a quality system concerned withthe organizational process and theconditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported
Purpose :to promote the development of qualitytest data and provide a tool to ensure asound approach to the management oflaboratory studies, including conduct,reporting and archiving.
GCP : Good Clinical Practice
GLP apply only to studieswhich :• are non-clinical, i.e. mostly studies onanimals or in vitro, including theanalytical aspects of such studies .• are designed to obtain data on theproperties and/or the safety of items withrespect to human health and/or theenvironment .• are intended to be submitted to anational registration authority with thepurpose of registering or licensing the
GLP requirements for non-clinicallaboratory studies conducted toevaluate drug safety cover the followingclasses of toxicity :• Single dose studies• Repeated dose toxicity (sub-acute and chronic)• Reproductive toxicity (fertility, embryo-foetal toxicityand teratogenicity, peri-/post natal toxicity)• Mutagenic potential• Carcinogenic potential• Toxicokinetics (pharmacokinetic studies whichprovide systemic exposure data for the above studies)• Pharmacodynamic studies designed to test thepotential for adverse effects (Safety pharmacology)• Local tolerance studies, including phototoxicity,irritation and sensitisation studies, or testing forsuspected addictive and/or withdrawal effects of drugs.
N.BGLP is not directly concerned with thescientific design of studies. The scientificdesign may be based on test guidelines andits scientific value is judged by the (Drug)Regulatory Authority that provides marketingauthorisation.However, adherence to GLP will remove manysources of error and uncertainty, adding to theoverall credibility of the study
GLP main points:1. Resources: Organisation, personnel, facilities and equipment2. Characterisation: Test items andtest systems3. Rules: Protocols, standardoperating procedures (SOPs)4. Results: Raw data, final report andarchives5. Quality Assurance: Independent
ResourcesOrganization and Personnel
GLP regulations require cleardefinitions of the structure ofthe research organisation andthe responsibilities of theresearch personnel ,and job descriptions give animmediate idea of the way inwhich the laboratory functionsand the relationships betweenthe different departments and
the manager of a test facilityhas overall responsibility for the implementation of both good science and good organisation, including compliance with GLP.
Good Science:1. • Careful definition of experimental design and parameters.2. • Performance of experiments based on valid scientific procedures.3. • Control and documentation of experimental and environmental variables.4. • Careful, complete evaluation and reporting of results.5. • Assuring that results become part of
Good Organization :1. • Provision of adequate physical facilities and qualified staff.2. • Planning of studies and allocation of resources.3. • Definition of staff responsibilities and training of staff.4. • Good record keeping and organised archives.5. • Implementation of a process for the verification of results.6. • Compliance with GLP
The master schedule must ensurethat:• All studies (contracted and in-house) are included.• Change control reflects shifts in dates andworkload.• Time-consuming activities such as protocol reviewand report preparation are incorporated.• The system is the “official” one (i.e. don’t have twoor more competing systems for the same purpose).• The system is described in an approved SOP.• Responsibility for its maintenance and updating aredefined.• The various versions of the master schedule areapproved and maintained in the archive as raw data.• Distribution is adequate and key responsibilitiesare identified.
All quality systems are based on makingpeople responsible for their actions. Definition of tasks and responsibilities• “Don’t perform a procedure if you don’tunderstand the reason, the context and theconsequences of it”.• “Signing your work means you take fullresponsibility for the correct completion ofyour task”.
TrainingThe training system should haveelements common to all GLP• Formal.• Approved.• Documented to a standard format.• Described in a Standard OperatingProcedure.• Possible to perform an historicalreconstruction of training through thearchived documents.
Facilities Buildings and Equipment
Buildings: General Principles• of suitable size, construction andlocation to meet the requirements ofthe study and to minimisedisturbances that could interferewith the study.• Physical Separation; e.g. walls,doors, filters or separate cabinets orisolators. In new buildings, or thoserecently renovated, separation will
• Organisational Separation; e.g. carrying outdifferent activities in the same area but atdifferent times, allowing for cleaning andpreparation between operations, maintainingseparation of staff, or by establishing definedwork areas within a laboratory.As an illustration of the principles involved weshall consider:Pharmacy and Dose Mixing Areas:concerned with test material control andmixing with vehicles (although the sameconsiderations would apply to other areassuch as analytical or histopathologylaboratories).Animal facilities
Pharmacy and Dose Mixing Areasreceipt, storage, dispensing, weighing, mixing,dispatch to the animal house and wastedisposal SizeConstructionArrangementThere should be separate areas for:• Storage of test items under different conditions.• Storage of control items.• Handling of volatile materials.• Weighing.• Mixing of different dose formulations, e.g. in the dietor as solutions or suspensions.• Storage of prepared dose formulations.• Cleaning equipment.• Offices and refreshment rooms.• Changing rooms.
Animal facilityRequirements will differ depending upon the natureand duration of the studiesA well designed animal house would maintainseparation by providing areas for:• Different species.• Different studies.• Quarantine.• Changing rooms.• Receipt of materials.• Storage;- bedding and diet,- test doses,- cages.• Cleaning equipment.• Necropsy.• Laboratory procedures.
Achievement of adequate separationby:• Minimising the number of staff allowed toenter the building.• Restricting entry into animal rooms.• Organising work flow so that clean and dirtymaterial are moved around the facility atdifferent times of day (if the construction ofthe facility does not permit other solutions)and so that corridors are cleaned betweenthese times.• Requiring staff to put on different clothing indifferent zones within the facility.
EquipmentGLP requirements is to ensure the reliabilityof data generated and to ensure that data arenot invalidated or lost as a result ofinaccurate, inadequate or faulty equipment.• Equipment suitability• Calibration• Maintenance Preventive maintenance Curative maintenance Documentation