浅析美国FDA动物法则的基本原理
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摘要
目的概述动物法则的主要内容,为业界具体实施动物法则提供参考。方法基于本文分析,阐述动物法则的基本原理和技术要点。结果美国食品药品监督管理局(FDA)针对治疗或预防严重威胁生命的化学药物或生物制品(包括疫苗),因伦理道德或不可操作性等原因无法开展临床有效性试验审批和注册,制定了动物法则,即可依据适当的动物有效性试验获得的数据及其他支持性临床试验数据批准该药物上市。笔者介绍了动物法则的基本原理,开展关键性动物药效试验的技术要点,分析外推人体有效剂量的策略。结论动物法则为那些"相当可能(resonably likely)"具有临床获益,但开展人体有效性试验不符合伦理或不可行的候选药物,提供了一种新的注册途径。
OBJECTIVE To summarize the theory about animal rule,in order to provide references for its implementation in industry. METHODS The basic principles and main technology points of the animal rule are analyzed based on the guidance and other literatures issued by the Food and Drug Administration( FDA). RESULTS FDA has formulated guidance,known simply as"animal rule",which applies when clinical efficacy studies in humans cannot be ethically conducted and field efficacy studies are not feasible for certain chemical drugs and biological products including vaccines that are intended to treat or prevent serious or life-threatening diseases. Namely,those applications may be approved for marketing based on evidence of effectiveness derived from appropriate animal studies and any additional supporting data. This article introduces briefly how to carry out the critical animal effective studies and how to extrapolate human effective dose. CONCLUSION Animal rule may provide a new registration strategy for drug candidates when their clinical efficacy studies in humans are not ethical or feasible but reasonably likely brings clinical benefits.
OBJECTIVE To summarize the theory about animal rule,in order to provide references for its implementation in industry. METHODS The basic principles and main technology points of the animal rule are analyzed based on the guidance and other literatures issued by the Food and Drug Administration( FDA). RESULTS FDA has formulated guidance,known simply as"animal rule",which applies when clinical efficacy studies in humans cannot be ethically conducted and field efficacy studies are not feasible for certain chemical drugs and biological products including vaccines that are intended to treat or prevent serious or life-threatening diseases. Namely,those applications may be approved for marketing based on evidence of effectiveness derived from appropriate animal studies and any additional supporting data. This article introduces briefly how to carry out the critical animal effective studies and how to extrapolate human effective dose. CONCLUSION Animal rule may provide a new registration strategy for drug candidates when their clinical efficacy studies in humans are not ethical or feasible but reasonably likely brings clinical benefits.
引文
[1]FDA.Product Development Under the Animal Rule Guidance for Industry[EB/OL].(2015-10)[2018-04-14].https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM399217.pdf.
[2]BEASLEY D W C,BRASEL T L,COMER J E.First vaccine approval under the FDA animal rule[J].NP J Vaccines,2016,1:16013.
[3]FDA.Anthrax:Developing Drugs for Prophylaxis of Inhalational Anthrax Guidance for Industry.(2016-02)[2018-04-14].https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM070986.pdf.
[4]BURNS D L.Licensure of vaccines using the animal rule[J].Curr OpinInvirol,2012,2(3):353-356.
[5]BERGMAN K L.The animal rule:the role of clinical pharmacology in determining an effective dose in humans[J].Clin Pharmacol Therap,2015,98(4):365-368.
[6]BERGMAN K L.The animal rule and emerging infections:the role of clinical pharmacology in determining an effective dose[J].Clin Pharmacol Therap,2009,86(3):328-331.
[7]BERGMAN K L,KRUDYS K,SEO S K,et al.Modeling and simulation in dose determination for biodefense products approved under the FDA animal rule[J].J Pharmacokinet Pharmacodyn,2017,44(2):153-160.
[8]YU S S,YIN H J,WANG Q L,et al.Overview of drugs approved under the Animal Rule and animal efficacy studies[J].Chin Pharm J,2018,53(22):71-77.
[9]LIU L,WANG J F,LI B.Research status and progress of plague vaccine[J].Chin Pharm J(中国药学杂志),2013,48(12):945-949.
[2]BEASLEY D W C,BRASEL T L,COMER J E.First vaccine approval under the FDA animal rule[J].NP J Vaccines,2016,1:16013.
[3]FDA.Anthrax:Developing Drugs for Prophylaxis of Inhalational Anthrax Guidance for Industry.(2016-02)[2018-04-14].https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM070986.pdf.
[4]BURNS D L.Licensure of vaccines using the animal rule[J].Curr OpinInvirol,2012,2(3):353-356.
[5]BERGMAN K L.The animal rule:the role of clinical pharmacology in determining an effective dose in humans[J].Clin Pharmacol Therap,2015,98(4):365-368.
[6]BERGMAN K L.The animal rule and emerging infections:the role of clinical pharmacology in determining an effective dose[J].Clin Pharmacol Therap,2009,86(3):328-331.
[7]BERGMAN K L,KRUDYS K,SEO S K,et al.Modeling and simulation in dose determination for biodefense products approved under the FDA animal rule[J].J Pharmacokinet Pharmacodyn,2017,44(2):153-160.
[8]YU S S,YIN H J,WANG Q L,et al.Overview of drugs approved under the Animal Rule and animal efficacy studies[J].Chin Pharm J,2018,53(22):71-77.
[9]LIU L,WANG J F,LI B.Research status and progress of plague vaccine[J].Chin Pharm J(中国药学杂志),2013,48(12):945-949.