IVRT and IVPT Methods: Best Practices and Scientific Considerations for ANDA Submissions

The Center for Research on Complex Generics (CRCG) hosted the online event, "In Vitro Release Test (IVRT) and In Vitro Permeation Test (IVPT) Methods: Best Practices and Scientific Considerations for ANDA Submissions," on Aug. 18-20, 2021.

About the Event:

The U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a free virtual public workshop on August 18-20, 2021, titled "In Vitro Release Test (IVRT) and In Vitro Permeation Test (IVPT) Methods: Best Practices and Scientific Considerations for ANDA Submissions.".

IVRT and IVPT are important methods used by the generic drug industry and in other contexts to support demonstrations of bioequivalence for generic topical drug products, evaluations of the heat effects and product quality for generic transdermal delivery systems (also known as patches), assessments of the bioavailability of ingredients in sunscreen products, and characterization of other biopharmaceutical aspects of topical and transdermal generic drug products.

The purpose of this workshop was to discuss the scientific principles and practical considerations that inform current FDA thinking and USP recommendations for IVRT and IVPT studies, explore challenging issues that would benefit from broader discussion, identify areas that would benefit from further research, and discuss opportunities for coordination and collaboration between the FDA, USP, academic institutions, product manufacturers, diffusion cell equipment manufacturers, contract research organizations, consultants, and other stakeholders.

FDA and the 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.

Workshop Topics and Agenda:

Topics that were covered during the workshop are outlined below. Attendees are also welcome to download the complete workshop agenda here.

  • IVRT study designs in different contexts including supporting a demonstration of bioequivalence for topical generics, scale-up and post-approval changes, and different dosage forms
  • IVPT study designs in different contexts including supporting a demonstration of bioequivalence for topical generics, heat effects for topical or transdermal delivery systems, and bioavailability for sunscreen products
  • Challenges with aberrant data, outliers, inclusion/exclusion criteria, and statistical analysis of IVPT data
  • Theoretical principles and practical challenges with IVRT and IVPT method development, validation, and transfer
  • Operational principles and practical challenges for IVRT and IVPT diffusion cell apparatus
  • Submission of IVRT and IVPT information in ANDAs, including reportable information, format of data/results, organization of information, and common deficiencies
  • Quality management systems, retention samples, laboratory qualification, documentation, and inspections for IVRT and IVPT studies submitted in ANDAs

Download speaker biographies to learn more about the experts who delivered presentations during the workshop.

Workshop Slides:

August 18, 2021

Keynote Address
The In Vitro Permeation Test (IVPT): Historical Perspective, Current Context, and Future Directions
Howard Maibach, MD Professor of Dermatology, University of California, San Francisco

Foundation Lecture
IVPT Fundamentals: Scientific and Practical Considerations
Sam Raney, PhD, Associate Director for Science, ORS, OGD, FDA

Scientific and Regulatory Uses of IVPT Studies
IVPT Studies with Sunscreen Products: Experimental Parameters
Yang Yang, PhD, Staff Fellow, DPQR, OTR, OPQ, FDA

IVPT Studies with Sunscreen Products: Potential Regulatory Utility
Dennis Bashaw, PharmD Senior Science Advisor, OCP, OTS, FDA (retired)

IVPT Studies with Topical and Transdermal Products
Audra Stinchcomb, PhD, Professor of Pharmaceutical Sciences, University of Maryland, Baltimore

IVPT Method Development, Validation, and Transfer
IVPT Studies During Topical Product Development
Leandro Santos, PhD, Associate Director for Clinical Research, Incyte

IVPT Data Challenges and Statistical Analysis
IVPT Data Challenges in the Real World
Paul Lehman, MS, Vice President and Head of Dermal and Transdermal Research, QPS, LLC

IVPT Data Analysis and Statistics
Elena Rantou, PhD, Lead Mathematical Statistician, DB-VII, OB, OTS, FDA

Panel Discussion
IVPT Data Challenges and Statistical Analysis
Priyanka Ghosh, Ph.D. Acting Team Lead/ Co-chair of the Bioequivalence Standards for Topicals Committee Office of Research and Standards (ORS), Office of Generic Drugs (OGD)

Panel Discussion
In-vitro Permeation Test (IVPT) Method Development, Validation, and Transfer
Hiren H. Patel, Ph.D. Staff Fellow, Division of Bioequivalence II Office of Bioequivalence, Office of Generic Drugs

August 19, 2021

Keynote Address
The In Vitro Release Test (IVRT): Historical Perspective, Current Context, and Future Directions
Vinod Shah, PhD, Consultant, VPS Consulting, LLC

Foundation Lecture
IVRT Fundamentals: Scientific and Practical Considerations
Sam Raney, PhD, Associate Director for Science, ORS, OGD, FDA

S. Pharmacopeia (USP) General Chapters <1724> and <1002>
USP General Chapter Revision Process
Margareth Marques, PhD, Principal Scientific Liaison, USP

USP and Prospective Scope and ContentLeandro Santos, PhD, Associate Director for Clinical Research, Incyte

IVRT Method Development, Validation, and Transfer
Key Aspects in Developing Appropriate IVRT Methods for Topical Generic Products: Advances and Challenges
Theo Kapanadze, PhD, Chief Science Officer, Diteba

IVRT Studies During Topical Product Development: Lifecycle Management for SUPAC-SS and Generics
Cristina Yen, BS, Senior Manager, IVRT, Tergus Pharma

IVRT Studies During Topical Product Development: Challenges in Method Development and Transfer
Kailas Thakker, PhD, President, TopiKail Consulting

Panel Discussion
IVRT Method Development, Validation, and Transfer Theoretical Principles and Practical Challenges
Tannaz Ramezanli, Pharm.D., Ph.D. Pharmacologist, Division of Therapeutic Performance I/Office of Research and Standards

August 20, 2021

Diffusion Cell Apparatus
Diffusion Cell Apparatus: Scientific Principles and Practical Challenges I
Ahmed Zidan, PhD, Senior Staff Fellow, DPQR, OTR, OPQ, FDA

Diffusion Cell Apparatus: Scientific Principles and Practical Challenges II (Slides not available)
Jon Lenn, PhD, Chief Scientific Officer, MedPharm Ltd.

Diffusion Cell Apparatus: Considerations for Design and Use I
Ashvin Patel, PhD, Director, Analytical Research and Business Development, Teledyne

Diffusion Cell Apparatus: Considerations for Design and Use II
Luke Lee, PhD, President, Logan Instruments Corp.

Submission of Information in Abbreviated New Drug Applications (ANDAs)
Expectations for IVRT Data and Information Submitted in ANDAs
Tian Ma, PhD, Staff Fellow, DB-I, OB, OGD, FDA

Expectations for IVPT Data and Information Submitted in ANDAs
Archana Manerikar, MS, PharmD, Pharmacologist, DB-I, OB, OGD, FDA    

Quality Management Systems (QMS)
QMS: Study Integrity Considerations
Sam Haidar, PhD, Senior Science Advisor, OSIS, OTS, FDA

QMS: Industry Perspectives
Kendall Powell, PhD, Senior Director of Bioanalytical, MedPharm Ltd.

Audience:

Generic drug industry stakeholders, including scientists/researchers, clinicians, and regulatory affairs professionals who work on or are interested in the development of IVRT and IVPT studies.

For More Information:

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