Managing the challenges in small volume parenteral manufacturing with an isolated filling line for lyo and liquid products.

Our ability to manage the design and construction of complex, integrated equipment in aseptic environments was key to securing the project we will now illustrate. The expertise needed to understand critical parameters and provide valuable solutions starting from an early stage proved essential to cope with the growing challenges of modern small-volume parenteral manufacturing for liquid and freeze-dried forms.

At a time when a new wave of therapeutic innovation is emerging for patients, our customer was faced with the need to respond to new challenges and adapt to a fast-moving environment. The company turned to IMA to implement a complete isolated filling line for small-volume parenteral manufacturing for liquid and freeze-dried forms, for lyophilised and liquid products.

First let’s take a look at the strategy we advised to improve product quality and manufacturing efficiency for the new injectable sterile products.

In the field of injectable products, quality in particular is the first and foremost requirement. Yet there is more to a strategy, which includes risk management, staff training and the implementation of a safety program, as well as advanced technologies, the use of flexible equipment and proper containment solutions for environmental control. These are all key issues needing to be addressed when taking a step toward aseptic production using isolation technology.

Preserving the integrity of pharmaceutical products, ensuring the maximum level of sterility while protecting both the operator and the environment with innovative containment systems are the main concerns to achieve long-term growth and value.

Close collaboration between customer and IMA Life from the very beginning of the project helped to find the solution best-suited to real needs.

Understanding the real needs from the early stages led to the design of the new production line as a unique, integrated process system, with a flexible manufacturing platform.

Many new medicinal and therapeutic product types feature different toxicological and pharmacological profiles with associated risks for operators and patients. There was consequently a precise need for a new containment strategy enabling higher levels of containment. Solutions based entirely on risk mitigation at health-based exposure limits were essential. Aseptic containment applied to the filling of sterile medicinal products must be based on a containment strategy using barriers that should operate in unison and meet specific process requirements and levels of hazard control.

The case in question was the perfect example of how flexibility can improve operational efficiency while turning innovation into product quality. Thanks to our proven experience in isolation technology, we were able to provide a valuable solution, allowing for easy operations within controlled barriers, containment measures of pressure differentials and protective HVAC airflow to meet EU GMP regulations, leading to product quality and efficacy, plus a correct balance between product, patient and process operator safety.

The containment isolator barrier surrounding the line is with a Grade A/ISO5 Classification: machine segregation ensures the processing of multiple compounds in single equipment, a huge advantage when market demands move one way or another. Furthermore, the VHP decontamination, the Cleaning & Sterilisation In Place (CIP SIP) systems significantly help to avoid any contamination risk. The WIP (Washing In Place) process ensures removal of surface contaminants, preventing and neutralising further contamination.

The line supplied includes decontamination, depyrogenation, a versatile high-speed filling & stoppering machine for lyo and liquid products with 100% In-Process Control, alu-capping and a double freeze-drying configuration with its integrated automatic vial loading and unloading system. The line is complete with a pass-through configuration in Grade A continuity and one independent capping machine for lyo and for liquid products, ensuring alternate production flows.

A further aid to isolation came in the form of a Compact Loading Unit (CLU) which is an effective containment solution, compared to the Transport and Loading Cart (T-CAR) solutions used elsewhere.

Intrinsic modularity of the single production units allowed the construction and the assembly of the whole line on a parallel timeline with on-site facility preparation. This ensured major advantages such as reduced costs, faster time-to-market and higher-quality assembly and fabrication. Modular design also helped to achieve a modern, space-efficient plant layout. The set-up modularity obtained matches perfectly with the operation of the line itself.

Enhanced SAL (Sterility Assurance Levels) derived from the use of SUT (Single-Use-Technology), combined with the advantages of isolation strategies.

The benefits of a strategy based on SUT are emphasized most of all during upstream processing. This is where volumes are greater, a growth environment is present as well as more in-process impurities, with an increased risk of bioburden. Single-Use-Technology strategies clearly raise the SAL and consequently the quality of the product.

Furthermore, implementation of SUT allowed for greater capacity at lower costs. Compared to stainless steel, less water, energy and chemicals were needed (as well as operator time) to clean and sterilise the components. They also helped in offering a quick response to changing market demands.

The centralised production line recipe management system benefitted from implementation of the SCADA supervisor.

The amount of data available, thanks to this system, enabled the customer to better understand each aspect of a process. Data-driven operations ultimately helped meet higher quality standards, respecting regulatory compliance, being sure of the validity of the information readily available.

Furthermore, the Integrated Automation Platform enhanced connectivity, internal data networking, management and control. Integrated data management led to greater efficiency in key business aspects.

The importance of an integrated strategy.

The lesson learned from a complex project such as this hinges on the coordinated approach aimed at achieving “Quality first”.  Only by implementing an integrated strategy made up of smart automation platforms, dedicated operator training sessions and proactive risk management were we able to put together a solution which ultimately satisfied customer demands relating to operating efficiency while ensuring maximum product quality.