APR March 2024 - 22
» FORMULATION AND DEVELOPMENT
»
resulted in the decision that SEDFIT/GUSSI use was the preferred route
to establish AUC as a GMP analysis at our laboratory. In September
2023 the NIH group leading the development of SEDFIT came up with
a solution to address the lack of GMP compliance of their software,
introducing a command line
configuration of SEDFIT, data loading and retrieval of results.18
interface that permits automated
By that
time, we had already established a pathway to surround SEDFIT with
a GMP environment that did not require programming in a secondary
software (e.g., MATLAB from MathWorks).
3. SEDFIT and GUSSI - Use within GMP
SEDFIT and GUSSI are both open source, non-commercial, and
community-supported software packages (i.e., there is no vendor/
company ownership).
When using software without vendor ownership, there may be a lack
of accountability and responsibility for the software's performance and
reliability. Partial mitigation of this risk was achieved by downloading
SEDFIT and GUSSI software specifically from https://sedfitsedphat.
github.io/ and https://www.utsouthwestern.edu/research/corefacilities/mbr/software/,
respectively (current available versions).
Apart from this, further risk mitigation was achieved through version
control of this software that is installed on the processing PC, and
this version control process will be described within our standard
operating procedure for this system. Since both software have no
login credentials, Microsoft Active Directory groups were created to
limit the access. The risk associated with the lack of different access
levels and role-based controls in both software was mitigated by using
an event log with Microsoft Event Viewer for each software, which
adds an entry every time a user opens each program on its respective
event log, documenting users who accessed the software and when.
Appropriate use of the software and settings employed is controlled
through screenshots assembled in a Word document that is printed
as a pdf to a data vault. This also allows 100% secondary review of the
analysis and the raw data within our GMP lab.
Calculations in the SEDFIT software are highly complex and cannot
be independently verified. The risk associated with the inability to
independently verify SEDFIT software calculations cannot be fully
mitigated but is justifiable as outlined below.
GUSSI allows the sedimentation distribution plot data to be exported
as a .dat file, which can be read into Excel to re-create the plots but
Excel cannot reproduce the area under the curve results. The .dat
file format could be converted into a .cdf file for import into Water's
Empower software, which is able to confirm area under the curve
calculations, but the conversion of .dat files to .cdf files would have
to employ an uncontrolled open-source conversion program from the
web, which is not a desirable pathway in a regulated environment.
Therefore, the relative concentration of the different species (area
under the curve) and the sedimentation coefficient for each species
calculated by GUSSI can also not be independently verified, posing an
additional quality risk.
We concluded that there is negligible risk associated with the use of
the processing applications associated with the AUC implementation
22 |
| March 2024
under GMP for which the calculations cannot be independently
verified. The following literature research is provided in support of
this assessment:
Garcia de la Torre, et al (2018)19
published an article on the development
of prediction software for the analysis analytical ultracentrifugation
experiments in which the goodness of the prediction software was
assessed by the results' proximity to the experimental results obtained
using SEDFIT. While this assessment was performed using SEDFIT
version 15.01b of 2015, we operate SEDFIT version 16.1-c of 2019,
which can reasonably be considered an improved version. If there
would be any doubt on the accuracy and precision of the SEDFIT
results, it can be expected that a different analysis software would be
employed for the prediction software assessment.
According to an article entitled " Reincarnation of the Analytical
Ultracentrifuge: Emerging Opportunities for Nanomedicine, " 20
SEDFIT
and recently intensively developed UltraScan are some of the most
popular software for data analysis. While popularity is not a measure
of precision and accuracy of a software, it is unlikely the scientific
community would stick with a software that could lead to false results.
In a recent study performed in Japan,21
SEDFIT and GUSSI were
employed to determine empty and full capsid ratios of different AAV
serotypes and compare results to those obtained based on A260 nm /
A280 nm absorbance ratios. Such a study would be meaningless if the
SEDFIT/GUSSI data could not be considered reliable.
In a commentary published by the NIH and the University of Texas
Southwestern Medical Center22
to supplement previous AUC
protocols, the authors recommend the SEDFIT software for the
analysis of AUC data.
With these appropriate controls in place at PPD Laboratory services,
the FDA has allowed one of our clients to use the Optima AUC with
SEDFIT and GUSSI to perform one of the GMP release tests for their
commercialized drug product. Several other companies are evaluating
AUC/SEDFIT use for AAV analyses, such as Genzyme,23
AstraZeneca,24
and Adverum (ACS Webinar on 20Sep2022). Genzyme Corporation
filed a patent application for the use of AUC in the characterization of
recombinant viral particles that included the use of SEDFIT.25
During the past year, our experience with the SEDFIT and GUSSI has
been a fairly consistent end result for determining sedimentation
coefficients of species and their continuous distribution plots (SEDFIT)
as well as the final percent empty, partially filled and full capsids
results determined by GUSSI, despite visual differences seen in the
distribution plots. This supports the robustness of the software in
determining the reportable results although the calculations cannot
be independently confirmed.
Furthermore, Edwards et al.13 found that analysis using analogous
UltraScan III or SEDFIT approaches results in nearly identical
descriptions of the sedimenting systems. While we cannot verify
calculations used in the processing applications (SEDFIT and GUSSI)
associated with AUC, the consensus in the scientific community
supports that the calculations are reliable.
https://sedfitsedphat.github.io/
https://www.utsouthwestern.edu/research/core-facilities/mbr/software/
https://www.utsouthwestern.edu/research/core-facilities/mbr/software/
APR March 2024
Table of Contents for the Digital Edition of APR March 2024
Message from the Editor
Editorial Advisory Board
BIOPHARMACEUTICALS - Getting to GMP-Quality Biotherapeutics From Today’s Bench-Scale Continuous Manufacturing Systems: A Gap Analysis
MICROBIOLOGY - Critical Behavioral Attributes and the Application of COM-B Framework in Aseptic Processing
FORMULATION AND DEVELOPMENT - Use of AUC in AAV Analysis in a GMP Setting
FORMULATION AND DEVELOPMENT - Precision Medicine in Clinical Trials: A Statistical Perspective
An Interview with Dan Smithey, PhD President & CEO, Serán
FORMULATION AND DEVELOPMENT - Still Early Days for AI in Drug Discovery...Says Who?
QC Corner - Enhancing Material and Equipment Availability in Production Isolators
BIOPHARMACEUTICALS - Technologies for Aseptic Filling: The Choice is Clear
Vendor Viewpoint - Data Integrity and Rapid Micro Methods: Transforming to a Modern Microbiology Lab
MICROBIOLOGY - Bacterial Spore Formers in Disinfectant Efficacy Testing
Partner Perspective - Nanoparticle Technologies: Enablers for Ocular Drug Delivery
DRUG DELIVERY - Your Nails and You
DRUG DEVELOPMENT - Battling Exorbitance: High Costs in Sickle Cell Gene Therapies and the Imperative of Global Patient Registries for Equity
FORMULATION AND DEVELOPMENT - How Pharma Companies Are Solving Regulatory Challenges with AI-based Technology
Event Preview - CPHI North America
Event Preview - Excipient World 2024
P.I.N. Points
Advertiser's Index
APR March 2024 - CoverTip01
APR March 2024 - CoverTip02
APR March 2024 - Cover1
APR March 2024 - Cover2
APR March 2024 - 1
APR March 2024 - 2
APR March 2024 - 3
APR March 2024 - 4
APR March 2024 - 5
APR March 2024 - Message from the Editor
APR March 2024 - Editorial Advisory Board
APR March 2024 - BIOPHARMACEUTICALS - Getting to GMP-Quality Biotherapeutics From Today’s Bench-Scale Continuous Manufacturing Systems: A Gap Analysis
APR March 2024 - 9
APR March 2024 - 10
APR March 2024 - 11
APR March 2024 - 12
APR March 2024 - 13
APR March 2024 - MICROBIOLOGY - Critical Behavioral Attributes and the Application of COM-B Framework in Aseptic Processing
APR March 2024 - 15
APR March 2024 - 16
APR March 2024 - 17
APR March 2024 - 18
APR March 2024 - FORMULATION AND DEVELOPMENT - Use of AUC in AAV Analysis in a GMP Setting
APR March 2024 - 20
APR March 2024 - 21
APR March 2024 - 22
APR March 2024 - 23
APR March 2024 - FORMULATION AND DEVELOPMENT - Precision Medicine in Clinical Trials: A Statistical Perspective
APR March 2024 - 25
APR March 2024 - 26
APR March 2024 - 27
APR March 2024 - An Interview with Dan Smithey, PhD President & CEO, Serán
APR March 2024 - 29
APR March 2024 - 30
APR March 2024 - FORMULATION AND DEVELOPMENT - Still Early Days for AI in Drug Discovery...Says Who?
APR March 2024 - 32
APR March 2024 - 33
APR March 2024 - QC Corner - Enhancing Material and Equipment Availability in Production Isolators
APR March 2024 - 35
APR March 2024 - BIOPHARMACEUTICALS - Technologies for Aseptic Filling: The Choice is Clear
APR March 2024 - 37
APR March 2024 - 38
APR March 2024 - 39
APR March 2024 - Vendor Viewpoint - Data Integrity and Rapid Micro Methods: Transforming to a Modern Microbiology Lab
APR March 2024 - 41
APR March 2024 - MICROBIOLOGY - Bacterial Spore Formers in Disinfectant Efficacy Testing
APR March 2024 - 43
APR March 2024 - Partner Perspective - Nanoparticle Technologies: Enablers for Ocular Drug Delivery
APR March 2024 - 45
APR March 2024 - 46
APR March 2024 - 47
APR March 2024 - DRUG DELIVERY - Your Nails and You
APR March 2024 - 49
APR March 2024 - 50
APR March 2024 - 51
APR March 2024 - DRUG DEVELOPMENT - Battling Exorbitance: High Costs in Sickle Cell Gene Therapies and the Imperative of Global Patient Registries for Equity
APR March 2024 - 53
APR March 2024 - 54
APR March 2024 - 55
APR March 2024 - FORMULATION AND DEVELOPMENT - How Pharma Companies Are Solving Regulatory Challenges with AI-based Technology
APR March 2024 - 57
APR March 2024 - Event Preview - CPHI North America
APR March 2024 - 59
APR March 2024 - Event Preview - Excipient World 2024
APR March 2024 - 61
APR March 2024 - P.I.N. Points
APR March 2024 - 63
APR March 2024 - Advertiser's Index
APR March 2024 - Cover3
APR March 2024 - Cover4
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