Bioavailability/Bioequivalence Guidelines

Sometimes its hard to find regulatory guidance documents on the web. One has to scroll through several pages before you actually find what you need. To make things easier, I previously had a webpage where the Bioavailability/Bioequivalence (BA/BE) guidances of various countries were put together under one page. Now, I will be posting the guidance documents on various topics on this blog. Today, I will start with BA/BE and cover as many topics in clincal pharmacology as possible in the future. If you are working in the generics industry and happen to do clinical studies supporting the ANDA (Abbreviated New Drug Application), you may want to bookmark this page and become familiar with following documents.

Note: All links have been updated (March 2014).

US FDA 

1. Bioavailability and Bioequivalence Studies for Orally Administered Drug Products - General Considerations (Issued 3/2003, Posted 3/19/2003)[PDF]
 NEW DRAFT FOR COMMENTS: Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs- General Considerations (Issued 3/2014)[PDF]

2.  Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application- Draft (12/2013) [PDF]
3. Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action (Posted 4/2/2003)[PDF]
4. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System (Issued 8/2000, Posted 8/31/2000) [PDF]
5. Food-Effect Bioavailability and Fed Bioequivalence Studies (Issued 12/2002, Posted 1/30/2003) [PDF]
6. Handling and Retention of BA and BE Testing Samples (5/25/2004) [PDF]
7. Statistical Approaches to Establishing Bioequivalence (Issued 2/2001, Posted 2/1/2001)[PDF]
8. Submission of Summary Bioequivalence Data for ANDAs (04/2009) [PDF]
9. Bioequivalence Recommendations for Specific Products (06/2010) [PDF]
10. Bioanalytical Method Validation (05/2001)[PDF]. This guidance is under revision  and the draft version dated 09/2013 has been distributed for comments.(09/2013)[PDF]
11. Dissolution Methods Database 

EMA

1. Guideline on the Investigation of Bioequivalence (08/2010)[PDF]

2.  Appendix IV of the guideline on the investigation on bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1): Presentation of biopharmaceutical and bioanalytical data in module 2.7.1 (06/2012) [PDF]
3. Questions & Answers:Positions on specific questions addressed to the pharmacokinetics working party (10/2013) [PDF]
4. Bioanalytical Method Validation (02/2012) [PDF]
5. Modified-release oral and transdermal dosage forms: Section II (01/2000) [PDF]
6. Pharmacokinetic and clinical evaluation of modified-release dosage forms- draft (2013)[PDF]

CANADA (HPMB)

Bioavailability and Bioequivalence [html]

AUSTRALIA (TGA)
Guidance on the Investigation of Bioequivalence [PDF].
TGA has adopted the EMA guidance document with the note "While this guidance suggests that the design and conduct of the study should follow EU regulations on Good Clinical Practice, sponsors should note that the EU Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) has been adopted in Australia with TGA annotations.

JAPAN [PMDA]
There is no official english version of the guidance document, but the presentation on "Approval Review of Generic Drugs in Japan" available here and here by the reviewers from the Office of Generic Drugs, PMDA may be beneficial.

INDIA [CDSCO]
Draft Guidelines for Bioavailability/Bioequivalence Studies on Conventional and Extended Release Dosage Forms

BEBAC- Helmut Schütz also maintains a comprehensive list of BABE guidelines for almost all the countries and you can find it here.

Let me know if I am missing something!