Aseptic processing by design: The flexible and efficient use of RABS and Isolators

The sterile liquid injectable industry has evolved from open cleanroom processing to highly automated, closed aseptic manufacturing. Laminar airflow and HEPA filtration improved environmental control in the 1960s/70s, while stricter regulatory requirements in the 1980s drove further advances. RABS emerged in the mid-1990s, followed by isolator technology in the late 1990s and 2000s, significantly reducing contamination risks through increased separation between operators and the product. Today, automation, robotics, real-time monitoring and Quality by Design (QbD) support robust, risk-based and data-driven manufacturing.

The global sterile injectable market continues to grow, driven by biologics, vaccines and oncology products. Increasing regulatory scrutiny, supply-chain disruptions and demand for resilient capacity are accelerating investment in advanced aseptic technologies and strengthening the role of CDMOs. Customers increasingly require flexibility, rapid scale-up and reliable global supply while maintaining the highest regulatory standards.

Aenova Latina: Dual Technology Platform

Aenova operates two complementary, fully automated sterile filling lines in Latina, Italy, combining different aseptic technologies:

• F&F1 – oRABS combo line: High-speed, high-capacity platform for vials from 2R–10R and PFS from 0.5–10 mL. It is particularly suited to high-volume campaigns and products sensitive to residual vaporized hydrogen peroxide (VHP).
• F&F2 – Isolator combo line: Highly flexible platform for vials from 2R–50R, PFS from 0.5–50 mL and cartridges from 1–20 mL. Configurable from ten-needle to single-needle operation, it supports small clinical batches through commercial-scale production.

Both lines support single-use systems, stainless steel or hybrid equipment and enable efficient technology transfers. Integrated cold storage and an advanced QC/microbiology laboratory provide end-to-end support.

The dual-platform concept enables customers to select the optimal technology based on product sensitivity, batch size and process requirements. F&F1 minimizes downtime and VHP-related risks, while F&F2 provides enhanced containment and broad format and batch-size flexibility. The site can support lifecycle transitions from early clinical 2R vials to commercial vial, PFS or cartridge presentations, reducing technology-transfer effort, timelines and regulatory complexity.

In line with EU GMP Annex 1, technology selection is governed by the site-wide Contamination Control Strategy (CCS), integrating facility design, process controls, environmental monitoring, operator qualification, cleaning, disinfection and aseptic process simulations.

Process Excellence: Filling Needle Residue Case Study

Aenova Latina’s MS&T and Engineering teams investigated residue formation on filling needles in PFS manufacturing, particularly for crystallization-prone formulations. Residues can result from droplets or micro-splashes depositing on the needle surface, followed by evaporation and crystallization. Key influencing factors include filling dynamics, needle geometry, pump parameters, pauses, humidity and formulation properties.

Studies demonstrated a clear relationship between fill-weight variability and residue formation: higher standard deviation indicates increased turbulence and droplet formation. Optimizing filling profiles, pump acceleration/deceleration, needle geometry, tubing support, environmental conditions and weighing systems significantly improved process stability.

The optimized process achieved:

• Fill-weight standard deviation below 0.003
• Average residue below 0.1 mg per needle
• Near-elimination of visible residue under optimized conditions
• Up to 30% higher filling speed through statistically based in-process weighing rather than 100% unit weighing

This demonstrates how process understanding and statistical process control can simultaneously improve quality, robustness and productivity.

People & Competence as a Strategic Asset

Technology is supported by Aenova Latina’s Competence Excellence training program. Training focuses not only on how tasks are performed, but on understanding the technical, scientific and quality-related reasons behind them. This builds operator awareness, autonomy and risk-based decision-making.

During technology transfer and ramp-up, Gap Analyses identify critical activities, followed by targeted Practice Plans, simulations and hands-on training. Competencies are monitored through Skill Matrices and continuously reinforced through on-the-job training and qualification programs.

The approach strengthens the connection between MS&T and Operations and accelerates readiness for new platforms. Training methods are continuously adapted to regulatory changes and new technologies, including Virtual Reality, mock lines and future AI-supported learning.

Customer Value

Aenova Latina combines advanced aseptic technology, multi-format flexibility, scalability, process expertise and highly trained teams. F&F1 delivers speed and stability for high-volume campaigns, while F&F2 enables flexible clinical-to-commercial scale-up on one platform.

Together, the two complementary technologies enable reliable sterile manufacturing for high-value, sensitive products such as monoclonal antibodies, recombinant proteins, peptides, oligonucleotides and innovative small molecules. The result is reduced contamination and transfer risk, faster scale-up, greater flexibility and shorter time-to-patient — positioning Aenova Latina as a high-performance sterile excellence center designed around product performance and client needs.