SWGDRUG Approach to Validation

1. SWGDRUG Approach to Validation Scott R. Oulton SWGDRUG Secretariat and Associate Laboratory Director for the Drug Enforcement Administration (DEA) Southwest Laboratory Vista, California

2. SWGDRUG Scientific Working Group for the Analysis of Seized Drugs

3. Mission of SWGDRUG The mission of SWGDRUG is to recommend minimum standards for the forensic examination of seized drugs and to seek their international acceptance.

4. SWGDRUG Objectives • Specifying requirements for practitioners’ knowledge, skills and abilities, • Promoting professional development, • Providing a means of information exchange within the forensic science community, • Promoting ethical standards of practitioners, • Providing minimum standards for examinations and reporting, • Establishing quality assurance requirements, • Considering relevant international standards, and • Seeking international acceptance of SWGDRUG recommendations

5. 2005 SWGDRUG Process • The SWGDRUG process is an international forensic science community endeavor • The role of the core committee is to vote to accept or reject subcommittee recommendations • In order for a proposal to become an official recommendation, 3/4s of the full core committee must be present. 2/3s of those present must vote in the affirmative (YES) for a proposal to become a recommendation

6. Website www.swgdrug.org

7. Website • Future features: • Search Engine • Questionnaire Form • Membership Login

8. SWGDRUG Core Committee • DEA – Nelson Santos • Secretariat – Scott Oulton (non-voting) • FBI - Eileen Waninger • ASCLD – Garth Glassburg • NIST - Susan Ballou • ASTM and NEAFS- Jack Mario • Educator – Dr. Chris Tindall • Educator – Dr. Suzanne Bell

9. SWGDRUG Core Committee • CAC & NWAFS - Jerry Massetti • MAFS - Richard Paulas • MAAFS - Linda Jackson • SAFS - Dr. Conrad Roberson • SWAFS - Gary Chasteen • South Africa - Tshepo Shole • Connecticut DPS – Dr. Robert Powers

10. SWGDRUG Core Committee • Canada - Richard Laing • Japan - Dr. Kishi Tohru • United Kingdom - Dr. Sylvia Burns • Australia - Catherine Quinn • Germany - Dr. Udo Zerell • ENFSI - Dr. Erkki Sippola • UNODC - Dr. Iphigenia Naidis

11. SWGDRUG Continued Success • All forensic drug analysts must stay involved in the process by contributing comments, criticisms and suggestions • If you agree with the process, let us know • If you don’t agree with what you are reading in the publication sources, let us know • Write or E-mail any core committee member

12. Validation • Definition and Purpose of Validation • Validation is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use or application have been fulfilled [ISO 9000:2005(E)] • Studies to determine method performance must be carried out by qualified/competent analysts using appropriate calibrated equipment

13. Validation • Why is validation necessary? • We make measurements every day that affect people’s lives (fines, incarceration, etc.) • Decisions are made by our results. There can be a high cost if we are wrong • Our customers expect to be able to trust the results • Methods must be sufficiently reliable that decisions can be made with confidence.

14. Validation • When to validate a method? • New method to address particular problem • Revise existing method for improvements or new problem • QA suggests method is changing with time • Use of another laboratory’s method or different instrument • Demonstrate equivalence between two different methods

15. Validation • Who decides how and to what degree of validation is required for method validation? • The Laboratory is responsible for ensuring methods are validated • Clients Input • Laboratory and client should agree to method used • Usually done retrospectively

16. SWGDRUG’s Approach to Validation • See PART IV B QUALITY ASSURANCE/VALIDATION OF ANALYTICAL METHODS • Analytical Scheme • Laboratory Responsibility • Operational Environment • Documentation • Validation Plan

17. SWGDRUGAnalytical Scheme • An analytical scheme shall be comprised of validated methods appropriate for the analyte • Identify analyte of interest, preclude false-positives and minimize false-negatives • For quantification the method should reliably determine the amount of analyte present

18. SWGDRUGAnalytical Scheme • Verification – shall be conducted on methods from non-routine, published literature, another laboratory’s protocols • demonstrate that a representative set of reference materials has been carried through the process and yielded the expected results

19. SWGDRUG Validating Methods • Laboratory responsibility to determine whether SOPs have been validated, verified or require further validation/verification • All methods shall be validated/verified to demonstrate performance in normal operating environments

20. SWGDRUG Validating Methods • The entire validation/verification process shall be documented. Documentation shall include, but is not limited to the following: • Personnel involved • Dates • Observations from the process • Analytical data • Conclusions and/or recommendations • Authorization approval signature

21. SWGDRUG GeneralValidation Plan • Purpose/scope – introductory statement (what, purpose and results required) • Performance specification – list of specific objectives • Process review – after completion, revisit objectives to ensure they were satisfactorily met • Analytical method – state the method to be validated (each step shall demonstrate satisfactory performance)

22. SWGDRUG GeneralValidation Plan • Reference materials – appropriate materials used for qualitative and quantitative procedures (traceability required) • Selectivity – assess capability of method to identify/quantify the analyte • Matrix effects – assess impact of interfering components • Recovery – Determine for quantitative analysis

23. SWGDRUG GeneralValidation Plan • Precision (Repeatability/Reproducibility) – determine: • Acceptable limits • Qualitative/Quantitative – run 10 times • Non-routing Methods – may differ • Trueness – quantitative analysis, assessed by: • Replicate measurements at different concentrations • Performance of standard addition method • Comparison to proficiency test results • Comparison with different validated methods

24. SWGDRUG GeneralValidation Plan • Range – determine concentration or amount limits for which the method is applicable • Limit of detection (LOD) – lowest amount of analyte to be detected and identified (not necessarily quantitatively accurate) • Limit of quantitation (LOQ) – lowest concentration that has acceptable level of uncertainty

25. SWGDRUG GeneralValidation Plan • Linearity – quantitative methods • Determine mathematical relationship (calibration curve) between concentration and response • LOQ forms lower end of working range • Determine acceptable variation from calibration curve • Determine upper limits of working range • Robustness – alter method parameters and determine any changes to accuracy

26. SWGDRUG GeneralValidation Plan • Ruggedness – assess the factors external to the method • Uncertainty – assess contribution of random and systematic errors • Quality control – establish acceptance criteria prior to implementation of the method

27. Validation Type • Qualitative analysis - the parameters that need to be checked are selectivity, limit of detection and reproducibility. • Quantitative analysis – the parameters that need to be checked are selectivity, matrix effects, recovery, precision, trueness, LOQ, linearity, robustness, ruggedness, reproducibility and uncertainty

28. SWGDRUG Supplemental Documents • Adopted by the Core Committee in August 2005 • The supplemental documents are not SWGDRUG recommendations • Intended to be a resource for those responsible for implementing SWGDRUG recommendations • Not inclusive and SWGDRUG recognizes that there are many ways of implementing the recommendations • Living documents and as such, SWGDRUG invites comments. Send your comments to swgdrug@hotmail.com

29. SWGDRUG Validation of Analytical Methods • Supplemental Document SD-2 for Part IVB entitled “Quality Assurance/Validation of Analytical Methods” was finalized for publication in February 2006 • Designed to assist laboratories develop a general validation plan which meet their individual requirements • Intended to be used in conjunction with SWGDRUG Recommendations, Part IVB, Section 2 • The document is organized into two sections: • Section I provides guidance on the issues to consider when using various analytical techniques • Section II is an example of a completed validation plan

30. SWGDRUG Properties for Validation Process • Section 1 of the document is organized into Categories of Analytical Techniques (IR, MS, HPLC, etc.) from Table 1 – Categories A, B and C • For each instrument or method, specific properties are detailed that could have an effect on how the validation process is formulated and executed

31. SWGDRUG Properties for Validation Process • Section II demonstrates a purpose-defined validation plan for a particular method. • The aim is to show how a complete validation plan may appear • The example should not be directly applied to methodology used by any laboratory without first considering the specific purpose of a method and its relevant operational environment

32. SWGDRUG Properties for Validation Process • Supplemental Document SD-2

33. SWGDRUG Future Plans • SWGDRUG intends on adding additional supplemental documents to help illustrate validations • Actual validated method • Example qualitative and quantitative validations • Uncertainty examples

34. US Validation Perspective • Disclaimer: This information is solely based upon my personal experiences in different laboratories in the US • Validation requirements generally thought of only for quantitative analysis • Qualitative methods exist, but in a general manner • Through influence of ISO, laboratory’s are developing more specific qualitative methods

35. US Validation Perspective • Smaller labs have simple qualitative methods, but only looking for a few specific drugs • We previously relied upon the analyst’s training and experience • Analyst discretion on which instrument and/or method to utilize

36. US Validation Perspective • Changing method parameter acceptable to achieve identification (e.g., GC oven temp.) • Fear of developing technicians as opposed to scientists

37. US Validation Perspective • DEA Analytical Sufficiency Document • Originally thought sufficient for qualitative analysis • However, no specific qualitative validation determining selectivity, limit of detection and reproducibility at a minimum

38. US Validation Perspective • DEA recently accredited in ISO 17025 • Developed general guidelines for qualitative testing • Although we were accredited, we are currently deciding what constitutes a qualitative method validation • Questions • Make methods instrument and drug specific? • Make methods only instrument specific?

39. US Validation Perspective • Problem with quantitative methods, we have numerous ones for the same analyte • In upwards of 5-10 different methods varying minimal parameters • Considering standardizing methodology and limit number of choices

40. Questions ?? Scott R. Oulton E-mail: scott.r.oulton@usdoj.gov Phone: (760) 597-7906 A copy of this presentation, can be downloaded at: www.swgdrug.org/events.htm