OVERVEIW OF ICH Q3,Q4,Q5 AND Q6 GUIDELINES Q3A-

Q3E IMPURITIES:
Q3A (R2) Impurities in new drug substances
➢ This document is intended to provide guidance for registration
applications on the content and qualification of impurities in new drug
substances produced by chemical syntheses and not previously
registered in a region or member state.

➢ It is not intended to apply to new drug substances used during the

clinical research stage of development. The following types of drug
substances are not covered in this guideline: biological/biotechnological
peptide, oligonucleotide, radiopharmaceutical, fermentation product
and semisynthetic products derived there from, herbal products, and
crude products of animal or plant origin.

➢ Impurities in new drug substances are addressed from two perspectives:

Chemistry aspects include classification and identification of impurities,
report generation, listing of impurities in specifications, and a brief
discussion of analytical procedures; and Safety aspects include specific
guidance for qualifying those impurities that were not present, or were
present at substantially lower levels, in batches of a new drug substance
used in safety and clinical studies

Classification of impurities Impurities can be classified into the following

categories:

• Organic impurities (process- and drug-related)

• Inorganic impurities
• Residual solvents Organic impurities can arise during the manufacturing process
and/or storage of the new drug substance. They can be identified or
unidentified, volatile or non-volatile, and include:

• Starting materials

• Intermediates

• Degradation products

• Reagents, ligands and catalysts Inorganic impurities can result from the
manufacturing process.

They are normally known and identified and include:

• Reagents, ligands and catalysts

• Heavy metals or other residual metals

• Inorganic salts

• Other materials (e.g., filter aids, charcoal)

Solvents are inorganic or organic liquids used as vehicles for the preparation of
solutions or suspensions in the synthesis of a new drug substance. Since these are
generally of known toxicity, the selection of appropriate controls is easily
accomplished (see ICH Guideline Q3C on Residual Solvents). Excluded from this
document are:

(1) extraneous contaminants that should not occur in new drug substances and
are more appropriately addressed as Good Manufacturing Practice (GMP)
issues,
(2) polymorphic forms, and

(3) enantiomeric impurities.

➢ Reporting impurity content of batches Analytical results should be provided

in the application for all batches of the new drug substance used for
 clinical, safety, and stability testing, as well as for batches representative of
the proposed commercial process.

➢ Quantitative results should be presented numerically, and not in general

terms such as “complies”, “meets limit” etc. Any impurity at a level greater
than (>) the reporting threshold (see Attachment 1) and total impurities
observed in these batches of the new drug substance should be reported
with the analytical procedures indicated. Below 1.0%, the results should be
reported to two decimal places (e.g., 0.06%, 0.13%); at and above 1.0%, the
results should be reported to one decimal place (e.g., 1.3%). Results should

be rounded using conventional rules (see Attachment 2). Tabulation (e.g.,

spreadsheet) of the data is recommended.

➢ Impurities should be designated by code number or by an appropriate

descriptor, e.g., retention time. If a higher reporting threshold is proposed,
it should be fully justified. All impurities at a level greater than (>) the
reporting threshold should be summed and reported as total impurities.

➢ When analytical procedures change during development, reported results

should be linked to the procedure used, with appropriate validation
information provided. Representative chromatograms should be provided.
Chromatograms of representative batches from analytical validation studies
showing separation and detect ability of impurities (e.g., on spiked
samples), along with any other impurity tests routinely performed, can
serve as the representative impurity profiles.

➢ The applicant should ensure that complete impurity profiles (e.g.,

chromatograms) of individual batches are available, if requested.
Tabulation should be provided that links the specific new drug substance
batch to each safety study and each clinical study in which the new drug
substance has been used.

For each batch of the new drug substance, the report should include: • Batch
identity and size
• Date of manufacture

• Site of manufacture

• Manufacturing process

• Impurity content, individual and total

• Use of batches

• Reference to analytical procedure used

Listing of impurities in specification In summary, the new drug substance

specification should include, where applicable, the following list of impurities:

• Organic impurities

• Each specified identified impurity

• Each specified unidentified impurity

• Any unspecified impurity with an acceptance criterion of not more than () the
identification threshold

• Total impurities.

Q3B (R2) Impurities in new drug products

➢ This document provides guidance for registration applications on the
content and qualification of impurities in new drug products produced from
chemically synthesized new drug substances not previously registered in a
region or member state.

➢ This guideline addresses only those impurities in new drug products

classified as degradation products of the drug substance or reaction
products of the drug substance with an excipient and/or immediate
container closure system (collectively referred to as “degradation products”
in this guideline).
 ➢ Generally, impurities present in the new drug substance need not be
monitored or specified in the new drug product unless they are also
degradation products. Impurities arising from excipients present in the new
drug product or extracted or leached from the container closure system are
not covered by this guideline. This guideline also does not apply to new
drug products used during the clinical research stages of development.

➢ The following types of products are not covered in this guideline:

biological/biotechnological products, peptide, oligonucleotides,
radiopharmaceuticals, fermentation products and semi-synthetic products
derived there from, herbal products, and crude products of animal or plant
origin. Also excluded from this document are:

(1) extraneous contaminants that should not occur in new drug products and are
more appropriately addressed as good manufacturing practice (GMP) issues

(2) polymorphic forms, and

(3) enantiomeric impurities.

➢ The applicant should summarize the degradation products observed during

manufacture and/or stability studies of the new drug product. This
summary should be based on sound scientific appraisal of potential
degradation pathways in the new drug product and impurities arising from
the interaction with excipients and/or the immediate container closure
system. In addition, the applicant should summarize any laboratory studies
conducted to detect degradation products in the new drug product.

➢ This summary should also include test results of batches manufactured

during the development process and batches representative of the
proposed commercial process. A rationale should be provided for exclusion
of those impurities that are not degradation products (e.g., process
impurities from the drug substance and impurities arising from excipients).
 ➢ The impurity profiles of the batches representative of the proposed
commercial process should be compared with the profiles of batches used
in development and any differences discussed. Any degradation product
observed in stability studies conducted at the recommended storage
condition should be identified when present at a level greater than (>) the
identification thresholds given.

➢ When identification of a degradation product is not feasible, a summary of

the laboratory studies demonstrating the unsuccessful efforts to identify it
should be included in the registration application. Degradation products
present at a level of not more than () the identification threshold generally
would not need to be identified. However, analytical procedures should be
developed for those degradation products that are suspected to be
unusually potent, producing toxic or significant pharmacological effects at
levels not more than () the identification threshold.

➢ In unusual circumstances, technical factors (e.g., manufacturing capability,

a low drug substance to excipient ratio, or the use of excipients that are
crude products of animal or plant origin) can be considered as part of the
justification for selection of alternative thresholds based upon

manufacturing experience with the proposed commercial process.

For each batch of the new drug product described in the registration application,
the documentation should include:

• Batch identity, strength, and size

• Date of manufacture

• Site of manufacture

• Manufacturing process

• Immediate container closure

• Degradation product content, individual and total

• Use of batch (e.g., clinical studies, stability studies)
Reference to analytical procedure used

• Batch number of the drug substance used in the new drug product

• Storage conditions for stability studies

In summary, the new drug product specification should include, where applicable,
the following list of degradation products:

• Each specified identified degradation product

• Each specified unidentified degradation product

• Any unspecified degradation product with an acceptance criterion of not more

than () the identification threshold

• Total degradation products

Q3C (R5) Residual solvents

➢ The objective of this guideline is to recommend acceptable amounts for
residual solvents in pharmaceuticals for the safety of the patient.

➢ The guideline recommends use of less toxic solvents and describes levels
considered to be toxicologically acceptable for some residual solvents.
➢ Residual solvents in pharmaceuticals are defined here as organic volatile
chemicals that are used or produced in the manufacture of drug substances
or excipients, or in the preparation of drug products.
➢ The solvents are not completely removed by practical manufacturing
techniques. Appropriate selection of the solvent for the synthesis of drug
substance may enhance the yield, or determine characteristics such as
crystal form, purity, and solubility.

➢ Therefore, the solvent may sometimes be a critical parameter in the

synthetic process. This guideline does not address solvents deliberately
 used as excipients nor does it address solvates. However, the content of
solvents in such products should be evaluated and justified. Since there is
no therapeutic benefit from residual solvents, all residual solvents should
be removed to the extent possible to meet product specifications, good
manufacturing practices, or other quality- based requirements. Drug
products should contain no higher levels of residual solvents than can be
supported by safety data.

➢ Some solvents that are known to cause unacceptable toxicities (Class 1)

should be avoided in the production of drug substances, excipients, or drug
products unless their use can be strongly justified in a risk-benefit
assessment. Some solvents associated with less severe toxicity (Class 2)
should be limited in order to protect patients from potential adverse
effects. Ideally, less toxic solvents (Class 3) should be used where practical.

➢ The lists are not exhaustive and other solvents can be used and later added
to the lists. Recommended limits of Class 1 and 2 solvents or classification
of solvents may change as new safety data becomes available. Supporting
safety data in a marketing application for a new drug product containing a
new solvent may be based on concepts in this guideline or the concept of
qualification of impurities as expressed in the guideline for drug substance
(Q3A, Impurities in New Drug Substances) or drug product (Q3B, Impurities
in New Drug Products), or all three guidelines
➢ Therefore, testing should be performed for residual solvents when
production or purification processes are known to result in the presence of
such solvents. It is only necessary to test for solvents that are used or
produced in the manufacture or purification of drug substances, excipients,
or drug product.
➢ Although manufacturers may choose to test the drug product, a cumulative
method may be used to calculate the residual solvent levels in the drug
product from the levels in the ingredients used to produce the drug
product. If the calculation results in a level equal to or below that
recommended in this guideline, no testing of the drug product for residual
solvents need be considered.
 ➢ If, however, the calculated level is above the recommended level, the drug
product should be tested to ascertain whether the formulation process has
reduced the relevant solvent level to within the acceptable amount. Drug
product should also be tested if a solvent is used during its manufacture.

➢ This guideline does not apply to potential new drug substances, excipients,
or drug products used during the clinical research stages of development,
nor does it apply to existing marketed drug products. The guideline applies
to all dosage forms and routes of administration. Higher levels of residual
solvents may be acceptable in certain cases such as short term (30 days or
less) or topical application. Justification for these levels should be made on
a case by case basis.

Q3D Guidelines for elemental impurities

➢ Elemental impurities in drug products may arise from several sources; they
may be residual catalysts that were added intentionally in synthesis or may
be present as impurities (e.g., through interactions with processing
equipment or container/closure systems or by being present in
components of the drug product). Because elemental impurities do not
provide any therapeutic benefit to the patient, their levels in the drug
product should be controlled within acceptable limits.

➢ There are three parts of this guideline: the evaluation of the toxicity data
for potential elemental impurities; the establishment of a Permitted Daily
Exposure (PDE) for each element of toxicological concern; and application
of a risk-based approach to control elemental impurities in drug products.
An applicant is not expected to tighten the limits based on process
capability, Provided that the elemental impurities in drug products do not
exceed the PDEs. The PDEs established in this guideline are considered to
be protective of public health for all patient populations.

➢ In some cases, lower levels of elemental impurities may be warranted

when levels below toxicity thresholds have been shown to have an impact
on other quality attributes of the drug product (e.g., element catalyzed
 degradation of drug substances). In addition, for elements with high PDEs,
other limits may have to be considered from a pharmaceutical quality
perspective and other guidelines should be consulted (e.g., ICH Q3A)

➢ . This guideline presents a process to assess and control elemental

impurities in the drug product using the principles of risk management as
described in ICH Q9. This process provides a platform for developing a
riskbased control strategy to limit elemental impurities in the drug
product. The guideline applies to new finished drug products (as defined in
ICH Q6A and Q6B) and new drug products containing existing drug
substances.

➢ The drug products containing purified proteins and polypeptides (including

proteins and polypeptides produced from recombinant or non-
recombinant origins), their derivatives, and products of which they are
components (e.g., conjugates) are within the scope of this guideline, as are
drug products containing synthetically produced polypeptides,
polynucleotide, and oligosaccharides.

➢ This guideline does not apply to herbal products, radiopharmaceuticals,

vaccines, cell metabolites, DNA products, allergenic extracts, cells, whole
blood, cellular blood components or blood derivatives including plasma
and plasma derivatives, dialyses solutions not intended for systemic
circulation, and elements that are intentionally included in the drug
product for therapeutic benefit. This guideline does not apply to products
based on genes (gene therapy), cells (cell therapy) and tissue (tissue
engineering). In some regions, these products are known as advanced
therapy medicinal products.

➢ This guideline does not apply to drug products used during clinical research
stages of development. As the commercial process is developed, the
principles contained in this guideline can be useful in evaluating elemental
impurities that may be present in a new drug product. Application of Q3D
to existing products is not expected prior to 36 months after publication of
 the guideline by ICH. The factors considered in the safety assessment for
establishing the PDE are listed below in approximate order of relevance:

• The likely oxidation state of the element in the drug product;

• Human exposure and safety data when it provided applicable information;

• The most relevant animal study;

• Route of administration

Elements classification

• Class:1

• Class:2

• Class :2A

• Class:2B

• Class: 3

Q4- PHARMACOPOEIAS:
Q4 B: EVALUATION AND RECOMMENDATION OF
PHARMACOPOEIAL TEXTS FOR USE IN THE ICH REGIONS
Objective of the Guideline This document describes a process for the evaluation
and recommendation by the Q4B Expert Working Group (EWG) of selected
pharmacopoeial texts to facilitate their recognition by regulatory authorities for
use as interchangeable in the ICH regions. Following favourable evaluations, ICH
will issue topic-specific annexes with information about these texts and their
implementation (the Q4B Outcomes).
Q4B Evaluation Process

➢ The process begins with a document submission to the Q4B EWG. For PDG
proposed pharmacopoeial text, the document submission should be
provided as soon as possible after PDG Stage 5B sign-off

➢ . The document submission should outline any issues for resolution and
should contain any appropriate supporting data.

➢ When the Q4B evaluation process results in a conclusion and

recommendation that the pharmacopoeial text can be used as
interchangeable in the ICH regions, a topicspecific Q4B annex will be issued
following the steps in the ICH process as detailed below

Step 1

➢ Each Q4B party independently evaluates the documents for regulatory

impact. Additional discussion within the Q4B EWG, and/or
communication/dialogue with the submitting party (e.g., the PDG), might
be warranted to resolve any issues that surfaced during the evaluation

➢ When the Q4B evaluation process results in a recommendation that the

pharmacopoeial text can be used as interchangeable in the ICH regions, the
Q4B EWG prepares and signs off on a draft Q4B which is submitted to the
Steering Committee for adoption at Step 2.

Step 2

➢ The Steering Committee agrees, based on the report of the Q4B EWG,
that there is sufficient scientific consensus on the technical issues for the
draft annex to proceed to Step 3 regulatory consultation and discussion.

Step 3

➢ The draft Q4B annex is made available for regulatory consultation in the
three regions (generally for 3 months). The regulatory consultation and
discussion should focus on the Q4B Outcome in the annex. The Q4B EWG
 can revise the annex based on comments received and submits a final draft
of the annex to the ICH Steering Committee.

Step 4

The ICH Steering Committee adopts the annex and issues it as a stand-alone
companion document to the ICH Q4B guideline.

Step 5

The annex moves to the regional regulatory implementation step. The Q4B
annexes will contain the following information at a minimum. Other
information might be incorporated on a case-by-case basis.

• Topic title;

• Introduction;

• Q4B Outcome;

• As appropriate, statements that will assist in the use of the referenced

pharmacopoeial text by stakeholders;

• Implementation timelines indicating regulators' advice on when stakeholders

can begin using the pharmacopoeial text as interchangeable;

• References to methods and acceptance criteria, as appropriate.

Q5A-Q5E QUALITY OF BIOTECHNOLOGICAL PRODUCTS

Q5A (R1) Viral safety evaluation of biotechnology products
derived from cell lines of human or animal origin
➢ This document is concerned with testing and evaluation of the viral safety
of biotechnology products derived from characterized cell lines of human or
animal origin (i.e., mammalian, avian, insect) and outlines data that should
be submitted in the marketing application/registration package.
➢ For the purposes of this document the term virus excludes nonconventional
transmissible agents like those associated with Bovine Spongiform
Encephalopathy (BSE) and scrape. Applicants are encouraged to discuss
issues associated with BSE with the regulatory authorities.

➢ The scope of the document covers products derived from cell cultures
initiated from characterized cell banks.

➢ It covers products derived from in vitro cell culture, such as interferon’s,

monoclonal antibodies and recombinant DNA-derived products including
recombinant subunit vaccines, and also includes products derived from
hybridoma cells grown in vivo as ascites. In this latter case, special
considerations apply and additional information on testing cells propagated
in vivo is contained in Appendix 1. Inactivated vaccines, all live vaccines
containing self-replicating agents, and genetically engineered live vectors
are excluded from the scope of this document.

➢ The risk of viral contamination is a feature common to all biotechnology

products derived from cell lines. Such contamination could have serious
clinical consequences and can arise from the contamination of the source
cell lines themselves (cell substrates) or from adventitious introduction of
virus during production.

➢ To date, however, biotechnology products derived from cell lines have not
been implicated in the transmission of viruses.

➢ Nevertheless, it is expected that the safety of these products with regard to

viral contamination can be reasonably assured only by the application of a
virus testing program and assessment of virus removal and inactivation
achieved by the manufacturing process, as outlined below. Three principal,
complementary approaches have evolved to control the potential viral
contamination of biotechnology products:
• Selecting and testing cell lines and other raw materials, including
media components, for the absence of undesirable viruses which
may be infectious and/or pathogenic for humans;

• Assessing the capacity of the production processes to clear infectious

viruses;

• Testing the product at appropriate steps of production for

 absence of contaminating infectious viruses.

➢ All testing suffers from the inherent limitation of quantitative virus assays,
i.e., that the ability to detect low viral concentrations depends for
statistical reasons on the size of the sample.

➢ Therefore, no single approach will necessarily establish the safety of a

product. Confidence that infectious virus is absent from the final product
will in many instances not be derived solely from direct testing for their
presence, but also from a demonstration that the purification regimen is
capable of removing and/or inactivating the viruses.

➢ The type and extent of viral tests and viral clearance studies required at
different steps of production will depend on various factors and should be
considered on a case-by-case and step-by-step basis.

➢ The factors that should be taken into account include the extent of cell
bank characterization and qualification, the nature of any viruses detected,
culture medium constituents, culture methods, facility and equipment
design, the results of viral tests after cell culture, the ability of the process
to clear viruses, and the type of product and its intended clinical use.

➢ The purpose of this document is to provide a general framework for virus

testing, experiments for the assessment of viral clearance and a
recommended approach for the design of viral tests and viral clearance
studies. Related information is described in the appendices and selected
definitions are provided in the glossary.

➢ The manufacturers should adjust the recommendations presented here to

their specific product and its production process. The approach used by
manufacturers in their overall strategy for ensuring viral safety should be
explained and justified. In addition to the detailed data which is provided,
an overall summary of the viral safety assessment would be useful in
facilitating the review by regulatory authorities.

➢
 This summary should contain a brief description of all aspects of the viral
safety studies and strategies used to prevent virus contamination as they
pertain to this document.

Q5B Quality of biotechnological products

➢ This document presents guidance regarding the characterization of the
expression construct for the production of recombinant DNA protein
products in eukaryotic and prokaryotic cells.

➢ This document is intended to describe the types of information that are

considered valuable in assessing the structure of the expression construct
used to produce recombinant DNA derived proteins.

➢ This document is not intended to cover the whole quality aspect of rDNA
derived medicinal products. The expression construct is defined as the
expression vector containing the coding sequence of the recombinant
protein.

➢ Segments of the expression construct should be analyzed using nucleic acid

techniques in conjunction with other tests performed on the purified
recombinant protein for assuring the quality and consistency of the final
product.

➢ Analysis of the expression construct at the nucleic acid level should be

considered as part of the overall evaluation of quality, taking into account
that this testing only evaluates neither the coding sequence of a
recombinant gene and not the translational fidelity nor other
characteristics of the recombinant protein, such as secondary structure,
tertiary structure, and post-translational modifications

Q5C Quality of biotechnological products Stability testing of

biotechnological/biological products
➢ The guidance stated in this annex applies to well-characterized proteins and
polypeptides, their derivatives and products of which they are components,
 and which are isolated from tissues, body fluids, cell cultures, or produced
using rDNA technology.

➢ Thus, the document covers the generation and submission of stability data
for products such as cytokines (interferons, interleukins, colony-stimulating
and tumor necrosis factors), erythropoietin’s, plasminogen activators,

blood plasma factors, growth hormones and growth factors, insulin,

monoclonal antibodies, and vaccines consisting of well-
characterized proteins or polypeptides.
➢ In addition, the guidance outlined in the following sections may apply to
other types of products, such as conventional vaccines, after consultation
with the appropriate regulatory authorities. The document does not cover
antibiotics, allergenic extracts, heparins, vitamins, whole blood, or cellular
blood components.

Q5E Comparability of biotechnological/biological products

subject to changes in their manufacturing process
➢ The objective of this document is to provide principles for assessing the
comparability of biotechnological/biological products before and after
changes are made in the manufacturing process for the drug substance or
drug product

➢ therefore, this guideline is intended to assist in the collection of relevant

technical information which serves as evidence that the manufacturing
process changes will not have an adverse impact on the quality, safety and
efficacy of the drug product.

➢ The document does not prescribe any particular analytical, nonclinical or

clinical strategy. The main emphasis of the document is on quality aspects

➢
Q6A-Q6B SPECIFICATIONS
Q6A Specifications: test procedures and acceptance criteria,
for new drug substances and new drug products
➢ This guideline is intended to assist to the extent possible, in the
establishment of a single set of global specifications for new drug
substances and new drug products.

It provides guidance on the setting and justification of acceptance criteria

and the selection of test procedures for new drug substances of synthetic
chemical origin, and new drug products produced from them, which have
not been registered previously in the United States, the European Union, or
Japan.

➢ The quality of drug substances and drug products is determined by their

design, development, in- process controls, GMP controls, and process
validation, and by specifications applied to them throughout development
and manufacture.

➢ This guideline addresses specifications, i.e., those tests, procedures, and

acceptance criteria which play a major role in assuring the quality of the
new drug substance and new drug product at release and during shelf life.

➢ Specifications are an important component of quality assurance, but are

not it only Component. All of the considerations listed above are necessary
to ensure consistent production of drug substances and drug products of
high quality.

➢ This guideline addresses only the marketing approval of new drug products
(including combination products) and, where applicable, new drug
substances; it does not address drug substances or drug products during
the clinical research stages of drug development

➢ this guideline may be applicable to synthetic and semi-synthetic antibiotics

and synthetic peptides of low molecular weight; however, it is not sufficient
 to adequately describe specifications of higher molecular weight peptides
and polypeptides, and biotechnological/biological products.

➢ The ICH Guideline Specifications: Test Procedures and Acceptance Criteria

for Biotechnological/Biological Products address guideline specifications,
tests and procedures for biotechnological/biological products.
Radiopharmaceuticals, products of fermentation, oligonucleotides, herbal
products and crude products of animal or plant origin are similarly not
covered

➢ Guidance is provided with regard to acceptance criteria which should be

established for all new drug substances and new drug products, i.e.
universal acceptance criteria, and those that are considered specific to
individual drug substances and/or dosage forms.

➢ This guideline should not be considered all encompassing. New analytical

technologies, and modifications to existing technology, are continually

being developed. Such technologies should be used when justified. Dosage

forms addressed in this guideline include solid oral dosage forms, liquid
oral dosage forms, and parenterals (small and large volume).

➢ This is not meant to be an all-inclusive list, or to limit the number of dosage

forms to which this guideline applies. The dosage forms presented serve as
models, which may be applicable to other dosage forms which have not
been discussed.

➢ The extended application of the concepts in this guideline to other dosage

forms, e.g., to inhalation dosage forms (powders, solutions, etc.), to topical
formulations (creams, ointments, gels), and to transdermal systems, is
encouraged.

➢
Q6B Specifications: Test procedures and acceptance criteria
for biotechnological/biological products
➢ The principles adopted and explained in this document apply to proteins
and polypeptides, their derivatives, and products of which they are
components (e.g., conjugates).

➢ These proteins and polypeptides are produced from recombinant or

nonrecombinant cell-culture expression systems and can be highly
purified and characterized using an appropriate set of analytical
procedures.

➢ The principles outlined in this document may also apply to other product
types such as proteins and polypeptides isolated from tissues and body
fluids. To determine applicability, manufacturers should consult with the
appropriate regulatory authorities.

➢ This document does not cover antibiotics, synthetic peptides and

polypeptides, heparins, vitamins, cell metabolites, DNA products,
allergenic extracts, conventional vaccines, cells, whole blood, and cellular
blood components.

A separate ICH Guideline, “Specifications: Test Procedures and

Acceptance Criteria for New Drugs Substances and New Drug Products:
Chemical Substances” addresses specifications, and other criteria for
chemical substances.

➢ This document does not recommend specific test procedures or specific

acceptance criteria nor does it apply to the regulation of preclinical
and/or clinical research material.