Good Laboratory Practices (GLP) History Reason behind GLP created Advantages and disadvantages of GLP Objectives of GLP Practice of GLP b pharma 6th sem pharmaceutical quality assurance

1. Good Laboratory Practices
(GLP)
Himanshu Kamboj
Assistant Professor

2. Contents
 Good Laboratory Practices (GLP)
 History
 Reason behind GLP created
 Advantages and disadvantages of GLP
 Objectives of GLP
 Practice of GLP

3. GLP: GOOD LABORATORY
PRACTICE
 GLP is an FDA regulation.
 Definition: GLP embodies a set of principles that
provides a framework within which laboratory studies are
planned performed, monitored, reported and archived.
 GLP is sometimes confused with the standards of
laboratory safety like wearing safety goggles.
 GLP help assure regulatory authorities that the data submitted are a
true reflection of the results obtained during the study and can
therefore be confidence upon when marking risk/safety assessment.

4. HISTORY
 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.
 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”.

5. REASON BEHIND GLP CREATED
 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

6. FAMOUS EXAMPLE
 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.

7. ADVANTAGES OF GLP
 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.

8. OBJECTIVES OF GLP
 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.

9. PRACTICE OF GLP
 General provisions
 Organization and Personnel
 Facilities
 Equipment
 Testing facilities operation
 Test and control articles
 Protocol for and the conduct of the study
 Records and Reports

10. General provisions
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.

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

12. Organization-Functions
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.
4) Coordinate the work of internal departments and outside
agencies

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

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

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.

16. Quality Assurance Unit
1) An individual or a group designated by management to assure
that the studies are in compliance with GLP principles.
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.

17. Quality Assurance Unit
6) 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
7) Determines any deviation from the approved protocol and report
to SD,PI and management.
8) Prepare statements to be included in the final report containing
dates and types of inspection.

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

19. General facilities
 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.
 Archive facilities- Secure storage and retrieval of study plans, raw
data, final report and specimens to prevent untimely deterioration.
 Waste disposal- Appropriate collection, storage and disposal
facilities and decontamination procedures.

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.

21. D. Equipment
1) Appropriate design and adequate capacity.
2) Equipment shall be adequately inspected, cleaned and
maintained.
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

22. MISSION OF GLP
 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

23. Standard Operating Procedures (SOP)
 Written procedures for a laboratories program.
 They define how to carry out protocol-specified activities.
 Most often written in a chronological listing of action steps.
 They are written to explain how the procedures are suppose to work

24. SOP
 Routine inspection, cleaning, maintenance, testing and calibration.
 Actions to be taken in response to equipment failure.
 Analytical methods
 Definition of raw data
 Keeping records, reporting, storage, mixing, and retrieval of data

25. Statistical Procedures for Data
Evaluation
 Statistical procedures are not simply chosen from a text book
 Practitioners in a particular field may adopt certain standards which
are deemed acceptable within that field.
 Regulatory agencies often describe acceptable statistical procedures.

26. Instrumentation Validation
 This is a process necessary for any analytical laboratory.
 Data produced by “faulty” instruments may give the appearance of
valid data.
 The frequency for calibration, re-validation and testing depends on
the instrument and extent of its use in the laboratory.
 Whenever an instrument’s performance is outside the “control
limits” reports must be discontinued

27. Instrument Validation (cont)
 Equipment records should include:
 Name of the equipment and manufacturer
 Model or type for identification
 Serial number
 Date equipment was received in the laboratory
 Copy of manufacturers operating instruction (s)

28. Reagent/ Materials Certification
 This policy is to assure that reagents used are specified in the
standard operating procedure.
 Purchasing and testing should be handled by a quality assurance
program.

29. Reagents and Solutions
 Requirements:
 Reagents and solutions shall be labeled
 Deteriorated or outdated reagents and solutions shall not be used
 Include Date opened
 Stored under ambient temperature
 Expiration date

30. Analyst Certification
 Some acceptable proof of satisfactory training and/or competence
with specific laboratory procedures must be established for each
analyst.
 Qualification can come from education, experience or additional
trainings, but it should be documented
 Sufficient people
 Requirements of certification vary

31. Laboratory Certification
Normally done by an external agency evaluation is
concerned with issues such as
 Adequate space
 Ventilation
 Storage
 Hygiene

32. Specimen/Sample Tracking
 Vary among laboratories
 Must maintain the unmistakable connection between a set of
analytical data and the specimen and/or samples from which they
were obtained.
 Original source of specimen/sample (s) must be recorded and
unmistakably connected with the set of analytical data.

33. Documentation and Maintenance
of Records
 Maintenance of all records provide documentation which
may be required in the event of legal challenges due to
repercussions of decisions based on the original analytical
results.
 General guidelines followed in regulated laboratories is to
maintain records for at least five years
 Length of time over which laboratory records should be
maintained will vary with the situation

34. Good Documentation
Practice
 Documentation should permit the complete
reconstruction of a study
 Record data directly, promptly and legibly in indelible
ink (never pencil)
 Initial and date all observations and any resulting
changes, but do not obscure original data
 Initial and date only work you’ve performed
 Do not document selectively or in advance of
performing the activity

35. Good Documentation Practice
 Do not use white-out correction fluid or tape
 Do not use ditto marks as raw data
 Copy all heat sensitive paper and stamp “exact
copy”
 Explain why any raw data was not used
 Verify critical calculations using a second person
and document this
 Notebook pages requiring a second signature
shall be completed with that signature

36. Good Documentation Practice
 Properly head all pages, tables, columns; identify
units
 Describe Statistical & Calculation Procedures used
 Sign, Date, and File automated printouts (e.g., QC
forms)
 Retain all Raw Data (original records) in the Study
File
 Do not document by exception. Use positive
documentation, even if only a check mark.

37. Good Documentation
Practice
 Documentation must allow another person to
be able to accurately reconstruct what you
have done
 Keep all original observations including those
observations recorded directly into a
computer
 Sign and date all computer printouts
 Never back-date anything
 Follow SOPs and Protocol

38. Good Documentation
Practice
 Document all deviations with accompanying
explanations
 Indicate in the record all applicable units and
equipment used

39. Important questions to be answered for any
analytical instrument
 What is the equipment being used for?
 Is the instrument within specification and is the
documentation to prove this available?
 If the instrument is not within specifications, how
much does it deviate by?
 If the instrument is not within specifications what
action has been taken to overcome the defect?
 Can the standards used to test and calibrate the
instrument be traced back to national standards?

40. What happens if a workplace
does not comply with federal
Good Laboratory Practice
standards?

41. Disqualification of a Facility
 Before a workplace can experience the consequences of
noncompliance, an explanation of disqualification is needed
 The FDA states the purpose of disqualification as the exclusion of a
testing facility from completing laboratory studies or starting any
new studies due to not following the standards of compliance set by
the Good Laboratory Practice manual

42. Possible Violations
 Falsifying information for permit, registration or any required
records
 Falsifying information related to testing~ protocols, ingredients,
observations, data equipment, ect.
 Failure to prepare, retain, or submit written records required by law

43. Grounds for Disqualification
 The testing facility failed to comply with one or more regulations
implemented by the GLP manual
 The failure to comply led to adverse outcomes in the data; in other
words, it affected the validity of the study
 Warnings or rejection of previous studies have not been adequate
to improve the facility’s compliance

44. Consequences of Noncompliance
The FDA states the following consequences of
noncompliance:
 The commissioner will send a written proposal of
disqualification to the testing facility A regulatory
hearing on the disqualification will be scheduled
 If the commissioner finds that after the hearing, the
facility has complied, then a written statement with an
explanation of termination of disqualification will be
sent to the facility.
 Thus, if it can be shown that such disqualifications did
not affect the integrity and outcome of the study itself,
or did not occur at all, then the study may be reinstated
at the will of the commissioner

45. Upon Disqualification…
 If the commissioner finds that the facility was
noncompliant on any of the grounds after the hearing,
then a final order of noncompliance will be sent to the
facility with explanations
 If a testing facility has been disqualified, any studies
done before of after the disqualification will need to be
determined as essential to a decision (acceptable or not)
 If the study is determined unacceptable, then the facility
itself may need to show that the study was not affected
by the noncompliance that led to the disqualification
 Once finally disqualified, the facility may not receive or
be considered for a research or marketing permit and
the study is rejected.

46. Upon Disqualification…
 The commissioner may notify the public and all
interested persons, including other federal agencies the
facility may have contacted
 The FDA may ask the other agencies to consider whether
to support the facility or not under the disqualification
 Civil or criminal proceedings may occur at the discretion
of the commissioner
 Fines of up to $50,000 if one knowingly commits crime and/or
1 year imprisonment~ for registration applicants and
producers
 Fines up to $5,000 all others~ civil penalty after failing to
improve after a minor violation warning was issued~ only
those involved in testing will be given civil penalties
 Those involved in the distribution or sales will be assessed
more heavy penalties, such as criminal penalties

47. Upon Disqualification…
 The FDA may turn it over to the federal, state or local law
enforcement
 The facility’s sponsor may terminate or suspend the facility from
doing any non- clinical study for a permit
 The sponsor is required to notify the FDA in writing within 15
working days that the facility is to be suspended or terminated
and why

48. Reinstatement of a Disqualified
Facility
 The testing facility may be reinstated as
acceptable non-clinical study to be turned into
the FDA if the commissioner can be certain that
future studies will be conducted in compliance
with the Good Laboratory Practice standards and
that any current studies integrity have not been
severely harmed by the disqualification
 The disqualified facility will be required to put in
writing to the commissioner reasons why it
should be reinstated and any actions the facility
will take or have taken to assure any
disqualification problems will not happen again

49. Reinstatement of a Disqualified
Facility
 The commissioner will inspect the facility and determine if it shall be
reinstated
 If it is reinstated, the commissioner is required to notify all persons
that were notified of the disqualification including the facility itself

50. THANK YOU