Good Laboratory Practice

CHARACTERISATION

Characterization

• Test ItemI. Control before formulationII. Preparation of the Dose formulation• Test systemI. FacilitiesII. Choice of Test systemIII. Suppliers, ordering , transport and receiptIV. AcclimatizationV. Animal identificationVI. Assignment to groupsVII. 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. ReceiptB. Storage of the Test ItemC. Test item useD. 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• Sponsorprovides: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:• Manufacturer’s name or sponsor’s 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 +4°C 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 planningB. Formulating the test itemC. Sampling and quality control of dose formulationD. Formulation recordsE. Dosing

A. Initial preparation and planning1. Dose levels, number of animals and dose volume- Calculate how much test item required- Purity2. 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 method6. 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

• Containero 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 RecordsDate.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 variationsc. 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 histopathologicalsigns, teratology, spontaneous tumour type and incidence etc.