Bioequivalence and Bioavailability Forum

Hi Miityri,

❝ ❝ I never referred to the bioanalytical method used for PK there.

❝ Could you specify, where do you include method preparation and vali­dation?

I give both the analytical and statistical reports as parts of the appendix. These reports contain their respective protocols as appendices within. Haven’t seen any information about method development in the E3 report so far.

❝ In accordance with your consent I would broaden the question:

❝ BE studies are very specific, and typical Report structure (from E3) should be deeply modified.

Absolutely. I hate to read reports, where you have headings on top of empty pages – or worse –

“this page contains no text”

printed across. Also brilliant: All of E3’s headings and some followed by “(not applic­able)”… E3 is almost twenty years old and it was not written having BE in mind.

❝ Sometimes keen discussions are conducted in our department about it. Many men, many minds...

Don’t you have NLYW in the department?

❝ I cannot find any recommendations to the structure of BE Report.

There are a few basic recommendations in national guidelines. They are all completely different but may inspire you. However, as a starter I recommend ICH’s Q&A on E3. Some quotes:

For example, pharmacokinetic […] results could be placed in appropriately iden­­­ti­­fied subsections of the efficacy and safety results sections, or they could be placed in new, appropriately identified results sections.
A rationale is not necessary if sections presented in E3 are re-ordered, re­named, or deleted (if warranted by the study design) or if new sections are added.
It should be noted that E3 was developed for submission of adequate and well-controlled clinical effectiveness studies. Nevertheless, the basic principles de­scribed can be applied to other kinds of trials, such as clinical pharma­co­logy studies […], recognizing that not all sections or data presentations may be appropriate or needed for these other types of trials. Sponsors are en­cour­aged to adapt the recommendations in the Guideline as needed (e.g., by de­let­ing sections that are not relevant or adding needed sections that are not mentioned in the Guideline).
It is appropriate to create new headings in the CSR and new Appendices for these topics. The Guideline provides for and focuses on Efficacy and Safety variables known at the time. Other topics should be well referenced in the CSR body and clearly identified in the Table of Contents.
Current submission options include:

1. Stand alone reports
   These can be placed in “parallel” with the main clinical study report in the eCTD. For example, a clinical pharmacology study might have the clinical study report, a PK report, and an assay validation report.

(my emphases)

Be creative rather than formalistic. BTW, I don’t write anything about statistics under 16.1.9.