Transcript Analytical Method Validation

FusionChrom
Analytical Method Development
And Method Validation
FusionChrom
Automated
Experimentation

Chemometric platform for analytical method validation.

Auto-control of instrument parameters, external solvent
selection valves, and column switching.

Auto-construction and export of methods and sequences
to your Chromatography Data System (CDS).

Auto-importing of results from the CDS.

Automated analysis and reporting that meet all FDA & ICH
Guidelines.
S-Matrix Corporation: www.smatrix.com
History
FusionChrom
• Early 1990’s – Major Pharma Company Project:
• Sponsored by an International Top 5 Pharma company.
• Carried out by ControlChrom BV
• Transform DOE output into HPLC methods and sequences
• Off-the-shelf components:
• PC-controlled HPLC instrumentation
• Commercial CDS
• Commercial DOE software
• Additional components:
• Software interface: DOE design (*.txt)  HPLC (*.mth, *.seq)
• Software control: accessory solvent valves
• Software control: column switching valve
History
FusionChrom
• Initially (mid 1990’s) PE Nelson Turbochrom was chosen because the
development toolkit had documented HPLC instrument control
• Peltier column oven
• Mobile phase valves:
• More phases
• pH
• Buffer
• Modifier
• Column switcher
• Automated DOE-based HPLC experiments - from design to report complete success
FusionChrom
History
• How could this DOE/HPLC system be improved?
• Ease of use = deeper integration
• Chromatography specific DOE interface
• Wizards for DOE design selection
• Adapt DOE to HPLC instrument parameters
• Create a method validation experiment suite
• Automate data exchange with CDS
• Expanded range of instruments and CDS
• Improvement requires a partnership:
• Chromatography/automation expert
• DOE expert
FusionChrom
• S-Matrix Corporation
• Validated DOE software in Pharmaceutical
usage
• Major Pharma customer sponsoring new
development
• Looking at new opportunities to expand DOE
applications
• Da Vinci Europe (ControlChrom BV)
• Specialists in software development for
chromatography systems (CDS)
• Partnerships with leading HPLC and CDS
companies
• Validated software in Pharmaceutical usage
• Looking to improve DOE prototype
FusionChrom
Automated
Experimentation
E-lab notebook
Interface for fast, easy
experiment setup
with correct planning
built in.
Automatically builds,
designs and exports
experiments to the
CDS as ready-to-run.
FusionChrom
Automated
Experimentation
E-lab notebook
Interface for fast, easy
experiment setup
with correct planning
built in.
Auto-analyzes
results and creates
reports that meet
FDA and ICH
guidelines.
Output formats
include RTF, DOC,
HTML, and PDF.
Experiments
run automatically
on the CDS.
FusionChrom
auto-imports all
results.
Automatically builds,
designs and exports
experiments to the
CDS as ready-to-run.
Pharma-guided Development:
FusionChrom
Analytical Method Validation
• Filter Validation
– Compares the response of the filtrate to that of a centrifuged or
other appropriate control - quantifies filtration effect on test
samples in the response region of interest.
• Accuracy
– The closeness of agreement between the value which is accepted
either as a conventional true value or an accepted reference value
and the value found.
• Linearity and Range
– The ability (within a given range) to obtain test results which are
directly proportional to the concentration (amount) of analyte in the
sample.
• Repeatability
– Precision under the same operating conditions over a short interval
of time. Repeatability is also termed intra-assay precision.
Pharma-guided Development:
FusionChrom
Analytical Method Validation
• Sample Solution Stability
– Quantifies the solution stability of the drug substance or drug
product after preparation according to the test method.
• Robustness (requires method development technology)
– The system's capacity to remain unaffected by small, but deliberate
variations in method parameters and provides an indication of its
reliability during normal usage.
• Ruggedness
– The degree of reproducibility of the same sample under a variety of
conditions: analyst, column, equipment, lab, day, etc.
• Specificity
– The ability to assess unequivocally the analyte in the presence of
components which may be expected to be present. Typically these
might include impurities, degradants, matrix, etc.
Unsurpassed Proven Value:
FusionChrom
% Time Spent per Method Validation Activity
50
40
% Time 30
Spent 20
No Automation
10
Automation
0
SPL Prep Data Research
& Seq. Analysis & Report
Setup
Stats
Creation
Activity
1. 2.5 FTE Years method validation (MV) effort per Project Life.
2. MV cost per project = $625,000.
3. Therefore, per project:

Minimum time saved using FusionChrom = 60%.

Minimum dollars saved using FusionChrom = $375,000.
Automated Experimentation
FusionChrom
 21 CFR 11 Compliant - compliance features include full audit trail,
e-signing Permissions/Authorities, and work flow administration.
 Automation - allows for easy tracking of aberrant data. Reduces the
need for costly Analysis Lab Investigation Reports (ALIRs).
 Easy setup of DOE-based experiments - tremendously facilitates
rigorous practice.
 Method Connectivity – early methods developed using other tools
can be optimized and/or validated using FusionChrom.
 Platform independence - works with PerkinElmer TotalChrom,
Waters Millennium32 and Empower, and Varian Galaxie
(and others in 2004).
 Simple documentation review - easy to defend and communicate.
 Standardized reporting - reports meet all FDA and ICH guidelines.