《新药评价》（英文版）长期毒性english

Long-term Toxicity Study Objective Procedures Problems >Mechanic? Innovative

Long-term Toxicity Study ▪ Objective ▪ Procedures ▪ Problems ➢Mechanic? Innovative ?

Obiective Toxic dosage a Safety margin Toxic reaction Target organ Reversibility

Objective ▪ Toxic dosage ▪ Safety margin ▪ Toxic reaction ▪ Target organ ▪ Reversibility

Procedures Animals Housing Test article Route Dosage and group Administration duration observation

Procedures Animals Housing Test article Route Dosage and group Administration duration Observation

Procedures 1- animals rodent non-rodent rat beagle dog mouse mongrel dog monkey

Procedures 1--- animals rodent non-rodent rat beagle dog mouse mongrel dog monkey

Procedures 2- housing Diet, T, humidity, light, ventilation a Rat: lw Dog: TB test, anthelmintic acclimation: 1-w/lm

Procedures 2---- housing ▪ Diet, T, humidity, light, ventilation ▪ Rat: ≤5 /cage , separated， acclimation ≥1w ▪ Dog: TB test, anthelmintic acclimation: 1-2w / 1m

Procedures 3---- test article test article/solvent /excipient name. batch no source, specification, purity, preserve condition, etc same quality criterion

Procedures 3---- test article test article / solvent / excipient name, batch No. , source, specification, purity, preserve condition, etc same quality criterion

Procedures 4- route a The same as intended route iv ip(rat) im or sc >change injection sites vd→iv Change route if necessary

Procedures 4---- route ▪ The same as intended route ▪ iv → ip (rat) im or sc →change injection sites vd → iv ▪ Change route if necessary

Procedures 5--- dosage and group Low Median High Vehicle/Control no slight or obvious solvent /excipient toxicity median or severe normal control ♂早 randomized separately same volume, different concentration

Procedures 5---- dosage and group Low Median High Vehicle /Control no slight or obvious solvent /excipient toxicity median or severe normal control ➢ ♂♀ randomized separately ➢ same volume, different concentration

Procedures 5--- dosage and group rat 3m hon-rodent 20/group ro/group 4-6/group ♂,%早♂,%早 ♂,早 )Limit test: LDko: ig>5 g/kg, iv> 2g/kg, one group: >=50ACD(rat), >=30ACD(non-rodent)

Procedures 5---- dosage and group rat ≤3m rat >3m non-rodent 20/group 40/group 4-6/group ½♂, ½♀ ½♂, ½♀ ½♂, ½♀ ➢ Limit test：LD50: ig > 5 g/kg, iv > 2g/kg , one group: >=50ACD (rat), >=30ACD(non-rodent)

Procedures 6- ad duration Tab. Correspond duration of clinical ad with animal ad clinical ad. duration animal ad. duration 1~3d 14d 1w 1m 4w 3 >1m 6m duration 23m ad. 6 day weekly(mon. to sat)

Procedures 6--- ad. duration Tab. Correspond duration of clinical ad. with animal ad. clinical ad. duration animal ad. duration 1～3d 14d 1w 1m 4w 3m ≥1m 6m ▪ duration ≥3m ad. 6 day weekly(mon. to sat. )