Maintaining Process Effectiveness

1. Maintaining Process Effectiveness

2. Regular Testing and Calibration Process equipments Analytical equipments Regularly test and calibrate Dosimetry systems Characterizing the magnitude, distribution, and reproducibility of the dose absorbed in a material of homogeneous density

3. Dosimetry System Calibration New batch of dosimeters Calibrate Analytical instruments Dosimeters in a conditions similar to those in the actual production irradiator Calibration verification should be performed periodically at the facility Routine dosimeters Measurement traceable to national standard The level of measurement uncertainty at a specified confidence level should be known

4. Documented Procedure • Product handling before, during and after irradiation Orientation of the product with diagrams Documented procedure Routine dosimetry Required activities and functions for the irradiation of the products

5. Documentation for Dosimetry system • Dosimeter manufacturer Dosimetry system selected Type and batch number Instruments used for analysis • Date Dosimeter Calibration Reference standard or transfer standard Reference the calibration facility used

6. Documentation for Dosimetry performance • Temperature, Humidity. light Effect of environmental conditions on dosimeter during irradiation and measurement Dose rate Energy spectrum Uncertainty associated with the measurement • Reference the method used to convert dosimetry measurements to absorbed-dose values in water Measurements Measurement quality assurance plan used for the routine dosimetry

7. Records • Provide documentary evidence showing that the product received correct treatment The main purpose of Records Fulfill obligations to and requirements of the authorities To settle disputes (if any)

8. Product Process record Reception and inspection of product • Unique code identifying each product Storage environment Scheduling the irradiation Record of Loading the product onto the irradiator system Unloading the irradiated product from the system Inspection checking of routine dosimetry, process parameters Sign-off of any non-conformances Approval for release and dispatch to the customer

9. Daily shift maintenance record Date & shift Personnel on duty - time in &out with signature Record various operational parameters such as Conveyor speed, cycle time, running time of the irradiator, total number of packages transferred System Condition Record of Technical details of each equipments employed for operation (exhaust fan, hydraulic motor, recirculation pump, etc) and values of other monitoring instruments such as survey meters, contamination monitors, conductivity, hydraulic pressure recirculation water temperature, pH, etc Shut down details Record shutdown details with time. Record reason for shut down Record action taken

10. Product log record Product Customer name, Unique ID of the box, Package number, Carrier no. If any, Details of product Required dose Cycle time Conveyor speed Record of Package in Date and time Product Processing Package out Date & time Dosimeter Dosimeter number

11. Irradiation Control record Date • Time Product type Record of Loading diagrams Absorbed doses for products processed Process parameters of specific production runs Reference the calibration of processing equipment Reference the calibration of dosimetry systems and other analytical instruments

12. Dosimetry record Absorbed dose for each specific production runs Calibration of dosimeters Record of Calibration of Dosimetry equipments Maintenance of the dosimetry equipment

13. Facility record Each lot of product that is processed with unique identification number Date the product is processed and the starting and the ending times of the irradiation Record of Any special conditions of the facility that could affect the absorbed dose to the product Name of the operator

14. Record for Review and Approval Certificate for delivery of the dose to the product for each production run. Record of Names of authorized personnel who issued the certificate Periodic audit of all documentation

15. Retention of Records at the facility Copies of receiving documents. Copies of shipping documents For each production run, retain record at the facility for inspection Dose calibration documents Irradiation control records Routine Dosimetry data Certificate of irradiation Retain the records for a period Time specified by relevant authorities

16. References Guidelines for the Development, Validation and Routine Control of Industrial Radiation Process. IAEA Radiation Technology Series No.4 (2013) ISO 11137:2006 “Sterilization of Healthcare Products – Radiation” Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices Part 3: Guidance on dosimetric aspects Trends in radiation Sterilization of Health Care Products. IAEA, STI/PUB/1313 (2008) ISO/ASTM 51649 “Standard Practice for Dosimetry in an Electron BeamFacility for Radiation Processing at Energies Between 300 keV and 25MeV” ISO/ASTM 51702 “Standard Practice for Dosimetry in Gamma Irradiation Facilities for Radiation Processing” ISO/ASTM 51261 “Standard Guide for Selection and Calibration of Dosimetry Systems for Radiation Processing”

17. Worked example Example. 1: The sterilization dose specified for a product is 25 kGy and maximum dose is specified as 40 kGy. Data from a dose mapping exercise at the irradiation facility for the product shows dose at Reference position - 30.5 kGy minimum position - 26.5 kGy maximum position - 37.0 kGy Find out the minimum and maximum reading that is permissible for the routine dosimeter during routine processing of the product at the facility? • Answer. • Minimum reading of the routine dosimeter • = Dose at the reference position X sterilization dose • Dose at the minimum position • = 30.5 x 25 kGy = 28.8 kGy • 26.5 • Maximum reading of the routine dosimeter • = Dose at the reference position X sterilization dose • Dose at the maximum position • = 30.5 x 40 kGy = 33.0 kGy • 37.0 • Therefore the minimum and maximum permissible reading of the routine dosimeter to register for the load to meet the specification are 28.8 kGy and 33 kGy respectively.

18. Worked example Example. 2: The sterilization dose specified for a product is 25 kGy and maximum dose is specified as 40 kGy. If the routine permissible range is from 27 kGy to 35 kGy, find out the absorbed dose at minimum and maximum dose position in the product if the routine dosimeter registers a reading of 31 kGy? Answer. Absorbed dose at the minimum dose position = Sterilization dose X Routine dosimeter reading Minimum routine permissible reading = 25 x 31 kGy = 28.7 kGy 27 Absorbed dose at the maximum dose position = Maximum specified dose X Routine dosimeter reading maximum routine permissible reading = 25 x 31 kGy = 35.4 kGy 35 Therefore the minimum and maximum absorbed dose corresponds to the above routine dosimeter reading are 28.7 kGy and 35.4 kGy respectively.

19. Questions ? • Multiple Choice • 1. Penetration of electrons depends on: • A. Current of electron beam, • B. Electron energy, • C. Speed of conveyor. • 2. Radiation sterilization is performed according to: • A. ISO 11134, • B. ISO 11137, • C. ISO 11135. • 3. What does “dose mapping” mean? • A. Determination of minimum dose • B. Determination of maximum • C. Measurement of dose distribution • 4. Which dosimeter is used for monitoring of radiation processing of products? • A. Reference dosimeter • B. Routine dosimeter • C. Transfer standard dosimeters • 5. In radiation processing application, calorimeter is used as • A. Primary dosimeter • B. Transfer standard dosimeter • C. Routine dosimeter • 6. For absorbed dose measurements for radiation sterilization, dose is referred in • A. Water • B. Air • C. Graphite

20. Questions ? Which standard do you follow for the sterilization of health care products? Which standard do you follow for the selection of dosimetry systems? Which standard do you follow for the calibration of dosimetry systems? Which standard do you follow for estimating uncertainty in your dosimetry systems? Name few reference standard dosimeters for calibration gamma irradiation facilities What are the differences between reference standard and routine dosimeters? What are the required procedures to validate the radiation processing of products? How do you achieve measurement traceability for your dosimetry systems? What are the roles of dosimetry in the validation of radiation processing? How do you ensure quality assurance during routine production of radiation processed product? Name few routine dosimeters used in the range of 400 Gy to 1 kGy dose range for food irradiation facilities. How do you calibrate 10 MeV electron beams?

21. Questions ? Name few routine dosimeters used in electron beam irradiators. What are important differences between the dosimetry of electron beam facility and gamma irradiation facility? What are the main aims of carrying out dose mapping in IQ, OQ and PQ? Why do you require different dosimeters during different stages of validation process? What are the important environmental conditions that affect the performance of the dosimeters during its applications? How do you ensure accuracy of measurement? How do you correct systematic error in your dosimetric measurement? What are operational and performance qualifications? How is dose mapping in operational qualification is different from performance qualification? Which standard do you follow for dose mapping during validation? Which standard do you follow for the validation of radiation processing gamma irradiator? What standard do you follow for the validation of electron beam irradiator?