Research

1. By:
Mr. Gunjan Srivastava
Associate Professor

2.  Medical Testing Laboratory
patient care
clinical drug trial
 Research Laboratory
discovery & development of new
drugs/therapy
fundamental research/mechanisms of
diseases
 Manufacturing
post clinical trials, bulk drugs, cell-based
therapy, plasma products, medical device

3.  Stage I Stage 2 Stage 3 Stage 4
Discovery Non-clinical Clinical Post-approval
Manufacturing
Time line approximately 10 yrs

4. Stage I : discovery of active substance
Stage II : non-clinical study on SAFETY
testing of drugs ,
Stage III : Studies in human/CLINICAL
TRIALS
Stage IV : Post approval Clinical trials

5.  Pre Study
 During Study
 End of Study
 Screening
 Enrolment : inclusion
criteria exclusion
Verify effects of drugs
clinical efficacy
 Monitoring of adverse
effects safety
 Clinical efficacy
 Data analysis
 verification

6.  safety testing of drugs ,
 toxicology,
 mutagenicity,
 safety pharmacology
 bioavailability

7. Numerous meanings depending on :
Research Laboratory
Sponsor
Regulatory body
Clients of Laboratory

8.  Regulatory Authorities responsible for registering and
controlling pharmaceuticals request :
laboratory to demonstrate data in registration
package for a new chemical/drugs has been gathered
using ‘good laboratory practice’
require organisation be certified (or accredited) by a
third party for ‘GLP’
 Organisations (researchers and medical laboratories)
often claimed that they are working under ‘glp’
 Clients of laboratories often request that their work be
done using ‘good laboratory practice’

9.  Apply when a non-clinical laboratory study
(e.g. Pre-Clinical animal testing) is intended
to support an application for an FDA-
regulated product.
 GLP is an FDA regulation.
 GLP embodies a set of principles that
provides a framework within which laboratory
studies are planned performed, monitored,
reported and archived.
 GLP describes good practices for non-clinical
lab studies that support research or marketing
approvals for FDA-regulated products.

10.  GLP is a formal regulation that was
created by the FDA (United states
food and drug administration) in
1978.
 Although GLP originated in the
United States , it had a world wide
impact.
 Non-US companies that wanted to
do business with the United states
or register their pharmacies in the
United States had to comply with the
United States GLP regulations.
 They eventually started making GLP
regulations in their home countries.
 In 1981 an organization named
OECD (organization for economic
co-operation and development )
produced GLP principles that are
international standard.

11. 1976 GLP guideline proposed
1978 GLP guideline finalised
1979 GLP guidelines effective
1987 additional changes ( Code of
Federal Regulation 21, part 58)
2000 : International GLP

12. 1970 1976 FDA GLP proposed
1978 FDA GLP regulations published
1980 1982 OECD GLP published (30 countries incl. U.S.),
UK GLP published, Japanese GLP published
1983 EPA GLP regulations published
1986 FDA GLP revised, European Union GLP
Directives
1989 EPA GLP revised
1990 1998 OECD GLPs revised, Canadian PMRA
adopted GLPs
2000 2002 OECD consensus document
2007 EPA may consolidate two parts of EPA GLPs

13.  In the early 70’s FDA became
aware of cases of poor laboratory
practice all over the United States.
 FDA decided to do an in-depth
investigation on 40 toxicology labs.
 They discovered a lot fraudulent
activities and a lot of poor lab
practices.
 Examples of some of these poor
lab practices found were
1. Equipment not been calibrated to
standard form , therefore giving
wrong measurements.
2. Incorrect/inaccurate accounts of
the actual lab study
3. Inadequate test systems

14.  One of the labs that went under
such an investigation made
headline news.
 The name of the Lab was Industrial
Bio Test. This was a big lab that ran
tests for big companies such as
Procter and Gamble.
 It was discovered that mice that
they had used to test cosmetics
such as lotion and deodorants had
developed cancer and died.
 Industrial Bio Test lab threw the
dead mice and covered results
deeming the products good for
human consumption.
 Those involved in production,
distribution and sales for the lab
eventually served jail time.

15. Good Laboratory Practice standards
(GLPs) are federal regulations
mandated in the United States by:
• Food and Drug Administration (FDA)
in 21 CFR Part 58
• Environmental Protection Agency (EPA)
both for FIFRA in 40 CFR Part 160 and for
TSCA in 40 CFR Part 792

16.  GLP = Good Laboratory Practice
GLP is a quality system concerned with the
organizational process and the conditions under
which non-clinical health and environmental
safety studies are planned, performed,
monitored, recorded, archived and reported.
 OECD Principles on Good Laboratory Practice
 What is the OECD?

17. They are NOT
ideas
They are NOT
governmental
philosophy
They are NOT
guidelines

18.  GLPs deal with:
• Planning
• Performance
• Monitoring
• Recording
• Reporting
 GLPs do not:
 Attempt to
regulate science
 Ensure
“good science”

19. Responsibility for establishing the safety
and efficacy of human and veterinary
drugs and devices, and the safety of food
and color additives is placed on the
sponsor (manufacturer) of the regulated
product.

20. Public agencies (FDA, EPA, OECD, etc) are
responsible for reviewing the sponsor’s test
results and determine if they demonstrate the
product’s safety and efficacy.
Only when the agencies are satisfied that
safety and efficacy have been established
adequately is the marketing of the product
permitted.

21.  In vivo or in vitro experiments in which test articles
are studied prospectively in test systems under
laboratory conditions to determine their safety. The
term does not include studies utilizing human
subjects or clinical studies or field trials in animals.
The term does not include basic exploratory studies
carried out to determine whether a test article has
any potential utility or to determine physical or
chemical characteristics of a test article.
• 21 CFR Part 58.3(d)

22. GLP is needed for: GLP is not needed for:
•Nonclinical safety studies of
development of drugs
•Agricultural pesticide
development
•Development of toxic
chemicals
•Food control (food additives)
•Test of substance with regard
to explosive hazards
•Basic research
•Studies to develop new
analytical methods
•Chemical tests used to
derive the specifications of a
marketed food product

23.  Purpose of GLPs: assure the quality &
integrity of data submitted to FDA in support
of the safety of regulated products
 GLPs have heavy emphasis on data
recording, record & specimen retention
 Requires each study to have a study director
 Study director: ultimate responsibility for
implementation of the protocol & conduct of
the study

24. Covers all nonclinical laboratory studies
Food & color additive petitions, NDA &
NADA
Toxicity studies (in vitro & in vivo)
Excluded: human subject trials, clinical or
field trials in animals, basic exploratory
studies

25.  Sponsor: person who initiates & supports
nonclinical laboratory study, a person who
submits nonclinical study to FDA or testing
facility that initiates & conducts the study
 Testing facility: person who actually
conducts a nonclinical laboratory study
 Test system: any animal, plant, or
microorganism to which test or control article
is administered

26.  Specimen: any material derived from a test
system for examination or analysis
 Raw data: any laboratory work sheets,
records, memoranda, notes or copies that are
result of original observations
 Quality assurance unit: monitor study
conduct
 Study director: individual responsible for the
overall conduct of a nonclinical laboratory
study

27.  formulated the first worldwide OECD Principles
of GLP 1981 ( revised in 1997)
 Intergovernmental organization
 30 industrialized countries
 Meet to co-ordinate and harmonize policies.
 Discuss issues of mutual concern
 Work together to respond to international
problems.
 Eliminate unnecessary duplication of
experiments

28. 1. Australia
2. Austria
3. Belgium
4. Canada
5. Czech
Republic
6. Denmark
7. Finland
8. France
9. Germany
10. Greece
21. Poland
22. Portugal
23. Slovak Republic
24. Spain
25. Sweden
26. Switzerland
27. Turkey
28. UK
29. USA
30. Norway
11. Hungary
12. Iceland
13. Ireland
14. Italy
15. Japan
16. Korea
17. Luxembourg
18. Mexico
19. Netherlands
20. New Zealand

29.  1981, Member countries
(31 member countries)
 1997, Non-member
countries, full adherence
(4)
 Non-member countries/
Provisional
 Mutual Acceptance of
data
 Compliance programme
 Compliance programme
Malaysia launched in 2009
if full adherence GLP safety data
will be accepted by members
(31) & non-members (4)

30. OECD Principles of GLP: No.1
Guidance Documents for Compliance
Monitoring Authorities : No.2, 3 & 9
Consensus Documents : No.5-8, 10 & 13
Advisory Documents of the Working Group
on GLP : No.11, 12 & 14
http://www.oecd.org

31.  GLP makes sure that the data submitted
are a true reflection of the results that are
obtained during the study.
 GLP also makes sure that data is
traceable.
 Promotes international acceptance of
tests.
 to promote the development of quality and
validity of test data used for determining
the safety of chemicals and chemicals
product.

32. Study Integrity
-Reconstruction
-Proper data acceptance/rejection
Research Integrity
-Training of personnel
-Responsibilities
-Record security
-Checks and controls
-Confidentiality
Data Integrity
-Accuracy
-Completeness
-Consistency

33. Data points
Each non-clinical study
The regulatory submission
The work/career of an investigator
All of the research conducted at a laboratory
Public health, safety and confidence in scientific research

34.  GLP should be applied to the non-clinical safety
testing of test items:
 Pharmaceutical product
 Pesticides product
 Cosmetic product
 Food additives
 Feed additives
 Industrial chemical
in the Laboratory, in greenhouses or in the field

35. Good Laboratory Practice applied in whatever
industry targeted, stresses the importance of the
following main points
 Resources : Organisation, personnel, facilities,
equipment
 Rules : Protocols, Standard Operating Procedures,
concept of Study Director
 Characterisation : Test items, test systems
 Documentation : Raw data, final report, archives
 Quality Assurance : Independence from study conduct

36.  Test systems
 Archiving of records and materials.
 Apparatus, material and reagent facilities.
 Quality assurance programs.
 Performance of the study.
 Reporting of study results.
 Standard operating procedures (SOP)
 Personnel and test facility organization

37. Physico-chemical properties
Toxicological studies designed to evaluate
human health effects
Ecotoxicological studies designed to
evaluate environmental effects
Ecological studies designed to evaluate
environmental chemical fate (transport,
biodegradation, and bioaccumulation)