Dry Heat Sterilization and Depyrogenation Validation and Monitoring

Limitations in predicting radiation-induced pharmaceutical instability during long-duration spaceflight

“…12–14 Studies have indicated that the concentration of these radicals from exposures to radiosterilization doses (25–50 kGy) is generally well below toxic levels. 15,16 A recent NASA technical paper indicated that nanomolar concentrations of radiation byproducts could be produced in exposed pharmaceuticals, but cited low anticipated radiolytic yield in liquid-based pharmaceuticals (based on modeled calculations) as sufficient evidence that irradiated pharmaceuticals should be stable in the space environment. 11…”

“…It has been theorized that high dose-rate increases oxygen consumption, resulting in decreased presence of oxygen radicals (or the rapid consumption of any radical species generated) and associated damage. 16,19 Shorter duration exposures may produce fewer long-lived oxygen radical species and, as a result, less prolonged opportunity for delayed damage than protracted exposures. In evidence to these arguments, one historical study of spaceflight-approved pharmaceuticals compared drug stability at variable radiation dose ranging from 0.1 to 50 Gy and found drug degradation associated with moderate radiation exposure where no instability was noted at higher doses.…”

“…Given the uncertainty of drug response to alterations of dose, dose-rate, or exposure time, radiosterilization is only approved for well-documented procedures of declared dosage (most commonly 25–50 kGy) and dose-rate, and deviation from the designated dose or dose-rate is assumed to be capable of altering the final drug product. 16,19 In evidence to this concern, the United States Pharmacopeia (USP) regards radiosterilized pharmaceuticals as entirely new products, and pharmaceutical companies are required to submit new drug applications and demonstrate safety, potency, and lack of toxic breakdown products for approval of radiosterilization in any marketed drug. 16,25 The use of terrestrial analog radiation to predict the response of pharmaceuticals in the space environment directly contradicts the standard approach to safety and stability review of irradiated pharmaceuticals.…”

“…16,19 In evidence to this concern, the United States Pharmacopeia (USP) regards radiosterilized pharmaceuticals as entirely new products, and pharmaceutical companies are required to submit new drug applications and demonstrate safety, potency, and lack of toxic breakdown products for approval of radiosterilization in any marketed drug. 16,25 The use of terrestrial analog radiation to predict the response of pharmaceuticals in the space environment directly contradicts the standard approach to safety and stability review of irradiated pharmaceuticals. Finally, it should be noted that many of the pharmaceuticals currently included in a spaceflight formulary are not approved by the U.S. Food and Drug Administration (FDA) for terrestrial radiosterilization procedures (Table 1).…”

Feasibility of in-house sterilization of laboratory plastic consumables using 2 MeV electron beam facility

“…A radiation dose of 25 kGy is suitable for sterilization purposes, chosen according to radiation resistance of bacterial spores of the radio-resistant micro-organism, Bacillus pumilus. Feasibility of radiosterilizing water in various container materials has been studied in several laboratories [2][3][4][5]. The 25 kGy dose is higher than necessary for achieving sterility and reaching a sterility assurance level of 10 -6 (SAL, one micro-organism surviving after treatment in a sample of 10 6 micro-organisms, or one non-sterile item after sterilization of a batch of 10 6 ) [6,7].…”