Disposable process equipment, once a tiny niche market, has seen dramatic growth in the past few years, as drug manufacturers adopt single-use systems to reduce cleaning, sterilization and their associated validation costs. A recent study by Stedim and Biopharm Services  found that shifting from traditional stainless steel to disposable process equipment can reduce biopharma manufacturing costs by 8-9% per batch, and overall capital costs by 21%.
Converts to single-use systems are now demanding larger and integrated systems; some vendors even offer prevalidated process systems, and others are joining forces to design new systems. However, some drug makers who haven’t made the switch to disposables are concerned about the plastic materials leaching into product or contaminating solvent, and want to avoid getting locked into one source of the materials .
To address these concerns and develop standards for disposable equipment, the Bio-Process Systems Alliance, a division of the Society for the Plastics Industry, was established last year. The organization, which came together at last year’s Interphex conference, has 40 members, all manufacturers of single-use bioprocessing systems, according to Jerold Martin, a Pall Corp. executive who is on the Alliance’s executive board and who chairs its Guidelines Committee. Martin expects that number to increase to 50 by the end of this year.
The organization’s standards subcommittees are focusing on specific components — films and containers, filter capsules, tubing and connectors — to review quality tests and methods, and establish a matrix of quality tests and references. The Alliance expects to publish qualification test methods this month, in time for Interphex 2007.
Throughout the world’s biopharmaceutical manufacturing facilities, disposable systems are being used as bioreactors to prepare and store buffers and cell cultures, filter virus, harvest cells and handle bulk sterilization. In January, Lentigen, Inc. selected Wave Biotech’s Cellbag disposable bioreactors and ancillary mixers, tube sealers and fusing devices, for the manufacturing of its gene delivery systems.
Materials consultant Don H. Miller, Ph.D., has outlined a systematic methodology for evaluating the risks of extractables or leachables in disposable equipment, which is accessible via the Alliance’s web site (www.bpsalliance.org). Test criteria must satisfy 21CFR211.65 as well as the ICH API Good Manufacturing Practices 5.11.
- Sinclar, A. and Monge, M. “Quantitative Economic Evaluation of Single-Use Disposables in Bioprocessing,” Biopharm Services.
- Monge, M., “Successful Project Management for Implementing Single-Use Bioprocessing Systems,” Biopharm International, November 2006.
Following is a small sampling of new disposable biopharmaceutical process equipment systems that some Alliance members have developed for pharma applications.
Based on a joint venture equally owned by HyClone and Alfa Laval Biokinetics Inc., Alfa Laval has developed a single-use mixing system based on the HyNetics mixing technology. This patented technology incorporates single-contact process surfaces with a complete stand-alone hardware platform. Capacities range from 30 L to 10,000 L. The mixers can be used to prepare media, buffer, final formulations, IV solutions, intermediate solutions and homogenous suspensions for adjuvanted vaccines.
Alfa Laval Biokinetics, Philadelphia, Pa.
Tel: (215) 656-2511; www.hynetics.com
This manufacturer offers a wide variety of biomedia containers that can be used to contain pH-sensitive sterile liquid cell-culture media, salt solution, serum products, cell cultures, buffers and artificial nutrient liquids. Standard sizes are offered using Class VI medical grade materials ranging from 250 mL to 2,500 L.
Advanced Scientifics, Millersburg, Pa.
Tel: (717) 692-2104; www.advancedscientifics.com
Tubing and Connectors
This manufacturer specializes in connectors for single-use process equipment. They may be customized, using Ys, Ts, cross Ts, reducers, mini and standard Tri-Clamps, bottle stoppers and sealers, and tubing. The tubing and connectors are designed to eliminate entrapment issues and leaks that have been associated with barbed fittings. Components are permanently bonded into one single-use unit, reducing the risk of cross-contamination.
AdvantaPure, Southampton, Pa.
Tel: (215) 526-2151; www.advantapure.com
AppliFlex is the result of an alliance between Applikon and Stedim. The combination of the bioreactor with sensors and control system offers opportunities for cGMP applications. The AppliFlex bioreactor is made of Stedim 7.1 film, with the bag and pH, dissolved oxygen and temperature sensors designed for single use.
Applikon Biotechnology, Foster City, Calif.
Tel: (650) 578-1396
Aseptic Sampling Device
This manufacturer’s aseptic sampling device was designed to sample ultrapure biopharma process fluids safely and efficiently. The ergonomic device comes fully assembled and ready to use in any closed system. The device is designed to minimize the chance of cross-contamination, and can be customized.