FDA Revises Eligibility for BA/BE Study Waivers
Sponsors of INDs, NDAs, ANDAs and supplemental applications for drugs that are highly soluble in water but not easily absorbed through the intestines can now request waivers of studies proving the drug has a systemic effect or is equivalent to a reference product.
These immediate-release solid oral drugs fall into the third class of a biopharmaceutics classification system that ranks them both by solubility and intestinal permeability. By comparison, Class 1 drugs have high solubility and high permeability and Class 2 drugs have low solubility but high permeability. Class 4 drugs aren’t overly efficient at either of these.
Sponsors looking to waive bioavailability and bioequivalence studies for Class 3 drugs should include evidence that the drug works in the body, the guidance says. This may include a comparison of the drug’s safety and effectiveness with that of other formulations, such as oral liquids, suspensions or injections.
Before requesting a biowaiver, sponsors of Class 3 drugs must prove their drugs are highly soluble and dissolve quickly in water. Firms should include a description of the methods used to test solubility, including analytical methods and the composition of any buffer solutions used, as well as information on the drug’s chemical structure, molecular weight, pH and how much liquid is required to dissolve the highest strength of the drug.
The FDA also wants sponsors to provide a description of immediate-release products used for dissolution testing, including the batch or lot number, expiry date, dimensions, strength and weight. Generics makers need to show that their drug and the reference product dissolve similarly in gastric fluid, intestinal fluid or a buffer.
Comments are due July 5 to regulations.gov, docket no. FDA-2015-D-1245. Read Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System at www.fdanews.com/05-05-15-BEstudiesguidance.pdf. — Lena Freund