Getting It “Right First Time” Seminar Series – Part 2
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Transcript of Getting It “Right First Time” Seminar Series – Part 2
1The world leader in serving science
Darren Barrington-LightProduct Specialist, Chromatography Software, Thermo Fisher Scientific
April 1, 2014
Getting It “Right First Time” Seminar Series – Part 2
Part #: PP71261-EN0414S
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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
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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 that’s ‘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)
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How to Get It Right the First Time?
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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
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Chromeleon CDS Tools for RFT Analysis
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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
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Standard Operating Procedures
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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
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Standard Operating Procedures
Sample check-inSample preparation
Instrument preparation
Eluent preparation
Sample analysis conditions
Data analysis conditions
Data reporting requirements
Regulatory requirements
Validation requirementsCustomer report requirements
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Standard Operating Procedures
• So how do we help the analyst?
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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
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Let’s Look at an Example…
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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
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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
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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
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Dissolution Testing – Sample Analysis
Example instrument conditions:• Column temperature: 30 ºC• Mobile phase: Solvent A (acetonitrile) and solvent B (water)
50:50• Flow rate: 1.0 mL/min• Injection volume: 10 μL• Detection wavelength: 254 nm• Running time: 20 min
• All controlled by the Instrument Method
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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
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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
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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%
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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
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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
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eWorkflows
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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
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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
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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
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How Do You Use eWorkflows?
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eWorkflows Category
• Category bars in the Chromeleon Console
• Provide immediate access to all your instruments, data and eWorkflows
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eWorkflows – Category
List of available eWorkflows
eWorkflow description & status
Available instruments & status
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eWorkflows – Ease of Use
1. Select eWorkflow
2. Select Instrument
3. Click Launch
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eWorkflows – Ease of Use
4. Input number of samples 5. Input position of first sample
Optional
6. Click Finish
Sequence preview
Sampler rack view
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eWorkflows – Ease of Use
• Wizard prompts for any missing information, for example:
Instrument method:Select or create new
Sequence: Define name and folder
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eWorkflows – Ease of Use
• Sequence created in 6 clicks with correct:• Name• Location• Methods• Report• Structure• Custom Variables
• Plus: • SOP attached• Can run immediately
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Chromeleon CDS Extension Pack
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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)
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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
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Sequence Custom Variables
• Sequence includes 4 Sequence Custom Variables
Custom Variable Name DescriptionBatch_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
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Sequence Custom Variables
• Sequence includes 6 Injection Custom Variables
Custom Variable Name DescriptionStage 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
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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
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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
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Collating Data
• Query results:
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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
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Dissolution Testing – Live Demo
• Let’s have a look at eWorkflows in action and how the Extension Pack performs dissolution testing…
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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.
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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!
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Content Uniformity
• Ensure consistency of dosage units, each unit in batch should have an active substance content within narrow range of label claim
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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
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GPC
• To determine molecular weight distributions in polymers, a commonly used technique is gel permeation chromatography (GPC), also known as size exclusion chromatography (SEC)
• Calibration in GPC is based on relation between molecular weight and retention time
• Peaks of unknown substances are divided into multiple peak slices. From these slices, molecular weight distribution curve and cumulative distribution curve are calculated and plotted.
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GPC
• Chromeleon CDS Extension Pack templates calculate and report molecular weight distributions in less than 1 minute
• Supports up to:• 3 peaks• 20 MW Standards
(Narrow Standard Calibration)
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Summary
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Summary
• eWorkflows can ensure your SOPs are followed:• Reduce errors and produce reliable results faster• Fully customizable for any application in any laboratory• Minimum amount of training required
• Extension pack:• Complete data acquisition, calculation, plotting and result reporting
using only Chromeleon CDS• Immediate review of all results after run/sequence is complete• PDF export and/or printing hardcopies of reports• Significant productivity gains achieved – saving time and money• No additional cost for users running Chromeleon CDS
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• Discover more Chromeleon CDS tools to ensure you get “right first time, every time” analysis
Next Time….
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Thank You!
Any Questions?