Biological medicines guidelines

12 February 2016

Please see the TGA glossary for a definition of Biological medicines included under this section.

To search for a guideline by key word on this page, use your browser's 'Find' function (Control-F or Edit, Find in most browsers).

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.

Drug substance

Manufacture, characterisation and control of the drug substance

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EMA/CHMP/BWP/151897/2013 (pdf,151kb)
Guideline on Quality of biological active substances produced by transgene expression in animals
Replaces: 3AB7a Use of transgenic animals in the manufacture of biological medicinal products for human use (Adopted by TGA 12 February 2002) and concept paper EMEA/CHMP/BWP/134153/2009 on this topic (provided for information 26 March 2010)
Effective: 1 April 2014

EMA/CHMP/BWP/429241/2013 (pdf,124kb)
Guideline on the use of starting materials and intermediates collected from different sources in the manufacturing of non-recombinant biological medicinal products
Effective: 10 November 2014

EMEA/CHMP/BWP/157653/2007 (pdf,117kb)
Guideline on Development, Production, Characterisation and Specifications for Monoclonal Antibodies and Related Products
Effective: 5 August 2009

CHMP/BWP/271475/2006 (pdf,48kb)
Guideline on Potency Testing of Cell Based Immunotherapy Medicinal Products for the Treatment of Cancer
Effective: 29 June 2009

EMEA/CHMP/BWP/48316/2006 (pdf,82kb)
Guideline on the quality of biological active substances produced by stable transgene expression in higher plants
Effective: 1 April 2014

CPMP/BWP/3354/99 (pdf,208kb)
Note for Guidance on the Production and Quality Control of Animal Immunoglobulins and Immunosera for Human Use
Effective: 7 September 2004

EMEA/CHMP/410869/2006 (pdf,400kb)
Guideline on Human Cell-Based Medicinal Products
Effective: 5 November 2010

CPMP/BWP/3088/99 (pdf,127kb)
Note for Guidance on the Quality, Preclinical and Clinical Aspects of Gene Transfer Medicinal Products
Effective: 7 May 2003

TGA annotation:
Sponsors are advised that consultation with the Office of the Gene Technology Regulator (OGTR) is required for applications covered by this guideline, as is described in Section 30C of the Therapeutic Goods Act 1989.

EMEA/CHMP/CPWP/83508/2009 (pdf,123kb)
Guideline on Xenogeneic Cell-based Medicinal Products
Effective: 5 November 2010

TGA annotation:
Sponsors should refer to the prevailing TGA requirements for minimising the risk of transmitting transmissible spongiform encephalopathies: 'Transmissible Spongiform Encephalopathies (TSE): TGA approach to minimising the risk of exposure'.

CPMP/ICH/294/95 (pdf,190kb)
ICH Topic Q 5 D
Note for Guidance on Quality of Biotechnological Products: Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products

Effective: 1 October 1999

CPMP/BWP/1143/00 (pdf,57kb)
Position Statement on the Use of Tumourigenic Cells of Human Origin for the Production of Biological and Biotechnological Medicinal products
Effective: 10 January 2002

EMEA/CHMP/BWP/304831/2007 (pdf,90kb)
Guideline on Allergen Products: Production and Quality Issues
Replaces CPMP/BWP/243/96
Effective: 29 June 2009

CPMP/ICH/139/95 (pdf,133kb)
ICH Topic Q 5 B
Quality of Biotechnological Products: Analysis of the Expression Construct in Cell Lines Used for Production of r-DNA Derived Protein Products

Effective: 1 May 2000

3AB1a (pdf,32kb)
Production and Quality Control of Medicinal Products derived by recombinant DNA Technology
Effective: 12 February 2002

3AB6a (pdf,62kb)
Gene Therapy Product Quality Aspects in the Production of Vectors and Genetically Modified Somatic Cells
Effective: 12 February 2002

3AB3a (pdf,64kb)
Production and Quality Control of Cytokine Products Derived by Biotechnological Processes
Effective: 12 February 2002

Specifications

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CPMP/ICH/365/96 (pdf,197kb)
ICH Topic Q 6 B
Note for Guidance on Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products

Effective: 1 May 2000

Comparability/biosimilarity

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EMA/CHMP/BWP/247713/2012 (pdf,140kb)
Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1)
Replaces: EMEA/CHMP/BWP/49348/2005. Guideline on Similar Biological Medicinal Products containing Biotechnology-Derived Proteins as Active Substance: Quality Issues. (Adopted by TGA December 2006)
Effective: 1 December 2014

TGA annotation:
Sponsors should also refer to TGA Guidance on the Evaluation of biosimilars

CHMP/437/04 Rev. 1 (pdf,120kb)
Guideline on similar biological medicinal products.
Replaces: CHMP/437/04 (adopted by TGA 15 June 2006).
Effective: 25 May 2015

CPMP/ICH/5721/03 (pdf,196kb)
ICH Topic Q 5 E
Comparability of Biotechnological/ Biological Products Note for Guidance on Biotechnological/Biological Products Subject to Changes in their Manufacturing Process

Replaces: EMEA/CPMP/BWP/3207/00, rev 1 (Adopted by TGA May 2005)
Effective: 26 March 2010

Plasma-derived medicinal products

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EMA/CHMP/BWP/706271/2010 (pdf,324kb)
Guideline on plasma-derived medicinal products
Replaces: CPMP/BWP/269/95 Rev 3
Effective: 1 June 2013

CPMP/BWP/269/95 Rev 3 (pdf,270kb)
Note for Guidance on Plasma-Derived Medicinal Products
Replaced by: EMA/CHMP/BWP/706271/2010

TGA annotation:
Annex V (CPMP/BWP/390/97) of Guidance CPMP/BWP/269/95 Rev 3 remains current.
Effective: 30 August 2001

CPMP/BWP/5180/03 (pdf,172kb)
Guideline on assessing the risk for virus transmission - New chapter 6 of the note for guidance on plasma - derived medicinal products (CPMP/BWP/269/95)
Effective: 20 May 2005

EMEA/CHMP/BWP/452081/2007 (pdf,105kb)
Guideline on the Replacement of Rabbit Pyrogen Testing by an Alternative Test for Plasma-derived Medicinal Products
Effective: 28 May 2010

EMA/CHMP/BWP/303353/2010 (pdf,209kb)
CHMP position statement on Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal products
Effective: 1 June 2013

CPMP/BWP/CPMP/5136/03 (pdf,223kb)
Guideline on the investigation of manufacturing processes for plasma-derived medicinal products with regard to VCJD risk
Effective: 12 May 2005

Plasma master file

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EMEA/CHMP/BWP/3794/03 Rev.1 (pdf,108kb)
Guideline on the Scientific Data Requirements for a Plasma Master File (PMF) Revision 1
Refer to the EMA website at Biologicals: Drug substance Plasma master file for a MS Word copy of Annexes to EMEA/CHMP/BWP/3794/03 Rev.1 [Annexes to Guideline on the Scientific Data Requirements for a Plasma Master file (PMF) Revision 1].
Effective: 15 September 2009

EMA/CHMP/BWP/548524/2008 (pdf,165kb)
Guideline on epidemiological data on blood transmissible infections
Replaces: EMEA/CPMP/BWP/125/04 Guideline on Epidemiological Data on Blood Transmissible Infections (Adopted by TGA 19 September 2008) and Concept paper EMEA/CHMP/BWP/505885/2008 on this topic (provided for information 14 April 2009)
Effective: 1 June 2014

EMA/CHMP/BWP/174129/2009
Appendices to Guideline on epidemiological data on blood transmissible infections
(EMA/CHMP/BWP/548524/2008)
Refer to the EMA website at Biologicals: Drug substance Plasma master file for a MS Word copy of these Appendices.
Effective: 1 June 2014

EMEA/CHMP/BWP/298388/05 (pdf,45kb)
Guideline on Validation of Immunoassay for the Detection of Antibody to Human Immunodeficiency Virus (Anti-HIV) in Plasma Pools
Effective: 5 February 2008

EMEA/CHMP/BWP/298390/2005 (pdf,52kb)
Guideline on Validation of Immunoassay for the Detection of Hepatitis B Virus Surface Antigen (HBSAG) in Plasma Pools
Effective: 5 February 2008

Vaccines

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EMA/CHMP/BWP/310834/2012 (pdf,284kb)
Guideline on Influenza Vaccines - Quality Module
Effective: 1 November 2014

TGA annotation:
This Module is proposed to replace the Quality requirements of the TGA-adopted guidelines listed below. Note that the nonclinical and clinical aspects of the guidelines listed below will continue to apply.

  • CPMP/BWP/214/96
    Harmonisation of Requirements for Influenza Vaccines
  • CPMP/BWP/2490/00
    Cell Culture Inactivated Influenza Vaccines - Annex to Note for Guidance on Harmonisation of Requirements for Influenza Vaccines CPMP/BWP/214/96
  • EMEA/CPMP/BWP/2289/01
    Points to Consider on the Development of Live Attenuated Influenza Vaccines.
  • EMEA/CPMP/VEG/4717/2003 Rev.1
    Guideline on Dossier Structure and Content for Pandemic Influenza Vaccine Marketing Authorisation Application (Revision)
  • CHMP/VWP/263499/06
    Guideline on Influenza Vaccines Prepared from Viruses with the Potential to cause a Pandemic and Intended for Use Outside of the Core Dossier Context
  • EMA/CHMP/BWP/368186/2011
    Guideline on quality aspects on the isolation of candidate influenza vaccine viruses in cell culture

CHMP/VWP/263499/06 (pdf,200kb)
Guideline on Influenza Vaccines Prepared from Viruses with the Potential to cause a Pandemic and Intended for Use Outside of the Core Dossier Context
Effective: 23 October 2008

TGA annotation:
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/VEG/134716/2004 (pdf,187kb)
Guideline on Adjuvants in Vaccines for Human Use
Effective: July 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 annotation:
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/CPMP/BWP/3734/03 (pdf,154kb)
Guideline on the Scientific Data Requirements for a Vaccine Antigen Master File (VAMF)
Effective: 24 August 2004

CPMP/BWP/214/96 (pdf,109kb)
Harmonisation of Requirements for Influenza Vaccines
Replaces: III/3188/91 (Adopted by TGA July 1994)
Effective: 12 February 2002

TGA annotation:
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.

CPMP/BWP/2490/00 (pdf,177kb)
Cell Culture Inactivated Influenza Vaccines - Annex to Note for Guidance on Harmonisation of Requirements for Influenza Vaccines CPMP/BWP/214/96
Effective: 5 March 2003

TGA annotation:
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.

EMA/CHMP/BWP/368186/2011 (pdf,70kb)
Guideline on quality aspects on the isolation of candidate influenza vaccine viruses in cell culture
In place of concept paper EMEA/CHMP/BWP/481473/2008
Effective: 24 February 2014

TGA annotation:
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/CPMP/BWP/2289/01 (pdf,204kb)
Points to Consider on the Development of Live Attenuated Influenza Vaccines
Effective: 17 September 2004

TGA annotation:
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.

CPMP/BWP/2517/00 (pdf,39kb)
Points to Consider on the Reduction, Elimination or Substitution of Thiomersal in Vaccines
Effective: 10 January 2002

CPMP/BWP/477/97 (pdf,75kb)
Note for Guidance on Pharmaceutical & Biological Aspects of Combined Vaccines
Effective: 13 February 2001

Stability

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CPMP/ICH/138/95 (pdf,58kb)
3AB5a; ICH Q 5 C
Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products

Effective: 1 May 2000

Drug product

Pharmaceutical development

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CPMP/BWP/328/99 (pdf,36kb)
Development Pharmaceutics for Biotechnological and Biological Products (Annex to Note for Guidance on Development Pharmaceutics)
Effective: 19 April 2001

Adventitious agents safety evaluation viral safety

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EMA/CHMP/BWP/457920/2012 rev 1 (pdf,130kb)
Guideline on the use of bovine serum in the manufacture of human biological medicinal products
Replaces: CPMP/BWP/1793/02. Note for Guidance on the Use of Bovine Serum in the Manufacture of Human Biological Medicinal Products. (Adopted by TGA 7 September 2004)
Effective: 15 September 2014

TGA annotation:
Sponsors should also refer to: TGA Supplementary information on Transmissible Spongiform Encephalopathies (TSEs) regulation.

EMA/CHMP/BWP/814397/2011 (pdf,125kb)
Guideline on the use of porcine trypsin used in the manufacture of human biological medicinal products
Effective: 10 November 2014

CPMP/ICH/295/95 (pdf,265kb)
ICH Topic Q 5 A (R1)
Note for Guidance on Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

Effective: 1 May 2000

CPMP/BWP/268/95 (pdf,53kb)
Note for Guidance on Virus Validation Studies: The Design, Contribution and Interpretation of Studies Validating the Inactivation and Removal of Viruses
Effective: August 1997

Transmissible Spongiform Encephalopathies (TSE) (Animal and Human)

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EMEA/410/01 Rev 3 (pdf,1Mb)
Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products
Replaces: EMEA 410/01 Rev 2 (adopted by the TGA 20 September 2005)
Effective: 1 April 2014
Adoption of this EU Guideline is in line with current pharmacopoeial standards.

TGA annotation:
This EU Guideline should be interpreted in the context of the TGA Supplementary information on Transmissible Spongiform Encephalopathies (TSEs) regulation.

CJD related

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CPMP/BWP/CPMP/5136/03 (pdf,223kb)
Guideline on the investigation of manufacturing processes for plasma-derived medicinal products with regard to VCJD risk
Effective: 12 May 2005

Investigational Medicinal Products

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EMEA/CHMP/BWP/466097/2007 (pdf,52kb)
Concept Paper on a Guideline on the Chemical and Pharmaceutical Quality Documentation concerning Biological Investigational Medicinal Products in Clinical Trials
For information: 10 February 2009

EMEA/CHMP/BWP/398498/2005 (pdf,72kb)
Guideline on Virus Safety Evaluation of Biotechnological Investigational Medicinal Products
Effective: 29 June 2009

EMEA/CHMP/ICH/607698/2008 (pdf,54kb)
ICH Considerations. Oncolytic Viruses
Effective: 28 May 2010

Batch release guidelines

Effective 1 June 2014: For batch release Guidelines on vaccines listed below, sponsors are referred to the European Directorate for the Quality of Medicines (EDQM) procedures and guidelines for the application of Official Control Authority Batch Release (OCABR), available from: Guidelines for EU Official Control Authority Batch Release for Human Biological Medicines. These replace the EDQM OCABR Guidelines previously adopted by TGA in October 2004 (Meningococcal C Polysaccharide Protein Conjugate Vaccine and Multivalent Pneumococcal Polysaccharide Conjugate Vaccine) or February 2003 (all other vaccine listed below).

Sponsors should note that for each of the vaccines listed below, Section 2 of the EDQM OCABR guideline (which refers to mandatory testing) is NOT adopted in Australia, however TGA reserves the discretionary right to take samples and test. Sponsors should also note in respect of Section 4 (which relates to certification that materials derived from ruminants are compliant with Directive 1999/82/EEC), that the 'Transmissible Spongiform Encephalopathies (TSE): TGA approach to minimising the risk of exposure' is relevant to assessment in Australia.

  • Cell Cultured Influenza Vaccine (Surface Antigen, Inactivated) (added 10 November 2014)
  • BCG Vaccine
  • Cholera Vaccine (Oral, Inactivated) (added 15 September 2014)
  • Diphtheria and Tetanus Vaccine (Adsorbed)
  • Diphtheria, Tetanus and Pertussis (Acellular Component) Combined Vaccine (Adsorbed)
  • Diphtheria, Tetanus, Pertussis (Whole Cell) Combined Vaccine (Adsorbed)
  • Diphtheria, Tetanus, Pertussis (Acellular Component) with separate Haemophilus Type B Conjugate Combined Vaccine (adsorbed) (added 15 September 2014)
  • Diphtheria, Tetanus, Pertussis (Acellular Component) and Hepatitis B (rDNA) Combined Vaccine (Adsorbed)
  • Diphtheria, Tetanus, Pertussis (Acellular Component), Poliomyelitis (Inactivated) and Haemophilus Type B Conjugate Combined Vaccine (Adsorbed)
  • Diphtheria, Tetanus, Pertussis (Acellular Component), Poliomyelitis (Inactivated), Hepatitis B (rDNA) with separate Haemophilus Type B Conjugate, Combined Vaccine (adsorbed) (added 15 September 2014)
  • Diphtheria, Tetanus, Pertussis (Acellular Component) and Poliomyelitis (Inactivated) Combined Vaccine (Adsorbed)
  • Haemophilus Type B Conjugate and Hepatitis B (rDNA) Combined Vaccine
  • Haemophilus Type B Conjugate Vaccine
  • Haemophilus Type B Conjugate and Meningococcal C Conjugate Combined Vaccine (added 15 September 2014)
  • Hepatitis A Vaccine (Inactivated) and Hepatitis B (rDNA) Combined Vaccine (Adsorbed)
  • Hepatitis A Vaccine (Inactivated, Adsorbed)
  • Hepatitis A (Inactivated) and Typhoid Polysaccharide Combined Vaccine (Adsorbed) for Mix-At-Use Format Products (added 15 September 2014)
  • Hepatitis B (rDNA) Vaccine
  • Human Papillomavirus (rDNA) Vaccine (added 15 September 2014)
  • Influenza Vaccine
  • Japanese Encephalitis Vaccine (Inactivated) (added 15 September 2014)
  • Measles, Mumps and/or Rubella Component Combined Vaccine
  • Measles Vaccine
  • Measles, Mumps, Rubella and Varicella Combined Vaccine (added 15 September 2014)
  • Meningococcal B Vaccine (Adsorbed) (added 15 September 2014)
  • Meningococcal Polysaccharide Vaccine
  • Monovalent or Multivalent Meningococcal Conjugate Vaccine, formerly under the title Meningococcal C Polysaccharide Protein Conjugate Vaccine (added 15 September 2014)
  • Multivalent Pneumococcal Polysaccharide Conjugate Vaccine
  • Pandemic Influenza Vaccine (added 15 September 2014)
  • Pertussis Vaccine (Acellular Component, Adsorbed)
  • Pneumococcal Polysaccharide Vaccine
  • Poliomyelitis Vaccine (Inactivated)
  • Poliomyelitis Vaccine (Oral) (OPV) Monovalent Bulk
  • Poliomyelitis Vaccine (Oral) (OPV)
  • Rabies Vaccine
  • Rotavirus Vaccine (added 15 September 2014)
  • Typhoid Polysaccharide Vaccine
  • Typhoid Vaccine (Live-Strain Ty21a, Oral)
  • Varicella Vaccine and Shingles Vaccine (added 15 September 2014)
  • Yellow fever vaccine
  • Live Attenuated Influenza Vaccine (added 2 February 2016)