A look at the speed, safety and economic benefitsof integrated, single-use filtration systems
By Holly Haughney, Ph.D.
Single-use products have become prevalent in almost every facet of life today, from cameras to contact lenses. They're cost-effective, convenient and easy-to-use. However, when you apply the benefits of disposability to the biopharmaceutical world, the implications are far greater. Single-use biopharmaceutical products not only transcend the economics of disposable consumer products, but they also improve the speed and safety of drug development and delivery.
Over the next couple pages, we'll explore the advantages of integrated, single-use filtration systems over stainless-steel, hard-piped systems and the applications in which they are used. The purpose is to demonstrate how biopharmaceutical companies can bring products to market faster and more economically by using disposable systems.
What are single-use filtration systems?
Integrated, single-use filtration systems are comprised of disposable bags and capsule filters and are coupled together with tubing, clamps, adaptors and connection devices.
The single-use system contains a bag coupled with a filter capsule. The heart of the system, the bag, is used as a substitute for stainless steel and glass containers. Photo courtesy of STEDIM S.A.
The heart of the system, the bag, is used as a substitute for the stainless-steel and glass containers traditionally used by the pharmaceutical industry for fluids such as media (serum- and non-serum-containing as well as special formulations), buffers, reagents, sanitizing agents, cell harvest fluid, intermediate and final products. The corresponding single-use capsule filter serves as an effective substitute for stainless steel housings that require installation of filter elements. To meet the needs of biopharmaceutical companies from pilot phase to production, a fully integrated, single-use filtration system should be able to filter 100 to 2,500 liters (or more) of fluids.
The single-use nature of this type of filtration system eliminates the need for system maintenance, cleaning and cleaning validation, and avoids any possibility of contamination from product to product or batch to batch. This not only provides economic benefits, but safety and time-to-market advantages as well.
Single-use systems are used for fluids such as media (serum- and non-serum-containing as well as special formulations), buffers, reagents, sanitizing agents, cell harvest fluid, intermediate and final products. Biopharmaceutical fluids require filtration, ranging from 0.2-micron filtration for sterilization, and 0.1-micron filtration for mycoplasma removal and virus filtration.
Bag and filter suitability
Respective suitability of the coupled bag and filter capsule are critical to realizing the benefits of these systems.
A single-use filtration system must be scaleable to meet biopharmaceutical manufacturers' changing process needs as they move from discovery to pilot, and eventually to production.
Capsules can be coupled together for large-volume single-use systems that require pre- and final filtration. Photo courtesy of Pall Corp.
As such, a variety of bags and filter capsule options must be available to biopharmaceutical companies to ensure that the most appropriate and economical disposable filter scheme is used. It is also important that the filtration system use the same materials of construction during scale up to ensure reproducible results. This saves time and simplifies process development and design.
Because a fully integrated, single-use system, including the filter, bag, tubing and other components, is manufactured and sterilized as one, it eliminates the contamination risks associated with aseptic connections during coupling.
Single-use filtration systems also ensure that operators do not come in contact with cleaning solutions, cytotoxic fluids or buffers with extreme pH.
Complete material traceability also has a strong impact on the safety and efficacy of the filtration system. To ensure complete material traceability, the filtration system provider must have control over the entire process, from raw materials used to make the bags and filters to sterilization of the final product.
Time and cost savings
In addition to the time and costs saved in eliminating cleaning, maintenance and sterilization, an integrated filtration system shaves off 10 to 15 minutes for each aseptic connection that need not be made. These connections can also be difficult to establish in cramped environments.
Stainless-steel, hard-piped systems and glass containers are not only costly to clean and sterilize on a batch-by-batch basis, but they also require proper cleaning validation documentation for regulatory authorities.
Biopharmaceutical companies can realize a cost savings of 50 percent at each phase of scale up by replacing stainless-steel, hard-piped systems with single-use systems. In this way, biopharmaceutical companies can save proportionately more as they scale toward production. Single-use systems generally have a smaller footprint than hard-piped systems, and are, therefore, more economical when expanded to filter greater volumes of fluid.
Seeing is believing
Unlike stainless-steel systems, single-use systems designed with translucent housings can show process fluids in the bag, tubing and capsule filters. The ability to see the fluid enables operators to observe fluid levels and flow, as well as spot fluid discoloration and air pockets immediately.
A different kind of sterilization
The process by which single-use filtration systems are sterilized provides another source of enhanced safety. Disposable systems are sterilized by gamma irradiation, and are supplied sterilized and ready for immediate use. Gamma rays from Cobalt 60 isotope provide electromagnetic energy that can penetrate materials to destroy microorganisms. This process is predictable, consistent and safe because products are irradiated in their final packaging.
Unlike gamma irradiation, stainless-steel systems are steam sterilized, which introduces production time delays and requires validation and maintenance of the steam assembly. In many cases, the filter is sterilized separately from the fluid-containing tank, and an aseptic connection is required.
Gamma irradiation works by using a sufficient amount of energy needed to kill microorganisms. However, the radiation dose should not be too high, as it can cause the material to be modified. The appropriate dose can be set and validated following the procedures for ISO 11137, which was developed by the Association for Advancement of Medical Instrumentation (AAMI) and has been in use for more than 15 years.
It is also important to consider the choice of materials, as gamma irradiation can degrade certain polymers, resulting in elevated extractables, and—in the worst cases—the polymers can be destroyed.
Because of this, single-use filtration system bags must use films that are gamma-stable. Recommended materials for gamma exposure include silicone tubing and most PVC tubings.
Gamma irradiation suitability of the capsule filter must also be considered. Hydrophilic polyvinylidene fluoride, hydrophilic polyethersulfone, amphoteric nylon filter media are proven to be gamma-irradiation tolerant, and are recommended for use in single-use filtration systems.
Single use is just the beginning
Because single-use products do not require cleaning or cleaning validation, they can be more easily combined to form an integrated solution, as is the case with the disposable bags and filters.
As single-use products gain wider acceptance in the biopharmaceutical industry, the integration of complementary disposable products will increase to provide safer, more efficient processing solutions. The introduction of fully integrated, single-use fluid filtration systems is an important milestone in helping biopharmaceutical companies realize these benefits. lll
Holly Haughney, Ph.D., is a marketing manager with Pall BioPharmaceuticals (East Hills, N.Y.) and responsible for fermentation and bioprocess applications and automated direct-flow filtration systems. She previously served seven years as a technical director in Pall Corp.'s Scientific and Laboratory Services department supporting process gas and fermentation applications and new separations technologies. She can be contacted at [email protected].