Is IQ/OQ/PQ part of irradiation process control?

Transcription

1 International Conference on Applications of Radiation Science and Technology (ICARST 2017) - 24 to 28 April 2017, Vienna, Austria Is IQ/OQ/PQ part of irradiation process control? Florent KUNTZ and Alain STRASSER Aerial-CRT, Illkirch France

2 Outline Introduction - Relevant standards/guides Installation, Operational and Performance Qualification Control absorbed dose to product Associated uncertainties The importance of traceable calibration and good practices Conclusion

3 Introduction Relevant standard/guides ISO ANSI/AAMI/ISO ANSI/AAMI/ISO ISO/ASTM 51649, 51702, ASTM E2303 Installation Qualification Irradiator supplied and installed in accordance with its specifications? Operational Qualification Irradiator, as installed, capable of operating and delivering appropriate doses within defined acceptance criteria? Sterilization of health care products Radiation Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices Part 3: Guidance on dosimetric aspects

4 Introduction Relevant standard/guides ISO ANSI/AAMI/ISO ANSI/AAMI/ISO ISO/ASTM 51649, 51702, ASTM E2303 Performance Qualification Obtaining and documenting evidence that the equipment, as installed and operated in accordance with operational procedures, consistently performs in accordance with predetermined criteria Sterilization of health care products Radiation Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices Part 3: Guidance on dosimetric aspects

5 Gamma/X Ray process Carried out to characterize the irradiator with respect to the distribution and reproducibility of dose and to establish the effect of process interruption on dose Operational Qualification ANSI/AAMI/ISO ISO/ASTM 51702, Source activity/geometry Source mechanism Ebeam power/energy Cycle Timer/Laps/Speed Conveyor path(s) Product density/filling Product transition Gamma plant, Danver Hydromatics, India

6 Operational Qualification Homogeneous material (various densities) ANSI/AAMI/ISO ISO/ASTM 51702, Example 7 MV X Ray Density 0.15 DUR /- 0.03

7 E Beam process ENERGY/CURRENT (8.2) 1 Installation Qualification ANSI/AAMI/ISO ISO/ASTM SPOT SIZE (8.5) SCAN WIDTH (8.2) 3 SCAN UNIFORMITY 4 (8.2) PRODUCT 5 PARALLELISM* CENTERING 6 (8.6) CONVEYOR SPEED (8.5) * optional

8 Operational Qualification Homogeneous material (various densities) Process Absorbed Dose interruption/restart at surface kgy for both conveyor and electron beam (9.3.6) Dsurf = 10,77 * (I/(V*W b )) + 0,04 Dose distribution K = 10,77 kgy.m 2 /(ma.min) Surface (9.3.4) Product Height dependence (9.3.5) Inside material (9.3.4, 9.3.8) Machine variability Absorbed dose as function of conveyor speed, beam current, scan width, (9.3.5) Dose variability / reproducibility (9.3.5) I / (Speed*SW) in ma.min/m 2

9 Performance Qualification Each processed product/family! ANSI/AAMI/ISO ISO/ASTM 51649, 51702, What for? Section 10 of ISO Establish the dose distribution inside the product Establish the relation between the routinely monitored dose and the maximum and minimum dose delivered to the product Establish the uncertainty of the mapping Establish the Dose interval allowed for the routine dosimeter Choose a target dose for the monitor dosimeter

10 Performance Qualification Gamma: Partial load of labware ANSI/AAMI/ISO ISO/ASTM 51649, 51702, P4 P3 P1 P1 P3 P4 DUR /- 0.04

11 Control the dose to product Real life (due to variability) Theoretical relationship Dmax Dmin Variability on DUR Variability on Rmin/mon and Rmax/mon Monitoring Dose vs. Min Dose or Max Dose Dmon

12 Reasons for variability Variability Uncertainty on dose to product ANSI/AAMI/ISO dose mapping uncertainty machine variability dosimeter reproducibility σ map min, σ map max σ mach σ rep dosimeter calibration uncertainty σ cal σ total min = (σ cal 2 + σ map min 2 + σ rep 2 + σ mach2 ) 1/2 σ total max = (σ cal 2 + σ map max 2 + σ rep 2 + σ mach2 ) 1/2 The lower σ total min, σ total max the easier the process management

13 Dose to product Average minimum dose must exceed dose required for sterilization D ster Average maximum dose must not exceed maximum acceptable dose D max acc guard band approach: Minimum dose to be 2 standard deviations greater than dose required for sterilization. (same for D max acc ) 2.5 % 2σtot min 2σtot max D ster D product lower D max acc D product upper

14 The importance of traceable calibration and good practices Example of dose intercomparison CRP: Development of Electron Beam and X Ray Applications for Food Irradiation (DEXAFI) Evaluate ability of participants to: - Deliver target dose values - Measure doses actually applied

15 Participating Organisations 13 Participants / Radiation Type Chengdu China / g P. R. China / EB 10MeV Egypt / g Hawaï / XRay Indonesia / g Japan / EB 10MeV Pakistan / g Poland / EB 10MeV Portugal / EB 10 MeV X-Rays E-Beam Syria / g Thailand / EB 10MeV USA / EB 10 MeV Vietnam / EB 10MeV 3 radiation types Gamma

16 Methods Performance indicator: -measured vs. applied dose (dosimetry) 1 kgy 5 kgy 10 kgy

17 Z score deviation Results: meas. vs. applied dose Particip. % deviation 1-1.6% % 3 4.1% 4 2.7% 5 0.0% 6 7.9% % % 9-1.9% % % % %* *Outlier(Grubbs test; α=5%) (outlier) Criteria 1 kgy Obs. 12 Minimum Maximum st Quartile Median rd Quartile Mean Variance (n-1) Std dev. (n-1) Box plot (filtered) Z scores % deviation (1 kgy) Participants XLSTATS v (Addinsoft) α = 1% α = 5%

18 Z score Results: meas. vs. applied dose Particip. % deviation 1 CC 1.2% 2 Pak 7.0% 3 PRC 4.4% 4 Pol 0.6% 5 Egy -2.2% 6 Vie -0.7% 7 Tha -10.9% 8 Syr -13.1% 9 Jap -2.2% 10 Haw 1.5% 11 Por 62.8%* 12 Ind -3.2% 13 USA -65.1%* *Outlier (Grubbs test; α=5%) 11, 13 11, 13 (outliers) Criteria 1 kgy Obs. 11 Minimum Maximum st Quartile Median rd Quartile Mean Variance (n-1) Std dev. (n-1) Box plot (filtered) Z score (filtered) Participants % deviation (5 kgy) XLSTATS v (Addinsoft) α = 1% α = 5%

19 Z score Results: meas. vs. applied dose Particip. % deviation 1 CC 0.3% 2 Pak 11.6% 3 PRC 3.0% 4 Pol -4.4% 5 Egy -4.0% 6 Vie 1.0% 7 Tha 2.6% 8 Syr -11.0% 9 Jap -1.0% 10 Haw 1.5% 11 Por 62.0%* 12 Ind -1.3% 13 USA -75.7%* *Outlier (Grubbs test; α=5%) 11, 13 11, 13 (outliers) Criteria 1 kgy Obs. 11 Minimum Maximum st Quartile Median rd Quartile Mean Variance (n-1) Std dev. (n-1) Box plot (filtered) Z scores (filtered) Participants % deviation (10 kgy) XLSTATS v (Addinsoft) α = 1% α = 5%

20 k(i) h(i) Measured vs. applied dose Particip. 1 kgy 5 kgy 10 kgy 1-1.6% 1.2% 0.3% % 7.0% 11.6% 3 4.1% 4.4% 3.0% 4 2.7% 0.6% -4.4% 5 0.0% -2.2% -4.0% 6 7.9% -0.7% 1.0% % -10.9% 2.6% % -13.1% -11.0% 9-1.9% -2.2% -1.0% % 1.5% 1.5% % 62.8% 62.0% % -3.2% -1.3% % -65.1% -75.7% Reproducibility 1.5 Mandel s k statistics (α = 0.05 / kcrit = 1,687) Trueness 11; % deviation (3 doses) Mandel s h statistics (α = 0.05 / hcrit = 1,815) Participants 11; Participants

21 The importance of traceable calibration and good practices 25% 20% 40% of participants only! 15% Auditing the metrology system: 10% 5% 0% < -7% -7% to -5% -5% to -3% -3% to -1% -1% to 1% 1% to 3% 3% to 5% 5% to 7% > 7% 1. Is dosimetry system calibration performed? When? 2. What is the reference dosimetry system used? 3. Is it traceable to certified calibration lab? 4. Is it in house calibration? In calibration plant? In industrial plant? 5. Does calibration geometry allow Reference dosimeter dose = Routine dosimeter dose? 6. Has calibration verification been performed? 7. Is measurement instrumentation calibrated/verified? What about Uncertainty?

22 Conclusion How to prove that the irradiation process is under control? Traceable calibration of dosimetry system(s) Traceable dose measurements (monitoring Dose, ) IQ/OQ Knowledge of the process PQ Capacity of process of delivering appropriate dose to product within defined acceptance criteria Process (total) uncertainty assessment

23 Conclusion Recommendation: apply ISO ANSI/AAMI/ISO ANSI/AAMI/ISO ISO/ASTM 51649, 51702, ASTM E2303 Process control: as important for industry as for research projects!

24 International Conference on Applications of Radiation Science and Technology (ICARST 2017) - 24 to 28 April 2017, Vienna, Austria IQ/OQ/PQ are definitely part of irradiation process control! Florent KUNTZ and Alain STRASSER Aerial-CRT, Illkirch France