Non-clinical safety studies for IND application

The Importance of Non-Clinical Safety Studies in IND Applications

In IND applications, non-clinical safety studies serve as "gatekeepers" to ensure safety before proceeding to first-in-human (FIH) administration. Based on data from animal models, such as the No Observed Adverse Effect Level (NOAEL), the initial dose and other parameters are established, demonstrating the appropriateness of clinical trials (Phase 1).

Regulatory authorities such as the PMDA and FDA strictly review toxicity data, and conducting studies based on reliability standards compliant with GLP is a mandatory requirement for application acceptance.

[Standard Package] Main Safety Test Items Required for IND Applications

General toxicity test

Through single and repeated dose toxicity studies, we will confirm systemic effects according to dosage. This data will be used to calculate the No Observed Adverse Effect Level (NOAEL), identify which organs exhibit toxicity, and subsequently determine a safe initial dose for the first human dose and the appropriateness of the dosing duration.

Safety pharmacology study

This study evaluates the effects on vital functions crucial for life maintenance, such as the central nervous system, cardiovascular system, and respiratory system. This study is called the "core battery study" and is conducted under GLP (Good Laboratory Practice) standards.

Genotoxicity/Immunotoxicity

Genotoxicity testing evaluates the risk of damage to DNA and chromosomes, such as with the Ames test, to identify early on the potential for causing carcinogenicity or genetic effects on future generations. Additionally, immunotoxicity testing is conducted to investigate adverse effects on the immune system, such as unintended suppression or overreaction of immune function caused by drugs. If widespread immunosuppression is observed, the risk of infection and tumor development is considered to increase.

Modalities and corresponding support

Testing strategies differ depending on the development modality and indication. For example, in the case of biopharmaceuticals such as antibody drugs (ICH D6), since their metabolism differs from small molecules, animal species that pharmacologically cross-react with humans are selected for evaluation. In the case of anticancer drugs (ICH S9), testing items are optimized based on the therapeutic need in serious diseases.

Non-clinical strategy for achieving an efficient IND application

Utilization of ICH Guidelines

By conducting study designs that comply with ICH guidelines, it is possible to eliminate redundant studies. By gathering internationally accepted data early on, additional studies and rework can be prevented, thus streamlining preparations for IND applications.

Timeline Optimization

It is important to manage non-clinical studies not in isolation, but by working backward and including the creation of the CTD (Common Technical Document) and responses to inquiries. By designing the study completion timing, analysis, report creation, and integration of application documents as a single process, delays can be prevented, and the time to application can be shortened.

Strategic Packaging

In cases of serious diseases with limited treatment options, such as advanced cancer, deferral of the start of certain clinical trials until after the commencement of treatment is permitted under guidelines like ICH S9. A strategic data package is required to demonstrate the scientific rationale for safely initiating First-in-Human (FIH) trials and to reasonably explain the risks associated with unconducted trials.

Criteria for selecting a CRO for IND safety testing consignment

Track record of regulatory compliance

When selecting a CRO, it is important to first check their track record in regulatory compliance. Specifically, experience in supporting IND/NDA applications to regulatory authorities both domestically and internationally, as well as know-how in responding to points of concern, are essential.

Animal resources and technology

Securing a stable supply of animal species required for testing, such as primates and miniature pigs, is key to preventing development delays, so it is recommended to confirm supply status in advance. Furthermore, in terms of technology, we will also confirm whether advanced bioanalytical technologies are possessed.

Application document creation support

When applying for an IND, it's important to check whether support is available for creating application documents. If you can receive assistance with creating data packages in eCTD format or with writing the Investigator's Brochure (IB), it can significantly reduce the burden of practical tasks. Therefore, please confirm the scope of support in advance.

Consulting skills

It is important to position CROs not simply as outsourcing vendors, but as scientific strategic partners. The success of development hinges on whether they have the consulting capability to not only submit trial results but also to develop strategies with face-to-face consultations with regulatory authorities in mind.