Enhancing Sterility: The Crucial Role of Isolators in Sterile Fill-Finish

Maintaining the highest levels of sterility is paramount to ensure the safety and efficacy of drugs, with good aseptic manufacturing playing a pivotal role in safeguarding patient health and wellbeing.

One critical stage where sterility is of utmost importance is the fill-finish process, where the drug product is filled into its final container, such as vials, syringes, or cartridges, and sealed. To achiev enhanced drug product sterility, especially in multi-product facilities, isolators play a crucial role.

The Significance of Isolators

Isolators are closed systems designed to create and maintain a controlled sterile environment. They provide a physical barrier around processing technologies such as injectable filling lines and capping machines. In sterile fill-finish operations, isolators play a multifaceted role to ensure the integrity and safety of the final drug product, including:

  • Preventing Contamination: Isolators create a barrier that prevents airborne particles, microorganisms, and other contaminants from entering the critical processing areas, thus safeguarding the integrity of the product.
  • Maintaining Sterility: By controlling factors such as temperature, humidity, and pressure differential, isolators ensure optimal conditions for maintaining sterility throughout the fill-finish process.
  • Protecting Operators: Isolators not only protect the product from contamination from operators but also shield operators from exposure to potentially hazardous substances and ensure their safety during pharmaceutical manufacturing processes.

Advantages of Isolators in Sterile Fill-Finish Processes

The integration of isolators into sterile fill-finish processes offers several significant advantages:

  • Enhanced Sterility Assurance: Isolators provide a robust barrier against contamination, ensuring the highest levels of sterility throughout the fill-finish process.
  • Improved Product Quality: By minimizing the risk of contamination, isolators contribute to the production of high quality drug products with consistent efficacy and safety profiles.
  • Operator Safety: Isolators protect operators from exposure to hazardous materials and provide a safe working environment within the pharmaceutical manufacturing facility.
  • Compliance with Regulatory Standards: Isolators comply with stringent regulatory requirements for sterile processing, and most notably EU Annex 1 compliance.

Latest Isolator Technology Investments at PCI Pharma Services

Over the past two years, PCI has invested significantly in bringing the latest in isolator technology into our global sterile manufacturing network, supporting early phase clinical trials through to large scale commercial launch.

Clinical scale isolator filling solutions

With a focus on supplying life-changing therapies to patients as quickly and efficiently as possible, PCI utilizes the latest advancements of robotic gloveless isolator sterile filling technologies. Located at PCIs clinical site in San Diego, California, the fully robotic isolators, Cytiva’s Microcell unit and a larger scale SA25 platform, provide flexible aseptic fill-finish solutions for both small and larger-scale clinical production runs across a variety of dosage forms including vials, syringes and cartridges for use in autoinjectors. The scalable solutions address our clients’ aseptic manufacturing needs from preclinical, through First in Human (FIH) trials and beyond, delivering products to patients safely and efficiently.

The Microcell platform offers fully automated, gloveless filling, performed through closed robotic isolator technology that provides both small batch flexibility and standardized manufacturing. The agility of this technology make it suitable for the production of both personalized medicine batches, preclinical and early phase clinical trial supplies delivering true speed to patients. Superior drug product quality is assured through advanced automation, removing the need for operator intervention during the filling process and limiting product contact. Importantly, the Microcell technology can fill up to 1,200 vial units per batch with fill volumes ranging from 1.0 –50mL.

Providing a scalable aseptic solution in support of clients progressing through the clinical lifecycle towards commercialization, the SA25 Aseptic Filling Workstation is a larger clinical scale, gloveless, isolator-based filling technology offering scalable batch production of up to 20,000 units, supporting fill volumes from 0.2 – 50mL. This technology provides flexible manufacturing solutions with the ability to fill multiple delivery device formats including vials, syringes and cartridges through the aseptic process.

Large scale commercial isolator filling solutions

Expanding our established sterile manufacturing and lyophilization capabilities and capacity at our Bedford, New Hampshire campus, we have invested $100MM in a new large scale 50,000ft2 high throughput facility. This commercial scale facility will provide increased capacity using Annex 1 compliant state-the-art isolator technology including high speed, large volume vial filling and twin lyophilization lines complete with automatic loading and unloading systems.

Processing batch sizes up to 300,000 vials at a rate of 400vpm provides much needed large scale capacity for our client partners in the filling of their life-changing biologics, mABs, oligonucleotides, proteins and peptide drug products. Smart fill technology, utilizing peristaltic pumps and re-stoppering functions ensure minimum vial losses of our clients’ valuable drug product.

With full isolator containment, auto-loading lyophilization technology and PUPSIT, the new facility is fully compliant with EU Annex 1 and will be operational early 2025 with capacity reservation available immediately to secure sterile supply chains in delivering life-changing therapies to patients.

Conclusion

In the complex landscape of pharmaceutical manufacturing, the use of isolators in sterile fill- finish processes is indispensable. These enclosed systems provide a vital line of defense against contamination, safeguarding the integrity of drug products and ensuring the safety of both patients and operators. With their ability to create and maintain a controlled sterile environment, isolators represent a cornerstone of modern aseptic processing and play a crucial role in maintaining the highest standards of quality and sterility in the pharmaceutical industry.

Author: Tom McGrath, VP Global Quality Development & Manufacturing Services
Bio: Tom has over 25 years of in drug development, quality, and regulatory roles, with the last decade+ focusing on aseptically processed pharmaceuticals and medical devices. Prior to assuming his current role in 2014, he was Sr. Director of Quality for Aseptic Services at AMRI–Burlington (now Curia), where he led successful remediation efforts. Before that he held development and quality positions of increasing responsibility at AMAG Pharmaceuticals, CombinatoRx and Praecis Pharmaceuticals. Tom received his B.A. degree in Chemistry from The College of the Holy Cross.

Enhancing Sterility: The Crucial Role of Isolators in Sterile Fill-Finish with Tom McGrath | As seen in Manufacturing Chemist | March 2024


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