The US FDA has issued a draft guidance for the active ingredient difluprednate which is an ophthalmic emulsion with a strength of 0.05 per cent. The drug is categorised under corticosteroids and works to stall the release of certain natural substances that cause swelling and pain. The drug which is used for eye surgery has the regulatory authority insisting on data of a comparative study which should be performed on at least three exhibit lots of both test and reference products.

In order to determine the strength of the product, the regulator has recommended two options: in vitro or in vivo study. Firstly, the manufacturer will need to qualify for the in vitro option for this drug product. It should ensure that the test and Reference Listed Drug (RLD) formulations are qualitatively and quantitatively the same.

Secondly, it is the acceptable comparative physicochemical characterization of the test and RLD formulations. The comparative study needs to be conducted of both test and reference products.

The regulator has also fixed parameters to measure the globule size distribution, viscosity profile as a function of applied shear, pH, zeta potential, osmolality, and surface tension. Sponsors should also submit information on the drug distribution in different phases within the formulation.

Population bioequivalence (PBE) is recommended in the case of globule size distribution. The other parameters do not require PBE analysis. The applicants should provide not less than 10 data sets from 3 batches with each of the test and reference products to be used in the PBE analysis. Sponsors should compare the size parameter upon serial dilution of the test and reference products, and provide histograms of size distribution data of each diluted sample, stated the regulatory note.

Under in-vivo option, the regulator recommends one bioequivalence study with pharmacokinetic (PK) endpoint. The subjects for this study should be patients undergoing indicated cataract surgery. In addition, the regulator calls to submit metabolite data as supportive evidence of therapeutic outcome.

According to the government ophthalmic care majors like MintoEye Hospital, affiliated to the Bangalore Medical College and Research Institute, the drug difluprednate is a corticosteroid and is approved for the treatment of post-operative ocular inflammation and pain. “There are efforts to extend its use for other ocular inflammatory diseases which are on the rise. Therefore, there is need for constant update on clinical efficacy and adverse drug reactions.”