Thermo Scientific inSITE Integrity Testing System

Overview

The Thermo Scientific™ inSITE™ Integrity Testing System is an engineered solution for non-destructive, real-time integrity verification of single-use bioprocessing containers (BPCs) across the entire handling and operational lifecycle—from warehouse storage through cleanroom deployment and up to final liquid fill. Based on differential pressure decay and controlled pressurization principles, the inSITE system quantitatively evaluates container and connection integrity by monitoring pressure differentials over defined time intervals under rigorously controlled conditions. It operates within the framework of current Good Manufacturing Practice (cGMP) and supports compliance with ISO 13408-2 (sterile processing of pharmaceutical products) and ASTM F2096 (bubble emission test standard), enabling objective, auditable evidence of system readiness prior to critical process steps.

Key Features

• Multi-channel integrity testing: Simultaneous evaluation of up to five BPCs (including configurations up to 5,000 L capacity), reducing batch release cycle time and supporting parallel process validation.
• Two-tiered leakage detection: Discriminates between gross (total) leaks (detectable down to ~100–1,000 µm equivalent orifice size) and micro-leaks (sub-micron sensitivity achievable via extended dwell-time protocols), each calibrated against traceable reference standards.
• Guided validation setup: Onboard wizard-driven configuration ensures consistent parameter selection (e.g., target pressure, hold duration, acceptance thresholds), minimizing operator-dependent variability and supporting IQ/OQ documentation requirements.
• Integrated inflation cycle: Automates controlled gas introduction to precondition BPCs—optimizing bag geometry, confirming proper mounting on support frames, and verifying valve alignment prior to integrity assessment.
• Fill-cycle pressure modulation: Dynamically regulates internal pressure during liquid introduction using coordinated control of coaxial valves, preventing over-pressurization, minimizing stress on weld seams, and maintaining structural stability throughout filling.
• Dual-sensor pressure comparison: Employs both sterilizable stainless-steel pressure transducers and single-use disposable sensors mounted directly on BPC ports, enabling cross-validated pressure readings and eliminating drift-related uncertainty.

Sample Compatibility & Compliance

The inSITE system is validated for use with standard single-use assemblies including 2D and 3D polyethylene (PE), ethylene vinyl acetate (EVA), and multi-layer films from major suppliers (e.g., Sartorius, Pall, GE Healthcare/Cytiva, Merck Millipore). It accommodates common BPC configurations: mixing bags, storage bags, harvest bags, and fluid management systems with integrated filters, connectors, and tubing manifolds. All hardware interfaces meet ISO 2852 (clamp-type aseptic connections) and ASME BPE-2022 surface finish requirements (Ra ≤ 0.8 µm). The system architecture supports 21 CFR Part 11-compliant electronic records and signatures when deployed with Thermo Scientific SampleManager LIMS or compatible third-party platforms, fulfilling GLP/GMP audit trail and data integrity mandates.

Software & Data Management

Controlled via Thermo Scientific inSITE Software v3.x (Windows-based), the system provides role-based user access, configurable electronic batch records (EBRs), and automated PDF report generation compliant with ALCOA+ principles. Audit trails record all parameter changes, test initiations, pass/fail decisions, and sensor calibrations with immutable timestamps and operator IDs. Raw pressure vs. time datasets are stored in HDF5 format for traceability and post-hoc reanalysis. Export options include CSV, XML, and direct integration with MES/SCADA systems via OPC UA protocol. Firmware updates follow IEC 62304 Class B software lifecycle standards, with full revision history and change control documentation available upon request.

Applications

• Pre-use integrity verification of BPCs following transportation, storage, and cleanroom installation
• Post-sterilization integrity confirmation after gamma or E-beam irradiation
• In-process monitoring during media preparation, buffer transfer, and cell culture expansion
• Final container qualification prior to aseptic filling operations
• Troubleshooting suspected leaks during troubleshooting campaigns (e.g., after abnormal pressure events or visual inspection anomalies)
• Supporting regulatory submissions requiring documented integrity assurance for single-use technologies (e.g., FDA BLA, EMA MAA)

FAQ

Can the inSITE system be integrated into existing automation infrastructure?
Yes—it supports Modbus TCP and OPC UA communication protocols for seamless integration with PLCs, SCADA systems, and manufacturing execution systems (MES). Hardware I/O modules provide discrete signals for pass/fail status, cycle completion, and fault conditions.
Is calibration traceable to NIST standards?
All pressure transducers ship with individual calibration certificates traceable to NIST or equivalent national metrology institutes (e.g., PTB, NPL), with recalibration intervals defined per ISO/IEC 17025 and documented in the system’s calibration management module.
Does the system support environmental temperature and humidity compensation?
Yes—integrated ambient sensors automatically adjust decay rate calculations based on real-time lab conditions, ensuring consistent sensitivity across varying cleanroom environments (ISO Class 5–8).
What training and qualification support is provided?
Thermo Scientific offers factory-authorized IQ/OQ/PQ protocol templates, on-site installation qualification, and operator competency assessments aligned with Annex 1 and USP guidance documents.
How is data security maintained during remote diagnostics?
Remote access utilizes TLS 1.2–encrypted VNC sessions with two-factor authentication; no data exfiltration occurs without explicit user consent and audit-log recording.