B.PHARM VI SEM

1. GOOD LABORATORY PRACTICE
By
BALASUNDARESAN M
MBS 1

2.  In the early 70’s FDA became aware of cases of poor laboratory
practice all over the United States.
 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.
GLP was first introduced in New Zealand and Denmark in 1972, and later in
the US in 1978 in response to the Industrial Bio Test Labs scandal.
MBS 2

3. Therapeutic
concept
Target
validation
Lead
finding
Target
selection
Lead
optimization
Preclinical
development
Clinical
development
Regulatory
approval
Product
Registration
Discovery
3
Development
Drug Discovery and Development Process
MBS 3

4. Good Laboratory Practice (GLP)
4
 GLP is a formal regulation created by USFDA as these regulations
were proposed on November 19,1976 and designated as a new part
of Chapter 21 of the Code of Federal Regulations(CFR) as 21 CFR
Part 58 in 1979.
 In 1981 an organization named OECD(Organization for
Economic Cooperation and Development) produced GLP
principles that are international standards.
 GLP in OECD principles is defined as “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”.
MBS 4

5. Why GLP was
created?
1) GLPs were initially invoked in a reaction to malpractices in the
laboratories conducting safety experiments of medicines.
2) In the early 1970s,research laboratories in the USA found doing
work in unethical ways ,like:
 Data generation without conduct of the study.
 Falsification of the laboratory work.
 Replacement of dead animals and fabrication of test results etc.
5
MBS 5

6. Advantages ofGLP
 Assures that the data are a true reflection of results obtained from
studies.
 Preclinical safety and residue safety.
 Generation of high quality and reliable test data.
 Mutual acceptance of data
 Increases public confidence.
 Shortens the time-to-market for new products.
Disadvantages of GLP
 More man power is required.
 Expensive process.
 Time consuming process. 6
MBS 6

7. Objectives of GLP
1) GLP makes sure that the data submitted are true reflection of the
results obtained from the studies.
2) GLP makes sure that the data is traceable.
3) Promotes international acceptance of tests.
7
MBS 7

8. GLP
Principles
Testing
facility
organization
and
personnel
Storage
and
retention
of records
and
materials
Reporting
of study
results
Quality
assurance
program
Facilities
Apparatus,
materials
,reagents
Test
systems
Test and
reference
substances
Standard
operating
procedures
Performance
of study 8
MBS 8

9. How to practice GLP?
9
A. General provisions
B. Organization and Personnel
C. Facilities
D. Equipment
E. Testing facilities operation
F. Test and control articles
G. Protocol for and the conduct of the study
H. Records and Reports
MBS

10. A. General provisions
10
1) It prescribes GLP for conducting non-clinical laboratory studies
that support research and marketing permits of products
regulated by FDA.
2) Applicability to studies performed under grants and contracts.
3) Inspection of the testing facility.
MBS

11. B. Organization and Personnel
11
1) Organization
2) Personnel
3) Testing facility management
4) Study director
5) Quality assurance unit
MBS

12. Organization-Functions
4) Coordinate the work of internal departments and outside agencie1s0.
1) Identification of quality activities.
2) Dividing the jobs among the personnel.
3) Define the authority and responsibility of each job and
relationship of each job with other jobs.
MBS 12

13. Personnel
Each individual engaged in the conduct or supervision of non-
clinical laboratory study shall have:
1) Education
2) Training:
a) General training
b) Specific training
3) Experience or combination
4) Personal sanitation and health precautions 13
MBS 13

14. Testing facility management
1) A sufficient number of qualified personnel, appropriate facilities,
equipment and materials are available for conductance of the
study.
2) Maintenance of records of qualifications, training and experience
of personnel and their job description.
3) Appointment of study director.
4) Quality assurance program with designated personnel. 14
MBS 14

15. Study Director
A scientist or other professional of appropriate education , training
and experience.
Responsibilities of the study director are:
1) Approval of protocol and study plans including amendments.
2) Technical conduct of the study.
3) Ensure that the QA personnel and study personnel are updated
with the study plan and SOPs.
4) Interpretation, analysis, documentation and reporting of the
results.
5) Also checks that experimental data is accurately recorded and
verified.
6) Sign and date the final report for acceptance of data.
15
MBS 15

16. QualityAssuranceUnit
1) An individual or a group designated by management to assure
that the studies are in compliance with GLPprinciples.
2) Monitors the study to assure management that the facilities ,
equipment, personnel, methods, practices, records and controls
are in conformance with the regulations.
3) Maintain the copies of master schedule sheet, protocol and
SOPs.
4) Access to updated study plans and SOPs.
5) Documented verification of compliance of the study with GLP
principles.
16
MBS 16

17. Cont.…
5) Inspections to determine the compliance of the study with GLP
principles and three type of inspections are:
a) Study based inspections
b) Process based inspections
c) Facility based inspections
6) Determines any deviation from the approved protocol and report
to SD,PI and management.
7) Prepare statements to be included in the final report containing
dates and types of inspection. 17
MBS 17

18. C. Facilities
18
1) General facilities:
a) Testing system facilities
b) Archive facilities
c) Waste disposal
2) Animal care facilities
MBS

19. General facilities
19
a) Testing system facilities
Suitable size, construction and location.
Adequate degree of separation of different activities.
Laboratories should be well ventilated, free of dust, drafts and
extreme temperatures.
Minimum 150sq.feet of floor space and minimum 6 linear feet of
usable bench space should be provide for each analyst.
b) Archive facilities- Secure storage and retrieval of study plans,
raw data, final report and specimens to prevent untimely
deterioration.
c) Waste disposal- Appropriate collection, storage and disposal
facilities and decontamination procedures.
MBS

20. Animal care
facilities
1) Located away form testing laboratories preferably in a separate building.
2) Contamination risk is reduced by “barrier” system ,as well as by providing
“clean” and “dirty” corridors .
3) Separate areas for animals of different species and studies.
4) Separate areas for diagnosis, treatment and control of laboratory animal
diseases.
5) Lightening should be proper as light intensity and noise level is sufficient.
6) Maintain room temperature, humidity and air changes in animal quarters.
20
MBS 20

21. D. Equipment
1) Appropriate design and adequate capacity.
2) Equipment shall be adequately inspected,
maintained.
cleaned and
3) Equipment used for generation, measurement or assessment of
data shall be adequately tested, calibrated and standardized.
4) Log books for each equipment should be there.
21
MBS 21

22. E.Testing FacilitiesOperation
1) Standard operating procedures(SOPs)
2) Reagents and solutions
3) Animal care
22
MBS 22

23. StandardOperating Procedures (SOPs)
• reference items, apparatus, materials and reagents, record
keeping, reporting, storage and retrieval, test systems and quality
assurance procedures.
4) Any deviation from SOP should be authorized by SD and
documented in the raw data.
1) Written documents specifying procedures for laboratories
programs.
2) Testing facility should have a written SOP approved by
management.
3) SOPs should be available wherever applicable e.g. test and
5) Routine inspection, cleaning, maintenance,
calibration.
6) Actions to be taken in response to routine failure.
testing and
MBS 23

24. Reagents and
solutions
1) Reagents used in the operation should be specified in the SOPs.
2) Reagents and solutions should be labeled.
3) Deteriorated or outdated reagents and solutions should not be used.
4) Store under ambient temperature. 24
MBS 24

25. Animal care
25
1) SOPs - for housing, feeding, handling and care of animals.
2) Animals should be free of any disease and if, during the course
of study, animals contract a disease then the diseased animals
shall be isolated.
3) Diagnosis, authorization of treatment, description and date of
treatment shall be documented and retained.
4) Animals of different species shall be housed in separated rooms
when necessary.
5) The animal cages, racks and accessory equipment shall be
cleaned and sanitized at appropriate intervals.
MBS

26. F.Test and ControlArticles
26
1) Test and control article characterization
2) Test and control article handling
3) Mixture of articles with carriers
MBS

27. Test and control article characterization
1) The identity, strength, purity and composition or other
characteristics of test and control article shall be determined and
documented for each batch.
2) Methods of synthesis, fabrication or derivation shall be
documented by the sponsor or the testing facility.
3) Stability of each test and control article is determined.
4) Storage conditions are maintained and each storage container
shall be labeled by name, chemical abstract number or batch
number.
27
MBS 27

28. Test and control article handling
28
Handling procedures of test and control articles ensures:
1) Proper storage.
2) Minimum risk of contamination and deterioration or damage.
batch
3) Receipt and distribution of each batch is documented.
4) Documentation include date and quantity of each
distributed or returned.
MBS

29. Mixture of articles with carriers
29
1) Appropriate analytical methods shall be conducted for
determination of uniformity of mixture and concentration of test
or control article in mixture.
2) Stability of mixture is determined.
3) Expiration date should be written on the container.
MBS

30. G. Protocol for and conduct of a
nonclinical laboratory study
30
1) Protocol
2) Conduct of a nonclinical study
MBS

31. Protocol
Contents of protocol
1.Identification
2.Title and statement of purpose
3.Identification of test(or control) items
4.Names and address of the sponsor, test facility and test site
5.Name of the study director and other personnel
6.Proposed dates
7.Justification for selection of the testsystem
8.Description of the test system
9. Experimentaldesign
31
MBS 31

32. Conduct of a nonclinical
laboratory study
32
1) Study shall be conducted in accordance with the protocol.
2) Information of the specimens should be present on the container
to avoid error in recording and storage of data.
3) All the data generated shall be recorded directly, promptly and
legibly by ink.
MBS

33. H. Records and Reports
33
1) Reporting of nonclinical laboratory results
2) Storage, retrieval and retention of records and data
MBS

34. Reporting of nonclinical laboratory
study results
34
Final report shall contain:
1) Information on sponsor and test facility.
2) Experimental starting and completion dates.
3) Objectives and procedures stated in protocol(including the changes
in protocol).
4) Description of materials and test methods.
5) A Quality Assurance Programstatement.
6) Storage(specimens, reference items, raw data and final report).
MBS

35. Storage, retrieval and retention
of records and data
1) Archives should be there for orderly storage and expedient of all
raw data, documentation, protocols, specimens and final reports.
2) Index of materials retained.
3) Master schedule sheet, copies of protocols and records of
Quality Assurance inspections shall be maintained by QAU.
4) Wet specimens and samples of test and control articles shall be
retained until the quality of preparation affords evaluation.
5) If any study plan is disposed of before expiry the reason to be
justified and documented. 35
MBS 35

36. Conclusion
36
GLP is a FDA regulation which is accepted and approved as
international standards by OECD to avoid fraud activities of the
testing laboratories for pharmaceuticals to save human and
environmental health.
Gives better image of company as a Quality producer in global
market.
Also it establish good relationship among the countries.
MBS

37. References
37
1.Rang HP. The drug discovery process: general principles and some
case histories. Drug Discovery and Development. 1sted. London:
Elsevier; 2006.p.43
2.Agrawal DK, Arevalo M, Bhalla S, Chai D, Gamaniel KS et al.
Introduction to the WHO/TDR Handbook on GLP. Handbook Good
Laboratory Practice(GLP). 2nded. Switzerland: TDR Publications;
2001.p.1-7
3.Huber L. Introduction to GLP/cGMP basics. A primerGood
laboratory practice and current good manufacturing practice.
Germany: Agilent Technologies;2000-2002.p.3-31
MBS

38. Cont.…
4.Seiler JP. Excerpts from the United States food and drug agency
good laboratory practice for nonclinical laboratory studies 21 code
of federal regulations part 58. good laboratory practice-the why and
the how. 2nded. New York: Springer-Verlag berlin Heidelberg;
2005.p.312-328
5.Sharma PP. Practice of GLP. How to practice GLP. 1sted. Delhi:
Vandana publications; 2000.p.214-309
6.Agrawal DK, Arevalo M, Bhalla S, Chai D, Gamaniel KS et al.
Good Laboratory Practice training. Handbook Good Laboratory
Practice(GLP). 2nded. Switzerland: TDR Publications; 2001.p.9-56
38
MBS

39. MBS 39