NAMs Resources

New Approach Methodologies (NAMs) refer to advanced, innovative testing methods that can reduce, refine, or replace traditional animal testing while maintaining or improving the quality of safety and efficacy assessments for medical products, food, cosmetics, and other regulated substances.

NAMs encompass a broad range of scientific approaches including:

• Human-relevant models – Testing approaches that better reflect human biology, physiology, and disease states
• In vitro methods – Cell-based assays and tissue models that can simulate human biological responses more accurately than animal models in many cases
• In silico approaches – Computer modeling, artificial intelligence, and computational toxicology that can predict how substances will behave in the human body
• Organ-on-a-chip technologies – Microfluidic devices containing human cells that mimic the structure and function of human organs
• Advanced analytical methods – High-throughput screening techniques and omics technologies (genomics, proteomics, metabolomics) that provide detailed molecular-level information

Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program

In 2021, the FDA announced the launch of the ISTAND Pilot Program. This program was made permanent on 31 July 2025. Modeled after other qualification programs, including the Biomarker Qualification Program (BQP), it aims to qualify novel Drug Development Tools (DDTs) that don’t fall within traditional qualification approaches.

These novel tools include:

• Application of patient-performed digital photography in dermatology trials
• Use of tissue chips (i.e., microphysiological systems) to assess safety or efficacy questions
• Development of novel nonclinical pharmacology/toxicology assays
• Use of artificial intelligence (AI)-based algorithms to evaluate patients, develop novel endpoints, or inform study design
• Use of novel digital health technologies (e.g., wearables) for patient assessment

Per the FDA:
“The Innovative Science and Technology Approaches for New Drugs (ISTAND) Program accepts submissions for qualification of types of drug development tools (DDTs) that are out of scope for existing DDT qualification programs but may still be beneficial for drug development.

DDTs are methods, materials, or measures that have the potential to facilitate drug development. As described in the 21st Century Cures legislation, DDTs include biomarkers, clinical outcome assessments, and other methods, materials, or measures that aid drug development and regulatory review. To support DDT development efforts, FDA has established qualification programs for biomarkers, clinical outcome assessments, and for animal models for use under the Animal Rule. The ISTAND was established to cover other types of DDTs.”

Per the FDA, “Qualification is a conclusion that within the stated context of use, the DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review. Once qualified, DDTs will be publicly available to be used in any drug development program for the qualified context of use. Additionally, the qualified DDT generally can be included in IND, NDA, or BLA submissions without needing FDA to reconsider and reconfirm its suitability.”

In practice, this may mean your tool could be strongly recommended or required to be used (in specific contexts) for an IND, NDA, or BLA submission to be successful.

A Context of Use statement is generally a required component of every stage of submission for a development tool qualification. The first COU is written by the applicant. In successive stages of submission, the FDA will provide direct feedback on the COU, shaping it (including potentially reducing its scope) until the final Context of Use is accepted in the Qualification Determination Letter.

Approval of NAMs through the ISTAND program follows the Biomarker Qualification Program and follows three steps; Letter of Intent (LOI) submission, Qualification Plan (QP) submission, and Full Qualification Package (FQP) submission. A NAM can only be considered a qualified DDT after review and acceptance of all three submissions.

The FDA maintains a publicly-available database of all submissions to any of the Drug Development Tool Qualification Programs. Searching for ISTAND submissions in this database provides access to a number of accepted and rejected LOI and LOI Determination Letters.

Because the ISTAND Program is relatively new, little information is available beyond that. However, InnovApproach specializes in the preparation of ISTAND Qualification Plans and Full Qualification Packages, with, to date, hands on experience with the only successful submissions of these documents to the FDA.

Yes. The EMA supports the “Qualification of Novel Methodologies (QoNM) for Medicine Development“. This program is far older than the FDA’s ISTAND program – being introduced in 2008. However, major differences exist in the submission mechanisms, types of technologies evaluated, and scope of outcomes between ISTAND and QoNM. InnovApproach consulting is fully prepared to help companies navigate the differences between the two.

In addition to ISTAND for DDT qualification, the FDA supports qualification pathways for Medical Device Development Tools (MDDTs). The MDDT qualification program is more mature than the ISTAND Pilot Program. As of November 19, 2024, 18 MDDTs have received qualification, with the first being qualified in 2017. While InnovApproach specializes in ISTAND and Drugs, we have strong relationships with consultants specializing in devices and would be happy to introduce you.

Yes. The EMA has the Qualification of Novel Methodologies for Medicine Development (QoNM) Program. This program is older and more developed than ISTAND, but less NAM focused. QoNM is structured like the FDA’s umbrella “DDT Qualification Program” which houses ISTAND but also support Biomarkers, Clinical Outcome Assessments, and Animal Model Qualification. InnovApproach has hands-on experience with QoNM and can support your submission for EMA qualification. We can also advise which qualification program is right for you.

All data found at https://force-dsc.my.site.com/ddt/s/
Accessed 18-Nov-2025