Dose Audits 101 February 4, 2016

Transcription

1 Dose Audits 101 February 4, 2016

2 Dose Audits 101 Jade Schiesser, Sterilization Specialist QTS since 2013 University of MN (2011) Member of AAMI working groups WG2 Radiation Sterilization WG8 Microbiological Methods

3 Outline Section 1: What is a Dose Audit? Section 2: Why are Dose Audits Required? Section 3: How are Dose Audits Performed? Section 4: Timing and Scheduling Section 5: Challenges with Dose Audits

4 What? Medical Device Sterilization Methods (single-use) E-Beam X-Ray Other Gamma Ethylene Oxide (EO)

5 What? Purpose of sterilization is to prove a Sterility Assurance Level (SAL) Radiation sterilization = dosage (measured in kgy) Sterility Assurance Level (SAL) pre-sterilization 1 in 10 are non-sterile 1 in 1,000,000 are non-sterile Sterilization Dose (or Time)

6 What? Audit of the sterilization Dose Dose audits prove efficacy of radiation sterilization through an abbreviated sterilization event, followed by tests of sterility Sterility Assurance Level (SAL) pre-sterilization Sterilization Dose (or Time) 1 in 10 are non-sterile Dose Audits Performed Here 1 in 1,000,000 are non-sterile Routine Sterilization

7 Outline Section 1: What is a Dose Audit? Audit of the sterilization Dose Longer/higher exposure increases sterilization probability Section 2: Why are Dose Audits Required? Section 3: How are Dose Audits Performed? Section 4: Timing and Scheduling Section 5: Challenges with Dose Audits

8 Why? Production dosage is always a range (e.g kgy) Dose substantiation study is completed to establish the minimum sterilization dose (e.g. 25 kgy) Following completion of dose substantiation study, dose audits are required by the ISO standard. Dose Substantiation Study Establish Families Establish Bioburden (3 Lots) Initial Verification (1 Lot) Dose Audit Bioburden (1 Lot) Dose Audits Dose Audit Verification (1 Lot)

9 Why? ISO Sterilization of health care products Radiation Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices Section : The continued effectiveness of the established sterilization dose shall be demonstrated through the conduct of A) Determinations of bioburden to monitor the number of microorganisms on product B) Sterilization dose audits to monitor the radiation resistance of the bioburden on product

10 Why? Effectiveness of radiation sterilization is dependent on bioburden Dose audits can detect shifts in bioburden counts and/or resistance Increased Counts Increased Resistance

11 Outline Section 1: What is a Dose Audit? Audit of the sterilization Dose Longer/higher exposure increases sterilization probability Section 2: Why are Dose Audits Required? Bioburden can change or shift over time Section 3: How are Dose Audits Performed? Section 4: Timing and Scheduling Section 5: Challenges with Dose Audits

12 How? Samples required: 20 product units from a single lot (Using Method Vdmax) Sample selection: Representative samples of the product family (if applicable) Selection Methods Master Product Equivalent Product Simulated Product

13 How? Master Product All the same general features and materials Bigger, more bioburden worst case

14 How? Equivalent Product Same but slightly different Mirror images Different finishes

15 How? Simulated Product Something you wouldn t normally produce/sell Represents equal or greater bioburden for each product being represented

16 How? Test Component 1: Bioburden 10 samples Used for monitoring/trending purposes NEVER used as Pass/Fail criteria for a dose audit

17 How? Test Component 2: Sterility 10 samples Samples sterilized at verification dose (e.g. 7-9 kgy), NOT at production dose (e.g kgy) Measures resistance of bioburden These results determine the success or failure of the dose audit

18 How? Bioburden Data from Dose Substantiation Study CALCULATE 0/10 or 1/10 positive = Pass Verification Dose 10-1 (e.g. 7-9 kgy) PROVES Production Dose SAL 10-6 (e.g kgy) 2/10 positive = Confirmatory dose experiment 3/10 or more positive = Fail

19 Outline Section 1: What is a Dose Audit? Audit of the sterilization Dose Longer/higher exposure increases sterilization probability Section 2: Why are Dose Audits Required? Bioburden can change or shift over time Section 3: How are Dose Audits Performed? Sterility results determine the success of your dose audit Bioburden results are just for monitoring purposes Section 4: Timing and Scheduling Section 5: Challenges with Dose Audits

20 Scheduling Once completed, 3 month window until next dose audit Can produce and sterilize any amount of product during that period Example: Dose audit is completed on January 1st. You would have until April 1st to sterilize product before the next dose audit would be due. 1/1/16 4/1/16

21 Scheduling Dose Audits are valid for 3 months Planning your TOTAL lead time: Receiving Cleaning Assembly/Production Shipping Bioburden Testing Sterility Testing Standard 7-8 weeks 1/1/16 2/1/16 3/1/16 4/1/16

22 Scheduling Dose Audits are valid for 3 months Planning your TOTAL lead time: Receiving Cleaning Assembly/Production Shipping Bioburden Testing Sterility Testing Expedited 4-6 weeks 1/1/16 2/1/16 3/1/16 4/1/16

23 Outline Section 1: What is a Dose Audit? Audit of the sterilization Dose Longer/higher exposure increases sterilization probability Section 2: Why are Dose Audits Required? Bioburden can change or shift over time Section 3: How are Dose Audits Performed? Sterility results determine the success of your dose audit Bioburden results are just for monitoring purposes Section 4: Timing and Scheduling Dose audits are valid for 3 months, but take a long time to perform You need to think about them when forecasting production Section 5: Challenges with Dose Audits

24 Challenges Result Generation & Interpretation

25 Challenges Result Generation & Interpretation

26 Challenges Sample Manufacturing & Testing Costs Sample preparation can be costly (need at least 20) Testing can vary between two seemingly similar product lines

27 Challenges Production Timing Long periods between production Skipped dose audits 1/1/16 4/1/16 7/1/16 10/1/16 TBD 3 months after Dose Audit Completed

28 Challenges Product or Manufacturing Changes From ISO :

29 Challenges Testing Failures & Complications Bioburden Spike Dose Audit affected? Over alert or action limits? Investigation required? Dose Audit Failure Too many positives? Impacts Dose augmentation Dose reestablishment

30 Challenges Testing Failures & Complications

31 Outline Section 1: What is a Dose Audit? Audit of the sterilization Dose Longer/higher exposure increases sterilization probability Section 2: Why are Dose Audits Required? Bioburden can change or shift over time Section 3: How are Dose Audits Performed? Sterility results determine the success of your dose audit Bioburden results are just for monitoring purposes Section 4: Timing and Scheduling Dose audits are valid for 3 months, but take a long time to perform You need to think about them while forecasting Section 5: Challenges with Dose Audits Radiation sterilization and dose audits can be challenging; QTS is the perfect partner to take all of the stress out of them

32 Outline Section 1: What is a Dose Audit? Audit of the sterilization Dose Longer/higher exposure increases sterilization probability Section 2: Why are Dose Audits Required? Bioburden can change or shift over time Section 3: How are Dose Audits Performed? Sterility results determine the success of your dose audit Bioburden results are just for monitoring purposes Section 4: Timing and Scheduling Dose audits are valid for 3 months, but take a long time to perform You need to think about them while forecasting Section 5: Challenges with Dose Audits Radiation sterilization and dose audits can be challenging; QTS is the perfect partner to take all of the stress out of them

33 Questions & Answers Session

34 Thank You! Contact information: Jade Schiesser Work: Slide Deck: Available at QTSpackage.com Resources Educational Materials

35 Additional Resources ANSI/AAMI/ISO :2006 Sterilization of health care products Radiation Part 1: Requirements for development, validation, and routine control of a sterilization process for medical devices ANSI/AAMI/ISO :2013 Sterilization of health care products Radiation Part 2: Establishing the sterilization dose ANSI/AAMI/ISO TIR13004:2013 Sterilization of health care products Radiation Substantiation of a selected sterilization dose: Method VD max SD ANSI/AAMI/ISO :2006 Sterilization medical devices Microbiological methods Part 1: Determination of a population of microorganisms on products ANSI/AAMI/ISO :2009 Sterilization of medical devices Microbiological methods Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process AAMI TIR29:2012 Guide for process characterization and control in radiation sterilization of medical devices AAMI TIR33:2005 Sterilization of health care products Radiation Substantiation of a selected sterilization dose Method Vd max AAMI TIR 35: 2006 Sterilization of health care products Radiation sterilization Alternative sampling plans for verification dose experiments and sterilization dose audits