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


Credit to Ingram Publishing/the Agency Collection/Getty Images
Increased regulatory expectations and the need to mitigate risk have popularised the use of redundant filtration for bulk and final fill operations. Single-use redundant filtration (SURF) assemblies are an efficient and flexible alternative to stainless steel systems because they eliminate clean in place (CIP), sterilisation steps and the associated validation protocols. Preparation time can also be significantly reduced when using single-use assemblies because of their pre-sterilised format and the ease with which they can be handled. Redundant filtration operations in multi-product facilities can be performed without spending the extra validation time that is often required for non-disposable systems.

This article identifies a suitable design for redundant filtration operations using single-use technology and standardised assembly components. The design was finalised with input from a global technical and quality team with consideration given to international regulatory requirements. The article also demonstrates the capability of the assembly to withstand the high pressure that is used for integrity testing and drying. Pre-use integrity testing was performed on both filters. Using hydrophilic/hydrophobic filters on the assembly outlet eliminated flush volume limitations caused by catch bag size. Assembly specifications, such as leachables and extractables, hold up volume and flushing requirements, were established for a single-use assembly.

Meeting regulatory expectations

As defined in PDA Technical Report 26, redundant filtration is a "type of serial filtration in which a second sterilising-grade filter is used as a backup in the event of an integrity failure of the primary sterilising filter." The pore size of the sterilising-grade filters may be the same or tighter than the primary filter (1). Other regulatory bodies (e.g., FDA, EMA and SFDA) have also issued their own guidelines for sterile filtration. According to the FDA's aseptic processing guidelines published in 2004, it is recommended that redundant filtration should be considered in many cases where liquid is sterilised by filtration (2). The EMA's 2008 GMP guidelines state that because of potential risks of sterilisation by filtration, a second filtration step as close to the filling point as possible is advisable (3).

Designing a redundant filtration system that meets regulations and recommendations is challenging. For stainless steel systems, the EMA recommends that integrity testing should be performed on sterile filters before use. To do this, filters must be fully wetted without breaching the sterility on the downstream side of the assembly. Many conventional stainless steel facilities employ a "catch can" with a sterile vent filter to collect the initial flush liquid from the wetting step. Prior to use, additional time is required to sterilise, maintain and store the catch can. In addition, use of a catch can constrains the total flush volume that can be used if the filters need to be rewetted (e.g., in a repeated filter integrity test).

Disposable or single-use redundant filtration (SURF) assemblies offer a flexible solution for this relatively complex operation (4). These assemblies can be presterilised by the supplier using gamma irradiation and there is no need for cleaning after use because assemblies are self-contained and entirely disposable.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

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

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
27%
Oversee medical treatment of patients in the US.
14%
Provide treatment for patients globally.
8%
All of the above.
41%
No government involvement in patient treatment or drug development.
11%
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Source: Pharmaceutical Technology Europe,
Click here