely manufacture highly toxic products and avoid any cross contamination within a facility requires a knowledgeable team as well as the design and implementation of an effective safety program to evaluate a compound’s potency and toxicity.
For injectable liquid products, the specific engineering controls to safeguard acceptable daily exposure (ADE) and threshold of toxicological concern (TTC) should be applied at both the facility level and to the production line configuration. The implementation of isolation technology, the use of disposable systems, the installation of flexible and intrinsically modular equipment, the use of air handling systems, coupled with cleaning and bio-decontamination procedures, as well as GMP validation at each stage of manufacturing are imperative to minimize the risk of contamination.
With the goal to maximise operational flexibility, smooth robotic technologies represent not just an evolution of the traditional fill-finish procedures, but a complete re-think of the overall process, offering a new approach to optimize manufacturing. This innovative design approach eliminates the risks and limitations of the conventional actuators and mechanisms connected to the significant amount of format parts necessary to enable this solution to process multiple containers. By the fully robotic approach all format parts have a simple design and are static, relying upon the robot for movement, thus eliminating common sources of particle generation. Therefore, cleaning, sterilization and bio-decontamination of the line between batches is reduced, increasing line performance and enhancing sterility assurance.
At IMA Life, an innovative match has been achieved with the INJECTA robotic filling machine and IMA Life’s “six wall isolator” engineered containment solution, featuring highly individual customizations, faster format changeover, superior cleanability and ready-to-gloveless, flexible configurations to enable multiple small batch capabilities. IMA Life’s six wall isolator integrates perfectly with INJECTA’s base frame, ensuring a unique design without a gasket between Isolator and air plenum. Meeting the new HPAPIs demands in terms of risk mitigation at health-based exposure limits, this is a significant step towards innovative aseptic containment strategies.
# High Containment is having the Perfect Match with IMA Life Six Wall Isolator System.
INJECTA’s extremely flexible and intrinsically modular design allows switching between production cycles of different pharmaceutical forms (syringes, vials or pre-capped cartridges) enabling the replacement of machine parts more quickly than a standard machine. This challenging solution leads to considerable advantages in isolated lines because, based on the line layouts and on the needs of each individual customer, it allows the isolator to be designed in a more ergonomic way having to interface with a single machine.
IMA Life’s engineered exclusive “six wall” containment design ensures:
Perfect integration of isolator and machine base frame
Absence of gaskets between isolator and air plenum
Easier cleaning operations (smooth surfaces and absence of interstices)
Superior life resistance (no gasket to be changed or repaired)
No need of silicon or other filling/sealing materials Higher leak tightness (no more maintenance)
INJECTA allows the isolator to be designed in a more ergonomic way having to interface with a single machine.
Thanks to its well-established experience in isolation technology, IMA Life has developed a valuable solution in aseptic containment based on qualified methodologies, control measures of pressure differentials and protective HVAC airflow, meeting EU GMP requirements for product quality, efficacy and patient safety. Furthermore, the containment isolator barrier surrounding the fill-finish processes ensures the processing of multiple compounds in single equipment, a huge advantage when market demands move one way or another, particularly in view of our highly diversified pipeline. Single-use materials such as ready-to-use primary containers, disposable inner/outer bags, etc. are automatically handled and disposed of within the system, with no human intervention. Finally, INJECTA supports a completely automated fill/finish process with the lowest presence of gloves and glove ports, guaranteeing a greater level of sterility.
# High Containment is Design Optimisation.
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.
# High Containment is Regular In-place Decontamination.
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 VHP 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 VHP. 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 VHP cycle, for all the possible configurations of INJECTA, results in time saving both for the first validation and for periodic re-validations.