Final report of GLP animal study
Study Groups
The groups in the study are as follows: Group 1 (Vehicle), Group2 (Low Dose), Group 3 (Medium Dose), Group 4 (High Dose) Group 5(High Dose with a 14 day Recovery Period) 10 male and 10 femalesper group Group 6 (Toxicokinetic Group - Vehicle (5 males & 5females) & High Dose (5 males & 5 females).
Outcomes:
1) The test item was stated to be >98% pure by the Sponsor;however no Certificate of Analysis was received.
2) Following issuing of the study plan the Sponsor asked thatthe higher dose of the test item be administered at 600 mg/kg/dayrather than 700mg/kg/day.
3) Due to an experimental error during the study, animals fromGroup 1 (vehicle) were administered vehicle twice rather than onceon the 14th day of dosing.
4) During acclimatisation period some females and males werehoused together for a single day. Fortunately assessment of thefemales during the course of the study indicated that they were notpregnant and therefore this error did not influence the studyoutcomes.
5) Three animals that received a low dose of the test item werewithout water for the 24 hours before necropsy. The Study Planstated that they were to be fasted but have access to water.
6) The humidity of the room the animals were housed in reached90% on day 14 of dosing. The Study Plan stated limits of30-70%.
Biochemical Analysis
Group 1: Values for all parameter were within historical andliterature range
Group 2: Values for all parameter were within historical andliterature range
Group 3: Values for most parameters were within historical andliterature range, with the exception of slightly elevated Alanineaminotransferase (ALT), Aspartate aminotransferase (AST) andSorbitol dehydrogenase (SDH)
Group 4: Values for most parameters within historical andliterature range, with the exception a significantly higher levelof Alanine aminotransferase (ALT), Aspartate aminotransferase (AST)and Sorbitol dehydrogenase (SDH). ALT, AST and SDH were very high(ALT>AST) in the animals that were euthanised.
Group 5: For those animals that completed the study the valuesfor all parameters, after a 14-day recovery period, were withinhistorical and literature range.
Haematology
White blood differentials were normal in all animals.
The Haematocrit was elevated in 3 animals that received the lowdose otherwise all other animals had Haematocrit levels within thenormal range.
Histology
Light microscopy of tissue sections showed an increasedrecruitment of inflammatory cells in the liver. There were nochanges in the spleen, kidney or any other organ examined.
General Observations
The vehicle and low dose groups exhibited no signs oftoxicity.
The mid-level group showed mild to moderate signs of toxicitymanifesting as an altered gait and lack of grooming in 3 of the 10animals.
The high dose group showed moderate signs of toxicitymanifesting as an altered gait and lack of grooming in 5 of the 10animals. Three animals (2 male, 1 female) from group 4 and 4animals from group 5 (2 male and 2 female) were found to exhibitsevere signs of toxicity and were euthanised between the 19th and24th day of dosing. These animals also exhibited a decrease in bodyweight of 5% per day for the 3 days prior. Blood was collected fromthese animals and all clinical biochemistry and haematologyperformed.
Toxicokinetics/Dose formulation
Toxicokinetic analysis indicated that mean Cmax, AUClast&T1/2 for the test item were comparable between males & femaleson Day 1.
Both Cmax & AUClast increased on Day 28, with mean valuesconsistently higher for males compared to the correspondingfemales. T1/2 remained similar to Day 1 values for both males andfemales.
Analysis of the dose formulation indicated that the dosesadministered were as stated in the study plan.
Question
Assume the role of QA and, taking into account all thedifferent aspects which may have been audited during the course ofthe study, prepare an appropriate QA Statement for inclusion in theFinal Report.
Pls write in detail and follow the requirementbelow
A Quality Assurance Programme statement listing thetypes of inspections made and their dates, including the phase(s)inspected, and the dates any inspection results were reported tomanagement and to the Study Director and Principal Investigator(s),if applicable. This statement would also serve to confirm that thefinal report reflects the raw data.
(Using OECD GLP # 1 & OECD Guideline 407 to assist you)
