In Vitro Permeation Testing (IVPT)

What is In Vitro Permeation and Penetration Testing (IVPT)?
The in vitro permeation and penetration test (IVPT) is a well-validated method for studying percutaneous absorption and determining the pharmacokinetics of topically applied drugs. Because in vivo testing is often costly, time-consuming, and difficult to conduct, most topical and transdermal developers rely on in vitro and ex vivo IVPT methodologies to optimize and compare formulations.

MedPharm is widely recognized by regulatory agencies in Europe, Japan, and the United States as subject matter experts in IVPT.

IVPT is a regulatory-grade tool for evaluating topical and transdermal drug delivery, supporting development decisions, claim support, and bioequivalence strategies for generics and 505(b)(2) programs.

What IVPT Studies Support

Formulation development and optimization

Local delivery to the site of action

Pharmacokinetics

Claim support

Product benchmarking

Life-cycle management

Clinical de-risking

Bioequivalence for generics and 505(b)(2) programs

Stages of IVPT for Skin

Method Development (IVPT and LC-MS/MS)

LC-MS/MS Method Validation

IVRT Method Validation (includes pilot study)

IVPT Pivotal (dependent on donors)

Laboratories

2,400 sq ft of purpose-built laboratories

Qualification and calibration of all instruments and equipment

SOPs defining use, maintenance, and calibration

All diffusion cells qualified per USP, FDA, and EMA guidance

IVPT Test Systems

High-Throughput Flow-Through Diffusion Cells (Bronaugh Type)

Optimized fluidics and continuous flow
Fully automated sample collection
USP compliant
Ideal for lipophilic compounds

Custom Diffusion Cells

Small and micro vertical diffusion cells (VDCs)
Proprietary micro-adapters for biopsies and ocular tissue
Zone-of-inhibition agar and microbial-based systems
Gaskets for hard tissue (e.g., nails)
High-throughput pharmacodynamic (HTPD) systems for PK/PD modeling

Barrier Integrity Measurement

Proprietary transepidermal water loss (TEWL) system
More predictive than TEER or radiolabeled water tests
Reproducible assessment correlated with permeation changes

Types of Epithelium for IVPT

Skin

Large repository of more than 100 frozen human skin samples (−80°C) to ensure no lead times
IRB-approved sample collection
Normal, healthy, and diseased tissue
Optimized collection, shipping, handling, and storage protocols to minimize variation

Nail

Repository of thousands of frozen human nail samples (−80°C) to ensure no lead times
IRB-approved sample collection
Access to diseased nails

Nasal

Proprietary reconstructed nasal epithelium with mucus and cilia
Active and passive delivery models
Intact tight junctions compared to leaky frozen tissue

Eye

Reconstructed corneal tissue
Blink and Tear model (in development)
Reconstructed whole eye (requires consultation)

Lung

Proprietary reconstructed fibrotic bronchial tissue
Reconstructed airway (requires consultation)

Mucosal

Reconstructed oral, rectal, and bladder tissues
Intact tight junctions versus leaky frozen tissue

Vaginal

Reconstructed vaginal and cervical tissue with mucus
Intact tight junctions versus leaky frozen tissue

Gastrointestinal / Urinary

Reconstructed gut and intestine
Reconstructed bladder (requires consultation)

Regulatory Applications for IVPT

United States

Abbreviated New Drug Applications (ANDAs)
Liquid and semisolid topical products
Cutaneous and mucosal applications
Bioequivalence vs. RLD

Europe

Quality and equivalence of locally applied, locally acting cutaneous products (EMA guideline)

China

Technical guidelines for IVRT and IVPT studies of locally acting chemical generic drugs

Canada

Generally receptive to internationally harmonized approaches (EMA and/or FDA)
IVRT and IVPT data can support regulatory submissions
Ask for a technical consult for your program

Brazil (ANVISA)

Increasing alignment with internationally harmonized approaches (EMA and/or FDA)
IVRT and IVPT data may support regulatory submissions, depending on program strategy
Ask for a technical consult for your program

Key Publications and Regulatory Contributions

EMA Scientific Guideline

Quality and equivalence of locally applied, locally acting cutaneous products MedPharm contributed to this scientific guideline.

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EUFEPS Open Discussion Forum (2019)

EUFEPS Annual Meeting and Conference Series MedPharm presented on translating IVPT guideline requirements into practice.

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FDA Public Workshop (2021)

IVRT and IVPT Methods: Best Practices and Scientific Considerations for ANDA Submissions FDA invited MedPharm to present at this public workshop.

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FDA Public Workshop (2021)

QMS: Industry Perspectives. One Company’s Journey from R&D to Regulated IVRT/IVPT Studies MedPharm presented on quality systems for regulated IVRT and IVPT studies.

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