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#advanced compliance

A move closer to perfection

The manufacture of sterile products is subject to special requirements in order to minimize risks of microbiological and particulate contamination. Even if much depends on the skill, training and attitude of the personnel involved, Quality Assurance is particularly important and carefully established and validated methods of preparation and procedure must be followed strictly.

Sterility is a critical quality attribute for all sterile substances, products and containers and must be assured by the use of a suitably designed, validated and controlled manufacturing process.

Sterility is achieved by controlling several factors like the sterilisation procedure, the integrity of the container closure system and, in the case of aseptic processing, the use of satisfactory aseptic techniques.

Reading the draft Annex 1, “Barrier Technologies” are the most preferred solutions to protect the product from operator and environment, if the drug package cannot be sterilised by terminal sterilisation. Isolator-based technology offers the ability to achieve high sterility levels as it removes the most significant source of microbiological contamination from the aseptic environment by eliminating direct interventions by gowned staff. Typically, a higher Sterility Assurance Level (SAL) is achieved with an isolator system. There are many possible designs of isolators, transfer devices and associated processes: all must comply with the regulatory requirements of FDA/EMA pharmaceutical authorities, so as to provide maximum protection of the grade A environment. 

Automation also plays a key role in aseptic fill/finish manufacturing. The existence of a reliable, advanced, process-integrated robotic system makes it feasible to eliminate operator interventions and consequently any contamination potential, while improving efficiency. To be compatible with aseptic manufacturing requirements, robotic systems must be easy to operate, ensure a “near zero particle generating” design and have complete tolerance to in-situ biodecontamination cycles with gaseous hydrogen peroxide. So, we can say that a “towards gloveless isolator solution” is an effect of the presence of highly automated aseptic processing and it means that the production process can run entirely without human manipulations. 

In this scenario, INJECTA’s revolutionary isolated robotic technology is a step ahead in the evolution of the fill-finish process, as it allows for superior contamination control. Meeting the Annex 1 requirements, INJECTA’s robotic ability can accomplish multi-product operations by a reliable and reproducible automated process and can also ensure very sophisticated process automation in change parts handling and assembly through RTP devices. The isolator remains the most logical environment in which to place INJECTA’s highly automated intervention-free aseptic fill-finish processes, leading to easier ways to operate and saving on running costs.

#AdvancedCompliance is Towards Gloveless Solutions

IMA Life is able to supply complete lines: from the initial washing of bottles, through depyrogenation, filling, capping, etc. … up to and including secondary packaging. All this with or without freeze-drying systems and, in the part where the product is exposed, using an isolator. Isolated solutions are applied to production lines for aseptic and non-toxic products and increase the safety of the final product, ensuring improved aseptic standards and lower operating costs.

All the equipment is produced inside the IMA Life facilities, which is a key factor today. Although we were not among the first to address this market segment, we have come up with a solution that is still unique today. Our isolators have “6 faces” (six walls) in view of the fact that the base of the cube-like structure is also the base of the machine which will then be integrated. This technical detail ensures greater sealing capability, avoiding gaskets between the isolator and the base of the machine, which are present in all other solutions on the market.

Towards a “gloveless” solution implies that the enclosed, fully automated aseptic processing can run completely without human intervention. Therefore, a highly automated machine like INJECTA requires a very minimal presence of gloves around its filling & stoppering “isles” thanks to its reliable, fully robotic system. Some gloves are installed for emergency access or cleaning, but they are not necessary during the production process.

INJECTA is perfectly integrated with IMA Life’s 6-sided isolator with reduced shell width, minimizing the presence of gloves.

INJECTA is designed to run with no mouse holes, conveyors, glass-to-glass contact or vibrating bowls which all create risks to the batch.Its multi-axis robotic arms are able to execute the safe, ergonomically uncompromised movement of difficult-to-handle containers offering also repeatability with the flexibility to easily change the process or the container type being filled, so as to efficiently produce high-mix batches. In absence of traditional, mechanical components, decontamination cycles are much shorter too.

“Glovelessness” implies that isolators can run much cleaner than a conventional isolator and be completely closed. All product contact parts are sterilised in place, avoiding need for an operator to directly enter the classified aseptic clean space. All of this drastically reduces the likelihood of a source of microbial contamination. In other words, sophisticated robotic systems operating in an isolator system, can ensure not only outstanding sterility assurance and product safety, but also product outcome reliability in commercial scale production.

INJECTA design is on a pathway leading to fully automated aseptic processing, towards a gloveless system that tends to run without any form of human intervention. Results: cost and time saving, major safety for operators and, thanks to the isolator environment, an increase in product quality and safety.

#AdvancedCompliance is Meeting Annex 1 Guidelines

New draft Annex 1 declaims that the design of the isolator shall take into account all critical factors associated with these technologies, including the air quality of the, the materials and component transfer, the decontamination, disinfection or sterilisation processes and the risk factors associated with the manufacturing operations and materials, and the operations conducted within the critical zone. The best practices for cleaning/decontamination of isolators require that all removable size parts that can be autoclaved (bowls, hoppers, tracks, filling circuit items) are then set in place with a plastic (Tyvek) cover per batch.

By adopting and optimizing robotic technology, at IMA Life we have reduced almost all size parts inside the isolator. Intrinsically an automated robotic line does not need any size parts, such as star wheels and corkscrew formats to guide and move vials. INJECTA’s revolutionary fully automated system can fill multiple container formats and change quickly between vial, syringe and cartridge. Robots can handle every type of RTU container in Nest or Tray in the same way, so there are limited change parts.

As far as the stopper feeding system is concerned, we can count upon an innovative group where the stoppering process is performed using a linear stopper feeding system. Unlike conventional systems, this pioneering group is made of small-sized components ideal for RTP transfer, which is in full compliance with Annex 1 requirements in terms of the sterilisation process. These small-sized parts can be autoclaved and transferred into the isolator via rapid-transfer canisters and ports, without breaking the sterility assurance level.

The use of linear stopper feeding systems reduces particle generation from vibratory bowls

In addition, thanks to its latest breakthrough, INJECTA ensures the fully automated assembly of the stopper feeding unit and of the filling group with no need for human interventions for fine-tuning or pick & place processes. Actually, the autoclaved sterile stoppering/filling parts and components, which are traditionally fed by RTP systems and handled with the use of glove ports, can enter the isolator automatically and be picked & placed by the robotic arms. By this innovative process, clean and sterile parts can be transferred and delivered into the stoppering/filling station inside the barrier system, with leak-tight and risk-free connections, without breaking containment.

So, a towards gloveless highly automated technology provides better aseptic assurance than conventional systems: avoiding the ergonomic constraints imposed by using gloves, the sterile parts and components can be automatically fed and internally assembled with reliability and precision, and all product contact parts can then be sterilised in place.

The use of robotic arms, leads to fewer requirements and easier ways to operate. It increases safety for the operators and the isolator environment, which, in turn, unquestionably increase the quality and safety of the product.

#Advanced Compliance is Real-Time Quality Control Strategies

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. 

INJECTA is ready to interact with new real-time airborne viable particle counting technologies to quickly react to possible microbial excursions

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.