Sterilisation of biopharmaceuticals: Effect of gamma irradiation, e-beam irradiation and nitrogen dioxide on human insulin.

Biopharmaceuticals are administered parenterally and therefore sterility is required. Sterility can be obtained via different processes including exposure to steam or dry heat. Sterilisation studies on biopharmaceuticals, which are highly sensitive medicinal products, are scarce. This study investigates the effect of different sterilisation processes on recombinant human insulin in solid state (gamma and e-beam irradiation (w/wo dry ice), nitrogen dioxide (NO2)) and in aqueous solution (gamma irradiation (w/wo dry ice, w/wo glycerin)) using ultra-high performance liquid chromatography-diode array detection-mass spectrometry. It is observed that NO2 substantially degrades the solid samples, while gamma and e-beam irradiation result in lower levels of degradation (mean normalized peak areas of 95.2-96.2 % with respect to the non-sterilised samples). Gamma irradiation of insulin solutions with and without dry ice at 2.5 kGy results in mean normalised peak areas of 85 % and <40 % with respect to the non-sterilised samples, respectively. It is concluded that sterilisation using ionising radiation of liquid biopharmaceuticals with insulin and sterilisation of insulin dry powder using NO2 is less suitable with the set-ups used here because of substantial degradation. In contrast, evidence is presented in favour of sterilisation of insulin dry powder using ionising radiation.

The effect of Gamma and Ethylene Oxide Sterilization on a Selection of Active Pharmaceutical Ingredients for Ophthalmics.

Ensuring the sterility of life science products plays a pivotal role in the healthcare sector. Gamma irradiation and ethylene oxide sterilization are two commonly applied methods for the sterilization of medical devices, packaging components and Active Pharmaceutical Ingredients (API) for medicinal products. Focussed studies on the effects of sterilization processes on APIs remain limited. In this research study, five APIs, frequently used in sterile ophthalmic preparations were subjected to both gamma irradiation and ethylene oxide under different process conditions. The following APIs of GMP quality were selected: dexamethasone, aciclovir, tetracycline hydrochloride, triamcinolone and methylprednisolone. Analyses were performed using High Performance Liquid Chromatography equipped with UV detection and the effect of sterilization conditions on the APIs was evaluated by the assay and related substances test prescribed by the European Pharmacopoeia (Ph. Eur.). It was concluded that exposure to ethylene oxide resulted in compliance with Ph. Eur. for all APIs. While dexamethasone and methylprednisolone did not meet the requirement for the Ph. Eur. after exposure to gamma irradiation, the other three APIs did meet the requirement under the specified irradiation conditions. Subsequent optimization of sterilization parameters positively influenced the compliance to the Ph. Eur. requirements.

Enhancing Service Capabilities by Adding Electron-Beam Irradiator to Gamma Irradiation Facility.

In 2013, Sterigenics undertook the addition of a 10-MeV electron beam (e-beam) accelerator at its facility in Jarinu, Brazil. A gamma irradiator was already located at this facility, which processed materials and provided irradiation services in Brazil. The decision to implement an e-beam accelerator at the same facility was made in order to diversify the technology that could be offered and to rapidly increase the overall capacity of the facility. In addition, the e-beam technology was complementary to the existing gamma pallet irradiator and thus provided an internal backup for some processes. The main challenge for staff at the Brazil facility was cross-validating processes carried out by the existing gamma irradiator with processes performed with the new e-beam accelerator. The overall success rate in the cross-validation of processes between the two modalities was positive. Products for healthcare, laboratory testing, and other low-bulk-density products that basically consisted of commonly used polymeric materials were most suitable for cross-validation. Products of higher bulk density, greater heterogeneity, or variability between packaging systems and products with dose specifications for a tote rather than a pallet gamma irradiator presented limitations in the cross-validation success rate. This article focuses on the transition approach, discusses the types of products that were successfully cross-validated in e-beam from gamma, and presents examples where such cross-validation was not pursued.