FDA Regulatory Navigator

Navigate the FDA regulatory landscape for New Approach Methodologies. Understand qualification pathways, ISTAND, and how to get your NAMs data accepted for submissions.

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FDA Modernization Act 2.0 (2022)

Landmark legislation removing the animal testing mandate for drug approval. The FDA can now accept data from NAMs including organ-on-chip, organoids, in silico models, and other non-animal methods for IND and NDA submissions.

๐Ÿงญ Find Your Regulatory Path

What is your primary goal for NAMs regulatory engagement?
Understanding your end goal helps determine which FDA pathway and engagement strategy will be most effective for your organization.
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Use NAMs data in a specific drug submission
Include NAMs results in an IND, NDA, or BLA filing
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Qualify a NAMs platform for broader use
Get FDA recognition that can be used across sponsors
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Replace a specific animal study requirement
Develop an alternative to an existing animal test
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Explore options / general guidance
Learn about available pathways and requirements
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What type of NAMs data are you generating?
Different NAMs types may have different levels of regulatory precedent and acceptance.
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Organ-on-Chip (OoC)
Microphysiological systems with fluidic flow
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Organoids / 3D Cell Models
Self-organizing tissue structures
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In Silico / Computational
PBPK, QSP, AI/ML models
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Other NAMs / In Vitro
Standard cell assays, biomarkers, etc.
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IND/NDA Submission with OoC Data
Recommended: ISTAND or Pre-IND Meeting

Organ-on-chip data has been accepted in FDA submissions. The first OoC platform (Emulate liver-chip) received ISTAND designation in 2024. For your submission:

1

Define Context of Use (CoU)

Clearly articulate what question your OoC data will answer and what regulatory decision it will support.

2

Request Pre-IND/Pre-NDA Meeting

Submit a Type B meeting request to discuss your NAMs strategy with the relevant review division.

3

Prepare Qualification Package

Include validation data, performance characteristics, and reference to ISTAND-qualified platforms if applicable.

4

Submit with Supportive Data

Include OoC data alongside (or instead of) traditional data, with clear rationale for interpretation.

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IND/NDA Submission with Organoid Data
Recommended: Pre-Submission Meeting

Organoid data is increasingly accepted, especially for oncology (PDO drug response) and disease modeling. There is no formal qualification pathway yet, but strong precedent exists.

1

Document Your Model Characterization

Provide genotypic/phenotypic validation, passage stability, and comparison to clinical outcomes if available.

2

Request Pre-Submission Meeting

Discuss with review division how organoid data will be evaluated in your specific context.

3

Align with Established Use Cases

Reference published studies and prior FDA acceptances for similar organoid applications.

4

Consider ISTAND Pre-Submission

If seeking qualification for broader use, consider ISTAND consultation for organoid platform.

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IND/NDA Submission with In Silico Data
Recommended: DDT Qualification or Direct Submission

Computational models (PBPK, QSP) have the longest regulatory acceptance history among NAMs. The DDT program provides formal qualification pathways.

1

Determine Model Type and Application

PBPK for PK questions, QSP for efficacy/safety, AI/ML for predictions - each has different acceptance levels.

2

Review Existing Guidance

FDA has issued guidance on PBPK (2018), model-informed drug development, and computational modeling credibility.

3

For Established Uses: Direct Submission

PBPK for DDI, pediatric extrapolation, and renal/hepatic impairment are routinely accepted.

4

For Novel Uses: DDT Qualification

Submit through Drug Development Tool program for formal qualification of novel computational approaches.

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IND/NDA Submission with In Vitro / Other NAMs
Recommended: Pre-Submission Discussion

Traditional in vitro assays and newer NAMs can be included in submissions. The key is demonstrating relevance and validation for your specific context.

1

Define the Regulatory Question

What specific question does your NAMs data answer? Safety, efficacy, mechanism, patient selection?

2

Provide Validation Data

Demonstrate assay performance, reproducibility, and relevance to human biology or clinical outcomes.

3

Request Feedback if Novel

For unprecedented applications, request FDA feedback through appropriate meeting type.

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ISTAND Qualification Program
Innovative Science and Technology Approaches for New Drugs

ISTAND is FDA's program to qualify NAMs platforms for a defined Context of Use. Once qualified, sponsors can reference the platform without needing to re-validate.

1

ISTAND Pre-Submission Meeting

Request a meeting to discuss qualification strategy and get FDA feedback on your approach.

2

Submit Qualification Package

Include validation studies, performance characteristics, and proposed Context of Use.

3

FDA Review (12-18 months typical)

FDA evaluates evidence and may request additional data or clarification.

4

Qualification Decision

If qualified, FDA publishes letter of support; platform can be referenced in submissions.

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Animal Study Replacement Strategy
Developing Alternatives to Required Tests

Under FDA Modernization Act 2.0, animal studies are no longer mandated. To replace a specific study, you'll need to demonstrate your NAMs provides equivalent or superior information.

1

Identify the Study to Replace

Which specific animal study? What question does it answer? What endpoint does it measure?

2

Develop Equivalent NAMs Assay

Design a NAMs approach that answers the same regulatory question with comparable or better data.

3

Validate Against Reference Data

Demonstrate concordance with historical animal data or clinical outcomes where available.

4

Propose via Pre-IND Meeting

Present your replacement strategy to FDA and get agreement before proceeding.

Review the regulatory pathways and milestones below

๐Ÿ“ Key Regulatory Pathways

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ISTAND
Innovative Science & Technology Approaches for New Drugs
Platform qualification program for NAMs. Once qualified, sponsors can reference without re-validation. First OoC (Emulate liver-chip) qualified in 2024.
12-18
Months
1
OoC Qualified
Free
No Fee
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DDT Program
Drug Development Tool Qualification
Formal qualification for biomarkers, endpoints, and tools. Includes computational models. Once qualified, available for all sponsors in defined context.
50+
Qualified DDTs
3
Stages
Public
Database
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IND/NDA Submission
Direct Inclusion in Drug Application
Include NAMs data directly in your drug submission. No pre-qualification needed. Evaluated case-by-case by review division.
Most
Common
Varies
Timeline
Case
By Case
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Pre-Submission Meetings
Type A, B, C FDA Meetings
Request feedback on NAMs strategy before submission. Pre-IND meetings are most common. Get FDA alignment on your approach early.
30-74
Days
Type B
Most Used
Written
Response

๐Ÿ“… NAMs Regulatory Milestones

December 2022
FDA Modernization Act 2.0 Signed
Removed animal testing mandate; FDA can accept NAMs data for drug approval.
2023
FDA ISTAND Program Expanded
Enhanced framework for qualifying NAMs platforms for regulatory use.
2024
First OoC ISTAND Qualification
Emulate liver-chip receives first organ-on-chip regulatory qualification.
2024
Unlearn.AI DDT Qualification
First AI digital twin qualified as Drug Development Tool for clinical trials.
2025+
Broader NAMs Acceptance Expected
Additional platform qualifications and expanded regulatory acceptance anticipated.

๐Ÿ“‹ Key Resources

  • FDA Modernization Act 2.0 (Public Law 117-328)
  • ISTAND Program guidance documents
  • DDT Qualification Program guidance
  • CDER Manual of Policies and Procedures
  • ICH guidelines (S5, M3, etc.)

๐Ÿ’ก Best Practices

  • Engage FDA early via pre-submission meetings
  • Define clear Context of Use for your NAMs
  • Document validation thoroughly
  • Reference qualified platforms when available
  • Stay current on regulatory developments

โš ๏ธ Common Pitfalls

  • Insufficient validation data for intended use
  • Unclear Context of Use statements
  • Waiting too long to engage FDA
  • Over-claiming capabilities
  • Ignoring division-specific requirements