Fusion Chrom Analytical Method Development And Method Validation

Fusion. Chrom Analytical Method Development And Method Validation

Fusion. Chrom Automated Experimentation Ø Chemometric platform for analytical method validation. Ø Auto-control of instrument parameters, external solvent selection valves, and column switching. Ø Auto-construction and export of methods and sequences to your Chromatography Data System (CDS). Ø Auto-importing of results from the CDS. Ø Automated analysis and reporting that meet all FDA & ICH Guidelines. S-Matrix Corporation: www. smatrix. com

History Fusion. Chrom • Early 1990’s – Major Pharma Company Project: • • • Sponsored by an International Top 5 Pharma company. Carried out by Control. Chrom 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 Fusion. Chrom • 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 • p. H • Buffer • Modifier • Column switcher • Automated DOE-based HPLC experiments - from design to report complete success

History Fusion. Chrom • 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

Fusion. Chrom • 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 (Control. Chrom 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

Fusion. Chrom 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.

Fusion. Chrom 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. Fusion. Chrom auto-imports all results. Automatically builds, designs and exports experiments to the CDS as ready-to-run.

Pharma-guided Development: Fusion. Chrom 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: Fusion. Chrom 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 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: Fusion. Chrom 1. 2. 5 FTE Years method validation (MV) effort per Project Life. 2. MV cost per project = $625, 000. 3. Therefore, per project: Ø Minimum time saved using Fusion. Chrom = 60%. Ø Minimum dollars saved using Fusion. Chrom = $375, 000.

Automated Experimentation Fusion. Chrom Ø 21 CFR 11 Compliant - compliance features include full audit trail, e-signing Permissions/Authorities, and work flow administration. Ø Automation - allows for easy tracking of aberrant data. Reduces the need for costly Analysis Lab Investigation Reports (ALIRs). Ø Easy setup of DOE-based experiments - tremendously facilitates rigorous practice. Ø Method Connectivity – early methods developed using other tools can be optimized and/or validated using Fusion. Chrom. Ø Platform independence - works with Perkin. Elmer Total. Chrom , Waters Millennium 32 and Empower, and Varian Galaxie (and others in 2004). Ø Simple documentation review - easy to defend and communicate. Ø Standardized reporting - reports meet all FDA and ICH guidelines.