Auditing gamma irradiation plants

The wide application of single-use sterile disposable technology means that the biotechnology company purchasing the materials should undertake an audit of the sterilization process in order to be satisfied that the process is robust and that the possibility of non-sterility is minimal (28). Furthermore, the diversity of radiation sterilization systems available today places renewed emphasis on the need for thorough quality assurance audits of these facilities. As with any sterilization process, gamma radiation should be subject to quality auditing to ISO 9001 standards and to good manufacturing practice as applicable (29, 30). When conducting an audit of gamma irradiation processes, the following areas should be considered when developing the audit checklist:

• Is the product suitable for sterilization? This requires a review of any physical changes to the material from the radiation process. This should include an assessment of extractables and leachables both before and after the sterilization process (31).
• The temperature sensitivity of the product, while undergoing gamma radiation, should be determined.
• Ensure that the packaging used for the product is suitable. Does the package, for example, allow the radiation dose to be absorbed by the product as defined in the validation and does the package remain intact post irradiation?
• Determining if the validation parameters are consistent (i.e., the volume and density of the product in packaging and the configuration of the load placed into the tote).
• The dose required should be checked. This should include assessment of the lower and upper range and the measures in place to ensure that each item of product within the tote has received the minimum dose required.
• The dose mapping validation data should be checked against the routine radiation cycles to determine if the parameters match.
• Determine evidence of sterility. This will include an assessment of radiation parameters and radiation indicators.
• Decontamination procedures.

In addition to the above, the plant should be checked to determine if it is compliant with appropriate regulations for nuclear facilities and that appropriate segregation and labeling of components is in place.

Conclusion

Single-use sterile disposable technology is rapidly becoming the norm for biotechnology and biopharmaceutical organizations. The application of the technology requires that the products are sterile and remain robust in terms of their construction. The material of construction, plastic, means that the primary method for sterilization is gamma radiation. Gamma radiation, as a sterilization method, confers the advantage of being relatively low cost, effective (in having a deep material penetration), and in avoiding leaving toxic residues. However, the radiation process may degrade some polymers rendering it unsuitable from some materials. In addition, the process parameters must be correctly defined in order for the sterilization process to be effective. There are several variables that could, if not carefully addressed, lead to non-sterility or to material degradation. To counter this possibility, an effective validation strategy must be developed and be supported by quality audits of the irradiation process. The end-user of the sterile disposable products, not the manufacturer or the sterilization plant, should adopt the lead role when undertaking such assessments.

This paper set out to provide a framework for establishing sterilization cycles and auditing such processes. In doing so, the paper has examined some of the key parameters required for sterilization by gamma radiation. The sterilization technique remains one of the less defined by regulatory agencies and yet it is seemingly the fastest growing technique used within the pharmaceutical industry as the trend towards sterile, plastic disposable consumables increases.

Tim Sandle, PhD*, is the head of the microbiology department at Bio Products Laboratory Limited, tim.sandle@bpl.co.uk
http://www.pharmig.blogspot.com/. Madhu Raju Saghee is a quality assurance professional at Gland Pharma Limited, India.

*To whom all correspondence should be addressed.