The document discusses Good Laboratory Practice (GLP) standards which were mandated by the FDA and EPA in the 1970s after cases of laboratory malpractice and fraudulent research studies surfaced. GLP standards establish rules for conducting non-clinical safety studies submitted to regulatory agencies and help assure the quality and integrity of study data. Key aspects of GLP compliance include requirements for documentation, equipment calibration and maintenance, proper labeling and use of reagents and chemicals.

1. Good Laboratory Practice
ALS 5204
PRESENTED BY
JEAN COBB
SENIOR PROJECT ASSOCIATE
PESTICIDE RESIDUE LAB
BIOCHEMISTRY
For Field and
Laboratory Research

2. What are GLPs?
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

3. Key Dates
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

4. Where are the EPA GLP
Regulations Published?

5. National Archives and
Record Administration
Code of Federal Regulations (CFR)
Title 40 Protection of Environment (laws and
regulations of U.S. EPA)
Part 160: Good Laboratory Practice Standards,
Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA), Subparts A-J
Part 792: Good Laboratory Practice Standards,
Toxic Substances Control Act (TSCA), Subparts A-J
Note: FIFRA regulates pesticides and TSCA regulates
toxic substances

6. Why Were the GLPs
Mandated?
• In the 1970s, numerous cases of
laboratory malpractice surfaced in
toxicity testing of food and drugs
in the U.S.
• FDA inspectors found inaccurate,
sloppy, and fraudulent research
studies
• Became a public safety issue

7. One of the first names to attract regulatory
and media attention was IBT…
Illustration by Dan Sherbo©
IBT: Industrial Bio-Test Laboratories

8. Problems at Test Facilities
Many of IBT’s (Industrial Bio-Test Laboratories)
test animals were housed in a water-logged
room known as the Swamp.
“ During the course of a two-year feeding study,
involving more than 200 animals, the mortality
rate in the Swamp reached 80 percent. Dead
rats and mice…decomposed so rapidly in the
Swamp that their bodies oozed through wire
cage bottoms and lay in purple puddles on the
dropping trays.”
- The Amicus Journal, Spring 1983, p.14

9. Problems with Sponsors
G. D. Searle Co. (Pharmaceutical Manufacturer)
“…’Because of the perfunctory nature of the
observations, tissue masses come and go and
animals die more than once.’ In fact some
rats listed as dead later were recorded as alive,
then dead, then resurrected once or even twice
more.”
– The Impact of Publicity on Corporate Offenders, Ch. 12,
p. 138

10. The Regulatory Process
Before GLPs – Few “checks and balances”
Test
Facility
Industrial Bio-Test Laboratories (IBT), Craven
Labs, Intertek Testing Services, & others
Submits
Data Regulatory
Sponsor Approve?
Agency
(EPA, FDA)
Yes!
Permission to
Market Regulated
Product
No!
Permission to
Market Regulated
Product Denied
Searle Co.
ChemAgro
Monsanto
& others
Test Facility: Field and laboratory (contract) research facilities
Sponsor: Pharmaceutical and pesticide manufacturers

11. The Regulatory Process
Before GLPs – Few “checks and balances”
Test
Facility
Inaccurate, sloppy, and fraudulent science???
Submits
Data Regulatory
Sponsor Approve?
Agency
(EPA, FDA)
Yes!
Permission to
Market Regulated
Product
No!
Permission to
Market Regulated
Product Denied
Poor Management
Practices ????
Would you want the FDA to issue a permit to manufacture of a
drug based on sloppy research? Or for the EPA to register a
pesticide based on fraudulent data? Probably not!

12. What Role Do GLPs Play?
Good Laboratory Practice standards
help to assure the quality and integrity
of studies submitted in support of FDA
and EPA regulated products

13. Test
Facility
The Regulatory Process
After GLPs
Internal audits and inspections (conducted by
Quality Assurance Unit)
Submits
Data Regulatory
Sponsor Approve?
Agency
(EPA, FDA)
Yes!
Permission to
Market Regulated
Product
No!
Permission to
Market Regulated
Product Denied
External audits and
inspections of sponsor and
test facility (conducted by
regulatory agency)

14. GLP Regulations
Greater scrutiny of
field and laboratory
studies of regulated
products
Auditor/
Inspector

15. Who must comply with
GLPs?

16. FDA GLP Compliance
Required:
Pre-clinical safety studies for the development
of food additives and drugs (before a marketing
permit is issued)
Regulated products: Pharmaceuticals,
cosmetics, food & color additives, human
medical devices
Note: “pre-clinical” refers to safety testing in animals,
plants, or microorganisms (not humans)

17. EPA GLP Compliance
Required:
Field and laboratory studies of pesticides
(before a marketing permit or application for
research is issued)
Regulated products: Pesticides and other
substances that could spread during
agricultural practice

18. GLP Regulations: Rules and Tools
GLP Regulations (Rules) Documentation (Tools)
ORGANIZATION AND Training records, CVs, GLP training
PERSONNEL
FACILITY OPERATION Standard operating procedures
Chemical and sample inventory,
track expiration dates, labeling
TEST, CONTROL, AND
REFERENCE SUBSTANCES
Timely reporting, storage of raw
data and reports
RECORDS AND REPORTS
Calibration, logbooks of use, repair,
and maintenance; check freezers
EQUIPMENT
Maintain adequate space/separation
of chemicals from office areas
FACILITIES

19. Documentation
If you didn’t write it
down, it NEVER
happened. (As far
as an auditor is
concerned…)
Auditor/
Inspector

20. Equipment
40 CFR Part 160 (EPA GLP regulations)
“Section 160.63 Maintenance and Calibration
of Equipment. (a) “Equipment used in the
generation, measurement, or assessment of
data shall be adequately tested, calibrated,
and/or standardized. (c) Written records
shall be maintained of all inspection,
maintenance, testing, calibrating, and/or
standardizing operations….”
Do you know the difference between
standardized, calibrated, and verified?

21. Equipment
• Verification (Testing): external check of
equipment accuracy (check balance accuracy
against weights at laboratory- no adjustment)
• Calibration: equipment is adjusted based on
comparison to certified or known reference
materials (balance adjusted after comparison
to certified weights by trained professional)
• Standardization: comparison with similar
equipment (use two thermometers of similar
design to compare readings)

22. Equipment
What about validation?
• Electronic data management systems
(computers, instrumentation) must be
“validated” to confirm that they will perform
their intended functions
• For example, a computer spreadsheet used
for calculations during a GLP study could be
validated as follows: enter identical raw data
as previously and compare the calculations
using the same software/options- they should
be identical!

23. Use Logbooks
AGILENT GAS CHROMATOGRAPH SERIES: 6890n VT#0000322580
New glass N/A
insert & gold
seal 9/17/07
S.J.
He-carrier,
1.0 mL/min,
H2/Air det.
gases
RTX-OPP 60-275°C 225°C 300°C
(30 m x
0.25 mm x
0.25 μm)
Standards N/A NPD
only
Sally
Jones
(lab
tech)
9/17/07
• Record all pertinent operating parameters
• Take the time to record routine service and how
problems were resolved (it may help if/when the
same problem arises!)
Power
outage
caused GC
shutdown
He-carrier, N/A
2.3 mL/min,
N2 makeup
RTX-5 (30 90-275°C 250°C 350°C
m x 0.25
mm x 0.25
μm)
μECD
#8128/
μECD
#5663
(dual
column)
Plant
Tissue
VCE07-
021
Sally
Jones
(lab
tech)
9/14/07
Replaced He N/A
gas - VAC052
9/13/07
J.E.S.
He-carrier,
2.3 mL/min,
N2 makeup
RTX-5 (30 60-275°C 250°C 350°C
m x 0.25
mm x 0.25
μm)
μECD
#8128/
μECD
#5663
(dual
column)
VCE07- Water
020
John
Smith
(lab
tech)
9/13/07
PROBLEM
(#)
ROUTINE
SERVICE (#)
DET GAS mL/min
TEMP °c
INLET
TEMP °c
OVEN
TEMP °c
COLUMN
TYPE/ SIZE
DETECTO
R TYPE
SAMPLE
MATRIX
DATE NAME PROJECT

24. Equipment
• Was the equipment
functioning properly?
Who performed the
work, what was the
date, and what specific
parameters did they
use?
• What was there a
problem? How was the
problem fixed?

25. Reagents and Solutions
40 CFR Part 160 (EPA GLP regulations)
“Section 160.83 Reagents and Solutions. “All
reagents and solutions in the laboratory
areas shall be labeled to indicate identity,
titer or concentration, storage
requirements, and expiration date.
Deteriorated or outdated reagents and
solutions shall not be used.”
How do you know what expiration date to
use?

26. Reagents and Solutions
General expiration guidelines:
• Dry reagents: 5 years (unless reevaluated)
• Solvents: 1 year from date opened or 2 years
from date received
• Solutions: Use the earliest date of components
in the solution or no longer than 6 months
Question: Which takes precedence: the
manufacturer’s expiration date or expiration date
as stated in the facility SOPs?
Answer: Whichever is earliest!

27. Use Labels
• Clearly label chemicals
and solution containers
• Make sure that the
expiration date and
storage requirements are
included on the label
• If a solution, what date
was it prepared?
CHEMICAL LABEL
CHEMICAL___ ____________ ________
CHEM ID#______________________________ _
DATE RECEIVED:___________________________
DATE OPENED: ____________________________
EXPIRATION DATE__ _ _______STORAGE______
SOLUTION LABEL
CONCENTRATION_____________________
SOLUTION____________________________
FROM CHEM ID#_____________________
DATE PREPARED_____________________
EXPIRATION DATE______ STORAGE______

28. Use Forms
• Assign a unique number
to each chemical received
by the facility
• Record the purity, date
received, storage
conditions, and source
• Use the form to “jog your
memory” about the
information you need to
collect
PESTICIDE RESIDUE LABORATORY
2007 CHEMICAL INVENTORY FORM
LAB CHEMICAL ID (s): __C070014______________
CHEMICAL NAME: ethyl acetate
CAS NO.: 141-78-6
SOURCE: Fisher Scientific
LOT NO.: 067720
PURITY/GRADE: Pesticide Grade
QUANTITY RECEIVED: 4 L
EXPIRATION DATE: 9/7/12
STORAGE CONDITIONS: ambient, in solvent cabinet
DATE RECEIVED: 9/7/07
SIGNATURE: Jean M. Cobb
COMMENTS: N/A
DATE INSPECTED/METHOD: N/A
NEW EXP
DATE: N/A

29. Test, Control, &
Reference Substances
• Are the test, control, and
reference substances of
known quality and
purity?
• Are these substances
used within expiration
dates?
• Are they adequately
stored?

30. Raw Data
Question:
What happens if you
make a mistake?
Answer:
Do not obscure original data!! Instead, draw a
single strikeout, then add reason code, initials,
and date of change. (Preserve the original data).

31. Documentation
• Record data using permanent ink (never pencil)
• Date and sign every entry (who is responsible?)
• Keep records in “real time” (no catching up later)
• No rewrites, need original entries (reduces
transcription errors)
Documentation is important in all
sorts of situations!!

32. Raw Data
40 CFR Part 160 (EPA GLP regulations)
“Section 160.3 Definitions. “’Raw data’
means any laboratory worksheets,
records, memoranda, notes, or exact
copies thereof, that are the result of
original observations and activities of a
study and are necessary for the
reconstruction and evaluation of the
report of that study.”
If you scribble some notes on a scrap of paper, are
those notes considered raw data? Answer: Yes!

33. Raw Data
Can you list examples of raw data?
• Logbooks (to record temperatures or equipment use,
repair, and maintenance)
• Field or laboratory notebooks
• Forms (for field or laboratory observations, chain-of-custody,
sample or chemical receipt)
• Training reports
• Computer printouts
• Recorded data from automated instruments

34. How can anyone remember
all these details?
Answer: You don’t have to… that’s one of
the functions of the Standard Operating
Procedures (SOPs).

35. Write Standard Operating
Procedures (SOPs)
SOPs are written, approved procedures
that describe routine activities that are
specific for daily operations at each facility.
SOPs should allow appropriately qualified
personnel to perform a procedure once
trained.

36. Standard Operating
Procedures
40 CFR Part 160 (EPA GLP regulations)
“Section 160.81 Standard operating
procedures. (a) A testing facility shall have
standard operating procedures in writing
setting forth study methods that
management is satisfied are adequate to
insure the quality and integrity of the data
generated in the course of a study.”
Personnel perform the same tasks using the
same procedures.

37. SOP Writing Guidelines
• SOPs should accurately reflect how routine
tasks are performed (written by each facility
based on their specific field and/or laboratory
operations)
• Make sure they are useful in daily operations
• They should be scientifically sound
• Remember to update as necessary, rewrites
are part of the process

38. Writing Guidelines
Cautions:
• Avoid restrictive language such as “vortex
for exactly 1 minute” but include clear
instructions such as “vortex until
homogenized” if that satisfies the purpose
• Don’t add unnecessary steps such as
“consult the manual” unless personnel are
required to follow this step

39. Writing Guidelines
The primary goal is to avoid confusion…
Did your supervisor say to make a 1 in 4
dilution… or was it a 1 to 4 dilution?
If it is written in an SOP, the instructions
can be verified.

40. What if you don’t have
to comply with GLP
regulations?

41. GLP Compliance
Not Required:
• Basic research (most of the research
conducted at universities like Virginia Tech)
• Studies to develop new analytical methods
• Chemical tests used to derive the specifications
of a marketed food product
• Instead, “emphasize GLP principles” during
research

42. GLP Principles
GLP principles are a good idea even if
you are not required to comply with the
regulations.
• Say What You Do (with written standard
operating procedures)
• Do What You Say (follow the
procedures)
• Be Able to Prove It (with good record
keeping)

43. Is GLP Experience
Important to Employers?
Yes! In some cases…

44. GLP Experience
An employer may find it useful if you have:
• Practical experience with working on a
study conducted in compliance with GLP
regulations
• Experience working at a facility that
emphasizes GLP principles
• Familiarity writing and using standard
operating procedures at a GLP facility

45. Why Do We Need GLPs?
• Everyone makes mistakes
• Mistakes cost $$$
• Increasing the quality of an
operation is good for business and
science

46. What GLPs SOPs Can’t Do
• Guarantee “good science”
• Guarantee good documentation
• Replace common sense
• Prevent all mistakes

47. What GLPs Can Do
• Fulfil the legal requirements of
some FDA and EPA research studies
• GLP principles can be followed to
increase the quality of basic research

48. Websites
• Code of Federal Regulations (CFR)- all
• EPA GLP Regulations
• FDA GLP Regulations
• USDA- Pesticide Data Program (PDP)
Standard Operating Procedures