eLearning Seminar
Back to Basics: Why, When, and How to Conduct Specialty Toxicology Studies for Eyes, Skin, and Immune System

Module 1: Photosafety Evaluation: Why, When, and How to Conduct? 

Daniel Bauer, PhD

Phototoxic properties of systemically applied pharmaceuticals may be the cause of serious adverse drug reactions. Despite being clinically manageable in principle, they can limit the use of a drug depending on the indication. Protective measures against sunlight can be applied very reasonably during a few days but may not be practicable for chronic treatments. Thus, both patients and health authorities are unlikely to accept a relevant photosensitization risk in such situations.

Since the global adoption of ICH S10 “Photosafety Evaluation of Pharmaceuticals” in 2013, both the industry and CROs have gained significant experience in conducting risk assessment for phototoxicity potentials for pharmaceuticals. However, it still requires an individual project toxicologist to consider various aspects of a pharmaceutical program to have a staged and integrated analysis of the risk.

Also, special experience and equipment are needed to conduct compliant studies, for which most of the toxicologists lack hands-on experience. This module focuses on providing details on the in vitro and in vivo studies as part of a tiered testing strategy and providing the scenarios and principles to guide an integrated human risk assessment.

Module 2: Immunotoxicity Studies: Why, When, and How to Conduct?

Florence Burleson, PhD
Marie-Soleil Piche, PhD

With the surge of immunotherapies and gene/cell therapies in the past two decades, the need to conduct immunotoxicity studies has increased dramatically. The studies needed for such programs are often case-by-case and there is little harmonization between organizations. This module focuses on the considerations, principles, and applicable regulatory guidances to design and conduct an immunotoxicity program for major drug modalities.

This eLearning module covers several key areas related to immunotoxicity studies. The module will begin with a review of immunotoxicity testing, highlighting the surge in immunotherapies, gene/cell therapies, and the resulting growing need for immunotoxicity studies. The module will discuss the immunotoxicity assays required to support these programs and how the design differs from traditional immunotoxicity testing. Additionally, the module will provide a brief overview of differences in immune responses between nonclinical species and humans. It will also explore the considerations and applicable regulatory guidances for designing immunotoxicity studies for major drug modalities highlighting the case-by-case nature of these studies and the current lack of harmonization between organizations.

Module 3: Dermatotoxicity Studies: Why, When, and How to Conduct?

Jean-Philippe Therrien, PhD
Jeffrey Klein, PhD, DABT

This eLearning module will focus on the in vitro and in vivo studies needed to support first-in-human clinical trials for pharmaceutical products intended for topical application.

In vitro early safety screening tools are essential in the initial stages of dermal drug development for identifying potential local toxicities and adverse skin effects. The prominent tools discussed in this module are in vitro skin irritation assays, in vitro skin sensitization assays, and in vitro permeation testing (IVPT). In vitro skin irritation assays are crucial for predicting the potential of drug substances and final products to cause skin irritation. in vitro skin sensitization assays evaluate the potential of novel drug substances to cause allergic reactions on the skin. IVPT plays a critical role in dermal drug development by enabling the early detection of potential safety issues, such as excessive permeation, irritation, and systemic absorption, thus allowing for timely intervention. Furthermore, IVPT aids in guiding formulation optimization to achieve the desired balance between efficacy and safety. Collectively, these assays help de-risking early on dermal drug product safety and efficacy, reducing animal testing, guiding formulation optimization, and aiding in regulatory compliance.

The module will also discuss the in vivo studies needed to determine both the local and systemic toxicity of dermal pharmaceutical products. These studies generally include the use of the rat as the rodent species and the minipig as the nonrodent species. As the set of in vivo nonclinical studies intended to support dermal administration are quite different from those intended for only systemic administration, these differences will be highlighted. In addition, the regulatory pathways for dermal products will be discussed to provide the differences between a novel dermal product and a previously approved systemic product that is being modified for use in a topical application. Together, this combination of in vitro and in vivo studies will provide a robust safety profile for regulatory agency review in supporting dermal drug development.

Module 4: Ocular Toxicity Studies: Why, When, and How to Conduct?

Brian Short, DVM, PhD, DACVP

Ocular toxicity studies of small molecules, biotherapeutics, oligonucleotides, and gene therapies by various routes of administration usually cause adverse ocular effects, especially for intraocular routes (intravitreal, subretinal, intracameral, and suprachoroidal) and less so for the topical ocular route. One critical aspect of ocular toxicity studies is the importance of correlating pathology findings with in-life findings by standard and specialized ophthalmic techniques to guide mitigation and monitoring for ocular adverse events in clinical trials. The advent of ocular sustained release formulations adds another layer of complexity to identifying ocular effects related to the formulation versus the drug. The contribution of adverse injection procedure-related effects can confound interpretation but does not usually factor into NOAEL determinations. Ocular biotherapeutics and gene therapy drugs are usually immunogenic via innate and/or adaptive responses that may or may not be relevant for human risk assessment. This module will discuss various ocular toxicity studies with practical principles that illustrate the challenges encountered and approaches needed for effective risk assessment and regulatory success with ocular drug development case studies.