The Importance of Validated Rapid Methods for International Trade

Transcription

1 The Importance of Validated Rapid Methods for International Trade 3M All Rights Reserved. Robert Koeritzer Sr. Technical Manager 3M Food Safety Past-President, AOAC International

2 Agenda Method validation Complex global web Comparison of various schemes Moving towards harmonization Trends in method validation. 2

3 Analytical Science in Trade/Commerce Codex Technical Committees Import Testing Quality Systems Emerging Chemical Contaminates Emerging Pathogens 3

4 EN ISO EN ISO 8261 / IDF 122 Vertical European standards EN ISO Accreditation Horizontal Methods Alternative methods 4 diluents Manufacturer QC/QA Preparation of test samples Routine National NF, NF, DIN, Reference methods International European national ISO NF ISO or EN NF EN, or EN ISO NF EN ISO EN ISO ISO : Guidelines on QA and performance testing of culture media ISO 7218 : General rules for microbial examination EN EN ISO ISO Validation

5 European Recognition Committees (Alternative Method) Country France Germany UK Nordic Europe Standards Bodies AFNOR D I N B S I NMKL CEN Recognition Systems AFNOR None, Technical report EMMAS NordVal MicroVal Since 2004, Standardisation of the alternative method performance assessment with EN ISO is possible

6 European requirements for alternative methods Requirements: The use of alternative analytical methods is acceptable, when the methods are validated against the reference method set in Annex and certified by a third party in accordance with the protocol set in EN/ISO standard or other internationally accepted similar protocols. If the food business operator wishes to use analytical methods other than those validated and certified as described above, the methods shall at least be well documented and scientifically validated. Consequences: AFNOR validated methods will be accepted everywhere in Europe AOAC validated methods will be accepted if they have been validated against an EN ISO method 6

7 Three major global validation AFNOR (ISO protocol) MicroVal (ISO protocol) AOAC International (AOAC protocol Harmonized with ISO 16140) 7

8 Validation Methods Comparison Overall AOAC R-I, PTM AOAC Intl OMA ISO 16140:2003(E) Type of Method Proprietary Proprietary & Noncommercial Proprietary & Non-commercial Reference Methods AOACI, FDA, USDA, ISO AOACI, FDA, USDA ISO, CEN Time to Validation 6-12 months months (minimum) 12 months (minimum) Methods Reviewed Required yearly N/A Required every 4 yrs 8

9 Part 1: Methods Comparison [Pre-collaborative] AOAC R-I, PTM AOAC Intl OMA ISO 16140:2003(E) Food Categories Claim Dependent 6 (for all or most foods) 5 (for all or most foods) Food Types Claim Dependent 20 representative food types 3 per category Level of Analyte Quantitative 3 (H, M, L) + uninoculated if necessary 3 (H, M, L) + uninoculated if necessary 5 levels # of Samples 5 per level 5 per level 2 per level (preferably 5-10) Competitive micro flora Required in 1 food type Required in 1 food type NA Ruggedness Required Suggested NA 9

10 Part 2: Methods Comparison Inter-laboratory study (Collaborative) AOAC R-I, PTM AOAC Intl OMA ISO 16140:2003(E) Participating Labs NA Minimum of 8 Minimum of 8 Food Categories NA 6 (for all or most foods) 1 Food Proposed 4/ Food Types NA 1 per category 1 Level of Analyte NA 3 contamination levels, plus uninoculated if necessary 3 contamination levels, plus uninoculated if necessary # of Samples NA 2 per level 2 per level 10

11 AFNOR The principles of the certification procedure The method validation study is carried out in 2 phases: [technical protocol based on EN ISO 16140] Phase 1: (preliminary study) Characterize the method and assess it s effectiveness by comparing it to the effectiveness of the standardized reference method. Comparison carried out at the expert laboratory. Diversity of samples and experimental conditions (sufficient number of naturally contaminated samples) reflect real conditions in the field. 11

12 AFNOR The principles of the certification procedure Phase 2: (inter-laboratory study) Compare the efficacy of the method to be validated and the reference method, in several laboratories (8-10 minimum). Under defined conditions of reproducibility and repeatability. AFNOR Difference Emphasis on sample diversity (natural contamination) Confirmation of positive results Evaluation of the quality assurance procedure at the production site 12

13 MicroVal Offers: An open platform for all European Certification Bodies. Aiming at a harmonized interpretation of the EN ISO Working towards a harmonized international market for all test kits. Is headed by one European platform with all European stakeholders involved. A neutral MicroVal secretariat not part of a certification organization. 13

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16 16 AOAC International Validation/Standardization

17 Volunteer Consensus Standards Process of developing standards is open and transparent, with written procedures covering each step of the process, such as you find in the Official Methods Program. System is known as voluntary because participation is on a voluntary basis and because compliance with the standards is voluntary (unless adopted or referred to by a government authority, like Official Methods) 17

18 Initial Method Validation Pre-collaborative Performance parameters Precision Accuracy Ruggedness Linearity Limit of detection Comparison to other methods Acceptable method performance (Expert Lab study) Meets Claims in package insert 18

19 Method Collaborative Study 8-10 laboratories minimum Minimum of 8 labs with acceptable data (chemistry and quantitative microbiology) Minimum of 10 labs (qualitative microbiology) 5 samples or test materials (chemistry) Materials must cover the range of assay applicability Blind duplicates Standard RM or Control 19

20 AOAC Communities model Issue/Need Training & Conferences Collaborative Study Validation Engagement Industry/Regulatory/Academia Single Lab Validation Community Formed Expert Review Panel Formed 20

21 AOAC Communities Marine & Freshwater Toxins Gathering Stakeholders (Industry and regulatory) International Workshops Prioritize methods needed Develop methods using best science Validate methods Set the industry standards 21

22 AOAC Communities Dietary Supplements Gathering Stakeholders (Industry and regulatory) Prioritize methods needed Develop methods using best science Validate methods Set the industry standards 22

23 Trends in Method Validation: Business Perspective Diagnostic Manufacturer Reference Lab Government/ Regulatory Routine Diagnostic Use Cost Time to Results Accuracy Inclusivity Food Processor Exclusivity Validation Costs: People/Resources, Time, Euros 23

24 Diagnostic Manufacturer Validation Costs and Time Validation Costs per Method $70,000 $60,000 $50,000 $40,000 $30,000 $20,000 $10,000 $- AOAC-PTM AOAC- OMA AFNOR Study/Lab Expenses Application Fees Time to Complete Validation (per Method) Acronyms: AOAC-PTM: Performance Tested Method AOAC-OMA: Official Method of Analysis Weeks AOAC-PTM AOAC-OMA AFNOR Protocol, Analysis, Submit Results Complete Study AOAC PTM Initial Approval 24

25 Food Processors: Wait and Re-Validate? Post Method Approval Validation Food Matrix and Diluent Validation Local Flora Evaluation Local Reference Method Validation For EACH country! Protection from Litigation OR: Internal Validation (AOAC or AFNOR protocol) Third-Party approvals are taking too long Internal Study: cost can be US$ 200,000 External (reference lab) Study usually very limited in scope Participation in Proficiency Testing Programs 25

26 Governments & Regulatory Agencies Validations Regulatory Balancing Act International approvals acceptable for international commerce Are validated proprietary methods acceptable for testing local foods? If yes, what validations are acceptable? Government Challenges Scarce Resources Who pays for the validation study? Proprietary Method Validation Processes Many proprietary methods are seeking governmental validation Better test Accuracy Consumer Safety Time and Resources 26

27 Governments & Regulatory Agencies Validations (con t) Collaborative Model: AOAC Official Method of Analysis Food Processor Government Agency Diagnostic Manufacturer AOAC Collaborative Regulatory Agency Method Adoption Are Third Party validations diminishing in importance? Fewer Food Processors are volunteering for collaborative studies AOAC Performance Tested Method 3 rd Party Validation Lower Cost; Shorter Time AOAC PTM approvals are more compatible with rapidly changing technology 27

28 Validation Trends Cost and Time Requirements Increasing Increasing number of products requiring validation Increasing numbers of regulatory agencies Products marketed to more and more countries (import regulations) Convergence Harmonization of methods AOAC and ISO closely aligned Fit for Purpose Validations AOAC Performance Tested Method (AOAC RI) Screening versus Actionable 28

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32 BPMM Methodology Review scientific literature. Review current International Standards. Consult other (topic) experts. Review ISO, AFNOR, and AOAC validation protocols. Discuss/Debate via teleconference and . Make consensus recommendations. 32

33 Key Issues To Address Does the intended purpose of a method necessitate different levels of sampling and testing. Consider factors influencing confidence (uncertainty) of data. Method Extension to new matrices and/or target organisms. 33

34 Key Issues To Address Validation in absence of a reference method, confirmation procedure, or superior performance of new method Scientific and statistical bases for: Determining the limit of detection Developing performance standards for methods How to validate performance to meet a performance standard? What are effective means for determining and articulating the uncertainty associated with microbiological methods? 34

35 BPMM Recommendations Statistics Work Group Use International Standards ISO (validation of proprietary methods) ISO 5725 (precision & trueness) ISO (capability of detection) ISO (measurement uncertainty) Use robust statistics Define Measurement Uncertainty Use LOD 50 for Qualitative methods Use ISO for Quantitative methods 35

36 BPMM Recommendations Matrix Extension Work Group Standardize recommended species/strains (include in ISO revision) Use categorization of food groups based key attributes Charts define when additional validation is needed (include in ISO revision) Focused on testing for inhibitory or other unique technical considerations that might prevent application of the method 36

37 BPMM Recommendations Sampling Work Group Follow ISO standards. (statistical process control) Identify and discuss sources of variation as part of method validation. 37

38 BPMM Recommendations Detection Limits Work Group Use a detailed protocol for preparation of inoculum. (include in ISO revision) Confirm method results where alternative method is more sensitive then reference method. (include in ISO revision) 38