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Regulatory Guidance on Use of Alternative Methods

View a list of regulations and test guidelines on a separate webpage

This page lists guidances that have been issued or accepted by U.S. and international regulatory authorities, organized by testing category. These documents do not necessarily establish legally enforceable responsibilities but should instead be viewed as recommendations. Appropriate use of these methods and approaches can reduce animal use and improve animal welfare.

Toxicity Area Method ICCVAM or ICCVAM Agency Contributions Regulatory Application or Acceptance
Multiple Toxicities Guidance regarding replacement, reduction, and refinement of animal use for testing done under the Federal Hazardous Substances Act CPSC activity
  • U.S.: 15 U.S.C. 1261–1278
Multiple Toxicities Guidance for waiving or bridging of mammalian acute toxicity tests for pesticides and pesticide products (reduction of animal use) EPA activity
  • U.S.: 40 CFR 158
Multiple Toxicities Process for evaluating and implementing alternative approaches to traditional in vivo acute toxicity studies for FIFRA regulatory use (replacement and reduction of animal use) EPA activity
  • U.S.: 40 CFR 158
Multiple Toxicities Guidance document on developing and assessing adverse outcome pathways  
  • U.S.: Accepted via OECD Guidance Document 184 (2013)
  • EU: Accepted via OECD Guidance Document 184
Multiple Toxicities Guidance document on the reporting of defined approaches to be used within integrated approaches to testing and assessment NICEATM and ICCVAM contributed to development of the guidance document
  • U.S.: Accepted via OECD Guidance Document 255 (2016)
  • EU: Accepted via OECD Guidance Document 255
Acute Oral Systemic Toxicity Acute toxicity in vitro starting dose procedure, 3T3 cells (reduction and refinement of animal use) ICCVAM 2001 workshop report; ICCVAM 2006 peer review and report; recommended in 2008
  • U.S.: Accepted by agencies in 2008
  • EU: Accepted via OECD Guidance Document 129 (2010)
Acute Oral Systemic Toxicity Acute toxicity in vitro starting dose procedure, NHK cells (reduction and refinement of animal use) ICCVAM 2001 workshop report; ICCVAM 2006 peer review and report; recommended in 2008
  • U.S.: Accepted by agencies in 2008
  • EU: Accepted via OECD Guidance Document 129 (2010)
Acute Oral Systemic Toxicity Harmonized guidance for nonclinical safety studies for pharmaceuticals (reduction of animal use) FDA activity
  • U.S.: Accepted via ICH Guidance Document M3(R2) in 2010
  • EU: Accepted via ICH Guidance Document M3(R2) in 2010
Acute Oral Systemic Toxicity Waiving or bridging of mammalian acute toxicity tests for pesticides and pesticide products (reduction of animal use) EPA activity
  • U.S.: EPA guidance (2012) provides for authorizing exemptions from standard requirements under 40 CFR 158.500, 40 CFR 161.340, other regulations and notices
Acute Oral Systemic Toxicity In vitro assays for paralytic shellfish toxin detection (replacement of animal use) FDA activity
  • U.S.: Receptor binding assay listed as approved method in National Shellfish Sanitation Program Guide for Control of Molluscan Shellfish (2013)
Acute Oral Systemic Toxicity Harmonized guidance for preclinical safety evaluation of biotechnology-derived pharmaceuticals (reduction of animal use) FDA activity
  • U.S.: Accepted via International Conference on Harmonisation Guidance Document S6(R1) in 2012
  • EU: Accepted via International Conference on Harmonisation Guidance Document S6(R1) in 2012
Acute Dermal Systemic Toxicity Guidance for waiving acute dermal toxicity tests for pesticide formulations and supporting retrospective analysis (reduction of animal use) EPA activity; NICEATM contributed to data analysis
  • U.S.: EPA guidance (2016) provides for authorizing waivers of required dermal toxicity testing for formulated pesticide products from standard requirements under 40 CFR 158
Biologics Testing FDA guidance on preclinical safety evaluation of biotechnology-derived pharmaceuticals (reduction of animal use) FDA activity
  • U.S.: Accepted via International Conference on Harmonisation Guideline S6 (1997, updated 2011)
  • EU: Accepted via International Conference on Harmonisation Guideline S6 (1997, updated 2011)
Biologics Testing FDA guidance on preclinical assessment of investigational cellular and gene therapy products (minimization of animal use) FDA activity
  • U.S.: Applies to products regulated under 42 U.S.C. 262(i)
Biologics Testing USDA provision for exemption to requirement for animal safety testing of veterinary biologics (reduction of animal use) USDA activity
  • U.S.: Applies to 9 CFR 113.4; VS Memo 800.116 (2013, updated 2017)
  • EU: Accepted via Veterinary International Conference on Harmonisation Guideline 50 (2014)
Biologics Testing USDA guidance for obtaining an exemption from in vivo testing of Leptospira bacterins USDA activity
  • U.S.: Applies to 9 CFR 113.101-104; VS Memo 800.102 (2013)
Biologics Testing USDA Guidelines for Validation of In Vitro Potency Assays USDA activity
  • U.S.: Applies to 9 CFR 102.3, 113.8; VS Memo 800.112 (2015)
Dermal Corrosivity and Irritation Guidance document on an integrated approach for testing and assessment for skin corrosion and irritation (replacement of animal use)  
  • U.S.: Accepted via OECD Guidance Document 203 (2014)
  • EU: Accepted via OECD Guidance Document 203 (2014)
Dermal Phototoxicity FDA guidance on photosafety evaluation of pharmaceuticals (reduction or replacement of animal use) FDA activity
  • U.S.: Accepted via International Conference on Harmonisation Guideline S10 (2015)
  • EU: Accepted via International Conference on Harmonisation Guideline S10 (2015)
Immunotoxicity: Allergic Contact Dermatitis Adverse outcome pathway for skin sensitization initiated by covalent binding to proteins
(Part 1) (Part 2)
 
  • U.S.: Accepted via OECD Guidance Document 168 (2012)
  • EU: Accepted via OECD Guidance Document 168 (2012)
Immunotoxicity: Allergic Contact Dermatitis CPSC guidance to clarify the definition of “strong sensitizer” (reduction or replacement of animal use) CPSC activity
  • U.S.: CPSC guidance (2014) clarifies acceptability of in vitro test data for testing required under 15 U.S.C. 1261–1278 (Federal Hazardous Substances Act)
Immunotoxicity: Allergic Contact Dermatitis Guidance document on the reporting of defined approaches and individual information sources to be used within integrated approaches to testing and assessment (IATA) for skin sensitisation NICEATM and ICCVAM submitted a case study included in the guidance document
  • U.S.: Accepted via OECD Guidance Document 256 (2016)
  • EU: Accepted by via OECD Guidance Document 256 (2016)
Ocular Corrosivity and Irritation Histopathological evaluation and collection of data for identification of nonsevere irritants using in vitro methods  
  • U.S.: Accepted via OECD Guidance Document 160 (2011)
  • EU: Accepted via OECD Guidance Document 160 (2011)
Ocular Corrosivity and Irritation Non-animal testing scheme for assessing eye irritation potential of antimicrobial cleaning products EPA activity
  • U.S.: EPA guidance (2013, updated 2015) describes a non-animal testing scheme to satisfy the in vivo data requirement for eye irritation in 40 CFR 158 for antimicrobial cleaning products
Pyrogen Testing In vitro monocyte activation type pyrogen test (replacement of animal use) ICCVAM agency initiative
  • U.S.: FDA guidance (2012) provides for use in place of USP methods