STRATEGIES FOR NANOFILTRATION OF THERAPEUTIC PLASMA PROTEINS
|
|
- Magdalen Newman
- 6 years ago
- Views:
Transcription
1 STRATEGIES FOR NANOFILTRATION OF THERAPEUTIC PLASMA PROTEINS Oral Presentation: Pere Ristol Faro M, Canal JM, Marzo N, Caballero S, Belda F, Gajardo R, Grancha S, Ristol P R&D Area, Instituto Grifols S.A. Barcelona, Spain 1
2 Contents: Historical Summary of the Protein Nanofiltration Rationality for Nanofiltration Grifols Nanofiltration Background Plasma Protein Nanofiltration Development Strategies Case-studies: Fibrinogen: A High Molecular Weight Protein IVIG: A Cost - effectiveness Case Conclusion 2
3 Historical Summary of the Protein Nanofiltration Facts - Transmission of HIV during the 1980s. - Transmission of HCV and other enveloped and non-enveloped viruses during the After the tragedy of HIV transmission by plasma derivates and other viruses (in special HCV), as well as the concerns about emerging & new-born viruses, manufacturers of filters and fractionation industry began to work together for developing a new strategy to reduce the presence of viruses by means of size exclusion. This barrier technology was later called: NANOFILTRATION. The effective nanofiltration was introduced into plasma industry at the end of the 80s and it was growing in the 90s for processing the relative small proteins & enzymes (typically with molecular weight less than ~ 150 kda). Since the end of the 90s new membrane developments made it possible to increase the application of effective nanofiltration to processes up to medium-large proteins (i.e. molecular weight e 150 kda). 3
4 Historical Summary of the Protein Nanofiltration THE MAIN CONSTRAINTS TO CARRY OUT THE NANOFILTRATION ARE: TIME-CONSUMING PROCESS PROTEIN LOSS MEMBRANE AREA NEEDED (= COST) 4
5 First approaches used (in the past & currently) to avoid clogging of the nanometric membrane and to maintain acceptable flow-through Choosing the membrane composition: For minimum protein adsorption (limited fouling) - Regenerated cellulose - Polyvinylidene difluoride (PVDF) Selection of appropriate pore size of membrane according to the protein size by: - Metric dimension of pores (15 nm, 35 nm, 75 nm), or - Molecular weight of proteins (70 kda, 180 kda) Configurations: Historical Summary of the Protein Nanofiltration - Multi-layer membrane (hollow fiber), dead-end filtration: Running by entrapment mecanism - Tangential flow filtration: Minimum and constant protein layer thickness on the membrane during nanofiltration 5
6 Historical Summary of the Protein Nanofiltration The current situation (from the end of the 1990s up today): New developments in membrane composition, more pore sizes and configuration (folder) have improved nanofiltration for general application in almost all plasma proteins. - New Polyethersulphone & new PVDF membranes (+ regenerated cellulose) are available. - More membrane pore sizes: 20 nm and 50 nm (+ 15 nm, 35 nm, 75 nm & 180 kda) can be selected. - Dead-end, single, double or triple layer as well as multi-layer membranes, in cartridge folder or hollow-fiber, are available. 6
7 Historical Summary of the Protein Nanofiltration: Nowadays Application EFFECTIVE NANOFILTRATION OF PLASMA PROTEINS (BY PORE SIZE 20 nm) MARKETED PROTEINS: (11) IN DEVELOPMENT (*): IMMUNOGLOBULINS (IVIG, IMIG) ALBUMIN (JP company) FVIII (pd) (JP & FR company) ANTITHROMBIN-III A1-ANTITRYPSIN FIX PCC C1-ESTERASE INHIBITOR FXI (FR company) THROMBIN PROTEIN C a (JP company) Nowadays application VON WILLEBRAND FACTOR / FVIII FIBRINOGEN IV / FIBRIN-SEALANT PLASMIN IgM / IgA Note (*): Feasible according to published data, and not marketed yet NANOFILTRATION APPLICATION (BY ANY TYPE OF PORE SIZE): ALMOST ALL PLASMA PROTEINS 7
8 Among the Safety Technologies, Nanofiltration is unique: Rationality for Nanofiltration It is a very robust, feasible and flexible clearance technology. It permits efficient removal of enveloped & non-enveloped model viruses, as well as other pathogens. Nanofiltration enables high protein recovery with no undesirable effects on the product. Grifols included this nanotechnology more than 15 years ago. 8
9 Grifols Nanofiltration Background Grifols experience in plasma proteins nanofiltration 9 Plasma Protein Molecular Weight (kda) Nanofilter Pore size (nm) Thrombin ± 2 α1 Proteinase Inhibitor ± 2 Factor IX ± 2 Antithrombin ± 2 Prothrombin Complex (*) ± 2 Immunoglobulin G ± 2 Fibrinogen ± 2 A width range of molecular weight Plasma Proteins can be nanofiltered through small-virus Retentive Filters membranes ( 20 nm). Note (*): Under development
10 Nanofiltration Development Strategies Methodology Critical parameters that allow optimal nanofiltration performance: - Protein Features - Manufacturing Process - Nanofiltration Performance 10
11 Nanofiltration Development Strategies Protein Features & Manufacturing Process: Selecting the best stage Protein Size: Intrinsic limitation. Isoelectric Point: Effects on protein solubility and aggregation level consider ph & Ω. Impurities and contaminants: Presence of HMW proteins and some reagents (i.e. PEG). Protein Content: Protein concentration Viscosity & protein interaction Amount of protein to be nanofiltered (kg protein/industrial batch) Expected Loading Capacity (L/m 2 ). Stability: Labile biological activity proteins Process time becomes a limiting factor. 11
12 Nanofiltration Development Strategies Nanofiltration Performance itself Nanofilter pore size Foreseen Viral Retention Capacity Membrane composition: protein compatibility, adsorption or fouling Nanofilter structure (asymmetric, multi-layer, ): Impact on membrane Loading Capacity Operative filtration conditions: Tangential flow, dead-end, constant pressure, constant flux, temperature, rinse in pre & post-wash, Cost of goods Impact of Protein Recovery on total Yield Profit product margin 12
13 Nanofiltration Development Strategies Plasma Protein Nanofiltration Development Platform Protein Features Facility fit Recovery & Cost Scalability & Robustness Retention Capacity (LRV) Filterability Performance (Flux, t, Vmax) Manufacturing Process Nanofilter characteristics 13
14 NANOFILTRATION DEVELOPMENT CASE STUDY FIBRINOGEN: A High Molecular Weight Plasma Protein 14
15 Fibrinogen: A High Molecular Weight Case-Study Fibrinogen is a glycoprotein of 340 KDa. Raw material comes from the beginning of plasma fractionation (Cohn s Fraction I) Potential risk of viruses presence. Structurally complex protein, hexamer containing two sets of three different chains (α, β, and γ), linked to each other by disulfide bonds and with tendency to form aggregates. ~ 6.5nm ~ 45nm 15
16 Fibrinogen: A High Molecular Weight Case-Study Grifols aimed to develop a high purity & high safety Fibrinogen incorporating an effective 20 nm nanofiltration technology. Due to Fibrinogen size ( nm), structural complexity and adhesiveness, gentle nanofiltration conditions were tested: Low protein concentration minimizing protein interactions. Addition of stabilizers enhancing monomer content & filamentous tridimensional structure of the protein. High Nanofiltration Temperature (> RT) less viscosity. Location at terminal and higher purity process stages. 16
17 Fibrinogen: A High Molecular Weight Case-Study 1.- Determining maximal Fibrinogen concentration for NF performance: [Fibrinogen] (mg/ml) Filtered protein (at V max ) (g protein/m 2 ) NF Step Recovery (%) /50 61/ Only if Fibrinogen was very diluted, at 1 mg/ml, consistent nanofiltration capacity values (g/m 2 ) were obtained. However, nanofiltration recovery was not acceptable and additional purification was explored. 17
18 Fibrinogen: A High Molecular Weight Case-Study 2.- Effect of an additional intermediate Freezing /Thawing Step before 20 nm nanofiltration: Fibrinogen concent. Volumen filtered Nanofiltration Productivity Filtration Time NF Step Recovery (mg/ml) (g) (g/m 2 /h) (h) (%) Fresh material Filter blocked Not applicable Frozen / thawed material 0.74 >> No flow decay at this point ~90% The intermediate Freezing/Thawing step at defined conditions (thawing temperature, addition of stabilizers ), allowed aggregates and aggregable material to be removed. This additional polishing step enables the Fibrinogen nanofiltration through 20 nm. 18
19 Fibrinogen: A High Molecular Weight Case-Study A deep knowledge of the protein features and manufacturing process allowed the development of a 20 nm nanofiltration step for a HMW protein. Amount Protein Filtered (g/m 2 ) Productivity Consistency (n=5) Time (min) Flow decay (%) Flow decay Consistency (n=5) V Amount Filtered Solution (L/m 2 ) Due to the Flux decay profile reported Nanofilter Capacity becomes a limiting factor and Gradual Pore-Plugging Model could be applicable to predict the maximal & optimal throughput of the nanofilter: Linear equation: 1/Q = A x t + B ; A (slope) = 1 / Vmax Voptimum = 0.5 x V max = V Q75 = V (Throughput at 75% of Flux decay) 56 L/m 2 19
20 Fibrinogen: A High Molecular Weight Case-Study Conclusion The optimized process developed was very consistent at manufacturing scale, resulting in a less than 6 hours process time, high capacity (>56 L/m 2 ) and therefore costeffective nanofilter surface area. The designed NF process allows obtaining a highly safe Fibrinogen product: Reduction factors (log10/ml) 4 for smaller non-enveloped viruses (PPV, B19 Virus model, nm). 20
21 NANOFILTRATION DEVELOPMENT CASE STUDY IVIG: Increasing biological safety while maintaining a high product yield 21
22 Nanofiltration Development Strategies IVIG: A cost-effective Case-Study Grifols aimed to incorporate a 20nm filtration step in the most costeffective way: Main NF Targets: Maximal protein recovery & Lowest cost of goods Effective retention of smallest viruses ( 4 LVR) Secondary NF Requirements: Process time As terminal location as possible (facility fit). 22
23 IVIG: A cost-effective Case-Study Determining optimal IVIG concentration on NF by different nanofilter pore-sizes: 8 1,8 Capacity (kg protein/m2) nm (P35N) 20 nm (PVDF) 15 nm (P15N) Protein Concentration (%) Capacity (kg protein/m2) 1,6 1,4 1,2 1 0,8 0,6 0,4 0, (20 nm (Last Previous generation PVDF) Protein Concentration (%) Optimal [IVIG] conc. depends on filter pore-size. P35N shows a capacity increase vs. [protein] Low protein recovery and low capacity make the filtration of IVIG through 15 nm unfeasible. Optimal [IVIG] for nanofiltration by 20nm at ~20 h process time is ~3%, but capacity was not enough 23
24 IVIG: A Cost-effective Case-Study Once the 20-nm hollow-fiber filter was available a better performance was observed, display a Stable Flux Profile leading to high NF Capacity ( V max ~800 L/m 2 ; V 75 = 400 L/m 2 ; then, Process time = 45 h & total Area = 4 m 2 /batch). In this case, factors other than Capacity become limiting a compromise between Process Time and Surface Area was needed: How to determine it? OPTIMIZING NANOFILTER SURFACE AREA vs PROCESS TIME: Area x Industrial batch (m 2 ) Nanofilter Sizing (m 2 ) vs NF Time ~15 h Time (hours) 20 nm Multi-layer Hollow Fiber Biphasic kinetics: 1 st Phase: Drastic Reduction of nanofilter area with time. 2 nd Phase: The increase in process time impacts on a minimal reduction area. TOTAL AREA NEEDED = 8 m2 / BATCH PROCESS TIME = 15 h 24
25 IVIG: A Cost-effective Case-Study Kinetic profile of new generation 20 nm filters of lower cost are promoting new evaluations on licensed nanofiltered products: 200 Loading Ratio (L/m 2 ) Loading Ratio (L/m2) Time (h) Pre-established IVIG Capacity Target 20 nm NANO A (Reg.cellulose) 20 nm NANO B (PVDF) 20 nm NANO C (PES) 20 nm NANO D (PES) Very different performance is observed with different nanofilters under identical process & protein conditions. The operative optimal area is adjusted to Plugging Model or Area-Time graphic according to kinetics. 25
26 Nanofiltration: Future TREND OF NANOFILTRATION IN THE PLASMA PROTEINS INDUSTRY To explore the application of effective nanofiltration for all proteins as much as possible (preferentially to 20 nm size). To search better cost-effective nanofilters. Interchangeability in the use of commercial nanofilters with equivalent performance for licensed proteins. Simplicity for handling and assembling in process as well as in testing the post-use integrity (automatic control). 26
27 Nanofiltration Development Strategies Conclusion Grifols experience shows that dedicated work is needed to fit a nanofiltration step in every plasma protein manufacturing process, taking into account: - Critical aspects that allow an optimal NF performance are specific of every protein & every manufacturing process & every nanofilter However, once successfully achieved, robust and consistent virus retention capacity has been found in Grifols validation studies, under a wide range of process conditions. 27
28 28 Thanks for your attention!
A MANUFACTURING PROCESS TO OBTAIN A HIGHLY-PURIFIED TRIPLE-SECURED FIBRINOGEN PRODUCT
A MANUFACTURING PROCESS TO OBTAIN A HIGHLY-PURIFIED TRIPLE-SECURED FIBRINOGEN PRODUCT Maduell P, Domingo N, López L, Gensana M, Caballero S, Belda P, Gajardo R, Grancha S, Ristol P R&D Area, Instituto
More informationPlanova as a Virus Barrier for Biopharmaceutical Plasma Products
Planova as a Virus Barrier for Biopharmaceutical Plasma Products Tomo Miyabayashi Technical Marketing Bioprocess Division Asahi Kasei Medical Co., Ltd March 9 th, 2016 IPFA ASIA PACIFIC WORKSHOP Taipei
More informationMonoclonal Antibody Purification and Technology for Improving Virus Clearance
Monoclonal Antibody Purification and Technology for Improving Virus Clearance BioProcessing Network Annual Conference Brisbane, September 2009 Germano Coppola Technology Transfer Manager CSL Limited Outline
More informationHuman Protein Process Sciences, Lille, France 2. Shabrawishi Hospital Blood Bank, Cairo, Egypt 3. University of Saskatoon, Canada
1 Human Protein Process Sciences, Lille, France 2 Shabrawishi Hospital Blood Bank, Cairo, Egypt 3 University of Saskatoon, Canada Why such a concept? Non-virally inactivated plasma components are still
More informationVirus Safety in Plasma- Derived Therapeutics: A Merck Perspective. IPFA Yogyakarta, March Louis Wong
Virus Safety in Plasma- Derived Therapeutics: A Merck Perspective IPFA Yogyakarta, March 2017 Louis Wong Associate director, Plasma Initiative, Asia-Pacific Content Regulatory Expectations for Plasma-Derived
More informationUse of Fluidised bed chromatography for plasma fractionation. Karl McCann*, John Wu, Peter Gomme & Joseph Bertolini
Use of Fluidised bed chromatography for plasma fractionation Karl McCann*, John Wu, Peter Gomme & Joseph Bertolini Plasma Fractionation Industry Mature with well established processes Revenue growth -
More informationCrossflow Filtration for Ink Jet Fluids
Crossflow Filtration for Ink Jet Fluids For ink jet ink and colorant formulation, efficient filtration makes all the difference. Improve your process and product with crossflow technology. In recent years,
More informationFiltration of Cell Culture Growth Media and Process Buffers
Customer Application Brief Bioprocess, Biologicals, & Pharmaceutical Filtration of Cell Culture Growth Media and Process Buffers Introduction Media feeds and process buffers are two universal additives
More informationPrion Removal Capacity of Plasma Protein Manufacturing Processes
Prion Removal Capacity of Plasma Protein Manufacturing Processes 1 A data collection from PPTA member companies Presented by Nathan Roth, Ph.D. Director, Global Pathogen Safety CSL-Behring on behalf of
More informationBiotechnology of Human Plasma-Derived Medicines in Scope of Collaboration Perspectives within The Central European Initiative
Biotechnology of Human Plasma-Derived Medicines in Scope of Collaboration Perspectives within The Central European Initiative Dr Vadim Sentchouk PHARMLAND LLC Deputy General Director PLASMAPHARM LLC General
More informationMembrane Filtration Technology: Meeting Today s Water Treatment Challenges
Membrane Filtration Technology: Meeting Today s Water Treatment Challenges Growing global demand for clean water and increasing environmental concerns make membrane filtration the technology of choice
More informationMembranes & Water Treatment
Latest Membrane Technologies in Industrial Water & Wastewater treatment Ajay Jindal Larsen & Toubro Limited, Mumbai CII Water India 2011 New Delhi, February 11-12, 12, 2011 Membranes & Water Treatment
More informationA Hands-On Guide to Ultrafiltration/ Diafiltration Optimization using Pellicon Cassettes
Application Note A Hands-On Guide to Ultrafiltration/ Diafiltration Optimization using Pellicon Cassettes In ultrafiltration (UF) tangential flow filtration (TFF) systems, operating parameter selection
More informationEmerging and Enabling Technologies in Membrane Separations
Emerging and Enabling Technologies in Membrane Separations Andrew L. Zydney Distinguished Professor of Chemical Engineering The Pennsylvania State University 2 nd International Symposium on Continuous
More informationCross-flow filtration for discovery, scale-up and process clarification/concentration applications
biopharmaceutical / bioindustrial Cross-flow filtration for discovery, scale-up and process clarification/concentration applications lower binding and higher yields less fouling and longer service life
More informationPROCEDURE FOR USE NICKEL NTA Magnetic Agarose Beads (5%)
1 AFFINITY HIS-TAG PURIFICATION PROCEDURE FOR USE NICKEL NTA Magnetic Agarose Beads (5%) DESCRIPTION Nickel NTA Magnetic Agarose Beads are products that allow rapid and easy small-scale purification of
More informationAFFINITY HIS-TAG PURIFICATION
DESCRIPTION Nickel NTA Agarose Cartridges 5ml are used for purification of histidine-tagged proteins in native or denaturing conditions. This cartridge can be used with an automated chromatography system,
More informationR R Innovation Way P/N SECKIT-7830 Newark, DE 19711, USA Tel: Fax: Website: Published in November 2013
5-100 Innovation Way Newark, DE 19711, USA Tel:302-3661101 Fax:302-3661151 Website: www.sepax-tech.com Published in November 2013 P/N SECKIT-7830 These Phases are developed based on innovative surface
More informationBeer Filtration Solutions Your Partner for All Your Filtration Needs
Beer Filtration Solutions Your Partner for All Your Filtration Needs Advanced Filtration for Enhanced Quality and Increased Sustainability TM Filtration for a Better Future... How can KMS help you? Over
More informationRecent Advances in Membrane Technologies Peter D Adamo, Ph.D., P.E Spring Conference Wilmington, NC April 13, 2015
2015 Spring Conference Wilmington, NC April 13, 2015 Recent Advances in Membrane Technologies Peter D Adamo, Ph.D., P.E. 2014 HDR, Inc., all rights reserved. Membrane Filtration Basics Recent Membrane
More informationTechnical guide for the ELABORATION AND USE OF MONOGRAPHS ON HUMAN PLASMA- DERIVED PRODUCTS
Technical guide for the ELABORATION AND USE OF MONOGRAPHS ON HUMAN PLASMA- DERIVED PRODUCTS European Pharmacopoeia EDQM 2015 Technical guide for the ELABORATION AND USE OF MONOGRAPHS AND GENERAL CHAPTERS
More informationAdsorptive and Mechanical Mechanisms of Fluid Purification Using Charge Modified Depth Filtration Media. Dr. Robert Conway, Ph.D.
Adsorptive and Mechanical Mechanisms of Fluid Purification Using Charge Modified Depth Filtration Media Dr. Robert Conway, Ph.D. Depth Filter Cartridge Construction Zeta Plus Media Materials of Construction
More informationPurification of MS2 Bacteriophage from Complex Growth Media and Resulting Analysis by the Integrated Virus Detection System (IVDS)
Purification of MS2 Bacteriophage from Complex Growth Media and Resulting Analysis by the Integrated Virus Detection System (IVDS) Charles H. Wick* and Patrick E. McCubbin Summary Purification and concentration
More informationA comparison of automated and manual buffer exchange methods
pplication Note comparison of automated and manual buffer exchange methods Introduction uffer preparation, exchange and sample concentration for a formulation screen can take 2 4 days of a scientist s
More informationProSEC 300S. Protein Characterization columns
ProSEC 300S Protein Characterization columns Agilent s ProSEC 300S is a silica-based material specifically designed for the analysis of proteins by aqueous size exclusion chromatography. With a proprietary
More informationDevelopment of Enzyme Immobilization Technique
Development of Enzyme Immobilization Technique Professor SEUNG-WOOK KIM Laboratory of Bioprocess Department of Chemical and Biological In this presentation Enzymes Enzymes are are biological biological
More informationIntroduction to TFF. Sengyong Lee Ph.D. Professor/ Program Chair Biotechnology/ Biology Ivy Tech Community College Bloomington, Indiana
Introduction to TFF Sengyong Lee Ph.D. Professor/ Program Chair Biotechnology/ Biology Ivy Tech Community College Bloomington, Indiana Main Agenda Biomanufacturing and Filtration Filtration Principles
More informationDr. Anneliese Hilger Chair, Blood Products Working Party (BPWP)
Reference: EMA16006a BY E-MAIL Dr. Peter Bachmann Chair, Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh) Email: peter.bachmann@bfarm.de; H-CMDhSecretariat@ema.europa.eu
More informationProtein stability assessment after automated buffer exchange
pplication Note Protein stability assessment after automated buffer exchange Introduction uffer preparation, exchange and sample concentration for a formulation screen can take 2 4 days of a scientist
More informationLaboratory investigation in the Bleeding Patient. Dr Craig Taylor Consultant Haematologist May 2016
Laboratory investigation in the Bleeding Patient Dr Craig Taylor Consultant Haematologist May 2016 Introduction Bleeding is common May consume significant resources Crossmatched blood Lab results may be
More informationOptimizing Membrane Filtration Using the Revised Self Assessment Guide. Ed Chescattie Planning Section Chief SC Safe Drinking Water Program
Optimizing Membrane Filtration Using the Revised Self Assessment Guide Ed Chescattie Planning Section Chief SC Safe Drinking Water Program Background Self Assessment Guide (SAG) for Water Treatment Plant
More informationSubject Index. chromatography step, 125-
A Alert limits, description, 70 Aluminum hydroxide based vaccine manufacture, start up and validation of sterile formulation and filling processes, 144-168 Anion-exchange chromatography step for clinical-grade
More informationMEMBRANES PROCESSES USED IN BEER FILTRATION
HENRI COANDA AIR FORCE ACADEMY ROMANIA INTERNATIONAL CONFERENCE of SCIENTIFIC PAPER AFASES 2012 Brasov, 24-26 May 2012 GENERAL M.R. STEFANIK ARMED FORCES ACADEMY SLOVAK REPUBLIC MEMBRANES PROCESSES USED
More informationFibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion
Supplementary Information Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion Irina N. Chernysh 1, Chandrasekaran Nagaswami 1, Prashant K. Purohit 2 and John W. Weisel
More informationExcipient Albumin CSL Behring Human Serum Albumin
Excipient Albumin CSL Behring Human Serum Albumin For more information, contact CSL Behring USA: (610) 878-4000 1020 First Avenue King of Prussia, PA 19406-0901 Switzerland: +41 31 344 44 44 Wandorfstrasse
More informationNovel Technologies in Plasma Fractionation. Dieter Fassnacht
Novel Technologies in Plasma Fractionation Dieter Fassnacht Agenda Grifols Overview Grifols Engineering Innovations in - Pooling - Fractionation - Filling Developing new technologies to provide innovative
More informationViresolve Pro Solution
Data Sheet Viresolve Pro Solution Proven parvovirus safety solution designed to provide the highest levels of retention assurance and productivity Robust. Productive. Proven. The Solution provides a comprehensive,
More informationProduct. Ni-NTA His Bind Resin. Ni-NTA His Bind Superflow. His Bind Resin. His Bind Magnetic Agarose Beads. His Bind Column. His Bind Quick Resin
Novagen offers a large variety of affinity supports and kits for the purification of recombinant proteins containing popular peptide fusion tags, including His Tag, GST Tag, S Tag and T7 Tag sequences.
More informationCOMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP)
The European Agency for the Evaluation of Medicinal Products Evaluation of Medicines for Human Use London, 25 July 2002 EMEA/ COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE
More informationMagSi Beads. Magnetic Silica Beads for Life Science and Biotechnology study
MagSi Beads Magnetic Silica Beads for Life Science and Biotechnology study MagnaMedics Diagnostics B.V. / Rev. 9.2 / 2012 Wide range of products for numerous applications MagnaMedics separation solutions
More informationAn effective platform for purification of IgM monoclonal antibodies using Hydroxyapatite
An effective platform for purification of IgM monoclonal antibodies using Hydroxyapatite Frank Hensel, Patrys, GmbH Pete Gagnon, Validated Biosystems 5th International Conference on Hydroxyapatite and
More informationAffinity Chromatography Media. Cellufine Sulfate. Technical Data Sheet
Affinity Chromatography Media Cellufine Sulfate Technical Data Sheet Cellufine Sulfate For concentration, purification and depyrogenation of virus, viral/microbial antigens and heparin-binding proteins
More informationProtein-Pak Hi Res HIC Column and HIC Protein Standard
Protein-Pak Hi Res HIC Column and HIC Protein Standard CONTENTS I. INTRODUCTION II. a. Mobile Phase b. Flow Direction CONNECTING COLUMN TO LC SYSTEM I. INTRODUCTION This offering contains non-porous, polymethacrylate-based
More informationBIOPHARMACEUTICAL PROCESS EVALUATED FOR VIRAL CLEARANCE
The purpose of Viral Clearance evaluation is to assess the capability of a manufacturing production process to inactivate and/or remove potential viral contaminants. Experience and knowledge in selecting
More informationSuitability of analytical methods for detection of thrombogenic factor XIa in Privigen
Suitability of analytical methods for detection of thrombogenic factor XIa in Privigen Absence of thrombogenic factors in Privigen M. Moses, K. Ruhwedel, H.-A. Stöhr, L. Duse, A. Feussner, W. Wormsbächer,
More informationPathogens in Water. Monitoring, Control and Technologies Available for Treatment. Prepared by; Paul O Callaghan M.Sc. Dr.
Pathogens in Water National Water Summit, Tuesday, 2nd October 2007 Monitoring, Control and Technologies Available for Treatment Prepared by; Paul O Callaghan M.Sc. Dr. Hans Gethke Filtration of drinking
More informationDesigning Next Generation Chromatography Media for Modern High-Throughput Plasma Processes. Mats Gruvegård PPB 09 Menorca, Spain
Designing Next Generation Chromatography Media for Modern High-Throughput Plasma Processes Mats Gruvegård PPB 09 Menorca, Spain utline Introduction Process needs Performance Designing a base matrix Screening
More informationPerformance Evaluation and Cleanability Study using Pellicon 3 Cassettes with 30 kd Biomax and Ultracel Ultrafiltration Membranes
Application Note Performance Evaluation Cleanability Study using Pellicon Cassettes with kd Biomax Ultracel Ultrafiltration Membranes Consistent, high performance ultrafiltration throughout multiple process
More informationLABORATORY APPROACH TO BLEEDING DISORDERS DR NISHANTH PG 1 ST YEAR DEPARTMENT OF PATHOLOGY
LABORATORY APPROACH TO BLEEDING DISORDERS DR NISHANTH PG 1 ST YEAR DEPARTMENT OF PATHOLOGY 1 WHEN IS THE LAB REQUIRED TO INVESTIGATE FOR A POSSIBLE BLEEDING DISORDER? Clinically suspected bleeding tendency
More informationMicro- and ultrafiltration
CT4471 Drinking water I Dr.ir. S.G.J. Heijman micro- and ultrafiltration Micro- and ultrafiltration Application area filtration processes Size, µm Approximate moleculair weight Relative size of materials
More informationINSTRUCTIONS The resins are adapted to work mainly in native conditions like denaturing.
1 AFFINITY HIS-TAG PURIFICATION PROCEDURE FOR USE Nickel NTA Agarose Beads DESCRIPTION Resins are products that allow batch or column purifications. This product is supplied as a suspension in 50% aqueous
More informationPOROS HQ 50 and PI 50 resins in flow-through polish chromatography applications
APPLICATION NOTE POROS HQ 50 and PI 50 Resins POROS HQ 50 and PI 50 resins in flow-through polish chromatography applications Why and where to start? Introduction Anion exchange (AEX) chromatography products
More informationCase Studies of POROS Chromatography for Use in Vaccine and Large Biomolecule Purification
Case Studies of POROS Chromatography for Use in Vaccine and Large Biomolecule Purification Rev 1 (Life Tech template) Shelly Cote Parra April 2011 Topics Introduction to POROS Chromatography Products Principles,
More informationNephelometry and turbidimetry are liquid based immunoassays based on the measurement of scattered or absorbed light.
1 Nephelometry and turbidimetry are liquid based immunoassays based on the measurement of scattered or absorbed light. Light scattering is the physical phenomenon resulting from the interaction of light
More informationDynamic High Capacity Mustang Q Membrane Units for Scaleable Anion Exchange Chromatography Purification of Adenoviral Vectors
Contact Us: www.pall.com/contact Dynamic High Capacity Mustang Q Membrane Units for Scaleable Anion Exchange Chromatography Purification of Adenoviral Vectors Dynamic High Capacity Mustang Q Membrane Units
More informationOverall progress in the first quarter of 2007
F I R S T Q U A R T E R R E P O R T 2 0 0 7 Overall progress in the first quarter of 2007 Grifols has obtained a turnover of 181.8 million euros in the first quarter of the year, an increase of 20.4% compared
More informationOverview of Desalination Techniques
Overview of Desalination Techniques The objective of this chapter is to present an overview of current and future technologies applied to the desalination of brackish and seawater to produce freshwater
More informationBioprocess streams using mammalian
Retrovirus and Parvovirus Clearance from an Affinity Column Product Using Adsorptive Depth Filtration Barbara Tipton, Jeri Ann Boose, William Larsen, Joanne Beck, and Thomas O Brien Two types of depth
More informationAbstract Process Economics Program Report 188B BIOTECHNOLOGY SEPARATION PROCESSES (June 2002)
Abstract Process Economics Program Report 188B BIOTECHNOLOGY SEPARATION PROCESSES (June 2002) The chemical industry has a renewed interest in developing processes for producing industrial chemicals from
More informationDiffusional Contributions and Electrostatic Interactions during Ultrafiltration
Diffusional Contributions and Electrostatic Interactions during Ultrafiltration Andrew L. Zydney Department Head and Walter L. Robb Family Chair Department of Chemical Engineering The Pennsylvania State
More informationAffinity Chromatography Media. Technical Data Sheet. Life Chemicals Launch Office
Affinity Chromatography Media Cellufine Sulfate Technical Data Sheet Life Chemicals Launch Office 2-1, Otemachi 2-Chome Chiyoda-ku, Tokyo 100-8105 JAPAN Phone +81-3-3243-6150 Fax +81-3-3243-6219 e-mail:
More informationFiltration in Preparation of Cell Culture Media and Buffers
Filtration in Preparation of Cell Culture Media and Buffers Cell Culture Media and Buffers in Biopharmaceutical Production Cell culture media and process buffers are used in all biopharmaceutical operations.
More informationSign up to receive ATOTW weekly -
BLOOD PHYSIOLOGY PART 2 ANAESTHESIA TUTORIAL OF THE WEEK 231 11 TH JULY 2011 Dr Karen Hayes Royal Devon & Exeter Correspondence to: kmhayes@hotmail.co.uk QUESTIONS Before continuing, try to answer the
More informationTable of Contents. II. Kit Components III. Materials required but not supplied VII. Experimental Examples IX. Troubleshooting...
Table of Contents I. Description... 2 II. Kit Components... 2 III. Materials required but not supplied... 2 IV. Storage... 3 V. Protocol... 3 VI. Workflow... 4 VII. Experimental Examples... 7 1. Total
More informationKirill Ukhanov, GE Water & Process Technologies, Russia, describes how advanced membrane technology is helping a Russian refinery to meet stringent
Kirill Ukhanov, GE Water & Process Technologies, Russia, describes how advanced membrane technology is helping a Russian refinery to meet stringent wastewater requirements. In Russia, there are strict
More informationCreating Miracles in Life
Creating Miracles in Life November 2017 China Biologic Products Holdings, Inc. (NASDAQ: CBPO) Safe Harbor Statement 01 This presentation contains forward-looking statements, including statements about
More informationHigh-throughput Process Development with PreDictor Plates
GE Healthcare High-throughput Process Development with PreDictor Plates Principles and Methods Handbooks from GE Healthcare GST Gene Fusion System Handbook 18-1157-58 Affinity Chromatography Principles
More informationAFFINITY HIS-TAG PURIFICATION
DESCRIPTION Resins are products that allow batch or column purifications. This product is supplied as a suspension in 50% aqueous suspension containing 30 vol % ethanol. INSTRUCTIONS The resins are adapted
More informationAffinity Chromatography Media. Technical Data Sheet. Fine Chemicals Sales Department
Affinity Chromatography Media Cellufine Sulfate Technical Data Sheet Fine Chemicals Sales Department 2-1, Otemachi 2-Chome Chiyoda-ku, Tokyo 100-8105 JAPAN Phone +81-3-3243-6150 Fax +81-3-3243-6219 e-mail:
More informationStrep-Tactin XT Spin Column
Strep-Tactin XT Spin Column Purification Protocol Last date of revision Last June date 2017 of revision June 2017 Version PR90-0001 Version PR90-0001 For research use only Important licensing information
More informationab Factor VIIIa Activity Assay Kit (Fluorometric)
ab204696 Factor VIIIa Activity Assay Kit (Fluorometric) Instructions for Use For rapid, sensitive and accurate detection of Factor VIII activity. This product is for research use only and is not intended
More informationAnalysts presentation
Analysts presentation Los Angeles, March 5, 2008 Analysts Presentation. March 5, 2008. Los Angeles 1 Forward Looking Statements This presentation contains forward-looking statements based on current assumptions
More informationab Factor Xa Inhibitor Screening Assay Kit (Fluorometric)
ab204712 Factor Xa Inhibitor Screening Assay Kit (Fluorometric) Instructions for Use For rapid, sensitive and accurate screening of potential Factor Xa inhibitors. This product is for research use only
More informationCUNO APPLICATION BRIEF
CUNO APPLICATION BRIEF CUNO Zeta Plus VR Filters for Viral Reduction in Biopharmaceutical Processes Introduction: The removal and/or inactivation to a high level of assurance of contaminating viruses from
More informationISOLATE II Blood DNA Kit. Product Manual
ISOLATE II Blood DNA Kit Product Manual 2 Product Manual www.bioline.com/isolate Blood DNA Kit ISOLATE II Blood DNA Kit ISOLATE II Blood DNA Kit 1 Kit contents 04 2 Description 04 3 Storage 05 4 Safety
More information3M Purification Inc. Filter Systems for Small Molecule Pharmaceutical Purification
3M Purification Inc. Filter Systems for Small Molecule Pharmaceutical Purification 2 Filter Systems for Pharmaceutical Separations 3M Purification Inc. Core Filtration Applications 3M Purification Inc.
More informationProduct# TM Intended Use. use only and not for use in diagnostic procedures.
3430 Schmon Parkway Thorold, ON, Canada L2V 4Y6 Phone: 866-667-4362 (905) 227-8848 Fax: (905) 227-1061 Email: techsupport@norgenbiotek.com Norovirus TaqMan RT-PCR Kit Product# TM41400 Product Insert Intended
More informationMaterial Safety Data Sheet
Material Safety Data Sheet Date of issue: 14.02.2014 Supersedes edition of: 31.01.2014 1. Chemical Product and Company Identification Trade name: Common name: Kcentra Prothrombin Complex Concentrate (Human)
More informationNanofiltration for removal of humic substances
Techneau, D5.3.5B February 2008 Nanofiltration for removal of humic substances Survey on operational strategies Techneau Feb 2008 Nanofiltration for removal of humic substances Survey on operational strategies
More informationIgG Purity/Heterogeneity and SDS-MW Assays with High- Speed Separation Method and High Throughput Tray Setup
IgG Purity/Heterogeneity and SDS-MW Assays with High- Speed Separation Method and High Throughput Tray Setup High Throughput Methods to Maximize the Use of the PA 800 Plus system Jose-Luis Gallegos-Perez
More informationUltrafiltration Technical Manual
Ultrafiltration Technical Manual Copyright by: inge AG Flurstraße 17 86926 Greifenberg (Germany) Tel.: +49 (0) 8192 / 997 700 Fax: +49 (0) 8192 / 997 999 E-Mail: info@inge.ag Internet: www.inge.ag Contents
More informationGUIDE FOR THE ASSESSMENT OF CLOTTING FACTOR CONCENTRATES
GUIDE FOR THE ASSESSMENT OF CLOTTING FACTOR CONCENTRATES 3 rd edition Prepared by Albert Farrugia, BSc, PhD for the World Federation of Hemophilia Published by the World Federation of Hemophilia (WFH)
More informationMOLECULAR GATE TECHNOLOGY FOR (SMALLER SCALE) LNG PRETREATMENT
MOLECULAR GATE TECHNOLOGY FOR (SMALLER SCALE) LNG PRETREATMENT Presented at the 2010 Gas Processors 89 th Annual Convention Austin, TX March, 2010 Michael Mitariten, P.E. Guild Associates, Inc. Dublin,
More informationR.Li, C.Swaelens, F.Vandermijnsbrugge, B.Cantinieaux BSTH Laboratory of haematology, Porte de Hal,
Institut J. Bordet Normal with Actin-FS avoids intrinsic pathway factors assays in the presence of an isolated prolongation of (Platelin-LS) without hemorrhagic history R.Li, C.Swaelens, F.Vandermijnsbrugge,
More informationNickel-NTA Agarose Suspension
Nickel-NTA Agarose Suspension Agarose beads for purification of His-tagged proteins Product No. A9735 Description Nickel-NTA Agarose Suspension is an agarose-based affinity chromatography resin allowing
More informationTo date, the majority of
B i o P r o c e s s TECHNICAL Evaluating Adsorptive Filtration As a Unit Operation for Virus Removal Mario Metzger, Anja Gerster, Marcus Peiker, Sabine Faust, Alexander Faude, Sybille Ebert, Sophie Winterfeld,
More informationImmunoglobulins. Harper s biochemistry Chapter 49
Immunoglobulins Harper s biochemistry Chapter 49 Immune system Detects and inactivates foreign molecules, viruses, bacteria and microorganisms Two components with 2 strategies B Lymphocytes (humoral immune
More informationab65354 Superoxide Dismutase Activity Assay kit (Colorimetric)
Version 9 Last updated 11 January 2018 ab65354 Superoxide Dismutase Activity Assay kit (Colorimetric) For the measurement of Superoxide Dismutase Activity in various samples. This product is for research
More informationMEMBRANE SEPARATION MEMBRANE PROCESSING METHODS
College of Agricultural Engineering and Technology Dept. of Agricultural Processing and Food Engineering Course : Dairy and Food Engineering Chapter 12 MEMBRANE SEPARATION (Membrane processing methods
More informationMicroCap Depth Filter Capsules. Uniquely Flexible to Meet Your Processing Needs
MicroCap Depth Filter Capsules Uniquely Flexible to Meet Your Processing Needs Efficient, Cost-Effective Batch Processing A Capsule Suite Customized to Fit Your Processing Needs Eliminate Batch Pooling
More informationRhinophase -AB, Zirconia-based Monoclonal Antibody Purification System
Rhinophase -AB, Zirconia-based Monoclonal Antibody Purification System Welcome to the sixth issue of ZirChrom's electronic newsletter. This newsletter introduces a biocompatible stationary phase useful
More informationab Plasmin Activity Assay Kit (Fluorometric)
ab204728 Plasmin Activity Assay Kit (Fluorometric) Instructions for Use For rapid, sensitive and accurate detection of Plasmin activity. This product is for research use only and is not intended for diagnostic
More informationReverse Osmosis Operation & Maintenance of RO Sytems OLC117 Online Training Information Packet
Reverse Osmosis Operation & Maintenance of RO Sytems OLC117 Online Training Information Packet Costs $319 USD Price includes o Narration o Many illustrations Video clips Animations Pictures o Interactive
More informationE.Z.N.A. Stool DNA Kit. D preps D preps D preps
E.Z.N.A. Stool DNA Kit D4015-00 5 preps D4015-01 50 preps D4015-02 200 preps April 2013 E.Z.N.A. Stool DNA Kit Table of Contents Introduction and Overview...2 Illustrated Protocol...3 Kit Contents/Storage
More informationab Fibrinogen Human ELISA Kit
ab108842 Fibrinogen Human ELISA Kit Instructions for Use For the quantitative measurement of Human Fibrinogen in plasma. This product is for research use only and is not intended for diagnostic use. Version
More informationSimplicity is the key Continuous purification of monoclonal antibodies
Simplicity is the key Continuous purification of monoclonal antibodies L. Landric-Burtin Head of Downstream Processing Development, France Integrated Continuous Biomanufacturing Conference, Barcelona,
More informationFiltration Applications for the Refining & Petrochemical Industries
Refining Petrochemicals Filtration Applications for the Refining & Petrochemical Industries Process Proven Performance Quality Filtration Made Simple Filtration Applications for the Refinery & Petrochemical
More informationAFFINITY HIS-TAG PURIFICATION
DESCRIPTION Resins are products that allow batch or column purifications. This product is supplied as a suspension in 50% aqueous suspension containing 30 vol % ethanol. INSTRUCTIONS The resins are adapted
More informationINNOVATIONS IN ADVANCED MEMBRANE TECHNOLOGIES
INNOVATIONS IN ADVANCED MEMBRANE TECHNOLOGIES QUA Group LLC QUA Group - China One Four Coins Drive Canonsburg, PA 15317 USA Tel: +1 877 782 7558 wieslerf@quagroup.com 15 Floor, Huilong 54-56 Zhongzhou
More information