This presentation explores the origin of good Clinical Practice, Need of GCP. Principals of Good Clinical Practices. Its a ICH guideline E6.This presentation is very useful to prepare for interviews in the field of Clinical Research. Elite Institute of Pharma Skills gives quality Education to Pharmacy and Life Science graduates in the field of Regulatory Affairs, Clinical Research, Pharmacovigilance and Medical Coding. for more details log on to www.elite-pharmaskills.com 7028042239

1. Name : Bhagyashri Dnyaneshwar Taralkar.
Student of The Elite Institute Of Pharma Skills,Pune.
(www.elite.pharmaskills.com)
Guided By :Mrs. Archana Gawade .
History and Background of Good Clinical Practice

2. History and Background of Good Clinical Practice
Sulfanilamide Disaster
( 1937 )
Thalidomide Disaster
(1962)
Nazi experiments
(1940-1945)
Nurembergs Code
(1947)
1 2
3 4
5 6Tuskegee syphilis Study
(1932-1972)
Belmont Report
(1979)

3.  Gerhard Domagk (1932) : Discovered Red Azo Dye Prontosil a
Derivative of Sulfanilamide(1908).
It protected mice from lethal dose of staph and hemolytic
strep He got Nobel prize
 January 1932 Animal and Human studies demonstrated
sulfanilamide efficacy in streptococcal infection because first
synthesized in 1908 sulfanilamide was not patentable. Within
months Squib , Merck , Eli lily , Parke Davis each had received
AMA endorsement .
 In 1937 S.E Massengill Company of Bristol,
Tennesse , Founded by Samuel E . Massengill
began to produce sulfanilamide solution that had
not been available due to lack of appropriate
vehicle.
Sulfanilamide Disaster
S
1

4.  The FDA was notified , and an extensive
research was conducted to recover the
distributed medicines massengill company sent
out 1100 telegrams requesting the return of elixi
.FDA prohibited elixir .
Ys
s
.
 After investigating several possible solvents
Harold Watkins ,Massengill chief chemist formulated
raspberry flavor dissolved in
DEG added to sulfa drugs and it was
called Elixir Sulfanilamide and
company marketed the product.
 Using DEG as a solvent which is
poisonous To humans but Watkins
the company's chief pharmacist
was not aware of it
(although it was known at time)
 The toxicity of the product was never
tested and there were no regulations‘
requiring premarket safety testing of new drugs
 By early September1937 ,240 gallons of elixir
sulfanilamide had been manufactured by the
massengill company. The company started
distributing the medication in September 1937.
One of the major points of delivery of the drugs was
Tulsa, Oklahoma.
 By October 11, The American
Medical Association received a
report of several deaths caused by
medication

5. Facial
Paralysis
Coma Drowsiness Lethargy
Side Effects of Sulfanilamide Elixir.

6. Birth deformity Deformed hand
forearm
Feet Deformity
Thalidomide Disaster2

7.  The drug was found to be
associated with a congenital
abnormality causing severe birth
defects
 Thalidomide was marketed in USA
1957 for morning sickness and
nausea and soon became the drug of
choice to help pregnant women in
first trimester
 In 1964 (WMA) World Medical
Assembly has developed guidelines
called as Declaration of Helsinki(DOH)
for ethical conduct of studies
 Children's were born with
missing ( amelia ) or abnormal
( phocomelia )legs, arms , feet
and hands
 A series of law demonstrated that
large prescriber's had been relying
on manufacturers for the
information about drugs which was
based on inadequate testing
 Thalidomide syndrome triggered
world wide response Safety
monitoring system were set to
prevent this tragedy

8. FINLAND
Set of ethical principles
Regarding human experimentation
developed for the medical
community by the world medical
association (WMA).
WMA encourages other participants in medical research involving
human subject to adopt these principles
Declaration is addressed primarily to physician,
The Declaration of Geneva of the wma binds the physicians with
words
It is duty of physician to promote and safeguard the
health of patients including who are involved in research
And the International code of medical ethics declares that ,
A physician shall act in the patients best interest when providing
medical healthcare
The health of my patients will be my first consideration
main purpose: to understand causes , development and effect of
disease and improve preventive, diagnostic and therapeutic
intervention like safety , effectiveness , efficiency , accessibility
Declaration Of Helsinki

9.  Many of subject dies as a result of
experiments conducted by Nazis while many
others where after tests where completed
 In response , Drs . Leo Alexander and
Andrew Conway Ivy drafted a ten point
memorandum entitled permissible medical
Experiment that went to be known as
Nuremberg code
 The code called for such standards as
voluntary consent of patients, avoidance of
unnecessary pain and suffering and that must
be a belief that experimentation will not end
as death
Outcome of Nazi experiments
Nazi Experiment3

10. Freezing Experiments
High Altitude Experiments
Experiments of twins
Experiments with Poisons
Incendiary Bomb Experiments
High Altitude Experiments
Malaria Experiments
Mustard gas Experiments
Sulfonamide Experiments
Sea water Experiments
Sterilization Experiments
List of Nazi experiments

11.  Experimentation on twin children's in concentration
camp were created to show similarities and
differences in genetic of twins also to see human
body can be unnaturally manipulated.
 It was performed on over 1,500 sets of imprisoned
twins, fewer than 200 survived.
 Twins were arranged by age and sex and kept in
barracks between experiments which ranged from
injection of diiferent chemical sinto eye of twins to see
whether it could change the color and literally try
creating conjoined twins at Auschwitz concentration
camp in Poland in may1943
.Twins Experiments

12. Sea Water Experiment
From about July 1944 to about
september1944 Experiment
were conducted in Dachau
concentration camp to study
various method of making sea
water Drinkable
High Altitude Experiment
In early 1942 prisoners at
Dachau camp were used in
experiments to aid German
pilots who had eject at high
altitudes of the 200subjects ,
80 died outright others were
executed
Freezing Experiments
The result of this experiment
were publicized at the 1942
medical conference entitled
Medical Problems Arising from
Sea and winter
Sterilization experiments
From march 1941 to about Jan
1945, Sterilization experiments
were conducted at Auschwitz
,Ravvensbruck ,
It was a try to make a method of
minimum time and efforts for
sterilizing million of peoples

13. Animals experiments first.
Avoid suffering.
Protected from harm.
No intentional death or disability.
Subject free to stop.
Qualified，investigator.
Investigator will stop if harm occurs.
PRINCIPLES OF NUREMBERG CODE
Voluntary Consent.
Anticipate scientific benefits.
Nuremberg Code (1947)4

14.  Clinical study conducted in
Tuskegee , Alabama by US
public health service
.Tuskegee Syphilis Study(1932-1972)5
 Investigator recruited 399 poor, mostly
illiterate African American sharecroppers
with syphilis for research.
Study began as clinical trial of syphilis in the
Macon County Population.
Initially subjects studied for six to eight months
then treated with contemporary methods
 This included Salvarsan , mercurial
ointments and bismuth which were
somewhat effective , but quite toxic
, they were all that was available
 People were uninformed about disease
and said to be treated
for bad blood by 1947 penicillin
had become standard treatment for syphilis

15.  White people were given penicillin and black
were given placebo just to observe the
progression of fatal disease
By end of the study in 1972, only 74 of test
subjects were alive, 28of the original
 And write regulation governing studies invlving human participants On may16,
1997 president Bill Clinton formally apologized and held ceremony for Tuskegee
participants
 399 men had died of syphilis , 100 were dies of
related complications , 40 of their wives had been
infected and 19 children's were born with
congenital syphilis in 1974 congress passed the
National research act and created a commission to
study
Tuskegee Syphilis Study(1932-1972)

16. The report was issued on 30 September 1978 and published in federal register on 18
april1979 the report took its name from the Belmont conference center where the document
was drafted as a part
Three core principles are : respect for people, beneficence, and justice Three primary
applications like informed consent, assessment of risks and benefits and selection of
subjects
Today the Belmont report continues as an essential reference for institutional review board
That review HHS conducted proposal involving human subjects meets ethical foundation of
regulation
Created by the National Commission for the protection of human subjects of biomedical And
behavioral Research ,Ethical principles and guidelines for the protection of the human subjects of
research , report of the national commission for the protection of human subjects of biomedical and
behavioral research
Belmont Report6

17. 202O
Thank you