This document discusses safety testing of pharmaceuticals. It covers the importance of safety testing to establish storage conditions and ensure stability. The major steps discussed are preclinical research in cells and animals, preclinical safety assessment testing in two animal species, clinical trials in humans proceeding from phase 1 to 4, and post-marketing surveillance. Toxicological studies evaluate toxicity, effects, and target organs while biocompatibility studies examine the interaction between drugs and tissues. Regulatory authorities like the FDA oversee safety testing to help safe products reach the market.

1. SAFETY TESTING OF
PHARMACEUTICALS
PRESENTED BY
ROOMA KHALID
M.phil
pharmaceutics
(2014_2016)
ISLAMIA
UNIVERSITY
BAHAWALPUR

2. INTRODUCTION
Drug Substance
“Active ingredient used in combination with excipient
for the diagnosis, treatment and prevention of disease”
Excipient
“Other than the active drug substance in the dosage
form”
Dosage Form
“A pharmaceutical drug delivery system such as tablet,
capsule, that contains an active ingredient in combination
with excipients”

3. INTRODUCTION
Re-test date
“The date after which samples of active substance
must be examined, to ensure that the material still
comply with the specifications, and suitable for use.”
Shelf life
“The time period during which a pharmaceutical
product is expected to remain within the approved
shelf life specifications, provided that it is stored
under the labeled storage conditions”

4. INTRODUCTION
Finished drug Product
“The dosage form in the final immediate packaging
intended for marketing”

5. INTRODUCTION
SAFETY OF PHARMACEUTICALS:
“The control of recognized hazards to
achieve an acceptable level of risk” .
This can take the form of being protected from the
event or from exposure to something that causes harm
to pharmaceutical products.

6. IMPORTANCE OF SAFETY TESTING
Evidence of change in quality under environmental
conditions.
Establishment of storage conditions.
Help to test the liability of the product against
physical, chemical and microbiological changes.

7. STEPS OF SAFETY TESTING
Safety testing is a complicated process that involves
many different steps to ensure the highest level of
safety.
1. Preclinical research
2. Preclinical safety assessment testing
3. Medical research
4. Pathologist research

8. STEPS OF SAFETY TESTING
1.PRECLINICAL RESEARCH:
The first step in developing and testing a new product.
Initially, scientists consult the vast amount of
published information and databases to obtain as
much background information as possible.
If necessary, they perform studies to determine which
germ, virus, chemical, or other factor causes a disease.

9. STEPS OF SAFETY TESTING
Then the mechanisms of the disease are studied and
new drugs are developed and evaluated for
effectiveness and side effects using cell culture and
whole animal models.

10. STEPS OF SAFETY TESTING
2.PRE CLINICAL SAFETY ASSESMENT TESTING:
Once a drug is shown to be effective in animals and to
have a low incidence of side effects, it proceeds to
safety assessment testing.
These tests are conducted to evaluate drug safety in
two different animal species, with animals receiving
high doses of the new drug for 30 or 90 days.

11. STEPS OF SAFETY TESTING
Animals are carefully monitored for side effects.
After the study period, pathologists examine their
organs for signs of drug toxicity.
This drug safety testing in animals is carried out under
guidelines mandated by law through the FDA.
It is the last safety testing performed before the drug is
given to people for clinical testing.

12. STEPS OF SAFETY TESTING
3.MEDICAL RESEARCH:
Medical research perfomed in laboratories using cell
cultures and animals.

13. STEPS OF SAFETY TESTING
4.PATHOLOGIST RESEARCH:
A medical expert, usually a physician, who studies the
effects of a disease or chemical on the body.
Two different animal species are used for testing at this
stage.
The reason is that no animal is exactly like a person in
every way.

14. STEPS OF SAFETY TESTING
A drug may not be toxic to rats but may be toxic to
guinea pigs, and, by using two different species, the
chances are greater that the toxicity of a drug will be
discovered before it is ever given to a person.

15. STEPS OF SAFETY TESTING
This stage of safety testing usually takes about 4 years.
Drug companies test for mutagenicity (ability to cause
genetic changes) and carcinogenicity (ability to cause
cancer).
The drugs are also tested to confirm that they do not
cause infertility (inability to have children) or birth
defects.

16. STEPS OF SAFETY TESTING
This stage of safety testing takes many years, because it
may take a long period of time for animals to develop
cancer or infertility as a result of a toxic drug.

17. CLINICAL TRIALS
If no problems arise during preclinical testing, the
drug company applies to the FDA for an
Investigational New Drug Application, which
authorizes the drug company to administer a new drug
to people for clinical testing.

18. CLINICAL TRIALS
PHASE 1 TRIALS:
A new drug is administered to a small number of
normal, healthy human volunteers to study its activity
and to monitor potential toxicity in people. If
successful, Phase I trials lead to clinical testing of
drugs in humans.

19. CLINICAL TRIALS
PHASE 2 TRIALS:
These are limited studies in which the drug is
administered to patients with the disease to establish
proper dosages and to give some indication of
effectiveness. If successful, Phase II trials lead to phase
3 trials.

20. CLINICAL TRIALS
PHASE 3 TRIALS:
Large multicenter studies enroll thousands of patients
to test the drug's effectiveness and to continue to
monitor for any side effects. If Phase III trials confirm
the drug is safe and effective, it is approved by the
FDA.

21. CLINICAL TRIALS
PHASE 4 (POST MARKETING SURVILLANCE)
After the drug is on the market, the drug maker and
FDA continue to monitor for side effects. Because of
genetic diversity among humans, it is possible that a
new drug will cause adverse effects in only a small
group of genetically similar people, which may not
have been apparent during clinical trials.

22. CLINICAL TRIALS
As the new drug is given to more and more people,
careful monitoring is necessary to avoid this
possibility. Drugs are taken off the market if
postmarketing surveillance reveals previously
undetected side effects.

23. CLINICAL TRIALS
Clinical testing is complex and time-consuming,
averaging 14 years to complete Phase I through III
testing to gain FDA approval. Sometimes, drugs will
fail in clinical tests because the animal tests did not
accurately predict their effects in humans.

24. SAFETY TESTING STRATEGIES
Safety testing is divided in following types of studies:
I. Toxicological studies of pharmaceuticals
II. Biocompatibilty studies of pharmaceuticals

25. 1.TOXICOLOGICAL STUDIES
Toxicology studies are conducted to determine the
degree of toxicity of a chemical substance, to establish
the relationship between dose and adverse effects, and
to provide information on target organs and target
functions.

26. 1.TOXICOLOGICAL STUDIES
Objectives of toxicological studies:
To identify hazards.
To evaluate risks.
To provide the basis for risk management

27. 1.TOXICOLOGICAL STUDIES
The toxicological and pharmacological tests must
show:
a) the potential toxicity of the product and any
dangerous or undesirable toxic effects that may occur
under the proposed conditions of use in human
beings; these should be evaluated in relation to the
pathological condition concerned;

28. 1.TOXICOLOGICAL STUDIES
b) the pharmacological properties of the product, in
both qualitative and quantitative relationship to the
proposed use in human beings.”

29. TYPES OF TOXICOLOGICAL STUDIES
1. Single dose acute toxicity studies:
Single dose acute toxicity studies deal with
the potential adverse effects of single doses. These
investigations should provide information about
possible dose levels for first applications to humans,
and give indications to the possible effects to be
expected with (accidental or intentional) over-dosing.

30. TYPES OF TOXICOLOGICAL STUDIES
2.Repeated dose toxicity studies:
The primary goal of repeated dose toxicity
is to characterize the toxicological profile of the test
substance following repeated administration. it
provides information on toxic effects, identification of
potential target organs, effects on physiological
functions, haematology, clinical chemistry and
pathology.

31. TYPES OF TOXICOLOGICAL STUDIES
3.Genotoxicity studies:
The aim of genotoxicity studies is to detect
compounds which induce genetic damage directly or
indirectly. The usual approach is to carry out tests
which provide information on gene mutations,
structural chromosome aberrations etc.

32. TYPES OF TOXICOLOGICAL STUDIES
4.Carcinogenicity studies:
The aim of carcinogenicity studies is
to identify the tumorigenic potential of a test
substance in animals and to assess the relevant risk to
humans.

33. 2.BIOCOMPATIBILTY STUDIES:
The word biocompatibility refers to the interaction
between a drug and the tissues and physiological
systems of the patient treated with the device. An
evaluation of biocompatibility is one part of the overall
safety assessment of a drug.

34. 2.BIOCOMPATIBILTY STUDIES
Biocompatibility of drugs is investigated using
analytical chemistry, in vitro tests, and animal models.
The biocompatibility of a drug depends on several
factors, including:
its chemical and physical nature
the types of patient tissue that will be exposed to the
drugs
the duration of that exposure

35. REGULATORY AUTHORITIES
FDA:
FDA (Food and Drug Administration)—A federal
agency whose mission is to promote and protect the
public health by helping safe and effective products
reach the market in a timely way and monitoring
products for continued safety after they are in use.

36. REGULATORY AUTHORITIES
Laboratory animals are not only crucial in
understanding diseases; they are also essential in
evaluating the safety of drugs, vaccines, food additives,
household products, workplace chemicals, cosmetics,
water and air pollutants, and many other substances.

37. REGULATORY AUTHORITIES
The Food and Drug Administration (FDA) oversees
this process for drug, vaccine, food additive, and
cosmetic safety testing. Other agencies like the
Consumer Product Safety Commission, the
Environmental Protection Agency, and the
Occupational Safety and Health Administration
regulate other types of testing.

38. REGULATORY AUTHORITIES
2. ICH SAFETY GUIDELINES:
ICH has produced a comprehensive set of
safety Guidelines to uncover potential risks like
carcinogenicity and genotoxicity.

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