PSS AccuSizer A2000 SIS CETAC Insoluble Particle Analyzer

Overview

The PSS AccuSizer A2000 SIS CETAC Insoluble Particle Analyzer is a high-precision, regulatory-compliant instrument engineered for quantitative characterization of insoluble particulate matter in parenteral drug products and biologics. It employs Single Particle Optical Sensing (SPOS) technology—specifically, light obscuration (LO)—to detect, size, and count individual particles as they pass through a precisely defined optical sensing zone. Unlike ensemble techniques such as laser diffraction (LD), which report volume-weighted distributions based on theoretical scattering models, SPOS delivers true number-based particle size distribution (PSD) with exceptional resolution at the micro- and sub-micron scale. The system achieves a validated detection range of 0.5 µm to 400 µm, enabling compliance with current pharmacopoeial standards—including USP , , , , Chinese Pharmacopoeia (ChP) 0903, European Pharmacopoeia (EP), Japanese Pharmacopoeia (JP), AAMI TIR42, and WHO QAS/11.405 5.7.1—while providing forward compatibility for emerging regulatory expectations targeting sub-10 µm particles.

Key Features

• Single-particle resolution via light obscuration with 1024 data channels and 32 user-definable channels, delivering ultra-high-resolution PSDs with ≤0.01 µm bin width fidelity.
• Validated minimum sample volume of 50 µL—fully compliant with USP volumetric precision requirements—with RSD ≤2.4% across 50–650 µL injection volumes.
• Particle counting sensitivity down to 10 parts per trillion (PPT), enabling reliable detection of trace-level large particles critical for safety assessment.
• Modular architecture supporting seamless integration of CETAC automated liquid handling systems (up to dual 96-well plate capacity) and APS automatic dilution modules for complex matrices including lipid emulsions and viscous formulations.
• LE-series optical sensors designed for rapid field replacement, minimizing downtime and supporting sensor calibration traceability to NIST-traceable PSL standards.
• Robust fluidic control with flow rate accuracy ≥98% (5–120 mL/min), particle counting accuracy ≥97.5%, and volumetric accuracy ≥99%.

Sample Compatibility & Compliance

The AccuSizer A2000 accommodates a broad spectrum of pharmaceutical dosage forms, including small-volume injectables (SVIs), large-volume parenterals (LVPs), monoclonal antibody (mAb) formulations, liposomal suspensions, and nanosuspensions. Its modular inlet configuration supports direct syringe aspiration, low-volume capillary sampling, and high-throughput 96-well plate analysis. All hardware and software components are designed and verified in accordance with cGMP principles and FDA 21 CFR Part 11 requirements for electronic records and signatures. Full audit trail functionality—recording all user actions (login/logout, method edits, data exports, report generation, firmware updates) with time stamps, operator ID, and event type—is exportable in CSV or PDF format for regulatory inspection. The system satisfies CSV (Computer System Validation) readiness through granular 22-tier permission management, role-based access control, and enforced electronic signature workflows.

Software & Data Management

The AccuSizer® Workstation is a validated, 21 CFR Part 11-compliant software platform built on Windows OS (7 or later). It provides end-to-end lifecycle data integrity: instrument control, real-time data acquisition, statistical analysis (including %RSD, mean, median, mode, cumulative counts), automated report generation against configurable pharmacopoeial templates (e.g., “Pass/Fail” determination per USP limits), and secure database archiving. Data backup policies support scheduled local storage, network drive synchronization, and LIMS integration. Electronic signatures adhere to ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, Available), with cryptographic hashing ensuring immutability. All raw sensor signals, processed histograms, and metadata are retained in native binary format for full reprocessing capability—essential for root cause investigations and regulatory audits.

Applications

• Quality control testing of sterile injectables per ChP 0903, USP , and EP 2.9.19.
• R&D stability studies tracking sub-visible particle growth under thermal, mechanical, or oxidative stress.
• Process development support for filtration validation, container closure integrity assessment, and leachables evaluation.
• Characterization of lipid nanoparticles (LNPs), protein aggregates, and colloidal dispersions where tail-end large particles impact immunogenicity or infusion safety.
• Root cause analysis of batch failures—leveraging high-resolution PSDs to distinguish between process-induced vs. container-related particulates.
• Regulatory submission support with fully traceable, auditable datasets meeting ICH Q5A(R2), Q5C, and FDA guidance on particulate matter in injectables.

FAQ

What regulatory standards does the AccuSizer A2000 comply with?
It meets USP , , , ; ChP 0903; EP 2.9.19; JP 6.07; AAMI TIR42; and WHO QAS/11.405 5.7.1—and is fully aligned with FDA 21 CFR Part 11 and cGMP data integrity expectations.
Can the system analyze highly concentrated or viscous samples?
Yes—when equipped with the optional APS automatic dilution module, it handles undiluted lipid emulsions and high-viscosity biologics without manual intervention or dilution error.
How does SPOS differ from laser diffraction for sub-visible particle analysis?
SPOS counts and sizes each particle individually, yielding number-weighted distributions with superior sensitivity to rare large particles (>5 µm); LD reports volume-weighted averages and lacks resolution below ~1 µm, often masking critical tail-end events.
Is the 50 µL minimum injection volume validated across all sensor configurations?
Yes—this specification is certified for the LE sensor with integrated micro-sampling pump and calibrated syringe drive, with full traceability to ISO/IEC 17025-accredited verification protocols.
Does the software support multi-user environments with audit-ready permissions?
Yes—the workstation implements 22 discrete permission tiers, supports concurrent login sessions, enforces password complexity policies, logs all administrative actions, and permits role-specific report customization and database access controls.