Understanding Gamma Sterilisation - Pharmaceutical Technology

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Understanding Gamma Sterilisation
Single-use systems used for the production of culture media and the filling of sterile APIs and drug products must be sterilised prior to use. This column will address some of the questions on how single use systems are sterilized by gamma irradiation and what documentation may be requested by regulators to support a sterile API, drug product or vaccine application.

Pharmaceutical Technology Europe
Volume 24, Issue 2

Radiation steriliser — dose mapping and quarterly audit

Cobalt 60 can be stored safely in a pool of water, while the chamber above the pool is surrounded by a thick concrete barrier that prevents gamma rays from escaping when the gamma source is elevated into the irradiation chamber. Product intended for sterilisation is packaged, palletised and transported into the irradiation chamber using a conveyor.

Once a minimum sterilising dose is established for the Master Product, a pallet load configuration and density is established. Dose measuring devices called dosimeters are distributed throughout the packaged load to confirm that the minimum sterilising dose is reached throughout the batch. Because the received dose can vary based on density, materials are typically qualified to withstand up to 50 kGy. On a quarterly basis, the process is audited by, again, determining bioburden in 10 current product, Master Product or SIP samples. Verification dose sterility tests are conducted on 10 additional samples.

Sterile product documentation

The sterilisation validation and irradiator batch data support both the supplier's claim for sterility for the singleuse system(s) and the user's claim for cellculture process control and finished product sterility. Several documents serve to support both system and finished product sterile claims. First, the supplier should provide a letter explaining the rationale for the sterile claim of each specified system by part number, based on actual or Master Product validation. Suppliers can insert a Certificate of Quality within the unit packaging stating that the product is sterile after irradiation. External irradiation indicators that change colour upon exposure are not sufficiently quantitative to confirm sterility. A summary Sterilisation Validation Report supporting the minimum sterilising dose, as well as the Dose Mapping Study Report and most current Quarterly Dose Audit Report generated by the irradiator, should be provided by the system supplier. Original data and irradiator certificates, however, may only be available during supplier audit. Lastly, the supplier should provide a Certificate of Irradiation for the system lots in the batch, certifying the minimum dose recorded by the batch dosimeters.

This combination of sterilisation validation rationale, minimum dose sterilisation validation, batch load dose map, batch irradiation dose certificate and quarterly dose audit serves to support the ongoing sterility of the single use system and the sterile products produced with them. For more information on this subject, a good resource is available free of charge in the form of the BPSA's Guide to Gamma Irradiation and Sterilization (3).


1. AAMI/ANSI/ISO 11137:2006, "Sterilization of health care products — Radiation — Part 1: Requirements for the development, validation and routine control of a sterilization process for medical products; Part 2: Establishing the sterilization dose; Part 3: Guidance on dosimetric aspects"(2006).

2. American Association of Medical Instrumentation, "Sterilization of health care products—Radiation—Substantiation of a sterilization dose—Method VDmax", Technical Information Report TIR33:2005 (2005).

3. BPSA, "Guide to Irradiation and Sterilization of Single-use Systems" (2008).


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