History of GLP

GLP is a formal regulation that was created by the FDA (the United States food and drug administration) in 1978. Although GLP originated in the United States, it had a worldwide impact. Non-US companies that wanted to do business with the United States or register their pharmacies in the United States had to comply with the United States GLP regulations. They eventually started making GLP regulations in their home countries. In 1981 an organization named OECD (organization for economic co-operation and development ) produced GLP principles that are international standard.

  Why Was GLP Created?

In the early 70’s FDA became aware of cases of poor laboratory practice all over the United States. FDA decided to do an in-depth investigation of 40 toxicology labs. They discovered a lot of fraudulent activities and a lot of poor lab practices. Examples of some of these poor lab practices found were Equipment not been calibrated to standard form, therefore giving wrong measurements; Incorrect/inaccurate accounts of the actual lab study; Inadequate test systems.

Famous Example

One of the labs that went under such an investigation made headline news. The name of the Lab was Industrial Bio Test. This was a big lab that ran tests for big companies such as Procter and Gamble. It was discovered that mice that they had used to test cosmetics such as lotion and deodorants had developed cancer and died. Industrial Bio Test lab threw the dead mice and covered results deeming the products good for human consumption. Those involved in production, distribution, and sales for the lab eventually served jail time.

Key areas in  GLP include 

1. Resources: Organisation, personnel, facilities, and equipment; 

2. Characterization: Test items and test systems;

3. Rules: Protocols, standard operating procedures (SOPs); 

4. Results: Raw data, final report, and archives; 

5. Quality Assurance: Independent monitoring of research processes. 

Purpose of GLP Principles are to ensure Safety 

To promote the development of quality test data

To provide the basis for mutual acceptance of data (MAD) among countries

To avoid duplicative testing, thereby saving time and resources

To avoid technical barriers to trade

To improve the protection of human health and environment. 

For a GLP inspector, it should be possible to look at the documentation and to easily find out the following:

Who has done a study?

How the experiment was carried out?

Which procedures have been used?

And Whether there has been any problem and if so How it has been addressed and solved where applicable? 

GLP Definition 

Good Laboratory Practice (GLP) is a quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported. 

GLP Documents

OECD PRINCIPLES OF GLP

No 1: OECD Principles on Good Laboratory Practice

GLP   Consensus Documents

No 4: Quality Assurance and GLP

No 5: Compliance of Laboratory Suppliers with GLP Principles(revised 1999)

No 6: The Application of the GLP Principles to Field Studies(revised 1999)

No 7: The Application of the GLP Principles to Short Term Studies (revised 1999)

No 8: The Role and Responsibilities of the Study Director in GLP Studies (revised  

          1999)

No 10: The Application of the Principles of GLP to Computerised Systems(1995)

No 13: The Application of the OECD Principles of GLP to the Organisation and 

            Management of Multi-Site Studies

Guidance Documents for Compliance Monitoring Authorities

No 2: Revised Guides for Compliance Monitoring Procedures for Good 

           Laboratory Practice

No 3: Revised Guidance for the Conduct of Laboratory Inspections and Study            

           Audit

No 9: Guidance for the Preparation of GLP Inspection Reports

ADVISORY DOCUMENTS OF THE WORKING GROUP ON GLP

No 11: The Role and Responsibility of the Sponsor in the Application of the 

             Principles of GLP

No 12: Requesting and Carrying Out Inspections and Study Audits in another 

             Country

No 14: The Application of the Principles of GLP to in vitro Studies

No 15: Establishment and Control of Archives that Operate in Compliance with 

             the Principles of GLP

No 16: Guidance on the GLP Requirements for Peer Review of Histopathology 

No 17: Application of GLP Principles to Computerised Systems

No. 19: Management, Characterisation and Use of Test Items

POSITION PAPERS

No. 18: OECD Position Paper Regarding the Relationship between the OECD 

             Principles of GLP and ISO/IEC 17025

Role and responsibility of Study Director

1. single point of study control, overall conduct of the study and for its final 

    report. 

2. These responsibilities should include, but not be limited to, the following 

    functions. The Study Director should: 

a) Approve the study plan and any amendments to the study plan by dated 

    signature; 

b) Ensure that the Quality Assurance personnel have a copy of the study plan 

    and any amendments in a timely manner and communicate effectively with     

    the Quality Assurance personnel as required during the conduct of the study;

c) Ensure that study plans and amendments and Standard Operating Procedures 

    are available to study personnel;

d) Ensure that the study plan and the final report for a multi-site study identify 

    and define the role of any Principal Investigator(s) and any test facilities and 

    test sites involved in the conduct of the study; 

e) Ensure that the procedures specified in the study plan are followed, and 

    assess and document the impact of any deviations from the study plan on the 

    quality and integrity of the study, and take appropriate corrective action if 

    necessary; acknowledge deviations from Standard Operating Procedures 

    during the conduct of the study;

f) Ensure that all raw data generated are fully documented and recorded; 

g) Ensure that computerised systems used in the study have been validated;

h) Sign and date the final report to indicate acceptance of responsibility for the 

    validity of the data and to indicate the extent to which the study complies with 

    these Principles of Good Laboratory Practice;

i) Ensure that after completion (including termination) of the study, the study 

    plan, the final report, raw data and supporting material are archived.

Role and responsibility of Study personnel

1) All personnel involved in the conduct of the study must be knowledgeable in 

    those parts of the Principles of Good Laboratory Practice which are applicable 

    to their involvement in the study. 

2. Study personnel will have access to the study plan and appropriate Standard 

    Operating Procedures applicable to their involvement in the study. It is their 

    responsibility to comply with the instructions given in these documents. Any 

    deviation from these instructions should be documented and communicated 

    directly to the Study Director, and/or if appropriate, the Principal 

    Investigator(s). 

3. All study personnel are responsible for recording raw data promptly and 

    accurately and in compliance with these Principles of Good Laboratory 

    Practice, and are responsible for the quality of their data. 

4. Study personnel should exercise health precautions to minimise risk to 

    themselves and to ensure the integrity of the study. They should communicate 

    to the appropriate person any relevant known health or medical condition in 

    order that they can be excluded from operations that may affect the study

Types of Inspections by Quality Assurance Personnel

Inspections can be of three types as specified by Quality Assurance Programme Standard Operating Procedures:

    – Study-based inspections,

    – Facility-based inspections,

    – Process-based inspections. 

TERMS CONCERNING THE ORGANISATION OF A TEST FACILITY

Test facility means the persons, premises and operational unit(s) that are necessary for conducting the non-clinical health and environmental safety study. For multi-site studies, those which are conducted at more than one site, the test facility comprises the site at which the Study Director is located and all individual test sites, which individually or collectively can be considered to be test facilities.

Test site means the location(s) at which a phase(s) of a study is conducted.

Test facility management means the person(s) who has the authority and formal responsibility for the organisation and functioning of the test facility according to these Principles of Good Laboratory Practice.

 

Test site management (if appointed) means the person(s) responsible for ensuring that the phase(s) of the study, for which he is responsible, are conducted according to these Principles of Good Laboratory Practice. 

Sponsor means an entity which commissions, supports and/or submits a non-clinical health and environmental safety study. 

Study Director means the individual responsible for the overall conduct of the nonclinical health and environmental safety study. 

Principal Investigator means an individual who, for a multi-site study, acts on behalf of the Study Director and has defined responsibility for delegated phases of the study. The Study Director’s 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 that all applicable Principles of Good Laboratory Practice are followed. 

Quality Assurance Programme means a defined system, including personnel, which is independent of study conduct and is designed to assure test facility management of compliance with these Principles of Good Laboratory Practice. 9. Standard Operating Procedures (SOPs) means documented procedures which describe how to perform tests or activities normally not specified in detail in study plans or test guidelines. 

TERMS CONCERNING THE NON-CLINICAL HEALTH AND ENVIRONMENTAL SAFETY STUDY 

Non-clinical health and environmental safety study, henceforth referred to simply as “study”, means an experiment or set of experiments in which a test item is examined under laboratory conditions or in the environment to obtain data on its properties and/or its safety, intended for submission to appropriate regulatory authorities. 

Short-term study means a study of short duration with widely used, routine techniques. 

Study plan means a document which defines the objectives and experimental design for the conduct of the study, and includes any amendments. 

Study plan amendment means an intended change to the study plan after the study initiation date.

Study plan deviation means an unintended departure from the study plan after the study initiation date.

Test system means any biological, chemical or physical system or a combination thereof used in a study. 

Raw data means all original test facility records and documentation, or verified copies thereof, which are the result of the original observations and activities in a study. Raw data also may include, for example, photographs, microfilm or microfiche copies, computer readable media, dictated observations, recorded data from automated instruments, or any other data storage medium that has been recognised as capable of providing secure storage of information for a time period.

Specimen means any material derived from a test system for examination, analysis, or retention. 

Experimental starting date means the date on which the first study specific data are collected.

Experimental completion date means the last date on which data are collected from the study. 

Study initiation date means the date the Study Director signs the study plan.

Study completion date means the date the Study Director signs the final report. 

TERMS CONCERNING THE TEST ITEM 

Test item means an article that is the subject of a study. 

Reference item (“control item”) means any article used to provide a basis for comparison with the test item.

Batch means a specific quantity or lot of a test item or reference item produced during a defined cycle of manufacture in such a way that it could be expected to be of a uniform character and should be designated as such.

Vehicle means any agent which serves as a carrier used to mix, disperse, or solubilise the test item or reference item to facilitate the administration/application to the test system.