Good Laboratory Practice

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.

Regulatory Bodies

Food and Drug Administration (FDA)

The Food and Drug Administration (FDA or USFDA) is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products.


Medicines and Healthcare Products Regulatory Agency (MHRA) 

The Medicines and Healthcare products Regulatory Agency is an executive agency of the Department of Health in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are acceptably safe.


Therapeutic Goods Administration (TGA)

The Therapeutic Goods Administration is the regulatory body for therapeutic goods in Australia. It is a Division of the Australian Department of Health established under the Therapeutic Goods Act 1989.

Registration, Evaluation Authorisation and Restriction of Chemicals (REACH) program 

Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) is a European Union regulation dating from 18 December 2006.[ REACH addresses the production and use of chemical substances, and their potential impacts on both human health and the environment. Its 849 pages took seven years to pass, and it has been described as the most complex legislation in the Union's history and the most important in 20 years. It is the strictest law to date regulating chemical substances and will affect industries throughout the world. REACH entered into force on 1 June 2007, with a phased implementation over the next decade. The regulation also established the European Chemicals Agency, which manages the technical, scientific and administrative aspects of REACH.


Central Drug Standard Control Organization (CDSCO)

The Central Drugs Standard Control Organization (CDSCO) is the national regulatory body for Indian pharmaceuticals and medical devices, and serves parallel function to the European Medicines Agency of the European Union, the PMDA of Japan, the Food and Drug Administration of the United States and the Medicines and Healthcare products Regulatory Agency of the United Kingdom.

Within the CDSCO, the Drug Controller General of India (DCGI) regulates pharmaceutical and medical devices, under the gamut of Ministry of Health and Family Welfare. The DCGI is advised by the Drug Technical Advisory Board (DTAB) and the Drug Consultative Committee (DCC). It is divided into zonal offices which do pre-licensing and post-licensing inspections, post-market surveillance, and recalls when needed. 

Though the CDSCO has a good track record with the World Health Organization, it has also been accused of past collusion with independent medical experts and pharmaceutical companies. CDSCO plans to open international offices in Beijing, China.


The Environmental Protection Agency (EPA)

The United States Environmental Protection Agency (EPA or sometimes U.S. EPA) is an agency of the federal government of the United States which was created for the purpose of protecting human health and the environment by writing and enforcing regulations based on laws passed by Congress.President Richard Nixon proposed the establishment of EPA and it began operation on December 2, 1970, after Nixon signed an executive order. The order establishing the EPA was ratified by committee hearings in the House and Senate. The agency is led by its Administrator, who is appointed by the President and approved by Congress. The current Administrator is Scott Pruitt. The EPA is not a Cabinet department, but the Administrator is normally given cabinet rank.

The EPA has its headquarters in Washington, D.C., regional offices for each of the agency's ten regions, and 27 laboratories. The agency conducts environmental assessment, research, and education. It has the responsibility of maintaining and enforcing national standards under a variety of environmental laws, in consultation with state, tribal, and local governments. It delegates some permitting, monitoring, and enforcement responsibility to U.S. states and the federally recognized tribes. EPA enforcement powers include fines, sanctions, and other measures. The agency also works with industries and all levels of government in a wide variety of voluntary pollution prevention programs and energy conservation efforts.

In 2016, the agency had 15,376 full-time employees. More than half of EPA's employees are engineers, scientists, and environmental protection specialists; other employees include legal, public affairs, financial, and information technologists. In 2017 the Trump administration proposed a 31% cut to the EPA's budget to $5.7 billion from $8.1 billion and to eliminate a quarter of the agency jobs.


Central Insecticides Board

Although most of the dangers from unregulated and indiscriminate use of pesticides were brought into focus as early as in the year 1958 when the Government of India appointed a Commission of enquiry to suggest Inter-alia remedial measures following a number of deaths in Kerela and Madras (Tamil Nadu) by poisoning through the consumption of imported wheat contaminated by pesticide accidentally which was shipped together with food grains. The whole question of pesticide use and legislation was studied in 1964-67 by an Expert Committee of Indian Council of Agricultural Research headed by Prof. M.S. Thacker. Based on the recommendations of the Expert Committee a comprehensive Insecticides Act was passed in 1968 to regulate the import, manufacture, sale, transport, distribution and use of insecticides with a view to prevent risks to human beings and animals and for other matters connected therewith. The enforcement of Act was tranferred to the Ministry of Agriculture in the year 1970 by the Ministry of Health and family Planning. The department of Agriculture of this Ministry took immediate steps to frame the Rules and constituted Central insecticides Board and Registration committee. The states were simultaneously advised to appoint all functionaries mentioned in the Act. After the stage was fully set, all the provisions of the Insecticides Act was brought into force with effect from 1st August, 1971. In the Act and the Rules framed there under, there is compulsory registration of the pesticides at the Central level and licence for their manufacture, formulation and sale are dealt with at the State level. With the enforcement of the Insecticides Act in the country pesticides of very high quality are made available to the farmers and general public for house-hold use, for protecting the agricultural crops from the ravages of their pests, humans from diseases and nuisance caused by public health pests and the health hazards involved in their use have been minimised to a great extent. For the effective enforcement of the Insecticides Act, the following bodies have been constituted at the Central level.