2 FDA Draft Guidences Released for Public Comment

 The FDA has released two draft guidance for public comment:

It has taken the FDA 6 weeks to release this draft ICH guidance:

BIOEQUIVALENCE FOR IMMEDIATE-RELEASE SOLID ORAL DOSAGE FORMS

1.1 Objective

This guideline is intended to provide recommendations on conducting bioequivalence (BE) studies during both development and post approval phases for orally administered immediate-release (IR) solid oral dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension.

For my bioanalytical colleagues, it covers what should be measured (prodrug, drug, and or metabolite, as well as enantiomers vs racemates) and does point to ICH M10 Bioanalytical Method Validation and Study Sample Analysis for how the analyses should be conducted.

For my PK and statistical colleagues: Normally, excluding subject data for inconsistencies is difficult, but M13 allows their data to be excluded for subjects with low exposure (<5% geometric mean AUC of the product in question, which should be calculated without inclusion of data from the subject)

The second draft guidance covers

Considerationsfor the Design and Conduct of Externally Controlled Trials for Drug andBiological Products

This guidance deals with the use of data from subjects not enrolled within the trial in comparison to subjects enrolled in the trial and on trial therapy. From the Introduction:

The guidance addresses considerations for the design and analysis of externally controlled trials to study the effectiveness and safety of drugs, including discussion of threats to the validity of trial results from potential bias. Although various sources of data can serve as the control arm in an externally controlled trial, this guidance focuses on the use of patient-level data from other clinical trials or from real-world data (RWD) sources, such as registries as well as electronic health records (EHRs) and medical claims.

There may be a number of challenges to ensure reliable and unbiased data, but this guidance paves the way for reducing costs and potentially including larger control arm data sets.