Bioequivalencia

European Medicines Agency

London, 20 January 2010
Doc. Ref.: CPMP/EWP/QWP/1401/98 Rev. 1/ Corr **
COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE
(CHMP)

GUIDELINE ON THE INVESTIGATION OF BIOEQUIVALENCE

DISCUSSION IN THE JOINT EFFICACY AND QUALITY
WORKING GROUP

December 1997 –
October 1998
July 1998

TRANSMISSION TO CPMP
RELEASE FOR CONSULTATION

December 1998DEADLINE FOR COMMENTS

June 1999

DISCUSSION IN THE DRAFTING GROUP

February –
May 2000

TRANSMISSION TO CPMP
RELEASE FOR CONSULTATION

July – December 2000
December 2000
March 2001

DEADLINE FOR COMMENTS
DISCUSSION IN THE DRAFTING GROUP

March - May 2001

TRANSMISSION TO CPMP

July 2001

ADOPTION BY CPMP

July 2001

DATE FOR COMING INTO OPERATION
DISCUSSION ON REV. 1IN THE PK-GROUP OF THE EFFICACY
WORKING PARTY

January 2002
May 2007-July 2008

DISCUSSION ON REV. 1 BY THE QUALITY WORKING PARTY

June 2008

DRAFT REV. 1 AGREED BY THE EFFICACY WORKING PARTY

8 July 2008

ADOPTION REV. 1 BY CHMP FOR RELEASE FOR
CONSULTATION
END OF CONSULTATION REV. 1 (DEADLINE FOR COMMENTS)

24 July 2008
31 January 2009

7 Westferry Circus, Canary Wharf,London, E14 4HB, UK
Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 86 13
E-mail: mail@ema.europa.eu http://www.ema.europa.eu
© European Medicines Agency, 2010. Reproduction is authorised provided the source is acknowledged.

REV. 1 AGREED BY THE EFFICACY WORKING PARTY
REV. 1 ADOPTION BY CHMP
REV. 1 DATE FOR COMING INTO EFFECT

January 2010
20 January 2010
1 August 2010

Thisguideline will replace the “Note for guidance on the investigation of bioavailability and
bioequivalence" CPMP/QWP/EWP/1401/98 and the related questions in the Q&A document
(CHMP/EWP/40326/06). This guideline includes recommendations on BCS-based biowaivers.
* The correction includes changes in section 4.1.4 "Study conduct", sub-section "Fasting or fed
conditions", last paragraph (page 10):replacement of the unit "calories" against "kcal"; correction in
section 4.1.8 "Evaluation", sub-section "Parameters to be analysed and acceptance limits", last
paragraph (page15): deletion of "for AUC" in the cross-reference to section 4.1.9.
** The correction concerns a typographical correction in Appendix II – paragraph on “Non-oral
immediate release dosage forms with systemic action”.KEYWORDS

Bioequivalence, pharmacokinetics, biowaiver, in vitro dissolution, generics

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GUIDELINE ON THE INVESTIGATION OF BIOEQUIVALENCE
TABLE OF CONTENTS
EXECUTIVE SUMMARY................................................................................................................... 4
1.
1.1
1.2
1.3

INTRODUCTION......................................................................................................................... 4
BACKGROUND ......................................................................................................................... 4
GENERIC MEDICINAL PRODUCTS ............................................................................................. 4
OTHER TYPES OFAPPLICATION................................................................................................ 4

2.

SCOPE............................................................................................................................................ 4

3.

LEGAL BASIS .............................................................................................................................. 5

4.

MAIN GUIDELINE TEXT.......................................................................................................... 5

4.1

DESIGN, CONDUCT AND EVALUATION OF BIOEQUIVALENCE STUDIES .................................... 5
4.1.1
Study design..................................................................................................................... 6
4.1.2
Reference and test product...