In the given ppt we get idea about safety pharmacology studies. learn why safety pharmacology is important. concept of safety pharmacology, also get the knowledge from where safety pharmacology is originated

1. SUBJECT NAME : PHARMACOLOGICAL AND TOXICOLOGICAL
SCRRENING METHOD-II
GUIDED BY: DR. A. K. KULKARNI
PRESENTED BY: ANKITA SANDESH HALDANKAR
(M. PHARM 1ST YEAR PHARMACOLOGY)
D. Y. PATIL COLLEGE OF PHARMACY AKURDI , PUNE

2.  INTRODUCTION
 ORIGIN
 CONCEPT
 IMPORTANCE OF SAFETY PHARMACOLOGY

3.  As per ICH S7A safety pharmacology are those studies that investigate the
potential undesirable pharmacodynamic effect of substance on physiological
function in relationship to exposure in therapeutic range & above.
 Sometimes primary & secondary pharmacodynamic properties of substance
may contribute to this safety evaluation for potential adverse effect in humans.
1. Safety pharmacology evaluation are essential step in assigning acute &
potential life threatening risk of novel pharmaceutical as a part of IND
enabling program.
2. Safety pharmacology study use to determine mechanistic effect vital
functions & evaluate potential adverse effect as organ effect such as renal,
GI tract.

4.  Serious injury or death of voluntary & patient participate in
early clinical trial are ray & thus distribute when it occurs the
organ system and function most frequently responsible in this
events of cardiac vascular, respiratory, CNS and Renal system
and their result almost always critical emergency.
 The origin of safety pharmacology are grounded upon
observation that organ functions can be toxicological target to
humans expose to normal therapeutic agents and that drugs
effect on organs functions are not readily detected by standard
toxicological testing.

5. 1) OBJECTIVE OF STUDIES
 To identify undesirable pharmacodynamic properties of a
substance that may hamper the human safety.
 To evaluate adverse pharmacodynamic & pathological effect
of substance observe in toxicology or clinical studies.
 To investigate mechanism of adverse pharmacodynamic effect
observed or suspected.
1) OBJECTIVE OF STUDIES
 To identify undesirable pharmacodynamic properties of a
substance that may hamper the human safety.
 To evaluate adverse pharmacodynamic & pathological effect
of substance observe in toxicology or clinical studies.
 To investigate mechanism of adverse pharmacodynamic effect
observed or suspected.

6. 2. GENERAL CONSIDERATION IN
SELECTION & DESIGN OF SAFETY
PHARMACOLOGY STUDIES
 The pharmacological affects varies as per specific properties of test substance so study
should selected & design accordingly.
1) Design of study should be as per class of drug may it should suggest specific adverse
effect of that class.
2) Ligand binding enzymes assay that suggesting a potential for adverse effects.
3) Adverse effects associate with member of chemical or therapeutic class but independent
of primary pharmacodynamic effect.
 Result from this
1. Previous safety pharmacologic studies
2. Secondary pharmacodynamic studies
3. Toxicology studies
4. Previous human use

7. 3. TEST SYSTEM
A. General consideration on test substance
B. Use of in vivo & in vitro studies
C. Experimental design
I. Sample size & use of control
II. Route of administration
A.General consideration on test substance
• The consideration should be relevant to selection of animal model or other test
system or that scientific valid information can derived.
• Selection factor can include pharmacokinetic profile. Pharmacodynamic
responsible of model, species, strain, gender, age of experimental animal.
susceptibility, sensitivity & reproducibility of test system.

8. B. Use of in vivo & in vitro studies
 In vivo & in vitro System can be include isolated organs
& tissue, cell culture, cell fragments, Subcellular
organelles, receptor & channel, transporters &
enzymes.
 In vitro system can be we in supportive studies.
for example to obtain profile of activity of substance to
investigate mechanism of effect. For conducting in vivo
studies is prefer to use anesthetize animal.

9. c) Experimental design
(i)Sample size & Use of control
• Size of group should be sufficient to allow meaningful
scientific interpretation of that generated i.e. each group a
sufficient animal should be included to conclude the final that
& no.at animal should be such so the presence of biologically
significant effect of that Substance should be evaluated.
(ii) Route of administration
• the expected clinical route of administration should be used
when possible.
• Study previous that in human if such information is available
assessment effects by more than one route may be appropriate.
• If the test substance is intended for clinical use by more than
one route of administration i.e. either oral / Parenteral

10. 4.Dose level or conc. of test substance
It divided into In vivo & In vitro studies.
a) In vivo Studies.
 Define the dose response curve of adverse effect
 The time course of adverse effect shows be investigate when possible.
b) In vitro studies
 In vitro studies should be designed to establish a conc. effect relationship.
 The range of conc. should be use in order to increase the likelihood of detecting
and effect of test substance.
5. Duration
 Safety pharmacology studies are generally performed by single dose
administration.
 Safety studies should be Rationale based it following condition occurs
For example
a. pharmacodynamic effect occur only after certain duration of treatment
b. If result from repeated dose non clinical studies.
c. If adverse effect result from use in humans.

11. 6. Safety pharmacology core Battery
• It is performed according to GLP std. as per ICH guideline
 Purpose
• To investigate the effects of test substance on vital functions &
vital organs which include.
1. CNS
2. Cardiovascular System
3. Respiratory system
• It is also implements Supplementary test to evaluate other
organ system like renal & &GI system

13. 7. Follow-up & supplemental safety
pharmacology studies
concern of adverse effect may arise from
a) Safety Pharmacology core battery
b) clinical trial
c) Pharmacovigilance.
d) Experimental in vitro or in vivo studies

14. 8.1) Follow up studies for safety Pharmacology
core battery
• Deal with studies follow up studies provide greater depth of
understanding & additional knowledge to that provide by core battery
on vital functions.
• The following list of studies further evaluate vital organ system for
potential adverse pharmacodynamic effects.
1. CNS
 Behavioral Pharmatology, leaming & memory, ligand Specific binding,
neurochemistry, visual, auditory, electrophysiology examination etc
2. Cardiovascular System
 cardiac output, ventricular contractility, vascular resistance, the effect of
endogenous or exogenous substance on Cardiovascular response etc
3. Respiratory system
 Airway resistance, compliance, pulmonary arterial pressure, blood
gases, blood pH etc

15. 8.11) Supplemental safety pharmacology studies
 They are meant to evaluate adverse pharmacodynamic effects on
organ system that not addressed by core battery studies.
Renal/Urinary system
• Effects of test substance on renal parameter should be assessed for e.g.
urinary volume, Specific gravity. osmolarity, pH, electrolyte balance,
proteins & blood chemistry determination such as blood, urea, nitrogen,
Creatinine & plasma Protein to be used
Gastrointestinal System
Effect of test substance on GI system should be assessed for e.g. gastric
secretion, GI injury potential, bile secretion, transit time in vivo, illegal
contraction in vitro gastric PH measurement and pooling can be used.

16. ANS
• Effect of test substance on ANS should be assessed for
example binding to relevant receptor, responses to
agonist or antagonist, measurement of cardiovascular
responses and heart rate variability can be used.
Other organs system
Effect of test substance on organ system not investigated
elsewhere should be assessed when there is a recon for
concern
Example: skeletal muscle, immune and endocrine
functions can be investigated.

17. 9.CONDITION UNDER
WHICH STUDIES ARE NOT
NECESSARY
Safety pharmacology studies may not be needed
1. For locally applied agents. ( example dermal or ocular)
2. For cytotoxic agent for treatment of end- stage cancer patient.
3. For biotechnology derived products that achieve highly specific
receptor targeting.
4. For exceptional cases like that of a new test substance having similar
pharmacokinetic and pharmacodynamic profile.

18. 10.TIMING OF SAFETY
PHARMACOLOGY STUDIES IN
RELATION TO CLINICAL
DEVELOPMENT
When planning a safety pharmacology program should be
reviewed to determine whether or not specific studies are
recommended.
a. Studies prior to administration in humans
b. Studies during clinical development
c. Studies before approval

19.  Safety pharmacology issues have a significant impact on clinical
development attrition ( both preclinical and during clinical development).
 Data are important for phase-1 dose setting
 Safety pharmacology studies are regulatory requirement for IND
submission prior to human exposure.
 The consequence of getting it wrong can have dramatic implication.
 Minimize unreliability of patient on pharmaceuticals via enduring safety.
 Ensure safety before clinical phase so validate preclinical phase to better
extent.

20. THANK YOU….