Good Laboratory Practice

CHARACTERISATION

Characterization
Test Item I. Control before formulation II. Preparation of the Dose formulation Test system I. Facilities II. Choice of Test system III. Suppliers, ordering , transport and receipt IV. Acclimatization V. Animal identification VI. Assignment to groups VII. Husbandry

The Test Item

Identity, activity, stability and bioavailability Test system= correct amount
Proper control of the test item Records and documents

I. Test item control before formulation

A. B. C. D. Receipt Storage of the Test Item Test item use Disposal

A. Receipt
Staff/ authorized technician/ study director - Receipt and handling - Record: receipt, identity, issue, retention and disposal - SOP or other documents - Informed= arrival of test item Sponsor provides: a. Handling and storage b. Dose formulation Manufacturer - Archive and store batch records

Transport of test item Container: robust Method of transport Duration of journey

Delivery form: Manufacturers name or sponsors name. Date of dispatch. Number of containers or items, type, amount of contents. Identity of the test Item. Batch number(s). Identity of the person responsible for dispatch. Name of the carrier.

Container: Test item name. Batch number. Expiry date. Storage conditions. Container number. Tare weight. Initial gross weight.

Test facility documentation: Test item name. Batch number(s). Description of the test item on arrival at the laboratory; Container number, to allow identification of the container in use. Container type. Net weight of the contents and container tare weight. Storage conditions and location of the container. Initials of the person receiving the container. Date of arrival of the container at the laboratory. Condition of goods on arrival.

B. Storage of the test item

ambient temperature, at +4C and at -20 C. minimize the risk of any cross contamination between items and containers. Primary containers = outer container Reserve sample
Test material identification (name or code number). Batch number. Storage conditions. Net weight. Date on which sample was taken.

C. Test item use

Recording use of test item
Provides traceability of the quantity of test item used Means of monitoring actual use vs. expected use.

Date of use. Study number Gross weight before use. Gross weight after use. Weight of test item used. Weight from dose preparation records. Discrepancy Stock remaining

D. Disposal
Surplus amount- disposed in an evironmetally acceptable way. Documented

II. Preparation of the Dose formulation

A. Initial preparation and planning B. Formulating the test item C. Sampling and quality control of dose formulation D. Formulation records E. Dosing

A. Initial preparation and planning

1. Dose levels, number of animals and dose volume - Calculate how much test item required - Purity 2. Concentration of the dose, amount or volume required - Base on animals weights. 3. SOPs must exist for each procedure in the preparation of the formulation, its analysis, the operation of all equipment and the way in which data will be collected.

4. The method of preparation of the dose form should be tested prior to study start. 5. Trial preparation - further development of the method 6. Stability of the dose form in the vehicle used must also be assessed.

B. Formulating the test item

workstation of adequate size preparation bench surface is clean adequate clean containers, spatulas and other small equipment at hand. Labels have been made out and are available. No other compound is being handled at the same time.

B. Formulating the test item

Identity of test item=protocol instructions and/or requisition form Control- first Placed in suitable containers
Composition. volume

 Container o Study number. o Group number / sex (if relevant). o Weight of container and contents. o Date formulated. o Storage conditions.

C. Sampling and quality control of dose formulation

To fulfill GLP requirements Assessed the concentration, stability and homogeneity of the test item/vehicle mixtures Trial preparation
To avoid waste of time and resources And useless dosing

C. Sampling and quality control of dose formulation

Samples identical to the dosing situation - Different position in the dosing vessel - Long term studies: aliquots -To assess shelf-life of the formulation - good estimate of the effectiveness of the dose preparation process

 Formulation Records Date. Confirmation of test item identity. Identity of formulation instruction (request). Weight of empty container. Weight of container + test item. Weight of added vehicle. Final weight of mixture. Signature/initials of all staff carrying out procedures

D. Dosing
deliver the required amount of test formulation to the required animal accurately and consistently Records Staff must be well trained Dose formulations should be checked Dosing should proceed in a fixed order

Precautions: - Animals are dosed group by group - Only one dose container is open at any time and for each dose level there is a separate, dedicated catheter and syringe. - All cages from one group should be identified before the group is dosed - The container, catheter and syringe used for one group are removed from the dosing station before a new group is dosed. - The outside of the catheter is wiped off with a clean tissue before each animal is dosed. - Only one cage of animals is open at a time. - the time of dosing, each animal is positively identified

Records should identify: - The staff involved in dosing. - The dose given to each animal. - The date and time of dosing. - The weight of each dose level container before and after dosing.

Test System

Test system
Animals, plants, bacteria, organs, cells or analytical equipment Any system exposed to a test item during a safety study

I. Facilities
Personnel, procedures, facilities and equipment Healthy animals Prevent spread of infectious disease.

II. Choice of test system

Observe quality and quantity define the animal for any study by considering the following points: -Appropriateness of the model -Study and project objectives. -Availability of historical background data and past experience.

III. Suppliers, ordering, transport and receipt

Best quality - animal, feed and bedding certificates of animal health, freedom from parasites, nutritional food quality, contaminants in bedding etc. Inspection of animals on arrival

IV. Acclimatization
Animals undergo a period of acclimatization Health status is evaluated Unsuitable individuals- eliminated Length- depends upon the species, the supplier and the type of study - Records: room preparation, animal receipt, husbandry, environmental conditions, etc

V. Animal Identification
cage cards -Temporary -Permanent Animal numbers - Unique - Appear on all data and specimens

VI. Assignment to group

Animals assigned in groups Random statistical or random table Rack and cage locations

VII. Husbandry
Routine (room, rack, and cage cleaning/changing, feeding, watering, environmental checks) Special (fasting) Recorded in animal room logbook

Husbandry
Control and monitoring of environmental variables - A description of all circumstances that may have affected the quality or integrity of the data. a. Source - Heating ventilation and Aircondition and Back-up generator - Bedding contaminants - Soap or detergent residue contamination - Air quality

b. Risk - Base on study species or project specific - E.g. feed characteristics, Basal dietary vitamin A level, bedding variations c. Monitoring - Cage rinse analyses, certificates of analysis for feed, water and bedding, environmental chart recorders, manometers, air renewal measurements, insect pheromone traps, etc.

d. Control - Light timers, barrier procedures, water and air filters, etc.

Husbandry
Data base: - species-specific normal control values: Age/weight, mortality curves, haematology and biochemistry, selected histopathological signs, teratology, spontaneous tumour type and incidence etc.