In Vitro Release Test and In Vitro-In Vivo Correlation of Complex Generic Ophthalmic, Injectable, Implantable, and Inserted Products

FDA and the Center for Research on Complex Generics (CRCG) will host a free public workshop on June 29, 2022 from 8:30 a.m. - 5:00 p.m.: In Vitro Release Test and In Vitro-In Vivo Correlation of Complex Generic Ophthalmic, Injectable, Implantable, and Inserted Products.

About the Event:

An in vitro release test (IVRT) can be an important tool to support a demonstration of bioequivalence and/or product quality for various generic drug products. In vitro-in vivo correlation (IVIVC) can allow a prediction of the in vivo performance of a drug based on the IVRT profiles, which can be used to support novel alternative in vitro-based bioequivalence approaches and/or post-approval changes to generic drugs.

The purpose of this workshop is to discuss the scientific principles and practical considerations that inform current FDA thinking for IVRT and IVIVC studies to support the development and approval of complex generic ophthalmic, injectable, implantable, and inserted drug products. The workshop will provide an update on the progress of Generic Drug User Fee Amendments (GDUFA)-funded research activities, explore challenging issues that would benefit from a broader discussion, identify areas that need further research, and discuss opportunities for coordination and collaboration between FDA, generic drug industry, academic institutions, dissolution equipment manufacturers, contract research organizations, and consultants.

FDA and the Center for Research on Complex Generics (CRCG), which is a collaboration between the University of Maryland School of Pharmacy and the University of Michigan College of Pharmacy, are dedicated to advancing programs that stimulate scientific dialogue, disseminate current insights about complex generics, and generate new knowledge in support of FDA’s mission to promote and protect the public health by increasing access to safe and effective generic medicines.

Topics:

  • IVRT study design considerations for supporting bioequivalence and product quality, when applicable, for complex generic ophthalmic products, including emulsions, suspensions, ointments, and implants
  • IVRT study designs for supporting a demonstration of bioequivalence and as part of quality control for complex injectable generic products including suspensions, polymeric microspheres, in situ forming gels/implants, as well as implantable generic products including solid implants, intrauterine systems and intravaginal systems
  • Novel IVRT methods for supporting generic product development and/or bioequivalence demonstration
  • Theoretical principles and practical challenges of IVRT and IVIVC method development, validation, and transfer
  • Submission of IVRT information in Abbreviated New Drug Applications, including format of data/results, organization of information, and common deficiencies

Audience:

The generic drug industry, academic institutions, dissolution equipment manufacturers, contract research organizations, consultants, and others interested in the development of complex generic drug products.

Workshop Recordings:

2022 IVRT-IVIVC Workshop Opening Remarks and Keynote Speaker

2022 IVRT-IVIVC Workshop Session 1 Presentations

2022 IVRT-IVIVC Workshop Session 2 Presentations

2022 IVRT-IVIVC Workshop Session 1 & 2 Panel Discussion

2022 IVRT-IVIVC Workshop Session 3 Presentations and Session 3 Panel Discussion

2022 IVRT-IVIVC Workshop Session 4 Presentations and Session 4 Panel Discussion

2022 IVRT-IVIVC Workshop Summary and Closing Remarks

Agenda and Workshop Slides:

CRCG Opening Remarks
James Polli, PhD, Co-Director, CRCG

Keynote Address
A Scientific and Regulatory Overview of IVRT: Current Considerations and Challenges
Darby Kozak, PhD, Deputy Director, DTP I, ORS, OGD, FDA 

Session 1: Scientific and Regulatory Roles of In Vitro Release Test (IVRT) Studies
This session will share information on how IVRT studies have been used to support 1) generic drug product development, and 2) scientific and regulatory assessment on complex generic parenteral and ophthalmic products.

Regulatory Uses of IVRT Studies on Complex Generic Ophthalmic, Injectable, Implantable, and Inserted Products
Bin Qin, PhD, DTP I, ORS, OGD, FDA

Role of IVRT in Supporting Generic Drug Development
Mark Halus, PhD, Teva Pharmaceuticals

Bioequivalence Considerations for IVRT Methods for Ophthalmic Products
Eunjung Park, PhD, DB II, OB, OGD, FDA

Session 2: IVRT Method Development and Validation
This session will address 1) general scientific and regulatory expectations for IVRT method development and validation, 2) common deficiencies observed during regulatory assessment; and 3) challenges faced during IVRT method development and validation.

Expectations and Common Deficiencies with IVRT Studies Submitted in ANDAs for Ophthalmic Emulsion Products
Alaa AbuZnait, PhD, DB I, OB, OGD, FDA

Common Deficiencies and Considerations on Setting Appropriate Specifications for Intravaginal Rings
Kalpana Paudel, PhD, DB, ONDP, OPQ, FDA

IVRT Method Development for API Suspension Products and Validation with In Vivo Models
Diane Burgess, PhD, University of Connecticut

Audience Q&A with panelists

  • Moderator: Bin Qin, PhD, DTP I, ORS, OGD, FDA
  • Panelists:
    Ripen Misri, PhD, Apotex Inc.
    Alaa AbuZnait, PhD, DB I, OB, OGD, FDA
    Eunjung Park, PhD, DB II, OB, OGD, FDA
    Kalpana Paudel, PhD, DB, ONDP, OPQ, FDA
    Bryan DeBarr, BS, Viatris Inc.
    Mark Halus, PhD, Teva Pharmaceuticals
    Diane Burgess, PhD, University of Connecticut

Session 3: In Vitro Vitro-In Vivo Correlation (IVIVC)for Complex Generic Parenteral and Ophthalmic Products
This session will address current research exploring IVIVCs for complex parenteral and ophthalmic products.

Challenges and Opportunities in the Development of IVRT and IVIVC of Complex Injectable Formulations
Xavier Pepin, PharmD, PhD, Simulations Plus, Inc.

Relevant Challenges with IVRT with Iron-Carbohydrate Complexes: Application to IVIVC Models
Amy Barton, PharmD, MHI, Vifor Pharma

Melt-extruded Dexamethasone Ophthalmic Implants – Process, Structure, and In Vitro Drug Release
Feng Zhang, PhD, University of Texas Austin

Audience Q&A with panelists

  • Moderator: Yan Wang, PhD, DTP I, ORS, OGD, FDA
  • Panelists:
    Xavier Pepin, PharmD, PhD, Simulations Plus, Inc.
    Amy Barton, PharmD, MHI, Vifor Pharma
    Feng Zhang, PhD, University of Texas Austin
    Harshil Parikh, MS, Teva Pharmaceuticals
    Mingliang Tan, PhD, DQMM, ORS, OGD, FDA

Session 4: Novel IVRT Methods
This session will address novel IVRT methods that may be used to support generic drug product development and a demonstration of bioequivalence for complex generic parenteral and ophthalmic products.

Thinking Outside the Box: Adaptive Perfusion Method to Study Drug Release from Emulsions
Xiaoming Xu, PhD, DPQR, OTR, OPQ, FDA

Developing Discriminatory IVRT Methods for Injectable Suspensions: Start with Why
William Smith, PhD, DPQR, OTR, OPQ, FDA

Advanced Imaging Technologies and AI-based Image Analysis for Mechanistic Characterization and Prediction of Complex Drug Release
Shawn Zhang, PhD, DigiM Solution LLC

Audience Q&A with panelists

  • Moderator: Xiaoming Xu, PhD, DPQR, OTR, OPQ, FDA
  • Panelists:
    Jie Shen, PhD, University of Rhode Island
    Shawn Zhang, PhD, DigiM Solution LLC
    Parnali Chatterjee, PhD, RPh DB, ONDP, OPQ, FDA
    Yoriko Harigaya, PharmD, DB II, OB, OGD, FDA
    William Smith, PhD, DPQR, OTR, OPQ, FDA

Workshop Summary
Yan Wang, PhD DTP I, ORS, OGD, FDA

Closing Remarks
Anna Schwendeman, PhD, Co-Director, CRCG

For More Information:

If you have any questions about this workshop please contact complexgenerics@rx.umaryland.edu.