ASTM D8282-19

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: D8282 − 19
Standard Practice for
Laboratory Test Method Validation and Method
Development
This standard is issued under the fixed designation D8282; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.7 This international standard was developed in accor-
dance with internationally recognized principles on standard-
1.1 The quality, efficacy, and safety of cannabis and prod-
ization established in the Decision on Principles for the
ucts containing cannabis extracts shall be evaluated by vali-
Development of International Standards, Guides and Recom-
dated testing methodologies used by trained staffed utilizing
mendations issued by the World Trade Organization Technical
qualified instruments and/or materials.
Barriers to Trade (TBT) Committee.
1.2 This practice provides the cannabis industry with guid-
anceforthedevelopmentandvalidationoftestingmethodsthat
2. Referenced Documents
adequately evaluate cannabis and products containing cannabis
2.1 ASTM Standards:
extracts for quality, efficacy, and consumer health safety in the
E2857 Guide for Validating Analytical Methods
absenceofvalidatedmethodsfromagencies.Thisincludes,but
2.2 Other Documents:
is not limited to, the potency of active substances and
United States 40 CFR Appendix B to Part 136 Definition
adulteration, including impurities stemming from potential
and Procedure for the Determination of the Method
adulteration during agricultural or manufacturing processes or
Detection Limit
both (for example, pesticides, residual solvents, and the pres-
USP 1224 Transfer of Analytical Procedures
ence of fungus and microorganisms) before product approval
USP 1225 Validation of Compendial Procedures
and release for use. Depending on the methodology and
ICH Q2(R1) –Validation ofAnalytical Procedures:Text and
precision and accuracy required, these methods may be both
Methodology
qualitative or quantitative.
1.3 This practice shall define the procedures for test method 3. Terminology
characterization (TMC), test method validation (TMV), and
3.1 Definitions:
test method transfer/transfer of analytical procedures (TMT/
3.1.1 acceptance criteria, AC, n—specification(s) that shall
TAP) of biological, chemical spectroscopic, and physical-
be met by a test sample or matrix specific method to be
based laboratory test methods.
considered suitable or validated for use, respectively.
1.4 Depending on the nature of the test in question
3.1.1.1 Discussion—State-specific criteria shall be met as
(chemical, microbiological, etc.) different variables will need
applicable.
to be considered for validation.The particular variables subject
3.1.2 accuracy, n—the closeness of agreement between a
to consideration are beyond the scope of this document. Refer
test result and an accepted reference value.
to Guide E2857 for more guidance.
3.1.2.1 Discussion—The term accuracy, when applied to a
1.5 This standard does not consider the specifics of accept-
set of test results, involves a combination of a random
able test method limits and users should consult relevant
component and of a common systematic error or bias compo-
standardliteraturetodeterminetheappropriatetestparameters.
nent.
1.6 This standard does not purport to address all of the
3.1.3 addendum, n—document written to make minor up-
safety concerns, if any, associated with its use. It is the
dates to an existing completed protocol or report.
responsibility of the user of this standard to establish appro-
priate safety, health, and environmental practices and deter-
mine the applicability of regulatory limitations prior to use. 2
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
Standards volume information, refer to the standard’s Document Summary page on
This practice is under the jurisdiction of ASTM Committee D37 on Cannabis the ASTM website.
and is the direct responsibility of Subcommittee D37.03 on Laboratory. Available from U.S. Government Printing Office, Superintendent of
Current edition approved Sept. 1, 2019. Published October 2019. DOI: 10.1520/ Documents, 732 N. Capitol St., NW, Washington, DC 20401-0001, http://
D8282-19. www.access.gpo.gov.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
D8282 − 19
3.1.3.1 Discussion—They may be used when a change in equipment, materials, personnel, location, and what constitutes
scope of a validation does not occur. acceptable validation results.
3.1.4 analytical method type, n—categorical classification
3.1.18 repeatability, n—precision under repeatability condi-
of a test method that provides general guidance on the
tions.
analytical performance characteristics to be characterized for
3.1.19 reporting limit, RL, n—depending on the regulatory
that test method type.
body, this limit applies to impurity tests and shall be at or
3.1.5 analytical performance characteristics, APC, n—test
higher than the limit of quantification (LOQ).
methodcharacteristicsthatmakethetestmethodsuitableforits
3.1.20 reproducibility, n—a quantitative expression of the
intended use.
randomvariabilityassociatedwithsuccessivemeasurementsof
3.1.6 application, n—applicationisthescopetowhichatest
the same measurand carried out by operators working in
method is applied.
different laboratories, each obtaining single results on identical
3.1.6.1 Discussion—A test method may have multiple ap- test material when applying the same method.
plications.
3.1.20.1 Discussion—Repeatability deals with results in a
3.1.7 common test method, CTM, n—group of test method
single laboratory while reproducibility deals with results ob-
applications that share common risk factors, analytical perfor-
tained in different laboratories.
mance characteristics, and elements that could impact the
3.1.21 robustness, n—a measure of the change of the
suitability of the test method for the intended uses of the group
required parameter with deliberate and systematic variations in
of applications.
any or all of the key parameters that influence it.
3.1.8 concentration, n—quantity of a substance contained in
a total unit quantity of sample. 3.1.21.1 Discussion—A useful discussion of robustness ex-
periment considerations is found in the ICH Validation of
3.1.9 end-user laboratory, EUL, n—third-party laboratory
Analytical Procedures Q2(R1) Guideline (1).
in which the test method is performed for the intended use and
3.1.22 selectivity, n—the ability of a measurement proce-
applications for which it has been validated.
dure to determine accurately and specifically the analyte of
3.1.10 extension, n—new application of the intended use of
interest in the presence of other components in the sample
a validated test method.
matrix under the stated conditions of the test.
3.1.10.1 Discussion—An extension shall be evaluated per
3.1.23 specificity, n—the ability to assess unequivocally the
change control and, if deemed appropriate, re-characterized
analyte in the presence of components which may be expected
and revalidated before official use.
to be present. Typically these might include impurities,
3.1.11 limit of quantitation, LOQ, n—concentration of ana-
degradants, matrix, etc.
lyte in a specific matrix for which the probability of producing
3.1.24 standardoperatingprocedure,SOP,n—definedsetof
analytical values above the method detection limit is 99 % or
instructions for performing an activity that ensures a specific
greater.
outcome within established acceptance criteria such as a test
3.1.12 linearity, n—the ability (within a given range) of an
method or protocol.
assay to provide results that are directly proportional to the
3.1.25 subject matter expert, SME, n—personhighlyknowl-
concentration (amount) of the analyte in the test sample.
edgeable on the subject through education or experience or
3.1.13 matrix, n—specific type of medium (for example,
both.
flower, oil, and hard candy) in which the analyte(s) of interest
3.1.26 supplements, n—documents written to update,
may be contained
correct, or augment the scope of an existing completed
3.1.14 method detection limit, n—minimum concentration
protocol or report.
ofananalytethat,inagivenmatrixandwithaspecificmethod,
has a 99 % probability of being identified, qualitatively or
3.1.26.1 Discussion—Also referred to as an addendum.
quantitatively measured, and reported to be greater than zero.
3.1.27 system suitability, n—checking of a system before or
during analysis of unknowns to ensure system performance.
3.1.14.1 Discussion—Also referred to as the limit of detec-
tion (LOD).
3.1.28 test method, TM, n—approved method that describes
3.1.15 method development team, n—team that consists of
how to perform an analysis.
subject matter experts (SMEs) from one or more functional
3.1.29 test method characterization, TMC, n—comprises
areas working on a project based on their expertise.
the studies performed that consider the intended use(s) of the
test method, the test method type, and the analytical perfor-
3.1.15.1 Discussion—A project team may also be called a
mance characteristics to be characterized to establish an
cross-functional team.
understanding of conditions that can affect the suitability of the
3.1.16 precision, n—closeness of agreement between test
test method for its intended use(s).
results obtained under prescribed conditions.
3.1.17 protocol, n—formally agreed upon and controlled 3.1.30 test method transfer, TMT, n—transfer of a validated
document that states in detail how a validation will be test method from one functional area (originating) to another
conducted, including test parameters, product characteristics, functional area (receiving).
D8282 − 19
3.1.31 test method validation, TMV, n—challenge of an 5.1.6 Place the test method into the appropriate test method
analytical method that was written based on the TMC. type category based on Table X2.2.
5.1.7 Determine if the TMC approach will be full charac-
3.1.32 test result, n—value of a characteristic obtained by
terization (validation) or a suitability for use characterization
carrying out a specific test method.
(verification) based on Table X2.3.
3.1.33 test sample, n—specific quantity that is characteristic
5.1.8 Identify anticipated APCs (Table X2.4) to be charac-
of a larger piece of material that could include a portion of a
terized. Although not all the validation characteristics are
manufactured product, botanical plant batch.
applicable for all types of tests (Table X2.5), typical validation
3.1.34 validation, n—confirmation by examination and pro-
characteristics include:
visionofobjectiveevidencethattheparticularrequirementsfor
5.1.8.1 Selectivity,
a specific intended use can be consistently fulfilled.
5.1.8.2 Specificity,
3.1.35 validity criteria, VC, n—validity criteria of a test
5.1.8.3 Linearity,
method is the system suitability criteria in a test sample.
5.1.8.4 Accuracy,
3.1.36 verification, n—confirmation by examination and 5.1.8.5 Precision (repeatability, intermediate precision, and
reproducibility),
provision of objective evidence that specified requirements
have been fulfilled.
5.1.8.6 Range,
5.1.8.7 Limit of Quantitation, and
4. Significance and Use
5.1.8.8 Method Detection Limit.
5.1.9 Identify the variance components (also called factors)
4.1 The demonstration that a method of analysis is fit for its
that negatively impact the test method APCs during the TMC
intended purpose and application is done through method
studies with the intent to understand how to control these
characterization and validation.
factors.
4.2 Resulting SOPs should be reproducible under the same
5.1.10 SeeTableX2.6forqualitytoolsthatmaybeusefulto
conditions by a different analyst working in a different labo-
help identify these factors. See Table X2.7 for factors that may
ratory.
negatively impact the capability of the test method if not
4.3 Test methods are designed to assess one or more of the appropriately understood through characterization studies and
following product attributes: identity, strength or
controlled in the execution of the test method.
concentration, quality, and purity.
5.1.11 Design and perform the TMC studies to evaluate the
test method APCs. Examples of TMC studies are:
4.4 The steps of this practice contain the basic procedures
5.1.11.1 Evaluation of historical data,
for performing aTMC, aTMV, and aTMT. It is not imperative
5.1.11.2 Designed studies to determine the APC limits for
that each procedural step be followed in the designated order,
system suitability in the test method SOP, and
but the ordered sequence is a logical progression of the steps
5.1.11.3 Designed studies to determine variance compo-
for performing a TMC, a TMV, and a TMT.
nents that impact the test method APCs.
5. Procedure 5.1.11.4 Labs that are in restrictive jurisdictions may not be
able to partake in proficiency testing programs and should seek
5.1 Test Method Characterization:
alternative approaches. Lack of proficiency testing should not
5.1.1 A method development team should be established to
restrict labs from maintaining a validated method.
identify scope, purpose, and intended use for a test method.
5.1.12 Evaluate the TMC Study Results—Determine which
5.1.2 The test method intended for use is determined by the
of the evaluated APCs (a subset or all of them) will be
matrix (or matrix class), analyte(s) or characteristic(s) of
incorporated into the final test method SOP as validity criteria
interest, and established acceptance criteria for that particular
(VC) (also known as system suitability).
analyte/characteristic. In the absence of established acceptance
5.1.13 Document the TMC Studies—The documentation
criteria, acceptance criteria shall be developed by taking into
shall include a purpose and rational for each study design.
consideration health safety and environmental impacts and the
TMCstudiescanbedocumentedinalaboratorynotebookorin
current limits of scientific testing.
a preapproved protocol.
5.1.3 It is possible to characterize the multiple test method
5.1.14 Prepare a draft test method SOP that meets internal
applications as a common test method (CTM) in a single
procedure requirements.
designed study that can addressAPCs in a way that will apply
5.1.15 Prepare the TMC final report. See Table X2.8 for
across the whole set of applications verses a unique character-
specific content to capture in a TMC report. Ensure that all
ization for each application individually.
TMC data and the draft TM SOP are available as attachments
5.1.4 If analytes are present in multiple matrices, then the
to the TMC report.
method shall be validated for each specific matrix.
5.1.5 In Table X2.1 assessment criteria are listed to deter- 5.2 Test Method Validation Process—Upon completion of
mine if multiple test method applications of a test method method development in 5.1, method validation may be com-
intended use may be categorized as a CTM and, therefore, pleted via an interlaboratory approach or, in the absence of
bundled together for characterization or validation efficiencies multiple laboratories, a single-laboratory approach. The fol-
or both. lowing steps may be flexibly applied to both approaches.
D8282 − 19
5.2.1 Identify the end-user laboratories (EULs) and person- 5.4 Test Method Transfer/Verification:
nel who will execute the validation runs. 5.4.1 The receiving area/site reviews the TMC/TMV report
5.2.2 Determine if the draft test method SOP is acceptable from the originating area with subject matter experts (SMEs)
or edits are required for it to be executable in the EUL.Anew who are familiar with the test method to confirm that the
draft test method SOPis acceptable as long as the intended use intended use in the original TMC/TMV is the same as the
and all associated applications are not impacted by these intended use at the receiving area/site.
changes and is supported by the TMC data.
5.4.2 If the intended use is not the same, the original
5.2.3 PrepareTMVprotocol.Theprotocolshallhaveclearly
TMC/TMV may be used as supporting characterization data.
defined validation acceptance criteria (AC) against which the The test method shall be characterized and validated per site
success or failure of the TMV will be evaluated. TheseAC are
procedure.
typically provided by regulatory bodies or pharmacopeia
5.4.3 If the intended use is the same, the receiving labora-
monographs. It is recommended that a minimum of threeTMV
tory reviews the TMC/TMV report from the originating area
runs be performed in the EUL. More or less runs may be
with SMEs familiar with the testing conditions. This is done to
acceptable, but the number chosen shall be justified.
determine if conditions in the receiving area/site could have
5.2.4 In the absence of regulatory body guidance, accep- any impact on the transferred method. These include differ-
tance criteria shall be clearly defined and justified in the TMV
ences in:
Report.
5.4.3.1 Operator training,
5.2.5 It is expected that all test method validity criteria will
5.4.3.2 Procedures,
be met.
5.4.3.3 Equipment,
5.2.6 The protocol also shall contain the draft test method
5.4.3.4 Facilities,
SOP that will be used (or referenced) to execute the TMV and
5.4.3.5 Utilities, and
any other documentation necessary to perform the TMV.
5.4.3.6 Environment.
5.2.7 See Table X2.9 for specific content to capture in a
5.4.4 If the testing conditions are not the same, the original
TMV protocol.
TMC/TMV may be used as supporting characterization data.
5.2.8 Ensure EUL personnel are trained on the draft TM
The test method shall be characterized and validated per site
SOP. Document the training.
procedure.
5.2.9 Review the TMV protocol with the EUL personnel.
5.4.5 If the testing conditions are the same (that is, any
Document the review.
differences will not impact the suitability of the test method for
5.2.10 EULpersonnel perform the TMV in the EULper the
its intended use), the receiving area/site can adopt the existing
preapproved TMV protocol.
validated test method.
5.4.6 Minimally, the receiving area/site performs and docu-
5.3 Test Method Validation Review:
ments suitability for use characterization (verification) per a
5.3.1 ASTM International may be used to conduct an
preapproved TMT protocol. Documentation shall include a
interlaboratory study (ILS) to challenge method performance.
purpose and rational for each study design.
The purpose of the interlaboratory study is to measure how
5.4.7 The receiving area/site completes a TMT protocol/
well the proposed method operates at different laboratories/
report that includes runs and data analysis that demonstrate the
locations. The data collected provide guidance to users of the
test method has been successfully transferred and the test
method on how well different instrument setups or users or
methodissuitableatthereceivingarea/siteforitsintendeduse.
both function on various materials.
This involves running the test method SOP three times in the
5.3.2 Review the data and results for conformance to the
EUL. More or less runs may be appropriate, but justification
preapproved TMV protocol and the draft SOPtest method. If a
shall be provided. If the runs are successful, the test method is
test method nonconformance occurred, an investigation is
considered validated for the receiving area/site. The test
performed to determine the cause(s).An assessment is made if
method SOP may be updated to add the new site.
the impacted portion of the TMV run(s) can be re-executed. If
so, justification is provided and the impacted portion of the
5.5 Cancellation—During the course of TMC, TMV, or
protocol is rerun. If not, a new a preapproved TMV protocol
TMT, it may become necessary to cancel an approved protocol
shall be generated to rerun the impacted portion of the TMV.
or report or both. The reason and justification for cancellation
Alternatively, if
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