Tolerance testing - Local tolerance studies

For many new formulations it is not only important to investigate toxicity following systemic exposure but also to investigate whether the compound give rise to local toxicity, this can be done in local tolerance studies.

Local tolerance studies not only apply for compounds administered by dermal application but also to a variety of other topical dosing routes.

 

Local tolerance studies with topical application or parenteral administration

At Scantox we have experience with topical application of oral patches and thin films placed either on the buccal surface or sublingual, further we also have experience with ocular administered compounds. It may also be necessary to investigate the local tolerance following parenteral administration such as intravenous, intramuscular, subcutaneous or intraperitoneal.

Local tolerance study in new compounds

For new compounds general toxicity studies are required.

Local tolerance studies in compounds already on the market

However, if a compound is already on the market and only the formulation is altered, it will be sufficient to perform a local tolerance study possibly in combination with a kinetic study.

Kinetic study and profile

These studies will evaluate the local tolerance at the application site and the systemic exposure will be assessed by investigating the kinetic profile of the compound.

This will determine if the new formulation give rise to a similar systemic exposure as the former formulation and determine if potential local reactions are reduced or absent.

Minipigs used in local tolerance studies

For several of the administration routes the minipig has proven to be an excellent model to study local tolerance.

Scantox has over the years developed a huge experience in administration of dermal formulations to minipigs ranging from very small to large volumes to ensure the model is clinically relevant and to ensure there will be no cross contamination.

Furthermore, we have experience in performing these local tolerance studies to ensure a long daily exposure as well as multiple daily dosing if necessary.

Due to the size of the minipig, it is an optimal species when screening different dermal formulation candidates. By using small test sites, several formulations or concentrations can be tested in the same animal in local tolerance studies. Once the drug candidate has been selected, the different concentrations of the formulation can be tested on larger areas in separate animals allowing for e.g. inclusion of blood and/or tissue collection for kinetic profiling.

Hamster and rabbit used in tolerance testing

Other species are also of relevance when testing for local tolerance is the hamster and rabbit. The hamsters are often recommended when testing for local tolerance at the mucous membrane (cheek pouch testing).

However, for some products, the size of the hamster is not optimal and a better choice would be to use either dogs or minipigs to assess the local tolerance orally.

The rabbit is used when testing on very sensitive skin is relevant. Furthermore, rabbits are often used when testing local tolerance following “unintended route of dosing”. For this specific test, a single intravenous, perivenous and intra-arterial dose can easily be performed in the rabbit.

Lymph node Assay (LLNA)

With respect to test for skin sensitization, the OECD 429: Skin sensitization test using the Local Lymph node Assay (LLNA) has been implemented for several years.


Study types

Scantox provide a range of different study types to clients within pharmacology, toxicology and histopathology. Our dedicated and highly qualified staff ensure that our clients are in focus in everything we do. We deliver quality work on time. Different study types are shown below and if the study type you seek is not shown, please get in contact.

General Toxicology

Safety pharmacology

Wound healing

Development and Reproductive Toxicology

Local tolerance studies

Juvenile studies in minipigs

Exploratory