permitted indications for listed medicines

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.

2017 Sponsor Education Workshops 1

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


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


Legislative overview

4

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


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


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


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


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


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


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)


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


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)


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


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


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


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)


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


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

192017 Sponsor Education Workshops

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


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


How to use permitted indications in your listing

application

22

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


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


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


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


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


Step 3: Selecting evidence qualifiers

Qualifiers will be included in the ELF code tables not in the permitted indications list


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’


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’


30

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


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.


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


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


How to apply for new permitted indications

35

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


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)


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?


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


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)


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)


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


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


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)


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

[email protected]


mailto:[email protected]

Development of the permitted indications list

46

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


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


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….’


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



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



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’


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?



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


Questions?

55

permitted indications for listed medicines

Health & Medicine