Single-Use Redundant Filtration - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Single-Use Redundant Filtration
The authors describe a new assembly for bulk and final drug product filling operations.


Pharmaceutical Technology Europe
Volume 24, Issue 3

Proposed single-use process solution: design considerations


Figure 1: Utilisation sequence options for single-use redundant filtration assemblies. F1 is the first liquid filter. F2 is the second liquid filter.
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. Below are the major design considerations for the assembly (see Figure 1):

  • A barrier filter (0.2 m, EMD Millipore) was included in the design as a combined liquid and gas outlet. The barrier filter contains both hydrophilic and hydrophobic sterilising-grade PVDF membrane, which can exhaust both air and water from the assembly. As a result, it can be used as the initial filter flush outlet and as a sterile air outlet during integrity testing and the filter drying step. Such a filter further solves the problem of flush volume constraints imposed by the catch bag/tank size. 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 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.

The catch bag on the first liquid filter is primarily in place to avoid the liquid spill that can occur during venting for water flush and product filtration. With some minor modifications, the catch bags on both the first and second liquid filters can also be used for in-process sampling. The catch bag on first liquid filter and the separate air inlet line (with an air filter near the feed inlet) are additional features that are incorporated to ensure cleanliness and ease of operation.

Pre-use, post-sterilisation integrity testing of a redundant filtration setup can be challenging. With either stainless steel or a singleuse assembly, 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 highvalue products, the drying step after integrity testing is crucial to minimise product dilution. Figure 1 outlines the utilisation sequence for SURF assembly before use. Along with the points mentioned above, operator convenience and regulatory compliance were also considered.


Figure 2: Total organic carbon (TOC) and conductivity (S/cm) versus flush volume (mL).
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. The assembly effluent was sampled at 1 L intervals and tested for conductivity and TOC. Analytical results for flush filtrate samples are summarised in Figure 2. At the end of 20 L reverse osmosis (RO)/DI water flush, TOC and conductivity were 0.231 ppm and1.1 S/cm, respectively.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
25%
Attracting a skilled workforce
29%
Obtaining/maintaining adequate financing
11%
Regulatory compliance
36%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatcchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Obama Administration Halts Attack on Medicare Drug Plans
Source: Pharmaceutical Technology Europe,
Click here