Clinical efficacy and safety guidelines

23 February 2016

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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.

Clinical pharmacology and pharmacokinetics

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EMA/CHMP/37646/2009 (pdf,166kb)
Guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products
Effective: 15 September 2014

EMA/CHMP/EWP/280/96 (pdf,499kb)
Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms (EMA/CPMP/EWP/280/96 Corr1)
Replaces: CPMP/EWP/280/96 Corr. Note for Guidance on Modified Release Oral and Transdermal dosage forms: Section II (Pharmacokinetic and Clinical Evaluation) (corrected version adopted by TGA 1 June 2014)
Effective: 1 June 2015

TGA annotation:
For multiple strengths of generic TDDS products, bioequivalence studies should be performed at least on the lowest and highest strengths versus the corresponding innovator products. If an applicant considers that this is unnecessary in a particular case, a justification for not submitting bioequivalence data should be submitted in accordance with the ARGPM guidance on Biopharmaceutic studies.

CPMP/EWP/560/95/Rev. 1 Corr.* (pdf,833kb)*
Guideline on the Investigation of Drug Interactions
Replaces: CPMP/EWP/560/95 (Adopted by TGA 19 April 2001), and EMEA/CHMP/EWP/297931/2008 Concept Paper on this topic (provided for information 10 February 2009)
Effective: 1 August 2014

CPMP/EWP/QWP/1401/98 Rev. 1/ Corr ** (pdf,233kb)
Guideline on the Investigation of Bioequivalence
Replaces: CPMP/QWP/EWP/1401/98 (Adopted by TGA 12 February 2002)
Effective: 16 June 2011

TGA annotation:
While this guidance suggests that the design and conduct of the study should follow EU regulations on Good Clinical Practice, sponsors should note that the EU Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) has been adopted in Australia with TGA annotations.
The procedure for abridged applications claiming essential similarity to a reference product (i.e., generics), which allows applications to be made to numerous Member States of the EU, based on bioequivalence with a reference product from one Member State, does not apply in Australia. An application for registration of a generic product in Australia should generally include a bioequivalence study versus a leading brand obtained in Australia.

EMA/CHMP/600958/2010/Corr.* (pdf,138kb)
Appendix IV of the Guideline on the Investigation on Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1): Presentation of Biopharmaceutical and Bioanalytical Data in Module 2.7.1

TGA annotation:

  1. The procedure for abridged applications claiming essential similarity to a reference product (i.e., for generic medicines), which allows applications to be made to numerous Member States of the EU, based on bioequivalence with a reference product from one Member State, does not apply in Australia. Unless otherwise justified, an application for registration of a generic medicine in Australia should generally include one or more bioequivalence studies, each versus the Australian reference product. Directions given in this guideline regarding "non-EU reference products" (Section 2), and "Member State where the reference product is purchased from" (Table 2.1) should be disregarded in favour of the advice given in TGA Guidance 15: Biopharmaceutic studies.
  2. Similarly, details of the (presumably most recent) EU Authority Inspection of the clinical and bioanalytical study sites and site of the PK and statistical analysis (Table 2.2) are GCP/GLP issues, and need not be provided.
  3. Table 3.1 should be amended according to the metrics that are suitable for the product and/or study type.

EMA/618604/2008 (pdf,479kb)
Questions & Answers: Positions on specific questions addressed to the pharmacokinetics working party
For information: 1 June 2014

EMEA/CHMP/EWP/192217/2009 (pdf,154kb)
Guideline on bioanalytical method validation
Effective: 1 June 2013

CHMP/EWP/89249/2004 (pdf,98kb)
Guideline on the Clinical Investigation of the Pharmacokinetics of Therapeutic Proteins
Effective: 6 January 2009

EMEA/CHMP/EWP/147013/2004 Corr (pdf,114kb)
Guideline on the role of Pharmacokinetics in the Development of Medicinal Products in the Paediatric Population
Effective: 24 August 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

CHMP/EWP/185990/06 (pdf,68kb)
Guideline on Reporting the results of Population Pharmacokinetic Analysis
Effective: 27 January 2009

CPMP/EWP/2339/02 (pdf,92kb)
Guideline on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients with Impaired Hepatic Function
Effective: 4 January 2006

CHMP/EWP/225/02 (pdf,213kb)
Note for guidance on the evaluation of the Pharmacokinetics of medicinal products in patients with impaired renal function
Effective: 24 November 2004

EMA/CHMP/203926/2012 (pdf,66kb)
Concept paper on the need for revision of the Note for guidance on the evaluation of the pharmacokinetics of medicinal products in patients with impaired renal function
For information: 1 August 2014

CPMP/EWP/1875/03/Final (pdf,149kb)
Points to Consider on the Clinical Requirements of Modified Release Products Submitted as a Line Extension of an Existing Marketing Authorisation
Effective: 7 June 2005

CPMP/EWP/2655/99 (pdf,86kb)
Points to Consider on Pharmacokinetics and Pharmacodynamics in the Development of Antibacterial Medicinal Products
Effective: 19 April 2001

3CC3A (pdf,39kb)
Pharmacokinetic Studies in Man
Effective: 12 February 2002

Alimentary tract and metabolism

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EMA/CHMP/336243/2013 (pdf,219kb)
Guideline on the evaluation of medicinal products for the treatment of chronic constipation (including opioid induced constipation) and for bowel cleansing
In place of: EMA/CHMP/462198/2012 Concept paper on the need of a guideline for clinical investigation of medicinal products for the treatment of chronic constipation (provided for information 1 August 2014)
Effective: 2 February 2016

CPMP/EWP/1080/00 Rev. 1 (pdf,225kb)
Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus
Replaces: CPMP/EWP/1080/00 (Adopted by TGA 23 October 2002)
Effective: 1 April 2014

EMA/CHMP/EWP/342691/2009 (pdf,464kb)
Guideline on the evaluation of drugs for the treatment of Gastro-oesophageal reflux disease
Effective: 15 September 2014

CPMP/EWP/2284/99 Rev. 1 (pdf,61kb)
Guideline on the Development of New Medicinal Products for the Treatment of Crohn's Disease
Replaces: CPMP/EWP/2284/99 (Adopted by TGA 10 January 2002)
Effective: 25 February 2009

CHMP/EWP/18463/2006 (pdf,115kb)
Guideline on the Development of New Medicinal Products for the Treatment of Ulcerative Colitis
Effective: 8 April 2009

CPMP/EWP/281/96 Rev. 1 (pdf,109kb)
Guideline on Clinical Evaluation of Medicinal Products Used in Weight Control
Replaces: CPMP/EWP/281/96
Effective: 26 March 2010

TGA annotation:
If a sponsor wishes to claim secondary benefits associated with weight loss (such as improved blood lipids, glycaemic control or blood pressure), then the relevant guidelines for these specific benefits should be independently satisfied.

EMEA/CHMP/EWP/517497/2007 (pdf,51kb)
Guideline on Clinical Evaluation of Medicinal Products Used in Weight Control (CPMP/EWP/281/96 Rev 1)
Addendum on Weight Control in Children
Effective: 25 February 2009

CPMP/EWP/4937/03 (pdf,112kb)
Guideline on Non-Clinical and Clinical Development of Medical Products for the Prevention of Nausea and Vomiting Associated with Cancer Chemotherapy
Effective: 16 March 2009

CPMP/EWP/785/97 Rev. 1 (pdf,231kb)
Guideline on the evaluation of medicinal products for the treatment of irritable bowel syndrome
Replaces: CPMP/EWP/785/97 Points to consider on the evaluation of medicinal products for the treatment of Irritable Bowel Syndrome (adopted by TGA September 2004).
Effective: 25 May 2015

EMA/CHMP/172616/2012 (pdf,74kb)
Concept paper on the revision of the CHMP points to consider on the evaluation of medicinal products for the treatment of irritable bowel syndrome (CPMP/EWP/785/97)
For information: 1 August 2014

CPMP/EWP/863/98 (pdf,42kb)
Points To Consider on Wording of Helicobacter Pylori Eradication Therapy in Selected SPC Sections
Effective: 15 December 2000

Blood and blood-forming organs

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CPMP/EWP/197/99 (pdf,44kb)
Points to Consider Concerning Endpoints in Clinical Studies with Haematopoeitic Growth Factors for Mobilisation of Autologous Stem Cells
Effective: 19 April 2001

Blood products (including biotech alternatives)

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CHMP/BPWP/585257/2009 (pdf,147kb)
Guideline on the clinical investigation of hepatitis B immunoglobulins
Effective: 2 February 2016

CHMP/BPWP/410415/2011 Rev 1 (pdf,246kb)
Guideline on the clinical investigation of human normal immunoglobulin for subcutaneous and/or intramuscular administration (SCIg/IMIg)
Replaces: EMEA/CPMP/BPWG/283/00 Note for Guidance on the Clinical Investigation of Human Normal Immunoglobulin for Subcutaneous and Intramuscular Use (Adopted by TGA 12 March 2003)
Effective: 2 February 2016

CPMP/BPWG/575/99 Rev. 1 (pdf,115kb)
Guideline on the Clinical Investigation of Human Anti-D Immunoglobulin for Intravenous and/or Intramuscular Use
Replaces: CPMP/BPWG/575/99 (Adopted by TGA 19 April 2001)
Effective: 10 February 2009

CPMP/BPWG/220/02 (pdf,142kb)
Guideline on the Clinical Investigation of Human Plasma Derived Von Willebrand Factor Products
Effective: 1 June 2006

CPMP/BPWG/1089/00 (pdf,61kb)
Guideline on the clinical investigation of Plasma derived Fibrin Sealant/Haemostatic Products
Effective: 13 January 2005

EMA/CHMP/BPWP/572810/2013 (pdf,125kb)
Concept paper on the need for revision of the guideline on the clinical investigation of plasma derived fibrin sealant/haemostatic products (CPMP/BPWG/1089/00) and the related Core SmPC
For information: 1 August 2014

CPMP/BPWG/2220/99 (pdf,168kb)
Note for Guidance on the Clinical Investigation of Plasma Derived Antithrombin Products
Effective: 16 October 2003

TGA annotation:
If a sponsor believes that the patient numbers specified in this guideline are not achievable in Australia, advice should be sought from the TGA.

EMA/CHMP/BPWP/144533/2009 (pdf,302kb)
Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products
Replaces: CPMP/BPWG/1561/99 Note for Guidance on the Clinical Investigation of Recombinant Factor VIII and IX Products (Adopted by TGA 19 April 2001); and CPMP/BPWG/198/95 rev 1 Note for Guidance on the Clinical Investigation of Human Plasma Derived Factor VIII and IX (Adopted by TGA 17 September 2004)
Effective: 1 June 2014

EMA/CHMP/BPWP/144552/2009 Rev 1 (pdf,332kb)
Clinical investigation of recombinant and Human plasma-derived factor IX products
Replaces: EMA/CHMP/BPWP/144552/2009
Guideline on clinical investigation of recombinant and human plasma-derived factor IX products (Adopted by TGA 1 June 2014)
Effective: 1 September 2015

EMA/CHMP/BPWP/94033/2007 rev. 2 (pdf,220kb)
Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg)
Replaces: CPMP/BPWG/388/95 Rev 1 (Adopted by TGA 19 April 2001)
Effective: 1 June 2014

Cardiovascular system

Hypertension

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EMA/238/1995/Rev. 3 (pdf,206kb)
Guideline on clinical investigation of medicinal products in the treatment of hypertension
Replaces: CPMP/EWP/238/95 Rev. 2 Note for Guidance on Clinical Investigation of Medicinal Products in the Treatment of Hypertension (adopted by TGA 15 June 2006)
Effective: 17 August 2015

EMA/CHMP/206815/2013 (pdf,191kb)
Paediatric addendum to the note for guidance on the clinical investigation on medicinal products in the treatment of hypertension
In place of: EMEA/CHMP/EWP/545456/2008 Concept Paper on the Need for the Development of a Paediatric Addendum to the Note for Guidance on the Clinical Investigation on Medicinal Products in the Treatment of Hypertension (Provided for information 1 May 2009)
Effective: September 2015

Lipid disorders

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EMA/CHMP/748108/2013 (pdf,178kb)
Guideline on clinical investigation of medicinal products in the treatment of lipid disorders
Replaces: CPMP/EWP/3020/03 Note for guidance on clinical investigation of medicinal products in the treatment of lipid disorders. (Adopted by TGA 20 May 2005)
Effective: 1 August 2014

EMA/CHMP/494506/2012 (pdf,124kb)
(EMEA/CHMP/EWP/213057/2010)
Paediatric addendum to CHMP guideline on clinical investigation of medicinal products in the treatment of lipid disorders
In place of: EMEA/CHMP/EWP/350495/2009 Concept paper (provided for information 26 March 2010)
Effective: 1 August 2014

Pulmonary arterial hypertension

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EMEA/CHMP/EWP/356954/2008 (pdf,62kb)
Guideline on the Clinical Investigations of Medicinal Products for the Treatment of Pulmonary Arterial Hypertension
Effective: 28 May 2010

EMA/CHMP/213972/2010 (pdf,105kb)
Paediatric Addendum to the CHMP Guideline on the Clinical Investigations of Medicinal Products for the Treatment of Pulmonary Arterial Hypertension
In place of: EMEA/CHMP/EWP/644261/2008 concept paper on this topic (provided for information 1 May 2009)
Effective: 1 August 2014

Arrythmias

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EMA/CHMP/341363/2014 (pdf,264kb)
Guideline on clinical investigation of medicinal products for prevention of stroke and systemic embolic events in patients with non-valvular atrial fibrillation
Effective: 26 December 2014

TGA annotation:

  • Section 8.1:
  • The collection of plasma/serum samples for the measurement of drug level and/or anticoagulant effect at the time of outcome events (e.g. bleeding, SEE, stroke) is recommended.
  • The dossier must include specific discussion regarding non-specific and specific reversal agents and/or antidotes.
  • The dossier must include a discussion regarding the utility of routine and/or ad hoc laboratory monitoring (drug levels or measures of anticoagulant effect) for the safe and efficacious use of the product. The availability of the laboratory tests mentioned should be included in the discussion.
  • Section 6.2 (3):
  • Where a study includes outcomes from 'VKA-naïve patients' meeting the definition provided in this guidance, a sensitivity analysis must be conducted with results from patients with no previous VKA exposure.

CHMP/ICH/2/04 (pdf,219kb)
ICH Topic E 14
Note for Guidance on Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs

Effective: 9 February 2006

TGA annotation:
QT prolongation would be of regulatory concern if either the estimated QT prolongation was >5ms OR the upper bound of the 95% confidence interval was >10ms

EMA/CHMP/ICH/310133/2008 (pdf,176kb)
ICH guideline E14 - questions and answers [on CHMP/ICH/2/04. The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs]
Effective: 15 September 2014

CPMP/EWP/237/95 (pdf,73kb)
Note for guidance on antiarrhythmics
Effective: August 1997

EMA/CHMP/EWP/213056/2010 (pdf,177kb)
Addendum to the Guideline on antiarrhythmics on atrial fibrillation and atrial flutter [CPMP/EWP/237/95]
Effective: 15 September 2014

Venous thromboembolism

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EMA/CHMP/325170/2012 (former CPMP/EWP/707/98 Rev. 1 corr) (pdf,227kb)
Guideline on clinical investigation of medicinal products for prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk surgery
Replaces: CPMP/EWP/707/98 Rev 1 Guideline on Clinical Investigation of Medicinal Products for Prophylaxis of High Intra- and Post-Operative Venous Thromboembolic Risk (Adopted by TGA 8 December 2008)
Effective: 1 August 2014

CPMP/EWP/6235/04 (pdf68,kb)
Guideline on Clinical Investigation of Medicinal Products for the Prophylaxis of Venous Thromboembolic Risk in Non-Surgical Patients
Effective: 29 September 2006

CPMP/EWP/563/98 (pdf,45kb)
Note for Guidance on Clinical Investigation of Medicinal Products for the Treatment of Venous Thromboembolic Disease
Effective: 25 January 2001

Heart failure

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CPMP/EWP/2986/03 Rev. 1 (pdf,194kb)
Guideline on clinical investigation of medicinal products for the treatment of acute heart failure
Replaces: CPMP/EWP/2986/03 Note for Guidance on Clinical Investigation of Medicinal Products for the Treatment of Cardiac Failure. Addendum on Acute Cardiac Failure (CPMP/EWP/235/95 Rev 1); and EMA/CHMP/EWP/215701/2010 Concept paper on the need for revision of the addendum on acute cardiac failure (CPMP/EWP/2986/03) (provided for information 1 August 2014)
Effective: 2 February 2016

CPMP/EWP/235/95 Rev 1 (pdf,63kb)
Note for Guidance on the Clinical Investigation of Medicinal Products in the Treatment of Cardiac Failure
Effective: 23 February 2001

Coronary artery disease (CAD)

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CPMP/EWP/234/95/rev. 1 (pdf,69kb)
Guideline on The Clinical Investigation of Anti-Anginal Medicinal Products in Stable Angina Pectoris
Replaces: 3CC20a (Adopted by TGA 12 February 2002)
Effective: 29 September 2006

CHMP/EWP/191583/2005 (pdf,41kb)
Questions and Answers Document on the Clinical Development of Fixed Combinations of Drugs Belonging to Different Therapeutic Classes in the Field of Cardiovascular Treatment and Prevention
Effective: 17 December 2010

CPMP/EWP/967/01 (pdf,187kb)
Points to Consider on the Clinical Development of Fibrinolytic Medicinal Products in the Treatment of Patients with St Segment Elevation Acute Myocardial Infarction (STEMI)
Effective: 17 September 2004

CPMP/EWP/570/98 (pdf,65kb)
Points to Consider on the Clinical Investigation of New Medicinal Products in the Treatment of Acute Coronary Syndrome (ACS) Without Persistent ST-Segment Elevation
Effective: 19 April 2001

Other

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EMEA/CHMP/EWP/311890/2007 (pdf,112kb)
Guideline on the Evaluation of Medicinal Products for Cardiovascular Disease Prevention
Effective: 29 June 2009

CPMP/EWP/714/98 Rev 1 (pdf,180kb)
Note For Guidance on Clinical Investigation of Medicinal Products for the Treatment of Peripheral Arterial Occlusive Disease
Effective: 7 May 2003

Dermatologicals

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CHMP/EWP/2454/02 corr (pdf,245kb)
Guideline on clinical investigation of medicinal products indicated for the treatment of Psoriasis
Effective: 28 July 2005

TGA annotation:
Section 5.2.5 on this guideline suggests that regulatory approval requires a comparison with an active comparator (e.g. cyclosporin, methotrexate etc). Placebo-controlled studies may also be acceptable in Australia.

3CC26a (pdf,53kb)
Clinical Investigation of Corticosteroids Intended for Use on the Skin
Effective: 12 February 2002

Genito-urinary system and sex hormones

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CPMP/EWP/18/01/Rev. 1 (pdf,224kb)
Note for Guidance on the Clinical Investigation of Medicinal Products for the Treatment of Urinary Incontinence
Replaces: CPMP/EWP/18/01 (Adopted by TGA 4 February 2004)
Effective: 1 August 2014

EMEA/CPMP/EWP/519/98 Rev 1 (pdf,59kb)
Guideline on Clinical Investigation of Steroid Contraceptives in Women
Replaces: EMEA/CPMP/EWP/519/98 (Adopted by TGA 19 April 2001)
Effective: January 2006

EMEA/CHMP/021/97 Rev. 1 (pdf,59kb)
Guideline on Clinical Investigation of Medicinal Products for the Treatment of Hormone Replacement Therapy of Oestrogen Deficiency Symptoms in Postmenopausal Women
Replaces: CPMP/EWP/021/97 (Adopted by TGA 15 December 2000)
Effective: 9 February 2006

Anti-infectives for systemic use

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EMEA/CPMP/EWP/633/02 Revision 2 (pdf,208kb)
Guideline on the Clinical Development of Medicinal Products for the Treatment of HIV Infection
Replaces EMEA/CPMP/EWP/633/02 Rev. 1 (Adopted by TGA February 2004)
Effective: 15 July 2009

EMEA/CHMP/EWP/30039/2008 (pdf,139kb)
Guideline on the Clinical Evaluation of Direct Acting Antiviral Agents Intended for Treatment of Chronic Hepatitis C
Effective: 28 May 2010

CHMP/EWP/1343/01 Rev. 1 (pdf,191kb)
Guideline on the clinical evaluation of antifungal agents for the treatment and prophylaxis of invasive fungal disease.
Replaces: CPMP/EWP/1343/01 (Adopted by TGA 17 September 2008)
Effective: 1 April 2014

CHMP/EWP/4713/03 (pdf,73kb)
Guideline on Clinical Investigation of Medicinal Products for the Treatment of Sepsis
Effective: 29 September 2006

CHMP/EWP/6172/03 (pdf,141kb)
Guideline on the Clinical Evaluation of Medicinal Products intended for Treatment of Hepatitis B
Effective: 1 September 2006

CPMP/EWP/558/95 rev 2 (pdf,240kb)
Guideline on the evaluation of medicinal products indicated for treatment of bacterial infections
In place of: EMEA/CHMP/EWP/435635/2008 concept paper on this topic (provided for information 1 May 2009)
Effective: 1 April 2014

TGA annotation:
The Report of the Joint Expert Advisory Committee on Antibiotic Resistance (1999) accepted by the Commonwealth, also includes recommendations for assessment of the propensity for promoting resistance and cross-resistance.

EMA/CHMP/351889/2013 (pdf,210kb)
Addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections
Effective: 1 August 2014

EMA/CHMP/EWP/14377/2008 (pdf,100kb)
Addendum to the Note for Guidance on Evaluation of Medicinal Products Indicated for Treatment of Bacterial Infections To Specifically Address the Clinical Development of New Agents to Treat Disease due to Mycobacterium Tuberculosis
Replaces: EMEA/CHMP/EWP/122355/2007 (Adopted by TGA 10 February 2009)
Effective: 17 December 2010

TGA annotation:
The Report of the Joint Expert Advisory Committee on Antibiotic Resistance (1999) accepted by the Commonwealth, also includes recommendations for assessment of the propensity for promoting resistance and cross-resistance.

CPMP/EWP/2655/99 (pdf,86kb)
Points to Consider on Pharmacokinetics and Pharmacodynamics in the Development of Antibacterial Medicinal Products
Effective: 19 April 2001

Antineoplastic and immunomodulating agents

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EMA/CHMP/153191/2013 (pdf,316kb)
Guideline on the clinical development of medicinal products intended for the treatment of chronic primary immune thrombocytopenia
Effective: 15 September 2014

EMA/CHMP/205/95/Rev.4 (pdf,354kb)
Guideline on the evaluation of anticancer medicinal products in man
Replaces: CPMP/EWP/205/95/Rev.3/Corr (Adopted by TGA June 2006)
Effective: 1 April 2014

EMA/768937/2012 (pdf,98kb)
Answers from the CHMP Scientific Advisory Group (SAG) for Oncology for Revision of the anticancer guideline
Effective: 1 April 2014

EMA/CHMP/27994/2008/Rev 1 (pdf,111kb)
Appendix 1 to the guideline on the evaluation of anticancer medicinal products in man Methodological consideration for using progression-free survival (PFS) or disease-free survival (DFS) in confirmatory trials
Replaces: EMEA/CHMP/EWP/27994/2008 (Adopted by TGA 16 March 2009)
Effective: 1 April 2014

EMA/CHMP/EWP/520088/2008 (pdf,277kb)
Appendix 2 to the Guideline on the Evaluation of Anticancer Medicinal Products in Man (CPMP/EWP/205/95 Rev. 3) on Confirmatory Studies in Haematological Malignancies
Effective: 17 December 2010

EMA/CHMP/703715/2012 (pdf,161kb)
Appendix 4 to the guideline on the evaluation of anticancer medicinal products in man Condition Specific Guidance
Supersedes EMA/CHMP/EWP/520088/2008, Appendix 2 (Adopted by TGA 17 December 2010)
Effective: 1 April 2014

TGA annotation:
The TGA acknowledges an updated revision of this Guideline (effective February 2016) was issued by the EMA in October 2015. Pending a decision as to whether provisional registration will be introduced following the Medicines and Medical Devices Review, the TGA is not adopting the updated revision of this Guideline.

EMEA/CPMP/555/95 Rev. 1 (pdf,62kb)
Guideline on Clinical Trials with Haematopoietic Growth Factors for the Prophylaxis of Infection Following Myelosuppressive or Myeloablative Therapy
Replaces: CPMP/EWP/555/95 (Adopted by TGA 1 May 2000)
Effective: 15 July 2009

Rheumatology / musculoskeletal system

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CHMP/51230/2013 (pdf,200kb)
Clinical investigation of medicinal products for the treatment of systemic lupus erythematosus, cutaneous lupus and lupus nephritis
In place of: EMEA/CHMP/EWP/604040/2009 Concept Paper on the Need for a Guideline on the Clinical Investigation of Medicinal Products Intended for Treatment of Systematic and Cutaneous Lupus Erythematosus (provided for information 26 March 2010)
Effective: September 2015

CPMP/EWP/552/95 Rev. 2 (pdf,64kb)
Guideline on the Evaluation of Medicinal Products in the Treatment of Primary Osteoporosis
Effective: 7 August 2008

CPMP/EWP/422/04 (pdf,116kb)
Guideline on Clinical Investigation of Medicinal Products for the Treatment of Juvenile Idiopathic Arthritis
Effective: 26 June 2009

EMA/CHMP/520782/2012 (pdf,74kb)
Concept paper on the need for revision of the guideline on clinical investigation of medicinal products for the treatment of juvenile idiopathic arthritis
For information: 1 August 2014

CHMP/EWP/438/04 (pdf,128kb)
Guideline on Clinical Investigation of Medicinal Products for the Treatment of Psoriatic Arthritis
Effective: 5 February 2008

CPMP/EWP/4891/03 (pdf,77kb)
Guideline on Clinical Investigation of Medicinal Products for the Treatment of Ankylosing Spondylitis
Effective: 23 February 2010

CPMP/EWP/556/95 rev 1/Final (pdf,175kb)
Points to Consider on Clinical Investigation of Medicinal Products other than NSAIDS for Treatment of Rheumatoid Arthritis
Replaces: CPMP/EWP/556/95 (Adopted by TGA February 2001)
Effective: 29 January 2007

CPMP/EWP/784/97 Rev. 1 (pdf,88kb)
Guideline on Clinical Investigation of Medicinal Products Used in the Treatment of Osteoarthritis
Replaces: CPMP/EWP/784/97 (Adopted by TGA 15 December 2000)
Effective: 17 December 2010

3CC17a (pdf,25kb)
Medicinal Products (Non-Steroidal Anti-Inflammatory Compounds) for the Treatment of Chronic Disorders
Effective: 12 February 2002

Nervous system

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EMA/CHMP/40072/2010 Rev. 1 (pdf,194kb)
Guideline on clinical investigation of medicinal products, including depot preparations in the treatment of schizophrenia
Replaces: CPMP/EWP/559/95. Note for Guidance on the Clinical Investigation of Medicinal Products in the Treatment of Schizophrenia. (Adopted by TGA 1 May 2000)
Effective: 1 June 2014

CPMP/EWP/49/01 (pdf,151kb)
Appendix to the Note for Guidance on the Clinical Investigation of Medicinal Products in the Treatment of Schizophrenia (CPMP/EWP/559/95) - Methodology of Clinical Trials Concerning the Development of Depot Preparations of Approved Medicinal Products in Schizophrenia
Effective: 17 September 2004

EMA/CHMP/457223/2011 (pdf,71kb)
Concept paper on the need for revision of the appendix to the Note for Guidance on the clinical investigation of medicinal products in the treatment of schizophrenia - methodology of clinical trials concerning the development of depot preparations of approved medicinal products in schizophrenia
For information: 1 June 2014

EMA/CHMP/185423/2010 Rev. 2 (pdf,239kb) previously (CPMP/EWP/518/97, Rev. 1)
Guideline on clinical investigation of medicinal products in the treatment of depression

Replaces: CPMP/EWP/518/97 Rev 1. (Adopted by TGA 7 August 2002); and Concept paper EMEA/CHMP/EWP/484366/2009 on this topic (provided for information 23 February 2010).
Effective: 1 June 2014

EMA/CHMP/607022/2009 (pdf,371kb)
Guideline on the treatment of premenstrual dysphoric disorder (PMDD)
In place of Concept paper EMEA/CHMP/EWP/11877/2009 on this topic . (provided for information 14 April 2009)
Effective: 1 June 2014

EMA/CHMP/EWP/20097/2008 (pdf,220kb)
Guideline on the Development of Medicinal Products for the Treatment of Alcohol Dependence
Effective: 17 December 2010

EMEA/CHMP/EWP/431734/2008 (pdf,158kb)
Guideline on the clinical investigation of medicinal products for the treatment of attention deficit hyperactivity disorder (ADHD)
Effective: 1 April 2014

EMA/CHMP/16274/2009 (pdf,162kb) previously (EMEA/16274/2009) Rev. 1
Guideline on medicinal products for the treatment of insomnia

Replaces: pp. 359 - 370 of Rules 1998 (3C) - 3CC27a. Clinical Investigation of Hypnotic Medicinal Products. (Adopted by TGA July 1994)
Effective: 1 June 2014

CPMP/EWP/252/03 Rev 1 (pdf,108kb)
Guideline on Clinical Medicinal Products Intended for the Treatment of Neuropathic Pain
Replaces: CHMP/EWP/252/03 (Adopted by TGA 1 June 2005)
Effective: 14 April 2009

CPMP/EWP/612/00 (pdf,183kb)
Note for Guidance on Clinical Investigation of Medicinal Products for Treatment of Nociceptive Pain
Effective: 12 May 2005

CPMP/EWP/788/01 Rev. 1 (pdf,67kb)
Guideline on Clinical Investigation of Medicinal Products for the Treatment of Migraine
Replaces: CPMP/EWP/788/01 (Adopted by TGA 19 April 2001)
Effective: 10 February 2009

CHMP/771815/2011 Rev. 2 (pdf,241kb)
Clinical investigation of medicinal products for the treatment of multiple sclerosis
Replaces: CPMP/EWP/561/98 Rev. 1
Guideline on clinical investigation of Medicinal Products for the Treatment of Multiple Sclerosis
Effective: 1 October 2015

CPMP/EWP/561/98 Rev. 1 (pdf,206kb)
Guideline on clinical investigation of Medicinal Products for the Treatment of Multiple Sclerosis
Replaces: CPMP/EWP/561/98 (Adopted by TGA 10 January 2002)
Effective: 1 December 2008

CHMP/EWP/358650/2006 Corr 2 (pdf,71kb)
Guideline on the Development of Medicinal Products for the Treatment of Post-Traumatic Stress Disorder (PTSD)
Replaces: CHMP/EWP/358650/2006 (Adopted by TGA 8 April 2009)
Effective: 23 February 2010

CHMP/EWP/3635/03 (pdf,82kb)
Guideline on Clinical Investigation of Medicinal Products Indicated for the Treatment of Social Anxiety Disorder (SAD)
Effective: August 2006

CHMP/EWP/369963/05 (pdf,124kb)
Guideline on the Development of Medicinal Products for the Treatment of Smoking
Effective: 5 August 2009

CPMP/EWP/4284/02 (pdf,81kb)
Guideline on the Clinical Investigation of Medicinal Products Indicated for Generalised Anxiety Disorder
Replaces: pp. 371 - 380 of Rules 1998 (3C) - 3CC28a (Adopted by TGA 12 February 2002)
Effective: July 2005

CHMP/EWP/4280/02 (pdf,98kb)
Guideline on the Clinical Investigation of Medicinal Products Indicated for the Treatment of Panic Disorder
Replaces: pp. 371 - 380 of Rules 1998 (3C) - 3CC28a (Adopted by TGA 12 February 2002)
Effective: July 2005

CHMP/EWP/4279/02 (pdf,87kb)
Guideline on Clinical Investigation of Medicinal Products for the Treatment of Obsessive Compulsive Disorder
Replaces: pp. 371 - 380 of Rules 1998 (3C) - 3CC28a (Adopted by TGA 12 February 2002)
Effective: July 2005

CPMP/EWP/560/1998 (pdf,68kb)
Points to Consider on Clinical Investigation of Medicinal Products for the Treatment of Acute Stroke
Effective: 4 September 2002

CPMP/EWP/567/98 (pdf,77kb)
Note for Guidance on Clinical Investigation of Medicinal Products for the Treatment of Bipolar Disorder
Effective: 30 August 2001

CHMP/EWP/566/98 Rev.2/Corr (pdf,249kb)
Guideline on Clinical Investigation of Medicinal Products in the Treatment of Epileptic Disorders
Replaces: CPMP/EWP/566/98 Rev 1 (Adopted by TGA 19 April 2001)
Effective: 17 December 2010

CPMP/EWP/565/98 (pdf,59kb)
Points to Consider on Clinical Investigation of Medicinal Products for the Treatment of Amyotrophic Lateral Sclerosis (ALS)
Effective: 23 February 2001

EMA/CHMP/59352/2012 (pdf,158kb)
Concept paper on the need for revision of the points to consider on clinical investigation of medicinal products for the treatment of Amyotrophic Lateral Sclerosis
For information: 1 August 2014

EMA/CHMP/330418/2012 rev. 2 (pdf,223kb)
Guideline on clinical investigation of medicinal products in the treatment of Parkinson's disease
Replaces: CPMP/EWP/563/95 Rev 1. Guideline on clinical investigation of medicinal products in the treatment of Parkinson's disease (Adopted by TGA 25 February 2009)
Effective: 1 June 2014

EMA/351466/2012 (pdf,107kb)
Questions and answers on additional clarification for inclusion criteria in the 'Guideline on clinical investigation of medicinal products in the treatment of Parkinson's disease' rev. 2
For information: 1 June 2014

CPMP/EWP/553/95 Rev 1 (pdf,140kb)
Guideline on Medicinal Products for the Treatment of Alzheimer's Disease and Other Dementias
Replaces: CPMP/EWP/553/95 (Adopted by TGA 1 May 2000)
Effective: 25 February 2009

Respiratory system

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CPMP/EWP/2922/01 (pdf,173kb)
Note for Guidance on the Clinical Investigation of Medicinal Products in the Treatment of Asthma
Effective: 7 January 2009

EMA/CHMP/483572/2012 - corr1 (pdf,208kb)
Guideline on clinical investigation of medicinal products in the treatment of chronic obstructive pulmonary disease (COPD)
Replaces: CPMP/EWP/562/98. Points to Consider on Clinical Investigation of Medicinal Products in the Treatment of Patients with Chronic Obstructive Pulmonary Disease (COPD), and concept paper EMEA/CHMP/EWP/8197/2009 on this topic (provided for information 1 May 2009)
Effective: 15 September 2014

EMEA/CHMP/EWP/9147/2008-corr (pdf,278kb)
Guideline on the Clinical Development of Medicinal Products for the Treatment of Cystic Fibrosis
Effective: 17 December 2010

EMEA/CPMP/EWP/504/97 Rev 1 (pdf,93kb)
Guideline On Clinical Investigation of Medicinal Products in the Treatment of Patients with Acute Respiratory Distress Syndrome
Effective: 7 October 2008

CPMP/EWP/4151/00 Rev. 1 (pdf,271kb)
Guideline on the Requirements for Clinical Documentation for Orally Inhaled Products (OIP) Including the Requirements for Demonstration of Therapeutic Equivalence Between Two Inhaled Products for Use in the Treatment of Asthma and Chronic Obstructive Pulmonary Disease (COPD) in Adults and for Use in the Treatment of Asthma in Children and Adolescents
Replaces: CPMP/EWP/4151/00 (Adopted by TGA January 2005)
Effective: 23 February 2010

3BR3a (pdf,43kb)
Replacement of Chlorofluorocarbons (CFC) in Metered Dose Inhalation Products
Replaces: III/5378/93 (Adopted by TGA 1 January 1995)
Effective: 12 February 2002

Biostatistics

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EMA/CHMP/EWP/117211/2010 (pdf,72kb)
Concept paper on the need for a Guideline on the use of Subgroup Analyses in Randomised Controlled Trials
For information: 1 August 2014

EMA/129698/2012 (pdf,104kb)
Concept paper on extrapolation of efficacy and safety in medicine development
For information: 1 August 2014

EMA/CHMP/295050/2013 (pdf,146kb)
Guideline on adjustment for baseline covariates in clinical trials
Replaces: CPMP/EWP/2863/99 Points to Consider on Adjustment for Baseline Covariates (Adopted by TGA 20 May 2005)
Effective: 1 September 2015

CPMP/EWP/908/99 (pdf,209kb)
Points to Consider on Multiplicity Issues in Clinical Trials
Effective: 23 June 2005

EMA/CPMP/EWP/1776/99 Rev. 1 (pdf,144kb)
Guideline on Missing Data in Confirmatory Clinical Trials
Replaces: CPMP/EWP/1776/99. Points to Consider on Missing Data. (Adopted by TGA 12 March 2003)
Effective: 1 June 2014

CHMP/EWP/83561/2005 (pdf,64kb)
Guideline on Clinical Trials in Small Populations
Effective: December 2006

EMEA/CHMP/EWP/5872/03 Corr (pdf,75kb)
Guideline on Data Monitoring Committees
Replaces: EMEA/CHMP/EWP/5872/03 (Adopted by TGA January 2006)
Effective: 23 March 2006

EMEA/CPMP/EWP/2158/99 (pdf,116kb)
Guideline on the Choice of the Non-Inferiority Margin
Effective: January 2006

CPMP/EWP/482/99 (pdf,110kb)
Points to Consider on Switching between Superiority and Non-inferiority
Effective: 29 June 2001

TGA annotation:
Please note that there is no requirement in Australia to demonstrate superiority.

CPMP/EWP/2330/99 (pdf,49kb)
Points to Consider on Application with

  1. Meta-Analyses;
  2. One Pivotal Study

Effective: 27 March 2002

TGA annotation:
Sponsors are reminded that they should submit all available new safety data that are relevant to the intended treatment population.

CPMP/ICH/363/96 (pdf,325kb)
ICH Topic E 9
Note for Guidance on Statistical Principles for Clinical Trials

Effective: 1 October 1999

CPMP/ICH/364/96 (pdf,252kb) (pdf,252kb)
ICH Topic E 10
Note for Guidance on Choice of Control Groups in Clinical Trials

Effective: 19 April 2001

General

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CPMP/EWP/1119/98/Rev. 1 (pdf,110kb)
Clinical Evaluation of Diagnostic Agents
Replaces: CPMP/EWP/1119/98
Effective: 28 May 2010

EMEA/CHMP/EWP/321180/2008 (pdf,57kb)
Appendix 1 to the Guideline on Clinical Evaluation of Diagnostic Agents (CPMP/EWP/1119/98 Rev. 1) on Imaging Agents
Effective: 28 May 2010

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/EWP/2747/00 (pdf,125kb)
Note for Guidance on Coordinating Investigator Signature of Clinical Study Reports
Effective: 12 March 2003

CPMP/EWP/240/95 Rev. 1 (pdf,266kb)
Guideline on Clinical Development of Fixed Combination Medicinal Products
Replaces: pp. 175 - 180 of Rules 1998 (3C) - 3CC10a
Effective: 28 May 2010

CPMP/EWP/239/95 final (pdf,39kb)
Note for Guidance on the Clinical Requirements for Locally Applied, Locally Acting Products Containing Known Constituents
Replaces: CPMP/EWP/239/95
Effective: August 1997

TGA annotation:
The following explanatory note was added on 28 October 2011:
The TGA does not consider this guideline to be applicable to applications seeking the registration of eye drops that exert their effect beyond the cornea (i.e. the deeper tissues of the eye). Examples of such eye drops include eye drops for the treatment of glaucoma.
Requirements for establishing the bioequivalence of such eye drops to an innovator product are set out in the EU guideline Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1) that has been adopted.

3CC29a (pdf,52kb)
Investigation of Chiral Active Substances
Replaces: III/3501/91
Effective: 1 January 1995

CPMP/ICH/375/95 (pdf,123kb)
ICH Topic E 1
Note for Guidance on Population Exposure: The Extent of Population Exposure to Assess Clinical Safety

Effective: 12 February 2002

TGA annotation:
Attention is drawn to:

  • Applicability, Section 7, which states that circumstances exist in which the Guidelines may not be applicable. It should be noted that the listing of exceptional circumstances is not exhaustive. Sponsors should give careful attention to whether, in any particular instance, the clinical safety of the product would be adequately supported by the numbers of subjects proposed, and;
  • Supplementary data, Section 8 is NOT ADOPTED. To permit decisions within legislated timeframes, the sponsor should include in the initial submission all clinical safety data necessary to support registration.

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pp. 127 - 132 of Rules 1998 (3C) - 3CC6a (pdf,27kb)
Clinical Investigation of Medicinal Products for Long-Term Use
Replaces: pp. 163 - 165 of Rules 1989
Effective: 12 February 2002

CPMP/ICH/377/95
Note For Guidance On Clinical Safety Data Management: Definitions And Standards For Expedited Reporting - Annotated with TGA comments
Published: TGA News October 2000
Effective: 1 August 2000

CPMP/ICH/137/95 (pdf,371kb)
ICH Topic E 3
Note for Guidance on Structure and Content of Clinical Study Reports

Effective: 1 May 2000

EMA/CHMP/ICH/435606/2012 (pdf,180kb)
ICH guideline E3 - questions and answers (R1)
Effective: 1 April 2014

CPMP/ICH/378/95 (pdf,170kb)
ICH Topic E 4
Note For Guidance on Dose Response Information to Support Drug Registration

Effective: 15 December 2000

CPMP/ICH/289/95 (pdf,180kb)
ICH Topic E 5 (R1)
Note for Guidance on Ethnic Factors in the Acceptability of Foreign Clinical Data

Effective: 1 May 2000

CPMP/ICH/5746/03 (pdf,100kb)
ICH Topic E 5 (R1)
Questions and Answers: Ethnic Factors in the Acceptability of Foreign Clinical Data

For information: 1 June 2014

CPMP/ICH/135/95
ICH Topic E 6
Note for Guidance on Good Clinical Practice - Annotated with TGA comments

Effective: 1 August 2000

CPMP/ICH/379/95 (pdf,141kb)
ICH Topic E 7
Note for Guidance on Studies in Support of Special Populations: Geriatrics

Effective: 1 January 1995

EMA/CHMP/ICH/604661/2009 (pdf,109kb)
ICH topic E7:
Studies in Support of Special Populations: Geriatrics - Questions and Answers

For information: 1 June 2014

CPMP/ICH/291/95 (pdf,245kb)
ICH Topic E 8
Note for Guidance on General Considerations for Clinical Trials

Effective: 1 October 1999

CPMP/ICH/2711/99 (pdf,157kb)
ICH Topic E 11
Note for Guidance on Clinical Investigation of Medicinal Products in the Paediatric Population

Effective: 19 April 2001

Radiopharmaceuticals and Diagnostic Agents

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CPMP/EWP/1119/98/Rev. 1 (pdf,110kb)
Clinical Evaluation of Diagnostic Agents
Replaces: CPMP/EWP/1119/98
Effective: 28 May 2010

EMEA/CHMP/EWP/321180/2008 (pdf,57kb)
Appendix 1 to the Guideline on Clinical Evaluation of Diagnostic Agents (CPMP/EWP/1119/98 Rev. 1) on Imaging Agents
Effective: 28 May 2010

Allergy/Immunology

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CHMP/EWP/18504/2006 (pdf,169kb)
Guideline on the Clinical Development of Products for Specific Immunotherapy for the Treatment of Allergic Diseases
Effective: 15 July 2009

CHMP/EWP/263148/06 (pdf,153kb)
Guideline on Clinical Investigation of Immunosuppressants for Solid Organ Transplantation
Effective: 8 April 2009

CHMP/EWP/2455/02 (pdf,202kb)
Guideline on the clinical development of medicinal products for the treatment of allergic rhino-conjunctivitis
Effective: 28 July 2005