Bioprocess Vision - Issue 3 - April 2012

Regional Versions (PDFs):


Market Trends

Your Path to Bioprocess Success

Pall Life Sciences will showcase its newest lineup of leading-edge products and services to enhance bioprocessing workflows at two upcoming international conferences. The company will demonstrate how its technologies for upstream and downstream processing can be "Your Path to Bioprocess Success" in drug development and production at Interphex and Achema. Interphex takes place May 1-3 in New York, USA; Achema will be held June 18-22 in Frankfurt, Germany. Visitors to Pall's booths will explore critical steps in bioprocessing and discover fast and flexible solutions at every stage of the process: Flexibility in Media Prep, Reliability in Cell Culture, Simplicity in Cell Clarification and Cell Harvest, Scalability in Downstream Processing, Safety in Contaminant Control and Polishing, and Consistency in Formulation, Filling, and Pharma QC. We are happy to explore all this together with you.

On the following pages you will find numerous new products worth considering for existing or new processes. At Interphex and Achema, all these will be featured together with other groundbreaking innovations, amongst them new bioreactor technologies, new chromatography sorbents, new membrane filters and new disposable devices such as single-use needles and plastic and transportation totes.

We are happy to provide reliable and fully integrated solutions for the design, manufacturing, and service of our products. All these will help you to ensure timely biopharmaceutical process development and procurement of production capacity. We are looking forward to seeing you soon at Interphex, Achema, or one of the many other events we attend all over the world!

For further information: Achema info

Product News

Allegro Single-Use TFF System

The system combines the advantages of Allegro single-use manifolds with an engineered automated system design, providing reliable control of key parameters and ease-of-use in manufacture.

Adopting a single-use approach for TFF can provide reductions in:
  • System preparation and cleaning time and costs
  • Downtime in the production area
  • Risk of batch or cross contamination
  • Validation time and costs
The system has 12-in. tubing and a feed pump capacity of 1000 L/hour. It can be run with 20 L or 100 L feed biocontainers, and run in fed batch mode for processing larger volumes.

Single-use TFF manifolds:
  • Are supplied gamma-irradiated
  • Incorporate pre-calibrated single-use instruments
  • Require simple installation (15 minutes)
For further information: Single-use TFF System

New Variants for Kleenpak Sterile Disconnectors

The addition of two smaller diameter versions of the Kleenpak sterile disconnector, 14 in. and 38 in. hose barb formats, provides users with a wider range of application potential.

  • Typical applications include:
    • Sample biocontainer
    • Separation for QC testing
  • Separation of fluid handling assemblies around bioreactors
  • Disconnection of sterile filters for offline integrity testing
  • Removal of sterile filtration sets from filtered buffer or media
The Kleenpak sterile disconnector allows for the separation of single-use systems, whilst maintaining the sterility of, or managing the general bioburden levels within, the separated sections. The demand for single-use systems integrating sterile disconnectors is increasing at a fast rate and the new size variants facilitate wider application of these enabling technologies, to further simplify operations and improve process safety.

For further information: KLeenpak sterile disconnectors

Allegro Bioprocessing Workstations for Single-Use Systems

The new Allegro bioprocessing workstations from Pall provide extreme ease-of-use around operations and activities that utilize disposable or single-use systems. The typical applications that these workstations can be used for include:
  • Clarification and product storage: using Stax™ depth filter modules
  • Filter and single-use system support for buffer filtration and storage.
  • Chromatography fraction collection and storage around downstream operations
  • Sterile filtration support with in situ integrity testing and product storage
Available in two basic formats (single or double column width) and with a range of frame extensions, plastic trays and supporting hardware (such as filter supports and document holders), these workstations can greatly assist in the safe handling, protection and general flexibility for a wide range of operations from small scale development activities through to full scale production.

For further information: Allegro bioprocessing workstations

Palltronic AquaWIT IV Filter Integrity Test System

Water Intrusion Testing is the most convenient in situ integrity test for hydrophobic filters. However – reliable, reproducible results can only be achieved with suitable measurement methods and tightly-controlled filling and temperature conditions.

Pall's new Palltronic AquaWIT IV system utilizes the on-board Flowstar IV instrument to control up to three pneumatic valves to isolate the test filter, fill the housing/capsule with water and perform the entire test automatically. The system can also perform a fully automated Forward Flow or Bubble Point test for liquid filters.

Features
  • Fully automated preparation and testing of hydrophilic or hydrophobic filters
  • All critical test parameters controlled to ensure reproducibility of test results
  • Fully supports electronic signatures according to 21 CFR Part 11
  • Internal open process control (OPC) server for communication with process control systems
For further information: Palltronic Aquawit IV

5 in. Fluorodyne EX Sterilizing Grade Filters

High capacity Fluorodyne EX filters with built-in prefiltration are now available in 5 in. filter cartridge and filter capsule configurations. These allow for the downsizing of single 10 in. or dual stage filter systems, and as a result, lower filtration costs.

0.2 μm-rated Fluorodyne EX grade EDF membrane filters are recommended for the sterile filtration of cell harvest, process intermediates, and for some niche applications such as the filtration of liposomal fluids in vaccine manufacturing.

0.1 μm-rated Fluorodyne EX grade EDT membrane filters combine high capacity performance with additional safety. With outstanding mycoplasma removal efficiency for A. laidlawii and M. orale (typically > 10 LRV), they are a primary recommendation for filtering cell culture media or growth media as bioreactor feeds and used during aseptic filling validation.

For further information: EDT membrane and EDF membrane

Pegasus Grade SV4 Small-Virus Removal Filters

Coming soon: The new Pegasus SV4 small-virus removal filter offers constant, stable flow-rate performance and outstanding throughput capacity, enabling maximum filtration economy. It demonstrates highly-efficient clearance of both small 'non-enveloped' viruses and large viruses, even showing constant, stable flow-rate performance when used with either dilute or complex/concentrated biological fluids. It also offers stable pressure/flux capability in more complex or concentrated feeds, helping improve virus filtration economy in highly-concentrated protein solutions, without unnecessary product dilution. Flow decay caused by unwanted membrane 'plugging' and gel polarization is also kept to a minimum over a wide range of process conditions and extended process times. All of these factors combine to ensure that Pegasus SV4 virus removal filters can be established as a platform technology enabling high virus safety and significantly reducing processing costs.

For further information: Pegasus Grade SV4

Membrane Chromatography in Process Development

Mustang XT Acrodisc units, the latest addition to Pall's membrane adsorbers, are available in Q and S chemistries. They have been designed to be fast, easy to use, and ideal for scale-down process development in a variety of applications. These include protein purification and sample preparation in research laboratories, contaminant removal in biotech and plasma fractionation as well as contaminant removal and large molecule capture in vaccines manufacturing. The new units can be easily connected to low pressure chromatography systems and offer excellent performance over a broad range of flow rates.

Features:
  • Device volumes <1 mL to minimize sample requirements
  • Easy scale up due to consistent 16 membrane layer format
  • Flow rates of up to 10 MV/min at low pressure drop
  • Female Luer Lock inlet/outlet connections
For further information: Membrane chromatography

Sentino Microbiology Pump

The Sentino pump streamlines analysis by replacing the traditional vacuum filtration system with a small peristaltic pump that channels fluid directly to drain. Simple operation, compact design, and portability make it easy to use in confined spaces and frees valuable benchtop space for better workflow efficiencies. The disposable fluid path provides easy maintenance and superior contamination control in a busy microbiology laboratory - no more cleaning, wrapping or autoclaving a bulky manifold.

Features
  • Compact Size - takes up less space
  • Portable - rechargeable battery or use a standard electrical outlet
  • Simple Operation - no programming or data storage to validate
  • Peristaltic Design - fluid flows in one direction
  • Disposable Fluid Path - replace before biofilm build-up becomes a problem
For further information: Sentino pump

Acrodisc MS Syringe Filter for LC/MS Applications

The Acrodisc MS syringe filter is the first syringe filter specifically designed and certified for low extractables in high performance liquid chromatography/mass spectrometry (LC/MS) applications. The filter improves the accuracy of testing, enhances LC/MS performance, and extends the longevity of sensitive testing instrumentation. The low extractable levels minimize interference with the ionization process and reduce the need for re-testing. These features lower costs while minimizing instrumentation downtime due to unexpected contamination.

Features
  • Certified low in LC/MS extractables
  • Low in ion suppression and ion enhancement
  • Excellent chemical resistance due to water wettable PTFE membrane
  • Low protein binding
For further information: Acrodisc syringe

Application

The Results are in.... Pall customers excel in 2012 FOYA

Every year, the International Society for Pharmaceutical Engineering (ISPE) makes awards in their Facility of the Year competition. For 2012, two category awards went to facilities where Pall played an extensive role in providing innovative equipment and support.

For "Equipment Innovation"1, Rentschler Biotechnologie GmbH (Laupheim, Germany) was the winner, with the citation concluding "Jointly developed was a highly automated skid for virus filtration that can accommodate a wide variety of manufacturing protocols." Pall also provided many other systems.
 
These systems were discussed by Rentschler at a conference hosted by the National Institute of Bioprocessing Research and Training (NIBRT) in Dublin, who won the "Novel Collaboration" category2. Pall's work with NIBRT was featured in a recent press release3 describing the "master class on the use of single-use systems in the development and manufacturing of biopharmaceuticals."
1 www.facilityoftheyear.org/foyawinners2012#Rentschler
2 www.facilityoftheyear.org/foyawinners2012#NIBRT
3 news.pall.com/article_display.cfm?article_id=4614

For further information: bpvision@pall.com

Interview

Two filters better than one?

Regulatory authorities around the world promote risk assessment to ensure drug product safety. We interviewed Jerold Martin about recent discussions with regulators.

Jerry, how is the expectation of regulators changing with regard to drug products that cannot be sterilized in their final container?
Sterilizing filtration is still the norm for these products. US FDA requires that sterilizing filtration be validated under worst case conditions (a service provided by Pall). EMA accepts this, but European GMP also recommends use of a second sterilizing filter (usually 0.2 micron rated) for added sterilization assurance.

Using two filters to do one job seems excessive, do the regulators mandate this?
Only selectively. It's optional under US FDA guidance and the European GMP guidance is not universally mandated across Europe. However, some European country inspectors do expect it.

Is integrity testing of both filters required?
Post-use integrity testing of the final sterilizing filter is always required. Testing of "double" (serial) filtration schemes, however, can vary. Where the first filter is used as a prefilter, it is not required to integrity test it because the product upstream of the final filter must be sampled for bioburden anyway. In a redundant scheme, if the second (final) filter passes a post-use integrity test, the product can be considered sterilized without testing the first filter. The benefit of redundancy is that if the final filter fails the integrity test, and the first filter passes, the product is still considered sterile. Where both filters are required for sterilization, then both will need to be integrity tested, at least post-use.

How about pre-use testing?
Although some EU Inspectors are requiring pre-use testing after steam sterilization, pre-use testing does not affect patient safety and is primarily a business decision to avoid loss of the batch or rework in the event of a non-integral filter. It can ensure that shipping, handling and installation, as well as the sterilization process, have been done correctly.

Lastly, can these test procedures be applied to single-use systems?
Certainly. For single use systems, Pall provides standard and customized designs suitable for use in compliance with regulatory requirements, as well as offering consultancy and training workshops on filtration system design, installation and integrity testing that many users find extremely beneficial.

References:
PDA Technical Report TR26 (2008)

FDA Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice (September, 2004)

EC Guide to GMP - Revision to Annex I - Manufacture of Sterile Medicinal Products (Revised Feb, 2008 - Effective March, 2009)

EMEA Committee for Proprietary Medicinal Products (CPMP). Note for Guidance on Manufacture of the Finished Dosage Form (CPMP/QWP/486/95) (April, 1996)
For further information: bpvision@pall.com

Internet Highlights

Biopharmaceutical Webinar Series

Detailing the latest industry trends and providing updates on new technologies, Pall Life Sciences' series of webinars are both educational and informative. The presentations are given by biopharmaceutical industry leaders and experts. Have you missed one of our live webinars? Not a problem. All Pall Biopharmaceutical webinars are also made available on-demand to be viewed at your convenience. See information on right for the content of our most recent live webinar.

Please visit www.pall.com/biopharmwebinars for more information and to register.

Biopharmaceutical Webinar Series (current topics)

  • Membrane Chromatography – A Flexible Solution to High Speed Contaminant Clearance
  • Thermal Stability and Aggregation Analysis – Clues to Better Formulations
  • Determination of Extractables/Leachables from Single-use Systems
  • Sterilization of Single-use Systems by Gamma Irradiation
Additional webinar topics will be announced several weeks in advance of their live dates. If you would like to be notified or have suggestions for future webinar topics, please send an email to bpvision@pall.com

Upcoming webinar topics include:
  • Post-Sterilization / Pre-Use Integrity Testing of Sterilizing Grade Filters: Regulatory Expectations, Technical Issues and Pall Recommendations
  • Complex Single-Use Unit Operations: The Process and Economic Benefits of Replacing Traditional with Single-Use Tangential Flow Filtration

Webinar Series – Recently Held

Membrane Chromatography - A Flexible Solution to High Speed Contaminant Clearance
Continual improvements in upstream processing have led to higher protein expression levels, resulting in downstream titers in excess of 1g/L, even reaching 10g/L. These advances directly impact the downstream process, leading to potential bottlenecks. However, trends such as the use of higher capacity chromatography sorbents with improved selectivity, and an increase in the use of single-use technologies such as membrane chromatography, are gaining momentum in the biopharmaceutical industry.

Efficient contaminant removal from such processes is very challenging and this is an application where membrane chromatography is proving very popular. Its ease of operation, speed, and efficiency are helping to reduce processing time and cost, as well as improve overall process productivity. This webinar will provide the basic principles of membrane chromatography and illustrate specific customer applications of how this technology, when incorporated into the process, saves time and cost.

The webinar is now available on-demand at www.pall.com/biopharmwebinars.

Further Information

For further information on any of the articles in this newsletter, please visit www.pall.com/biopharm or email us at bpvision@pall.com