Real-Time LC Bioreactor Process Analytics on the Production Floor

Transcription

1 Real-Time LC Bioreactor Process Analytics on the Production Floor When is Often Too Often But Not Often Enough International Forum Process Analytical Technology Alexandre Paccou Principal Scientist EU Process Analytics Team 24 January Waters Corporation 1

2 Agenda: Waters Philosophy Keen Understanding Unparalleled Insight into Customer Operations Purposeful Innovation Pioneering Valuable and Sustainable Breakthroughs Meaningful Impact Fundamental Contributions to Our Customers Success 2012 Waters Corporation 2

3 Inprocess Material Analysis: Impact on Quality, Efficiency, & Productivity 2012 Waters Corporation 3

4 Definitions Inline Testing PROCESS STREAM Online Testing PROCESS STREAM Atline Testing PROCESS STREAM Offline Testing PROCESS STREAM 2012 Waters Corporation 4

5 Many Tools in the Analytical Toolbox 2012 Waters Corporation 5

6 Sensor Technology Utilized for PAT Applications Today Probes (Temp, ph) Dissolved Gas (0 2, CO 2 ) Headspace / Environmental (Mass Spec) Total Organic Carbon (TOC) Near-Infrared (NIR) Infrared (IR) Raman UV-visible Fourier Transform Infrared (FTIR) X-Ray Powder Diffraction (XRPD) Terahertz Pulse (TP) Spectroscopy Acoustic Resonance (AR) Spectrometry 2012 Waters Corporation 6

7 Limitations of Current PAT Technologies Minimal Dynamic Range Poor Sensitivity Dependent on strong compound signal Limits of Detection (LOD) Limited Quantitation capability Limits of Quantitation (LOQ) Dependent on dissimilar compound spectra Minimal Resolution Still requires a Reference Standard or Gold Standard Technique for comparison and validation Vibrational spectroscopic data not easily compared/correlated to data from Discovery, Research, Development, and QC? CHECK 2012 Waters Corporation 7

8 HPLC for Inprocess Analysis Reference Standard LC is a major analytical technique in every QC lab But it is not a major tool for Online/Atline analysis What perceptions are impacting the lack of LC adoption on the production floor? Too slow, too slow too slow; not real-time, it just takes too long to get an answer Long run times delay processes Not rugged enough for continuous operation Requires considerable maintenance Excessive down-time Too expensive to operate Requires consumables and highly skilled technicians Not automated Real-time Online/Atline LC Systems don t exist 2012 Waters Corporation 8

9 Agenda: Waters Philosophy Keen Understanding Unparalleled Insight into Customer Operations Purposeful Innovation Pioneering Valuable and Sustainable Breakthroughs Meaningful Impact Fundamental Contributions to Our Customers Success 2012 Waters Corporation 9

10 PATROL UPLC Process Analyzer Key Requirements for an inprocess analyzer Real-time results Ease of Use Flexible Rugged & Robust Serviceability 2012 Waters Corporation 10

11 Original HPLC Method TOO SLOW for Online Analysis 30 minute cycle time Transfer to UPLC and optimize 2012 Waters Corporation 11

12 New UPLC Method Real-TIME LC Analysis Overlay of 10 Replicate Injections 2012 Waters Corporation 12

13 Atline Dilution Capabilities Linearity (n = 6) Excellent linearity across the entire dilution range R 2 = /x Weighting Aqueous rprotein sample diluted with 6M urea Undiluted 2x Dilution 4x Dilution 10x Dilution 20x Dilution 100x Dilution Dilution %RSD Undiluted x x x x x Waters Corporation 13

14 Agenda: Waters Philosophy Keen Understanding Unparalleled Insight into Customer Operations Purposeful Innovation Pioneering Valuable and Sustainable Breakthroughs Meaningful Impact Fundamental Contributions to Our Customers Success 2012 Waters Corporation 14

15 Automated Process Analysis Biopharm Downstream Processing UPSTREAM DOWNSTREAM 2012 Waters Corporation 15

16 Basic Sampling For samples requiring Sterile Sampling Flownamics FISP probe 0.2µm Ceramic Membrane 2012 Waters Corporation 16

17 PATROL UPLC Laboratory Analyzer UltraPerformance Liquid Chromatography System Fully automated online analyzer Sample o Direct sampling from reactor or slipstream Data o Fully integrated into DCS or LIMS o Capable of autonomous workstation operation Fully automated atline analyzer Sample o Automated operation with barcode vials o Manual operation without barcode vials Data o Fully integrated into DCS (OPC only) or LIMS o Capable of autonomous workstation operation Cart configured for mobility o Standard touchscreen 2012 Waters Corporation 17

18 SEC at line HPLC vs SEC online Patrol UPLC with Waters BEH µm 4.6 * 150 mm mau _ WVL:280 nm AU Minutes min 0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0 45,0 50,0 55,0 60, Waters Corporation 18

19 Hydrolisis of a protein: 1 sampling every 6 minutes AU Minutes 2012 Waters Corporation 19

20 Hydrolisis of a protein: 1 sampling every 6 minutes AU Minutes 2012 Waters Corporation 20

21 T0 to T T AU T Minutes 2012 Waters Corporation 21

22 Monitoring of Downstream Process: Diafiltration (sampling every 6 minutes) Data Missing AU Minutes 2012 Waters Corporation 22

23 Monitoring of Downstream Process: Diafiltration (sampling every 6 minutes) Data Missing AU Minutes 2012 Waters Corporation 23

24 Process completed after 30 minutes AU Minutes 2012 Waters Corporation 24

25 UPLC for Inprocess Analysis UPLC performance for use on the Manufacturing Floor UPLC enables LC to have real time LC speed Large linear dynamic range with excellent selectivity and sensitivity Ability to quantitate major components and low-level impurities User Friendly Reduces sample handling and prep variability Full automation from sample to report Single technology from Discovery through Manufacturing Archived data for Quality by Design efficiency Achieve consistent quality output, increased efficiency, and greater productivity 2012 Waters Corporation 25

26 2012 Waters Corporation 26