IMA LIFE approach to No-Touch Transfer (NTT) of pre-sterilised Ready-To-Use (RTU) containers.

Introduction

The pre‑filled syringe manufacturing industry faces increasing demands for enhanced sterility assurance while maintaining high‑speed production capabilities. This white paper examines how IMA LIFE NTT technology reduces contamination risks, supports productivity up to 36,000 syringes per hour, and ensures GMP compliance in modern pharmaceutical manufacturing.

Industry context and current challenges

The pre‑filled syringe manufacturing sector is experiencing significant transformation driven by evolving pharmaceutical demands and regulatory requirements. The process of introducing RTU materials into the aseptic area involves high risks from a sterility assurance perspective, particularly during critical operations such as material transfer between classified areas, bag opening and container loading inside Grade A aseptic isolators.

Contemporary production requirements reveal substantial shifts in manufacturing demands:

• Small batches, cell and gene therapies and personalized medicines require smaller, more flexible batch sizes.
• High-volume products like vaccines, antibiotics, biologics and obesity treatments demand hourly production rates reaching between 24,000 and 36,000 units.
• Modern flexible facilities typically have to handle various products and types of primary packaging, with flexible fill‑finish lines that can be quickly adapted to different production modes.

The adoption of RTU containers has accelerated, eliminating the need for in‑house sterilization and increasing production flexibility. However, this transformation also creates logistical and regulatory challenges.

IMA Life has positioned its No-Touch Transfer implementation as a direct response to these evolving requirements, combining robotic flexibility with proven expertise in aseptic processing.

What is No-Touch Transfer (NTT) technology

No‑Touch Transfer technology represents a mechanized method for introducing pre‑sterilized RTU containers into aseptic isolators while eliminating direct contact throughout the transfer process. The system operates on the principle that RTU packaging, such as tubs or trays, remains uncontaminated because they are opened with a rigorous technique up to the Grade A environments.

Technical implementation

The NTT system operates through a staged de‑bagging process utilizing advanced robotic automation:

1. First NTT step – RTU containers in double protective bags enter from lower‑grade environments, where the outer bag is opened and the inner bag is released into a Grade B area or Grade C protected with Grade A Air supply. Handling takes place without direct contact with the clean part of the packaging and through the protection of localized unidirectional airflow, capable of preventing contamination of the tub and the higher‑classified area.
2. Second NTT step – RTU containers with a single protective bag enter Grade B environments, where the outer bag is opened and the internal tub is released into a Grade A area. As in the first step, the protection is provided by localized unidirectional airflow capable of preventing contamination of the tub and the Grade A chamber.
3. Third NTT step – The RTU packaging reaches the Grade A aseptic zone where the lid or lining is removed (peeling) without manual intervention, preserving the sterility of the primary containers and the first air requirements.

Technical implementation involves 6‑axis articulated robots specifically designed for aseptic environments, with the Kawasaki robot selected for its internal‑routing capabilities and superior cleanability. The robotic system mimics gentle human manipulation while maintaining precise control over contamination‑sensitive operations.

System integration

NTT systems are integrated into high‑speed filling lines, particularly the IMA Life INJECTA series machines. The INJECTA 36 robotic fill‑finish solution incorporates fully automated NTT configurations capable of processing up to five RTU containers per minute while maintaining productivity rates of up to 36,000 syringes per hour. The technology is implemented across various machine configurations (INJECTA 6, INJECTA 10 and INJECTA 36), providing scalability from development phases to full commercial production.

Contamination-risk reduction

Traditional RTU‑container introduction processes present multiple contamination vulnerabilities, particularly at transition points between classified areas and during automated bag‑opening procedures. Contamination may occur due to:

• Incorrect air flow protection during de‑bagging.
• Contact with mechanical parts of the inner RTU layers during handling and de‑bagging.
• Particle generation during bag‑cutting and removal operations.
• Turbulence in the RTU transfer process between classified chambers and mouse‑holes.

IMA Life NTT contamination-control mechanisms

GMP regulations — particularly the recently updated Annex 1 — impose rigorous requirements for aseptic processing systems with specific emphasis on contamination control and first air protection. The regulations demand comprehensive risk assessments for any procedure that may lead to contamination of aseptic areas where critical filling and stoppering operations occur.

NTT technology addresses these contamination sources through several validated mechanisms:

• Advanced automation using robots – Allows complex manipulation to correctly handle the RTU‑material and to manage it introduction processes. Robotic automation enables format changes with minimal downtime and reduces the risk of particle generation during machine dynamics.
• Protective airflow management – Maintains pressure differentials between differently graded environments implementing pressure and airflow cascades that prevent back‑flow contamination. Computational Fluid Dynamics (CFD) analysis and smoke testing demonstrate that protective airflows prevent contamination from upstream units to downstream units.
• Optimized cutting operations – The robotic de‑bagging process positions cutting operations away from critical transfer zones, preventing particle contamination toward downstream equipment. Specialized grippers ensure bags remain closed during cutting, preventing particles from entering and contaminating inner bags or tub exteriors.

Validation evidence

Validation activities performed by IMA Life engineering teams include CFD simulations confirming intended airflow features, smoke‑pattern testing demonstrating preservation of sterility classifications, and innovative docking‑port designs that allow airflow circulation without blockage while maintaining pressure cascades.

Productivity impact: up to 36,000 syringes per hour

The IMA Life INJECTA 36 system demonstrates that NTT implementation enhances productivity, achieving output rates of up to 36,000 nested syringes per hour. This high‑speed capability makes the system suitable for large‑scale production of generic injectables, vaccines and biologics while maintaining complete automation of critical transfer operations. The designed NTT system processes up to five RTU containers per minute, supporting high‑speed line requirements.

Real-world implementation

Active installations demonstrate consistent productivity achievements. INJECTA 36 units installed at Thermo Fisher facilities are designed to maintain specified production rates while ensuring sterility assurance. Multiple INJECTA 6 installations across sites such as Thermo Fisher Italy, MSD USA, Adienne Italy, Polfa SA Poland, Libbs Farmaceutica Brasil and Bayer Germany provide evidence of scalable productivity across different production volumes.

INJECTA 6 systems with NTT capabilities operate in facilities producing various product types, from traditional small molecules to advanced biologics and high‑containment applications. The technology has been successfully implemented for productions requiring different containment levels, including OEB 5 applications and BSL-2 bio-hazardous production sites.

NTT technology demonstrates broad compatibility with various RTU formats — vials, syringes and cartridges delivered in tubs and trays.

The system accommodates different container sizes and configurations through flexible robotic‑handling capabilities, supporting both standard production requirements and customized applications.

Conclusion

IMA Life NTT technology delivers three primary benefits that position it as essential for modern injectables manufacturing:

1. Enhanced sterility assurance ‑ Implementation of new robotic solutions significantly reduces risk of contamination during critical operation such as bag opening, and handling and transferring of RTU packaging.
2. Improved productivity – High‑speed automated operations handle up to 36,000 syringes per hour while maintaining complete process control and quality assurance.
3. High flexibility – Easy productivity scale‑up, able to adapt to different production needs and different types of RTU packaging and primary containers.

The technology proves particularly suitable for large‑scale pharmaceutical manufacturers and CDMOs managing medium and high‑volume production campaigns, facilities producing large‑scale drug products and companies transitioning from traditional bulk processing to RTU‑container systems.

Implementation timing favours early adoption, as regulatory trends increasingly emphasize automation and contamination control. The proven track record of IMA Life across multiple installations ‑ combined with ongoing enhancements in robotic capabilities and process integration ‑ provides confidence in long‑term value and total regulatory compliance.