Abstract��OBJECTIVE To investigate similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration.METHODS The comparisons of these bioequivalence recommendations were performed and based on bioequivalence study designs, selection of bioequivalence subjects,dosage, selection of reference products, method of pharmacokinetic calculations and bioequivalence acceptance limits,bioequivalence waiver on multiple-strength products and and implementation of the Biopharmaceutics Classification System, which are issued by Australia, the European Medicines Association, Japan,the USA, and the World Health Organization.RESULTS There were lots of differences were found in bioequivalence approaches among the regulatory authorities surveyed, although there are more similarities.CONCLUSION Discussion of the similarities and differences among bioequivalence approaches used by international regulatory authorities would provide instructive and practical assists to the equivalence assessment of quality and curative effect for generic products in China.
���������������������Ƽ������������ϼ. �ڷ��������ҩƷ�����Ч���о�����ָ��ԭ��Ҫ�����[J]. �й�ҩѧ��־, 2016, 51(20): 1807-1814.
ZHU Feng-chang,WANG Ai-guo,HAN Feng,CAO Xiu-ping,JIANG Kui,DING Li-xia. A Survey of International Guidelines for Bioequivalence of Systemically Available Orally Administered Generic Drug Products. Chinese Pharmaceutical Journal, 2016, 51(20): 1807-1814.
CFDA. Guidance on Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. (2016-3-18). http://www. sda. gov. cn/WS01/CL0087/147583. html.
[2]
ZHANG Y F, ZHONG D F. Main points and inspirations of guidance for bioequivalence studiesof oral solid products in European and American countries . Chin J New Drug(�й���ҩ��־),2014,23(13):1501-1505.
[3]
FDA. Guidance for industry: Waiver of in invo bioequivalence studies for immediate-release solid oral dosage forms based on a Biopharmaceutics Classification System .(2015). http://www. fda. gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070246. pdf.
[4]
GAO Y, GENG L D. Comparison and discussion of FDA,WHO and EMA guidelineson BCS-based biowaiver. Chin J New Drug(�й���ҩ��־),2012,21(24):2861-2869.
[5]
FDA. Guidance for industry:food-effect bioavailability and fed bioequivalence studies.(2002). http://www. fda. gov/downloads/regulatoryinformation/guidances/ucm126833. pdf.
[6]
FDA. Bioavailability and bioequivalence studies for orally administered drug products-general considerations . (2003). http://www. fda. gov/Drugs /Guidance ComplianceRegulatory Information / Guidances / ucm064964.htm.
[7]
Center for Drug Evaluation and Research(CDER). Guidance for Industry. Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA(Draft Guidance). . http://www. fda. gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm377465. pdf.
[8]
FDA. Guidance for industry: bioavailability and bioequivalence studiessubmitted in NDAs or INDs-general considerations (Draft Guidance). (2013) http://www. fda. gov/Drugs / Guidance compliance regulatory Information / Guidances /ucm064964. htm.
[9]
FDA. Bioequivalence Recommendations for Specific Products(2010). . http://www. fda. gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072872. pdf. FDA. Product-Specific Recommendations for Generic Drug Development(2015). . http://www. fda. gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm075207. htm. EMA. Note guidance on Investigation of Bioavailability and Bioequivalence (2000). . http://www. ema. europa. eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003519. pdf EMA. Guideline on the Investigation of Bioequivalence . (2010) . http://www. ema. europa. eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039. pdf EMA. Product-specific bioequivalence guidance . (2010). http://www. ema. europa. eu/ema/index. jsp?curl=pages/regulation/general/general_content_000625. jsp& mid=WC0b01ac0580848f74. WHO. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability . (2015) http://www. who. int/medicines/areas/quality_safety/quality_assurance/Annex7-TRS992. pdf. WHO. Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products . (2002). http://www. who. int/medicines/areas/quality_safety/quality_assurance/GuidanceSelectionComparatorPharmaceutical Products Equivalence AssessmentInterchangeable Multisource Products TRS902 Annex11. pdf. WHO. Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products . (2015) http://www. who. int/medicines/areas/quality_safety/quality_assurance/Annex8-TRS992. pdf. WHO. Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms . (2006) http://www. who. int/medicines/areas/quality_safety/quality_assurance/Proposal Waive Vivo Bioequivalence Requirements ModelList Essential Medicines Immediate Release Solid Oral Dosage Forms TRS937 Annex8. pdf?ua=1. WHO. Guidance for organizations performing in vivobioequivalence studies . (2016) http://www. who. int/medicines/publications/pharmprep/WHO_TRS_996_annex09. pdf?ua=1. SONG C L, NIU J Z, ZHANG Q M, et al. Introduction of Reevaluation of Generic Drug in Japan . Chin Pharm J(�й�ҩѧ��־), 2014, 49(12):1087-1090. Guideline for Bioequivalence Studiesof Generic Products . (2012) http://www. nicpbp. org. cn/fzy/CL0626/4398. html. Guideline for Bioequivalence Studiesof Solid Oral Dosage Forms with multiple strengths. (2012) http://www. nicpbp. org. cn/fzy/CL0626/4397. html. HUANG H W, NIU J Z,LIN L,et al. Introduction of Orange Book in USA and Japan and discussion of thedirectory selection principle for reference formulations in China. Chin J Pharm Anal(ҩ�������־), 2013,33(11)2009-2012. TGA. Australian Regulatory Guideline on Over-the-Counter Medicines(ARGOM) Appendix I, Section 6, generic products . (2012) . http://www. tga. gov. au/industry/otcargom-app1-06-generic. htm. TGA. Guidelines on efficacy and safety aspects of OTC . (2015) http://www. tga. gov. au/book/export/html/71157. AMIDON G L,LENNEMAS H,SHAH V P,et al. A theoretical basis for a biopharmaceutic drug classification: the correlation ofin vitro drug product dissolution and in vivo bioavailability.Pharm Res,1995,12(3) :413-420. MalinsA, Milne C P. Application of biopharmaceuticsclassificationsystem in drug development. Pharma Focus Asia, Ochre Press . (2012) http://www. pharmafocusasia. com/research_development/application-Biopharmaceutics-Classification-System-Drug-Development. htm. CHEN J C, Introduction of FDAAnnounced Bioavailability and bioequivalence studies for orally administered drug products-general considerations. (2007) . http://www. cde. org. cn/dzkw. do?method=largePage&id=246.
2016, Vol. 51 
