Modern business drivers are continually pushing to reduce the time it takes to get a product or service to market, reduce the risk and cost associated with that, and to improve quality. In laboratories, delivering an analytical result thats right first time (RFT) is the answer. There is no reprocessing data or re-running injections and no out of specification (OOS) results or reporting/calculation errors. Getting RFT analysis automatically gives high quality of results and confidence in results, lower cost of analysis, improved lab efficiency, and faster release to market and return on investment (ROI).
<ul><li> 1 The world leader in serving science Darren Barrington-Light Product Specialist, Chromatography Software, Thermo Fisher Scientific April 1, 2014 Getting It Right First Time Seminar Series Part 2 Part #: PP71261-EN0414S </li> <li> 2 Agenda Introduction How to get it right the first time? Thermo Scientific Dionex Chromeleon Chromatography Data System (CDS) tools for RFT analysis Standard Operating Procedures eWorkflows What they are, how they help and how you use them Example: Chromeleon Extension Pack - Dissolution Templates Summary </li> <li> 3 Introduction Modern business drivers are continually pushing to reduce the time it takes to get a product or service to market, reduce the risk and cost associated with that, and to improve quality In laboratories, delivering an analytical result thats right first time (RFT) is the answer No reprocessing data or re-running injections No out of specification (OOS) results or reporting/calculation errors Getting RFT analysis automatically gives: High quality of results and confidence in results Lower cost of analysis Improved lab efficiency Faster release to market and return on investment (ROI) </li> <li> 4 How to Get It Right the First Time? </li> <li> 5 How to Get It Right the First Time? Robust and reliable instrumentation Qualification automation Monitor instrument status Robust, reproducible, and reliable methodology Standard operating procedures Method validation Automated sequence creation Run-time checks In-run reactions to actual chromatographic results Automated result calculation and export Operators Make learning curve as shallow as possible Provide tools to help inexperienced users with more complex tasks </li> <li> 6 Chromeleon CDS Tools for RFT Analysis </li> <li> 7 Chromeleon CDS Tools for RFT Analysis Instrumentation Predictive performance instrument qualification, service and wear part monitors Methodology ICH Method Validation Templates eWorkflows Sequence Ready Check Smart Startup System Suitability Tests with Intelligent Run Control Spreadsheet-based Report Designer with integral Report Check Operators All the above combine to ensure ANY operator can achieve RFT analysis </li> <li> 8 Standard Operating Procedures </li> <li> 9 Standard Operating Procedures What is a Standard Operating Procedure (SOP)? The International Conference on Harmonisation (ICH) defines SOPs as detailed, written instructions to achieve uniformity of the performance of a specific function or A document describing all steps and activities of a procedure that can be followed to attain a specific outcome </li> <li> 10 Standard Operating Procedures Sample check-in Sample preparation Instrument preparation Eluent preparation Sample analysis conditions Data analysis conditions Data reporting requirements Regulatory requirements Validation requirements Customer report requirements </li> <li> 11 Standard Operating Procedures So how do we help the analyst? </li> <li> 12 Standard Operating Procedures In laboratories, SOPs are used: To ensure an analysis is always performed the same way no matter who performs it To provide a step-by-step guide to analysts To ensure compliance To guarantee a specific outcome for an analysis </li> <li> 13 Lets Look at an Example </li> <li> 14 Dissolution Testing Used for immediate release dosage forms to: Assess the lot-to-lot quality of a drug product Guide development of new formulations Ensure continuing product quality and performance All pharmacopeias provide details on how to perform dissolution experiments United States Pharmacopeia 28, Chapter 711, Dissolution Test, 2005. European Pharmacopoeia 6.1, Chapter 2.9.3 Dissolution Test for Solid Dosage Forms, 2008. Japanese Pharmacopoeia 15th Edition, 6.10 Dissolution Test, 2007. British Pharmacopoeia 2014, Volume 5, Appendix 336, Dissolution, 2014 Cover procedures/apparatus for running experiments and for assessing the data </li> <li> 15 Dissolution Testing Dissolution experiments can use one of 7 methods: Method used depends on dosage form Paddle apparatus is most common for solid dosage forms Analyze a minimum of 6 separate dosage units </li> <li> 16 Dissolution Testing At the end of the time period, withdraw an aliquot of the fluid and perform the analysis using a suitable assay method. Suitable assay method: Sample analysis Instrumental conditions Injection requirements Data analysis Processing requirements Reporting requirements </li> <li> 17 Dissolution Testing Sample Analysis Example instrument conditions: Column temperature: 30 C Mobile phase: Solvent A (acetonitrile) and solvent B (water) 50:50 Flow rate: 1.0 mL/min Injection volume: 10 L Detection wavelength: 254 nm Running time: 20 min All controlled by the Instrument Method </li> <li> 18 Dissolution Testing Sample Analysis Example injection requirements: Assay 6 or 12 units individually A set of 6 check standard preparations should be analyzed to ensure system suitability Make single injections of all of the standard preparations Make single injections of sample preparations To monitor method variance, a control sample of known composition should be assayed at the end of each batch All controlled by the sequence structure </li> <li> 19 Dissolution Testing Data Analysis Example processing requirements: Accurately identify and integrate each component Prepare a linearity curve for the standards with the origin ignored, using peak area vs. concentration (mg/mL). The r2 must be 0.999 for each calibration curve. The Tailing Factor, Theoretical Plates, and %RSD should be calculated for the main analyte in the SST samples Controlled by the Processing Method </li> <li> 20 Dissolution Testing Data Analysis Reporting requirements (solid dosage forms): Average of the 12 (S1+S2) units is Q and no unit is less than Q 15% </li> <li> 21 Dissolution Testing Data Analysis Example other reporting requirements: The standard correlation should be calculated for the first and last standard of the sequence Chart the results of the control samples for each batch Typically, due to complexity of calculations, results are manually transcribed to external spreadsheets Introduces errors Time consuming reviews needed In the Chromeleon CDS software controlled by the Report Template </li> <li> 22 Dissolution Testing Most components of analysis are already in the CDS Many areas where manual sequence creation causes errors How do you ensure that your sequence is created and structured correctly? How do you know you have the right methods and report? How can you simplify analysis setup and execution? eWorkflows for fast, easy, accurate sequence creation </li> <li> 23 eWorkflows </li> <li> 24 eWorkflows Definition An electronic procedure for automating laboratory processes related to a chromatographic analysis Assists user in creating an appropriate sequence for a suitable instrument with pre-defined associated files and a well-defined structure Guides you from samples to reliable results in the minimum number of steps </li> <li> 25 eWorkflows Contents Instruments on which the analysis can be run All associated files: Instrument methods Processing methods Reports Spectral libraries External documents (e.g. the SOP!) Template for sequence name and storage location Custom variables Signature requirements Rules for sequence layout Ensures consistency of analysis </li> <li> 26 eWorkflows eWorkflows can ensure your SOP is followed Reduces errors and produces reliable results faster Fully customizable for any application in any laboratory QA/QC laboratories Method development laboratories Research & Development laboratories Walk-up instrument workflows Minimizes amount of training required </li> <li> 27 How Do You Use eWorkflows? </li> <li> 28 eWorkflows Category Category bars in the Chromeleon Console Provide immediate access to all your instruments, data and eWorkflows </li> <li> 29 eWorkflows Category List of available eWorkflows eWorkflow description & status Available instruments & status </li> <li> 30 eWorkflows Ease of Use 1. Select eWorkflow 2. Select Instrument 3. Click Launch </li> <li> 31 eWorkflows Ease of Use 4. Input number of samples 5. Input position of first sample Optional 6. Click Finish Sequence preview Sampler rack view </li> <li> 32 eWorkflows Ease of Use Wizard prompts for any missing information, for example: Instrument method: Select or create new Sequence: Define name and folder </li> <li> 33 eWorkflows Ease of Use Sequence created in 6 clicks with correct: Name Location Methods Report Structure Custom Variables Plus: SOP attached Can run immediately </li> <li> 34 Chromeleon CDS Extension Pack </li> <li> 35 Chromeleon CDS Extension Pack Allows you to quickly and easily perform and report common tests that otherwise can take considerable amounts of time to process Most tests involve comparing results to specifications. The templates do this for you automatically and let you know immediately if your tests have passed or failed. Currently templates for: Dissolution Testing ICH Method Validation Content Uniformity Testing Gel Permeation Chromatography (GPC) </li> <li> 36 Dissolution Testing USP provides details on how to perform dissolution experiments - procedures for running the experiments and for assessing the data In many labs, results are manually copied into spreadsheets to perform calculations and generate charts. Time consuming process and transcription errors are common problem </li> <li> 37 Sequence Custom Variables Sequence includes 4 Sequence Custom Variables Custom Variable Name Description Batch_No Batch number of the tested product Disso_No Unique experiment number Initial_Volume Initial volume in the vessels Volume_Taken Volume taken at each time point </li> <li> 38 Sequence Custom Variables Sequence includes 6 Injection Custom Variables Custom Variable Name Description Stage Dissolution stage number Sampling_No Identifies 1st, 2nd, 3rd, etc., sample withdrawal Time_Point Actual time at which sample is taken Bath_No ID number of the dissolution bath Vessel_No Dissolution vessel the sample was drawn from Print_Diss Identifies the last sample of a test stage </li> <li> 39 Component Custom Variables Processing Method includes 8 Component Custom Variables Custom Variable Name Description Media_Replacement Defines if the medium removed from the vessel is replaced Q_Sampling_No Defines which sampling number relates to the Q-value Q_Value Target amount of dissolved active substance at specified time Q_Value_DP Number of significant decimal places for Q-value Compensation Defines how to compensate for changes in the dissolution bath Analyte_LC Label claim of the analyte in the product Treat_NA_as_Zero Define what should happen if a result is not available Report_Peak Defines which peaks should be reported </li> <li> 40 Collating Data Queries bring data from Stage 1, Stage 2 and Stage 3 together if needed Search based on unique test number (Disso_No) Report is included in the Query </li> <li> 41 Collating Data Query results: </li> <li> 42 Dissolution Testing Chromeleon CDS Extension Pack templates calculate and report dissolution test results in less than 1 minute (97-99% time saving) Supports up to: 3 stages 3 components 10 time points </li> <li> 43 Dissolution Testing Live Demo Lets have a look at eWorkflows in action and how the Extension Pack performs dissolution testing </li> <li> 44 ICH Method Validation ICH is an organization that provides guidelines to pharma industry on method validation Major validation processes are Specificity Accuracy Precision Detection Limit Quantitation Limit Linearity Range Robustness It can take as long as 5 man days to calculate, collate, and report validation results. </li> <li> 45 ICH Method Validation Chromeleon CDS Extension Pack templates calculate and report validation results in less than 5 minutes for all these tests 5 man days = 2400 minutes = 2395 minutes saved 99.8% saving! </li> <li> 46 Content Uniformity Ensure consistency of dosage units, each unit in batch should have an active substance content within narrow range of label claim </li> <li> 47 Content Uniformity Templates Calculate and report CU test results in less than 1 minute giving huge time savings Supports up to: 2 stages 3 components </li> <li> 48 GPC To determine molecular weight distributions in polymers, a commonly used technique is gel permeation chromatography (GPC), also known a...</li></ul>