Paliperidone Palmitate BE Guidance Revised Again

Back in January 2016, we posted a blog that described a revision in the bioequivalence (BE) Guidance for Paliperidone Palmitate extended-release suspension for intramuscular use (here). That draft Guidance revision was dated December 2015, just a few months ago.  Now another revision takes its place.

Some interesting changes are noted.  We reported that the December 2015 changes included using only patients on a stable 156 mg dose of the drug, while in the June 2016 revision, FDA now recommends that subjects should include “male and nonpregnant female patients with schizophrenia or schizoaffective disorder who are already receiving a stable regimen of paliperidone palmitate extended release suspension via the intramuscular route. Patients who are already receiving any dosage regimen of paliperidone palmitate injection every month would be eligible to participate in the study by continuing their established maintenance dose” (emphasis added).

Again, the FDA does not recommend using healthy volunteers or subjects on a different antipsychotic medication, that both injection sites (gluteal and deltoid) be included in the study design. FDA also states that: “All strengths of the test product need to be from the same bulk in order for all strengths of the test to be administered in the PK BE study.”  This implies that the bulk suspension product must be from a single lot that was filled into differing vial sizes.

As previously noted, the innovator has submitted a petition requesting certain requirements to establish BE of a test product to their reference listed drug.  That link can be found in our previous post above.  A copy of the revised June 2016 BE Guidance can be found here. How this will impact potential ANDA applicants is unclear.  There is currently no listing on the FDA Paragraph IV database for this product.