2007/2008 SWGDRUG 2007/2008 SWGDRUG ACCOMPLISHMENTSACCOMPLISHMENTS

Drug Enforcement AdministrationDrug Enforcement AdministrationOffice of Forensic SciencesOffice of Forensic Sciences

sponsored by the

National Institute of StandardsNational Institute of Standardsand Technologyand Technology

and the

SWGDRUGSWGDRUG

Scientific Working Scientific Working Group for the Analysis Group for the Analysis

of Seized Drugsof Seized Drugs

CORE COMMITTEECORE COMMITTEE

• DEA – Nelson Santos DEA – Nelson Santos (Chair)(Chair)• Secretariat – Scott Oulton Secretariat – Scott Oulton (non-voting)(non-voting)

• FBI - Eileen WaningerFBI - Eileen Waninger• ASCLD – Garth GlassburgASCLD – Garth Glassburg• NIST - Susan BallouNIST - Susan Ballou• ASTM and NEAFS- Jack ASTM and NEAFS- Jack MarioMario• Educator – Dr. Chris Educator – Dr. Chris TindallTindall

• Educator – Dr. Suzanne Educator – Dr. Suzanne BellBell

CORE COMMITTEECORE COMMITTEE

• CAC & NWAFS - Jerry CAC & NWAFS - Jerry MassettiMassetti• MAFS - Richard PaulasMAFS - Richard Paulas• MAAFS - Linda JacksonMAAFS - Linda Jackson• SAFS – Christian MatchettSAFS – Christian Matchett• Toxicology – Dr. Robert Toxicology – Dr. Robert PowersPowers

CORE COMMITTEECORE COMMITTEE

• Canada - Richard LaingCanada - Richard Laing• Japan – Mr. Osamu Japan – Mr. Osamu OhtsuruOhtsuru• United Kingdom - Dr. United Kingdom - Dr. Sylvia BurnsSylvia Burns• Australia - Catherine Australia - Catherine QuinnQuinn• Germany - Dr. Udo ZerellGermany - Dr. Udo Zerell• ENFSI - Dr. Michael ENFSI - Dr. Michael BovensBovens• UNODC - Dr. Iphigenia UNODC - Dr. Iphigenia NaidisNaidis

APPROVED APPROVED RECOMMENDATIONS (Since RECOMMENDATIONS (Since

1997)1997) Code of Professional PracticeCode of Professional Practice Education & TrainingEducation & Training Methods of AnalysisMethods of Analysis

Drug IdentificationDrug Identification Sampling Seized Drugs For Qualitative Sampling Seized Drugs For Qualitative

AnalysisAnalysis Quality AssuranceQuality Assurance

General PracticesGeneral Practices Method ValidationMethod Validation Uncertainty Uncertainty

AnnexAnnex Code of Professional Practice: ExamplesCode of Professional Practice: Examples Glossary of Terms and DefinitionsGlossary of Terms and Definitions

WHY UNCERTAINTY?WHY UNCERTAINTY?

Forensic community was asking for Forensic community was asking for guidance.guidance.

Accrediting bodies are establishing Accrediting bodies are establishing measures of assessing conformity with measures of assessing conformity with ISO.ISO.

User requirements (Threshold Amounts)User requirements (Threshold Amounts) Legal requirementsLegal requirements

Transparency (nothing to hide)Transparency (nothing to hide) Potential Exculpatory Information Potential Exculpatory Information

Development of an Uncertainty Development of an Uncertainty DocumentDocument

The core committee voted in January 2008 to The core committee voted in January 2008 to release the draft uncertainty document for release the draft uncertainty document for public comment. public comment. Posted on the website since February 2008Posted on the website since February 2008

A SWGDRUG meeting was held July 21-23, A SWGDRUG meeting was held July 21-23, 2008 in New Orleans, LA.2008 in New Orleans, LA.

Comments were addressed and the core Comments were addressed and the core committee voted to adopt the document on committee voted to adopt the document on July 22, 2008.July 22, 2008.

The document should be posted on the The document should be posted on the website by the end of ??? 2008.website by the end of ??? 2008.

SWGDRUG’S GOALS IN SWGDRUG’S GOALS IN ADDRESSING UNCERTAINTYADDRESSING UNCERTAINTY

There is a wealth of information that already There is a wealth of information that already exists on uncertainty. We had no intentions of exists on uncertainty. We had no intentions of repeating existing information.repeating existing information.

Our Goal was to tailor the recommendations to Our Goal was to tailor the recommendations to answer specific seized-drug-analysis-uncertainty answer specific seized-drug-analysis-uncertainty questions, questions, andand do so before others did. do so before others did.

Provide Guidance To Accrediting Bodies and To Provide Guidance To Accrediting Bodies and To Laboratories in meeting their responsibilities.Laboratories in meeting their responsibilities. Uncertainty is associated with both qualitative Uncertainty is associated with both qualitative

and quantitative procedures.and quantitative procedures. Consider user requirements and address Consider user requirements and address

uncertainty through training, procedures, and uncertainty through training, procedures, and documentation.documentation.

SWGDRUG’S GOALS IN SWGDRUG’S GOALS IN ADDRESSING ADDRESSING

UNCERTAINTYUNCERTAINTY Raise AwarenessRaise Awareness Uncertainty is not doubt, it provides Uncertainty is not doubt, it provides

assurance that results and assurance that results and conclusions are fit for purpose.conclusions are fit for purpose.

Other BenefitsOther Benefits Provide enhanced confidence Provide enhanced confidence

through increased understanding of through increased understanding of results.results.

Provide mechanism to express Provide mechanism to express reliability of results.reliability of results.

HOW?HOW?

Two Primary Two Primary SectionsSections Qualitative Qualitative

DeterminationsDeterminations Quantitative Quantitative

DeterminationsDeterminations PurityPurity WeightsWeights

QUALITATIVE QUALITATIVE DETERMINATIONSDETERMINATIONS Individual methods have limitations and, Individual methods have limitations and,

consequently, uncertainty.consequently, uncertainty. Understanding limitations allows analysts Understanding limitations allows analysts

to build an appropriate analytical scheme to build an appropriate analytical scheme to correctly identify drugs or chemicals. to correctly identify drugs or chemicals. “It is expected that an appropriate “It is expected that an appropriate qualitative analytical scheme will result qualitative analytical scheme will result in, effectively, no uncertainty in reported in, effectively, no uncertainty in reported identifications.”identifications.” Use Part III B Methods of Analysis/Drug Use Part III B Methods of Analysis/Drug

Identification, e.g., IR and Identification, e.g., IR and microcrystalline test positive for microcrystalline test positive for cocaine – effectively NO uncertainty.cocaine – effectively NO uncertainty.

QUALITATIVE DETERMINATIONSQUALITATIVE DETERMINATIONS

Relevant limitations of an Relevant limitations of an analytical scheme should be analytical scheme should be documented and may need to be documented and may need to be in report. For example,in report. For example, Marquis test positive for Marquis test positive for

methamphetamine – could be methamphetamine – could be methamphetamine or other similarly methamphetamine or other similarly structured compound.structured compound.

MS test positive for ephedrine – could MS test positive for ephedrine – could be ephedrine or pseudoephedrine.be ephedrine or pseudoephedrine.

QUANTITATIVE QUANTITATIVE DETERMINATIONSDETERMINATIONS

Uncertainty is defined as “an Uncertainty is defined as “an estimate attached to a test result estimate attached to a test result which characterizes the range of which characterizes the range of values within which the true value values within which the true value is asserted to lie.” (ISO 3534-1: is asserted to lie.” (ISO 3534-1: 1993)1993)

Very precise calculations of Very precise calculations of measurement uncertainty measurement uncertainty is not always required. is not always required.

QUANTITATIVE QUANTITATIVE DETERMINATIONSDETERMINATIONS

Primary numerical values reported in Primary numerical values reported in the analysis of seized drugs arethe analysis of seized drugs are Weight and PurityWeight and Purity

Where a value is critical, an appropriate Where a value is critical, an appropriate measurement uncertainty determination measurement uncertainty determination shall be applied. Illustrations of shall be applied. Illustrations of “critical” include,“critical” include, where weight is close to a statutory where weight is close to a statutory

thresholdthreshold where purity of drug affects sentencing.where purity of drug affects sentencing.

UNCERTAINTY OF UNCERTAINTY OF WEIGHTWEIGHT DETERMINATIONSDETERMINATIONS

Uncertainty of a reported value is Uncertainty of a reported value is dependant on the weighing process. dependant on the weighing process. Factors include,Factors include, Single item versus multiple items (# of Single item versus multiple items (# of

weighing operations)weighing operations) Tare function as separate weighing operationTare function as separate weighing operation Extrapolation of population weight from Extrapolation of population weight from

limited sampling of multiple itemslimited sampling of multiple items Incomplete recovery of material from Incomplete recovery of material from

packagingpackaging Balance selection (e.g., readability, capacity)Balance selection (e.g., readability, capacity) Balance operation (e.g., sample placement, Balance operation (e.g., sample placement,

environmental conditions)environmental conditions)

UNCERTAINTY OF UNCERTAINTY OF PURITYPURITY DETERMINATIONSDETERMINATIONS

Sources of uncertainty for purity Sources of uncertainty for purity determination include,determination include, Sampling plan (e.g., handling of multiple Sampling plan (e.g., handling of multiple

items)items) Sample homogeneitySample homogeneity

Analytical methodAnalytical method Sample preparation (e.g., size, matrix effects, Sample preparation (e.g., size, matrix effects,

solubility)solubility) Analytical techniqueAnalytical technique Reference material (e.g., purity of standard)Reference material (e.g., purity of standard) Equipment and instrumentation performance Equipment and instrumentation performance

(e.g., glassware, pipetters, balances, (e.g., glassware, pipetters, balances, chromatographs)chromatographs)

Concentration of analyteConcentration of analyte Environmental conditionsEnvironmental conditions

GENERAL CONSIDERATIONS FOR GENERAL CONSIDERATIONS FOR ASSESSING UNCERTAINTY IN PURITY ASSESSING UNCERTAINTY IN PURITY

DETERMINATIONSDETERMINATIONS Analytical ErrorAnalytical Error

Address both systematic and random error Address both systematic and random error through method validation and quality through method validation and quality assurance.assurance.

Sampling ErrorSampling Error Pay particular attention to the sampling Pay particular attention to the sampling

process as it is often the largest process as it is often the largest contributor to measurement uncertainty contributor to measurement uncertainty of the test result.of the test result.

Where appropriate, confidence levels Where appropriate, confidence levels (e.g., 95%) shall be selected based on (e.g., 95%) shall be selected based on considerations relevant to the considerations relevant to the analytical context.analytical context.

Record uncertainty information in Record uncertainty information in validation documents or case records.validation documents or case records.

SPECIFIC APPROACHES: I. SPECIFIC APPROACHES: I. UNCERTAINTY BUDGETUNCERTAINTY BUDGET

All sources of error are separately All sources of error are separately identified and tabulated.identified and tabulated.

Assign values to each error source usingAssign values to each error source using Empirical dataEmpirical data

Validation process, Historical performance data, Validation process, Historical performance data, Control chart data, proficiency testsControl chart data, proficiency tests

Published dataPublished data Combination of empirical and published Combination of empirical and published

data.data. Can exclude insignificant sources.Can exclude insignificant sources. Calculate combined and expanded Calculate combined and expanded

uncertainty using significant values for uncertainty using significant values for procedure.procedure.

II. NON-BUDGET OR EMPERICAL II. NON-BUDGET OR EMPERICAL APPROACHAPPROACH

Example 1:Example 1: Use data from replicate Use data from replicate analyses from a validated method with an analyses from a validated method with an appropriate sampling plan.appropriate sampling plan. Sources of uncertainty that are separately Sources of uncertainty that are separately

assessed in the budget method are collectively assessed in the budget method are collectively assessed by experimental measurements.assessed by experimental measurements.

Example 2:Example 2: Use two standard deviations Use two standard deviations (2(2σσ) of test method results from ) of test method results from reproducibility data from validation reproducibility data from validation studies.studies. Provides an approximation of the Provides an approximation of the

measurement uncertainty for non-critical measurement uncertainty for non-critical values.values.

WHEN TO REPORT?WHEN TO REPORT? Reporting of measurement Reporting of measurement

uncertaintyuncertainty Uncertainty shall be Uncertainty shall be

documented but may not documented but may not need to be reported.need to be reported.

It should be reported when It should be reported when result impacts user.result impacts user.

Whether reported or not, Whether reported or not, analysts shall be cognizant analysts shall be cognizant of the uncertainty of the uncertainty associated with their associated with their results—Most important results—Most important point of all!point of all!

REPORTINGREPORTING Factors to consider when reporting Factors to consider when reporting

include:include: JurisdictionalJurisdictional

Prevailing statutory requirementPrevailing statutory requirement Relevant governing body (agency) requirementsRelevant governing body (agency) requirements User requestsUser requests Potential exculpatory valuePotential exculpatory value

AnalyticalAnalytical Qualitative results where limitations are known Qualitative results where limitations are known

(e.g., inability to differentiate isomers)(e.g., inability to differentiate isomers) Quantitative measurements where a value is Quantitative measurements where a value is

critical (e.g., weight or purity level close to critical (e.g., weight or purity level close to statutory threshold)statutory threshold)

Laboratory accreditation requirementsLaboratory accreditation requirements

REPORTING EXAMPLESREPORTING EXAMPLES Qualitative:Qualitative:

Contains Ephedrine or Pseudoephedrine. Contains Ephedrine or Pseudoephedrine. Item tested: 5.2 grams netItem tested: 5.2 grams net

Visual examination determined that the Visual examination determined that the physical characteristics are consistent with physical characteristics are consistent with a Schedule IV pharmaceutical preparation a Schedule IV pharmaceutical preparation containing Diazepam. There was no containing Diazepam. There was no apparent tampering of the dosage unit and apparent tampering of the dosage unit and no further tests are being conducted.no further tests are being conducted.

Contains cocaine (salt form not Contains cocaine (salt form not determined)determined)

REPORTING EXAMPLESREPORTING EXAMPLES Quantitative:Quantitative:

Positive for cocaine in the sample tested Positive for cocaine in the sample tested Net weight of total sample: 5.23 Net weight of total sample: 5.23 grams ± 0.03 grams grams ± 0.03 grams Quantitation: 54.7% ± 2.8% Quantitation: 54.7% ± 2.8%

Sample tested positive for cocaine Sample tested positive for cocaine Net weight: 5.23 grams Net weight: 5.23 grams Purity: 54.7% Purity: 54.7% Confidence Confidence Range: ± 2.8%* Range: ± 2.8%* Calculated net weight of drug: 2.8 grams of Calculated net weight of drug: 2.8 grams of cocaine *Confidence range refers to a cocaine *Confidence range refers to a 95% confidence level 95% confidence level

TRAININGTRAINING ““Individuals responsible for determining, Individuals responsible for determining,

evaluating and documenting uncertainty evaluating and documenting uncertainty shall be capable of demonstrating shall be capable of demonstrating familiarity with foundational concepts and familiarity with foundational concepts and principles of estimating uncertainty.principles of estimating uncertainty. General metrology (terminology, symbols, etc.)General metrology (terminology, symbols, etc.) Concepts of random and systematic error, Concepts of random and systematic error,

accuracy, precision, propagation of error, etc.accuracy, precision, propagation of error, etc. Reporting conventions (sig. figs, truncating, Reporting conventions (sig. figs, truncating,

rounding)rounding) Basis statistics (i.e., confidence interval, Basis statistics (i.e., confidence interval,

probability, etc)probability, etc)

Analysts shall be capable of explaining Analysts shall be capable of explaining their laboratory’s procedures for their laboratory’s procedures for evaluating uncertainty of qualitative and evaluating uncertainty of qualitative and quantitative analyses.”quantitative analyses.”

A helpful list of references is provided.A helpful list of references is provided.

SUPPLEMENTAL SUPPLEMENTAL DOCUMENTS TO FOLLOWDOCUMENTS TO FOLLOW Summing weights from individual Summing weights from individual

exhibitsexhibits

Expression of sampling uncertainty Expression of sampling uncertainty based on confidence interval using based on confidence interval using multiple samplingsmultiple samplings

Uncertainty budget exampleUncertainty budget example

May All Your Uncertainties May All Your Uncertainties Be Small OnesBe Small Ones

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