Submissions of Test Methods for Evaluation

Validation, Qualification, and Regulatory Acceptance of New Approach Methodologies

March 2024 -

This document, prepared by the ICCVAM Validation Workgroup with input from stakeholders, describes an approach to NAMs validation that reflects modern toxicity testing, placing less emphasis on replacement of in vivo tests with a single alternative method and more emphasis on integrating results from multiple in vitro and in chemico assays and in silico approaches. Guided by the principles articulated in the 2018 ICCVAM Strategic Roadmap, it presents a flexible approach to how confidence is established to help ensure the adoption of new methods by federal agencies and regulated industries once validated for a specific application or context of use.

ICCVAM welcomes submission of innovative test methods that may be acceptable for specific regulatory uses. Acceptability for regulatory use is generally demonstrated by completion of adequate validation studies to characterize the usefulness and limitations of a test method in accordance with ICCVAM test method submission guidelines.

To maximize the potential for effective implementation of new test methods or approaches, ICCVAM will only conduct evaluations and prepare recommendations on test method submissions proposed for regulatory uses that align with ICCVAM member agency needs and priorities. Test method developers are encouraged to consult with NICEATM and ICCVAM throughout the test method development, prevalidation, and validation process, as well as during submission preparation to ensure that:

  • The test method aligns with the needs and priorities of one or more ICCVAM agencies, and there is at least one agency willing to sponsor the test method for evaluation.
  • Validation studies conducted using the test method adequately characterize its usefulness and limitations for a particular regulatory application.
  • The test method submission package contains data and information required by the sponsoring agencies to determine if a test method will meet their regulatory needs.

Test method submissions may be made by contacting ICCVAM. Guidance for preparing adequate submission packages is available in the ICCVAM Guidelines for the Nomination and Submission of New, Revised, and Alternative Test Methods (NIH Publication No. 03-4508 - September 2003).

NIEHS and other organizations offer funding for validation studies of new test methods: see our Funding Opportunities for Test Method Developers page for current opportunities.

Update of ICCVAM Document on Validation and Regulatory Acceptance

The ICCVAM Validation Workgroup was established in 2021 to update the 1997 ICCVAM report, “Validation and Regulatory Acceptance of Toxicological Test Methods.” The new document, available above, aligns with principles articulated in the 2018 ICCVAM publication, “A Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States.” ICCVAM invited public comments from all stakeholders on the draft document, which was also discussed at the September 21-22 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods.

View Federal Register notice (August 10, 2023 - View as PDF)

Public Comments Received

Past Nominations and Submissions

Please note: some of the documents attached below may not be fully accessible to some readers. If you need assistance, send an email to the NICEATM Webmaster.

Nominations to ICCVAM
Nominator Nominated Test Method Activity Activity
NIOSH/CDC Nomination of the Electrophilic Allergic Screening Assay for the Detection of Substances Causing Allergic Contact Dermatitis
View Nomination Cover Letter
Validation study in progress NICEATM preliminary evaluation
BioSentinel Pharmaceuticals Submission of the BoTest™, BoTest™ Matrix, and BoCell™ Botulinum Neurotoxin Activity assays for interlaboratory validation studies by ICCVAM and NICEATM.
View Nomination Cover Letter
No agency support for moving forward (2013) -
MB Research Labs Nomination of the In Vitro Sensitivity Assay for Detection of Substances That Cause Dermal Sensitization
View nomination letter
Evaluation suspended View March 2013 letter to test method sponsor
Biotest AG Nomination of an in vitro test method for assessing pyrogenicity of pharmaceuticals and other products for further evaluation in order to expand its applicability domain to non-endotoxin pyrogens
View Nomination Cover Letter
Evaluation completed FDA Document:
"Guidance for Industry — Pyrogen and Endotoxins Testing: Questions and Answers"
CPSC CPSC Nomination: Request for Assessment of the Validation of the Local Lymph Node Assay for Classification of Sensitizers Evaluation completed List of references
HSUS Alternative Methods to Replace the Mouse LD50 Assay for Botulinum Toxin Potency Testing

(Dec. 15, 2005) View HSUS Letter to Allergan, Inc.
Workshop completed Workshop report
CertiChem, Inc MCF-7 Estrogenic Activity Cell Proliferation Assay
View Nomination Cover Letter
View Documentation Provided with Nomination
Validation study and evaluation completed Draft validation study report
Xenobiotic Detection Systems LUMI-CELLTM Estrogen Receptor High-Throughput System for Screening Estrogen-Like Chemicals for Validation Studies
View Nomination Cover Letter
View Documentation Provided with Nomination
Validation study and evaluation completed Test method evaluation report
(Redacted at nominator's request) NTP Two-Year Toxicology and Carcinogenesis Rodent Studies (received Oct. 24, 2007)

Additional nominating material (received May 13, 2008)
Under consideration Draft ICCVAM Recommended Priority
Submissions to ICCVAM
Sponsor Test Method Evaluation
Alternatives Testing Steering Committee:
Johnson Diversey
S.C. Johnson & Son, Inc.
The Procter & Gamble Company
The Accord Group
In Vitro Test Method for Assessment of the Eye Irritation Potential of Antimicrobial Cleaning Products

View Submission Cover Letter from IIVS, Inc.
Evaluation completed ICCVAM test method evaluation report
ECVAM In Vitro Pyrogenicity Test Methods Peer review complete Pyrogenicity test methods