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GLP Training
Protocols and SOPs
Wayne Jiang, PhD
IR-4, Michigan State University, jiangwa@msu.edu
Michael Braverman, PhD
IR-4 Headquarters, Rutgers University
Protocols and SOPs
Protocol and SOP
Game: Count number of squares.
How many squares ?
No. squares = n
2
1 555
Protocol
Study Plan
2
Protocol
Every study needs an approved protocol
that contains at least:
Descriptive title and purpose of the study Descriptive title and purpose of the study
ID of test, control and reference substance
Name and address of the sponsor and
testing facility
Appropriate dates
Justification for selection of test system
Protocol
The number, body weight, sex, source of
supply, species, strain, substrain and age of
the test system
Procedure for ID of the test system y
Description of the experimental design,
including control of bias
A description of the diet, including
acceptable levels of contaminants, if
applicable
Route of administration and the reason for
its choice
Protocol
Each dosage level in appropriate units and
the method and frequency of administration
Type and frequency of tests, analyses and
measurements measurements
Records to be maintained
Date of protocol approval by the sponsor and
the dated signature of the study director
Proposed statistics
3
Protocol
Amendment
Changes or revisions of an approved
t l d th th f protocol and the reasons therefore
shall be documented, signed by the
study director, dated and maintained
with the protocol
Sample Protocol
Standard Operating
Procedures
SOPs
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SOPs
Management-approved
Insure the quality and integrity of data
I di t l il bl l d Immediately available manuals and
SOPs relative to the procedures being
performed
Historical file of SOPs
SOPs
Established for:
Test system room preparation
Test system care
Receipt ID storage handling mixing Receipt, ID, storage, handling, mixing
and method of sampling of the test,
control and reference substances
Test system observations
Laboratory or other tests
Handling of test systems found moribund
or dead during study
Necropsy or postmortem examination
SOPs
Established for:
Collection and ID of specimens
Histopathology Histopathology
Data handling, storage and retrieval
Maintenance and calibration of
equipment
Transfer, proper placement and ID of
test systems
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SOPs
Deviations must be authorized by the
study director and documented in the
raw data
Significant changes to SOP must be
authorized in writing by management
Note: Instructions in the protocol
override SOP
Sample SOP
You might be wondering
What does this all mean?
How do we make it work effectively?
Where does it fit in?
Test
Syste
m
3/6/2013 15
Where does it fit in?
Protoc
ol
Field
Laboratory
SOPs
QA
Archives
Study
Director
Raw
Data
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Sample SOP Format
Header
Author,
Version,
etc
Managements Title g
Signature,
Date
Containing SOP No.
Page No.
Footer
Subtitle and
Numbering
Organization and Personnel
Organization Chart
MANAGEMENT
Director of IR-4 NCR Center
Michigan State University
(MSU)
Project Management Committee
(IR-4)
FIELD
Coordinator
QA
Coordinator
LABORATORY
Coordinator
Associate
Lab Director
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Question: True or False?
Study Director
Management Designates study
director; Assures characterization;
Assures availability
Study director Single point of study
control; Responsible for GLP
compliance
Quality Assurance
Personnel
compliance
QA Monitors each study; Reports
to management; Entirely separate
and independent
Personnel (Lab and Field)
conducts the study; adequately
trained; avoid contamination, etc.
Personnel
Must have relevant education, proper
training and experience to perform
assigned functions
Must be knowledgeable in GLPs as
applicable to involvement in the study
Sufficient number of personnel
to perform the work in a timely
and proper manner
Personnel
Personal sanitation and health
precautions to avoid contamination
Immediate access to the protocol and
applicable SOPs
Responsible for recording raw data
promptly and accurately and
in compliance with GLPs
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Personnel
Job Description
Department, group
Name, position, level
Name position of direct supervisor Name, position of direct supervisor
Position summary
Responsibilities, work relationships
Approval signature
/date
Management
Designates a study director before the
study is initiated
Replaces the study director promptly if
necessary
Assures there is a Quality Assurance Unit
Assures that test, control and reference
substances or mixtures have been
appropriately tested for identity, strength,
purity, stability and uniformity
Management
Assures that personnel, resource,
facilities, equipment, materials and
methodologies are available as
h d l d scheduled
Assures that personnel
clearly understand the
functions they are to
perform
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Management
Assures that deviations reported by
QAU are communicated to the study
director and corrective actions are
taken and documented
Study Director
Is the single point of study control
Has overall responsibility for the conduct,
interpretation, analysis, documentation and
reporting of the study reporting of the study.
Must assure the protocol is approved & followed
Must assure all data and unanticipated
events are accurately recorded
and verified
Study Director
Assures unforeseen circumstances that may affect the
quality and integrity of the study are noted when they
occur, and corrective action is taken and documented.
Assures test systems are as specified in the protocol.
Assures that all raw data, documentation,
protocols, specimens & final report are
transferred to the archives during or at
the close of the study.
Signs the GLP compliance
statement
Takes Responsibility for
GLP compliance
10
Quality Assurance Unit
Responsible for monitoring each study to assure
management that the following comply with GLPs:
facilities
equipment
personnel
methods
practices
records
controls
Quality Assurance Unit
Entirely separate from the conduct of the study
Conducts inspections and maintain records of inspections
Maintains the master schedule
Maintains copies of all protocols p p
Keeps management informed of the status of each study
Makes sure no protocol or SOP deviations occurred
without proper authorization and review
Assures the final report accurately describes the study
Provides QA statement in the final report
Agency inspection can include QA records, but not
inspection findings
Questions: True or False
True or False
- For GLP study compliance issues, the y p
final decision maker is the QA.
11
Multi-Site Studies
Multi-Site Studies
Study director is single point of study
control
Clear lines of communication between Clear lines of communication between
the Study Director, Principal
Investigator, QA and study personnel
Multi-Site Studies
If needed, a Principal Investigator (PI)
is designated
appropriately trained, qualified and appropriately trained, qualified and
experienced
Principal Investigator (PI) ensures that
the delegated phase(s) of the study
are conducted in accordance with
applicable GLPs.
12
Multi-Site Studies
Principal Investigator (PI)
An individual who, for a multi-site study,
acts on behalf of the Study Director and
has defined responsibility for delegated has defined responsibility for delegated
phases of the study. The Study Directors
responsibility for the overall conduct of the
study cannot be delegated to the Principal
Investigator(s); this includes approval of
the study plan and its amendments,
approval of the final report, and ensuring
all GLPs are followed.
Multi-Site Studies
Study plan (protocol) and final report
identify and define the role of any
Principal Investigator(s) and any test p g ( ) y
facilities and test sites involved in the
conduct of the study.
Multi-Site Studies
SOP deviations acknowledged by the
Study Director and the Principal
Investigator. g
Deviations from the study plan
(protocol) should be described,
explained, acknowledged and dated in
a timely fashion by the study director
and/or principal investigator(s) and
maintained with the raw data.
13
Testing Facilities
Facilities
Must be of suitable size and construction
To avoid contamination
To facilitate the proper conduct of studies
To ensure proper separation of species
Regulation of environmental conditions
temperature
humidity
photoperiod
p p p p
Facilities
Storage areas separated from test system and
protected against infestation or contamination
Separate areas to preserve the identity, strength,
purity and stability of substances and mixtures
Receipt and storage of the test, control and
reference substances
Mixing of the test, control and reference
substances with a carrier
Storage of the test control and reference
substance mixtures
14
Equipment
Equipment design
Equipment used in the generation,
measurement or assessment of data and
equipment used for facility environmental
control shall be of appropriate design and
adequate capacity to function according
to the protocol and shall be suitable
located for operation, inspection, cleaning
and maintenance.
Equipment Maintenance and Calibration
Adequately inspected, cleaned and
maintained
Equipment used for the generation Equipment used for the generation,
measurement or assessment of data
shall be adequately tested, calibrated
and/or standardized
15
Equipment Maintenance and Calibration
SOP must include methods, materials
and schedules for:
Routine inspection Routine inspection
Cleaning
Maintenance
Testing
Calibration and/or
Standardization
Equipment Maintenance and Calibration
SOP shall specify, when appropriate,
remedial action to be taken in the event of
failure or malfunction of equipment.
SOP shall designate the person responsible
for the performance of each operation
Equipment Maintenance and Calibration
Written records shall contain be
maintained of all:
Inspection
M i t Maintenance
Testing
Calibrating and/or
Standardizing operations
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Equipment Maintenance and Calibration
Records must contain the date of operation
and describe whether maintenance was
routine and followed SOP.
Records must be kept of nonroutine repairs Records must be kept of nonroutine repairs
as a result of failure and malfunction.
Nature of defect
How and when defect was discovered
Any remedial action taken
Questions ?
Any questions?
Sample SOP TOC
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Sample SOP TOC-contd
Thank
Y ! You!
jiangwa@msu.edu