Regulatory guidance discourages re-use of sterilization filters, particularly for sterile drug products. Where justified,
sterilizing filters may be re-used in some cases, but their re-use must be validated to not compromise filter sterilizing
performance or filtrate quality. In addition to basic sterilizing validation studies, as recommended in PDA Technical Report
26 and FDA's aseptic processing guidance, validation of multiply re-used sterilizing filters should include thorough testing
of process filters exposed to the maximum specified number of cleaning, resterilization, drying, and re-use cycles. Such testing
should include bacterial challenges as well as filter-integrity tests. These tests should assess chemical compatibility of
the filter to process fluids and re-use cycle conditions, validity of the integrity test limits under re-use conditions, and
include a chemical analysis of rinse effluents to qualify any leaching of bacterial, product, or cleaning agent residues.
Integrity testing alone cannot be relied on to predict sterilizing performance of re-used filters without adequate bacterial
challenge validation employing used filter cartridges. Finally, users should consider carefully the level of risk and validation
costs involved in satisfactory re-use of sterilizing filters versus the seemingly apparent economics of re-use when designing
and qualifying sterilization filtration processes.
Jerold Martin is senior vice-president of Scientific Affairs at Pall Life Sciences, 2200 Northern Blvd., East Hills, NY 11548, tel. 516.801.9086,
jerold_martin@pall.com
.
References
1. FDA, Q7A: Guidance for Industry: Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (Rockville, MD, August 2001).
2. EMEA, Note for Guidance on Good Manufacturing Practice for Active Pharmaceutical Ingredients (London, November 2000).
3. "Current Good Manufacturing Practice for Finished Pharmaceuticals: Equipment Construction" in Code of Federal Regulations, Title 21, Food and Drugs (Government Printing Office, Washington, DC), Part 211, Subpart D, Section 211.65.
4. FDA, Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing: Good Manufacturing Practice (Rockville, MD, Sept. 2004).
5. European Commission, EU Guidelines to Good Manufacturing Practice—Medicinal Products for Human and Veterinary Use, Annex 1, Manufacture of Sterile
Medicinal Products (Rev., Brussels, Feb. 2008).
6. PDA, "Sterilizing Filtration of Liquids," Technical Report No. 26 (1998), Revised, 2008, in press.
7. FDA, CDER Warning Letter, Sept. 24, 1999, accessible at
http://www.fda.gov/foi/warning_letters/archive/M3132n.pdf, accessed Oct. 20, 2008.
8. FDA, CDER Warning Letter, Aug. 16, 2005, accessible at
http://www.fda.gov/foi/warning_letters/archive/g5463d.htm, accessed Oct. 20, 2008.
9. N. Sweeney, "Sterility Assurance: Optimization of Sterility Assurance Submissions," presented at the Generic Pharmaceutical
Association (GPhA) Fall Technical Conference, Bethesda, MD, Oct. 11, 2007.
10. Personal communication.
11. ASTM, "F838-83 Standard Test Method for Determining Bacterial Retention of Membrane Filters Utilized for Liquid Filtration"
(Reissued as F838-05), ASTM Book of Standards 11.02 (1983).
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