Good Laboratory Practices

Good Laboratory Practices (GLP) is an official regulation that was created by the FDA in 1978. Good Laboratory Practice (GLP) is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.

The purpose of GLP is to

  • Ensure quality test data
  • Ensure sound laboratory laboratory management
  • Ensure robust conductance of laboratory testing
  • Ensure accurate reporting of test findings
  • Ensure safe archival of laboratory data

The GLP Principles basically encompasses following points

1. Test facility organization and personnel

  • Test facility management should designate personnel to assume responsibility for the quality assurance programme, and these personnel should not be involved in the conduct of the regulatory work being assured.
  • Test facility management should ensure that there is a quality assurance programme, with designated personnel, and assure that the quality assurance programme is being performed in accordance with the principles of GLP.
  • Study Director’s Responsibilities
    • Has the responsibility for the overall performance of the study and the final report.
    • Approves the study plan and amendments and communicate them to the QA personnel.
    • Ensures that SOPs, study plans and their amendments are available to study personnel.
    • Ensures that the SOPs are followed, assess the impact of any deviations and takes appropriate corrective and preventive action.
    • Ensures that raw data are documented and recorded.
    • Computerized systems are validated.
    • Sign and date the final report to indicate acceptance of responsibility.
  • Study Personnel Responsibilities
    • Knowledge of the GLP principals
    • Access to the study plan and appropriate SOPs
    • Comply with the instructions of the SOPs
    • Record raw data
    • Study personnel are responsible for the quality of their data
    • Exercise health precautions to minimize risk
    • Ensure the integrity of the study

2. Quality Assurance (QA) programme

  • Quality control is the process, procedures and authority used to accept or reject all components, drug product containers, closures, in-process materials, packaging material, labeling and drug products and the authority to review production records to assure that no errors have occurred, that they have been fully investigated.
  • The quality and reliability of test data count on the state and condition of the test system which is used in its production.
  • The test facility should have a documented Quality Assurance Programme to guarantee that studies performed comply with these Principles of Good Laboratory Practice.
  • The Quality Assurance Programme should be performed by an individual or by individuals designated by.
  • The Quality Assurance personnel should be responsible of maintaining copies of all approved study plans and Standard Operating Procedures in use in the test facility and have access to an up-to-date copy of the master Schedule, verifying that the study plan contains the information required for compliance with these Principles of Good Laboratory Practice, conducting inspections to determine if all studies are conducted in accordance with these Principles of Good Laboratory Practice.
  • Inspections should also determine that study plans and Standard Operating Procedures have been made available to study personnel and are being followed.
  • Inspections are made in order to determine compliance of the study with GLP principles.
  • Three types of inspection are basically carried out: Study-based inspections, Facility-based inspections, Process-based inspections.
  • These inspections should involve those parts of a study that have particular importance for the validity of the data and the conclusions to be drawn from there, or where deviations from the rules of GLP would most heavily have a powerful effect on the integrity of the study.
  • Quality Assurance thus has to find a balance in their inspectional activities, evaluating the study type and “critical phases”, in order to achieve a well supported view of the GLP compliance at the test facility and within the studies conducted.
  • In the final reports it should be confirmed that the methods, procedures, and observations are accurately and completely described, and that the reported results accurately and completely reflect the raw data of the studies.
  • Inspections of the final reports are done for accurate and full description.
  • The audit of the final report, hence serves to ascertain the quality and integrity of the specific study with its detailed assessment of GLP compliance throughout the study and with its concomitant review of all relevant information, records and data.

3. Facilities

  • GLP requires that test facilities be of appropriate size, construction and location to meet the requirements of the study and minimize disturbances that would interfere with the validity of the study.
  • They should be designed to provide an adequate degree of separation between the various activities of the study.
  • Separation renders the assurance that different functions or activities do not interfere with each other or affect the study.
  • Minimizing disturbance by separation can be achieved by:
    • Physical separation: this can be achieved by walls, doors or filters, or by the use of isolators. In new buildings or those under transition or renovation, separation will be part of the design.
    • Separation by organization, for example by the establishment of defined work areas within a laboratory carrying out different activities in the same area at different times, allowing for cleaning and preparation between operations or maintaining separation of staff, or by the establishment of defined work areas within a laboratory.
  • Isolation of test systems and individual projects to protect from biological hazards.
  • Suitable rooms for the diagnosis, treatment and control of diseases.
  • Storage rooms for supplies and equipment.
  • Separate areas for receipts and storage of the test and reference items.
  • Separation of test items from test systems.
  • Archive facilities for easy retrieval of study plans, raw data, final reports, samples of test items and specimens.
  • Handling and disposal of waste in such a way not to jeopardize the integrity of the study.
  • Documented inspection, cleaning, maintenance and calibration of apparatus.

4. Test systems

  • Equipment, including validated computerized systems, used for the generation, storage and recovery of data, and for controlling environmental factors relevant to the study should be suitably located and of appropriate design and adequate capacity.
  • Equipment records should include: name of the equipment and manufacturer, model or type for identification, serial number, and date equipment was received in the laboratory, copy of manufacturers operating instruction(s).
  • Equipment used in a study should be periodically inspected, cleaned, maintained, and calibrated according to Standard Operating Procedures.
  • Records of these activities should be maintained.
  • Calibration should be traceable to national or international standards of measurement.
  • Instrumentation validation is a process necessary for any analytical laboratory.
  • Data produced by “faulty” instruments may give the appearance of valid data.
  • The frequency for calibration, re-validation and testing depends on the instrument and extent of its use in the laboratory.
  • Chemicals, reagents, and solutions should be labeled to indicate identity, expiry date and specific storage instructions.
  • Information concerning source, preparation date and stability should be available.
  • Appropriate design and adequate capacity of apparatus used for the generation of data.
  • Integrity of physical/chemical test systems and biological test systems.
  • Proper conditions for storage, housing, handling and care.
  • Humanely destruction of inappropriate test systems.
  • Records of source date of arrival and arrival conditions of test systems.
  • Acclimatization of biological systems to the test environment.
  • Proper identification of test systems in their housing or container or when removed.
  • Cleaning and sanitization of housings or containers.

5.Test and reference items

  • Records including test item and reference item characterization, date of receipt, expiry date, quantities received and used in studies should be maintained.
  • Handling, sampling, and storage procedures should be identified in order that the homogeneity and stability are assured to the degree possible and contamination or mixup are precluded.
  • Storage container(s) should carry identification information, expiry date, and specific storage instructions.
  • Each test and reference item should be appropriately identified (e.g., code, Chemical Abstracts Service Registry Number [CAS number], name, biological parameters).
  • For each study, the identity, including batch number, purity, composition, concentrations, or other characteristics to appropriately define each batch of the test or reference items should be known.
  • In cases where the test item is supplied by the sponsor, there should be a mechanism, developed in co-operation between the sponsor and the test facility, to verify the identity of the test item subject to the study.
  • The stability of test and reference items under storage and test conditions should be known for all studies.
  • If the test item is administered or applied in a vehicle, the homogeneity, concentration and stability of the test item in that vehicle should be determined.
  • For test items used in field studies (e.g., tank mixes), these may be determined through separate laboratory experiments.
  • A sample for analytical purposes from each batch of test item should be retained for all studies except short-term studies.
  • The register for all reference substances and reference materials should be maintained and contain the following information:
  1. a) the identification number of the substance or material
  2. b) a precise description of the substance or material
  3. c) the source
  4. d) the date of receipt
  5. e) the batch designation or other identification code
  6. f) the intended use of the substance
  7. g) the location of storage in the laboratory, and any special storage conditions
  8. h) expiry date or retest date
  9. i) certificate (batch validity statement) of a pharmacopoeial reference substance and a certified reference material which indicates its use, the assigned content, if applicable, and its status (validity)
  10. j) in the case of secondary reference substances prepared and supplied by the manufacturer, the certificate of analysis

6.Standard Operating Procedures (SOP’s)

  • Standard Operating Procedures (SOPs) are intended to describe procedures that are routinely employed in the performance of test facility operations. Indeed they are defined as “documented procedures which describe how to perform tests or activities normally not specified in detail in study plans or test guidelines.”
  • A test facility should have written Standard Operating Procedures approved by test facility management that are intended to ensure the quality and integrity of the data generated by that test facility.
  • Revisions to Standard Operating Procedures should be approved by test facility management.
  • Each separate test facility unit or area should have immediately available current Standard Operating Procedures relevant to the activities being performed therein.
  • Published textbooks, analytical methods, articles and manuals may be used as supplements to these Standard Operating Procedures.
  • Laboratory management must be sure that the SOPs used in the laboratory are useful in daily operations and they should be scientifically sound and also, they should always be updated as necessary and rewrites should be the part of the routine process.
  • While writing SOP guidelines there must be some precautions such as avoiding restrictive language such as “vortex for exactly 1 minute” but include clear instructions such as “vortex until homogenized” if that satisfies the purpose. Unnecessary steps should not be added such as “consult the manual” unless personnel are required to follow this step.
  • Study personnel should easily access the study plan and appropriate Standard Operating Procedures should be applicable to their involvement in the study.
  • It is their responsibility to comply with the instructions given in these documents. Study personnel should exercise health precautions to minimize risk to themselves and to ensure the integrity of the study.
  • Deviations from Standard Operating Procedures related to the study should be documented and should be acknowledged by the Study Director and the Principal Investigator(s), as applicable.

7. Performance of the study

  • Performance of the Study should be monitored carefully.
  • All the standards supplied by the GLP should be followed from the beginning of the study to the end by the final report.
  • For each study, a written plan should exist prior to the initiation of the study.
  • The study plan should contain the following information: Title, nature and purpose of the study, test item identity, reference item used etc.
  • Information concerning the sponsor and facility, names and address (sponsor, test facility, study director), dates approval, dates of the study plan, estimated starting and completion dates etc.
  • The study plan should be approved by a dated signature of the Study Director and verified for GLP compliance.
  • Deviations from the study plan should be described, explained, recognized and dated in a timely fashion by the Study Director and/or Principal Investigator(s) and maintained with the study raw data.
  • Computerized system design should always supply for the retention of full audit trails to show all changes to the data without obscuring the original data.
  • It should be possible to associate all changes to data with the persons having made those changes. Reason for changes should be given.

8. Reporting of study results

  • All studies generate raw data that are the original data gathered during the conduct of a
  • Raw data refers to any laboratory worksheets, records, memoranda, notes, or exact copies that are the results of original observations and activities of a study.
  • The term covers all data necessary for the reconstruction of the report of the study.
  • Raw data may include handwritten notes, photographs, microfiche copies, computer print-outs, magnetic media, dictated observations, and electronically recorded data from automated instruments.
  • They are essential for the reconstruction of studies and contribute to the traceability of the events of a study.
  • Raw data are the results of the experiment upon which the conclusions of the study will be based.
  • Some of the raw data may be used directly, and some of them will be treated statistically.
  • The results and their interpretations provided by the scientist in the study report must be a true and accurate reflection of the raw data.
  • A final report should be prepared for each study.
  • The study report, like all the other scientific aspects of the study, is the responsibility of the Study Director. He/she must ensure that it describes the study accu Reports of Principal Investigators or scientists involved in the study should be signed and dated by them.
  • The final report should be signed and dated by the Study Director to indicate acceptance of responsibility for the validity of the data.
  • If necessary, corrections and additions to a final report should be in the form of amendments.
  • Amendments should clearly specify the reason for the corrections or additions and should be signed and dated by the Study Director.
  • The Study Director is responsible for the scientific interpretation included in the study report and is also responsible for declaring to what extent the study was conducted in compliance with the GLP Principles.
  • The GLP Principles list the essential elements to be included in a final study report.
  • The final report should include the following information: A descriptive title; identification of the test item by code or name, characterization of the test item including purity, stability and homogeneity.
  • Information concerning the sponsor and the test facility should imply; name and address of the sponsor, any test facilities and test sites involved, the study Director, the Principal Investigator(s) and the phase(s) of the study, delegated and scientists having contributed reports to the final report, experimental starting and completion dates.
  • A Quality Assurance Programme statement listing the types of inspections made and their dates, including the phase(s) inspected, and the dates any inspection results should be reported to management and to the Study Director and Principal Investigator(s).
  • This statement should also serve to confirm that the final report reflects the raw data.
  • It should contain the Description of Materials and Test
  • A summary of results should be
  • All information and data required by the study plan; A presentation of the results, including calculations and determinations of statistical significance; An evaluation and discussion of the results and, where appropriate, conclusions.
  • It should imply the location(s) where the study plan, samples of test and reference items, specimens, raw data and the final report are to be stored.
  • A computerized system to be used in a GLP area should include both the dating and timing of the original entry and the retention of a full audit trail.
  • Such identification could be possible either by the use of personal passwords recognized by the computer or by digital
  • Therefore GLP wants to ensure that data safety and integrity remains the same electronically as in manually recorded data, irrespective of how they were recorded, and that reconstruction of the way in which the final results and conclusions were obtained remains fully possible.
  • The Study Director must sign and date the final report to indicate acceptance of responsibility for the validity of all the data.

Storage and retention of records and materials

The following should be retained in the archives for the period specified by the appropriate authorities:

  • a) The study plan, raw data, samples of test and reference items, specimens, and the final report of each study;
  • b) Records of all inspections performed by the Quality Assurance Programme, as well as master schedules;
  • c) Records of qualifications, training, experience and job descriptions of personnel; d) Records and reports of the maintenance and calibration of apparatus;
  • e) Validation documentation for computerised systems;
  • f) The historical file of all Standard Operating Procedures;
  • g) Environmental monitoring records.
  • In the absence of a required retention period, the final disposition of any study materials should be documented.
  • When samples of test and reference items and specimens are disposed of before the expiry of the required retention period for any reason, this should be justified and documented.
  • Samples of test and reference items and specimens should be retained only as long as the quality of the preparation permits evaluation.
  • Material retained in the archives should be indexed so as to facilitate orderly storage and retrieval.
  • Only personnel authorized by management should have access to the archives.
  • Movement of material in and out of the archives should be properly recorded.
  • If a test facility or an archive contracting facility goes out of business and has no legal successor, the archive should be transferred to the archives of the sponsor(s) of the study(s).

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