Nonclinical guidelines

24 January 2017

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Please note: Where European Union (EU) guidelines adopted in Australia include references to EU legislation (including EC Directives and Regulations), the requirements contained in the referenced EU legislation are not applicable to the evaluation of prescription medicines by the TGA. The Australian legislative requirements applying to prescription medicines are contained in the Therapeutic Goods Act 1989 and the Therapeutic Goods Regulations 1990, as well as in various legislative instruments such as Therapeutic Goods Orders, Notices and Determinations, see Legislation.

Pharmacology

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EMA/CHMP/ICH/731268/1998 (pdf,237kb)
ICH guideline S6 (R1) - preclinical safety evaluation of biotechnology-derived pharmaceuticals
Replaces: CPMP/ICH/302/95. Note for Guidance on Preclinical Safety Evaluation of Biotechnology Derived Pharmaceutical (Adopted by TGA 1 October 1999)
Effective: 1 June 2014

EMA/CHMP/ICH/646107/2008 (pdf,151kb)
ICH Topic S 9
Note for Guidance on Non-clinical Evaluation for Anticancer Pharmaceuticals

Effective: 17 December 2010

CPMP/ICH/423/02 (pdf,217kb)
ICH Topic S 7 B
Note for guidance on the Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT interval prolongation) by Human Pharmaceuticals

Effective: 4 January 2006

CPMP/ICH/539/00 (pdf,177kb)
ICH Topic S 7 A
Note for Guidance on Safety Pharmacology Studies for Human Pharmaceuticals

Effective: 10 January 2002

EMA/CPMP/ICH/286/1995 (pdf,263kb)
ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals
Replaces: CPMP/ICH/286/95 Modification. (Adopted by TGA 17 December 2010)
Effective: 1 June 2014

EMA/CHMP/ICH/507008/2011 (pdf,210kb)
ICH guideline M3 (R2) - questions and answers
For information: 1 June 2014

Pharmacokinetics

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CPMP/ICH/384/95 (pdf,188kb)
ICH Topic S 3 A
Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies

Effective: April 1996

CPMP/ICH/385/95 (pdf,116kb)
ICH Topic S 3 B
Repeated Dose Tissue Distribution Studies

Effective: April 1996

EMEA/CHMP/SWP/1991104/2014 (pdf,375kb)
Questions and answers on the withdrawal of the 'Guideline on pharmacokinetics and metabolic studies in the safety evaluation of new medicinal products in animals (3BS11A)'
Replaces: Guideline 3BS11a (Adopted by TGA 12 February 2002)
Effective: 15 September 2014

TGA annotation:
Guideline 3BS11a has been withdrawn, as explained in the above Question and Answer Guideline; however, the guidance contained within Guideline 3BS11a remains applicable in Australia, as in the EU, and has been incorporated into TGA Guidance 23: Nonclinical studies.

Toxicology

Single-dose toxicity

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EMA/CHMP/SWP/81714/2010 (pdf,65kb)
Questions and answers on the withdrawal of the 'Note for guidance on single dose toxicity'
Replaces: 3BS1a Single Dose Toxicity
Effective: 24 February 2014

Repeat-dose toxicity

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CPMP/SWP/1042/99 Rev 1 Corr (pdf,191kb)
Guideline on repeated dose toxicity
Effective: 17 December 2010

CPMP/ICH/300/95 (pdf,118kb)
ICH Topic S 4.
Note for Guidance on Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity Testing)

Effective: 30 August 2001

Genotoxicity

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EMA/CHMP/ICH/126642/2008 (pdf,339kb)
ICH guideline S2 (R1) on genotoxicity testing and data interpretation for pharmaceuticals intended for human use
Replaces and combines CPMP/ICH/141/95 (ICH S2A) and CPMP/ICH/174/95 (ICH S2B)
Effective: 24 February 2014

CPMP/SWP/5199/02 (pdf,56kb)
EMEA/CHMP/QWP/251344/2006
Guideline on the Limits of Genotoxic Impurities

Effective: November 2006

EMA/CHMP/SWP/431994/2007 Rev. 3 (pdf,167kb)
Questions and answers on the 'Guideline on the limits of genotoxic impurities'
Replaces: EMA/CHMP/SWP/431994/2007 Revision 2
Effective: 24 February 2014

Carcinogenicity

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EMEA/CHMP/SWP/194898/2006 (pdf,49kb)
Guideline on Carcinogenicity Evaluation of Medicinal Products for the Treatment of HIV Infection
Effective: 6 April 2009

CPMP/SWP/2592/02 Rev 1 (pdf,238kb)
CHMP SWP Conclusions and recommendations on the use of genetically modified animal models for carcinogenicity assessment
Effective: 25 May 2015

CPMP/SWP/2877/00 (pdf,157kb)
Note for Guidance on Carcinogenic Potential
Effective: 5 March 2003

CPMP/SWP/372/01 (pdf,157kb)
Points to Consider on the Non-Clinical Assessment of the Carcinogenic Potential of Insulin Analogues
Effective: 4 September 2002

CPMP/ICH/299/95 (pdf,164kb)
ICH Topic S 1 B
Note for Guidance on Carcinogenicity: Testing for Carcinogenicity of Pharmaceuticals

Effective: 1 May 2000

CPMP/ICH/140/95 (pdf,126kb)
ICH Topic S 1 A
Note for Guidance on The Need for Carcinogenicity Studies of Pharmaceuticals

Effective: December 1998

EMA/CHMP/ICH/752486/2012 (pdf,96kb)
ICH guideline S1 Regulatory notice on changes to core guideline on rodent carcinogenicity testing of pharmaceuticals
Effective: 1 August 2014

EMEA/CHMP/ICH/383/1995 (pdf,121kb)
ICH Topic S 1 C (R2)
Note for Guidance on Dose Selection for Carcinogenicity Studies of Pharmaceuticals

Effective 23 October 2008

Reproductive and Developmental Toxicity

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EMEA/CHMP/203927/2005 (pdf,163kb)
Guideline on Risk Assessment of Medicinal Products on Human Reproduction and Lactation: From Data to Labelling
Effective: 22 June 2009

EMEA/CHMP/SWP/169215/2005 (pdf,72kb)
Guideline on the need for Non-Clinical Testing in Juvenile Animals of Pharmaceuticals for Paediatric Indications
Effective: 27 January 2009

CPMP/SWP/2600/01 (pdf,153kb)
Points to Consider on the Need for Assessment of Reproductive Toxicity of Human Insulin Analogues
Effective: 5 March 2003

CPMP/ICH/386/95 (pdf,265kb)
ICH Topic S 5 (R2)
Note for Guidance on the Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility

Effective: 1 January 1995

Local tolerance

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CHMP/SWP/2145/2000 Rev. 1 (pdf,128kb) Guideline on non-clinical local tolerance testing of medicinal products
To replace: CPMP/SWP/2145/00 Note for Guidance on Non-Clinical Local Tolerance Testing of Medicinal Products
Effective 1 May 2016

Other toxicity

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CHMP/ICH/752211/2012 (pdf,91kb)
ICH Guideline S10 on photosafety evaluation of pharmaceuticals. See also:
Finalised guideline (pdf,265kb)
Replaces: CPMP/SWP/398/01 Note for Guidance on Photosafety Testing (Adopted by TGA 17 September 2004) and EMA/CHMP/SWP/336670/2010 Question and answers on the 'Note for guidance on photosafety testing' (provided for information 24 February 2014)
Effective: 1 August 2014

CHMP/167235/2004 (pdf,133kb)
ICH Topic S 8
Note for Guidance on Immunotoxicity Studies for Human Pharmaceuticals

Effective: April 2006

General guidelines

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EMA/CHMP/ICH/646107/2008 (pdf,151kb)
ICH Topic S 9
Note for Guidance on Non-clinical Evaluation for Anticancer Pharmaceuticals

Effective: 17 December 2010

CPMP/QWP/1719/00 Rev 1 (pdf,102kb)
Guideline on Medicinal Gases: Pharmaceutical Documentation (Including Recommendation on Non-Clinical Safety Requirements for Well Established Medicinal Gases)
Replaces: CPMP/QWP/1719/00 (Adopted by TGA 12 March 2003)
Effective: 26 June 2009

EMEA/CHMP/SWP/28367/07 (pdf,83kb)
Guideline on Strategies to Identify and Mitigate Risks for First-In-Human Clinical Trials with Investigational Medicinal Products
Effective: 26 June 2009

EMEA/CHMP/GTWP/125459/2006 (pdf,68kb)
Guideline on the Non-Clinical Studies required before First Clinical Use of Gene Therapy Medicinal Products
Effective: 8 April 2009

EMEA/CHPM/SWP/4446/2000 (pdf,155kb)
Guideline on the Specification Limits for Residues of Metal Catalysts or Metal Reagents
Effective: 1 May 2009

CPMP/SWP/799/95 (pdf,39kb)
Guideline on the Non-Clinical Documentation for Mixed Marketing Authorisation Applications
Effective: April 2006

EMEA/CHMP/SWP/258498/2005 (pdf,47kb)
Guideline on the Non-Clinical Development of Fixed Combinations of Medicinal Products
Effective: 23 October 2008

CPMP/SWP/1094/04 (pdf,38kb)
Guideline on the Evaluation of Control Samples in Nonclinical Safety Studies: Checking for Contamination with the Test Substance
Effective: 1 September 2005

EMEA/CPMP/VEG/4717/2003 Rev.1 (pdf,145kb)
Guideline on Dossier Structure and Content for Pandemic Influenza Vaccine Marketing Authorisation Application (Revision)
Replaces: CPMP/VEG/4717/03 (Adopted by TGA 16 August 2004)
Effective: 1 April 2014

TGA annotations:
Section 1.1.2. Pandemic variation
If the pandemic influenza virus is of a HN subtype for which nonclinical and clinical data have not been included in the Core Pandemic Dossier, it is highly desirable that nonclinical and clinical data obtained from studies with the pandemic HN subtype be included in the pandemic variation dossier.
Section 3.1.1
Candidate influenza vaccine virus should be taken to include the most recently available candidates and technologies, as noted on WHO website.

Effective 1 November 2014: the Quality aspects of this Guideline are replaced by EMA/CHMP/BWP/310834/2012 Guideline on Influenza Vaccines - Quality Module.
The nonclinical and clinical aspects of this Guidelines continue to apply.

EMEA/CHMP/BMWP/101695/2006 (pdf,118kb)
Guideline on Comparability of Biotechnology-Derived Medicinal Products after a change in the Manufacturing Process - Non-Clinical and Clinical Issues
Replaces: EMEA/CPMP/3097/02 (Adopted by TGA 12 May 2005)
Effective: 8 April 2009

CPMP/ICH/2738/99 (pdf,151kb)
ICH Topic Q 3 B (R2)
Note for Guidance on Impurities in New Drug Products

Status: Replaces CPMP/ICH/2736/99-ICH Q3B(R) (Adopted by TGA 16 August 2004)
Effective: 1 May 2009

CPMP/ICH/2737/99 (pdf,63kb)
ICH Topic Q 3 A (R2)
Note for Guidance on Impurities Testing: Impurities in New Drug Substances

Replaces: CPMP/ICH/2737/99. ICH Topic Q 3 A (R) (Adopted by TGA 12 March 2003)
Effective: 1 June 2014

CPMP/QWP/159/01 (pdf,26kb)
EMEA/CVMP/271/01
Note for Guidance on Limitations to the Use of Ethylene Oxide in the Manufacture of Medicinal Products

Replaces: 3AQ3a
Effective: 22 May 2002

TGA annotation:
Sponsors should note that the British Pharmacopoeia (BP 2014) states under Herbal Drugs (Ph Eur monograph 1433) that "the use of ethylene oxide for the decontamination of herbal products is prohibited."

CPMP/SWP/465/95 (pdf,46kb)
Note for Guidance on Pre-Clinical Pharmacological and Toxicological Testing of Vaccines
Effective: 1 May 2000

EMA/CHMP/ICH/731268/1998 (pdf,237kb)
ICH guideline S6 (R1) - preclinical safety evaluation of biotechnology-derived pharmaceuticals
Replaces: CPMP/ICH/302/95. Note for Guidance on Preclinical Safety Evaluation of Biotechnology Derived Pharmaceutical (Adopted by TGA 1 October 1999)
Effective: 1 June 2014

3CC29A (pdf,52kb)
Investigation of Chiral Active Substances
Effective: 1 January 1995

EMA/CHMP/ICH/82260/2006 (pdf,229kb)
ICH guideline Q3C (R5) on impurities: guideline for residual solvents
Replaces: CPMP/ICH/283/95. ICH Topic Q3C (R4) (Adopted by TGA 1 June 2014)
Effective: 1 June 2013