Australian regulatory guidelines for
prescription medicines
Appendix 16: Preservative efficacy testing
June 2004
Therapeutic Goods Administration
About the Therapeutic Goods Administration (TGA)
 The TGA is a division of the Australian Government Department of Health and Ageing, and is
responsible for regulating medicines and medical devices.
 TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management
approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards
of quality, safety and efficacy (performance), when necessary.
 The work of the TGA is based on applying scientific and clinical expertise to decision-making, to
ensure that the benefits to consumers outweigh any risks associated with the use of medicines
and medical devices.
 The TGA relies on the public, healthcare professionals and industry to report problems with
medicines or medical devices. TGA investigates reports received by it to determine any
necessary regulatory action.
 To report a problem with a medicine or medical device, please see the information on the TGA
website.
Copyright
© Commonwealth of Australia 2004
This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any
process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights
should be addressed to the Commonwealth Copyright Administration, Attorney General’s Department, National Circuit, Barton
ACT 2600 or posted at http://www.ag.gov.au/cca
Australian regulatory guidelines for prescription medicines – Appendix 16
June 2004
Page 2 of 5
Therapeutic Goods Administration
Appendix 16: Preservative
efficacy testing
Sponsors should note that Preservative Efficacy Testing should be conducted in accordance with
the relevant British Pharmacopoeia (BP) monograph.
The Australian Regulatory Guidelines for Prescription Medicines (ARGPM) Appendix 14 (Stability
Testing) and the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance on
Stability Testing of New Drug Substances and Products (CPMP/ICH/2736/99)1 require that stability
testing for preservatives includes both the level of preservative and its efficacy:
The range of testing should cover not only chemical and biological stability but also loss
of preservative, physical properties and characteristics, organoleptic properties, and
where required microbiological attributes. Preservative efficacy testing and assays on
stored samples should be carried out to determine the efficacy and content of
antimicrobial preservatives.
and:
Any differences between the release and shelf life specifications for antimicrobial
preservatives should be supported by preservative efficacy testing.
These requirements are elaborated in three further Notes for Guidance adopted in Australia:
1.
Note for Guidance on the Inclusion of Antioxidants and Antimicrobial
Preservatives in Medicinal Products (CPMP/CVMP/QWP/115/95)2
2.
Note for Guidance on Developmental Pharmaceutics (CPMP/QWP/155/96)3
These documents address the requirements for preservatives in liquid and semi-solid formulations
that are not self-preserving. Preservative efficacy testing should be performed at the end of shelflife and at the lower preservative limit in the end of shelf-life specification. Testing for content only
is not sufficient because chemical concentration is not necessarily indicative of antimicrobial
efficacy. In addition, for multi-dose containers, the efficacy must be established under simulated inuse conditions, to justify the proposed in-use shelf-life. If it is not logistically possible to conduct the
complete in-use testing schedule in the original container, the use of an alternative container is
acceptable provided that the product has been stored in the original container prior to the start of
the in-use test.
This testing could take the form of pharmacopoeial preservative efficacy testing with additional
microbial challenges. Guidance may be obtained from the normative part of the international
standard ISO 14730: 2000 Ophthalmic Optics – Contact lens care products – Antimicrobial
preservative efficacy testing and guidance on determining discard dating 45 which describes a test
http://www.tga.gov.au/industry/pm-euguidelines-quality.htm
http://www.tga.gov.au/industry/pm-euguidelines-quality.htm
3 http://www.tga.gov.au/industry/pm-euguidelines-quality.htm
4 http://www.iso.ch/iso/en/ISOOnline.frontpage
5 It should be noted that this reference is not being identified as a standard that must be applied to
the product. It does, however, demonstrate the elements of the type of tests that may be applied to
support an open shelf-life period.
1
2
Australian regulatory guidelines for prescription medicines – Appendix 16
June 2004
Page 3 of 5
Therapeutic Goods Administration
procedure and performance criteria for preservative efficacy over an open shelf life period of 28
days. The informative annexes include protocols where an open shelf-life of longer than 28 days is
required. Where the open shelf-life is less than 28 days, the testing schedule should be adapted
accordingly.
Alternatively, testing for microbial limits, preservative efficacy or sterility testing may be conducted
on containers that have been used by patients or exposed to a pattern of use similar to that likely to
be encountered during routine use.
3.
Note for Guidance on Maximum Shelf Life for Sterile Products After First
Opening or Following Reconstitution (CPMP/QWP/159/96 Corr)2
This document requires that information on how long sterile products may be used after opening
should be included in the Product Information (PI). The information must be based on data
generated in appropriate studies (described above), and recommendations.
Australian regulatory guidelines for prescription medicines – Appendix 16
June 2004
Page 4 of 5
Therapeutic Goods Administration
PO Box 100 Woden ACT 2606 Australia
Email: info@tga.gov.au Phone: 02 6232 8444 Fax: 02 6232 8605
www.tga.gov.au
Reference/Publication #