Fusion AE. Analytical Method Development And Method Validation

Transcription

1 Analytical Method Development And Method Validation

2 Automated Experimentation Chemometric platform for analytical method development and 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. Full 21 CFR 11 Compliance Feature Set. S-Matrix Corporation:

3 History Early 1990 s Major Pharma Company Project: Sponsored by an International Top 5 Pharma company. Transform DOE output into HPLC methods and sequences Off-the the-shelf components: PC-controlled HPLC instrumentation Commercial CDS Commercial Design of Experiments (DOE) software Additional components: Software interface: DOE design (*.txt) HPLC (*.mth mth,, *.seq) Software control: accessory solvent valves Software control: column switching valve

4 History Initially (mid 1990 s) PE Nelson Turbochrom was chosen because the t 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 History How S-Matrix S improved the DOE-HPLC system! 1. Built a chromatography-specific DOE interface 2. Adapted DOE to HPLC instrument parameters 3. Automated data exchange with CDS 4. Expanded range of instruments and data systems 5. Created a full Method Validation experiment suite

6 Improved DOE / HPLC system by: 1. Built a chromatography-specific DOE interface 2. Adapted DOE to HPLC instrument parameters

7 Generic DOE Interface - Experiment Design

8 Chromatography-specific Interface - Experiment Design

9 Generic DOE Interface - Results Entry

10 Chromatography-specific Interface - Results Importing

11 Adapted DOE to HPLC Instrument Parameters

12 Improved DOE / HPLC system by: 3. Automated data exchange with CDS* 4. Expand the range of Instruments and data systems * - Joint development with S-Matrix S technology development partner Da Vinci Europe, a world leader in analytical instrument automation.

13 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 to-run.

14 Automated Experimentation Experiments run automatically on the CDS. Auto-analyzes results and creates reports that meet FDA and ICH guidelines. auto-imports all results. Output formats include RTF, DOC, HTML, and PDF.

15 Improve DOE / HPLC system by: 5. Created a full Method Validation experiment suite* * - Joint development with international pharmaceutical company sponsors.

16 Pharma-guided Development: Analytical Method Validation Filter Validation Accuracy Compares the response of the filtrate to that of a centrifuged or o other appropriate control - quantifies filtration effect on test samples in the response region of interest. 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 Repeatability The ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. Precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay assay precision.

17 Pharma-guided Development: Analytical Method Validation Sample Solution Stability Robustness Ruggedness Specificity Quantifies the solution stability of the drug substance or drug product after preparation according to the test method. 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. The degree of reproducibility of the same sample under a variety of conditions: analyst, column, equipment, lab, day, etc. 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.

18 Automated Experimentation 21 CFR 11 Compliance - 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. Platform independence - works with PerkinElmer TotalChrom, Waters Millennium 32 and Empower,, and Varian Galaxie (others coming in 2005). Simple documentation review - easy to defend and communicate. Standardized reporting - reports meet all FDA and ICH guidelines.

19 Benchmarking International Pharma Co. Benchmarking Project Realized Time Savings = 85%. Using historical records* and adjusting for project complexity Minimum Expected Time Savings per Project = 60%. % Time Spent per Method Validation Activity % Time Spent SPL Prep & Seq. Setup Data Analysis & Stats Research Report Creation No Automation Automation Activity * - on average 2.5 FTE equivalent years spent in method validation support work over 10 year life span of drug.