Moving analytical ultracentrifugation software to a good manufacturing practices (GMP) environment

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.

Analytical band centrifugation for the separation and quantification of empty and full AAV particles

“…Savelyev et al. 10 outlined challenges for potential good manufacturing practice validation of AUC methods and highlighted the need for auditable software for data acquisition, processing, and reporting.…”

“…External calibration references for scan velocity, temperature, radial magnification, and data acquisition elapsed time correction were demonstrated to further reduce method variability. Savelyev et al 10 outlined challenges for potential good manufacturing practice validation of AUC methods and highlighted the need for auditable software for data acquisition, processing, and reporting.…”

Best Practices for Aggregate Quantitation of Antibody Therapeutics by Sedimentation Velocity Analytical Ultracentrifugation

“…Quantitation of trace oligomers is challenging with g*(s) because of limitations intrinsic to its single-species origin and characteristic distortions, 49,50 despite later extrapolations and adjustments in the graphical output implemented in the software program ULTRA-SCAN. 51,52 At the same time, the g*(s) transform is a valuable tool to visualize sedimentation boundaries in the space of sedimentation coefficients as an intermediate inspection between raw data space (signal vs. radius and time) and the detailed c(s) analysis discussed below.…”

Reincarnation of the Analytical Ultracentrifuge: Emerging Opportunities for Nanomedicine

“…Though AUC is being represented by a relatively small research community, multilaboratory calibration accuracy and performance with external standards have been published, 82 as well as attempts reported to move it into a good manufacturing practice (GMP). 83 Another interesting development is that of rotor speed ramping conditions with the AUC. Such experiments bear great potential as particularly broadly distributed samples may be assessed over the covered fullsize range, as addressed in recent studies.…”