Single-use equipment comes of age

11th December 2014

Posted By Paul Boughton

The Flexsafe range of single-use bags initially will be used for validation purposes before being rolled out into other applications
The KUBio concept has single-use technology at its heart

Single-use equipment such as bags, containers, fermenters, mixers and rectors help to keep production costs down and improve plant flexibility. Sean Ottewell reports.

Demand continues to grow for the single-use (disposable) equipment used in biopharmaceutical manufacturing. Advantages over traditional stainless steel solutions include the lack of need for cleaning in place procedures – and the associated savings in steam and water – reduced investment costs and better use of space.

One supplier, Sartorius Stedim Biotech, has just introduced its latest offering, a scalable range of single-use bags. The Flexsafe product family enables the implementation of single-use bioprocessing throughout all steps of drug manufacture, from process development to production, upstream and downstream – all using just the one innovative polyethylene film.

Sartorius says that the innovative concept of the Flexsafe family addresses key industry requirements for future-proof single-use manufacturing of commercial vaccines and drugs.

Flexsafe is based on a multi-layer, proprietary polyethylene (PE) film called S80 and has been developed in close collaboration with resin and film suppliers. A standardised cell growth assay has been used to optimise film formulation, determine the operating ranges for extrusion, welding and gamma-irradiation processes, and to establish specifications and process controls.

The company says that this ensures excellent and reproducible cell growth behaviour of the most sensitive cell lines. The optimisation of the resin formulation, the complete control of raw materials, the extrusion process and the bag assembly together guarantee lot-to-lot consistent cell growth performance.

“With its robust 400μm thick PE film, Flexsafe is the strongest and most flexible bag currently on the market. The bags enable safe and easy-to-use operation, even in the most demanding applications such as liquid shipping and large-scale stirred bioreactors,” notes the company.

An added benefit is that batch-to-batch consistent extractables and leachables profiles support drug manufacturers throughout the entire lifecycle of modern biological treatments from clinical development to commercial supply many years after launch. This gives users the assurance they need that their initial extractable and leachable qualification work and data remain valid every time they operate a single-use Flexsafe bioprocess.

Sartorius has also moved to tackle another issue raised by single-use solutions; security of supply. The company says that this is guaranteed as a result of its long-term contracts with suppliers and its business continuity plans with defined safety stocks and global manufacturing capabilities – including resin manufacturing.

To begin with the company is launching a 1-200 litre range of the new bags for validation purposes. Bags for single-use reactors and additional applications such as storage, mixing, shipping freeze and thaw will be rolled on a step-by-step basis.

Off-the-shelf production plant

Worldwide demand for monoclonal antibodies for the treatment of cancer and rheumatoid arthritis – as well as for a new generation of vaccines – is increasing, driven by the global ageing population, and the global effort to reduce the incidence of vaccine-preventable diseases.

Although increasing in popularity, monoclonal antibodies are among the world’s most expensive categories of drugs. The reason for this is that to retrieve the antibodies, the manufacturers must go through a long process of harvesting cell cultures and then purifying the antibodies. Once this process is completed, the drug-makers have removed proteins and other cell debris present in the cell culture, leaving only the desired antibodies. The production facilities needed to do this are an added cost.

An off-the-shelf solution from GE Healthcare known as KUBio can help meet the manufacturing needs of cancer-fighting monoclonal antibodies. Effectively a set of preassembled units, a cGMP-compliant KUBio facility capable of manufacturing over 100 kg/year of monoclonal antibodies can be up and running in 14-18 months. However, the concept would not be a success without the high-performance, single-use technology at its heart (Fig. 2). This includes GE Healthcare’s WAVE bioreactor, part of the company’s ReadyToProcess platform – which in turn is part of its ecomagination portfolio. Ecomagination is an initiative which helps GE’s customers to improve their bottom line and reduce environmental impact.

“KUBio represents the first manufacturing activity in-country-for-country in the growing economies, supporting the sustainable supply of biologic drugs, reducing import costs and increasing accessibility and affordability to local populations. We are very proud of this product and it could make a real difference to emerging economies,” said GE Life Sciences enterprise solution leader, Olivier Loeillot.

Meanwhile, Applikon Biotechnology is focused on pre-sterilised and pre-qualified single-use modules, citing as benefits faster facility set-up, reduction in down time, simplified validation and more efficient use of plant floor space.

The company offers a selection of single-use bioreactors in three basic formats: flexible bag bioreactors; rigid stirred tank bioreactors; and flexible stirred tank bioreactors. All bioreactor designs offer measurement and control of important process parameters.

The Appliflex flexible bag systems support both classical electrochemical sensor technology and optical sensors for pH and dissolved oxygen. Appliflex bioreactors are supplied in 10 litre, 20 litre and 50 litre total volumes.

For its part the CellReady bioreactor is a disposable version of the Applikon three-litre glass autoclavable bioreactor and can be used as a direct replacement of these systems.

The HyClone SUB (single use bioreactor) is available in volumes ranging from 50-2000 litres. The system can be equipped with classic sensors or with PreSens fluorophor sensor technology for pH and dissolved oxygen.

Single-use addresses specialised needs

During scale-up of cell culture in the manufacturing of biotherapeutics, specialised approaches are used to address the novel characteristics of these bioproduction processes. Cell culture conditions and consistent growth are critical to the biochemistry of the active components during expression, recovery, and purification.

According to Life Technologies, single-use technologies address these specialised needs. Single-use products have revolutionised the field of biomanufacturing: “With single-use technologies, it’s now possible to make small amounts of drug product that might be suitable for preclinical and clinical testing. Prior to the availability of these single-use systems, this would have required substantial facilities to produce the material needed,” says the company.

Today single-use technologies are used throughout the workflow of bioproduction, from buffer and media preparation to bioreactor cultures for vaccines to the storage and shipping of intermediates and bulk biologics.

To this end the company now offers a comprehensive suite of single-use technology products to support all bioproduction needs, including bioprocess containers and bags, manifold assemblies, outer support containers, single-use fermenters, single-use bioreactors, and single-use mixers. Life’s single-use technologies are also designed to integrate perfectly with its portfolio of cell culture serum, media, supplements, buffers, and other process liquids.

For example, the stirred-tank reactor is one of the most commonly utilised reactor types in biotechnology. Life’s single-use bioreactors (SUB) are designed as stirred-tank reactors for animal cell culture, using traditional stainless steel bioreactor principles for optimal cell culture performance - with the novel advantage of utilising completely single-use product contact surfaces to help reduce contamination and minimise clean-up.





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