The FDA has updated its draft guidance on bioequivalence studies with fresh advice for developers of drugs in a range of dosage forms. Publication of the updated draft comes almost eight years after the FDA released the first version of the document for consultation.
FDA’s updated draft features new, brief sections on orally disintegrating tablets, sublingual tablets and transdermal delivery, dosage forms that are only mentioned in passing, if at all, in the 2013 text. The section on transdermal delivery occupies the most space, with the FDA using the update to recommend the use of in vivo single-dose, two-treatment, two-period crossover studies with pharmacokinetic endpoints to show the bioequivalence of transdermal delivery systems.
The FDA wants developers of transdermal medicines to apply the systems to the skin as directed unless product-specific guidelines say otherwise. If a product can be applied to multiple sites on the body, the FDA is generally advising companies to use a single site to demonstrate bioequivalence.
The new sections on orally disintegrating and sublingual tablets feature a few lines each. For orally disintegrating tablets, the main recommendation is that bioequivalence studies should test products without water if the labeling permits consumption with or without water. The FDA used the section on the testing of sublingual dosage forms to say the tablets should be put under the tongue until dissolved.
Other changes to the 2013 draft include revisions to existing sections on immediate and modified-release products. In updating the immediate-release section, the FDA has deleted a line that said in vitro data may be acceptable for products that are highly soluble, highly permeable and rapidly dissolving, and added advice about which strength of a medicine to test.
The modified-release section now includes advice about how differences in the coating polymers of the test and reference product can impact the pharmacokinetic profiles. The FDA is advising developers of delayed-release products to view the draft alongside relevant product-specific texts to determine whether “dissolution testing in additional pH/media may be warranted.”