Bioprocess Vision - Issue 2 - October 2011

Regional Versions (PDFs):

Market Trends

New Single-Use Mixer Improves Process Efficiency

The single-use market has developed over the last few years from simple liquid filtration and containment applications to progressively more complex process operations. One area where such progress has been widely reported is in the applications of single-use mixing.

Single-use mixing is used throughout manufacturing processes to perform a variety of operations from preparation of upstream media and downstream buffers, to final formulation prior to filling.

As with other single-use technologies, implementing single-use mixing provides significant savings relative to cleaning and cleaning validation costs, as well as providing faster, more flexible methods for solution preparation and improved risk management through added safety for containment and removing risks of cross-contamination.

Pall Allegro 200 L single-use mixerA single-use mixing device should be designed based on proven engineering principles to provide efficient, robust mixing performance. It should also be designed to be user-friendly, due to the increased interaction of operators with these types of systems (installation and removal of the single-use component of the mixers needs to be easy and quick).

The new Pall Allegro 200 L single-use mixer incorporates the same design principles and film material as our existing 200 L biocontainer and tote products, providing extreme ease-of-use and materials consistency for reduced validation requirements. The mechanically coupled low shear pitched blade impeller provides exceptional mixing performance in critical applications, such as formulation.

For further information: Allegro™ 200 L Single-Use Mixer

Product News

Advanced Filtration for Growth Media

Growth media used in cell culture or for aseptic process validation may be susceptible to contamination with mycoplasma - cell-wall free bacteria capable of penetrating 0.2 micron (μm) rated sterilizing grade filters. To minimize the risk of contamination of these fluids, Pall recommends 0.1 μm rated sterilizing grade filters validated for removal of both Brevundimonas diminuta bacteria and mycoplasma such as Acholeplasma laidlawii.

Fluorodyne® EX EDT Filters
These innovative sterilizing-grade filters incorporate a highly asymmetric upstream PES pre-filtration layer over dual 0.1 μm PVDF membrane layers. They feature a unique “laid-over pleat” construction in 254 mm (10 in.) sub-assembly formats, with a narrow core design for the highest effective filtration area per device. This combination of innovative features allows for optimal filtration performance for moderate to high fouling complex culture media, and can enable the downsizing of multi-stage filter systems to single stage operations. In addition to enabling process economical advantages these features facilitate the introduction of these sterilizing-grade filters into single-use systems.

Fluorodyne II DJL Filters
With a 0.2 μm/0.1 μm dual PVDF membrane layers, these sterilizing-grade filters offer the highest flow rates and good capacity - well suited for low-fouling, defined growth media.

For further information: Sterile Filtration and Bioburden Control

Chromatography Systems for GMP Applications

PKP Chromatography SystemsDesigned for optimum performance in a flexible GMP operating environment, the PKP Chromatography Systems are offered in a broad flow range that ensures maximum reproducibility and yield. System versatility is key at pilot scale, when product quality and throughput are top priorities. PKP Chromatography Systems facilitate either conventional or membrane chromatography in small-scale production, as well as being highly suitable for process optimization studies.




Features:
  • Family of 3 systems encompassing a flow range of 1-150 L/h
  • Modular system design
  • Stainless steel construction is cGMP compliant
  • Optimized clean-in-place CIP design
  • 21 CFR Part 11 compliant software automation
  • The Pall PKP and PK Chromatography Systems cover a flow range of 1-4000 L/h, ensuring robust operation and flexibility for all biochromatography applications.

For further information: PKP Chromatography Systems

Chromatography Columns for Pilot Scale

Pall’s Resolute FM columnsPall’s Resolute FM columns are specifically designed for purification processes from development to small-scale GMP production. Several innovative features of these columns ensure ease-of-use combined with optimal packing and performance. A unique tilt mechanism facilitates air removal and eliminates manual handling of the adjuster for improved safety.






Features:
  • Unique constant compression adjuster seal simplifies operation
  • Three column sizes: 100, 140 and 200 mm diameter
  • Easy air removal prior to column packing
  • Adjuster enables packing without removal from the column
  • Packing compression factor to x1.2cf

Resolute FM columns complement larger Resolute DM/DP columns (280-2000 mm). In combination with the PKP or PK Chromatography system platform, they provide comprehensive solutions for biochromatography applications.

For further information: Resolute® FM Chromatography Columns

Application

The Pall Scientific and Laboratories Services (SLS) department provides technical and validation support for Allegro single-use processing systems used in drug development as well as clinical and production manufacturing operations. Services include study design and execution, with protocol and reports ready to support regulatory submission for the following:

  • Extractables / Leachables Testing (incl. NVR, FTIR, TOC, GC/MS, LC/UV/MS/MS, and ICP/MS)
  • Sterilizing Filter Validation
  • Filter and System Compatability
  • Shipping Studies
  • Particle and Endotoxin Analyses
  • Mycoplasma and Bacteriophage Retention Testing 

Validation Services for Allegro Single-Use SystemsAll testing is conducted in accordance with industry best practices, including Parenteral Drug Association (PDA) and BioProcess Systems Alliance (BPSA) recommendations. Our global team of scientists and engineers provides rapid local response to your GMP validation needs.

For further information: Single-use Validation





Interview

WFI and Process Fluids Filled into Allegro Biocontainers

hameln pharmaceuticals gmbh is a contract manufacturer of parenteral solutions. Within a diverse product range they offer water for injection (WFI) and process fluids, all prepared to cGMP. High QA standards are applied to these products making them suitable for use in biopharmaceutical development and production. All fluids are distributed in Pall Allegro single-use systems.

Who are your customers for WFI and buffers filled into bags?
Mainly biopharmaceutical companies with a demand for high quality solutions, but they may not have the expertise, equipment, capacity or time to prepare WFI or buffers according to cGMP. They find a number of benefits in using disposable items: ease-of-use, high flexibility of system design and short timelines - all of which may be relevant to the demands of each project. They find that disposable systems minimize the risk of cross contamination, and reduce the demand for post-use cleaning and cleaning validation. Consequently, single-use systems also offer significant potential for cost reductions.

Which requirements do you have for your equipment?
We apply exactly the same quality requirements to our suppliers that we apply to ourselves. A key aspect is compliance with regulatory demands, which has been confirmed to us repeatedly in numerous audits by authorities like FDA or ANVISA (Agência Nacional de Vigilância Sanitária; National Health Surveillance Agency of Brasil). Comprehensive validation data is also extremely important.

Why did you choose Pall for your program?
The quality aspect of Pall’s portfolio fits perfectly with our own requirements. Allegro single-use systems are flexible in design and the application of the same film material across the range has important scalability benefits. KleenpakTM Sterile Connectors and Kleenpak Sterile Disconnectors are excellent options for maintaining sterility during product transfers.

What about customized solutions?
This is routine for us: most of our customers look for individual solutions that cannot be provided by off-the-shelf products. Pall’s Allegro concept offers versatility and scope for such designs, as our services also include customized stability studies and storage of bags for clients.

What do you expect in the future?
The market for biopharmaceuticals will grow and result in increasing demand for process specific solutions of the highest quality. It is our intention to align ourselves with the growth of the industry: it is a natural expansion of our service portfolio, building on our broad experience in cGMP-compliant production and filling of sterile solutions. We look forward to further successful collaborations with Pall!

For further information: bpvision@pall.com

Internet Highlights

Biopharmaceutical Webinar Series

We are pleased to offer a series of webinars designed to be educational and informative on the latest industry trends and to provide updates on new technologies. The presentations are given by biopharmaceutical industry leaders and experts. Have you missed one of our live webinars? Not a problem, as all Pall Biopharmaceutical webinars are also made available on-demand. 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)

  • Determination of Extractables/Leachables from Single-Use Systems: How Pall Life Sciences Helps Users Meet Regulatory Expectations While Minimizing Test Time and Cost
  • Sterilization of Single-Use Systems by Gamma Irradiation: How Pall Life Sciences Ensures Sterility of Irradiated Systems

 Additional webinar topics will be advertised on the web several weeks in advance of their live dates. Should you have any suggestions for future webinar topics, please email your ideas 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
  • Mustang® Membrane Chromatography - The Flexible Solution to High Speed Contaminant Clearance
  • Protein Stability and Aggregation – Clues to Better Formulations

Webinar Series – Recently Held

Sterilization of Single-use Systems by Gamma Irradiation: How Pall Life Sciences Ensures Sterility of Irradiated Systems
Sterilization by gamma irradiation has been well established for over 25 years in the medical device and healthcare product industries. However, for many in the biopharmaceutical industry gamma irradiation represents a “new” sterilization method with significant differences from moist heat sterilization and validation procedures. As single-use systems become more applied in critical sterile product manufacturing processes, it is important for users to have a clear understanding of procedures and quality systems designed to ensure drug product sterility.

This webinar provides an introduction to gamma irradiation and how sterilization is validated to meet regulatory cGMP requirements for sterile processing, according to harmonized industry standards. Topics include system evaluation and bioburden level determination, minimum dose verification and sterility assurance levels, irradiator design, dose quantification and mapping, load density effects, dose and sterility audits.

For further information: Biopharmaceutical Webinar Series

For further information on any of the articles within this newsletter, or to suggest topics for future editions of BioProcess Vision please  contact us.