Sera PES Double Layer

Sterilizing Grade 0.2 Micron PES Membrane Filter Cartridge

Serene validated PES Pharmaceutical Grade Filters are designed for product sterility and ease of wettability for final aseptic filtration in biopharmaceutical. This validated 0.2um PESfilter combine two asymmetric polyethersulfone (PES)membrane layers with new innovative Advanced Pleat Technology design. This combination results in a robust filter that

is optimized for both high throughput and fast flow applications. SERENE PES filter exhibits low protein binding and excellent drug compatibility to maximize recovery of critical media components.It’s doublelayer membrane configuration makes it ideally

suited for final filtration in critical applications especially those involving fluid at high temperature. The unique hydrophilic polyethersulfone membrane wets easily for integrity testing and is ideal for applications where low protein binding is critical.

Advance Membrane Technology

SERENE validated filters incorporate two layers of polyethersulfone membrane. The upstream layer is highly asymmetric and provides optimized prefiltration capacity for the downstream layer that contains a robust, centrally located, retention zone. Both membrane layers are asymmetric and together result in a filter with multiple filtration zones providing extremely high contaminant capacity, fast flow rates and reliable sterilizing filtration performance.

This design technology maximizes the useful surface area of the filter while maintaining open flow paths between media pleats. This new technology provides those membrane surface properties that areresponsible for the outstanding wettability and low protein binding character of theSERENE PTFE Membrane, even after extreme thermal and chemical stress,allowinge.g. multiple cycles of wet and dry steaming in both directions withoutaffecting wettability and integrity testing.

Microbial Challenge Testing of Filters

Filters used in the production of sterile products are always less than or equal to0.2um pore size rating. This physical characteristic is always a primary requirement for a filter to be considered acceptable for use in the production of a sterile product stream. Further confirmation of a filter’s suitability is established by means of the challenge with B. diminutadiscussed previously in this chapter. The FDA has defined a proper challenge as one that confronts every square centimeter of the available filtration area with 1_107 CFU of this model organism. As previously mentioned, it is important to consider that this challenge test does not confirm the unequivocal ability of a filter to produce a process stream that is always free of microbial contamination. The true mission of the filter is to adequately abate microbiological risk in terms of infection of the end user, absolute sterility being impossible to establish by this or any other widely applied test including the so-called “sterility test.” The sterility test is of course, itself often dependent upon filter sterilization.

Protein Adsorption by Sterilizing Grade Filters

The adsorption of proteins onto polymeric filters is of considerable practical interest. The technique of preparing new drugs by way of fermentation processes includes their downstream purification by separation procedures such as filtration or liquid–solid chromatography. Separation of the extracellular products from the cell remnants is achieved by filtration in a clarification step; microporous membranes are employed. The debris is retained by the filter; the effluent contains the desired proteins. Ultrafiltration by way of tangential flow operations is a technique often used to concentrate the sought-after products. Alternatively, liquid-solid chromatography is utilized to bond the proteinaceous products to a carrier surface. Subsequently, the desired (protein) product is released in purer form.Purifying activities based on filters can be complicated by blockage of the filter pore caused by protein and/or other depositions. The same may result when preparations containing proteins undergo filtrations designed for sterilizations, and for virus removal. The hindrance of the filtration process by protein adsorption is termed “fouling” a word whose pejorative implication is one of unwelcome interference. Actually, fouling is a poorly understood phenomenon. Protein adsorptions studies are undertaken in pursuits of its amelioration. The loss of time and effort attendant upon a filter blockage translates to a monetary loss. An even greater direct loss may occur when valuable proteins, the product of present biochemical efforts, are irreversibly adsorbed to a filter to become discarded with it. The strong interest in securing high yields of high-value proteins is self apparent.

The adsorptive strength of a membrane is, thus, expressible in terms of its adsorption to a specific protein, both in terms of the quantity of protein it binds to the point of saturation, and in the extent available for adsorption beyond the point of contact.

Scalability

Serene sterilizing grade filter is available to meet your scale up process needs from R&D to production scale. This range includes disposable capsules, mini-cartridges and full size cartridges. In addition, filter discs are available when even smaller membrane surface area is required.

Validation of the Filter and of the Filtration Process

The validation of sterilizing filtrations, and of the sterilizing filters involved is critical to the production of a sterile drug product, or of a sterile active pharmaceutical ingredient (API). The sterility of the drug preparation cannot be ascertained by analysis of its samples. It is impossible to test every drug container to assess its sterility. Similarly, a statistical determination of sterility would require so large a sampling as to be impractical. Validation of a process provides the assurance that its product is sterile. Such validation is a regulatory requirement (FDA, 1985). Validation of the filters used to achieve a sterile API is also necessary. It serves to assure that they perform in the manner intended; this may also be a regulatory requirement if there are no further sterilizing steps for the ingredient after its being formulated into the final product. Validation of a sterilizing filtration process used for pharmaceutical liquids essentially involves three things: determining the effect of the liquid on the filter, determining he effect of the filter on the liquid, and demonstrating that the filter removes all microorganisms from the liquid under actual processing conditions, resulting in a sterile filtrate (Madsen, 2006). One further point may need to be considered, namely, the interaction among the contaminating organisms, the solution, and the filter. Therefore, several studies are necessary to perform a complete filter validation. Such would include investigating extractables, chemical compatibility, initial filter performance, and bacterial retention testing. If the filter is to be post-use integrity tested in product-wet condition then validation of product-wet integrity test specifications is also necessary. Reuse testing is indicated if the intention is to use the filters more than once. This latter practice is not encouraged because of the heightened possibilities of cross-contamination.

Industrial Application

Final 0.2 μm sterilizing fi ltration Media and fermenter feed streams Serum and blood fractions Biologicals

Vaccines Chromatography column protection Cell culture fluids (debris clarification) High protein feed streams Parenterals (SVP, LVP) Reagents and Buffers

Solvent filtration Reagents & Buffers Ophthalmics

Bulk pharmaceutical chemicals Orals and Topicals

Features & Benefits

Ensures easy wet out for integrity testing and low protein binding

Easy to wet for a reliable integrity test Validated     0.2um          Membrane   for                  reliable sterilizing filtration

High-strength    design    allows    for    multiple autoclave cycles and extended use

High steam cycle lifetimes and long service Benefits  USFDA CFR Title 21 materials of construction, USP Class VI Biological Safety Test, Validation Guide and Drug Master File listing eases validation and regulatorysubmission

Capsule filters are available in both gamma compatible and sterile formats whichEliminate cleaning and cleaning validation step associated with stainless steel housings for maximal ease-of-use.

Nominal Dimension

Operating Parameter

Technical Specification

Sterilization & Autoclaving

The filters can be sterilized by autoclaving for up to 50 cycles at 275°F/135°C. The filters can also be sterilized by steam-in-place procedure up to 30 cycles at 287.6°F/142°C for 30 minutes at less than 0.3 bar differential pressure. The filters can also sanitized by hot water or common chemicals that are compatible with filter components.

Intergrity Data

Nominal Dimension

Retention

sComplete retention of > 107 organisms/cm2 of Brevundimonasdiminuta in accordance with the current HIMA challenge methodology (ASTM F838-83). Validation Guide available upon request.

Integrity tested

All cartridges are 100% integrity tested—Validation Guide available upon request.

Product validation guide available on request. All SERENE cartridges are manufactured under strict control with batch number identification, giving full traceability on all components.

Ordering Information

SFSCT                 PES