Abstract
Recent advances in instrumentation have moved analytical ultracentrifugation (AUC) closer to a possible validation in a Good Manufacturing Practices (GMP) environment. In order for AUC to be validated for a GMP environment, stringent requirements need to be satisfied; analysis procedures must be evaluated for consistency and reproducibility, and GMP capable data acquisition software needs to be developed and validated. These requirements extend to multiple regulatory aspects, covering documentation of instrument hardware functionality, data handling and software for data acquisition and data analysis, process control, audit trails and automation. Here we review the requirements for GMP validation of data acquisition software and illustrate software solutions based on UltraScan that address these requirements as far as they relate to the operation and data handling in conjunction with the latest analytical ultracentrifuge, the Optima AUC by Beckman Coulter. The software targets the needs of regulatory agencies, where AUC plays a critical role in the solution-based characterization of biopolymers and macromolecular assemblies. Biopharmaceutical and regulatory agencies rely heavily on this technique for characterizations of pharmaceutical formulations, biosimilars, injectables, nanoparticles, and other soluble therapeutics. Because of its resolving power, AUC is a favorite application, despite the current lack of GMP validation. We believe that recent advances in standards, hardware, and software presented in this work manage to bridge this gap and allow AUC to be routinely used in a GMP environment. AUC has great potential to provide more detailed information, at higher resolution, and with greater confidence than other analytical techniques, and our software satisfies an urgent need for AUC operation in the GMP environment. The software, including documentation, are publicly available for free download from Github. The multi-platform software is licensed by the LGPL v.3 open source license and supports Windows, Mac and Linux platforms. Installation instructions and a mailing list are available from ultrascan.aucsolutions.com.
Highlights
Analytical ultracentrifugation (AUC) is a nearly one hundred year old technique for the solution characterization of colloidal molecules
AUC aids in the development of formulations by monitoring forced degradation studies to quantify the amount of aggregates, with quality control, research and development of novel therapeutics, and characterization of interactions between biopolymers in pharmacological applications [7]
As it is accepted procedure to periodically test the validation of other Good Manufacturing Practices (GMP) methods like high performance liquid chromatography (HPLC) by measuring an appropriate standard, the same procedure can be used for AUC as well
Summary
Analytical ultracentrifugation (AUC) is a nearly one hundred year old technique for the solution characterization of colloidal molecules. Consistent and reproducible routine AUC analysis can be achieved by implementing appropriate workflow validation, instrument diagnostics, and greater automation in the data acquisition and analysis processes This ability is greatly aided by the arrival of the new Optima AUC analytical ultracentrifuge from Beckman Coulter (Optima), which features important upgrades that provide much higher data quality and density, and contemporary technology and design choices that greatly facilitate the operation of the analytical ultracentrifuge in an automated GMP environment. A significant challenge for analytical ultracentrifugation performed in a GMP environment is that the operation of the analytical ultracentrifuge involves multiple hardware components that are responsible for experimental observables and parameters that directly affect analysis results Included in this list are rotor speed, recorded time and centrifugal force integrals, temperature, radial calibration, light intensity, optical alignment and focus, chromatic aberration, and stretching or contraction of the rotor in response to rotor speed changes. The UltraScan timestate object can be examined in a graphical user interface to assure accuracy (see S1 Fig)
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