Buffer In-line Dilution: Superior Performance with Volume Based Control. Mary Jo Wojtusik, Ph.D.

Transcription

1 Buffer In-line Dilution: Superior Performance with Volume Based Control Mary Jo Wojtusik, Ph.D. / 2017

2 Agenda Buffer in-line dilution (BID) Approaches to BID BID with volumetric flow control LPLC with integrated BID Summary /

3 What is Buffer In-line Dilution? A process where two or more liquid streams are brought together in an automated and controlled fashion to deliver a target diluted solution concentration. Diluted Buffer Reduce buffer storage space f1 f1 f1 Reduce manual buffer preparation Improve consistency with automated buffer preparation Buffer B WFI Buffer A Enhance flexibility with point-ofuse buffer production 3

4 Approaches to buffer in-line dilution Centralized buffer supply Delivers buffers to several production suites Can server a larger plant Only one system to operate and maintain Requires large piping system More complex engineering, higher risk Requires large tanks and space Localized buffer supply Close to specific production suite and dedicated to one suite or several downstream unit operations. Less complex system Amenable to single-use bags and containers for buffer concentrates Greater flexibility to serve multiple unit operations Integrated BID and chromatography / 2017 Dilute buffer concentrate at point-of-use One system saves space On-demand buffer where it is needed Amenable to single-use bags and containers for buffer concentrates Facilitate fast process change-over Nominal cost for two unit operations in the same system 4

5 Approaches to buffer in-line dilution Centralized buffer supply Delivers buffers to several production suites Can server a larger plant Only one system to operate and maintain Requires large piping system More complex engineering, higher risk Requires large tanks and space EcoPrime Central BID system

6 Approaches to buffer in-line dilution Localized buffer supply Close to specific production suite and dedicated to one suite or several downstream unit operations. Less complex system Amenable to single-use bags and containers for buffer concentrates Greater flexibility to serve multiple unit operations EcoPrime Local BID system 6

7 Approaches to buffer in-line dilution Integrated BID and chromatography Dilute buffer concentrate at point-ofuse One system saves space On-demand buffer where it is needed Amenable to single-use bags and containers for buffer concentrates Facilitate fast process change-over Nominal cost for two unit operations in the same system EcoPrime LPLC / BID system 7

8 Buffer in-line dilution systems with volume-based control Volumetric Flow Control Flow meters and pumps are more accurate and stable than ph or conductivity detectors Peristatic pump Accuracy ± 5% LEWA ecodos pump Accuracy ± 2% ecodos pump with intellidrive Accuracy ±0.5% Volumetric flow control delivers sustainable performance for consistent buffer preparation. ph control Accuracy, ± 1% In addition: o Tendency to drift o Memory effect often observed o Frequent calibration required Conductivity control Accuracy, ± 1% In addition: o Frequent calibration required 8

9 Implementing BID Conclusion: We determined that inline control of ph and conductivity is not necessary to guarantee accurate blends since tracking flow rate through a Coriolis mass flow meter is inherently more accurate. LEWA Bioprocess Technologies BID with accurate volumetric flow control delivers predictable and consistent buffer composition and ph 9

10 Digital pump technology delivers superior volumetric flow performance over analog controlled pump Analog, traditional pump Mechanical functions Transfers rotating drive energy into oscillating pump energy. Uses mechanical stroke length and speed adjustment to vary flow rate Electrical functions Uses a variable frequency drive (VFD) to adjust motor speed Digital, intellidrive pump Mechanical functions Transfers rotating drive energy into oscillating pump energy. Integrated mechanical & electrical functions Uses an integrated closed-loop control system to adjust volume flow with precise plunger movement Separate stroke length actuator (mechanical) and motor speed (electrical) adjustment. 10

11 Digital, intellidrive control reduces pumping variation Digital servo motors, +/ % accuracy Analog (asynchronous) motors +/- 1.0% of Max RPM + 30 RPM + 18 RPM 9 L/min -18 RPM -30 RPM 0.4 LPM 0.06 L/min ERROR RPM Motor RPM Motor - Digital Servo Motor 11

12 The benefit of intellidrive and ecodos pumps technology for BID intellidrive pump feature Extraordinarily wide control range Integrated structures for speed control, position control, and synchronization High dynamic control of plunger speed and positioning Pulsation-free volume flows enabled with electronic synchronization of multiple pumps Drives are compact, have no fans and use one integrated power and control system High energy efficiency from lasted motor design Result Provides dilution factors up to 150x Extremely precise and accurate flow rates Fluid kinematics (displacement, time, acceleration and velocity) adaptable process demands for maximum flexibility Extremely precise and accurate flow for chromatographic gradient formation Simplicity improves reliability Lowers operating costs 12

13 Buffer in-line dilution (10x to 150x) using two channels % Error % Error Target Target Actual Actual Variation of target buffer concentration is below 0.5% for dilution factors from 10x to 150x 13

14 Buffer in-line dilution (10x to 150x) using three channels % Error % Error Target Target Actual Actual 14

15 EcoPrime LPLC with integrated BID 15

16 EcoPrime LPLC gradient performance with integrated BID Upper Spec UV Predicted UV % Error Operational Higher Operational Lower Lower Spec 16

17 Summary Automatically preparing buffers from concentrates: Reduces buffer storage space Reduces manual buffer preparation burden Improves consistency Volumetric flow control based buffer in-line dilution: Assures better control of buffer composition Minimizes process variables (ionic strength and concentration, ph, and conductivity) Facilitates validation with straight-forward process controls Integrating enhanced buffer in-line dilution with chromatography on the same skid: Enhances flexibility with point-of-use buffer production Maintains high chromatographic performance Two unit operations on one skid saves space at additional nominal cost 17

18 Volumetric flow control delivers sustainable performance for consistent buffer preparation.

19 For more information: America s Europe Asia LEWA-Nikkiso America, Inc. 132 Hopping Brook Road MA Holliston Tel: Fax: sales@lewa-inc.com Headquarters LEWA GmbH Ulmer Str Leonberg GERMANY Tel: Fax: lewa@lewa.de NIKKISO CO. LTD. Yebisu Garden Place Tower 22nd Floor 20-3, Ebisu 4-Chome, Shibuya-ku Tokyo Tel: Fax: LEWA, Creating Fluid Solutions, the LEWA logo, LEWA Intellidrive and LEWA EcoPrime are trademarks of LEWA GmbH. All goods and services are sold subject to the terms and conditions of sale of the company within LEWA which supplies them. A copy of these terms and conditions is available on request. Contact your local LEWA representative for the most current information LEWA All rights reserved. LEWA Bioprocess Group Systems Engineering & Production Plant 8 Charlestown Road Devens, MA USA Tel: sales@lewapt.com

20 By coupling mechanical drives with decoupled multiple pump heads and digital synchronization we achieve superior accuracy with low pulsation ideal for chromatography. LEWA metering pump LEWA ecodos pump with intellidrive Very robust design Characteristic flow pattern ± 2% accuracy Discharge stroke Suction stroke Digitally controlled piston movements Constant piston speed ± 0,5% accuracy LEWA Bioprocess Technologies 20