Australian regulatory guidelines for
complementary medicines
Part B: Listed complementary medicines
January 2013
Therapeutic Goods Administration
About the Therapeutic Goods Administration (TGA)

The Therapeutic Goods Administration (TGA) is part of the Australian Government
Department of Health and Ageing, and is responsible for regulating medicines and
medical devices.

The 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 decisionmaking, 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 <www.tga.gov.au>.
Copyright
© Commonwealth of Australia 2013
This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal
use or, if you are part of an organisation, for internal use within your organisation, but only if you or your
organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all
disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or
allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any
part of this work in any way (electronic or otherwise) without first being given specific written permission from the
Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA
Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to
<tga.copyright@tga.gov.au>
Confidentiality
All submissions received will be placed on the TGA’s Internet site, unless marked confidential. Any confidential
material contained within your submission should be provided under a separate cover and clearly marked “IN
CONFIDENCE”. Reasons for a claim to confidentiality must be included in the space provided on the TGA submission
coversheet. For submission made by individuals, all personal details, other than your name, will be removed from
your submission before it is published on the TGA’s Internet site. In addition, a list of parties making submissions will
be published. If you do not wish to be identified with your submission you must specifically request this in the space
provided on the submission coversheet.
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Contents
ARGCM Part B: Listed complementary medicines
7
Listed therapeutic goods ___________________________________________________ 7
Medicines that can be listed on the ARTG ________________________________ 7
Ingredients approved for use in listed complementary medicines ___________________ 8
Legislative requirements for listed medicines __________________________ 9
Requirements of 26A of the Act _________________________________________________________ 9
Conditions of listing____________________________________________________________________ 14
Variations & sponsor’s rights to appeal against imposition of conditions of listing 16
Consent to supply goods that are not compliant with certain legislative
requirements ___________________________________________________________________________ 16
The listing process via the electronic listing facility__________________ 17
Listed medicine application lodgement via the electronic listing facility __________ 17
Validation system within the electronic listing facility ______________________________ 17
Payment for applications ______________________________________________________________ 18
TGA processing of application ________________________________________________________ 18
Product variation __________________________________________________________ 20
Changes that result in ‘separate and distinct’ goods _________________________________ 20
Provisions for product amendment___________________________________________________ 20
Changing information in the ARTG for ‘grandfathered’ products ___________________ 21
Post-market compliance __________________________________________________ 22
Listing compliance reviews ___________________________________________________________ 22
Laboratory testing program ___________________________________________________________ 24
Good manufacturing practice inspections ____________________________________________ 24
Product vigilance activities ____________________________________________________________ 24
Co-regulatory approach to control advertising ______________________________________ 25
Targeted and random surveillance in the marketplace _____________________________ 25
Product recalls _________________________________________________________________________ 25
Attachment 1: Compositional guidelines for complementary
medicine substances ______________________________________________________ 27
Attachment 2: Data requirements for proprietary ingredients _____ 28
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Attachment 3: Data requirements for herbal materials _____________ 30
Attachment 4: Identification of herbal materials & extracts Q & A _ 31
Attachment 5: Guidance on equivalence of herbal extracts in
complementary medicines _______________________________________________ 32
Attachment 6: Guidance on the use of modified unprocessed herbal
materials in complementary medicines ________________________________ 33
Attachment 7a: Quality of listed complementary medicines ________ 34
Attachment 7b: Raw material specifications __________________________ 36
Attachment 7c: Impurities and incidental constituents _____________ 37
Attachment 7d: Finished product specifications ______________________ 38
Attachment 7e: Finished product stability _____________________________ 47
Attachment 7f: Certificates of analysis for finished products _______ 48
Attachment 8: Medicine labels ___________________________________________ 50
Attachment 9a: Guidance on the use of the term ‘quantified by input’
for listed complementary medicines. ___________________________________ 53
Attachment 9b: Questions and answers on the use of ‘quantified by
input’ ________________________________________________________________________ 59
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Abbreviations
AAN
Australian Approved Name (chemical)
ABN
Australian Biological Name
ACCC
Australian Competition and Consumer Commission
AFN
Australian Food Name
AHN
Approved Herbal Name
AHS
Australian Herbal Substance Name
AAT
Administrative Appeals Tribunal
AQIS
Australian Quarantine Inspection Service
ARGB
Australian Regulatory Guidelines For Biologicals
ARGCM
Australian Regulatory Guidelines for Complementary Medicines
ARGMD
Australian Regulatory Guidelines for Medical Devices
ARGOM
Australian Regulatory Guidelines for Over-the-Counter Medicines
ARGPM
Australian Regulatory Guidelines for Prescription Medicines
ARTG
Australian Register of Therapeutic Goods
AUST L
A unique number assigned to products listed on the ARTG
AUST R
A unique number assigned to products registered on the ARTG
BP
British Pharmacopoeia
CHMP
Committee for Medicinal Products for Human Use
CITES
Convention on International Trade in Endangered Species of Wild
Fauna and Flora
CG
Compositional guidelines
EMA
European Medicines Agency
Ph.Eur
European Pharmacopoeia
EPBC
Environment Protection and Biodiversity Conservation
EU
European Union
Evidence Requirements
Evidence required to support indications for listed medicines
(excluding sunscreens and disinfectants)
The Food Standards
Code
Australia New Zealand Food Standards Code
FSANZ
Food Standards Australia New Zealand
GM
Genetically modified
GMO
Genetically modified organisms
GMP
Good Manufacturing Practice
GT
Gene Technology
The GT Act
Gene Technology Act 2000
HCN
Approved Herbal Component Name
HINC
Herbal Ingredient Naming Committee
NICNAS
National Industrial Chemicals Notification and Assessment
Scheme
OGTR
Office of the Gene Technology Regulator
OTC
Over-The-Counter
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Abbreviations
Proprietary ingredient
A confidential formulation about which information is not in the
public domain
RASML
Required Advisory Statements for Medicine Labels
RDI
Recommended Dietary Intake
SUSMP
Standard for the Uniform Scheduling of Medicines and Poisons
The Act
Therapeutic Goods Act 1989
The Advertising Code
Therapeutic Goods Advertising Code 2007
The Regulations
Therapeutic Goods Regulations 1990
TGA
Therapeutic Goods Administration
TGOs
Therapeutic Goods Orders
TGO 69
Therapeutic Goods Order No. 69 – General requirements for
labels for medicines, as amended
TGO 77
Therapeutic Goods Order No. 77 – Microbiological Standards for
Medicines
TGO 78
Therapeutic Goods Order No. 78 – Standards for Tablets and
Capsules
TGO 80
Therapeutic Goods Order No. 80 – Child-resistant Packaging
Requirements for Medicines, as amended
TSE
Transmissible Spongiform Encephalopathy
URPTG
Uniform Recall Procedure for Therapeutic Goods
USP/NF
United States Pharmacopoeia – National Formulary
WHO
World Health Organization
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ARGCM Part B: Listed
complementary medicines
Listed therapeutic goods
Medicines are either registered or listed on the Australian Register of Therapeutic Goods
(ARTG) depending on their ingredients and the indications made for the medicine (refer to
ARGCM Part A for an overview of the regulatory framework for listed and registered
medicines).
Most, but not all, complementary medicines are listed, rather than registered, on the ARTG
(however, note that not all listed medicines are complementary medicines).
Regulation 10 of the Therapeutic Goods Regulations 1990 (the Regulations) provides the
therapeutic goods that should be either listed or registered on the ARTG. In relation to
therapeutic goods that should be listed, Regulation 10b states:
Therapeutic goods, and classes of therapeutic goods, of a kind mentioned in Part 1 of Schedule 4
that are included in the Register are to be included in the part of the Register for listed goods.
Part of 1 Schedule 4 provides the types of therapeutic goods that should be listed on the
ARTG, such as: sunscreens, medicated throat sprays, disinfectants, export only medicines,
medicated space sprays, uncompounded medicine substances packed for retail sale, device
kits and medicine kits. With respect to complementary medicine substances, Part 1 of
Schedule 4 provides the following substances that can be included in listable goods:

certain vitamins

certain minerals

certain amino acids

certain herbal substances

substances included in Part 5 of Schedule 4 to the Regulations (e.g. fish oils)

mother tinctures; and

certain homoeopathic preparations.
Medicines that can be listed on the ARTG
To be listed on the ARTG, a medicine may only contain low risk ingredients that are
eligible for use in listed medicines (see ‘Ingredients approved for use in listed
complementary medicines’); must not contain substances that are prohibited imports for
the purposes of the Customs Act 1901; must not contain substances that are included in a
Schedule to the Poisons Standard or Appendix C of the Poisons Standard; and the medicine
must not be required to be sterile. There are also additional restrictions on some herbal
ingredients -see ‘Herbal ingredients permitted for use in listed medicines’.
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In addition, a listed medicine can only have indications (describing therapeutic use) for
health maintenance, health enhancement or certain indications for non-serious, selflimiting conditions (for more information on indications for listed medicines refer to the
draft 'Evidence required to support indications for listed medicines (excluding sunscreens
and disinfectants)’.
Listed medicines are included on the ARTG using a streamlined electronic application and
validation process – via the Electronic listing facility (ELF) which provides for early
market access for low risk medicines.
Upon submission of a listing application, a sponsor must certify under section 26A of the
Therapeutic Goods Act 1989 (the Act) that the therapeutic goods meet all applicable
legislative requirements (see ‘Requirements of 26A of the Act’ below), which includes that
the applicant holds information or evidence to support any claim that the applicant makes
relating to the medicine.
Listed medicines are required to meet certain criteria in relation to safety and quality of
manufacture, but the TGA does not evaluate their effectiveness prior to inclusion on the
ARTG. However, after listing on the ARTG, a proportion of listed medicines are reviewed
for compliance with regulatory requirements as part of the TGA’s random and targeted
post-market monitoring activities (see ARGCM Part B ‘Post-market compliance’).
Ingredients approved for use in listed complementary medicines
Schedule 4 to the Regulations and listing notices made under subsection 9A(5) of the Act
provide the types of ingredients that may be included in listed medicines.
The majority of ingredients that can be included in listed medicines are those that were
included in therapeutic goods supplied in Australia before the Act came into operation in
1991. Since then, all new ingredients approved for use in listed medicines have undergone
safety assessment by the TGA.
To be consistent with their low risk, regulatory limits/requirements may be placed on the
use of certain ingredients in listed medicines. A searchable database of active and
excipient ingredients is accessible via the TGA eBusiness Services (eBS) website.
If a person wishes to include an ingredient that is not currently approved for use in listed
medicines, the substance must be evaluated by the TGA to ensure it is safe before such use
is permitted (refer to ARGCM Part C).
Herbal Ingredients permitted for use in listed medicines
In relation to herbal ingredients, Division 1, Part 4 of Schedule 4 provides a list of herbal
substances that are not permitted in listed medicines. Further, Division 2 of Schedule 4
provides a list of plant materials from which herbal substances may be derived for
inclusion in listed therapeutic goods, provided they are compliant with certain
qualifications.
An additional requirement for a herbal ingredient (to be eligible for inclusion in listed
medicines) is that it meets the current definition of a herbal substance, as provided in
Regulation 2 of the Regulations (refer to ARGCM Part A: Herbal medicines).
An isolated substance derived from a plant, or synthesised to mimic a naturally occurring
plant constituent would not be permitted in listed medicines as a ‘herbal ingredient’.
However, the isolated plant constituent may be eligible for use as a new substance if
evaluated and approved by the TGA for use in listed medicines (refer to ARGCM Part C).
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Colouring ingredients
Colours used in oral products must be approved for such use. Refer to the document
‘Colourings permitted in medicines for oral use’.
Legislative requirements for listed medicines
Requirements of 26A of the Act
A medicine is listed on the ARTG on the basis of information provided by the applicant and
a certification by the applicant that the goods (that are the subject of the application) are
eligible for listing and meet the requirements of Section 26A of the Act. The Act allows for
cancellation of a product from the ARTG if the goods are ineligible for listing and a
sponsor’s certification is incorrect.
The applicant certifies (electronically via ELF) that the goods that are the subject of the
application meet the requirements for each of the matters referred to in paragraphs
26A(2) (a)-(k) inclusive, and if applicable, paragraph 26A(3) of the Act, that is:
26A (2) The applicant must certify that:
(a) the medicine is eligible for listing; and
(b) the medicine is safe for the purposes for which it is to be used; and
(c) the presentation of the medicine is not unacceptable; and
(ca) the medicine does not contain an ingredient that is not specified in a determination under
paragraph 26BB(1)(a); and
(cb) if a determination under paragraph 26BB(1)(b) specifies requirements in relation to
ingredients being contained in the medicine--none of the requirements have been contravened;
and
(d) the medicine conforms to every standard (if any) applicable to the medicine and to every
requirement (if any) relating to advertising applicable under Part 5-1 or under the regulations;
and
(e) if the medicine has been manufactured in Australia--each step in the manufacture of the
medicine has been carried out by a person who is the holder of a licence to carry out that step;
and
(f) the medicine complies with all prescribed quality or safety criteria that are applicable to the
medicine; and
(fa) the medicine's specifications comply with any requirements that are prescribed by the
regulations for the purposes of this paragraph and that are applicable to the medicine; and
(fb) the medicine's label:
(i) complies with any requirements that are prescribed by the regulations for the purposes of
this subparagraph and that are applicable to the medicine; and
(ii) does not make a claim that is inconsistent with any claim made by the applicant in relation
to the medicine in, or in connection with, the application; and
(fc) the applicant holds information or evidence showing the medicine's specifications will be
maintained under the conditions set out on the medicine's label until the medicine's expiry date;
and
(g) the medicine does not contain substances that are prohibited imports for the purposes of the
Customs Act 190, and
(h) all the manufacturers of the medicine are nominated as manufacturers in the application;
and
(i) the applicant has, with manufacturers of the medicine who are manufacturers of the
prescribed kind, written agreements containing such matters as are prescribed; and
(j) the applicant holds information or evidence to support any claim that the applicant makes
relating to the medicine; and
(k) the information included in or with the application is correct.
26A(3) The applicant must certify that:
Subject to subsection (7), if a step of manufacture of the medicine has been carried outside
Australia, the Secretary must have certified, prior to the application being made, that the
manufacturing and quality control procedures used in each step is acceptable.
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TGA Note: In relation to subparagraphs 26A(2)(ca) and (cb) of the Act, these
will come into effect when a determination has been made under the
provisions of section 26BB of the Act.
Further clarification on the requirements, as per section 26A of the Act, is provided below.
The medicine is eligible for listing
Schedule 4 to the Regulations and listing notices made under subsection 9A(5) of the Act
provides the types of medicines/medicine ingredients that are eligible for inclusion on the
ARTG as listed medicines.
The medicine is safe for the purposes for which it is to be used
A listed complementary medicine can only: contain ingredients that have been assessed by
the TGA to be of low risk; be manufactured in accordance with the principles of good
manufacturing practice (GMP); and only carry indications for health maintenance and
enhancement or certain indications for non-serious, self-limiting conditions.
Certain regulatory restrictions and/or controls may be imposed to ensure that the use of a
listed medicine is consistent with low risk e.g.

label advisory statements

restrictions on dosage

route of administration

plant part or plant preparation; and/or

restriction of the form in which the substance can be presented.
Sponsors must ensure that they are fully aware of any condition or restriction affecting the
use of ingredients in their products so that the product fully complies with all legislative
requirements applicable in Australia.
Ingredients derived from animal materials may present a safety risk to consumers, as they
may contain certain viruses and/or agents capable of transmitting transmissible
spongiform encephalopathies (TSEs). Information on the TGA’s approach to minimising
the risks associated with TSE is available at Supplementary requirements for therapeutic
goods for minimising the risk of transmitting transmissible spongiform encephalopathies
(TSEs). Pre-clearance of animal derived ingredients should be sought from TGA before
making an application -refer to ‘Pre-clearance application for animal-derived ingredients’.
TGA Note: The TGA approach to minimising the risks associated with TSEs is
currently under review.
The medicine presentation is acceptable
The Act provides the following definition:
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‘presentation, in relation to therapeutic goods, means the way in which the goods are presented
for supply, and includes matters relating to the name of the goods, the labelling and packaging
of the goods and any advertising or other informational material associated with the goods.’
All aspects of the product are considered to comprise the ‘presentation’ including: the
name; indications; directions for use; warning and cautionary statements; packaging;
dosage form; logos; symbols and pictures on a medicine label.
The medicine label may not include any indication that is inconsistent with the
information included in the ARTG for the medicine and must comply with applicable
standards and advertising requirements (refer to Attachment 8 for more information
regarding the requirements for medicine labels).
Section 3(5) of the Act and 3(A) of the Regulations state when the presentation of a good is
considered unacceptable.
Section 3(5) of the Act
For the purposes of this Act, the presentation of therapeutic goods is unacceptable if it is
capable of being misleading or confusing as to the content or proper use or identification of the
goods and, without limiting the previous words in this subsection, the presentation of
therapeutic goods is unacceptable:
a) if it states or suggests that the goods have ingredients, components or characteristics that
they do not have; or
b) if a name applied to the goods is the same as the name applied to other therapeutic goods
that are supplied in Australia where those other goods contain additional or different
therapeutically active ingredients; or
c) if the label of the goods does not declare the presence of a therapeutically active ingredient;
or (ca) if the therapeutic goods are medicine included in a class of medicine prescribed by the
regulations for the purposes of this paragraph—if the medicine’s label does not contain the
advisory statements specified under subsection (5A) in relation to the medicine; or
d) if a form of presentation of the goods may lead to unsafe use of the goods or suggests a
purpose that is not in accordance with conditions applicable to the supply of the goods in
Australia; or
e) in prescribed cases.
Regulation 3A of the Regulations: Unacceptable presentations
(1) For paragraph 3 (5) (e) of the Act, any labelling, packaging or presentation of therapeutic
goods (including novelty dosage forms in the shape of animals, robots, cartoon characters or
other similar objects) that is likely to result in those goods being mistaken for or confused with
confectionery or toys is an unacceptable presentation of the goods.
(2) For paragraph 3 (5) (e) of the Act, the presentation of therapeutic goods is unacceptable if
the name applied to the goods is not sufficiently distinctive to allow for the identification of the
goods for the purposes of recovery.
Generally, the presentation of therapeutic goods is unacceptable if it is capable of being
misleading or confusing as to the content or proper use or identification of the goods.
Examples of ‘unacceptable’ presentations include:

therapeutically active ingredients are present in the formulation but not declared as
such on the label (and/or misleadingly declared as ‘excipients’ in the application)

statements are made attributing a therapeutic role to ingredients that have not been
declared as active ingredients (i.e. excipient ingredients)

statements or pictures suggest that the product has uses or actions different from, or
in addition to, the indications for use included on the ARTG

presentation of a product is in a form likely to result in its being confused with food
(e.g. in confectionery-like novelty shapes and packaging)
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
product names are used that are likely to be misleading as to the composition of the
medicine

the appropriate dosage for all age-groups in the likely target population is not stated
(e.g. ‘adults’, ‘children 6-12 years’ etc., as appropriate)

the dosage form or directions are inappropriate for the target population (e.g. a
capsule dosage form is not appropriate for infants)

warning or cautionary statements needed for proper usage of the product are omitted

a reformulated product uses the same name as a product previously supplied, without
labelling that adequately informs the consumer that the reformulated product has
different active ingredients from the product previously supplied

as a general guideline, label flashes such as ‘New formulation’ or ‘Now with …’ should
not be used to describe any product, presentation or therapeutic indication / claim
which has been available and promoted in Australia for more than 12 months

claims are made that a formulation is ‘hypo-allergenic’ or ‘non-irritant’, unless the
sponsor holds supportive evidence from clinical tests that can be produced on request;
and

claims are made that a product is ‘free from artificial colours’ if not true.
The medicine conforms to every standard applicable
Therapeutic goods must comply with applicable standards. Criminal or civil penalties can
be imposed on persons who import, export, manufacture or supply goods that do not
comply with applicable standards (unless a sponsor has consent to supply such a good
under Section 14 of the Act – see ‘Consent to supply goods not compliant with certain
legislative requirements’). The official standards for regulatory purposes in Australia are
the British Pharmacopeia (BP), European Pharmacopoeia (Ph. Eur) and United States
Pharmacopoeia – National Formulary (USP/NF) and Therapeutic Goods Orders (TGOs).
The following TGOs are relevant to listed medicines:

Therapeutic Goods Order No. 69: General requirements for labels for medicines, as
amended (TGO 69) (refer to Attachment 8: Medicine labels)

Therapeutic Goods Order No. 77: Microbiological standards for medicines (TGO77).

Therapeutic Goods Order No. 78: Standards for tablets and capsules (TGO 78); and

Therapeutic Goods Order No. 80: Child-resistant packaging requirements for
medicines, as amended (TGO 80).
The medicine complies with manufacturing requirements
Australia has codes of good manufacturing practice (GMP) and quality system
requirements for the manufacture of therapeutic goods, including complementary
medicines. For more information refer to ‘Manufacturing therapeutic goods’.
In Australia, the Act requires, with certain exceptions, that manufacturers of therapeutic
goods hold a licence. Where a product is imported, or if any steps in the manufacture of a
listed medicine take place outside Australia, a delegate of the Secretary must have certified
the acceptability of the overseas manufacturer’s GMP before the listing application is
made. The information needed to establish the standard of an overseas manufacturer is
available on the TGA website: ‘For overseas manufacturers’.
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Sponsors must ensure that all the manufacturers of the medicine are included in the
product ARTG entry. If a sponsor wishes to use a manufacturer that is not included in the
ARTG entry, the entry must be amended to include the new manufacturer (see ARGCM
Part B: ‘Product variation’).
The medicine conforms to every requirement relating to advertising
Sponsors and advertisers should ensure that all advertising for the medicine complies
with any applicable requirements of Part 5-1 of the Act and the Therapeutic goods
advertising code 2007 (the Advertising Code). Australian based websites promoting use or
supply of therapeutic products are also considered advertising and must comply with all
aspects of the Advertising Code.
The medicine complies with all applicable prescribed quality or safety criteria
The sponsor is responsible for the quality of a listed complementary medicine (refer to
Attachment 7a: Quality of listed medicines) and must hold information or evidence to
demonstrate that the medicine complies with requirements and meets all specifications
for the shelf life of the medicine, at the recommended storage conditions and the expiry
date included on the label. Sponsors are required to certify under paragraph 26A(2)(fc) of
the Act at the time of listing that they hold this information. A delegate of the Secretary can
request information or documents about the quality of a listed medicine under paragraph
31(2) (ca) of the Act; and can cancel a listing if it appears to the delegate that the quality of
the medicine is unacceptable.
The sponsor holds evidence to support indications made for the medicine
Consistent with their low risk, listed complementary medicines may only carry
appropriate indications that are true, valid, not misleading and will not lead to their unsafe
or inappropriate use.
At the time of listing, applicants of listed medicines certify under paragraph 26A(2)(j) of
the Act that they hold information or evidence to support any claim that they will make
about the medicine. Subsection 28(6) of the Act provides conditions of listing that a
sponsor must hold evidence which supports the indications made for their medicine and
must provide this evidence to the TGA if requested to do so. The evidence to support
indications for listed complementary medicines are not subject to pre-market evaluation
before listing; however, the TGA may undertake a compliance review of evidence held by
sponsors as part of its random and targeted post-market monitoring activities- see ‘Listed
complementary medicine compliance reviews’.
Evidence that may be used to support indications can be based on history of traditional
use or scientific data. The draft 'Evidence required to support indications for listed
medicines (excluding sunscreens and disinfectants)' specifies the type of evidence
required to support indications made for listed medicines. Should an applicant wish to
make a higher level indication than those permitted for listed medicines (refer to ARGCM
Part A: Registered and listed medicines), then the product is required to be registered and
undergo full pre-market evaluation by the TGA for quality, safety and efficacy. For further
information on medicine registration refer to Part D of the ARGCM.
The information included in the application is correct
Applicants must ensure that the information contained in the application is correct. An
incorrect certification against paragraph 26A(2)(k) of the Act could result in the product
being cancelled from the ARTG under the provisions of paragraph 30(2)(ba) of the Act.
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Conditions of listing
Statutory conditions of listing
There are a number of statutory conditions of listing that automatically apply when the
medicine is listed on the ARTG. Failure to comply with a condition of listing may result in
the cancellation of the medicine from the ARTG.
Section 28 of the Act provides the following statutory conditions of registration or listing.
(2B) If the Secretary includes therapeutic goods in the Register in relation to a person, the
Secretary may, by notice in writing given to the person, impose conditions on the registration or
listing of those goods.
(3) The Secretary may, by notice in writing given to the person in relation to whom therapeutic
goods are registered or listed, impose new conditions on the registration or listing or vary or
remove conditions imposed under subsection (2B) or this subsection.
(5) In addition to any conditions imposed under subsection (1), (2B) or (3), the registration or
listing of therapeutic goods (the subject goods) is subject to the conditions that the person in
relation to whom the subject goods are registered or listed will:
(aa) not supply a batch of the subject goods in Australia, or export a batch of the subject goods
from Australia, after the expiry date for the goods; and
(ab) not, by any means, advertise the subject goods for an indication other than those accepted
in relation to the inclusion of the goods in the Register; and
(e) comply, in relation to the subject goods, with any reporting requirements that are
prescribed; and
(f) if a manufacturer who was not nominated as a manufacturer of the subject goods in the
application for the registration or listing of the goods becomes a manufacturer of the goods—
inform the Secretary in writing of that fact, no later than 10 working days after the
manufacturer becomes a manufacturer of the goods; and
(g) if premises that were not nominated as premises to be used in the manufacture of the
subject goods in the application become premises used in the manufacture of the goods—
inform the Secretary in writing of that fact, no later than 10 working days after the premises are
first used for that purpose.
(5A) In addition to any conditions imposed under subsection (1), (2B), (3) or (5), the listing of a
medicine under section 26A is subject to a condition that the person in relation to whom the
medicine is listed will deliver a reasonable number of samples of the medicine if the Secretary
so requests:
(a) within the period specified in the request; and
(b) in accordance with any other requirements specified in the request.
The period specified in the request must include at least 10 working days
(5B) The listing of a medicine under section 26A is subject to a condition that:
(a) each step in the manufacture of the medicine that is carried out in Australia is carried out by
a person who is the holder of a licence to carry out that step or who is exempt from the
operation of Part 3-3 in relation to that step; and
(b) each step in the manufacture of the medicine that is carried out outside Australia is the
subject of a certification in force under subsection 26A(3) or 28A(2).
(5C) Subsection (5B) does not apply if the medicine is exempt from the operation of Part 3-3.
(6) If:
(a) in, or in connection with, an application for the listing of therapeutic goods, a claim is made
by the applicant in relation to the goods; and
(b) the claim is included in the Register in respect of the goods;
the listing of the goods is subject to the following conditions:
(c) a condition that the sponsor of the goods had, at the time when the claim was made,
information or evidence that supported the claim and complied with the requirements (if any)
of the regulations;
(d) a condition that the sponsor retains the information or evidence at all times while the goods
remain listed;
(e) a condition that, at any time while the goods remain listed, the sponsor will, if asked to do so
by the Secretary, give the information or evidence to the Secretary.
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General additional conditions of listing
Section 28 of the Act provides legislative powers for the Secretary to impose, vary or
remove additional conditions on listed therapeutic goods at the time the medicine is listed,
or any time thereafter. The following general ‘Additional conditions of listing’ are imposed
by the delegate of the Secretary at the time a medicine is listed on the ARTG and are
notified to the sponsor in writing:

The sponsor shall keep records relating to this listed medicine as are necessary to: (a)
Expedite recall if necessary of any batch of the listed medicine, (b) Identify the
manufacturer(s) of each batch of the listed medicine. Where any part of or step in
manufacture in Australia of the listed medicine is sub-contracted to a third party
who is not the sponsor, copies of relevant Good manufacturing practice agreements
relation to such manufacture shall be kept.

The sponsor shall retain records of the distribution of the listed medicine for a period
of five years and shall provide the records or copies of the records to the Office of
Complementary Medicines, Therapeutic Goods Administration, upon request.

The sponsor of the listed medicine must not, by any means, intentionally or recklessly
advertise the medicine for an indication other than those accepted in relation to the
inclusion of the medicine in the ARTG.

All reports of adverse reactions or similar experiences associated with the use or
administration of the listed medicine shall be notified to the Head, Office of Product
Review, Therapeutic Goods Administration, as soon as practicable after the sponsor
of the goods becomes aware of those reports. Sponsors of listed medicines must
retain records of such reports for a period of not less than 18 months from the day
the Head, Office of Product Review is notified of the report or reports.

The sponsor shall not supply the listed medicine after the expiry date of the goods.

Where a listed medicine is distributed overseas as well as in Australia, product recall
or any other regulatory action taken in relation to the medicine outside Australia
which has or may have relevance to the quality, safety or efficacy of the goods
distributed in Australia, must be notified to the National Manager Therapeutic Goods
Administration, immediately the action or information is known to the sponsor.

Colouring agents used in listed medicine for ingestion, other than those listed for
export only under section 25 of the Act 1989, shall be only those included in the list of
'Colourings permitted in medicines for oral use' as amended from time to time.
Substance specific conditions of listing
Specific conditions of listing may be imposed on a medicine in relation to specific
ingredients included in the medicine. These conditions are imposed when the product is
listed on the ARTG and are notified to the sponsor in writing. For example, the following
condition of listing is imposed on listed complementary medicines that contain
preparations of the herbal material, Ginkgo biloba leaf extract:
‘The Ginkgo biloba leaf extract used in the manufacture of this medicine must
comply with the requirement of Identification Test B of the monograph Powdered
Ginkgo Extract in the United States Pharmacopeia 32 - National Formulary 27
(USP32-NF27). This condition does not apply to powdered or dried leaf’.
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Variations & sponsor’s rights to appeal against imposition of conditions of listing
Under subsections 28(2B) and 28(3) of the Act, while a medicine is listed on the ARTG,
new conditions of listing may be imposed and/or existing conditions may be varied or
removed, as determined by a Delegate of the Secretary. A sponsor may also request that a
condition of listing be imposed or varied (an application fee may apply) - the Delegate of
the Secretary will review the request and sponsors will be advised in writing of the
decision.
The imposition or variation of a condition will take effect:

on the day on which the notice is given, if the notice states that the action is necessary
to prevent imminent risk of death, serious illness or serious injury; or

in any other case, on the day specified in the notice, which will be a day not earlier
than 28 days after the notice is given.
Sponsors are advised in writing of any conditions of listing and may appeal against a
decision made under subsections 28(2B) and 28(3) of the Act to impose, vary or remove a
condition of listing. There is a time limit for such an appeal and this interval, together with
details of the process for an appeal, is advised in the letter from the TGA imposing the
conditions (refer ARGCM Part A: ‘Appeal mechanisms’).
Consent to supply goods that are not compliant with certain legislative
requirements
Sponsors are able to apply for consent to supply certain therapeutic goods that do not
comply with some of the requirements set out in the therapeutic goods legislation. There
are two main types of requests, as below.
Non-compliance with prescribed standards
Sponsors can apply to the TGA, in writing, under sections 14 and 14A of the Act, to request
consent to supply goods that do not comply with a relevant standard (e.g. BP, Ph Eur, USP
or TGOs). Requests should explain why the standard(s) cannot be met and provide details
and reasons for proposed alternative(s). Such a request will incur an application fee.
The Delegate of the Secretary will review the request and sponsors will be advised in
writing of the decision. Any consent that is provided by the Delegate may have conditions
attached to that decision.
Decisions to ‘consent to supply goods that do not comply with a standard’ are required by
the Act to be gazetted in the Commonwealth of Australia Gazette.
Request to use a restricted representation
Therapeutic goods advertisements cannot refer to a serious form of a disease, condition,
ailment or defect as specified in the Advertising Code. These are known as restricted
representations. In some cases, under the Act, the Secretary can permit the use of a
restricted representation on the label or in information included in the package of the
listed medicine. This permission is defined by Section 42DK(1) of the Act.
If the sponsor or advertiser wishes to publish or broadcast an advertisement containing a
restricted representation, the sponsor must make an application under section 42DE of
the Act. The application may be sent to the Director of the TGA’s advertising section.
Permission must be obtained before using the representation in advertising therapeutic
products to consumers.
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Therapeutic Goods Administration
Permission for use of restricted representations (on the label or in information included in
the package of the listed medicine) is required by the Act to be gazetted in the
Commonwealth of Australia Gazette or published on the TGA website.
For listed complementary medicines, approval to use a restricted representation is only
likely to be granted if the goods are required to have a warning relating to a disease e.g.
“this product should not be used by individuals with diabetes”.
The listing process via the electronic listing facility
Listed medicine application lodgement via the electronic listing facility
Applications to list medicines on the ARTG are done via the electronic listing facility (ELF),
which is part of the TGA’s eBusiness services (eBS) framework.
Access to the ELF system is via a secure login on the eBS homepage and requires a user
name and password. The electronic listing facility (ELF) user guide is available on the TGA
website. In order to get access to ELF, applicants must first submit a client details form to
obtain a ‘client identification number’. Having obtained a client identification number, an
eBS access request form can be submitted. The TGA will establish access for the applicant
to become the ‘E-business administrator’ for their company and then applications for user
accounts for themselves and other personnel in their company can be made. For further
information about obtaining a client identification number or gaining access to eBS,
contact the TGA by phone: 1800 010 624 or email: ebs@tga.gov.au.
Access to ELF allows for two types of user:

drafter – users who are drafters can carry out all functions relating to applications,
excluding their final submission; and

submitter – users who are submitters can carry out all the same functions as a drafter
and also submit completed, validated applications.
The ELF system allows users to:

create new draft applications

create draft applications from an existing ARTG entry

change certain information for current listings

submit completed applications to the TGA for processing

view previously submitted applications

view the details of medicines already listed on the ARTG

view the label checklist; and

view the latest news relating to ELF.
Validation system within the electronic listing facility
An application (to either list a new complementary medicine or update information on an
existing listed medicine) must pass ELF validation before it can be submitted to the TGA.
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When the ‘validate’ button in ELF is initiated, the information in the application is
compared against the rules and restrictions surrounding listed medicines.
Successful validation of an application does not mean that the product has
been approved by the TGA nor does it mean that the product meets all the
requirements for listing. The ELF system is a tool designed to allow electronic
submission of an application for a listed medicine. The onus of responsibility is
with the applicant to certify, upon submission, that the goods that are the
subject of the application meet all the requirements of listing.
If the application fails validation, a validation report is generated providing the reasons for
failure e.g. if a sponsor applies to list a medicine on the ARTG that requires a mandatory
label advisory statement, which was not included in the application, the ELF system will
‘fail validation’ and prevent the sponsor from submitting the application to the TGA. The
user will need to update the application accordingly before attempting to re-validate.
If the application passes validation, the status of the application will change from ‘draft’ to
‘passed validation’. Only applications that have the status of ‘passed validation’ can be
submitted (via ELF) to the TGA. Note that if the application is not submitted at this time,
the status of the application will revert from ‘passed validation’ to ‘draft’ and will be
required to undergo re-validation before being able to be re-submitted.
Payment for applications
Fees for a listing application are non-refundable or transferable and must be paid within
14 days of the application being submitted to the TGA. If payment is not received, an email
is sent to the applicant notifying them that the application has been rejected. Should the
sponsor wish to proceed with the application, a new application will be required.
TGA processing of application
Once payment is processed, the application is released into the listing part of the TGA’s
eBS system and assigned an AUST L number. Further processing includes:

initiation of the automated ELF random review selection process

an e-mail message is automatically sent to the sponsor informing them that the
product has been successfully listed on the ARTG and providing the AUST L number

a ‘Certificate of medicine listing’ is generated for downloading by the sponsor; and

a ‘Conditions of listing’ letter is generated and sent to the sponsor by the TGA.
The product details will usually be viewable on the eBS website the day after
the information has been written to the ARTG.
Diagram 1 shows the process for listing a medicine on the ARTG via the ELF.
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Therapeutic Goods Administration
Diagram 1: The process for listing a medicine on the ARTG via ELF
1.
Sponsor obtains a client ID number.
2.
Sponsor obtains a user ID and password to access ELF.
3.
Sponsor enters product details in ELF.
4.
Application passes validation in ELF (note this is not an approval process).
5.
Sponsor electronically signs a declaration whereby they certify (as per Part 26 A
of the Act) that the application meets all conditions of listing.
6.
Sponsor submits application to the TGA.
Application fees paid within 14 days of application.
Yes
TGA identification number (TGAIN) assigned to
application and application written to ARTG.
No
The application is rejected and
sponsor is notified by email.
AUST L number generated. ELF may randomly select product for a compliance review.
Sponsor notified by email of application completion and provided the AUST L number.
Certificate of listing available in eBS for downloading by the sponsor.
Product can be marketed.
Application checked by the TGA and ‘Conditions of listing’ letter sent to sponsor.
If selected for random compliance review, the sponsor receives a letter requesting
information (under Section 31 of the Act). The sponsor is usually given 20 working days
to respond.
Response received from sponsor within allocated timeframe.
Yes
Response evaluated by TGA. Further steps may
include: no action; more information requested; or
proposal to cancel product from ARTG.
ARGCM Part B
January 2013
No
Product cancelled from ARTG
(under provision of Section 30
(1C) of the Act.
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Therapeutic Goods Administration
Product variation
Following the inclusion of a product as a listed medicine on the ARTG, sponsors may need
to update certain product details. Changes in manufacturer, changes in product
ingredients or developing marketing strategies may require amendment of the product
details of a medicine included listed on the ARTG.
Where the intended change does not create another product altogether i.e. a ‘separate and
distinct’ therapeutic good (see below), there are provisions in the legislation for certain
details to be amended in a medicines’ ARTG entry. However, if the intended change would
create a ‘separate and distinct’ good sponsors are required to submit a new application to
list the goods and a new AUST L number will be issued (unless the two medicines are
eligible for ‘grouping’ under the Therapeutic Goods (Groups) Order- see ‘The Therapeutic
Goods (Groups) Order’ below).
Changes that result in ‘separate and distinct’ goods
Section 16 (1A) of the Act outlines those criteria which make listed medicines (other than
‘export only’1 medicines) ‘separate and distinct’ from other therapeutic goods.
(1A) Medicines that are listable goods (other than export only medicines) are taken to be
separate and distinct from other therapeutic goods if the medicines have:
(a) different active ingredients; or
(b) different quantities of active ingredients; or
(c) a different dosage form; or
(d) such other different characteristics as the regulations prescribe;
In relation to 16 (1A) (d) of the Act, ‘different characteristics’ for listed medicines (other
than ‘export only’ medicines) are provided in Regulation 11:
(a) a different name; or
(b) different indications; or
(c) a different excipient; or
(d) for medicines that contain any restricted ingredients:
(i) a different quantity of a restricted ingredient that is an excipient; or
(ii) if the restriction on a restricted ingredient relates to its concentration in a relevant
medicine — a different concentration of the restricted ingredient; or
(iii) if the restriction on a restricted ingredient relates to its quantity in the recommended
single or daily dose in a relevant medicine —
Provisions for product amendment
Where the intended change does not create a ‘separate and distinct’ good, a sponsor may
request for certain details to be amended on a medicines’ ARTG entry and maintain the
same AUST L number (please be aware that legislation is subject to change and should be
regularly checked).
Minor changes to listed medicines on the ARTG (other than those listed for export only)
are made via the ELF system. For further information, including the types of changes that
incur a fee, refer to ‘Guidance on product changes in ELF 2’.
The ELF system has been designed to allow sponsors to make the same minor changes to
multiple current listings under certain circumstances using the ‘Change multiple listings’
form in ELF. These changes are limited to: product names, common manufacturing steps;
1
as defined in subsection 3(1) of the Act
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and manufacturers. Note that where the type of change incurs a fee, this fee is applicable
to each medicine listing that is changed.
Variation under section 9D of the Act
A sponsor may request, in writing, to the TGA to vary certain information in the ARTG
listing for a medicine. The allowable types of requests are set out in section 9D of the Act
and include:

Correction of an entry if the entry contains information that is incomplete or incorrect
- see subsection (9D(1) of the Act).

Variation of the entry where the only effect would be to either reduce the class of
persons for whom the medicine is suitable; or to add a warning, or precaution that
does not include any comparison of the medicine with any other therapeutic goods by
reference to quality, safety or efficacy (9D(2) of the Act).

Other variations relating the medicine where the Secretary (or Delegate) is satisfied
that the variation does not indicate any reduction in the quality, safety or efficacy of
the goods for the purposes for which they are to be used (9D(3) of the Act).
The Therapeutic Goods (Groups) Order
As stated above, if a sponsor’s request for variation of a listing entry for a medicine would
result in the varied medicine being ‘separate and distinct’ from the existing medicine, then
the varied medicine is regarded as a new medicine and must be listed separately.
However, in certain circumstances, the new medicine may be listed on the ARTG with the
same AUSTL number as the existing medicine (however, individual products within the
group are considered separate and distinct products under section 16(1) and (1A) of the
Act). This process is called ‘grouping’.
Eligibility for ‘grouping’ is determined by an Order made under section 16 of the Act –
currently the Therapeutic Goods (Groups) Order No. 1 of 2001 (Groups Order). The usual
fee for an application for new listing applies, but there is only one annual charge for the
two grouped medicines.
The circumstances in which two or more therapeutic goods can be ‘grouped’ are set out in
the Groups Order and include, for example, where a new medicine is listed by a sponsor
that is intended to replace an existing medicine and differs from that medicine by only one
of the following:

particular kinds of excipients

indications and/or directions for use; or

product name.
Changing information in the ARTG for ‘grandfathered’ products
‘Grandfathered products’ are those products that were available in Australia prior to the
Act coming into effect. When products were ‘grandfathered’ on the ARTG, some entries
may not have included indications. In such cases, the following statement is included in the
ARTG record:
‘This product accepted for registration/listing as ‘currently supplied’ at the time of
commencement of the Act. Indications held in ARTG paper records’.
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If a sponsor of a ‘grandfathered’ listed medicine wants to change information in the ARTG
for their medicine, the same rules as for other listed medicines apply.
Post-market compliance
The TGA has a comprehensive risk-based system for post market compliance activities
which provides timely identification and appropriate regulatory responses to problems
associated with the formulation, manufacture, labelling and advertising of medicines.
Information on the TGA's approach to managing compliance risk is available at TGA
regulatory framework.
The objectives of the TGA’s post-market program for listed complementary medicines are
to:

provide assurance of the safety of complementary medicines through a risk-based
program of post market monitoring and surveillance

provide consumer confidence in the safety, quality and efficacy of complementary
medicines; and

ensure industry compliance with regulatory standards for complementary medicines.
The measures used within the TGA to meet these objectives include:

targeted and random desk-based compliance reviews of listed complementary
medicines

targeted and random laboratory testing of medicines and ingredients

inspections of manufacturers to ensure compliance with good manufacturing practice

product vigilance activities

effective co-regulatory approach to control product advertising

targeted and random surveillance of the products in the market place; and

an effective, responsive and timely product recall procedure.
The compliance review of a listed complementary medicine involves:

assessing information about the product against the relevant legislative requirements,
including, where relevant, the certifications given by the sponsor at the time the
product was listed; and

taking appropriate actions when a breach of the legislative requirements is identified.
A listed complementary medicine may be subject to a number of compliance reviews while
it remains on the ARTG.
Listing compliance reviews
A proportion of newly listed medicines are randomly selected by computer, based on a
mathematical model, for compliance review. Compliance reviews initiated from this
source are referred to as ‘random reviews’.
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The TGA also conducts ‘targeted reviews’ when a listed complementary medicine is
identified with potential non-compliance issues. These potential non-compliance issues
may be brought to the TGA’s attention by internal or external sources. Internal sources
may include regular screening of new ARTG entries and information gathered from
previous compliance reviews. External sources may include: the public, media, health care
professionals, industry, international alerts and information from other regulatory
agencies.
Random reviews
If a recently listed medicine is randomly selected at the time of listing for a compliance
review, the following information will usually be requested from the sponsor under the
provisions of section 31(2) of the Act:

actual label(s) used for the product as it is supplied in Australia

finished product specifications

a certificate of analysis for the last released batch (i.e. a statement about results of
testing of the product and how they compare with established acceptance criteria)

a summary of the evidence held by the sponsor that supports the indications and
claims made in relation to the product (detailed evidence may be requested during the
review, if required); and

copies of completed TSE (transmissible spongiform encephalopathy) questionnaire/s
and supporting data, if applicable to ingredients.
The TGA may also view Australian websites for the purpose of considering whether
advertising for the product complies with the Advertising Code.
Targeted reviews
If a listed complementary medicine with potential-non compliance issues is chosen for a
targeted review, the review may be conducted upon information provided in a complaint
or referral (if appropriate), information from other sources and/or information included
on the ARTG. A request for information by notice under section 31(2) of the Act may also
be required. In addition to the type of information that can be sought for the purposes of a
random review (as outlined above), the information requested under section 31 (2) of the
Act for a targeted review may include (but is not limited to):

raw material specifications and certificates of analysis

methodology and results in relation to a specific test

copies of permits and/or licences allowing the importation of the medicine if it
contains substances that are prohibited imports for the purposes of the Customs Act
1901

details of manufacturing process

promotional and advertising material; and/or

detailed evidence (i.e. full copies of all references ) used to support the indications and
claims made in relation to the product.
For more information on the random and targeted compliance reviews, including possible
regulatory actions and appeal rights, refer to Listed complementary medicine compliance
reviews.
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Therapeutic Goods Administration
Safety and efficacy reviews
Further to the compliance reviews described above, specific safety and efficacy reviews in
response to issues arising in the market place may be carried out for:

ingredients

individual medicines; and

medicine groups.
Laboratory testing program
The TGA undertakes a laboratory testing program which complements the desk-based
compliance reviews of listed complementary medicines and evaluation of registered
medicines, as well as other post market regulatory activities. The laboratory testing
program prioritises therapeutic goods considered to carry a higher risk, while still
allowing for responsive testing for issues arising in the marketplace e.g. adverse events
and complaints about specific medicines.
The testing program involves the selection of both random and targeted samples for
analysis. Samples for the testing program are obtained from manufacturers, wholesalers,
pharmacies, hospitals, retail outlets or consumers.
For more information on the laboratory testing program, refer to The Office of
Laboratories and Scientific Services (OLSS) activities.
Good manufacturing practice inspections
Manufacturers of therapeutic goods supplied in Australia are subject to regular
inspections by the TGA’s Office of Manufacturing Quality. Details of the requirements for
the manufacture of listed medicines are specified in the ‘PIC/S guide for good
manufacturing practice for medicinal products’. For more information regarding the GMP
inspection of medicine manufacturers please refer to ‘Audit of medicine manufacturers’.
Product vigilance activities
The TGA monitors therapeutic products in the market using a range of product vigilance
tools to collect and evaluate information relating to the benefits and risks associated with
their use. For more information on Australia's processes refer to ‘Therapeutic product
vigilance’.
Adverse reaction reporting
The Act and Regulations requires sponsors of all therapeutic goods currently included on
the ARTG to report to the TGA adverse reactions that they become aware of for their
medicines. The TGA has developed the ‘Australian requirements and recommendations for
pharmacovigilance responsibilities of medicine sponsors’ which outlines specific reporting
requirements for sponsors of Australian medicines.
The TGA also relies on the public, healthcare professionals and industry to report
problems with therapeutic goods so that potential and actual safety concerns can be
identified and action taken where required. Refer to ‘Reporting problems’ on the TGA
website for the various mechanisms by which adverse reactions and events can be
reported.
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Therapeutic Goods Administration
Co-regulatory approach to control advertising
In Australia all advertisements and generic information provided about therapeutic goods
directed to the public must comply with provisions of the Act, the Regulations and the
Advertising Code. The advertising of therapeutic goods is controlled by a combination of
statutory measures administered by the TGA and self-regulation through Codes of Practice
administered by the relevant therapeutic goods industry associations.
Further information, on Australia's co-regulatory system of advertising for therapeutic
goods, including details of the Therapeutic Goods Advertising Code Council (TGACC), the
Complaints Resolution Panel (CRP) and the Complaints Register, may be obtained from the
TGACC internet site.
Targeted and random surveillance in the marketplace
The TGA is responsible for on-going surveillance, enforcement and related activities,
including investigations into illegal and counterfeit therapeutic goods. Investigations by
the TGA may be initiated on the basis of a:

complaint by the public or a healthcare practitioner

referral from a section within the TGA

referral from another Australian agency, such as the Australian Quarantine and
Inspection Service, Food Standards Australia New Zealand or Australian Customs; or

referral from an international agency.
Product recalls
A product recall is the removal of therapeutic goods from supply on the Australian market.
Recall of any distributed goods may be required for a number of reasons relating to their
quality, efficacy or safety e.g. a recall can occur because of problems such as: labelling or
packaging errors; contamination issues; or an increase in unexpected side effects etc.
Further information on recalls of therapeutic goods is provided on the TGA website: About
recalls.
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Therapeutic Goods Administration
Attachments are common to all parts of the ARGCM (A,
B, C & D). Note that the list of attachments and the
content will be updated as each part of the ARGCM is
released for consultation.
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Therapeutic Goods Administration
Attachment 1: Compositional guidelines for
complementary medicine substances
The purpose of the information contained in a compositional guideline is to provide
detailed characterisation of the starting material. For simple complementary substances,
this is generally straightforward and may be only a simple extension of the specifications.
For complex complementary substances, the compositional information is generally more
detailed and contains a significant amount of additional qualitative and quantitative
information.
Compositional guidelines are available on the TGA website.
Guidance on compositional guidelines for complementary substances is being developed
by the TGA and will be released as part of the consultation process for ‘ARGCM Part C:
Evaluation of complementary medicine substances’.
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Therapeutic Goods Administration
Attachment 2: Data requirements for proprietary
ingredients
TGA Note: The information in this Attachment has been revised following
feedback from the consultation process for ARGCM Part A.
While there is no safety assessment or evaluation of a proprietary ingredient formulation
or ingredients at the time of application, consideration is given to the suitability of the
ingredients in the formulation for inclusion in a therapeutic good.
For a proprietary ingredient to be eligible for inclusion in listed complementary
medicines, all ingredients (except flavours, fragrances or inks) included in the proprietary
ingredient’s formulation must be permitted for use in listed medicines.
Where a listed complementary medicine is the subject of a listing compliance review, the
TGA may request additional information on the proprietary ingredient, given that the
formulation details for a proprietary ingredient are supplied in isolation of the finished
product formulation.
If an ingredient in the proprietary ingredient formulation is not permitted for use in listed
medicines (and the proprietary ingredient is not a flavour, fragrance or ink) the ingredient
must be evaluated, either as a new substance in listed medicines (see ARGCM Part C) or as
part of the evaluation process for a registered medicine, before it can be included in a
proprietary ingredient.
While in the proprietary ingredient notification process the advising of a manufacturer is
optional, where the manufacture of an ingredient is considered a significant step in the
manufacture of the finished product (e.g. a tablet granulation, a tablet coating, an active /
excipient pre-mix, or a vehicle for a topical product), evidence of licensing or approval of
the manufacturer may be required.
Where a proprietary ingredient is not considered a significant step in the manufacture of
the finished product (e.g. most colours, printing inks, flavours and fragrances, and
proprietary ingredients whose sole purpose is as a source of the preservative system for
the finished product) evidence of Good Manufacturing Practice (GMP) is not required
Information to be included in a notification of a new proprietary ingredient for use in
listed medicines
The following information is required to be submitted in the notification of a new
proprietary ingredient for use in listed medicines:
1.
The purpose of the proprietary ingredient e.g. colour, flavour, fragrance, ink, coating
solution, preservative or active pre-mix.
2.
The names of all ingredients, in an approved name format consistent with the
Australian approved terminology for medicines (e.g. ‘Approved herbal name (AHN)’).
3.
The quantitative composition of all ingredients, expressed as a concentration of the
total proprietary ingredient.
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Therapeutic Goods Administration
An exception to points 2 and 3 above are proprietary ingredients used as fragrances and
flavours where the declaration of quantitative composition and use of Australian approved
terminology, while preferable, is not mandatory.
In addition to the requirements above, specific requirements for different types of
proprietary ingredients include:
Colours
Proprietary ingredients used as colours in oral listed medicines are required to contain
only colours currently approved for use in oral medicines.
Flavours, fragrances and inks
A limit applies to the concentration allowed in listed medicines for proprietary ingredients
that are flavours, fragrances and inks, as provided in the table below:
Proprietary ingredient type
Maximum concentration permitted in listed medicines
Flavours
5%
Fragrances
1%
Inks
0.1%
Active pre-mixes
Proprietary ingredients that are classified as active pre-mixes must contain at least one
active ingredient and an excipient ingredient.
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Therapeutic Goods Administration
Attachment 3: Data requirements for herbal materials
Guidance on data requirements for herbal medicines is being developed by the TGA and
will be released as part of the consultation process for ‘ARGCM Part C: Evaluation of
complementary medicine substances’.
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Attachment 4: Identification of herbal materials &
extracts Q & A
<http://www.tga.gov.au/industry/cm-identification-herbal-extracts.htm>
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Attachment 5: Guidance on equivalence of herbal
extracts in complementary medicines
<http://www.tga.gov.au/industry/cm-herbal-extracts-equivalence.htm>
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Therapeutic Goods Administration
Attachment 6: Guidance on the use of modified
unprocessed herbal materials in complementary
medicines
<http://www.tga.gov.au/industry/cm-herbal-modified-unprocessed.htm>
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Attachment 7a: Quality of listed complementary
medicines
It is a requirement under the Act (26A subsection 5B) that each step in the manufacture of
a medicine in Australia is carried out by a licensed manufacturer (unless the therapeutic
good is exempt from this requirement). For more information refer to ‘Manufacturing
therapeutic goods’. It is an offence, carrying heavy penalties, to manufacture therapeutic
goods for human use without a licence unless the manufacturer or goods are exempt. The
manufacturer’s licence carries details of the types of manufacture permitted under the
licence.
Where a product is imported, each nominated overseas manufacturer must demonstrate
an acceptable standard of good manufacturing practice (GMP) as would be required of an
Australian manufacturer. Pre-clearance of overseas manufacturers is mandatory for listed
complementary medicines. The information needed to establish the standard of an
overseas manufacturer is available on the TGA website: ‘For overseas manufacturers’.
Australia has a code of good manufacturing practice and quality system requirements for
the manufacture of therapeutic goods, including complementary medicines. Each
code/quality system sets out requirements relating to quality management, personnel,
premises and equipment, documentation, production, quality control, contract
manufacture and analysis, complaints and product recall and self inspection. The
observance of these requirements is necessary through all stages of manufacture to
consistently provide a high level of assurance of the quality, safety, and efficacy of
therapeutic goods. Compliance with the code of good manufacturing practice and quality
system requirements in Australia is determined by carrying out regular on-site
inspections.
Some complementary medicines are comprised of relatively simple ingredients (e.g. amino
acids, mineral salts, vitamins) and the quality parameters applying to such products are
essentially the same as for other medicines. Special considerations are required for those
complementary medicines that contain complex ingredients that are difficult to
characterise and/or certain combinations of multiple active ingredients.
Sponsors should be aware of the following documents that provide specific guidance for
complementary medicines:

Annex 7 of the ‘Guide to good manufacturing practice for medicinal products’ provides
specific guidance on the manufacture of herbal medicinal products.

‘Supplier qualification’ provides the steps by which supplier qualification may be
achieved.

‘Identification of herbal materials and extracts’ provides common questions and
answers relating to identification of herbal materials. The overarching principle for the
identification of herbal starting materials is traceability to a primary source or
certified herb and testing must discriminate between related species and/or potential
adulterants/substitutes that are likely to be present.

Sampling and testing of complementary medicines covers the sampling and testing
requirements for raw materials used in the manufacture of intermediate, bulk or
finished complementary medicine products. It also describes a plan for reduced
sampling and testing once an approved supplier has been qualified.
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Therapeutic Goods Administration

The guideline ‘Starting material analytical procedure validation for complementary
medicines’ describes the minimum approach acceptable to achieve validation of the
test procedures used for starting materials for use in complementary medicines. In
determining the minimum validation activities to be applied to a test procedure, a riskbased assessment should be undertaken; different approaches may be acceptable but
must be documented and able to be justified. Additional validation activities may also
be undertaken at the discretion of the sponsor.

The document ‘Equivalence of herbal extracts in complementary medicines’ assists
sponsors of medicines containing herbal extracts to determine how and when a herbal
extract may be considered 'equivalent' to an ingredient currently included in a
therapeutic good and when it may be used as a substitute without causing the product
to be considered a different therapeutic good.

‘Use of modified unprocessed herbal materials in complementary medicines’ assists
sponsors in identifying situations where the composition of an unprocessed herbal
material has been modified to the extent that it is significantly different from the
original material approved for use in listed or registered medicines.

‘On-going stability testing for listed complementary medicines’ provides guidance on
the development of a stability protocol for complementary medicines. The approach
taken by TGA in relation to stability testing of herbal and certain other listed
complementary medicines, recognises the differences between these types of
therapeutic products and pharmaceutical products that usually contain a single,
chemically defined, active. The approach also recognises the technical difficulties that
may be associated with stability testing of complex multi-ingredient complementary
medicines.

‘Stability testing of listed complementary medicines’ provides common questions and
answers on stability testing.

‘Product quality review for listed complementary medicines’ provides guidance on
product quality reviews, which are part of GMP requirements.

The guideline ‘Process validation for listed complementary medicines’ provides
guidance to ensure that the validation process used is effective in producing a quality
medicinal product.
The TGA has also adopted a number of European guidelines which are provided on the
TGA website. Of particular relevance to listed medicines are:

‘Guideline on stability testing: stability testing of existing active substances and related
finished products’.

‘Note for guidance on quality of herbal medicinal products’ has been adopted by the
TGA and provides guidance to achieve consistent quality for products of herbal origin.

‘Note for guidance on specifications: test procedures and acceptance criteria for herbal
drugs, herbal drug preparations and herbal medicinal products’ has been adopted by
the TGA and provides general principles for setting and justification of a uniform set of
specifications for products of herbal origin.
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Attachment 7b: Raw material specifications
Guidance on raw material specifications is being developed by the TGA and will be
released as part of the consultation process for ‘ARGCM Part C: Evaluation of
complementary medicine substances’.
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Therapeutic Goods Administration
Attachment 7c: Impurities and incidental constituents
Guidance on ‘impurities and incidental constituents’ is being developed by the TGA and
will be released as part of the consultation process for ‘ARGCM Part C: New
complementary substance for use in listed medicines.
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Attachment 7d: Finished product specifications
TGA note: The information below is relevant to Listed complementary
medicines (ARGCM Part B). When Parts C and D are revised, the content will be
expanded to provide any additional, specific information relevant to registered
complementary medicines and new substances for use in listed medicines.
The finished product specification is a description of the product formulation and the set
of tests and limits that are applied to the finished medicinal product in order to ensure
that every batch is of satisfactory and consistent quality at release and throughout its shelf
life. The specifications should monitor all parameters (generally by physicochemical
testing) in which variations would be likely to affect the safety or efficacy of the product
e.g. storage conditions.
The specifications against which a finished product is tested before release for sale are
referred to as the ‘batch release specifications’. The specifications against which a finished
product is tested to ensure satisfactory quality throughout its shelf life are referred to as
the ‘expiry specifications’. Products tested by the TGA are tested for compliance with the
limits in the expiry specifications.
The European guideline ‘Note for guidance on specifications: test procedures and
acceptance criteria for herbal drugs, herbal drug preparations and herbal medicinal
products’ has been adopted by the TGA and provides general principles for setting and
justification of a uniform set of specifications for products of herbal origin.
Where a finished product meets the definition of a monograph in the BP, Ph. Eur. or
USP/NF, this is the minimum standard that must be applied in its entirety, otherwise a
consent of a Delegate is required (refer to ARGCM Part B ‘Consent to supply goods that are
not compliant with certain legislative requirements’).
Note that the BP, Ph. Eur. or USP/NF specifications are expiry specifications. The
requirements of applicable general monographs of the BP, Ph. Eur. or USP/NF must also be
met unless consent is granted/ provided by the TGA. Examples of these general
monographs are those entitled ‘Herbal Drugs’, ‘Herbal Drug Preparations’ and ‘Herbal
Extracts’. Note that the most recent edition of any cited pharmacopoeial monograph or
standard should be used, or a justification for not doing so included.
Data requirements
Batch formulation
A batch formula should include all of the components that will be used in the manufacture
of the finished product and their amounts on a per batch basis (including any overages).
Description of manufacturing process and process controls
Manufacturing steps for listed medicines typically include the manufacture of the dosage
form, packaging and labelling, chemical and physical testing, microbiological testing and
release for supply. Details of the manufacturing process for the finished product should be
available for each manufacturing site and should include information about solvents used,
even if they are evaporated from the product during manufacture.
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Tests, methods and limits
A table of the tests, test methods and limits should be held by the manufacturer and
provided to the sponsor (e.g. assay (GC): 95 to 105 per cent). For dissolution tests, brief
details of the apparatus, medium and limit should be available e.g. dissolution (paddle at
50rpm, 900mL of water, 75% (Q) at 30 minutes).
The specifications must include the requirements listed in any TGO and in the BP, Ph. Eur
or USP/NF general monograph applicable. If there is no BP, Ph. Eur. or USP/NF
monograph specific to the product, the specifications must include all of the requirements
in the BP, Ph. Eur. or USP/NF general monographs (for dosage forms).
Batch release and expiry specifications for all ingredients including excipients
Where the product is subject to a monograph in the BP, Ph. Eur. or USP/NF, the expiry
specifications must include all of the tests and limits in that monograph. It is a legal
requirement for finished products that have a monograph in the BP, Ph. Eur. or USP/NF to
comply with the requirements of that monograph unless another appropriate method has
been validated. Note that this refers to the current editions of each pharmacopoeia.
A summary list that gives details of both the batch release and expiry specifications should
be included. Where the expiry specifications differ from the batch release specifications,
this should be noted. It is unusual for batch release specifications and expiry specifications
to be identical. If this is the case, it should be specifically noted. The specification code
number and date should also be included.
The batch release limits must be chosen so as to guarantee that all batches will comply
with the expiry specifications throughout the product’s shelf life. At a minimum, the expiry
specifications should include all of the tests that are included in the batch release
specifications. Tighter limits are usually applied to critical parameters at batch release, to
allow for possible changes to the product during storage (e.g. decomposition of the active
ingredient).
Proprietary ingredients
The specifications applied to proprietary ingredients should be appropriate to the type of
ingredient, and its function and proportion in the finished product. For an ingredient
blend that contains the active substance, it may be appropriate to have tests for the
identification and content of the active ingredient, and impurity tests.
Colouring ingredients
The document ‘Colourings permitted in medicines for oral use’ is available on the TGA
website. While topical products may include colours other than those listed in this
document, the specifications for colourings used in topical products should be comparable
with those permitted for oral use.
In the absence of a BP, Ph. Eur. or USP/NF Monographs, colours shall conform either to the
specifications in the FAO / WHO Compendium of Food Additive Specifications (as
published by the Joint Food and Agriculture Organization (FAO)/World Health
Organization (WHO) Expert Committee on Food Additives (JECFA) on its website), or to
those defined in the European Commission Directive 95/45/EC (on specific purity criteria
concerning colour for use in foodstuffs – as amended from time to time).
Batch-to-batch variations in the amount of ingredients
The reasons for a proposed range or ranges in the quantities of any ingredients should be
recorded.
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Therapeutic Goods Administration
For some active ingredients, such as herbal substances, the weight of the active raw
material used in a batch of the formulated product may vary according to the content of a
standardised component. Details of the actual weight of active raw material used for each
batch of finished product must be recorded.
Losses of active ingredient may occur during the manufacturing process or during storage,
as a result of the instability of the substance. An overage is where the amount of an
ingredient added during manufacture is greater than that nominated on the product label.
Overages may be used to ensure compliance with expiry specifications. The use of
overages must be justifiable- the use of an overage to compensate for poor analytical
methodology or poor stability performance is not usually considered sufficient
justification. Manufacturers should ensure that batch release assay values (where
performed) reflect any overages used in the product.
Expiry limits for active ingredients are included in Therapeutic Goods Order 78 (TGO 78).
An exemption is required where use of an overage leads to specifications that are broader
than that allowed by the BP/TGO 78.
It is recognised that it may be necessary to vary the quantities of certain excipients from
batch to batch in order to achieve acceptable results during the manufacturing process.
For immediate release complementary medicines, Table 1 provides the permissible
changes to the nominal amounts of certain excipients.
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Therapeutic Goods Administration
Table 1. Changes permitted to the nominal amounts of certain excipients
Excipient type
Acceptable range around the
nominal formulation
pH-adjusting ingredients
qs*
Volume-adjusting fluids
qs
Quantity of ingredients whose function is to contribute to viscosity
+/- 10%
Colour in tablet coating (but not in body of tablet)
qs
Solvent in granulating fluid
qs
Granulating fluid (fixed composition)
+/- 10%
Disintegrant (even if the excipient serves more than one role in the
formulation)
up to +25%
Coating solution
qs
Talc and water-soluble lubricants and glidants
-25% to +100%
Water-insoluble lubricants and glidants, except talc
(e.g. magnesium stearate, stearic acid)
+/- 25%
Filler (bulking agent) in hard gelatin capsules
+/- 10%
Polishing agents
qs
Carriers and potency adjusting ingredients for materials of biological
and herbal origin
+/- 10%
Filler (bulking agent) in tablets and soft gelatin capsules to account
for the changes in the item above
+/- 10%
*qs – quantum satis or ‘as required’
Control of critical steps and intermediates
Tests and acceptance criteria that are applied to critical steps or intermediates in the
manufacture of the finished product should be documented; for example, manufacturing
acceptance criteria for a tablet granulation or in-process controls for pH during mixing of a
syrup.
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Therapeutic Goods Administration
Information required for a finished product specification
Product details

name of product

product code

date of specification

revision or version number

name and signature of the appropriate company official

description of physical appearance

detail of physical tests performed (and limits) including total weight, weight variation,
tests and limits, disintegration tests and limits

a description of the dosage form including any special character (e.g. modified
release); and

packaging type and closure

recommended storage conditions

recommended shelf-life

details of the full formulation including all active and all excipient ingredients
(including coatings and capsule shell ingredients)

the type of container and closure for the product, including the materials used; and

a table of the ingredients in the product and their purpose in the formulation (e.g.
active, disintegrant, antimicrobial preservative). Note this table should provide greater
detail than just the product formulation. It should include overages, if any, and a
reference to the quality standard for each of the ingredients (e.g. compendial
monograph reference or manufacturer’s specifications number); and
Information required for every ingredient in the product should include:

the Australian approved name (AAN)

the quality standard and / or grade

any overages used

the nominal (label claim) amount; and

clear identification as to whether the amount of substance is expressed in terms of the
salt/complex, or base. If the label claim is not in the same terms, the amount in terms
of the label statement should also be stated.
Additional information required for each active ingredient in the product
Information on the active ingredient should be sufficient to adequately characterise the
active ingredient and demonstrate that the active ingredient used in the complementary
medicine will be of appropriate and consistent quality.
The types and level of detail of information depend on the nature of the active ingredient.
The following information should be provided:
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Therapeutic Goods Administration

what is analysed in each batch (marker vitamin for a multi-vitamin product)

what is analysed on rotation, and the frequency

what is not analysed at all, and how the ingredient’s presence is verified in such cases

describe briefly the analytical procedure (HPLC, AA, TLC) applied to each ingredient in
the final product; and

unless covered in a separate document; both the expiry and release limits – upper and
lower.
Where the active ingredient is difficult to characterise quantitatively, such as some
complex herbal extracts, it may be difficult to adequately control the active ingredient
through quantitative specifications. In this case, a combination of specifications and the
detailed method of manufacture may be required to adequately characterise the
substance.
Additional information required for herbal ingredients in the product is:

botanical species and plant part

if an extract, the amount of the extract, the extraction ratio, extracting solvent and
diluting medium and the equivalent amount of dried plant; and

if direct compression tableting materials are used, then, as with herbal extracts,
describe the amount of material used, its equivalence to active substance, and describe
the diluent.
For additional guidance on herbal ingredients, see Attachment 3 ‘Data Requirements for
herbal materials and Attachment 9a: ‘Guidance on the term ‘quantified by input’ for listed
complementary medicines’.
Residual solvents
It is necessary to consider the total amount of residual solvents that may be present in the
finished product. This includes solvent residues resulting from the manufacture of the
finished product.
Depending on the amounts and types of solvent residues, it may be appropriate to include
a test and limits for residual solvents in the finished-product specifications. Tests and
limits in the specifications, or justification for not including them, should be based on the
BP Appendix VIIIL – Residual Solvents.
If the control of residual solvents in the finished-product specifications is deemed to be
unnecessary, then the basis for this decision should be justified and available to the TGA.
Microbiological requirements
Note that medicines required to be sterile cannot be included on the ARTG as listed
medicines.
All non-sterile dosage forms should include limits for microbial content in the finished
product batch release and expiry specifications. The Therapeutic Goods Order No. 77 –
Microbiological Standards for Medicines (TGO 77) specifies the minimum microbiological
requirements with which a medicine must comply throughout its shelf life.
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Microbial specifications for solid oral or dry powder products may not be necessary if it
can be demonstrated during product development that the product is at a very low risk of
contamination and microbial growth.
It is not a requirement that every batch of a product (with a low risk of contamination) be
tested at batch release. Once it has been demonstrated, by testing a number of routine
production batches to establish a product history, that the manufacturing processes do not
permit contamination by excessive numbers of microorganisms, testing may be reduced to
once every 6 to 12 months or some other selected basis (e.g. every tenth batch).
However, products likely to support microbial growth such as products with significant
water content (e.g. creams, gels and oral liquids) should include tests and limits for
microbial content in both the batch release and expiry specifications.
For products containing an antimicrobial preservative(s), expiry specifications should
include tests to ensure the efficacy of preservatives. Given that the effectiveness of many
preservatives is pH dependent, the specifications for such products should usually include
the pH range within which preservative efficacy will be ensured. The expiry limits for the
preservative should be supported by preservative efficacy testing that is performed during
stability testing.
Analytical procedures and validation
Details should be available for all analytical methods used in the specifications, together
with validation data that demonstrate (among other things) accuracy, precision, specificity
(e.g. freedom from interference by excipients, degradation products and other likely
impurities), and linearity.
Guidance on validating analytical test methods can be found in ‘Process validation for
listed complementary medicine’. Complete validation data are not required for methods
described in a TGA recognised monograph or standard. However, data must be available
to show there is no excipient interference and the equipment used must be suitable for the
purpose.
Justification of finished product specifications
The suitability of the tests, limits and test methods for the finished product should include
reference to the results of the method validation studies and the ability of the
specifications to guarantee the quality and consistency of the finished product. A
justification for any unusual features in the finished-product specifications should be
detailed.
The limits applied at batch release should be available and justified in terms of their ability
to ensure that the product will remain within the expiry specification throughout the
product shelf life. For example, if the batch release and expiry limits for assay are identical,
the implication is that there will be no loss of the active ingredient throughout the shelf
life. Any changes or unusual variability in the results obtained in the stability studies
require justification in this respect.
The reasons for proposed range(s) in the quantities of any ingredients should be able to be
justified. Validation data should be provided in support of any unusually wide range(s).
Container information
A description of the container and closure system should be provided, including the
materials used. The suitability of the container should be justified in terms of its
compatibility with the product and its capacity to protect the product from mechanical
damage, moisture and light.
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Therapeutic Goods Administration
In the case of commonly used types of pharmaceutical package, it may be sufficient to
simply describe the packaging. If the packaging material is unusual, then detailed
information should be provided on the composition of the material, together with an
assessment of the potential for undesirable material to be leached from the packaging into
the medicine.

Child-resistant closures
‘TGO 80 – Child-Resistant Packaging Requirements for Medicines’ applies to medicines
containing any of the substances specified in the First Schedule to the Order, as well as
other medicines that imply, through their presentation, that the packaging is childresistant. Presentations considered to indicate child-resistant packaging include closures
with the push-down and turn graphics, typically used on child-resistant caps, and label
statements referring to the closure as being child-safe or designed to prevent access by
children.
TGO 80 specifies requirements relating to the use of child-resistant packaging (CRP) for
medicines which may present a significant risk of toxicity to children if accidentally
ingested and also specifies the performance requirements that packaging must meet in
order to be considered child-resistant.

Tamper-evident packaging
Tamper-evident packaging of therapeutic goods that may be vulnerable to tampering
(either deliberate or accidental) is important in ensuring consumer safety and the
integrity of the goods.
‘The code of practice for the tamper-evident packaging (TEP) of therapeutic goods’ refers
to therapeutic goods that are unscheduled or in Schedule 2 or 3 of the SUSMP and are
administered transdermally, orally or come into contact with mucous membranes.
Sponsors may choose to apply TEP to therapeutic products.

Dose measuring device
Where the packaging includes or refers to a dose measuring device, the device should be
shown to comply with the test and limits of the BP Appendix XIIL – Uniformity of Weight
(Mass) of Delivered Doses from Multi-dose Containers. This is to ensure that the device
consistently delivers an accurate amount of oral dosage forms such as granules, powders
and liquids.
Dose measuring devices included with a container may be required to be included on the
ARTG as a device. Refer to the ‘Australian regulatory guidelines for medical devices’ for
further information.

Dose dispensing from a container
Where the packaging dispenses a dose from a container, other relevant standards may be
applicable. For example, oral drops must comply with the test for dose and uniformity of
dose of oral drops included in the BP monograph for Oral Liquids.
Information for tablets and capsules
If the product is in tablet or capsule form, sponsors should ensure that it complies with the
applicable TGO or general monographs of the BP, Ph. Eur. and USP/NF. Where this is the
case, the finished-product specifications must include details of any test required (e.g.
disintegration), referencing the test limits and test method defined in the Order or
monograph.
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Therapeutic Goods Administration
Dissolution may be an indicator for bioavailability and is considered an important part of
quality control for solid, oral-dosage forms. Sponsors of all solid dosage forms where
feasible, are encouraged to employ dissolution testing. Disintegration testing is not
required where dissolution testing has been performed. TGO 78 specifies the tablets and
capsules for which dissolution testing must be included in the specifications. Further
information on dissolution requirements for specific dosage forms can be found in USP
‘Drug Release’ and ‘Disintegration and Dissolution of Dietary Supplements’.
If there is a BP monograph for the product, but it does not include a dissolution test, and
there is also a USP/NF monograph for the product that does include a dissolution test,
sponsors are encouraged to include the USP/NF dissolution test in the finished-product
specifications.
If there are no pharmacopoeial monographs for the product, or a related product, that
includes a dissolution test, the development of a dissolution test at the time of product
development is encouraged. Once developed, dissolution testing is a valuable tool in
validating changes to the product post-listing.
The results of dissolution testing from stability studies should be used in setting the
dissolution limits for expiry. Note that the inclusion of a dissolution test in the finished
product specifications means that the product must meet the limits throughout its shelf
life, but it does not necessarily mean that every batch must be tested at release.
Modified release products should include dissolution testing data in the finished product
specification. If sponsors wish to employ a non-pharmacopoeial dissolution test, a
justification for the proposed test and limit should be available.
Information for Modified-release products
Modified-release products are dosage forms that have been formulated to release the
active ingredient(s) at a different rate or to release the active ingredient(s) in a different
region of the body compared to a conventional counterpart.
They include products that have been developed for exceptionally rapid release of the
active ingredients. Examples of when modified-release dosage forms may be appropriate
include:

the active ingredient is absorbed and eliminated rapidly (e.g. it has a half-life of less
than 6 to 8 hours) and has a correspondingly rapid loss of effectiveness

the site of absorption is not restricted to a particular part of the gastrointestinal tract

the product is intended for use in conditions of sufficient duration to warrant the use
of a sustained-release formulation; or

the product has to provide therapeutically effective doses of the active ingredient
throughout the dosage interval.
Information about different types of modified-release tablets and capsules is given in
Therapeutic Goods Order No. 78 (TGO 78) General Standard for Tablets and Capsules.
Modified-release formulations should be supported by evidence to demonstrate that the
product meets controlled-release claims. Data should include a justification for the
modified-release formulation based on physiological, clinical and/or bioavailability data.
In vitro and animal studies may be used as supporting data.
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Attachment 7e: Finished product stability
Guidance on finished product stability is being developed by the TGA and will be released
as part of the consultation process for ‘ARGCM Part D: Registered complementary
medicines’.
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Attachment 7f: Certificates of analysis for finished
products
A certificate of analysis (used for ‘release for supply’ purposes) is a document certified as a
truthful statement of the tests and test results for an individual, manufactured batch of a
particular finished product.
The certificate should provide the following information:

the primary manufacturer

the product name

the date of the certificate and the date of the testing

the batch number of the product

the tests and the test results

the acceptable test specifications; these are the test limit or the range of results for
each test with which the batch must comply before release for supply; and

the signature of the appropriate company official.
The range of tests applied to a product is at the discretion of the manufacturer and will
depend on a number of factors including the type(s) of active ingredients and the
pharmaceutical dosage form. Reference should be made to standard pharmacopoeial texts
for guidance on tests and test methods. Some products are also subject to requirements
under Therapeutic Goods Orders (TGOs). For example, a herbal tablet formulation should
include tests for at least:

identity tests for the presence of actives

disintegration time

uniformity of weight

assay of actives (if possible); and

tests for contaminants (if the starting materials are not tested for these individually)
such as microbiological contaminants, heavy metals and foreign matter.
Quantified by input
Guidance on the use of the term ‘quantified by input’ for listed complementary medicines’
(Attachment 9A) describes the criteria under which a manufacturer is not required to
analyse an ingredient in a finished product. It also details the wording that should be used
on a certificate of analysis, where an actual ingredient has been ‘quantified by input’.
Variations in content of some active ingredients
For some active ingredients, such as herbal substances, the weight of the active raw
material used in a batch of the formulated product may vary according to the content of a
standardised component. Details of the actual weight of active raw material used for each
batch of finished product must be held.
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Overages of active ingredients
Overages may be used during manufacture. An overage is where the amount of an
ingredient added during manufacture is greater than that nominated on the product label.
Overages may be used to ensure compliance with end-of-shelf-life specifications. Losses of
active ingredient may occur during the manufacturing process or during storage, as a
result of the instability of the substance. For regulatory compliance purposes, TGO 78
includes expiry limits for active ingredients.
Manufacturers should ensure that batch release assay values (where performed) reflect
any overages used in the product.
Details and justification for overages must be available. An exemption is required where
use of an overage leads to specifications that are broader than that allowed by the
BP/TGO 78.
The use of an overage to compensate for poor analytical methodology or poor
stability performance is not usually considered sufficient justification.
NB: Overages are not to be included in the formulation details section of an
ELF application
Routine variations in excipients
It is recognised that it may be necessary to vary the quantities of certain excipients from
batch to batch in order to achieve acceptable results during the manufacturing process.
Consistent with the requirements for non-prescription medicines, the following changes to
the nominal amounts of certain excipients may be made. Note that this applies to only
immediate release complementary medicines (See Table 1 Attachment 7C.)
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Attachment 8: Medicine labels
TGO 69 provides the following definition:
‘label’ means a display of printed information upon, or securely affixed to, the
container and any primary pack containing the goods’
A product’s ‘label’ includes the label attached to the container (e.g. bottle, tube, sachet or
blister pack) and the primary pack (e.g. carton). Sponsors must ensure the product label
and any printed information supplied (e.g. a package insert) complies with all relevant
legislation and advertising requirements and also, is appropriate for the claimed
therapeutic use in the targeted population group e.g. an illustration of an infant would be
inappropriate for a product with a dose range starting at 6 years.
Medicine labelling must comply with the following:

The ‘Therapeutic Goods Order No 69- General requirements for labels of medicines’
(TGO 69) (and amendments TGO 69A, TGO 69B and TGO 69C) provides the
requirements for medicine labels including how information should be displayed, e.g.
active ingredient, dose, directions for use, expiry date, batch number etc.

Part 5-1 (Advertising and generic information) of the Act and the Advertising Code
outline the advertising requirements for therapeutic goods so that the marketing of a
product promotes quality use and does not mislead or deceive the consumer.

The ‘Required advisory statements for medicine labels’ (RASML) provides a list of
mandatory advisory statements that, under TGO 69, must be included on a medicine
label.

Any conditions of listing (see ‘Conditions of listing’ ARGCM Part B).
Language on medicine labels
The information on the labels should be written in clear and easily understood English.
Text in languages other than English may be included on labels, provided that all
mandatory information is on the label in English. A certified declaration may be required,
during a listing compliance review of the product, to confirm that the meaning in the other
language text is the same as that given in the English text.
Ingredient details on medicine labels
The TGO 69 and Part 2 of Schedule 2 to the Regulations require that labels include the
name and quantity of all active ingredients, any preservative in a topical product and the
names of specified excipients. All information on medicine labels should use Australian
approved terminology (refer to ARGCM Part A and the TGA’s approved terminology for
medicines). If sponsors wish to include details of other ingredients (that are not required
to be declared) on a label, the following conditions apply:

The selective disclosure of an individual excipient on a medicine label is generally not
acceptable (with the exception of cosmetic components in a sunscreen), as this could
imply that the excipient has a therapeutic activity. For example, it is not acceptable to
make a statement, ‘contains vitamin C’ when the product contains a sub-therapeutic
dose of ascorbyl palmitate (vitamin C) as an antioxidant excipient.

It is acceptable to declare on a medicine label excipients that are known to cause
adverse effects in some individuals (however, in most cases, this is already a
requirement under the First Schedule to TGO 69).
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
Quantitative or qualitative statements on the medicine label of all excipient
ingredients in the product are permitted.
Directions for use and dosage on medicine labels
TGO 69 requires that labels state the product’s method, dose and frequency of
administration. Non-specific directions such as ‘take as required’ are generally not
appropriate. Directions for use must clearly identify the dose for each target population
for which the product is intended i.e. adult and child doses. If the product is not intended
for use in children, the label should specify that the dose is an adult dose (e.g. ‘adult dose:
10 mL’). Where the labelling gives doses for children over a specified age, the label should
include a statement such as ‘Do not give to children under 12 years’ or ‘Not recommended
for children under 12 years’.
Where a product has multiple indications and the different indications require different
doses (as supported by the evidence held by the sponsor), the directions for use should
specify the particular recommended daily dose for each indication.
Labelling should recommend use of metric measuring devices to accurately measure
doses. Where the recommended doses cannot be measured using a readily available
metric measuring device, a suitable measuring device should be provided in or as part of
the pack. References to culinary ‘spoonful’ (e.g. teaspoon, dessertspoon, tablespoon etc.)
are not acceptable.
Warning statements and required representations on medicine labels
The TGO 69 and Part 2 of Schedule 2 of the Regulations require warning statements and
required representations, where these apply to the medicine, to be included on the
medicine label. Some warning statements have specific requirements in relation to the text
appearance and position on labels.
Many warning statements relate to safe use of the medicine (e.g. where an incorrect route
or method of administration may be hazardous) and sponsors should be aware that failure
to include them on a medicine label could result in product recall.
Some indications require mandatory warning statements on the label. For example,
products with the indication ‘relief of the symptoms of colds’ require two warnings to be
included on the label, in addition to directions for use:

‘If symptoms persist consult your healthcare practitioner’ (or words to that effect);
and

‘Adults only’ or ‘Not to be used in children under two years of age without medical
advice’ (or words to that effect).
Negative disclosure statements on medicine labels
A product label may include a statement that the product does not contain a substance
known to cause adverse effects in some individuals (e.g. ‘gluten free’, ‘alcohol free’)
provided the statement is true.
If the label includes a statement that the product does not contain a substance, sponsors
should ensure that the substance is not contained in any ingredient in the product
formulation. For products containing proprietary ingredients, sponsors must check with
the manufacturer of the ingredient to ensure the integrity of the label statement.
Inclusion of a statement that the product contains no sugar is acceptable provided sucrose,
glucose, fructose and other sugars with a cariogenic potential or the potential to affect
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diabetics are not included in the formulation. In addition, the formulation of the active
ingredient(s) (in addition to excipients) should be carefully examined to ensure that
carriers etc. do not contain sugars with a cariogenic potential.
Distinctiveness of labels and reference to other products
To reduce the possibility of confusion among consumers, the name and presentation of a
new product should be clearly distinguishable from other products.
A sponsor may refer to another product (within their product range) on the medicine
label, provided that their other product is included on the ARTG (or exempt from the
requirement to be included on the ARTG).
Product labels for listed medicines are not submitted to the TGA at the time of listing via
ELF and are therefore not approved by the TGA. However, medicine labels may be
reviewed as part of the TGA’s random and targeted compliance reviews (see ARGCM Part
B: ‘Listing compliance reviews’).
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Attachment 9a: Guidance on the use of the term
‘quantified by input’ for listed complementary
medicines.
This guidance document should be read in conjunction with the Attachment 9B ‘Questions
& answers on the use of ‘quantified by input’.
Background
Under good manufacturing practice (GMP), for medicinal products it is a requirement that
all active ingredients in medicines be tested to confirm that the content complies with
prescribed standards. However, it is recognised that in some circumstances this may not
be possible or practical to achieve. Where it is established that such medicines are
manufactured in accordance with the principles of the GMP, and other criteria are met,
quantitative testing of the active ingredient in the finished product may be omitted and the
ingredient in the product ‘Quantified by input’ (QBI).
Scope
This guidance document describes the criteria under which a manufacturer of a listed
complementary medicine would not be required to assay an active ingredient in a finished
complementary medicine product. The document also provides wording that a
manufacturer could use on a certificate where an active ingredient (see note 1) has been
QBI. Please note that the guidance provided in this document does not override or replace
the need to comply with all relevant statutory requirements. This guidance does not
extend to medicines other than complementary medicines nor is it applicable to other
medicines containing a complementary medicine component.
It is intended that this document be used by manufacturers, in consultation with the
relevant sponsor, as part of product development. It is most relevant where a quantitative
claim (see note 2) is made for a particular active ingredient in a complementary medicine.
However, in certain circumstances, these principles may also be applied to excipients
and/or components in ingredients that are considered to be ‘restricted ingredients’ (see
note 3). Diagram 1 provides a flow chart that outlines the assessment process that should
be applied.
Principles
Consistent with the Therapeutic Goods Administration’s (TGA) risk-based approach to the
regulation of medicines, it may be possible to justify certain situations where it is not
necessary to assay an active ingredient in every batch of finished product. In such
situations, the content of an active ingredient may be estimated from the amount
dispensed during the manufacture of the product. This practice is termed ‘Quantified by
input’ (QBI). However, based on risk to consumers, it is not appropriate to apply this
practice to all ingredients. The application of the principles of QBI to a particular active
ingredient in a product is based on the following factors:
1.
The manufacture of the complementary medicine product must be undertaken in
a facility that is deemed by the TGA to be GMP complaint.
2.
The ingredient in the medicine is approved for use in listed medicines. For
ingredients that have quantity-based restrictions, it is expected that an assay in
the finished product would be performed. However in some specific
circumstances, where justified, rotational testing or the performance of a
validated limit test may be acceptable.
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Where a manufacturer does not intend to assay an active ingredient in a batch of a
complementary medicine, this decision must be supported by written justification. The
justification may be reviewed at a TGA GMP inspection of the manufacturer or by the TGA
during a listing compliance review. In justifying the use of QBI and therefore not
undertaking an assay, the issue of what constitutes a reasonable attempt at performing an
assay is difficult to judge with objectivity. It may often be a subjective judgement as to
whether the justification for not assaying is sufficient. In such cases discussion with the
TGA may help to resolve the issue.
Assessing the suitability of an active ingredient in a batch of a listed complementary
medicine for quantifying by input:
When determining whether the content of an active ingredient/component in a listed
complementary medicine could be QBI, the following points need to be addressed:

the intent to make quantitative claims for the ingredient in the finished product

any restrictions applicable to the ingredient or any component in the ingredient, e.g.
referred (see Note 4) to in the Standard for the Uniform Scheduling of Drugs and
Medicines(SUSMP) or inclusion in Schedule 4, Part 4, Divisions 1 and 2 or Schedule 4,
Part 5, Division 2 of the Therapeutic Goods Regulations 1990 (the Regulations)

the performance of any relevant quantitative testing (assay) of the active raw material
by a TGA licensed or approved manufacturer; and

the availability of a validated assay method for the ingredient/component in the
finished product.
Many ingredients of biological origin used in complementary medicines are not single
component ingredients (e.g. shark cartilage, non-standardised herbal extracts). In these
situations, where the ingredient/component is not subject to any restrictions and no
associated quantitative claims are made in the finished product, the ingredient may be
quantified by input. The words ‘Not assayed, quantified by input’, or words to that effect,
may be used on the certificate of analysis of the finished product.
In cases where the active ingredient consists of a single component, or where a
quantitative claim is made for any component within an ingredient, it is usually expected
that the ingredient/component would be assayed in the finished product. This is
particularly important when, to ensure the safety of the medicine, an ingredient/
component is subject to restrictions in any relevant legislative instrument.
However, in certain situations it may be justifiable to QBI such ingredient/components,
including those that are restricted, and not assay the finished product. This could occur as
part of a rotational testing program (see Note 5), where, for certain batches of medicine,
the assay of a specified ingredient/component would not be performed. In these cases, a
statement such as: ‘Quantified by input. This ingredient is part of a rotational testing
program and was not assayed in this batch’ may be used on the certificate of analysis of
the finished product.
Further, the use of a validated limit test (see Note 6) may be able to be justified. The use of
such a test may provide an acceptable level of assurance that the ingredient/component is
present at a level which would exclude the medicine from a schedule of the SUSMP or
restriction as defined in the Regulations.
In other instances, the formulation of the medicine may be of such complexity that a
validated assay method for the ingredient in the finished product is unavailable or is
difficult to achieve. To be able to apply the principles of QBI to the manufacture of these
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medicines, the potency of the ingredient/component must have been established by a TGA
licensed or approved manufacturer prior to inclusion in the formulation. Once this has
been done, the words ‘Not assayed. Quantified by input’ may be used for the
ingredient/component on the certificate of analysis of the finished product.
For multi-active medicines (e.g. multivitamin/mineral complexes) it may be justifiable to
use QBI for ingredients for which a validated assay method for testing the finished product
is available. If the quality and safety of the medicine is assured through other testing, the
assay of certain ingredients may be put on a rotational testing program. Again, this can
only be applied if the potency of the ingredient/component has been established by a TGA
licensed or approved manufacturer prior to inclusion in the formulation. Once this has
been done, the words ‘Not assayed, quantified by input’ or ‘Quantified by input. This
ingredient is part of a rotational testing program and was not assayed in this batch’ may
be used for the ingredient/component on the certificate of analysis of the finished product.
Implementation
Consistent with the principles and guidance in this document, some testing must be
performed on each batch of the finished product where a quantitative claim is made on the
label. That is, there must be sufficient testing to provide assurance that the product is of
intended quality (see Diagram 1: Flow chart for determining the requirement for assay of
an active ingredient).
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Diagram 1: Flow chart for determining the requirement for assay of an active
ingredient
Is the ingredient, or any component in the ingredient, referred to in a schedule of the SUSDP or
otherwise restricted?
Any ingredient or component subject to a restriction or referred to in the SUSDP should
be assayed in the finished product. Rotational testing may be acceptable where
supported by documentation. With suitable justification, the ingredient can be quoted
on the certificate for the finished product as ‘Quantified by input. This ingredient is part
of a rotational assay program and was not assayed for this batch’.
Yes
Tex
t
No
Tex
Tex
t
t
Tex
Tex
t
t
Is the active ingredient primarily a single component ingredient?
Tex
t e.g vitamin
Yes
No e.g. herbal extract
Text
Text
Text
Text
Is a quantitative claim made for any component in the documentation for the product?
Text
Text
Yes e.g. standardised herbal
extracts
No e.g. shark cartilage with no equivalency statements or
a simple herbal extract stated as being equivalent to the
fresh herb.
The words ‘Not assayed, quantified by input’ (or words to this effect) may be used
on certificates for the finished product
Has the potency of the active ingredient/component been tested by a TGA licensed or approved
manufacturer?
The finished product manufacturer should assay the ingredient at input. The
ingredient should be quoted on the certificate for the finished product as ‘Not
assayed, quantified by input’ (or words to this effect). In all cases, some testing must
be performed on each batch of the finished product. That is, sufficient testing to
provide assurance that the product is of intended quality should be carried out.
Yes
No
Is a valid assay available for the ingredient or component in the finished product?
Yes
The ingredient should be assayed in each batch of the finished product.
No
Ingredient or component can be quoted on the certificate for the finished product as
‘Not assayed, quantified by input (or words to this effect). Rotational testing for this
ingredient/component should be considered. In all cases, some testing must be
performed on each batch of the finished product. That is, sufficient testing to provide
assurance that the product is of intended quality should be carried out.
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Refer to notes 7, 8 and 9 when considering this flowchart
Notes
Note 1: An ‘active ingredient’ is the therapeutically active component in a medicine’s final
formulation which is responsible for its physiological or pharmacological action (as
defined in Section 52F of the Act).
Note: 2: A ‘quantitative claim’ is a claim made for a medicine which states that a particular
quantity of an ingredient, or component in an ingredient, is present in the medicine.
Note 3: An ingredient, or component within an ingredient, is considered to be ‘restricted’
where there is a quantity or concentration based restriction referred to in a legislative
instrument such as the SUSMP, Schedule 4 of the Regulations, a condition of listing, etc
(see definition of ‘restricted ingredient’ below).
11(2) A substance is a restricted ingredient if:
(a) it is an ingredient in a relevant medicine; and
(b) for that medicine to be, or to remain, eligible for listing, the permissible quantity or
concentration of the substance in the medicine is restricted by operation of any of the following:
(i) Schedule 4;
(ii) the Poisons Standard;
(iii) a condition imposed under section 28 of the Act;
(iv) a standard under section 10 of the Act;
(v) the Required Advisory Statements for Medicine Labels document;
(vi) any other provision in these Regulations or in the Act that deals with eligibility of medicines
for listing.
11(3) In this regulation:
relevant medicine means a medicine that is listable goods or listed goods and that is not an
export only medicine.
Where a quantity based restriction may apply to an ingredient or component it is
generally not appropriate for that ingredient to be QBI because of the on-going need to
confirm that the medicine meets the quantity based restriction and remains safe. This
means that any ingredient referred to or mentioned in any of the legislative instruments
may generally not be QBI, irrespective of whether or not the quantity based restriction
applies.
Note 4: A substance may be ‘referred’ to or mentioned in the SUSMP, but it may not be
‘included’ in a Schedule. That is, it may not be subject to the requirement of the SUSMP
entry because the quantity/concentration of the ingredient is below that specified in the
entry. It should be noted that, by definition, a listed medicine cannot contain any
substance that is included in a Schedule.
For example, Vitamin D preparations are referred to in the SUSMP for internal human
therapeutic use, although preparations containing 25 micrograms or less of vitamin D per
recommended daily dose are not subject to restrictions in the SUSDP. Therefore:

medicines which contain vitamin D at levels that provide a daily dose of more than 25
micrograms are included in Schedule 4 and cannot be used in Listed medicines; and

for Listed medicines which provide 25 micrograms or less of Vitamin D, a Vitamin D
assay of the finished product must be performed.
In instances where reference to an ingredient in a legislative instrument only relates to a
requirement for a warning statement (e.g. Hypericum perforatum in Schedule 4, Part 4,
Division 2 of the Regulations), that ingredient may, subject to the principles of this
document, be eligible for quantification by input. Please note that this would not be the
case if the warning statements are quantity dependent.
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Note 5: Rotational testing is the performance of specified tests on pre-selected batches
and/or at predetermined intervals, rather than on a batch-to-batch basis with the
understanding that those batches not fully tested must still meet all acceptance criteria
established for that product. This represents a less than full schedule of testing and should
be supported by written justification. This justification may be reviewed at a TGA GMP
inspection of the manufacturer or by the OCM.
Note 6: A ‘limit test’ is a semi-quantitative assay for a component in a product. It generally
provides a pass/fail result for the component. It should be developed with suitable
specificity, precision and accuracy, but it is not expected to provide an exact value.
The use of a validated limit test may provide an acceptable level of assurance that a
particular ingredient or component is present in a product at levels consistent with low
risk and, subject to the principles of this document, be eligible for quantification by input.
In instances where restrictions in the SUSDP or in Schedule 4 of the Regulations apply to
an amount of an ingredient/ component in a recommended daily dose, the application of a
limit test will require knowledge of the recommended dose. In instances where this is not
known, manufacturers should liaise with the product’s sponsor to ascertain this
information.
Note 7: QBI does not replace the need to comply with relevant statutory requirements.
Note 8: Any alternative wording must clearly indicate that an assay of the ingredient in
the finished product has not been performed.
Note 9: The use of a validated limit test to establish that an ingredient, or component in an
ingredient, is not subject to a quantity based restriction, may provide suitable justification
to permit the ingredient to be quantified by input.
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Attachment 9b: Questions and answers on the use of
‘quantified by input’
The approach taken by TGA (to permit the quantification by input of low risk ingredients
in a finished complementary medicine) recognises the technical difficulties that may be
associated with quantifying certain ingredients in multi-ingredient products.
The sponsor of a medicine has ultimate responsibility for the product. However, the
certifying of a product to be in compliance with its marketing authorisation is considered a
step of manufacture. This step, also known as ‘Release for supply’ requires a suitably
licenced to manufacturer (within Australia) or that the sponsor hold a suitably annotated
GMP clearance on behalf of an overseas manufacturer. Some third parties, such as
consultants, may hold a licence to manufacture therapeutic goods which is limited to the
step of ‘Release for supply’. In releasing the product for supply, the site authorised to
perform that step must ensure (among other requirements) that the product label,
manufacturing formula, and specifications are consistent with the entry in the Australian
Register of Therapeutic Goods (ARTG).
1. Could a new formulation (product) be produced that uses QBI for an ingredient,
or a component in an ingredient, in the product without a QBI justification having
been completed prior to launch?
NO: It is important, when developing a new product, to ensure that justification of the use
of QBI for any component, or ingredient, is included as part of development, including
verification of a starting material supplier's competency to provide a valid assay result.
2. In the case of a finished product containing a herbal extract, where no
quantitative claim is being made for a component in the extract:
i. Is it appropriate to state on the Certificate of Analysis, ‘Not assayed,
quantified by input’?
YES: Provided the ingredient or component of the ingredient is not referenced in
the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP), or not
otherwise restricted.
ii. Do I have to do a profile test for QBI release?
NO: Profile testing is considered to be an identity test and identity tests are not
relevant to QBI. The identity of each ingredient should be assured before it is used
in manufacture.
3. A generic test method has been validated for a particular active ingredient in a
defined group of products, but has not been fully validated for the assay of the
ingredient in a new product. The method gives expected and reproducible results
for the active in batches of the new product.
i. Can the result of the assay of the active be included on a certificate of
analysis for that batch of the finished product?
NO: The analytical result cannot be included on the certificate of analysis for that
batch. Validation needs to be performed to confirm the validity of the test method
when applied to the new product. See guidance document ‘Finished product
(medicine) analytical procedure validation’.
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ii. Should the ingredient be declared as QBI because the test method has not
been fully validated for the active in this product?
NO: A QBI statement may only be used for the ingredient if it meets QBI guidance
criteria. That is, there is written justification that a validated assay method is not
available for the ingredient or component in the finished product. Otherwise a
validated analytical test method must be applied.
It should be possible to validate an analytical method for a group of products,
provided the grouping justification is scientifically sound and defendable. In this
case the justification should be documented. The information may be reviewed by
an inspector during a GMP inspection or by the TGA during a listing compliance
review.
Note: It is expected that each laboratory will have a standard operating procedure
for assay validation. This could include reference to the TGA or other validation
guidance document. Laboratories are expected to follow their standard operating
procedure to develop a valid assay method.
4. (a) In terms of equipment, level of knowledge and cost, how much effort should be
made to develop a valid assay for an active in a finished product?
There are a range of techniques that most laboratories would be expected to have
available or have access to. These techniques would be expected be consistent with those
generally used for quality assurance in pharmacopoeial monographs. The use of novel or
highly specialised technologies is not expected for testing complementary medicines.
It is expected that analysts will have a full working knowledge of the equipment and its
capabilities, and the operators in a company should be able to develop new methods using
the equipment. Preferably, there should be a standard operating procedure for the
development of new assay methods which includes searching the relevant literature. For
example, when using a high-performance liquid chromatography (HPLC) assay method, if
appropriate markers, reference compounds and columns are reasonably available, then
these should be used. It would not be acceptable to justify the use of QBI because the HPLC
conditions could not be varied sufficiently to produce a valid assay.
4. (b) While a valid assay is being developed, in the interim can QBI be used?
NO: This is not acceptable practice for either an existing or new product (see also question
1 above).
As the question of whether or not QBI is appropriate for a particular ingredient should be
part of product development, the relevant decisions should be made before generation of a
certificate of analysis. Therefore, written justification for use of QBI should be developed
and included with product specifications. Although this involves the manufacturer, the
sponsor is still ultimately responsible for the product and is required to obtain such
details from the manufacturer prior to commencement of supply.
5. Does the QBI guideline apply to both listed (AUST L) and registered (AUST R)
complementary medicines?
QBI generally applies to listed complementary medicines. However, the use of QBI for a
registered complementary medicine could form part of the TGA registration application/
evaluation process where, in certain instances, the principles may be able to be applied.
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6. In some situations, the use of QBI for an ingredient, or a component in an
ingredient, is subject to a validated limit test*. If the limit test has not yet been
validated for the product containing the ingredient/component can QBI be used?
No: The limit test must be validated before QBI can be used.
*A 'limit test' is a semi-quantitative assay for an analyte in a product. It should be developed with suitable specificity,
precision and accuracy, but it is not expected to provide an exact value.
7. Can QBI be used if a manufacturer states that they cannot perform a validated
limit test:
(a) on a restricted component in the finished product?
YES: If the level of the restricted component in the herbal extract has been tested
by a TGA licensed or approved manufacturer AND the level has been shown to be
acceptably low. In all cases, some testing must be performed on each batch of the
finished product. That is, sufficient testing should be carried out to provide
assurance that importantly, the medicine is safe, and of intended quality.
(b) of the standardised component of a herbal extract in a finished product?
YES: If the potency of a standardised component has been tested by a TGA licensed
or approved manufacturer. In all cases, some testing must be performed on each
batch of the finished product. That is, sufficient testing should be carried out to
provide assurance that importantly, the medicine is safe, and of intended quality.
8. My manufacturer is using a herbal extract that is standardised to a particular
component. However, I am not relying on that component in my claim
substantiation, nor is it included on the product label or in my electronic listing
facility application. Do I have to assay the component if no quantitative claim is
being made?
NO: It is not subject to QBI requirements, because no claim is included in the Australian
Register of Therapeutic Goods (ARTG) or made on the label for the standardised
component in the herbal extract that is used in the finished product.
9. In the case of an ingredient that is not subject to restrictions, may I choose
whether to quantify the ingredient by input or to include the ingredient as part of a
rotational testing program?
NO: Rotational testing and QBI are based on separate principles. If a valid assay is
available for the ingredient in the finished product, this testing must be performed. It is
possible that a rotational testing program may be implemented, with appropriate
justification. In this case, for specific batches, the ingredient may be noted on the
certificate of analysis as 'Quantified by input - part of a rotational testing program'.
Conversely, if a valid assay is NOT available, and other relevant criteria are met, the
ingredient may be able to be 'Quantified by input' in the finished product. The use of QBI is
based on the inability to assay the ingredient at all.
10. When using rotational testing, can the testing laboratory (or the sponsor) select
a particular active(s) to be tested from all eligible actives that might be rotationally
tested?
NO: Rotational testing is the performance of specified tests on pre-selected batches and/or
at predetermined intervals, rather than on a batch-to-batch basis. A predetermined
rotational testing program for all relevant actives should be applied. This is undertaken
with the understanding that those batches not being tested still must meet all acceptance
criteria established for that product. It is inappropriate to always test the same active(s)
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January 2013
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Therapeutic Goods Administration
from a list of rotationally tested actives. Under a rotational testing program,
manufacturers and/or sponsors can require additional testing of an active for any reason,
for any batch, containing that active.
11. What is meant by a validated assay method and a valid assay result?
As a minimum, a validated assay method for an active ingredient in a finished product is
one that meets the requirements of the TGA's ‘Finished product (medicine) analytical
procedure validations for complementary medicines’ guideline'. A valid assay result is one
that has been obtained using a validated assay method.
A valid assay result may be in or out of specification. Batches out of specification may be
acceptable in certain circumstances - where they are in accordance with the ARTG record
of the product and all deviations and 'out of specification' results have been satisfactorily
addressed. These activities and their records are subject to inspection by the TGA.
12. Is there standard template that can be used for a QBI justification statement?
NO: There are certain essential elements that should be included in QBI justification
documentation. Documentation should be appropriately authorised. As a minimum, the
following information should be included:

the identity of the product (AUST L)

the sponsor and manufacturer

the ingredient(s) that have been QBI; and

justification of why QBI has been used, consistent with the criteria detailed in
Attachment 9a: Guidance on the use of the term ‘quantified by input for
complementary medicines.
ARGCM Part B
January 2013
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Therapeutic Goods Administration
PO Box 100 Woden ACT 2606 Australia
Email: info@tga.gov.au Phone: 1800 020 653 Fax: 02 6232 8605
www.tga.gov.au
Draft ARGCM Part B R12/1074080