Asia Pesticide Residue Mitigation through the Promotion of Biopesticides and Enhancement of Trade Opportunities (APRMP), Virtual lab meeting 14 August 2020

1. GLP TRAINING
 Wayne Jiang, PhD
IR-4, Michigan State University, jiangwa@msu.edu
 Michael Braverman, PhD
IR-4 Headquarters, Rutgers University
Raw Data and Records

2. Review
• LOD / LOQ / LLMV
• GLP Standards required
• Enforcement method, reference method
• MV, SS (Triplicates)
• Document approval from SD
• Major changes, minor changes
• Calibrating balances, calibration pipets
• Sets, Sequence/Worklist
• Double injection, linearity
• Bracketing residue ranges
• Data acceptance criteria

3. True or False
A change in extraction method from
homogenizing (high speed blending) to
QuEChERS is a minor change.
A change in extraction solvent from acetonitrile
to acetone is a major change.

4. True or False
A change in analytical instrument from
HPLC/UV to LC/MS/MS is considered to be a
minor change. Therefore, SD does not have to
approve it.
Using a grade ‘A’ glass volumetric pipet is
accurate. It is not necessary to calibration it
before spiking MV samples.

5. True or False
Raw data should contain the signature/initial of
the user and the time when entry was made.
A change in entries shall be made so as not to
obscure the original entry, shall indicate the
reason for such change, and shall be dated and
signed or identified at the time of the change.

6. Q & A
When the GLP ‘clock’ starts in a pesticide
analytical lab?
A. SD signs the protocol
B. Analytical reference standard is received
C. The date of the first application is performed in the field
D. First field sample is received by lab
E. MV is completed and SD approves to start sample
analysis

7. Q & A
Which sample is in required in an analytical set
for analysis ? (select all correct answers)
(A) Control sample (untreated)
(B) Fortified sample (QC)
(C) Calibration standards
(D) Solvent blank

8. Q & A
Which of the following lab records are raw
data ? (Select all correct answers.)
(A) Laboratory worksheets
(B) Exact copies of protocols
(C) Memoranda
(D) Balance logs
(E) Phone log

9. Q & A
Which of the following are general
practices in IR-4 laboratories for their data
acceptance? (Select all correct answers.)
(A) Spike recovery 70-120%
(B) Double injection on weathered samples
(C) Five (5) calibration levels or more
(D) Days between extraction and analysis ≤ 14 days
(E) Residues in treated bracketed by spike levels

10. Q & A
How long are the raw data for pesticide
registration kept in archives? (Select all
correct answers.)
(A) One year after MRL is granted
(B) Two years after submission
(C) Five years of analysis of the last sample
(D) Lifetime of the MRL
(E) SD decides

11. Raw Data
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.
GLP definition from 21 CFR 58, 40 CFR 160, 40 CFR 792

12. Raw Data Formats
Raw Data may include photographs,
microfilm or microfiche copies,
computer printouts, magnetic media,
including dictated observations, and
recorded data from automated
instruments.
GLP definition from 21 CFR 58, 40 CFR 160, 40 CFR 792

13. “Raw Data” Proof
• All data generated during the conduct of
a study, except those that are generated
by automated data collection systems,
shall be
recorded directly,
promptly and
legibly in ink.
GLP definition from 21 CFR 58, 40 CFR 160, 40 CFR 792

14. “Raw Data” Proof
• All raw data entries shall be
dated on the date of entry
signed or initialed by the person
entering the data.
GLP definition from 21 CFR 58, 40 CFR 160, 40 CFR 792

15. “Raw Data” Proof
• Any change in entries shall be made so
as not to obscure the original entry,
shall indicate the reason for such
change, and shall be
dated and signed or identified at the
time of the change.
GLP definition from 21 CFR 58, 40 CFR 160, 40 CFR 792

16. • In automated data collection systems,
the individual responsible for direct
data input shall be
identified at the time of data input.
GLP definition from 21 CFR 58, 40 CFR 160, 40 CFR 792
“Raw Data” Proof

17. “Raw Data”
• Raw data shall be sufficiently detailed to
allow reconstruction of the study, so that
such reconstruction is capable of
generating SIMILAR RESULTS and
CONCLUSIONS.
• You still need to document what you did - even
if the protocol spells out the requirement

18. “Raw Data”
• All experimental data, including
observations of unanticipated
responses, shall be ACCURATELY
recorded and VERIFIED.

19. Rules for Good Documentation
• Make original hand-written entries directly into
notebook/logbook or appropriate study record
• Record legibly using indelible ink
– Use a ball-point pen or permanent ink pen
– Do not use pencil
– Do not use water soluble or erasable inks
• Affix “loose papers” into notebooks or binders
• Label data with Trial/Sample Information
• Sign/date lab records daily as work progresses

20. Do’s and Dont’s
• Draw a large diagonal line through unused or
blank pages
• Do not erase/obliterate an entry
• To correct errors
– Line through an incorrect entry
– Add the correct entry
– Document the reason for the change or correction
– Initial/Date

21. • Do NOT scribble out mistakes (obscures entry)
• Do NOT write correct entries over top of incorrect
entries (writeovers obscure original entries)
• Do NOT forget to enter all required information
• Do NOT forget to initial and date the entry
• Do NOT use colored ink/pencil/white-out
• Do NOT leave mistakes uncorrected (check your
entries)
Do’s and Dont’s

22. • Do take time, commitment and attention to
detail by all employees
• The time spent on doing the work correctly the
first time will prevent, or at least minimize, time-
consuming and costly reviews, corrections, and
time/money involved in repeating work
conducted incorrectly.
Do’s and Dont’s

23. Example: Entry Corrections
• Date corrections
– 8/14/2020 (correct date)
– Corrections: line through the wrong entry
• 8 / 15 / 2020  14-Aug-2020 (Good)
• 8 / 15 / 2020  8/14/2020 (OK)
• 8/ 15 / 2020  8/14/20 (not recommended)
– footnote the reason for change
– initial and date

24. Example: Error Codes
Code
Explanation
No Letter
1 WE Wrong entry due to typographic error
2 HE Human error (similar to EC 1)
3 ME Mathematical error, calculation mistake
4 UE Unnecessary entry
5 IE Illegible entry
6 LE Late entry
7 NA Not applicable or no data necessary
8 NE No entry (left blank on purpose)

25. Record Keeping

26. Golden Rules
• Document everything related to the study
• Keep everything (used and unused data)
• Clearly mark with necessary information
(such study # and sample ID, etc)
• Provide reasons why data were not used
• Initial and date raw data to show who collected
data or who performed each operation

27. Important Points
• Traceability
• Reproducibility
• Re-constructability

28. Late Documentation
• FDA Warning Letter
– In the absence of contemporaneous
documentation, FDA does not have
confidence that the final report can accurately
and completely describe these operations
more than 18 months after the study was
conducted.

29. Late Documentation
• FDA Warning Letter
– The Study Director has not noted
unforeseen circumstances or deviations that
may affect the quality and integrity of
nonclinical studies when they occurred and
failed to document what corrective actions,
if any, were taken at that time. In several
cases, deviations that occurred were noted
six months to more than one year later.

30. Electronics data
Separate Powerpoint slides

31. Archives
• All raw data, documentation, records,
protocols, specimens and final reports
shall be retained in the archives
• Orderly, secure storage and expedient
retrieval of all items
• Conditions of storage shall minimize
deterioration
• An individual shall be identified as
responsible for the archives

32. Retention of Records
• Length of retention is dependent upon
regulation
• Some items are not stable and may not
need to be retained for the entire
retention period
• Master schedule, copies of protocols,
records of QA inspections, training
records, equipment records need to be
retained for the retention period

33. jiangwa@msu.edu

34. GLP TRAINING
 Wayne Jiang, PhD
IR-4, Michigan State University, jiangwa@msu.edu
 Michael Braverman, PhD
IR-4 headquarters, Rutgers University
Analytical Summary Report
(ASR)

35. Report Requirements

36. Report Requirements
Must be written for the study and GLPs list
minimum components
• Cover page
• GLP compliance statement signed and dated
by Laboratory Research Director and
analysts
• QA Statement signed and dated by QA.
• Lab Personnel

37. ASR Cover Page

38. GLP Compliance

39. QA Statement

40. Report Requirements
• Table of Contents
• Location of Raw Data
• Analytical Reference Substance
• Summary
• Introduction
• Working Method
• Residue Sample Results (MV, Field trials, Storage Stability)
• LOQ/LOD Calculations
• Calculation pages and calibration curves
• Representative Chromatograms

41. Working Method Example

42. Calculation Pages

43. LOD/LOQ Calculations

44. COAs
Original COA Re-Certification

45. True or False
A change in extraction method from
homogenizing (high speed blending) to
QuEChERS is a minor change.
A change in extraction solvent from acetonitrile
to acetone is a major change.

46. True or False
A change in analytical instrument from
HPLC/UV to LC/MS/MS is considered to be a
minor change. Therefore, SD does not have to
approve it.
Using a grade ‘A’ glass volumetric pipet is
accurate. It is not necessary to calibration it
before spiking MV samples.

47. Q & A
Raw data should contain the signature/initial of
the user and the time when entry was made.
A change in entries shall be made so as not to
obscure the original entry, shall indicate the
reason for such change, and shall be dated
and signed or identified at the time of the
change.

48. Q & A
When the GLP ‘clock’ starts in a pesticide
analytical lab?
A.SD signs the protocol
B.Analytical reference standard is received
C.The date of the first application is performed in the field
D.First field sample is received by lab
E.MV is completed and SD approves to start sample
analysis

49. Q & A
Which sample is in required in an analytical set
for analysis ? (select all correct answers)
(A) Control sample (untreated)
(B) Fortified sample (QC)
(C) Calibration standards
(D) Solvent blank

50. Q & A
Which of the following lab records are raw
data with initial/date? (Select correct answers)
(A) Laboratory worksheets
(B) Exact copies of protocols
(C) Memoranda
(D) Balance logs
(E) Phone log

51. Q & A
Which of the following are general
practices in IR-4 laboratories for their data
acceptance? (Select all correct answers.)
(A) Spike recovery 70-120%
(B) Double injection on weathered samples
(C) Five (5) calibration levels or more
(D) Days between extraction and analysis ≤ 14 days
(E) Residues in treated bracketed by spike levels

52. Q & A
How long are the raw data for pesticide
registration kept in archives? (Select all
correct answers.)
(A) One year after MRL is granted
(B) Two years after submission
(C) Five years of analysis of the last sample
(D) Lifetime of the MRL
(E) SD decides

53. True or False
Since QA is independent, QA does not
have to sign a page in a laboratory
analytical summary report (ASR)?

54. Questions ?
• Any questions?

55. jiangwa@msu.edu

56. Congratulations
Congratulations !
You successfully attended the GLP
training for Residue Mitigation Project
The training certificate will
be sent per the attendance.
An example of certificate is
shown on right.

57. Thanks to
APAARI
USDA–FAS
USAID
STDF
The IR-4 Project
and all participating countries