The ICH guidelines regarding the safety of animals during animal trials are discussed in this presentation.

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2. PRESENTED BY- AMEENA MEHABOOB
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3. CONTENTS
• WHAT IS ICH
• PURPOSE
• GUIDELINES
• GUIDELINES ON SAFETY OF ANIMALS
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4. WHAT IS
EUROPEAN
UNION
JAPANUNITED
STATES
• International Conference of
Harmonization of technical
Requirements for registration of
pharmaceuticals for human use.
• Created in 1990
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5. PURPOSE
• Harmonization of technical requirements
• Ensure safety, efficacy and quality of medicines.
• Prevent duplication of clinical trials in humans.
• Minimize the use of animal without compromising safety and
effectiveness.
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6. Refinements in Animal
Testing – Applying the 3Rs
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7. ICH GUIDELINES
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8. • Guideline on the need for carcinogenicity studies of pharmaceuticals
• Nov 1995S1A
• Testing for carcinogenicity of pharmaceuticals
• July 1997S1B
• Dose selection for carcinogenicity studies of pharmaceuticals
• Mar 2008S1C(R2)
• Guidance on genotoxicity testing and data interpretation
• Nov 2011
•
S2(R1)
• Note for guidance on toxicokinetics: The assessment of systemic
exposure in toxicity studies
• Oct 1994
S3A
• Pharmacokinetics: Guidance for repeated dose tissue distribution
studies
• Oct 1994
S3B
• Duration of chronic toxicity testing in animals (rodent and non rodent
toxicity testing)
• Sep 1998
S4
ICH GUIDELINES ON SAFETY OF ANIMALS
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9. • Detection of toxicity to reproduction for medicinal products and toxicity
to male fertility
• June 1993
S5(R2)
• Preclinical safety evaluation of biotechnology derived pharmaceuticals
• June 2011S6(R1)
• Safety pharmacological studies for human pharmaceuticals
• Nov 2000S7A
• Non clinical evaluation of potential for delayed ventricular repolarization
(QT interval prolongation) by human pharmaceuticals
• May 2005
S7B
• Immunotoxicity studies for human pharmaceuticals
• Sep 2005S8
• Non clinical evaluation for anticancer pharmaceuticals
• Oct 2009S9
• Photo safety evaluation
• Nov 2012S10
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10. S1A (NOV 1995)
NEED FOR CARCINOGENICITY
STUDIES OF PHARMACEUTICALS
• This document provides a consistent definition of circumstances under
which it is necessary to undertake carcinogenicity studies on new drugs.
These recommendations take into account the known risk factors as well
as intended indications and duration of exposure.
• Results from genotoxicity studies, toxicokinetics, and mechanistic
studies can now be routinely applied in preclinical safety assessment.
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11. S1B (JULY 1997)
TESTING FOR CARCINOGENICITY OF
PHARMACEUTICALS
• Guidance on the need to carry
out carcinogenicity studies in
both mice and rats, and
guidance is also given on
alternative testing procedures
which maybe applied without
jeopardizing safety.
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12. S1C-R2 (MARCH 2008)
DOSE SELECTION FOR
CARCINOGENICITY STUDIES OF
PHARMACEUTICALS
• Addresses the criteria for the selection of high dose to be
used in carcinogenicity studies on new therapeutic agents
to harmonize current practices and improve the design of
studies.
• The pharmacokinetic end point of 25 is declared to be
applicable also for pharmaceuticals with positive
genotoxicity signals.
• This change has implications on reducing the pain and
discomfort of animals at maximally tolerated dose (MTD)
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13. S2-R1 (MARCH 2008)
GUIDANCE ON GENOTOXICITY
TESTING AND DATA
INTERPRETATION FOR
PHARMACEUTICALS INTENDED
FOR HUMAN USE
• S2A: GUIDANCE ON SPECIFIC ASPECTS OF REGULATORY
GENOTOXICITY TESTS FOR PHARMACEUTICALS:
o Specific guidance and recommendations for in vitro and in vivo tests
and on evaluation of test results. It includes a glossary of terms related
to genotoxicity tests to improve consistency in applications.
• S2B: GENOTOXICITY: A STANDARD BATTERY FOR
GENOTOXICTY TESTING FOR PHARMACEUTICALS:
o The identification of a standard set of assays to be conducted for
registration, and the extent of confirmatory experimentation in any
particular genotoxicity assay in the standard battery.
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14. S3A (OCT 1994)
NOTE FOR GUIDANCE ON
TOXICOKINETICS: THE ASSESSMENT
OF SYSTEMIC EXPOSURE IN
TOXICITY STUDIES
• Gives guidance on developing test strategies in toxicokinetics
and the need to integrate pharmacokinetics and need to
integrate pharmacokinetics into toxicity testing, in order to aid
in the interpretation of the toxicology findings and promote
rational study design development.
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15. S3B (OCT 1994)
PHARMACOKINETICS: GUIDANCE FOR REPEATED
DOSE TISSUE DISTRIBUTION STUDIES
•This study is required when appropriate data cannot be derived
from other sources
•A comprehensive knowledge of the ADME of a compound is
important for the interpretation of pharmacology and toxicology
studies
• Useful for designing toxicology and pharmacology studies
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16. S4(SEP 1998)
DURATION OF CHRONIC
TOXICITY TESTING IN ANIMALS
(RODENT AND NON RODENT
TOXICITY TESTING)
• Safety evaluation of a medicinal product
• For the development of medicinal
products with the exception of those
already covered by the ICH guideline
Safety Studies for Biotechnological
Products, eg., Monoclonal antibodies,
recombinant DNA proteins.
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17. S5-R2 (NOV 2000)
DETECTION OF TOXICITY TO REPRODUCTION FOR
MEDICINAL PRODUCTS & TOXICITY TO MALE FERTILITY
• This document provides
guidance on tests for
reproductive toxicity.
• It defines the period of
treatment to be used in
animals to better reflect
human exposure to medical
products and allow more
specific identification of stages
at risk.
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18. S6 (OCT 2009)
ADDENDUM TO ICH S6: PRECLINICAL
SAFETY EVALUATION OF
BIOTECHNOLOGY DERIVED
PHARMACEUTICALS
• It addresses the use of animal models of disease, determination
of when genotoxicity assays and carcinogenicity studies should
be performed, and the impact of antibody formation on duration
of toxicology studies.
• Clarification on species selection, study design, immonogenicity,
reproductive and developmental toxicity and assessment of
carcinogenic potential.
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19. S7A (NOV 2000)
SAFETY PHARMACOLOGY STUDIES FOR HUMAN
PHARMACEUTICALS
• Addresses the definition,
objectives and scope of safety
pharmacology studies.
• Also addresses which studies
are needed before initiation of
Phase 1 clinical studies as well
as information needed for
marketing
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20. S7B (MAY 2005)
NON- CLINICAL EVALUATION OF THE POTENTIAL
FOR DELAYED VENTRICULAR REPOLARIZATION (QT
INTERVAL PROLONGATION) BY HUMAN
PHARMACEUTICALS
• This guideline describes a non
clinical testing strategy for
assessing the potential of a test
substance to delay ventricular
repolarization.
• Includes non clinical assays
and integrated risk
assessments.
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21. S8 (SEP 2005)
IMMUNOTOXICITY STUDIES FOR HUMAN
PHARMACEUTICALS
• Addresses the recommendations on non clinical testing for
immunosuppression induced by low molecular weight drugs (non-
biologicals) and how each immunotoxicity study should be performed.
• It applies to new pharmaceuticals intended for use in humans, as well as
to marketed drug products proposed for different indications or other
variations on the current product label in which the change could result
in unaddressed and relevant toxicologic issues.
• Also applicable during CT and following approval to market.
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22. S9(OCT 2009)
NON CLINICAL EVALUATION FOR ANTI CANCER
PHARMACEUTICALS
• Provides information for pharmaceuticals that are only intended
to treat cancer in patients with late stage or advanced disease
regardless of the route of administration, including both small
molecule and biotechnology-derived pharmaceuticals. It
describes the type and timing of non clinical studies in relation
to the development of anticancer pharmaceuticals and
references other guidance as appropriate.
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23. S10(JUNE 2010)
PHOTOSAFETY EVALUATION OF
PHARMACEUTICALS
• This new guideline is adjunct
to M3(R2) guideline
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24. REFERENCES
• www.ich.org
• www.wikipedia.com
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