Making a point of sterilising prefilled syringes

Noxilizer’s Evan Goulet and Stephen Morley outline the advantages that nitrogen dioxide (NO₂) technology is able to provide over more traditional methods in the sterilisation of prefilled syringes

Sterilisation of prefilled syringes today is predominantly accomplished using steam, EO or gamma radiation. While these methods are well established, their limitations could impede innovation and progress in the pharmaceutical and biotechnology industries. More than 60% of new drug products being developed today are biologics, such as protein therapies^[1]. This rapid rise in biological drug development is expanding the market for new sterilisation technologies that can overcome the limitations of current methods.

No single sterilisation method will be compatible with every product on the market. Steam sterilisation has been around for more than a century and is well understood in both industrial and hospital settings. EO has a long track record with the broadest material compatibility, and gamma radiation offers a low-temperature option. Each of these methods has specific weaknesses with respect to sterilisation of prefilled syringes. These weaknesses were the driving force behind the development of NO₂ sterilisation.

Noxilizer’s advanced room temperature sterilisation process uses NO₂, a well-researched gas, in combination with humidity to inactivate resistant microorganisms and deliver sterile product. The FDA recommends adding an adjunct process, or additional sterilisation step, to “increase the level of sterility confidence” when aseptic processing is used in drug manufacturing^[2]. This is especially true for products that are intended for use in ophthalmic applications or in the sterile field of the operating room. NO₂ gas is a surface sterilant that does not penetrate the container closure system and results in low surface residuals.

Noxilizer’s NO₂ technology is especially well suited to, and can be conveniently installed as, an adjunct process for products that require surface sterilisation. By providing solutions to the challenges presented by steam, EO and gamma sterilisation, NO₂ can help broaden the horizon for use of all types of prefilled syringes, including dual chamber and combination devices, as the drug delivery system of the future.

NO₂ works as an oxidiser that inactivates microorganisms through degradation of DNA, providing a sterility assurance level (SAL) of 10^-6 at relatively low gas concentrations (typically 10 to 20 mg/l).  Process validation and routine monitoring of NO₂ sterilisation proceed per ISO 14937^[3].Biological indicators for the NO₂ sterilisation process consist of spores of Geobacillus stearothermophilus, which is the same organism used for steam sterilisation.

Noxilizer’s demonstrated ability to sterilise the exterior surfaces of glass and polymeric prefilled syringes using a rapid cycle, minimal vacuum and a truly room temperature process suggests that NO₂ sterilisation is an ideal solution for manufacturers of sensitive biopharmaceuticals. The table provides a comparison of NO₂ sterilisation with EO.

In addition to the advantages outlined in the table, the financial benefit of using NO₂ instead of EO could also be substantial (up to 40 to 60% cost savings). NO₂ sterilisation equipment is significantly less expensive and does not require extensive facility modifications to be installed. This would allow manufacturers currently using contract sterilisation to move their sterilisation process in-house, thereby reducing costs and turnaround times.

References:

[1] Prefilled Syringes & Parenteral Contract Manufacturing — Product Differentiation Is Critical. Drug Development and Delivery. May 2014.

[2] Guidance for Industry — Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice. Draft Guidance. US Department of Health and Human Services – Food and Drug Administration – CDER – CBER – ORA. August 2003.

[3] ISO 14937:2009 — Sterilization of health care products — General requirements for characterization of a sterilizing agent and the development, validation, and routine control of a sterilization process for medical devices.

[4] Chien YC, Su PC, Lee LH, Chen CY. Emission characteristics of plastic syringes sterilized with ethylene oxide — a controlled study. J Biomed Mater Res Part B Appl Biomater. 2009;91(2):579-86. Doi: 10.1002/jbm.b.31432.