Kk Test item characterization

TEST ITEM CHARACTERIZATION IN
REGULATORY TOXICOLOGY
STUDIES
(ACCORDING TO OECD - GLP
ADVISORY GUIDELINES
DOCUMENT NO.19)
PREPARED BY
KESHARI KUMAR SRIWASTAWA
M.PHARM (PHARMACOLOGY),1ST YEAR

OBJECTIVE OF THE GUIDELINES
• This guidance provides clarity for test facilities on
the expectations of national Good Laboratory
Practice (GLP) compliance monitoring authorities on
how test items are transported, received, identified,
labelled, sampled, handled, stored, characterised,
archived and disposed.
• The document consolidates existing OECD guidance
on test items that are used in studies conducted in
compliance with the Principles of GLP.
• It also aims to promote a consistent approach that is
appropriate to the objective of the study and the
nature of the test item.

• This document is designed to provide guidance on
– The transportation, receipt, identification, labelling, sampling,
handling, storage, characterisation, archiving and disposal of
all test items used in GLP studies.
– The expectations on the characterisation of different types of
test items that are used in the conduct of a broad range of non-
clinical studies carried out in compliance with the Principles of
GLP.
– Test items could be from different origins such as chemical,
biological, synthetic, natural, living organisms, transgenic
organisms, items from complex industrial or biological
processes, complex mixtures or part of them. The final use of
test items includes but is not limited to agrochemicals,
industrial chemicals, pharmaceuticals (human and veterinary),
cosmetics products, food/feed additives and medical devices.

• The amount of information required for transportation, receipt,
identification, labelling, sampling, handling, storage,
characterisation, archiving and disposal can vary from study-to-
study.
• This is due to the wide variety of test items, the objectives of the
study and the development stage of the test item.
• Because of the diverse nature of test items there is an expectation
that Test Facility Management will undertake appropriate and
proportionate risk-based assessments of the management,
characterisation and use of each test item throughout their use on
GLP studies.
• This should enable the test facility personnel to maintain a
controlled approach in assessing whether information they have
available on the test item is sufficient.
• Adoption of a risk-based approach to decision making should also
serve to ensure that the test item is what it purports to be and is
suitable to fulfil the objectives of the study.

Test Item Test item is defined as an article that is the subject of a
study. The conclusion of a GLP study provides
information on the properties of the test item which allows an
assessment of the risk it presents to the safety of humans,
animals or the environment. It should be noted that test item is
also referred to as "test chemical" in some of the OECD Test
Guidelines.
Batch Batch (or lot) is defined as a specific quantity of a test
item produced during a defined cycle of manufacture in such a
way that it could be expected to be of a uniform and
homogeneous character and should be designated as such.
Vehicle Vehicle is defined as any agent that serves as a carrier and is
used to mix, disperse, suspend or solubilise the test item to
facilitate the administration and/or application to the test
system.
Formulation A formulation (or mixture) is a combination of a test item and
different ingredients such as excipients that are combined and
administered and/or applied to the test system in a different
form, e.g. tablet, capsule, solution.
BASIC TERMINOLOGIES

Test system Test system means any biological,
chemical or physical system or a
combination thereof used in a study
Expiry Date Expiry Date (or Expiration Date) is
the designated date a test item is
expected to remain within established
shelf life specifications if stored under
defined conditions and after which it
should not be used.
Retest Date Retest Date is the date a test item
should be re-examined to ensure that
it is still suitable for use.
Characterisation Determines attributes of the test item
and provides the evidence to support
its suitability for use in GLP studies.

PREPARATION OF THE TEST ITEM
• Preparation of test item (or prepared test item) could be a
formulation (or mixture) containing the test item or the test item
in a vehicle, where the combination is obtained by dilution,
mixing, dispersion, suspension, solubilisation and/or another
process with the intention to be administered to the test system.
• The test facility can be supplied with the 2 Unclassified test item
or with preparation(s) of the test item to be processed again or
preparation(s) of the test item ready to be applied or
administrated to the test system (also called “ready-to-use”).
• A test item which is encapsulated or packed in some other way,
in the absence of excipients or a vehicle, for the purposes of
delivery to the test system is not regarded as a prepared test item
as per these guidelines

• General information
 The Principles of GLP require information on identity, such as name, code, CAS
number, biological parameters, batch number, purity, composition, concentrations,
and, in case of several batches of test item, characteristics to appropriately define
each batch. Stability of the test item under storage and test conditions should also
be available.
 No or inadequate information on the characterisation of the test item constitutes a
deviation from the Principles of GLP. The impact the deviation has on the validity of
the study data and the extent of compliance with the Principles of GLP should be
described by the Study Director in the GLP compliance statement of the final study
report.
 Consideration should always be given to whether information on the characteristics
of the test item is needed in order to design the study and issue the study plan.
 There is an expectation that test item administration or application only occurs
when sufficient information is available that confirms the identity of the test item.
 The characterisation of the test item, including stability, should always be
completed by the end of the study so that information can be detailed in the final
study report.
 Where multiple batches of test item are used during a GLP study, characterisation
information should be available for each batch of the test item used.
CHARACTERISATION OF THE TEST ITEM

SOURCES OF CHARACTERIZATION DATA
 The characterisation of the test item may be carried
out by the sponsor, a supplier or the test facility.
 If characterisation is performed by the sponsor or a
supplier, Test Facility Management should ensure
that documented procedures are in place to verify
the integrity and quality of the information provided.
 In every case, the final study report should describe
who is responsible for test item characterisation and
who performed it.
 The report may also provide other relevant
information such as the quality system under which
the characterisation was performed.

DATA ON STABILITY DATA ON IDENTITY
The test facility should be provided
with information on the stability of
the test item under storage and test
conditions, or the test facility should
determine such information. The
stability of the test item can only be
assured if the material is handled and
stored appropriately, and is used
before expiration.
The Principles of GLP require that
for each study, the identity, including
batch number, purity, composition,
concentrations, or other
characteristics necessary to
appropriately define each batch of
the test item, should be known.
The available data (e.g. retest
or expiry date or any other
indicator of stability) should
be reported in as detailed a
fashion as possible in the
final study report.
The test facility may be supplied with a
certificate of analysis, which usually
provides basic information on the
physical characteristics of the test item.
In the absence of a certificate of analysis,
information needed to confirm the
identity and properties of the test item
may be supplied in alternative formats
such as a laboratory report, safety data
sheet, memorandum, letter or email from
the sponsor.

CHARACTERIZATION OF SPECIFIC
TEST SUBSTANCES
1. Test items in the early stage of development
2. Biochemicals
3. Living Organisms
4. Transgenic organisms
5. Medical devices
6. Test items with complex composition
7. Radiolabeled test items

1.TEST ITEMS IN THE EARLY STAGE OF
DEVELOPMENT
• The extent to which a test item will be
characterised may be commensurate with the
stage of product development.
• In the earlier stages of test item development
there may be less characterisation
information available.
• However, the Study Director should always
be able to demonstrate that the test item used
in the study is what is required in the study
plan.

2. BIOCHEMICALS
• If the test item is a biochemical, for example an
antibody, a peptide, a protein, a viral vector or an
enzyme, the need for information to verify biological
activity should always be considered, including the
determination method and its quantification
(potency) as part of the characterisation process.
• If no information is provided to demonstrate the
biological activity of the test item, the reasons why
the test item is still considered suitable for use in the
study should be clearly outlined in the study plan
and in the final study report.

3. LIVING ORGANISMS
• If the test item is a living organism, for example a cell, a virus or
a microorganism, the characterisation may require specific
information on properties which are unique to the test item. For
example, if the test item is a cell line, it may be appropriate to
confirm passage number.
• Other biological properties that may have to be taken into
consideration because they have an impact on the viability of
the test item may include viability rate, proliferation rate,
culture conditions or infectious titer determination.
• Information required to characterise living organisms should
be considered on a case-by-case basis and the rationale for
performing the tests described in the study plan.

4. TRANSGENIC ORGANISMS
• A test item may be a transgenic
organism . If a unique identifier is
available this can be included.
• If information is available on seed
certification this can be used and may
include:
– The name of the host species,
– A description of the inserted genetic material,
– The trait and the name of the developer.

5. MEDICAL DEVICES
• For studies on medical devices, characterisation data can include the
description of the device, the lot number, the types of materials of
which the device is made (and method of manufacture and name of
the manufacturer of any polymers, colorants, metals), the methods of
manufacture and synthesis of the final device (e.g. injection molding)
and the location of manufacturing facilities.
• Illustrations or photos could be the best way to show the entire
configuration of the medical device.
• The date of manufacture, stability, and storage conditions should be
known and documented. Where applicable, information on the
sterilisation status of the device used as a test item should be
provided by the supplier.
• If the test item is only a component part or a representative sample of
a medical device, information of the full medical device should be
available when possible.

6. TEST ITEMS WITH COMPLEX
COMPOSITION
• Substances of unknown or variable composition, or
biological materials (UVCBs), complex reaction
products or products from animal or vegetable or
natural origin cannot be sufficiently identified by
their chemical composition because the number of
their constituents is relatively large and/or the
composition is, to a significant part, unknown and/or
the variability of composition is relatively large or
poorly predictable.
• In such cases, the composition could then be
defined by the manufacturing process and/or by the
origin description.

7. RADIOLABELLED TEST ITEMS
• Radiolabeled test items are generally unstable;
however, their exact stability characteristics are not
normally known so it is not possible to provide a
retest or expiry date or any other stability indicator
for them.
• Therefore, their radiopurity should be checked at the
start of the study and be reported.
• Characterisation data should also include the
amount of radioactivity per unit mass or volume –
i.e. specific activity and/or specific concentration.

Kk Test item characterization

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