Waters Corporation · NYSE:WAT
Waters — Technical Presentation (May 2012)
47 slides from Waters's technical presentation, May 22, 2012
Slide 1: Finland UPLC Users Meeting
Finland UPLC Users Meeting Mai, 22th Frederic Forini Waters European Headquarters ©2012 Waters Corporation 1
Slide 2: What is the USP?
What is the USP? The United States Pharmacopeia (USP) is an independent, official public standards-setting authority – Prescription and OTC medicines – Healthcare products – Food ingredients – Dietary supplements USP standards recognized and used in >130 countries Head quarters and offices ©2012 Wat
Slide 3: What is the USP-NF?
What is the USP- USP-NF? The United States Pharmacopeia – National Foundry (USP-NF) is a book of pharmacopeial standards – Drugs substances & preparations monographs: USP – Dietary supplements & ingredients monographs: USP – Excipient monographs: NF – More than 4500 monographs The USP-NF is the offi
Slide 4: What is the Pharmacopeial Forum (PF)
What is the Pharmacopeial Forum (PF) USP standards are established and maintained through public participation 1. Sponsors provide draft standards and supporting data 2. USP scientific staff and volunteer experts review, test and forward new/revised monograph to PF 3. Monograph is refined and finali
Slide 5: Why are Such Changes to Chromatography <621> Important?
Why are Such Changes to Chromatography <621> Important? Question From CURRENT USP-NF Online FAQs1 – Q. How much can I modify a chromatographic procedure and still be in compliance? Can column length, internal diameter, mobile phase composition be modified? – A. Chromatography <621> contains a list o
Slide 6: Working with USP: ACQUITY UPLC Columns “L” Listing
Working with USP: ACQUITY UPLC Columns “L” Listing Back in August 2007: ACQUITY UPLC® Columns included in USP LC columns “L” listings – Waters was instrumental in changing minimum particle size ©2012 Waters Corporation 6
Slide 7: Current Regulation Allowed Adjustments
Current Regulation Allowed Adjustments Chromatography <621> describes the adjustments Allowed HPLC Adjustment allowed in theUSP chromatography (Ref: General Chapter <621>) system EP when system (Ref: General Chapter 2.2.46) suitability test fails Column Length ±70% ±70% Internal Diameter Can be adju
Slide 8: The Beginning of A Significant Change to Chromatography <621>
The Beginning of A Significant Change to Chromatography <621> Because Waters is THE acknowledged leader in separation science, we were asked (by a customer) to help modernize LC column selection in General Chapter <621> Chromatography In the summer of 2009 Dr. Uwe Neue et. al. wrote a paper (article
Slide 9: What Does This Stimuli Article Propose?
What Does This Stimuli Article Propose? Stimuli Article PF 35(6) [Nov-Dec 2009] ©2012 Waters Corporation 9
Slide 10: What Does This Stimuli Article Propose?
What Does This Stimuli Article Propose? Allowable Changes Variable Current Rgulation Stimuli Article Proposal Particle Size -50% L/dp = Cst (±25%) Column Length ±70% Flow Rate ±50% Accordingly to L, dp and column ID Column ID Any allowed Any allowed Injection Volume Any reduction Any allowed Column
Slide 11: USP-NF Development Process
USP--NF Development Process USP Nov-Dec 2009 Waters Stimuli Submission PF 35(6) 2nd May, 2011 Amended Chromatograhy <621> Posted in PF 37(3) 131 March, st st 2012 July, 2011 Comment Revised Period Proposal Ended Posted in Expert PFCommittee 38(2) Discussions Began 29th Dec, 2011 Chromatography <621>
Slide 12: What Does This Revision Status Change Mean?
What Does This Revision Status Change Mean? How do you behave concerning revalidation? – Do you NEVER revalidate (never change methods) OR – Do you ALWAYS revalidate (even though changes were within USP allowable adjustments – audit fears) OR – Do you SOMETIMES revalidate (when changes are outside o
Slide 13: What are we doing until the finalized USP Chapter <621>
Lets Take a Concrete Example Original HPLC Method L/dp = 30’000 Geometrical Transfer Allowed with Current Regulation L/dp = 28’571 What are we Geometrical Transfer Allowed doing until with Current Regulation the finalized L/dp = 30’000 Geometrical USP Chapter <621> Transfer Allowed if <621> will be
Slide 14: Industry Trends: The Market has Changed
Industry Trends: The Market has Changed Transitioning from HPLC to UPLC Technology Increasing number of organizations have realized the business and scientific advantages of UPLC Technology Increased availability of UHPLC instruments and sub 3 µm chemistries provides vendor choice Technology shift h
Slide 15: Introducing The Waters 2.5 µm eXtended Performance Column Family
Introducing The Waters 2.5 µm eXtended Performance Column Family ©2012 Waters Corporation 15
Slide 16: 2.5 µm eXtended Performance Columns: Product Scope
2.5 µm eXtended Performance Columns: Product Scope Packed in ultra-low dispersion hardware to What are the differences bewteen minimize band spreading regular 2.5µm HPLC columns and 2.5µm XP columns ? Designed to withstand high pressure • 2.5µm XP can withstand – 4.6 mm ID capable of 9,000 PSI highe
Slide 17: Based Upon Two Fully-Scalable LC Column Platforms
Based Upon Two Fully- Fully-Scalable LC Column Platforms Family designed and optimized Family designed and optimized for for pH stability selectivity Most MS-compatible HPLC Multiple particle substrates to columns on the market solve multiple chromatographic problems 2.5 µm XP eXtended Performance C
Slide 18: Matching the Correct Column & System
Matching the Correct Column & System Two compendial (USP) method transfer examples 1. Isocratic Assay: Levonorgestrel and Ethinyl Estradiol – Compare original HPLC method with: o XP column methods on Alliance HPLC system o XP column method on ACQUITY UPLC H-Class system o ACQUITY UPLC column method
Slide 19: Positioning the Right Column with the Right System
Positioning the Right Column with the Right System System HPLC UPLC 1.7/1.8 µm UPLC, 1.7/1.8 µm UPLC, Particle Size 3.5 µm, 5 µm 2.5 µm XP 2.5 um XP, 3.5 µm, 5 µm 2.5 um XP, 3.5 µm, 5 µm Routine Pressure < 4000 psi < 4000 psi < 15000 psi (H-Class) < 18000 psi (I-Class) Column ID 4.6 mm 4.6 mm 2.1 &
Slide 20: Original Isocratic USP Assay
Original Isocratic USP Assay: 4.6 x 150 mm, 5 µm (Alliance HPLC) Flow Rate: 1.00 mL/min System Suitability Requirements Pressure: 1400 psi USP Resolution: NLT 2.5 0.070 Run time: 8.00 min Peak Area Precision: NMT 2.0% RSD USP Res: 6.9 0.060 levonorgestrel ethinyl estradiol 0.050 0.040 AU 0.030 0.020
Slide 21: Compiled Status – Isocratic Method
Compiled Status – Isocratic Method Criteria USP Res>2.5 LC Column Column Particle Ratio Flow Pressure Retention USP Instrument Comments Mode ID Length Size L/dp Rate (PSI) Time Res. (mm) (mm) (µm) (ml/min) (min) HPLC 4.6 150 5 30’000 1 1400 8 6.9 Alliance Original HPLC Method HPLC 4.6 75 2.5 30’000
Slide 22: Isocratic Method Transferred to 4.6 mm XP Columns (Alliance HPLC)
Isocratic Method Transferred to 4.6 mm XP Columns (Alliance HPLC) 4.6 x 75 mm XP 2.5 µm Could not run at SCALED flow rate Flow Rate: 1.00 mL/min due to system pressure limitations 0.070 Pressure: 2600 psi Run time: 4.00 min levonorgestrel 0.060 Results: USP Res: 6.5 Rs = 0.9X 0.050 Run time = 0.5X e
Slide 23: Compiled Status – Isocratic Method
Compiled Status – Isocratic Method Criteria USP Res>2.5 LC Column Column Particle Ratio Flow Pressure Retention USP Instrument Comments Mode ID Length Size L/dp Rate (PSI) Time Res. (mm) (mm) (µm) (ml/min) (min) HPLC 4.6 150 5 30’000 1 1400 8 6.9 Alliance Original HPLC Method HPLC 4.6 75 2.5 30’000
Slide 24: Isocratic Method Transferred to 4.6 mm XP Columns (Alliance HPLC)
Isocratic Method Transferred to 4.6 mm XP Columns (Alliance HPLC) 4.6 x 75 mm XP 2.5 µm Could not run at SCALED flow rate Flow Rate: 1.00 mL/min due to system pressure limitations 0.070 Pressure: 2600 psi Run time: 4.00 min levonorgestrel 0.060 Results: USP Res: 6.5 Rs = 0.9X 0.050 Run time = 0.5X e
Slide 25: Compiled Status – Isocratic Method
Compiled Status – Isocratic Method Criteria USP Res>2.5 LC Column Column Particle Ratio Flow Pressure Retention USP Instrument Comments Mode ID Length Size L/dp Rate (PSI) Time Res. (mm) (mm) (µm) (ml/min) (min) HPLC 4.6 150 5 30’000 1 1400 8 6.9 Alliance Original HPLC Method HPLC 4.6 75 2.5 30’000
Slide 26: LC Systems and Column Positioning: Transfer to ACQUITY UPLC H-Class
LC Systems and Column Positioning: Transfer to ACQUITY UPLC H- H-Class System System HPLC UPLC 1.7/1.8 µm UPLC, 1.7/1.8 µm UPLC, Particle Size 3.5 µm, 5 µm 2.5 µm XP 2.5 um XP, 3.5 µm, 5 µm 2.5 um XP, 3.5 µm, 5 µm Routine Pressure < 4000 psi < 4000 psi < 15000 psi (H-Class) < 18000 psi (I-Class) Col
Slide 27: Isocratic Method Transferred to ACQUITY UPLC H-Class System
Isocratic Method Transferred to ACQUITY UPLC H-H-Class System 2.1 x 75 mm XP, 2.5 µm Flow Rate: 0.5 mL/min 0.08 Pressure: 5200 psi Run Time: 1.80 min 0.06 levonorgestrel Results: ethinyl estradiol USP Res: 7.9 Rs = 1.1X AU 0.04 Run time = 0.25X 0.02 Pressure = 3.1X 0.00 0.00 0.20 0.40 0.60 0.80 1.00
Slide 28: Compiled Status – Isocratic Method
Compiled Status – Isocratic Method Criteria USP Res>2.5 LC Column Column Particle Ratio Flow Pressure Retention USP Instrument Comments Mode ID Length Size L/dp Rate (PSI) Time Res. (mm) (mm) (µm) (ml/min) (min) HPLC 4.6 150 5 30’000 1 1400 8 6.9 Alliance Original HPLC Method HPLC 4.6 75 2.5 30’000
Slide 29: Matching the Correct Column & System
Matching the Correct Column & System Two compendial (USP) method transfers 1. Isocratic Assay: Levonorgestrel and Ethinyl Estradiol – Compare original HPLC method with: o XP column methods on Alliance HPLC system o XP column method on ACQUITY UPLC H-Class system o ACQUITY UPLC column method on ACQUI
Slide 30: Gradient USP Impurities Assay: Abacavir Method Transfer
Gradient USP Impurities Assay: Abacavir Method Transfer System HPLC UPLC 1.7/1.8 µm UPLC, 1.7/1.8 µm UPLC, Particle Size 3.5 µm, 5 µm 2.5 µm XP 2.5 um XP, 3.5 µm, 5 µm 2.5 um XP, 3.5 µm, 5 µm Routine Pressure < 4000 psi < 4000 psi < 15000 psi (H-Class) < 18000 psi (I-Class) Column ID 4.6 mm 4.6 mm 2
Slide 31: Original Gradient USP Impurities
Original Gradient USP Impurities: 4.6 x 150 mm 5 µm (Alliance HPLC) System Suitability Requirements Flow Rate: 1.00 mL/min USP Res: NLT 1.5 0.020 Max Pressure: 2800 psi Gradient time: 35 min 0.018 descyclopropyl abacavir 1R, 4R trans abacavir 0.016 USP Res: 3.1 o-pyrimidine abacavir 0.014 0.012 abac
Slide 32: Compiled Status – Gradient Method
Compiled Status – Gradient Method Criteria USP Res>1.5 LC Column Column Particle Ratio Flow Pressure Retention USP Instrument Comments Mode ID Length Size L/dp Rate (PSI) Time Res. (mm) (mm) (µm) (ml/min) (min) HPLC 4.6 150 5 30’000 1 2800 35 3.1 Alliance Original HPLC Method HPLC 2.1 75 2.5 30’000
Slide 33: Gradient USP Impurities Method Transferred to 2.1 mm ID Columns
Gradient USP Impurities Method Transferred to 2.1 mm ID Columns (UPLC H- H-Class) Scaled (same) linear velocity as 0.020 0.018 2.1 x 75 mm XP, 2.5 µm original HPLC separation Flow Rate: 0.5 mL/min 0.016 Max Pressure: 8630 psi Gradient time: 7.30 min descyclopropyl abacavir 0.014 USP Res: 2.9 (0.94X)
Slide 34: Compiled Status – Gradient Method
Compiled Status – Gradient Method Criteria USP Res>1.5 LC Column Column Particle Ratio Flow Pressure Retention USP Instrument Comments Mode ID Length Size L/dp Rate (PSI) Time Res. (mm) (mm) (µm) (ml/min) (min) HPLC 4.6 150 5 30’000 1 2800 35 3.1 Alliance Original HPLC Method HPLC 2.1 75 2.5 30’000
Slide 35: Running a 2.1 mm XP Column: Alliance vs. ACQUITY UPLC H-Class
Running a 2.1 x 75 mm XP Column: Alliance vs. ACQUITY UPLC H- H-Class Lower flow rate based upon HPLC ACQUITY UPLC H-Class descyclopropyl abacavir system pressure limit 0.020 Flow Rate: 0.21 mL/min 1R, 4R trans abacavir o-pyrimidine abacavir 0.015 Max Pressure: 3600 psi Gradient Time: 17.0 min abaca
Slide 36: What is Band Spreading?
What is Band Spreading? Any component of the chromatographic system [instrument and column] that contributes to the distortion and broadening of a chromatographic band – Wide chromatographic band – Narrow chromatographic band o Increased peak width o Decreased peak width o Dilution effect decreases
Slide 37: Waters Disruptive Technology and Separation Integrity
Waters Disruptive Technology is the Providing a Complete (Holistic) Solutions for Meaningful Impact of Achieving Theoretical Promise of Separation σ v2,total = σ v2,injector + σ v2, precolumn + σ v2,column + σ v2, postcolumn + σ v2,det ector + τ det 2 ector ⋅ F 2 Injection Tubing Column Tubing Band-
Slide 38: Summary: Positioning Column Configurations with LC Systems
Summary: Positioning Column Configurations with LC Systems Recommended Column ID Chromatographic System Band Spread* Primary Secondary Shimadzu Prominence UFLC 41 µL Alliance 2695 HPLC 29 µL 4.6 mm 3.0 mm Agilent 1260 UHPLC (600 bar) 28 µL Thermo Accela UHPLC 21 µL 3.0 mm 2.1 mm Agilent 1290 UHPLC (
Slide 39: Compiled Status – Gradient Method
Compiled Status – Gradient Method Criteria USP Res>1.5 LC Column Column Particle Ratio Flow Pressure Retention USP Instrument Comments Mode ID Length Size L/dp Rate (PSI) Time Res. (mm) (mm) (µm) (ml/min) (min) HPLC 4.6 150 5 30’000 1 2800 35 3.1 Alliance Original HPLC Method HPLC 2.1 75 2.5 30’000
Slide 40: Method Transfer Summary
Method Transfer Summary Methods can be transferred to 4.6 mm ID XP columns on HPLC systems – May need to reduce flow rate when using >50mm length columns – If column length and particle size are not scaled, resolution values will be different than original Improved performance for 2.1 mm ID XP and U
Slide 41: Summary
Summary Encouraging sign from regulatory agencies to facilitate adoption of new technology Waters will continue to work with USP and other regulatory bodies worldwide – We are committed to advance and modernize separation science USP Method Transfer Project gives us a keen understanding of challenge
Slide 42: Concrete Summary Example
Concrete Summary Example XSelect CSH C18 Tolmetin 0.30 4.6 x 100 mm, 3.5 µm Diclofenac HPLC System 3.5 µm Naproxen Fenoprofen 1ml/min Indomethacin 0.20 AU 0.10 0.00 0.00 4.00 8.00 12.00 16.00 24.00 28.00 Minutes 20.00 0.30 XSelect CSH C18 XP 0.30 2.1 x 75 mm, 2.5 µm 4.6 2.5 µm XP 0.25 UPLC System HP
Slide 43: Questions?
Questions? For how many years do you envisage the system that you are purchasing remaining “fit for purpose” ©2012 Waters Corporation 43
Slide 44: State of System LifeCycle
State of System LifeCycle Year 2020 Year 2012 Year 2016 State of the art Run existing legacy HPLC Technology in hand technology fully methods fully optimized deployed ©2012 Waters Corporation 44
Slide 45: Investment Protection Approach
Investment Protection Approach… ACQUITY UPLC I-Class •New chemical entities, research, impurity analysis •1.7/1.8 µm UPLC columns ACQUITY UPLC H-Class Performance Level •Method development, method transfer, QA/QC •Changing priorities from small – to – large molecules •1.7/1.8 µm UPLC columns as well
Slide 46: Thank You For Your Time and Attention
Thank You For Your Time and Attention Questions? ©2012 Waters Corporation 46
Slide 47: What Happen at the European Level
What Happen at the European Level Will EurP follow USP? – USP and EurP are harmonizing both chapter <621> and 2.2.46 to the extent possible What about the EurP Chapter 2.2.46? – Draft 2.2.46 chapter has already been written When will this be released? – EurP expect to release the new 2.2.46 chapter