permitted indications for listed medicines
TRANSCRIPT
Complementary medicines reforms
sponsor education workshops
Permitted indications for listed medicines
Michael Shum
Director, Complementary and OTC Medicines Branch
Medicines Regulation Division, TGA
Recommendation 38: Permitted Indications
Recommendation 38
The Panel recommends that the TGA establishes the list of Permitted Indications, from
which sponsors must exclusively draw, for listed medicinal products in the ARTG.
Government response
The Commonwealth accepts Recommendation 38, noting that implementation of the list of
Permitted Indications will require legislative change and will be subject to consultation with
consumers, sponsors and health professionals.
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Objectives
The purpose of establishing the list of permitted indications is to:
• ensure that listed medicines can only make low level indications that are suitable
for medicines that do not undergo pre-market assessment
• provide transparency for sponsors on what indications are suitable for listed
medicines to help prevent inadvertent non-compliance
• avoid consumers from being misled by inappropriate indications on listed
medicine labels
These objectives need to be balanced to ensure flexibility for industry
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What does this mean for sponsors?
• Sponsors listing a medicine on the ARTG will only be able
to use indications from a permitted indications list
• “Free text” field will no longer be available
• Sponsors must continue to hold supporting evidence for
their medicine indications
• There must not be inconsistency between the indications
that are listed in the Register and on the label
• 3 year transition period for existing listed medicines
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Legislative overview
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Legislative framework
• Medicines, including complementary medicines, are regulated
under the Therapeutic Goods Act 1989 (the Act)
The Act sets out the legal requirements for the import, export,
manufacture and supply of therapeutic goods in Australia
The Act is supported by the Regulations, and various legislative
instruments (e.g. Orders and Determinations) which provide
further details of matters covered by the Act
• Introduction of the permitted indications reform requires a number of legislative and
regulatory changes and new legislative instruments
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Legislative changes for permitted indicationsApplication and certification changes
• Introduce new requirement for medicines that are
listed under 26A must only make permitted indications
• Indications on the label and in the Register must be
consistent
Establishing the list of permitted indications
• Enables the Minister to determine
a list of ‘permitted indications’ or
a list of ‘non-permitted indications’
Application procedures and criteria for new indications
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Legislative changes for permitted indications
• Consequential amendments
– Conditions of listing
– Cancellation provisions
• Transitional arrangements for existing products
– All existing products to be re-listed
– Provisions to ensure that sponsors can maintain
continuous legal supply
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Transition arrangements
• From 1 January 2018, all new listed medicines must select permitted indications
(free text will be turned-off)
• Sponsors of existing listed medicines will be required to transition their existing
indications to ‘permitted indications’ by 31 December 2020:
AUST L numbers will not change (where ‘grouping’ applies)
Fee waiver if indications changed by 30 June 2019
• Listed medicines that do not transition to permitted indications will be cancelled
from the ARTG from 1 January 2021
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Transition arrangements – product changes
• During the transition period, any product that is the subject to changes that amount to it
being a separate and distinct good under the Act must transition at the time of making
the change
• These include changes to:
active ingredient or quantity of active ingredient
dosage form
product name
excipients
indications
• Other product changes (9D variations) will not be required to transition at the time of the
change
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What if my indication is not on the permitted list?
• Before the end of the 3 year transition period,
sponsors will be required to either:
1. transition to ‘permitted indications’ by
selecting appropriate indications from the list
2. apply to add a new indication to the list and
then apply to list their product; or
3. if the medicine has higher-level indications,
apply to list their medicine through the new
assessed list medicine pathway
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Regulation amendments
Is your medicine eligible for listing?
Approved
ingredients
Preparation not in
Poison StandardQty restrictions not
exceeded
Not required to
be sterile
Must only make permitted indications
Sponsor certifies that the medicine is eligible for listing
Product is listed – assigned ARTG number
(AUST L XXXX)
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Establishing the list of permitted indications
• The list of permitted indications will be made as a legislative
instrument containing:
a comprehensive list of low risk indications that must be
used to list a medicine in the ARTG
'requirements‘ relating to the use of indications
‒ including general rules for how permitted indications
are entered in the register and used on medicine
labels
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What is a permitted indication?
• A permitted indication describes a therapeutic use for a listed
medicine
• Therapeutic use for listed medicines means use in, or in connection
with, ‘influencing, inhibiting or modifying a physiological process in
persons’
• Indications can be:
specific (e.g. refer to a named non-serious condition); or
non-specific (e.g. general health maintenance)
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Permitted indications – structure• Permitted indications have a consistent structure and terminology to describe the
therapeutic uses that are appropriate for listed medicines
• All permitted indications contain an ’action’ and a ’target’
Action
qualifier
E.g ‘Help’
Action
E.g. ‘maintain/
support’
Target
qualifier
E.g. ‘healthy’
Target
e.g. ‘joints’
E.g. Help to maintain/support healthy joints
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Non-indication statements and claims• Statements that do not describe a therapeutic use will not be included in
the permitted indication list, for example:
Marketing statements
• e.g.: ‘Fast action formula’
Claims of effectiveness
• e.g.: ‘Improves by 10%’ or ‘Water resistant’
Structure, function, and/or mechanism of action statements
• e.g.: ‘Calcium is a natural component of bone’.
In some cases you may need to ensure you have chosen a
related permitted indication
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Non-indication statements and claims
• Non-indication statements are not required to be included on
the ARTG in order to be used on product labels or other
promotional material
• However, you must certify that you hold information or
evidence to support any statement/claim included on your
medicine label
• Your medicine may be cancelled from the ARTG if you hold
incomplete or insufficient evidence to support all claims made for
your product
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Criteria for permitted indications• Permitted indications meet the criteria for low-level indications:
health enhancement, e.g. ‘May reduce fatigue’
health maintenance, e.g. ‘Helps support healthy joints’
prevention of dietary deficiency, e.g. ‘May prevent calcium
deficiency’
a non serious form of a disease or ailment etc., e.g. ‘Helps
decrease/ reduce/relieve symptoms of common cold’
These are conditions that are self-diagnosable or self-
manageable
An exception to these criteria will be made for indications linked to substance-based
restricted representation approvals (folic acid, calcium and vitamin D)
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Requirements – Type of evidence
‘General’ indications Can be supported by either scientific evidence or a tradition of use, e.g. ‘Relieve dry
skin’
Traditional indications Include traditional terms that may be applicable across multiple traditional
paradigms, e.g. ‘cholagogue’, ‘alterative’ ‘adaptogen’ and must be support by a
tradition of use.
Traditional Chinese
Medicine indications
Contain TCM specific terminology and must be supported by evidence of TCM use,
e.g. ‘Increase Qi flow’
Traditional Ayuvedic
Medicine indications
Contain Ayuvedic specific terminology and must be support by specific evidence of
use, e.g. ‘Balance Vata
Scientific indications Must be supported by scientific evidence only, e.g. ‘Helps maintain/support bone
mass/density’
Traditional medicines must include a traditional use qualifier in the ARTG and on the product label
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Specific requirements for permitted indications
• There will be requirements relating to the use of certain indications in a listed medicine
• The requirements may specify circumstances when an indication can or cannot be used
or specify conditions that must be met. For example, requirements may:
Require a warning statement to be included on product labels, e.g.: 'If symptoms
persist consult your healthcare practitioner (or words to that effect)'
Specify a vulnerable population for which the indication is not suitable, e.g.: ‘Not
suitable for use in children under the age of 12 months’
Require that the presentation of the medicine must not refer to or imply a serious
form of a disease
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Permitted indications - Examples
The legislation will allow for cancellation
of a medicine from the ARTG if the
requirements relating to the use of the
permitted indication are not complied with
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Indications catalogue
• All listed medicine indication information and associated
restrictions will also be available in an online database
• Updates to the online database will be made to
match updates to the Permissible Indications
Determination
• Ability to conduct searches using indication
information such as; key words, phrases,
evidence requirement or body part/system
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How to use permitted indications in your listing
application
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How to select permitted indications for your
medicine
• Step 1: Review the evidence that you hold for your permitted indications
• Step 2: Select a ‘core’ permitted indications (action and target only)
• Step 3: Select qualifying terms to align indications with the evidence you hold for
your medicine.
• Step 4: Ensure that the medicine label is compliant with all necessary regulatory
requirements
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Step 1: Review the evidence for your medicine
• Sponsor must hold evidence for all indications and claims
• Best practice to review your evidence to make sure they
supported your indications
• Evidence Guidelines provide guidance on:
Types of indications and evidence sources
Assessing relevance, quality and credibility
Obtaining, recording and presenting evidence
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Step 1: Review the evidence for your medicine
• We will make minor modifications to the Evidence
Guidelines for Listed Medicines prior to the permitted
indication reform coming into effect
• We are planning a complete review of the evidence
guidelines next year
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Step 2: Selecting a core permitted indication
• ELF will allow you to search for and add permitted indications into your
ARTG entry.
Evidence Requirement, e.g.:
Scientific or tradition of use
Key word / phrase, e.g.: ‘cough’ or
‘itchy’
Body system / part, e.g.: ‘Body - ear’
or ‘Gastrointestinal - Bowel’
Indication Code, eg: BDEYH-S-MS
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Step 3: Selecting evidence qualifiers • You will be able to select appropriate evidence qualifiers to make a permitted indication
more specific and align with the evidence you hold for your medicine
• If a qualifier is included on the Register, it must be included on your product label
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Step 3: Selecting evidence qualifiers
Qualifiers will be included in the ELF code tables not in the permitted indications list
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Step 4: Including indications on medicine label
Indications will not have to be included ‘word for word’ on your
label or advertising material:
• the intent and meaning of the indication must not change
• i.e. the same therapeutic action and target
For example:
ARTG indication: ‘Maintain/support gastrointestinal health’
Label indication - same meaning: ‘Maintains healthy gut’
Label indication - different meaning: ‘Maintain healthy intestinal flora’
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Step 4: Including indications on medicine labelsThe permitted indications list will contain ‘primary’ indications referring to diseases or
conditions and indications referring to general symptoms
For example:
These indications can be combined on the product label to form a simple sentence, e.g.:
‘Relieve symptoms of common cold such as cough, runny nose and itchy eyes’
Helps
decrease/
reduce/relieve
symptoms of
common cold
• Helps decrease/reduce /relieve cough
• Helps decrease/reduce /relieve
watery eyes
• Helps decrease/reduce /relieve nose
These symptoms
can be linked to
‘symptoms of
common cold’
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Step 4: Including indications on medicine label
• Some indications will have mandatory qualifiers or required warning statements
• Where these are specified in the permitted indications determination, they must
also be included on your medicine label.
For example:
Indication Specific requirement relating to the use of the indication in the medicine
Decrease/reduce/relieve
symptoms of mild
arthritis/mild
osteoarthritis
Label statement: 'If symptoms persist consult your healthcare practitioner (or
words to that effect)'
Must be qualified by 'mild'
Must not be for serious forms of arthritis e.g. rheumatoid arthritis, juvenile arthritis,
debilitating osteoarthritis
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Summary – Using permitted indications
1. Select tradition of use
(Optional)
Indications that do not
specify a tradition of use
are by default scientific.
2. Select core permitted
indication
(Mandatory)
At least one core
indication is selected in
ELF using drop down lists
or key word search.
3. Select specifying qualifiers
(Optional)
Sponsors can choose to apply one or more pre-
approved qualifiers from a drop down list.
Healthy target
populationTime of use
Tradition of use
N/A
Core permitted indication
’Relieves muscle aches
and pains
Specifying qualifiers
Healthy target population: ‘in healthy individuals’
Time of use: ‘after exercise’
Final permitted indication on product label
Relieves muscle aches and pains after exercise in healthy individuals.
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Listed Medicines Compliance Framework
Pre-approved ingredients
Good manufacturing
practice (GMP)
Permitted indications
Medicine listed
on ARTG
Post-market Compliance
review
Cancelled
from ARTG
Fully compliant Non compliant
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Post market compliance review outcomes
• Where we identify a compliance issue we can:
Issue a proposal to cancel notice
• sponsor is given a reasonable opportunity to correct the
issue
Cancel the product immediately
• Medicines making indications not covered by the permitted
indications would be cancelled immediately
In general, we will work with you to bring your product back
into compliance
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How to apply for new permitted indications
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Applying for a new permitted indication• After 1 January, an application form will be
available for new permitted indications to be
added to the list
A fee of $1000 will apply
• Evidence to support a proposed indication will not
be evaluated by the TGA. However, applications
will be assessed against the legislated criteria
• The permitted indication list is likely to be updated
on a quarterly basis, as is the process for new
ingredients
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Agreed criteria for new permitted indications
1. Must be a therapeutic indication (describe a therapeutic use)
2. Must be a low level indication
3. Must be capable of complying with the Advertising Code when
included on promotional materials
4. Must be consistent with the treatment paradigm
(scientific/ tradition of use)
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Criterion What this means Examples
Health maintenance Normal physiological effects of
substances in;
growth, development and normal
functions of the body
Maintain eye health
Maintain healthy liver function
Support healthy connective tissue / joints
Health enhancement Beneficial effects of substances on the
physiological and /or psychological
state of the body;
- above and beyond normal growth,
development and functions of the body
Improve immune system defence
Promote bowel regularity
Digestive stimulant
Prevention or
alleviation of a dietary
deficiency
Prevention of mild dietary deficiency
(not prevention of diseases resulting
from severe deficiency)
Helps prevent dietary calcium deficiency
Helps prevent dietary vitamin B12 deficiency
Is it a low-level indication?
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Criterion What this means Examples
A non-serious
disease, ailment,
defect or injury
Those low risk conditions that are
non-serious and self manageable.
May be related to;
- reduction in risk/frequency/duration
- relief
- management or improvement in
quality of life
…without resolution of the
underlying non-serious disease,
ailment, defect, condition or injury.
Relieve joint stiffness associated with
mild osteoarthritis
Relieve symptoms of common colds
Relieve menstrual cramps
Relieve dry skin associated with mild
eczema
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Indications NOT suitable for permitted indications
list
The indication, must not:
• refer to, or imply, the prevention or cure of any form of a disease, ailment, defect or
injury
• contain a prohibited representation
• contain a restricted representation
• be specified in a non-permitted indications list (if made)
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What is a prohibited representation?
Under the Therapeutic Goods Advertising Code 2015, a prohibited representation is
defined as:
(i) any representation regarding abortifacient action; or
(ii) any representation regarding the treatment, cure or prevention of the following
diseases:
Neoplastic (i.e. cancer)
Sexually Transmitted Diseases (STD)
HIV AIDS and/or HCV; or
Mental illness (e.g. depression, anxiety, low mood)
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What is a restricted representation?A restricted representation is serious form of a disease, condition, ailment or defect
included in Table 1, Appendix 6 Part 2 of the Therapeutic Goods Advertising Code 2015
For example:
• Cardiovascular diseases
• Diseases of joint, bone, collagen, and rheumatic disease
• Diseases of the eye or ear likely to lead to blindness or deafness
• Diseases of the liver, biliary system or pancreas
• Endocrine diseases and conditions including diabetes and
prostatic disease
• Gastrointestinal diseases or disorders
• Infectious diseases
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What is a serious form?
‘Serious’, means those diseases, conditions, ailments
or defects that are generally accepted:
• not to be appropriate to be diagnosed and/or
treated without consulting a suitably qualified
healthcare professional, and/or
• to be beyond the ability of the average consumer to
evaluate accurately and to treat safely without
supervision by a qualified healthcare professional
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Other considerations• Must be capable of complying with the Advertising Code when
included on promotional materials:
must not be likely to mislead consumers (e.g. improves the IQ of
your unborn child)
can’t imply the medicine is infallible, unfailing, magical, miraculous
or that is certain or guaranteed to cure
must not state or imply that the product is effective in all cases of
the condition
• Must be consistent with the treatment paradigm (scientific/ tradition of use)
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Further information• New guidelines:
‘Permitted indications for listed medicines guidelines’
Update to the ‘Evidence Guidelines for Listed
Medicines’
• New permitted indications webpage
Frequently asked questions page
Permitted indications factsheets
• Contact us
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Development of the permitted indications list
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Development of the permitted indications list
• The list of permitted indications has been developed
in consultation with stakeholders based on agreed
criteria
• Draft list is based on industry submissions to
previous consultations and refined following
stakeholder feedback
• Targeted consultation on the list also included
stakeholders concerned with traditional paradigms,
such as TCMs
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Development of the permitted indications list• Draft list published on TGA website in July 2017
• Stakeholders were able to provide TGA with feedback on the
list and propose new indications free of charge
• New indications proposed after this time will incur a fee
• Comment period closed on 1 October 2017 to enable
the drafting and publication of the legislative instrument
More than 3000 proposals for additional indications
More than 900 proposals for additional qualifiers
• We are still in the process of reviewing the comments received
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Issues arising from comment period1. Indications covered by advertising exemptions for restricted representations
Restricted representations will require assessment through the new assessed listed medicines
pathway.
Exception: Indications with substance based restricted representation approvals, for folate
(neural tube defect), calcium and vitamin D (osteoporosis) will be included in the permitted
indications list, based on a safe history if use, and an established evidence base
2. Biomarker indications e.g. cholesterol, blood glucose, blood pressure
Only low level biomarker claims are included in the permitted list – e.g. ‘ ‘Maintain cholesterol
health’
Higher level indications are indicators of serious disease – these may be assessed through
the new listing pathway – e.g. ‘Maintain within the normal range….’
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Issues arising from comment period
3. Inclusion/non inclusion of vulnerable populations as evidence qualifiers
E.g. pregnancy, foetal development, infants
Potential safety concern if these population groups are used as population
qualifiers for any indication
4. Use of the term ‘medically diagnosed’
Included for a limited number of conditions
Requests to include other conditions e.g. benign prostatic hypertrophy, tinnitus
‒ Only appropriate for a person to self-manage and assess the symptoms of
their condition after an initial diagnosis has been made
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Issues arising from comment period
5. Use of mild and mild/moderate qualifiers
‘Mild’ is used to ensure that indications do not refer to a serious
condition
Comments that mild qualifier is unnecessary for some
indications e.g. stress and migraine
Requests ‘mild to moderate’ to be acceptable for certain
indications e.g. mild to moderate osteoarthritis, mild to
moderate temporomandibular joint pain
Indications for diseases or conditions of moderate severity may be
appropriate for the new assessed listed medicine pathway
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Issues arising from comment period
6. Requirement for sunscreen indications to be compliant with new guidelines
All listed medicines will be required to transition to permitted indications
Only indications compliant with ARGS will be included in the list
Previously grandfathered sunscreens will have to comply with new ARGS
7. Clarification required of when function/ mechanistic claims can be used
If you wish to use a structure/function claim on your label that implies a
therapeutic use you should enter an appropriate permitted in the Register
‒ Label statement: ‘Source of calcium. Calcium strengthens bones’.
‒ ARTG indication: ‘Maintains/supports bone strength’
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Issues arising from comment period8. Inclusion /removal of cosmetic claims
Clarification required for distinction between cosmetic
claims and therapeutic indications
‒ Are they for health enhancement?
9. Inclusion of cellular level indications
Concern expressed that there is lack of evidence to
support cellular level indications
Are the suitable for listed medicines and/or meaningful to
consumers? More general indications are often available
Do they describe a therapeutic use?
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Issues arising from comment period
10. Inclusion of TCM and Ayurvedic specific terminology
Concern that these are not understandable for average consumer
However, if not included, general indications are not meaningful to consumers and
practitioners familiar with these traditional paradigms
Concern combinations of indications can imply serious conditions
‒ 1000 additional TCM indications proposed
‒ We will seek expert advice to assist us determine if these are appropriate for
listed medicines
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Questions?
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