Abstract
The following study was conducted to determine the effect of different preservatives commonly used in the biopharmaceutical industry on the product-specific bubble point of sterilizing-grade filters when used to filter product processed with different types of tubing. The preservatives tested were 0.25% phenol, m-cresol, and benzyl alcohol. The tubing tested was Sani-Pure® (platinum-cured silicone tubing), Versilic™ (peroxide-cured silicone tubing), C-Flex,® Pharmed,® and Cole-Parmer® (BioPharm silicone tubing). The product-specific bubble point values of sterilizing grade filters were measured after the recirculation of product through the filter and tubing of different types of materials for a total contact time of 15 h. When silicone tubing was used, the post-recirculation product-specific bubble point was suppressed on average 13 psig when compared to the pre- recirculation product-specific bubble point. Suppression was also observed with C-Flex,® but to a much lesser extent than with silicone tubing. Suppression was not observed with Pharmed® or BioPharm tubing. Alcohol extractions performed on the filters that experienced suppressed bubble points followed by Fourier transform infrared spectroscopy analysis indicated the filters contained poly(dimethylsiloxane). Direct addition of poly(dimethlysiloxane) to solutions filtered through sterilizing-grade filters suppressed the filter bubble points when tested for integrity. Silicone oils most likely reduced the surface tension of the pores in the membrane, resulting in the ability of air (or nitrogen) to pass more freely through the membrane, causing suppressed bubble point test values. The results of these studies indicate that product-specific bubble point of a filter determined with only product may not reflect the true bubble point for preservative-containing products that are recirculated or contacted with certain tubing for 15 h or greater. In addition, tubing material placed in contact with products containing preservatives should be evaluated for impact to the product-specific bubble point when being utilized with sterilizing-grade filters.
- ATR
- Attenuated total reflectance
- BP
- bubble point
- CPBP
- Corrected product-wetted bubble point
- FTIR
- Fourier transform infrared spectroscopy
- HPLC-UV
- high-performance liquid chromatography—ultraviolet
- IPA
- Isopropyl alcohol
- MMWBP
- Minimum manufacturers water-wetted bubble point specification
- LC/MS
- Liquid chromatography/mass spectroscopy
- PDMS
- Poly(dimethylsiloxane)
- THF
- Tetrahydrofuran
- psig
- Pounds per squareinch gauge
- USP
- United States Pharmacopeia
Footnotes
- Copyright © Parenteral Drug Association. All rights reserved.
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