血漿分画製剤


© CSL Ltd, 2010


New, improved production methods and technology are helping to significantly improve product purity, ensuring optimal safety and improving yields of plasma-derived proteins in plasma fractionation.Pall leads the way with an unrivalled range of innovative products, technologies and integrated processes to protect and enhance both the quality and safety of your plasma products, including:
 
 
For full support with your Plasma Applications
DOWNLOAD ARTICLE
DOWNLOAD ARTICLE
Removal of immunoglobulins and Factor (F)XI from Human Plasma IgG
READ ARTICLE
READ ARTICLE
Removal of S/D Inactivating Agents with HyperD Sorbents
DOWNLOAD POSTER
DOWNLOAD POSTER
Optimising IVIG Manufacturing Around Established Precipitation Techniques
Download Poster
Download Poster
Evaluation of Single-pass TFF for Plasma Proteins

Intravenous immunoglobulin (IVIG) Processing

IVIGs are increasingly used to treat immunodeficient patients as well as autoimmune, inflammatory or neurological disorders, and continue to be one of the dominant drivers of growth in plasma fractionation today.

Bringing its latest state-of-the-art products and technologies together, Pall introduces a new strategy for the purification of IVIGs, enabling significant improvements in both quality and yield.

At the heart of this strategy is a new chromatographic purification method combining consistently high-yield manufacturing with dedicated removal of contaminants – all without impairing IgG recovery1.

1 Wu Y.W., Champagne J., Toueille M., Gantier R., Burnouf T., “Dedicated removal of immunoglobulin (Ig)A, IgM, and Factor (F)XI/activated FXI from human plasma IgG”, Transfusion, 2014 Jan; 54(1):169-78.doi:10.1111/trf.12243. Epub 2013 May 23 (link to external site)

  • High IgG yield:recovery >85% total, final purity >99.5%
  • High removal of potentially side-effect-causing contaminants:<0.5% IgA and IgM, Factor XI undetectable
  • No UF/DF between HyperCel™ S capture step and HyperCel Star AX sorbent intermediate step
  • If required, ムスタング S membrane absorber can be used to remove Factor XI to processes starting with Fraction II+III

沈渣物分離

Modern plasma fractionation processes include ethanol precipitation, with precipitates usually separated using a combination of plate-and-frame filtration and depth filter sheet technology.目的タンパク質を沈渣物として回収することや、ろ過によって清澄化(溶液中に溶けている場合)することの両方の場合に使用できます。この手法は、デプスフィルターと組み合わせることによって、さらに容易な操作となり、迅速で定量的で循環しないシングルパスでの清澄ろ過や、多量でも高収率の沈渣物回収を実現します。

Filtration offers higher protein yield in simplified and faster separation processes.



Clarification and Pre-Filtration

Cost reduction in subsequent steps in the 'downstream' process can be achieved by optimizing clarifying filtration.Our wide range of ザイツ® depth filters allows a cost-effective, convenient format to achieve the right balance between filter life and downstream protection in the bulk of applications.Specially-developed ザイツ depth filters for color removal, lipid removal, PKA removal and prion removal represent very efficient purification technologies.

Filtration of Resuspended Precipitate

The clarification of resuspended precipitate by filtration is an important step for the efficiency of further downstream steps.Depth filtration with スタックス systems offers significant advantages in terms of yield increase, cost reduction and GMP compliance.

Benefits include:
  • Up to 75% reduction in hold up volume
  • Up to 80% reduction in draining time
  • Significant reduction in post-wash volume due to favourable filter area/housing volume ratio
  • Yield increase compared to conventional depth filter systems
  • Single use, no CIP required
  • No costs for cleaning validation
  • No risk of cross contamination
  • Movable system and flexible to use at different process steps
Read more about スタックス systems



クロマトグラフィーによるタンパク質の回収と精製

クロマトグラフィーは、工程を改善するために重要な技術課題となっています。近年、イオン交換やアフィニティークロマトグラフィーは、血漿分画製剤製造の幅広い工程で使用されています。高性能の樹脂担体や、効率性を高めたカラム本体、そして高いタンパク質回収率と高い精製効率を両立させるためのシステム、ソフト、さらには、 ウイルス不活化除去、例えば、溶媒/界面活性剤の除去用の技術を提供します。ポールは、幅広い溶媒域での高い吸着容量のあるイオン交換担体ミックスモード、溶媒/洗浄剤 (S/D) 除去用担体、さらに高い溶出速度を実現したメンブレンクロマトグラフィーを提供しています。

Read more about Pall's chromatography capabilities



Removal of Solvent and Detergent Viral Inactivating Agents

Solvent/detergent inactivation (SDI) is a robust, well established method for viral clearance of protein solutions, widely applied in plasma fractionation and receiving increasing attention in the Biotech industry as well.A key challenge of SDI however, is the removal of the S/D agents from the treated protein solution.

Pall’s SDR HyperD Solvent-Detergent Removal Chromatography sorbent combines a high protein exclusion limit to maximize proteins recovered in the flowthrough and a purpose-designed adsorbent chemistry that provides efficient, high capacity removal of the S/D agents.

Read more about Pall’s chromatography sorbents



限外ろ過と脱塩操作

Tangential Flow Filtration (TFF) has long been established as a leading technology for concentration and diafiltration of plasma proteins.Continuous improvement of the cassette performance and new Innovations ensures further improvements in modern plasma fractionation processing.High performance PES and regenerated cellulose membrane cassettes combined with significant material and design improvements deliver:
  • Optimum mass transfer
  • Lower extractables
  • Easy scalability
Read more about Pall’s TFF technologies



Single-use TFF ケイデンス single-use tangential flow filtration modules are supplied gamma-irradiated and ready-to-use.Providing ease-of-use, quick turnaround and increased flexibility, safety and containment in cGMP operations, they are easily implemented in アレグロ single-use TFF systems, scalable from R&D to full production.

Preferably used for small and mid size plasma batches like hyperimmunes as well as less abundant proteins (like coagulation factors, antithrombin, α1-antitrypsin protease inhibitors).

Read more about ケイデンス single-use TFF modules



High-Quality Bioprocessing Solutions

Pall provides scalable, benchtop or custom designed TFF systems to suit your specific plasma fractionation process needs, covering the full technology range from conventional stainless steel systems to single-use TFF systems.

ケイデンス™ Single Pass Tangential Flow Filtration Technology (SPTFF) Systems are capable of achieving high concentration in direct flow operation which substantially simplifies and streamlines downstream processing.
  • Successful use of ケイデンス single pass TFF systems for concentration of albumin and IgG solutions demonstrated in case studies (see reference)
  • The single pass TFF technology is ideally suited for processing of higher concentrated intravenous and subcutaneous IgG formulation
  • Concentrate chromatographic column eluates in-line
  • その他のダウンストリーム工程との直接接続
  • 高い回収率 (98%以上)
  • せん断力に対し、不安定な目的物質のプロセス最適化
  • 低コストで高い能力を発揮
  • 高価なストレージタンクが不要
  • 少ないホールドアップ容量
Read more about ケイデンス single-pass TFF systems



Single-use, In-Process Volume Reduction

ケイデンス Single-Pass TFF In-line concentrator modules incorporate a patented fluid path design that enables in-process volume reduction without the need for a holder.The modules can easily be connected to a pressure source (pump or pressure vessel), or can be implemented in a system to reduce process volumes by a factor of 2–4 in direct flow operation.

Read more about the ケイデンス single-pass TFF in-line concentrator



Virus Filtration

For all plasma-derived medicinal products, it is an objective to incorporate effective steps for inactivation/removal of a wide range of viruses of diverse physico-chemical characteristics.

In order to achieve this, it is desirable to incorporate at least two distinct effective steps.Virus filtration has demonstrated robust and reliable viral reduction and is a state of the art virus safety step in plasma fractionation processing.

ペガサス™ SV4 Virus Removal Filters combine high viral clearance and process cost control.They demonstrate highly-efficient clearance of both small "non-enveloped" viruses and large viruses and offers high retention robustness to pressure interruption (also described as pressure release or start/stop).

The filter membrane ensures a constant and stable flow-rate when used with either dilute or complex/concentrated biological fluids, which significantly improves virus filtration economy in plasma fractionation processing.All cartridge filters and single-use capsules can be autoclaved.In addition cartridge filters are fully compatible with SIP (steam-in-place).An easy and reliable in-situ integrity test can be applied pre-use and post-use.The filter is complemented by fully-automated virus filtration systems including the アレグロ MVP system designed with a fully disposable fluid path.All these systems enable consistent and precise operation with improved process efficiency.

Read more about ペガサス SV4 Virus Removal Filters



Virus Inactivation

The アレグロ MVP single-use system was designed to perform the pH adjustment steps needed in media preparation and virus inactivation, with fully automated addition of acid and base stock solutions.アレグロ mixers can be used with the MVP system, to ensure rapid dispersal of the added fluids during these process steps.

A large selection of pre-designed manifolds is available, with a specially designed manifold selection tool to help identify the most suitable manifold for your application.A choice of sensors, connectors, tubing type, filters and pre-filters when selecting a flowpath ensures the manifold is completely suited to your process application.ムスタング® membrane adsorbers add the capability to remove viruses by chromatography in highly-efficient way.Where SDI inactivation is used, SDR HyperD® Solvent-Detergent Removal chromatography sorbent is also used to achieve satisfactory removal of the S/D agents, without reducing protein yields.

Read more about the アレグロ MVP single-use system



Read more about SDR HyperD membrane adsorbers

ろ過滅菌とバイオバーデン管理

All the way through the process - for buffer, vents and right up to final filling, Pall® filters for both gases and liquids assure the highest level of protection in IVIG processing.

New Pall-patented technologies are incorporated into several new sterilizing-grade filters, contributing to higher flow rates and superior throughput performance to meet the increasing demand in high concentration IVIG application.

スーポア® ECV filters and フロロダイン EX Grade EDF filter cartridges are validated high-flow, high-capacity sterilizing-grade filters.They are constructed with patented laid-over pleat technology combined with a built-in asymmetric prefilter layer.
  • Enables superior high flow rates and throughputs also in complex and high concentrated IVIGs
  • Significantly reduces COGS
Read more about スーポア® ECV filters and フロロダイン EX Grade EDF filter cartridges



シングルユーステクノロジー

A proven technology alternative in plasma fractionation offering several significant advantages over standard reusable stainless steel systems, single-use technologies can improve the handling of intermediates (freeze/thaw, liquid transport, storage), and can also:
  • Reduce the risk of cross-contamination
  • Remove the need for cleaning and associated cleaning validation
  • Minimise capital investment
  • Reduce lead times and the number of connections, to enhance sterility assurance
  • Hold up volume and post wash volume
  • Reduce COGS in water consumption and autoclaving
  • Reduced consumption from utilities and energy
Read more about Pall single-use technologies