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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

Getting It “Right First Time” Seminar Series – Part 2

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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. 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).

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Page 1: 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?