ABSTRACT
In the development process from the preclinical stage to the subsequent clinical phase,one critical risk controlling step is the determination of the first-in-human (FIH) dose.There is difference in the mechanisms of action and toxic risks between biopharmaceuticals and small molecule drugs,therefore different considerations will be involved in the determination of the FIH dose for biopharmaceuticals.This paper presents the overall review of the preclinical studies supporting the determination of FIH dose and the approaches based on the NOAEL,MABLE,and PK/PD model.The experience-based views that the MABLE-based FIH dose for immune activating products would be reasonably safe,although the NOAEL approach remains conservative and widely used for a majority of biopharmaceuticals are also presented.It is suggested that sponsors should determine the appropriate and safe FIH dose by diverse approaches according to the characteristics of product.Early communication between sponsors and regulators is always beneficial.
ABSTRACT
Most monoclonal antibodies (mAbs) can induce immune responses.For immunomodulatory mAbs,immunotoxicity is the major toxicity.This article summarizes the characteristics of immunotoxicity,the factors associated with immunotoxicity,and the general considerations of nonclinical studies and evaluations.Before the clinical trials,comprehensive nonclinical studies on immunotoxicityshould be step by step conductedbased on mAbs' characteristics.If needed,some additional studies should be conducted.Attention should be paid to combination of in vivo and in vitro studies,combination of animal species and humanex vivo cells,and multiple approaches for studies.
ABSTRACT
In the development process from the preclinical stage to the subsequent clinical phase,one critical risk controlling step is the determination of the first-in-human (FIH) dose.There is difference in the mechanisms of action and toxic risks between biopharmaceuticals and small molecule drugs,therefore different considerations will be involved in the determination of the FIH dose for biopharmaceuticals.This paper presents the overall review of the preclinical studies supporting the determination of FIH dose and the approaches based on the NOAEL,MABLE,and PK/PD model.The experience-based views that the MABLE-based FIH dose for immune activating products would be reasonably safe,although the NOAEL approach remains conservative and widely used for a majority of biopharmaceuticals are also presented.It is suggested that sponsors should determine the appropriate and safe FIH dose by diverse approaches according to the characteristics of product.Early communication between sponsors and regulators is always beneficial.
ABSTRACT
OBJECTIVE@#To identify sarcosaphagous flies and their larvae, pupa.@*METHODS@#Sarcosaphagous flies and their larvae, pupas were collected from human corpses and their surroundings in the Weifang city. A 304 bp region in COI gene was analyzed by mtDNA sequencing.@*RESULTS@#The studied region showed no sequence divergence within same species and significant difference were found between different species in all samples.@*CONCLUSION@#It is a practical approach to identify these Sarcosaphagous flies and their larvae, pupas by sequence analysis of the 304bp region of the COI in mtDNA.
Subject(s)
Animals , Humans , Base Sequence , China , DNA Primers , DNA, Mitochondrial/genetics , Diptera/genetics , Electron Transport Complex IV/genetics , Forensic Medicine , Genes, Insect , Larva/genetics , Phylogeny , Polymerase Chain Reaction/methods , Pupa/genetics , Sequence Analysis, DNA/methods , Species SpecificityABSTRACT
<p><b>OBJECTIVE</b>To increase the recovery rate of ethyl acetate after extracting tripterygium wifordii extractum and to decrease product cost.</p><p><b>METHOD</b>After extracting tripterygium wifordii extractum with ethyl acetate, 3 times saturated salt water was added in it so as to recovery ethyl acetate distilled under normal atmospheric pressure. Ethyl acetate containing salt water was purified through Na2SO4 column.</p><p><b>RESULT</b>Ethyl acetate purified could be used repeatedly and the recovery rate was up to 85%.</p><p><b>CONCLUSION</b>This method is completely adapted for mass production.</p>