Trends in Quality Management -

Quality Management Systems beyond ISO/IEC 17025

6. The Difference Between

glp and GLP

Stewart Jones
8 May 2015
glp (good laboratory practices)
The generally accepted organizational activities, process, facilities, staff
and conditions that ensure that chemical analyses are performed,
monitored, recorded and reported to ensure the quality of the result.

GLP (Good Laboratory Practice)

A system of management controls as per the OECD Principles to
ensure consistency and reliability of results for non-clinical studies
conducted for the assessment of the safety of chemicals to man,
animals and the environment.
glp or GLP?
 Good food safety practices
GCP Good Cultivating Practices.
GHvP Good Harvesting Practices.
GHdP Good Handling Practices.
GMP Good Manufacturing Practices.
cGMP Current Good Manufacturing Practices.
GDP Good Distributing Practices.
GIP Good Inspection Practices.

Good Weighing Practice.

Good Titration Practice.
glp Good Pipetting Practice.
Good Electrochemistry Practice.
Good Density and Refractometry Practice.
 Australian Standard AS2830.1-1985
glp GOOD LABORATORY PRACTICE
Part 1—CHEMICAL ANALYSIS
A document that sets out general requirements for the
technical competence of laboratories engaged in chemical
analysis:
• Laboratory Organization.
• Personnel.
• Safety.
• Quality Assurance System. (Similar to the
• Laboratory Facilities. requirements of
• Testing and Measurement Equipment. ISO/IEC 17025)
• Apparatus and Reagents.
• Test Methods and Procedures.
• Calibration of Testing and Measuring Equipment.
• Samples and Test Data Storage.
• Test Reports.
• Inspection and Assessment.
GLP History of GLP
• During 1950 to 1970, Industrial Bio-Test
Laboratories (IBT) performed almost 40% of all U.S.
toxicology testing.
• However, in US Food and Drug Administration (FDA)
audits, more than 70% of the studies were invalid due
to numerous data discrepancies.
• The FDA sued and four IBT managers were found
guilty of fraud.
GLP
OECD GLP
• GLP was first introduced in New Zealand and
Denmark in 1972.
• As a result of the IBT fraud, the FDA
introduced GLP guidelines in 1976.
• The Organisation for Economic Co-
operation and Development (OECD), an
international economic organisation of
34 countries, introduced its Principles of GLP
in 1992.
The Difference Between glp and GLP
• General guidelines for operating a ‘good’
glp laboratory, similar to ISO/IEC 17025.
• No accreditation available for ‘glp’.

• Is mostly a management system in which

GLP laboratory studies are planned, performed,
monitored, recorded, reported and
archived.
• Is required because non-clinical safety
studies generate data to assess risks and
are used to make public health decisions.
• Is a recognised program for accreditation
to the OECD GLP Principles.
 GLP Definitions
Non-clinical Safety Studies:

• In-vivo or in-vitro experiments in which test

articles are studied prospectively in test systems
under laboratory conditions to determine their
safety.

• NOT studies utilizing human subjects, clinical

studies, field trials in animals, basic exploratory
studies for utility, or for determining physical or
chemical characteristics of a test article.
 The Australian GLP program
• Recognition is offered by NATA for compliance with the OECD
Principles of GLP.
• “For any facility undertaking non-clinical health and environmental
safety studies for the purpose of registering or licensing for use
pharmaceuticals, pesticides, veterinary drug products and similar
products, and for the regulation of industrial chemicals”.
• Examples of the types of studies:
– Physical-chemical testing toxicity studies.
– Mutagenicity studies.
– Environmental toxicity studies.
– Bioaccumulation residue studies.
– Studies on the effects of natural ecosystems.
– Target animal safety studies.
– Worker exposure studies.
 The Australian GLP program

Nata Accredited GLP Facility

Number: 89

This facility is accredited by the National Association of Testing Authorities (NATA),

Australia, for compliance with the OECD Principles of Good Laboratory Practice (GLP).
This study has been conducted in compliance with these Principles.

• It does do not apply to clinical studies or routine QC testing. The

standard for this testing is ISO/IEC 17025.
• Accreditation to ISO/IEC 17025 demonstrates technical competence
and shows the laboratory is following 'good laboratory practice‘ (glp).
GLP Definitions

Important people
in a GLP Study:

1. Sponsor
2. Management
3. Study Director (SD)
4. Quality Assurance Unit (QAU)
5. If multi-site: Test Site Management
6. If multi-site: Test Site Quality Manager
7. Principal Investigator
GLP 1. Sponsor
– A person who initiates and supports a Study with
financial or other resources.
– A person who submits a non-clinical Study to the
FDA (or relevant authority).
– A testing facility, if it both initiates and actually
conducts the Study.
GLP 2. Management
– Designates a Study Director before the Study starts.
– Assures that there is a Quality Assurance Unit.
– Assures that test and control articles or mixtures are tested for
identity, strength, purity, stability, and uniformity.
– Assures that personnel, resources, facilities, equipment,
materials, and methodologies are available as scheduled.
– Assures that personnel clearly understand the functions they
are to perform.
– Assures that any deviations from these regulations reported
by the quality assurance unit are communicated to the Study
Director and corrective actions are taken and documented.
GLP 3. Study Director
– Scientist of appropriate education, training and
experience.
– Responsible for overall technical conduct of a non-
clinical laboratory Study and for the interpretation,
analysis, documentation and reporting of results.
– Assures that all Study records are archived at the
end of the Study.
 GLP 3. Study Director (cont)
• Assures the protocol and any amendments have been
properly approved and are followed.
• Assures that all data are accurately collected, recorded
and verified according to the protocol and SOPs.
• Documents unforeseen circumstances and implements
corrective action.
• Assures that Study personnel are familiar with and
adhere to the Study protocol and SOPs.
• Assures that Study data are transferred to the archives at
the close of the Study.
GLP 4. Quality Assurance Unit
– any person or organizational element,
designated by management to perform the
duties relating to QA of non-clinical
laboratory studies.
GLP 4. Quality Assurance Unit (cont)

Duties
– QAU monitors each Study to assure
management that all systems are in conformance
with GLP regulations.
– QAU shall be entirely independent of personnel
conducting a particular Study.
GLP 4. Quality Assurance Unit (cont)

Duties (continued)
– The quality assurance unit shall maintain a
master schedule sheet of all studies, indexed
by test article and listing these elements:
• Test system, nature of Study, Study initiation date,
current status, sponsor identity, and name of the
Study Director.
GLP 4. Quality Assurance Unit (cont)

Duties (continued)
– Maintain copies of all GLP protocols.
– Inspect each non-clinical laboratory Study at
adequate intervals and maintain written signed
records of periodic inspections.
– Bring to the attention of the Study Director and
management immediately any problems found
during an inspection that may affect Study
integrity.
 GLP Quality Assurance Unit (cont)

Duties (continued)
– Submit to management and to the Study Director
regular written status reports on each Study,
noting problems and corrective actions taken.
– Determine that no deviations from approved
protocols or standard operating procedures were
made without authorization and documentation.
GLP 4. Quality Assurance Unit (cont)
Duties (continued)
– Review the final Study report to assure accuracy
in description of methods and Standard
Operating Procedures, and that results
accurately reflect the raw data of the Study.
– Prepare and sign a statement specifying dates
of inspections and when findings were reported
to management and Study Director.
 GLP 5. Test Site Management
a) Identifies the individual(s) within a test site who fulfil the responsibilities of
management.
b) Ensures that a sufficient number of qualified personnel, appropriate facilities,
equipment, and materials are available for the timely and proper conduct of the
Study.
c) Ensures the maintenance of a record of the qualifications, training, experience
and job description for each professional and technical individual.
d) Ensures that personnel clearly understand the functions they are to perform
and, where necessary, provides training for these functions.
e) Ensures that appropriate and technically valid Standard Operating Procedures
are established and followed, and approves all original and revised Standard
Operating Procedures.
f) Ensures that there is a Quality Assurance Program with designated personnel
and that the quality assurance responsibility is being performed adequately.
g) Ensures that for each Study an experienced individual is designated as the
Principal Investigator before the Study is initiated.
 GLP 5. Test Site Management (cont)
a) Ensures documented approval of the Study Plan by the Study Director.
b) Ensures that the Study Director has made the approved Study Plan available to the
Quality Assurance personnel.
c) Ensures the maintenance of an historical file of all Standard Operating Procedures.
d) Ensures that an individual is identified as responsible for the management of the
archive(s).
e) Ensure the maintenance of a master schedule.
f) Ensure that test facility supplies meet requirements appropriate to their use in a Study.
g) Ensure that clear lines of communication exist between the Study Director, Principal
Investigator(s), the Quality Assurance Programme(s) and Study personnel.
h) Ensures that test and reference items are appropriately characterised.
i) Establishes procedures to ensure that computerised systems are suitable for their
intended purpose and that computerised systems used in the Study have been validated.
j) Is responsible for the replacement of the Study Director and/or Principal Investigator,
ensuring continuity in accordance with GLP principles.
k) Deputises for the Laboratory Quality Manager.
GLP 6. Test Site Quality Manager
a) Maintains copies of all approved Study Plans and Standard
Operating Procedures and the master schedule.
b) Verifies the Study Plan and Study Plan Supplement (analytical
phase) for compliance with GLP, and documents this approval.
c) Conducts QA inspections in accordance with the GLP and ensures
Study Plans and Standard Operating Procedures are available and
used by Study personnel.
d) Inspects the final reports to confirm that the methods, procedures,
observations, reported results and raw data are accurate and
complete.
e) Promptly reports any inspection results in writing to management and
to the Study Director, and to the Principal Investigator(s).
f) Prepares and signs a statement, to be included with the final report,
which specifies types of inspections and their reporting dates.
 GLP 7. Principal Investigator
1. Approves the Study Plan and Supplement and any amendments to them.
2. Ensures that the Quality Assurance personnel have a copy of the Study Plan
and Supplement.
3. Ensures that Study Plans, Supplements, and Procedures are available to Study
personnel and are followed.
4. Assesses and documents and corrects if necessary the impact of any
deviations from the Study Plan and Supplement on the quality and integrity of
the Study and ensures these deviations are acknowledged by the Study
Director.
5. Is authorised to correct original test data.
6. Signs and dates the final report to indicate acceptance of responsibility for the
validity of the data and that the Study complies with the Principles of GLP.
7. Ensures that all raw data and reports generated are fully documented, recorded
and archived.
GLP Animal Care
• Where animals are used by the test facility, animal care and
housing must minimize stress and uncontrolled influences
that could alter the response of test system to the test article.
• Inspection of animal room(s) that will be housing the Study.
• Review pest-control procedures, document the chemicals
used and identify individuals responsible for the program.
• Determine the facility has clearance from authorities to
conduct animal studies.
 GLP GLP Documentation
Documentation should permit the complete
reconstruction of a Study:
• Record data directly, promptly and legibly in ink (never pencil) and do not use
white-out correction fluid or tape.
• Initial and date all observations and any resulting changes, but do not obscure
original data.
• Do not document selectively or in advance of performing the activity.
• Explain why any raw data not used was not used.
• Verify critical calculations using a second person and document this.
• Properly head all pages, tables, columns and identify units.
• Describe statistical and calculation procedures used.
• Retain all raw data (original records) in the Study File.
• Keep all original observations, including those observations
recorded directly into a computer.
• Sign and date all computer printouts.
• Document all deviations with accompanying explanations.
• Indicate in the record all applicable units and equipment used.
 CONDUCT OF GLP STUDIES
1. Initial Contact
• A Laboratory (Test Site) will usually conduct GLP studies in co-operation with a Sponsor
and a Test Facility.
• The laboratory will identify a Principal Investigator and will prepare a Study Plan
Supplement (analytical phase) to cover the analytical work.

2. Preparation of the Study Plan

• A Study Plan shall be completed, and approved by the Study Director.
• Once approved, a Study Plan Supplement (analytical phase) shall be prepared.
• The Study Plan Supplement (analytical phase) and any amendments to the Study Plan
should be approved by dated signature of the Study Director, Sponsor, and the Principal
Investigator and verified by the Laboratory Quality Manager.

Study Plans must include:

The purpose of the Study, so that it is clear that the Study is within the scope of the
OECD Principles of GLP.
The identity of the test and reference items.
Reference to all of the SOPs (Standard Operating Procedures) to be used.
The names and addresses of the Test Facility, Test Sites and Study Director.
 CONDUCT OF GLP STUDIES
3. Conduct of the Study
• Samples are received in accordance with documented procedures.
• Sample Submission Forms (SSF) will be filled out for all samples, and all labelling
information will be transferred from sample containers to the SSF forms, including the
number of the GLP Study.
• The samples will be stored under appropriate conditions in a designated locked freezer.
• The temperature of the storage area shall be monitored and recorded for the period of
storage, and records shall be kept of sample movements in and out of the storage area.
• Records must be kept for reference items that include the quantities received and used
in the studies.
• Chromatography software shall record any changes to the sample data by the use of
audit trails.
• Where Excel spreadsheets are used to calculate results and manipulate data, the cells
shall be locked by the Principal Investigator.
• Data entries must be signed or initialled and dated by the individual entering the data. .
• Any changes to raw data must be dated and initialled or signed by the individual making
the change.
• A signed and dated record of the samples shall be kept in the appropriate GLP file when
they are discarded.
 CONDUCT OF GLP STUDIES
4. Quality Assurance Program
• The Laboratory Quality Manager shall manage the Quality Assurance program for GLP
studies.
• This program shall ensure the currency of the Study Plan and the Study Plan Supplement
(analytical phase) and the Procedures and Methods associated with the conduct of the
Study.
• The Study Plan and the Study Plan Supplement (analytical phase) shall be audited prior to
the conduct of the Study.
• An audit of the final report shall be conducted on completion of the Study, which must
encompass the entire report and not just the transfer of data.
• The Laboratory Quality Manager shall also conduct an internal audit during the lifetime of
the Study, on any one or all of the following bases; Study-based inspection, facility-based
inspection, or process-based inspection.
• QA findings shall be reported promptly to test site management, the Study Director, the test
facility management and the lead Quality Assurance Officer.
• Details of all reference materials used in the Study must be retained with the raw data.
Primary reference standard records must include a copy of the statement of purity or
certificate, date and where from acquired, CAS number or IUPAC name, and use by dates.
• At the end of the Study, the Quality Manager shall sign off on the Report of Analysis that
the Study has complied with the above QA requirements.
 CONDUCT OF GLP STUDIES
5. Reporting the Results of the Study
A final report shall be prepared for each Study and shall include the following information:
• A descriptive title.
• Identification of the test item by code or name (IUPAC, CAS number, biological parameters).
• Identification of the reference item by name.
• Characterisation of the test item, including purity, stability and homogeneity.
• Name and address of the sponsor.
• Name and address of the test facilities and test sites involved.
• Name and address of the Study Director.
• Name and address of the Principal Investigator(s) and the phase(s) of the Study delegated, if applicable.
• Name of other scientists who contributed reports to the final report.
• Experimental starting and completion dates.
• A Quality Assurance statement, listing among other things the types of audits done and their dates,
including the phase(s) audited, and the dates any audit results were reported to test facility and site
management, and to the Study Director and Principal Investigator(s).
• Description of methods and materials used.
• Reference to OECD Test Guidelines or other test guidelines or method.
• A summary of results.
• All information and data as required by the Study Plan.
• A presentation of results, including calculations and determinations of statistical significance.
• An evaluation and discussion of the result and, where appropriate, conclusions.
• The location(s) where the Study Plan, samples of test and reference items, specimens, raw data and the
final report are to be stored.
• An endorsement.
 CONDUCT OF GLP STUDIES
6. Storage and Retention of Records and Materials
• The following must be retained (archived) for the period specified by the appropriate
authorities:
• Study Plan, raw data, samples of test and reference items, specimens and final report
for each Study.
• Records of instrument calibrations and maintenance.
• Records and reports of equipment calibrations and maintenance.
• Records of reference material details (certificates, weighings, dilution records)
• Records of all quality assurance inspections and audits, as well as master schedules.
• Records of qualifications, training, experience and job descriptions (CVs) of
personnel.
• Validation documentation for computerised systems.
• Historical file of Standard Operating Procedures.
• Environmental monitoring records.
• Original raw data (not copies) should be archived.
• Archived copies of authorised methods and SOPs must be taken from the original hard
copy controlled document, and not an electronic version.
• All records associated with a GLP Study shall be filed under the Study number.
• Archive records shall be kept in secure storage in the administration area, and a log shall
be maintained of all movements of the records.
• Copies of records must be legible, certified as true copies and annotated with the original
source of data.
 THIRD PART ASSESSMENT OF GLP RECOGNITION

Assessment Scope:
• Usually a multi-site Study with the laboratory being the test site for the analytical component.
• The Study is assessed for compliance with the OECD Principles of Good Laboratory Practice.

Assessment Findings:
1. Test Facility Organisation and Personnel
M The laboratory must ensure that records of qualifications, training, experience and job
descriptions are available for all personnel. No records were available for the Sample
Preparation Officer in charge of receiving GLP specimens.
M Test site management must ensure maintenance of the master schedule of Studies.
Although the final report for the analytical phase of the Study was completed, the master
schedule of Studies had not been updated accordingly. It was also not clear which
individual had been assigned responsibility for maintenance of the master schedule.
2. Quality Assurance Programme
C There are records to show that the results of QA inspections were reported to the Study
Director, test site management and the Principal Investigator. Records must also reflect
that the results were reported to test facility management and the Quality Manager.
THIRD PART ASSESSMENT OF GLP RECOGNITION
(cont)
Assessment Findings:
3. Facilities The archive facilities were inspected as part of the Study audit, and found to be
satisfactory.
4. Apparatus, Material and Reagents
C The laboratory must ensure that checks on analytical balances are undertaken in
accordance with the requirements listed in the OECD Principles of GLP, that is 6-
monthly repeatability checks and monthly one point checks.
5. Test Systems Satisfactory for the Study audited.
6. Test and Reference Items
C The laboratory must ensure that procedures and records allow for full reconciliation of
the quantities of reference items received and used in GLP studies. Currently, records
only show amounts of reference items used to prepare stock solutions for use in
studies. No record is kept of the amount of reference item received or available at the
start of a Study.
7. Standard Operating Procedures
M The laboratory must ensure that all SOPs are approved by test site management rather
than just the Quality Manager.
M The procedure must be updated to reflect the current NATA requirements for user
checks of analytical balances.
THIRD PART ASSESSMENT OF GLP RECOGNITION
(cont)

8. Performance of the Study Satisfactory for the studies audited.

9. Reporting of Study Results
C The Quality Assurance Programme statement in the final report
must list the dates that any inspection results were reported to the
to the Study Director, test facility management, test site
management, the Principal Investigator and the Quality Manager.
10. Storage and Retention of Records and Materials
C The laboratory must ensure that the following records are archived
for the Study:
• Records of the qualifications, training, experience and job
description of the Sample Preparation Officer in charge of
receiving GLP specimens.
• Records of the 3 yearly calibration of the analytical balance by a
NATA accredited facility.
Questions?