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GLP Training
GLP History and Enforcement
Wayne Jiang, PhD
IR-4, Michigan State University, jiangwa@msu.edu
Michael Braverman, PhD
IR-4 Headquarters, Rutgers University
GLP History and Enforcement
Historical Perspectives
Underlying assumption
at the FDA
Reports submitted by p y
the sponsors
accurately described
study conduct and
precisely reported the
study data.
Historical Perspectives
Mid-1970s
FDA suspicion during review of studies
submitted by a major pharmaceutical
manufacturer (G.D. Searle & Co.) in ( )
support of New Drug Applications (NDAs)
for two important therapeutic products.
Data inconsistent
Unacceptable laboratory practices
Deliberately tried to minimize chance of toxic
results
Impossible to draw conclusions regarding
toxic potential of tested products
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Historical Perspectives
FDA requested a for cause
inspection of the manufacturers
laboratories to determine the cause
and extent for the discrepancies
Revealed defects in design, conduct and
reporting of the studies
Further inspections at other sites
revealed similar problems.
FDAs Reaction
Alarm that many of the studies on which
proof of safety had been based
could be invalid.
Task forces formed quickly
FDA GLPs proposed Nov. 19, 1976
FDA GLPs finalized 1979
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EPA Follows Suit
EPA issued almost identical
regulations in 1983.
EPA GLPs extensively amended in EPA GLPs extensively amended in
1989 to encompass all pesticide
research data.
Why Comply?
Compliance with GLPs promotes the quality
and integrity of test data
An inspector must be able to easily
determine
Why, how and by whom the work was done
Who was in control
What equipment was used
Results obtained
Any problems and how they were overcome
Too Abstract and Historical?
Wh t d t
Aspartame
What product
tested at Searle
have most of us
consumed?
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Research Misconduct
fabrication, falsification or plagiarism in
proposing, performing or reviewing
research, or in reporting research
lt d t i l d h t resultsdoes not include honest error or
differences of opinion.
Federal Policy on Research Misconduct
Office of Science Technology and Policy
Executive Office of the President
December 6, 2000
Basic GLP Principles
Study Integrity
-Reconstruction
-Proper data acceptance/rejection
Research Integrity
-Training of personnel
-Responsibilities
-Record security
-Checks and controls
-Confidentiality
Data Integrity
-Accuracy
-Completeness
-Consistency
Integrity Affects.
Data points
Each non-clinical study
The regulatory submission g y
The work/career of an investigator
All of the research conducted at a laboratory
Public health, safety and confidence in scientific research
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Flexibility vs Requirements
GLPs do not have to specify
exactly how everything is to
be done
Flexible
SOPs shall set forth in sufficient detail
Equipment shall be adequately
inspected cleaned and maintained inspected, cleaned and maintained
People shall be appropriately trained
QAU shall inspect each study at
intervals adequate to assure the integrity
of the study
Required
Protocol and SOP deviations shall be
documented
Written records shall be maintained
Use of pest control materials shall be
documented
Maintain a current summary of training
and experience and job description for
each individual.
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Good Documentation is the
PROOF of What You Do
Golden Rule #1
1. If it isnt written down, it didnt happen.
DOCUMENTATION !
No
Document
Did Not
Happen
Golden Rule #2
2. If it isnt written down correctly or
legibly, it may not have happened either.
DOCUMENTATION !
Incorrect
Document
Not
Happened
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Golden Rule #3
3. Must be able to determine
who did what and when he/she did it.
DOCUMENTATION !
Documentation should contain
Who, what, when
Enforcement and
Effects of Non-Compliance
Enforcement of GLPs
Each government agency may perform
inspections of any laboratory facility
within its jurisdiction at reasonable
times and in a reasonable manner times and in a reasonable manner.
Inspections may be
Routine periodic determination of the
labs compliance; may include data audit.
For cause conducted less frequently;
may be triggered by suspicion or
previous non-compliance.
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Regulatory Inspections:
What will they do & what can they see?
An Investigator may physically observe
any area, equipment or process
Facility tour
Observe in-progress study activities
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Observe in progress study activities
Interview individuals
Perform process inspections (e.g., following
samples from collection through analysis)
Look at peripheral equipment such as HVAC
systems, etc.
Regulatory Inspections
FDA inspections are typically
unannounced.
EPA typically gives notice prior to EPA typically gives notice prior to
inspection.
Regulatory Inspections:
Do Not give these to the Investigator
Quality Assurance Audits
Personnel information
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Personnel information
Financial Information
Gifts/Company Promotional
Materials
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Agency Inspections
If a testing facility were to refuse an
inspection or be found to have conducted
studies that were not in compliance with
GLPs, the agency would refuse to
approve test articles that were tested at
that facility.
In addition, management personnel may
be subject to civil or criminal penalties.
What does non-compliance
mean?
The study did not follow some part of
GLPs
Data are false or misleading
Data contain significant omissions
Inspection was refused
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Statement of compliance
or non-compliance
EPA and OECD require the extent to
which GLPs were followed to be
described in the final report
Three options
Study complied with GLPs
Study (or parts thereof) did not comply
with GLPs
Dont know if study complied with GLPs
Win-Win
Win-Win
When You Follow
Good Laboratory Practices
Questions ?
Any questions?
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Sample ASR Page
GLP Compliance Statement
Sample ASR Page
Quality Assurance Report
In-Life Inspection
Raw Data Inspection
Analytical Report Inspection
Thank
Y ! You!
jiangwa@msu.edu