Recently FDA published revised draft guidance “BE Studies with PK Endpoints for Drugs Submitted under an ANDA.”


This revised draft supersedes the same which was announced on December 5, 2013.


This revised draft guidance provides recommendations to applicants planning to include BE information in ANDAs and ANDA supplements.


In addition, this guidance describes how to meet the BE requirements set forth in FD&C Act and FDA regulations.


This guidance is generally applicable to dosage forms intended for oral administration and to non-orally administered drug products.


This guidance will also be useful to applicants planning BE studies intended to be conducted during the post-approval period for changes to a drug product approved in an ANDA.


3 additional dosage forms are added in establishing BE section:  


- Orally Disintegrating Tablets

- Sublingual

- Transdermal


2 additional special topics are included:


- Enteral Feeding Tube

- Orally Administered Drugs Intended For Local Action


2 additional APPENDIXes are included:


- APPENDIX A: general design and data handling of bioequivalence studies with pharmacokinetic endpoints. (Revised)


- APPENDIX B: method for statistical analysis using the reference scaled average bioequivalence approach: highly variable drugs (new)


- APPENDIX C: method for statistical analysis using the reference scaled average bioequivalence approach: narrow therapeutic index drugs (new)


This guideline referred following useful guidelines:


1. Bioavailability Studies Submitted in NDAs or INDs — General Considerations (February 2019)  


2. Referencing Approved Drug Products in ANDA Submissions (October 2020)


3. Submission of Summary Bioequivalence Data for ANDAs (May 2011).


4. Statistical Approaches to Establishing Bioequivalence (February 2001).


5. Controlled Correspondence Related to Generic Drug Development (December 2020).


6. Bioanalytical Method Validation (May 2018)


7. Biopharmaceutics Classification System Based Biowaivers (May 2021).


8. Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations (September 1997).


9. Immediate Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation (November 1995)


10. Modified-Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation (October 1997)


11. Assessing Adhesion with Transdermal and Topical Delivery Systems for ANDAs (October 2018)


12. Assessing the Irritation and Sensitization Potential of Transdermal and Topical Delivery Systems for ANDAs (October 2018)  


13. Handling and Retention of BA and BE Testing Samples (May 2004).


14. Providing Regulatory Submissions in Electronic Format—Standardized Study Data (October 2020)