Simplifying Validation of Disposable Technologies with Presterilization by Gamma Irradiation - - BioPharm International


Simplifying Validation of Disposable Technologies with Presterilization by Gamma Irradiation

BioPharm International

Gamma Irradiation

The gamma irradiation process can be used for a variety of filtration applications spanning discovery to production. In use for more than 15 years, gamma irradiation uses well-defined operating parameters to ensure accurate validation methods and dose settings. The relatively simple process works by emitting gamma rays (electromagnetic energy) from a cobalt-60 isotope to penetrate deep into materials, thus destroying microbial bioburden. In a well-designed irradiation facility, for any given density of material, the only variable determining the amount of radiation the product receives is the time the material spends within the radiation field. As a constant and predictable sterilization method, gamma irradiation provides a safe and efficient start to the drug development process.

In addition to eliminating sterilization and sterilization validation procedures, presterilization using gamma irradiation provides cost, safety, and time benefits. Gamma irradiation's ability to demonstrate reproducible results helps biopharmaceutical companies improve the predictability of their applications. Because products are not exposed to heat, humidity, pressure, or vacuum, gamma irradiation presents fewer opportunities for product degradation. It also produces minimal waste byproducts, and does not require quarantine for out-gassing or biological testing. At $0.50–$4.00 per cubic ft., gamma irradiation's comparable cost to other forms of sterilization make it a very viable option.

In general, gamma irradiation is outsourced to specialty radiation facilities, such as Isotron Steris, SteriGenics, and RTI in the US. These facilities are subject to quarterly radiation dose audits. They are ISO-certified, maintain thorough records, and provide information, as needed, for submission to FDA. They also are equipped with safety containment walls that form a concrete shield around the facility to protect against the irradiation source (cobalt-60). To ensure the safety of the operators and the process, radiation facilities are monitored and regulated by a number of organizations.

Material Suitability

As with any sterilization method, the material to be sterilized must be compatible with the type of method used. Materials that are suitable for gamma irradiation include: polyethersulfone (PES), polyvinylidiene fluoride (PVDF), nylon and stabilized polypropylene. Materials that are not suitable include polytetrafluoroethylene (PTFE) and unstabilized polypropylene.

Setting the Parameters for Radiation

The objective of sterilization by gamma irradiation is to ensure that there is sufficient energy to kill microorganisms without compromising the integrity of the device materials.

The degree of sterilization or the Sterility Assurance Level (SAL) provides a benchmark for determining what the minimum radiation dose setting should be for a given material. SAL is a measurement of the theoretical probability of there being a viable microorganism present on the device. The industry accepted SAL for terminally sterilized products is expressed as 10-6. This means the theoretical probability of there being a viable microorganism present on the device shall be equal or less than one in a million.

In setting the radiation dose, it is important to understand that not all parts of a device receive the same dose because of density, thickness, and geometric differences within the device. Some parts may need to receive a 30%–50% higher dose than the minimum dose needed to ensure that the devices are effectively sterilized.

The membrane filters used in disposable capsules can consist of different materials (e.g., PVDF, PES, or nylon) and thus, these materials need to be tested to ensure that the appropriate dose is established for sterilization. The method described below can be used to establish a suitable gamma irradiation dose for presterilization of capsule filters.

Establishing the Minimum Dose for Disposable Capsules

Methods set forth by the Association for Advancement of Medical Instrumentation (AAMI) are typically used to establish the minimum radiation dose setting that can routinely meet the preselected SAL requirements. Specifically, Method One of ANSI/AAMI/ISO 11137 has been used for filter capsules.

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