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GLP Training
Reference Standards
Wayne Jiang, PhD
IR-4, Michigan State University, jiangwa@msu.edu
Michael Braverman, PhD
IR-4 headquarters, Rutgers University
Contents
Sample Receipt
Sample Handling and Processing
Sample Storage
R f S d d d S l i Reference Standards and Solutions
Reference Method and Working Method
Method Validation and Sample Analysis
Storage Stability
Raw Data
Analytical Summary Report
Differences in GLP Definitions for Test,
Control and Reference Substances
FDA
Test & Control Articles
OECD
Test & Reference (Control) Substances ( )
Vehicle (Carrier)
MOHW
Test & Control Articles
MAFF
Test & Control Substances (no definitions)
METI
Test & Control Substances
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Standards
Test Substance
A substance or mixture administered or added to a test
system in a study, which substance or mixture: 1) Is the
subject of an application for a research or marketing
permit supported by the study, or is the contemplated
bj t f h li ti 2) I i di t subject of such an application; or 2) Is an ingredient,
impurity, degradation product, metabolite or radioactive
isotope of a substance described by paragraph (1) of
this definition, or some other substance related to a
substance described by that paragraph, which is used
in the study to assist in characterizing the toxicity,
metabolism, or other characteristics of a
substance described by that paragraph.
Control Substance
Any chemical substance or mixture, or any other
material other than a test substance, feed, or water,
that is administered to the test system in the course
of a study for the purpose of establishing a basis for
comparisonwith the test substance for known comparison with the test substance for known
chemical or biological measurements.
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Reference Substance
Any chemical substance or mixture, or analytical
standard, or material other than a test substance,
feed, or water, that is administered to or used in
analyzing the test system in the course of a study
for the purposes of establishing a basis for for the purposes of establishing a basis for
comparison with the test substance for known
chemical or biological measurements.
Reference Substance
Section 28 in an IR-4 protocol describes how to
obtain reference substance and the contact
information.
Reference Standards
Laboratory Research Director (LRD) or other
designated personnel contacts by email, fax, or
telephone the Chemical Company (registrant)
representative cited in the study protocol to receive
appropriate standards and documentation appropriate standards and documentation.
Analytical Reference Standards (ARSs) should be
shipped with Certificates of Analyses (COAs) which
must include lot number, purity, storage conditions,
characterization, and expiration date.
Certifications should be in compliance with GLP
Re-Certifications (same lot number).
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COA Example
Name, Lot #, storage,
purity, exp. date
Lab unique ID,
date received, initial
GLP
compliance
purity, exp. date
True copy
of COA
COA Example
Same
L t #
Original COA Re-Certification
Lot #
Extended
exp. date
Same lab
unique ID
exp. Date
(original)
Reference Standards
Analytical Reference
Standards ARS
(reference standards)
are logged into a
Primary Reference
Standard Book
All uses (weighings) of
ARS are recorded in
Part I.
A portion of ARS is
archived.
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Standard Form - Part 1
For pure standard only
Analytical Reference
St d d R d d U Standard Record and Use
Log Part 1.
Standard Form - Part 2
For standard solution
only
- Analytical Reference Standard - Analytical Reference Standard
Record and Use Log Part 2.
- The % purity of the reference
standard is taken into account
when the stock solution
concentration is calculated.
Form Examples
A similar form
from other IR-4
lab, showing the
purity of the
standard is used
to calculate the
concentration
when standard
solutions are
prepared.
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Standard Solution Labels
All containers of reagents
and solutions must be
labeled correctly including
chemical name,
concentration solvent (when concentration, solvent (when
used), preparation, and
expiration dates as well as
storage conditions.
Handwriting is also
acceptable as long as all
information is included and
they are legible.
Expired Standards
Expired Analytical Reference Standards
o Be Kept in a freezer (by default) or conditions
that COAs specify
Expired Standard Solutions
o Be discarded in a timely manner (by default); or
o May be kept in a location separated from working
solutions and clearly marked Expired.
o May be used for method development.
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Reagents & Solutions
For standard, reagents, and solvents:
Be Kept in original bottles (with exp. date)
For all solutions:
Add adequate labeling, including
Identity
Concentration
Solvent
Storagerequirements
Expiration date
Prepared by and prep date
Reagents & Solutions
Questions ?
Any questions?
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Non-GLP
Standards Standards
- NOT to be
used in GLP
studies
Non-GLP Standards
Three types of reference standards are usually used:
(1) Certified reference standards (e.g., USP
compendial standards, ISO, but Non-GLP);
(2) Commercially supplied reference standards without (2) Commercially supplied reference standards without
proper certificates, obtained from a reputable
commercial source;
(3) Other materials of documented purity custom-
synthesized by an analytical laboratory or other
noncommercial establishment
Thank
Y ! You!
jiangwa@msu.edu