Shifting paradigms: biopharmaceuticals versus low molecular weight drugs

被引:133
作者
Crommelin, DJA [1 ]
Storm, G
Verrijk, R
de Leede, L
Jiskoot, W
Hennink, WE
机构
[1] Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, NL-3508 TB Utrecht, Netherlands
[2] OctoPlus, Leiden, Netherlands
关键词
biopharmaceuticals; biologicals; biogenerics; immunogenicity; PK-PD;
D O I
10.1016/S0378-5173(03)00376-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Biopharmaceuticals are pharmaceutical products consisting of (glyco)proteins. Nowadays a substantial part of the FDA-approved drugs belong to this class of drugs. Biopharmaceuticals deserve special attention as they have a number of characteristics that set them aside from low molecular weight drugs. Their activity depends on their complicated shape based on secondary, tertiary and (sometimes) quaternary structures. These structures cannot be fully defined with our present set of analytical techniques and approaches for potency testing. They often are the same as (or closely resemble) endogenous proteins. This means that in safety testing and clinical test programs questions have to be addressed regarding species specific responses, selection of dosing schedules and route of administration, and the possible occurrence of immunogenicity. As the conformational structure of a protein is easily disturbed, formulation and handling of biopharmaceuticals needs special attention in order to optimize the therapeutic effect and minimize adverse reaction, among which immune responses. The issue of biogenerics is gaining more and more interest and different critical elements in the development of biogenerics are touched upon. In conclusion, biopharmaceuticals cannot be characterized fully in terms of their structure like low molecular weight drugs. The performance of biopharmaceuticals relies on strict production protocols and close monitoring of their activity in the clinical situation. 2003 Published by Elsevier B.V.
引用
收藏
页码:3 / 16
页数:14
相关论文
共 28 条
[1]  
ARAKAWA T, 2002, PHARM BIOTECHNOLOGY, P25
[2]   CURRENT GUIDELINES FOR THE PRECLINICAL SAFETY ASSESSMENT OF THERAPEUTIC PROTEINS [J].
BASS, R ;
KLEEBERG, U ;
SCHRODER, H ;
SCHEIBNER, E .
TOXICOLOGY LETTERS, 1992, 64-5 :339-347
[3]  
BRAECKMAN R, 2002, PHARM BIOTECHNOLOGY, P105
[4]   Outlook - Preclinical safety evaluation of biotechnology-derived pharmaceuticals [J].
Cavagnaro, JA .
NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (06) :469-475
[6]  
Crommelin DJ, 2003, EUR J HOSP PHARM, V8, P89
[7]  
CROMMELIN DJA, 2002, PHARM BIOTECHNOLOGY, P73
[8]  
EVENS RP, 2002, PHARM BIOTECHNOLOGY, P389
[9]   Novel crosslinking methods to design hydrogels [J].
Hennink, W. E. ;
van Nostrum, C. F. .
ADVANCED DRUG DELIVERY REVIEWS, 2012, 64 :223-236
[10]  
HERRON J, 1995, PHYSICAL METHODS CHA