Considerations on Re-Use of Sterilizing-Grade Filters - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Considerations on Re-Use of Sterilizing-Grade Filters
The author examines re-use of hydrophilic- or hydrophobic-membrane sterilizing-grade filters in liquid sterilizing applications.


Pharmaceutical Technology


Case Study: Risk of re-use

The case study described here highlights an example of the risk of re-use of sterilizing filters without conducting a full re-use process-scale validation. Specific process details are excluded to maintain confidentiality.

In this case, a pharmaceutical company was using a high-area, pleated, sterilizing grade membrane filter cartridge assembly to prepare a bulk sterile API antibiotic in a solvent for which the selected filter membrane had some limited compatibility. The limited capability was deemed acceptable and unrelated. Filters were rinsed with water after each use, followed by cleaning with a caustic solution. The caustic was rinsed from the filter with water (the degree of removal was not quantified or validated). The filter was then subjected to an SIP cycle between each batch for which it was re-used. The filter was integrity-tested before and after each batch and consistently passed its recommended integrity test limit for the maximum number of re-use cycles specified. Sterility tests of each filtered batch were unremarkable, and there were no reports of product nonsterility.

To supplement the level of confidence provided by the filter integrity tests and batch sterility tests, the drug manufacturer conducted a bacterial challenge on a filter that had reached its maximum specified re-use life. Following challenge conditions based on the ASTM Standard Test Method for Determining Bacterial Retention of Membrane Filters Utilized for Liquid Filtration (11), bacterial penetration of the filter was demonstrated. It was determined that the used filter no longer met the definition of a sterilization grade filter (i.e., 100% retention of B. diminuta bacterial at a challenge level of >107 cfu/cm2 effective filtration area) (4). The bacterial retention test of the reused filter failed despite the fact that the filter continuing to pass integrity tests correlated to 100% bacterial retention under comparable challenge conditions performed on previously unused filters by the filter manufacturer.

Several key observations were made from this study. First, after re-use, the filter still showed a high bacterial retention efficiency, but was no longer capable of meeting its 100% B. diminuta retention claim and the regulatory definition of a sterilizing-grade filter. Second, the controlled low bioburden in the product, coupled with the reduced but still significant retention properties of the filter, was sufficient to prevent detectable bacterial penetration in the process, as evidenced by the successful sterility tests and absence of product nonsterility events. Third, the damage to the filter from the re-use process was not detectable by a standard filter integrity test.

This third observation may seem contradictory to those who believe that filter integrity tests can detect any oversized pores, leaks, or defects that can compromise sterilizing filter performance. The correlation of such tests as forward flow or bubble point is based on bacterial challenges of intact filters and those with actual membrane or cartridge damage or defects incurred during filter manufacturing, handling, and installation. The population of filters subjected to the filter manufacturer's bacterial retention validation and integrity test correlation studies does not include filters with damage caused by end-user re-use process incompatibilities. These incompatibilities can occur with unvalidated, cleaning, resterilization, and re-use.


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,
Click here