How to Characterise a Test Item for a GLP Study
Establish what was actually administered, so the study can be attributed to a substance.
What a how-to is not
A how-to is SPEQ’s practitioner method, not a procedure. It does not replace your own SOP, it is not a validated approach, and the judgement calls in it belong to your quality unit.
A nonclinical safety study is evidence about a substance. If the identity, strength, purity, composition and stability of what was administered are not established, the study is evidence about something unknown, and no amount of rigour downstream repairs that. This is the quietest failure mode in good laboratory practice because everything else in the study can be immaculate.
- 1
Establish identity, strength, purity and composition before dosing
Characterise the test item and record the method used. Characterisation performed after the in-life phase describes the material as it is now, not necessarily as it was when animals received it, and the difference is exactly what stability testing exists to detect.
- 2
Determine stability under the conditions of the study
Stability must be known under the storage conditions used and for at least the period of use. A test item stable in a freezer says nothing about a dosing formulation held on a bench for a working day.
- 3
Verify the dosing formulation, not only the neat substance
Confirm concentration, homogeneity and stability in the vehicle at the concentrations actually dosed. Homogeneity failures in a suspension are a common source of animals that received a different dose from the one recorded, and the record will not show it.
- 4
Retain reserve samples for the studies that require them
Reserve samples from each batch let a question about the material be answered later. A study whose material has been consumed cannot answer the question that arises when a signal appears years afterwards, and that question does arise.
- 5
Control receipt, storage, distribution and return
Record what was received, its batch, where it was stored, what was issued to the study, and what was returned or disposed of. The accountability record is what lets a reviewer confirm that the material dosed was the material characterised.
- 6
Characterise the vehicle and the control article too
The vehicle and any control article need the same treatment. An uncharacterised vehicle turns the control group into an uncontrolled comparison, which removes the interpretive basis for the whole study.
- !Characterisation performed after the in-life phase, describing the material as it is now rather than as dosed.
- !Stability established for the neat substance but not for the formulation at the concentrations actually used.
- !Homogeneity unverified in a suspension, so recorded dose and delivered dose diverge invisibly.
- !The vehicle or control article left uncharacterised, undermining the comparison the study rests on.
How to Characterise a Test Item for a GLP Study: frequently asked questions
Common questions on characterise a test item for a glp study.
Why does the formulation need separate testing?
Because a substance can be stable and pure on its own and unstable, heterogeneous or adsorbed onto container walls in the vehicle at the concentration dosed. The animals received the formulation, so that is what the study is evidence about, and characterising only the neat substance leaves the delivered dose unverified.
What are reserve samples for?
Answering later questions about the material — identity, purity, degradation — when a finding needs re-examination. Studies supporting long-term exposure retain them for that reason. Without a retained sample, a question raised years afterwards has no material to be settled against.
Does the control group need characterisation?
Yes. If the vehicle is uncharacterised, an effect seen in the control group has no explanation and an effect absent from it has no baseline. The control is only a control if what it received is as well established as what the treated groups received.