Pharmaceutical Technology Europe - March 2012 - (Page 7)

FOCUS Single-use redundant filtration The authors describe a new assembly for bulk and final drug product filling operations. Designing a redundant filtration system that meets regulations and recommendations is challenging. Disposable or single-use redundant filtration (SURF) assemblies, however, offer a flexible solution because they can be pre-sterilised by the supplier using gamma irradiation and there is also no need for cleaning after use because assemblies are self-contained and entirely disposable. Many biopharmaceutical companies already use variations of SURF assemblies for final and bulk fill operations. However, preparation and utilisation sequences may differ across processes and geographies because of differing national guidelines. This study reviewed different redundant filtration assembly designs and operating sequences, and proposes a new SURF assembly that has greater operational robustness and minimises the risk of product contamination. The major design considerations are: • A barrier filter (0.2 µm, EMD Millipore) was included in the design as a combined liquid and gas outlet. The barrier filter contains both hydrophilic and hydrophobic sterilisinggrade PVDF membrane, which can exhaust both air and water from the assembly. The assembly can be wetted and tested for integrity multiple times without breaching the sterile envelope. • Catch bags were attached to the vents of the liquid filters to 2 SPECIAL FEATURE 11 PARAMETRIC RELEASE 7 REDUNDANT FILTRATION 12 COLUMN CRUNCH collect liquid during venting. • Gamma stable vent filters were attached to the bags to enable passage of air during venting. • A hydrophobic PVDF filter was added on the air inlet line to ensure sterility of the air coming into the assembly for integrity testing. • Single-use sterile connectors were used at the assembly’s inlet and outlet to assure sterile connections during operation. • In-line liquid filter capsules were selected (as opposed to T-line capsules) to reduce the hold-up volume. • The assembly was used in the vertical orientation to achieve better draining after wetting and during product recovery after filtration. Pre-use, post-sterilisation integrity testing of a redundant filtration setup can be challenging. With either stainless steel or a single-use assembly, 8 NEWS BITES 13 PEER REVIEW it is critical to maintain setup sterility during every step. The efficiency of the filter wetting step is also important to avoid false negative integrity test results. For high-value products, the drying step after integrity testing is crucial to minimise product dilution. A flushing test was conducted to record the reduction of total organic carbon (TOC) and conductivity with flush volume. The filters and assembly were flushed with deionised (DI) water at a flow rate of 250 mL/min for a total of 20 L. At the end of 20 L reverse osmosis (RO)/DI water flush, TOC and conductivity were 0.231 ppm and1.1 µS/ cm, respectively. Read the full text at PharmTech.com/SURF Ranjeet Patil, Michael Felo and George Oulundsen 9 BLOG 14 TOP TECH http://www.PharmTech.com/SURF

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - March 2012

Pharmaceutical Technology Europe - March 2012
Contents
Innovations, drivers and trends in adjuvant filtration
Focus: Redundant filtration
News Bites
Blogs Abridged
Interview: Parametric release and real-time release testing
Column Crunch: Counterfeits and outsourcing trends
Evaluating drug impurities
Top Tech

Pharmaceutical Technology Europe - March 2012