SWGDRUG Approach to Validation

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SWGDRUG Approach to Validation
Scott R. Oulton
SWGDRUG Secretariat and Associate Laboratory
Director for the Drug Enforcement Administration
(DEA) Southwest Laboratory Vista, California
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SWGDRUG
Scientific Working Group for the Analysis of
Seized Drugs
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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.
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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

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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

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Website www.swgdrug.org
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Website

• Future features
• Search Engine
• Questionnaire Form
• Membership Login

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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

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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

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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

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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 dont agree with what you are reading in
  the publication sources, let us know
• Write or E-mail any core committee member

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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
  90002005(E)
• Studies to determine method performance must be
  carried out by qualified/competent analysts using
  appropriate calibrated equipment

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Validation

• Why is validation necessary?
• We make measurements every day that affect
  peoples 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.

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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 laboratorys method or different
  instrument
• Demonstrate equivalence between two different
  methods

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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

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SWGDRUGs Approach to Validation

• See PART IV B
• QUALITY ASSURANCE/VALIDATION OF ANALYTICAL
  METHODS
• Analytical Scheme
• Laboratory Responsibility
• Operational Environment
• Documentation
• Validation Plan

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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

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SWGDRUGAnalytical Scheme

• Verification shall be conducted on methods from
  non-routine, published literature, another
  laboratorys protocols
• demonstrate that a representative set of
  reference materials has been carried through the
  process and yielded the expected results

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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

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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

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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)

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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

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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

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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

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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

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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

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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

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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_at_hotmail.com

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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

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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

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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

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SWGDRUG Properties for Validation Process

• Supplemental Document SD-2

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SWGDRUG Future Plans

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

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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, laboratorys are
  developing more specific qualitative methods

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US Validation Perspective

• Smaller labs have simple qualitative methods, but
  only looking for a few specific drugs
• We previously relied upon the analysts training
  and experience
• Analyst discretion on which instrument and/or
  method to utilize

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US Validation Perspective

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

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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

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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?

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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

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Questions ??

• Scott R. Oulton
• E-mail scott.r.oulton_at_usdoj.gov
• Phone [phone]
• A copy of this presentation, can be downloaded
  at
• www.swgdrug.org/events.htm