U.S. flag An official website of the United States government
  1. Home
  2. For Industry
  3. FDA User Fee Programs
  4. Generic Drug User Fee Amendments
  5. FY2015 Regulatory Science Research Report: Ophthalmic Products
  1. Generic Drug User Fee Amendments

FY2015 Regulatory Science Research Report: Ophthalmic Products

Introduction

Ophthalmic drug products are formulated in a variety of dosage forms including suspensions, emulsions, ointments, gels, and implants. Demonstration of BE for non-solution dosage forms can be challenging, especially for ophthalmic products that are locally acting. Even for products that are the same in their qualitative features and composition, some differences in product manufacturing may result in physicochemical differences that, in turn, may affect clearance, distribution, and release of the drug in ocular tissues. Understanding the relationship between physicochemical properties and their effect on ocular bioavailability will help FDA establish scientifically-sound approaches to the determination of BE of non-solution ophthalmic products.

Research

In 2013 and 2014, OGD funded nine research grants focusing on ophthalmic products. Seven of the nine projects focus on development of in vitro release and physical characterization methodologies that can be used to detect differences in product performance resulting from various manufacturing processes and to project in vivo performance. In addition to evaluating existing USP methods, we are currently investigating several novel in vitro dissolution methods that can more closely mimic the in vivo environment of the eye. With our collaborators, we also are studying dissolution, physicochemical characterization, and in vitro/in vivo correlations (IVIVCs) of ophthalmic products formulated as suspensions, emulsions, ointments, and implants. Two projects focus on physiologically-based pharmacokinetic (PBPK) modeling and simulation approaches to predict the effect of formulation-related factors on ophthalmic drug absorption, distribution, and clearance in various eye tissues. Knowledge gleaned from these projects will help FDA determine BE methods for ophthalmic products and help industries develop generic products.

Figure 3. Schematic of a dissolution apparatus designed to mimic the vitreous

Figure 3. Schematic of a dissolution apparatus designed to mimic the vitreous

The apparatus is capable of optical characterization and comprises an upper and lower chamber to isolate the particle and gel solution and prevent it from leaching out of the apparatus (currently being developed by the University of California San Diego).

Figure 4. Schematic diagram of an ocular delivery model*

Figure 4. Schematic diagram of an ocular delivery model*

*provided by CFD Research Corp.

ORS staff facilitating research in this area

  • Stephanie Choi, Mohammad Absar, Yan Wang, Bryan Newman


Projects and Collaborators

  • An IVIVC system to facilitate the development of a generic Vitrasert
    • Site PI: Thomas Smith
    • Grant #: 1U01FD004927-01
  • In Vitro-In Vivo Correlation of Ocular Implants
    • Site PI: Uday Kompella
    • Grant #: 1U01FD004929-01
  • Modeling of the vitreous for in vitro prediction of drug delivery of porous silicon particles and episcleral plaques
    • Site PI: Michael Sailor
    • Grant #: 1U01FD005173-01
  • Dissolution Methods for Predicting Bioequivalence of Ocular Semi-Solid Formulations
    • Site PI: Xiuling Lu
    • Grant #: 1U01FD005174-01
  • Evaluation and Development of Dissolution Testing Methods for Semisolid Ocular Drug Products
    • Site PI: Diane Burgess
    • Grant #: 1U01FD005177-01
  • Topical Ophthalmic Suspensions: New Methods for Bioequivalence Assessment
    • Site PI: Arto Urtti
    • Grant #: 1U01FD005180-01
  • Dissolution Methods for Topical Ocular Emulsions
    • Site PI: Srinath Palakurthi
    • Grant #: 1U01FD005184-01
  • PBPK Modeling and Simulation for Ocular Dosage Forms
    • Site PI: Michael Bolger
    • Grant #: 1U01FD005211-01
  • An integrated multiscale-multiphysics modeling and simulation of ocular drug delivery with whole-body pharmacokinetic response
    • Site PI: Kay Sun
    • Grant #: 1U01FD005219-01

Publications and Presentations

  • Fluorometholone Ocular Suspension PBPK simulations using the OCAT model in GastroPlus. Michael B Bolger, Jessica Spires, James M Mullin, Joyce Macwan, Jayeeta Ghosh, Viera Lukacova. GTBio, San Diego, March 2015.
  • Self-reporting Drug Delivery with Porous Silicon Particles for Ocular Therapeutics. Joanna Wang and Michael Sailor. UC San Diego Research Expo, April 16th, 2015.
  • Sustained release dexamethasone implants for in vitro-in vivo correlations. Yunpeng Bai, David Bourne, Yan Wang, Stephanie Choi, Uday B. Kompella. The Association for Research in Vision and Ophthalmology (ARVO), Denver CO (May 3–7, 2015)
  • Effect of particle size and viscosity of ophthalmic suspensions on ocular bioavailability. David Bourne, Sunil Vooturi, Jiban Panda, Stephanie Choi, Hyewon Kim, Sarath Yandrapu, Uday B. Kompella. ARVO, Denver CO (May 3–7, 2015)
  • Protein Delivery with Porous Silicon Particles. Joanna Wang, David Warther, Maite Bezem, Aurora Martinez, and Michael J. Sailor. 5th Asian Silicon Symposium, October 18-21, 2015.
  • Effect of physicochemical properties of Q1/Q2 ophthalmic suspensions on ocular bioavailability and bioequivalence. Sunil Vooturi, David Bourne, Jiban Panda, Stephanie Choi, Hyewon Kim, Sarath Yandrapu, Uday Kompella. AAPS Orlando, FL (October 25-29, 2015)
  • Influence of Excipients on Physicochemical Characteristics of Ocular Semisolid Formulations and Their In Vitro Drug Release. Shilpa Patere, Khaetthareeya Sutthanut, Bryan Newman, Stephanie Choi, Michael Jay and Xiuling Lu. AAPS Orlando, FL (October 25-29, 2015)
  • Preparation and Evaluation of Difluprednate Topical Ocular Emulsions. Srinath Palakurthi, Defu Cai, Jiang Qiu, Mohammad Absar, Stephanie Choi. AAPS Orlando, FL (October 25-29, 2015)
  • Bioequivalence Requirements for Ophthalmic Products: CMC and Clinical/Pharmacokinetic Considerations. Stephanie Choi. AAPS Orlando, FL (October 25-29, 2015)
  • Venkata Kashyap Yellepeddi, Srinath Palakurthi. Recent advances in topical ocular drug delivery. J Ocular Pharmacol. Ther., 2015 (In press)

Outcomes

  • Revision of Product-Specific Recommendation on Cyclosporine Ophthalmic Emulsion
  • Product-Specific Recommendation on Difluprednate Ophthalmic Emulsion

ResourcesForYou