Food and Drug Administration

Description

Dissolution testing is recommended as part of the demonstration of bioequivalence between test and reference products in the approval of most generic drugs. Drug release measurements are useful for evaluating the effect of manufacturing differences and to assess performance characteristics of a semisolid dosage form. Generally, a generic drug product intended for ocular use contains the same inactive ingredients (“Q1”) and in the same concentration (“Q2”) as the Reference Listed Drug (RLD). However, there may be differences in manufacturing of the generic and RLD products, which may affect bioavailability. Dissolution testing can be used as one of several standard methods to evaluate physicochemical differences of the drug product caused by manufacturing differences. The purpose of this study is to investigate dissolution methods for an ocular semisolid drug product. The results from this study will help the FDA in developing recommendations to determine bioequivalence of generic ocular semisolid drug products.Objectives(1) To formulate Q1/Q2 semisolids (intended for topical ocular administration) under different manufacturing conditions(2) To conduct dissolution studies with the prepared semisolid formulations using various in vitro release methods(3) To identify a dissolution method that can discriminate different semisolid formulations Detailed DescriptionAdditional details regarding the study objectives listed above:(1) The ocular semisolid chosen to serve as the reference product for this study can either be a marketed product or an investigational formulation. Formulations which are Q1/Q2 to this reference product should be developed under different manufacturing conditions. Physicochemical characterization should be performed on these test formulations to determine key attributes that may affect bioavailability.(2) Before initiating the dissolution studies, an analysis of current dissolution methods used for semisolid products should be conducted. A report of this analysis should include the advantages and disadvantages for each method and an assessment on the capability of detecting manufacturing differences, predicting in vivo performance, and method robustness. Test formulations which have the largest differences in physicochemical properties (and which are expected to affect bioavailability) are chosen for testing in the dissolution study. Dissolution methods should be developed with considerations in drug substance and drug product properties and the physiological release environment.(3) An analysis of the dissolution methods used in the study should include the advantages and disadvantages for each method and an assessment on the capability of detecting manufacturing differences, predicting in vivo performance, and method robustness.

Who can apply

• State governments
• County governments
• City or township governments
• Special district governments
• Independent school districts
• Public and State controlled institutions of higher education
• Native American tribal governments (Federally recognized)
• Public housing authorities / Indian housing authorities
• Native American tribal organizations (other than Federally recognized)
• Nonprofits with 501(c)(3) status (other than higher education)
• Nonprofits without 501(c)(3) status (other than higher education)
• Private institutions of higher education
• For-profit organizations other than small businesses
• Small businesses
• Others

Contact

Gladys Melendez-Bohler <br/>Grants Management Specialist <br/>Phone 301-827-7175
gladys.bohler@fda.hhs.gov