FusionChrom 

1. FusionChrom Analytical Method Development And Method Validation

2. AutomatedExperimentation FusionChrom • 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

3. FusionChrom History • Off-the-shelf components: • PC-controlled HPLC instrumentation • Commercial CDS • Commercial DOE software • 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 • Additional components: • Software interface: DOE design (*.txt)  HPLC (*.mth, *.seq) • Software control: accessory solvent valves • Software control: column switching valve

4. FusionChrom History • 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

5. 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

6. S-Matrix Corporation Validated DOE software in Pharmaceutical usage Major Pharma customer sponsoring new development Looking at new opportunities to expand DOE applications FusionChrom • 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

7. AutomatedExperimentation FusionChrom 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.

8. AutomatedExperimentation FusionChrom 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. 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.

9. FusionChrom Pharma-guided Development: 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.

10. FusionChrom Pharma-guided Development: Analytical Method Validation • 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. • Sample Solution Stability • Quantifies the solution stability of the drug substance or drug product after preparation according to the test method. • 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.

11. FusionChrom Unsurpassed Proven Value: 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.

12. 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.