GMP-Compliant Filling of Cryo Vials

CGT Manufacturing

Product Line

Cell and Gene Therapy

The Challenge

In Cell & Gene Therapy (CGT) manufacturing, tiny volumes are often processed under extreme time pressure and highest purity requirements. The status quo in many laboratories, however, is characterized by risky manual activities that can barely meet modern GMP standards.

Identified Pain Points & Risks:

Manual Variability: Filling is today predominantly performed manually by pipetting, leading to massive precision fluctuations. Coefficient variations (CV) of 5-10% are not uncommon – an unacceptable risk for high-potency CGT products with unit costs of several thousand euros per vial
Contamination Risk: Manual interventions in a conventional workbench or biosafety cabinet offer no optimal product protection. Every human interaction increases the risk of microbial contamination, which can lead to rejection of the entire patient batch in autologous therapies
Lack of Data Integrity: With manual processes, complete digital traceability (audit trail) is barely achievable. Handwritten protocols, retrospective corrections, and missing timestamps jeopardize data integrity according to ALCOA+ principles
Regulatory Compliance: Many customers have no option to perform the process in an isolator, which complicates regulatory approval and GMP compliance. FDA and EMA increasingly demand higher sterility assurance for CGT products
Scalability Issues: Manual processes are not scalable. With increasing patient volumes or commercial production after market approval, manual methods reach their limits
Skilled Labor Shortage: Highly qualified personnel for sterile work is difficult to find and expensive. Every manual process step binds valuable resources

The consequence: Delayed market launches, high rejection rates, compliance risks during regulatory inspections, and lack of competitiveness. An automated, sterile solution was urgently required.

Our Solution

The CRYO-Filler from Pharmabotix offers a highly flexible, robot-assisted alternative specifically developed for the requirements of sterile filling of small batches in Cell & Gene Therapy.

System Architecture & Components:

Precision Robotics: A 6-axis robot handles safe vial handling and guarantees smooth, contamination-free material flow. The repeatability of ±0.03mm ensures reproducible positioning even with small cryo vials
Modular Design: The system can be flexibly expanded with modules for opening, closing, filling, as well as scales and vision systems. Customers can start with a basic configuration and upgrade stepwise with increasing requirements
Environmental Protection: The CRYO-Filler can be operated either in a laminar flow cabinet (ISO 5) or for highest demands in an isolator (ISO 5 with cGMP Grade A environment). Isolator integration is via standardized RTP (Rapid Transfer Port) systems
Intelligent Control: Use of Siemens Unified Platform for intuitive operation and complete integration of the robot into the HMI. All robot functions are directly controllable via touch panel – without teach pendant

Technology Highlights:

Automatic Handling: Complete automation of pipetting and closing eliminates human error sources. The system works with precision dosing pumps that achieve CV values of <0.5%
Comprehensive Software: Integrated recipe management, order control, and real-time analysis of process data. Electronic Batch Records (eBR) are automatically generated and can be transferred directly to MES/LIMS
Closure Flexibility: Compatible with various primary packaging materials and formats – from 0.5 ml to 5 ml cryo vials with screw cap or crimp cap
Vision System: Optional camera recognition for vial inspection, fill level control, and identification of defective closures before cryostorage
Track & Trace: Each vial receives a unique barcode or DataMatrix code that is tracked throughout the entire process