May 1, 2008 (Vol. 28, No. 9)

Single-Use Components Take Center Stage at Interphex 2008
Thousands of professionals from the pharmaceutical and biopharmaceutical industries gathered at “Interphex” in Philadelphia on March 26–28. Educational presentations, workshops, and the opportunity for companies to display and demonstrate their latest products, technologies, and service offerings spanned the four major components of Interphex: facilities, outsourcing and contract services, information technology, and manufacturing/processing.

During a press briefing at the meeting, Sartorius Stedim Biotech announced the culmination of a collaborative effort with NewAge Industries to produce a line of single-use bag products with a built-in identification and tracking system. Sartorius has integrated the AdvantaPure GammaTag™ Radio Frequency Identification (RFID) technology into its disposable Flexboy® bioprocess containers to provide traceability and documentation for the lifecycle of the bag.

Sartorius plans to phase in implementation of the RFID biobag tracking system over the next six to eight months and will begin offering the system as an option to customers by the end of this year.

When a bag first comes into a facility it is logged in with its date of manufacture, lot number, part number, and a description all entered onto a microchip embedded in the bag. The end user can read the chip and see that the bag has passed quality control and can then enter his or her name, the date, and the intended use of the bag onto the chip. The bags can be gamma irradiated for sterilization without erasing or damaging the chip.

PreVAS is a prevalidated, preassembled, and presterilized line of disposable, single-use dosing systems from Bosch Pharma designed for the filling markets. Customized systems are clean-room assembled, gamma irradiated, and ISO 11137 validated for sterility. They are scalable to clinical and production quantities and are supplied ready-to-use, requiring only drug compatibility testing. The PreVAS system uses a positive-displacement, rolling-diaphragm pump composed of pharmaceutical-grade plastic fittings, tubing, connectors, and filling needles intended for one-time use.

Disposable Bioreactors

When ATMI Life Sciences acquired LevTech in January, it added the company’s mixing technology, single-use mixing hardware, and disposable agitators to its line of specialty plastics and single-use processing systems.

At “Interphex,” ATMI highlighted its Nucleo™ single-use bioreactors: the Nucleo-50 available with a 25 or 50 L bag and the Nucleo-1,000 for use with the currently available 200 L bag and with a 500 or 1,000 L bag in the future.

With an integrated internal paddle mixing system, Nucleo functions like a classical stirred-tank bioreactor, except that the bag, paddle, and fittings are disposable. The gamma-sterilizable bags are made of a multilayer film with the contact layer composed of ultralow-density polyethylene resins. A jacketed container for the Nucleo systems offers temperature control with a thermo-circulator optional.

Nucleo features include the Pad-Drive™ mixing system with speeds adjustable from 20 to 130 rpm. Both models include two fixed-speed peristaltic pumps with an option for two more as well as two external variable-speed peristaltic pumps for fed-batch and perfusion applications. The Nucleo-50 has three ports for probes and sensors and 10 multipurpose ports for inoculation, feeds, sampling, or reagent additions. The 1,000 L capacity model includes three to six probe/sensor ports and 14 multipurpose ports. Both systems are operated by the company’s Neptune™ SCADA process control software.

Thermo Fisher Scientific expanded its range of HyClone single-use bioreactors, adding 100 L and 500 L maximum working volume units to the existing range of 50, 250, and 1,000 L units. These stirred-tank bioreactor systems with a reusable stainless steel outer container and disposable inner bag have a heating/cooling water-jacketed design to allow for temperature control.

“The 1,000 L unit, introduced in 2007, is now jacketed as well,” added Kent Nelson, marketing communications manager.

Filtration and Chromatography

GE Healthcare showcased its suite of disposable filtration and chromatography products including single-use crossflow devices and prepacked and presanitized chromatography columns containing, for example, Capto Q, MabSelect SuRe, or Capto adhere media.

To fulfill its vision of a fully disposable, sterile biopharmaceuticals manufacturing process flow based on its line of single-use WAVE Bioreactor™ systems, GE acquired exclusive rights to BioQuate’s Disposable Aseptic Connector for use in connecting its ReadyToProcess and Wave bioprocessing components to upstream and downstream feed lines and process-fluid sources.

These single-use connectors feature a genderless locking design, eliminating the need for male-to-female connections. Advantages include rapid connections, a variety of sizes, and direct connection of different size tubing, thus reducing inventory needs, according to the company. Verified aseptic connections are possible without special operator training, tools, or a clean-room environment. The connectors can be gamma irradiated or autoclaved.

In addition, GE Healthcare has a strategic partnership with Finesse Solutions to develop a WAVE Bioreactor control package based on the company’s TruLogic™ controller and TruBio™ SCADA control software.

New from Pall Life Sciences is the PallSep™ Biotech vibrating membrane filter system. It is designed for processing bioactive materials such as vaccines that may be difficult to process using traditional tangential-flow filtration devices or centrifugation, explained Gareth Leach, Ph.D., global marketing manager. The system is compatible with highly fouling feedstocks as the combination of continuous vibration and a hydrophilic membrane prevents filter clogging while enabling retention and concentration of insoluble proteins through multiple washes.

The system offers the advantages of higher shear and higher recovery rates compared to other methods that require multiple reslurrying steps and is energy efficient, according to Dr. Leach. The vibrational energy generates shear forces of greater than 50,000/sec at the membrane surface.

The membrane stack—containing polyethersulfone filter membranes in areas of 0.2, 1.0, and 5 m2—is manufactured as a single, encapsulated module for enhanced durability and ease of installation and cleaning. Product development has focused on therapeutic protein recovery, clarification of high suspended-solids broths, and processing of plant and animal extracts. The company has worked with industry partners to test the unit in recombinant vaccine production and allergen purification for vaccine manufacturing.

Pall also introduced the Allegro™ 3-D, single-use biocontainers. They are designed for ease of installation without the need for additional tooling or operator intervention during filling processes.

These disposable containers are composed of the same film as in Pall’s 2-D, single-use biocontainers. They have low extractables and leachables and offer broad chemical compatibility. It thereby simplifies operational scale up by eliminating the need for film re-evaluation, according to the company. They are available in process volumes of 100, 200, or 500 L and are compatible with Allegro System components including filters, tubing, connectors, and separation devices.

Process Enhancements

New Brunswick Scientific featured the new BioFlo 510® fermentor, a sterilize-in-place benchtop or mobile system with a working volume of 19.5 L or 40 L. The vessel headplate and sidewall contain several ports for flexibility in positioning probes, spray balls, valves, or a pressure transducer, for example.

Users have the option of incorporating up to four thermal mass flow controllers or a rotameter and can select from three impeller options. The Reactor Process Controller, also used in the company’s BioFlo 310 and 415 fermentors as well as the CelliGen 310 and 510 bioreactors, can simultaneously regulate up to 32 process loops with integration of up to 14 sensors, analyzers, flow controllers, or other external devices. Process control software can monitor trends in eight process parameters at one time and retain up to 10 batch recipes.

SciLog’s SciPure™ automated tangential flow filtration system is designed for methods development as well as pilot-plant and small-scale production. It provides real-time data collection during concentration and diafiltration processes as well as continuous control and monitoring of feed, retentate, and permeate line pressures as well as trans-membrane pressure, the company reported. Pressure data feeds into a software-driven fluid-handling system that automatically adjusts the pressure and/or flow rates.

To aid in methods development, the system can simultaneously generate flow rate and pressure scans. The SciPure™ 300 GMP system offers automated purification (ultrafiltration, microfiltration, concentration, and diafiltration) and documentation for GMP manufacturing, according to SciLog.

Althea Technologies discussed its cGMP contract production of recombinant proteins, DNA-based therapeutics, and vaccines as well as commercial formulation and aseptic filling processes that meet both FDA and EU regulatory requirements. Althea’s Express PathwaySM program helps companies identify and develop genetic biomarkers for clinical diagnostics production.

Earlier this year, Althea announced the spin-off of Althea Diagnostics, which will commercialize the company’s genetic-testing technology and gene-expression products for use in monitoring and managing cancer treatment.

Rapid Micro Biosystems showcased its recently commercialized Growth Direct™ system, an automated digital-imaging system for detecting microbial contamination in pharmaceutical and biotechnology products. The system includes consumable Growth Cassettes™.

Previous articleInvestigators Generate Sequence-Based Map of Structural Variations
Next articleTorreyPines Licenses Glutamate-Receptor IP from Johns Hopkins