An overview of recommendation thirty-nine from the Review of Medicines and Medical Devices Regulation relating to improving access to evidence based listed complementary medicines.

1. Complementary Medicines Regulatory Obligations Seminar
Improving access to evidence based
listed complementary medicines
Lyndall Soper
Assistant Secretary, Complementary and OTC Medicines Branch
Medicines Regulation Division, TGA
Complementary Medicines: Regulatory Obligations Seminar

2. Recommendation 39
3 assessment pathways for complementary medicines
Panel recommendation:
3 options by which sponsors may seek ARTG entry for complementary medicines:
Option 1: Listing in the ARTG following self-declaration by the sponsor regarding
safety, quality and efficacy (current listing pathway)
Option 2: Listing in the ARTG following self-assessment of the safety and quality but
a TGA assessment for efficacy (new pathway)
Option 3: Registration in the ARTG following full TGA assessment of safety, quality
and efficacy (current registered pathway)
Complementary Medicines: Regulatory Obligation Seminar 1

3. Recommendation 39
Three assessment pathways for complementary medicines
Government Response
The Commonwealth accepts the recommendation;
noting that legislative amendments are required to
implement Option Two.
Implementing this recommendation would increase
transparency for consumers, provide additional flexibility
for sponsors and support innovation.
Complementary Medicines: Regulatory Obligation Seminar 2

4. New Pathway: Key Features
• A new assessment pathway sitting between the existing listed medicine (low risk)
and registered medicine (high risk) pathways
• Maintains low risk status based on their ingredients, the way they are presented
and the potential harm associated with their use
• Can use ‘intermediate claims’ which are not included on the permitted indications
list:
 Low level indication: ‘May help relieve muscle aches and pains’
 Intermediate level indication: ‘May help relieve arthritis’
Complementary Medicines: Regulatory Obligation Seminar 3

5. New Pathway: Key Features cont.
• Still required to comply with GMP requirements
• TGA evaluates the evidence for efficacy before it is listed
• Option to include a claimer on all promotional material stating it has been
independently assessed.
– ‘The efficacy of the product has been independently assessed for the approved indication’
– ‘Evidence has been reviewed by the TGA’
Complementary Medicines: Regulatory Obligation Seminar 4

6. Proposed Complementary Medicines Framework
Listed Medicines New Pathway Registered Medicines
Permitted ingredients Permitted ingredients Not limited to selecting from
permitted ingredients list
Good Manufacturing Practice Good Manufacturing Practice Good Manufacturing Practice
Low level permitted indications
only
At least one ‘intermediate
indication’
May have higher level
indications
No pre-market assessment Pre-market assessment of
evidence for efficacy
Full pre-market assessment
Ability to claim that efficacy
has been assessed
Complementary Medicines: Regulatory Obligation Seminar 5

7. Indications to accepted through the new pathway
Listed medicines New pathway Registered medicines
Low level indications
may refer to:
• health enhancement
• health maintenance
• prevention/alleviation of dietary
deficiency
• a health benefit for a non-
serious disease or condition
(symptomatic relief)
Eg: maintain/support healthy bones
Intermediate level indications
may refer to:
• a health benefit for a serious disease
(i.e. restricted representations)
• prevention, alleviation or management
of a non-serious disease or condition
(of a higher risk to consumers than low
level indications)
Eg: prevention of osteoporosis
High level indications
may refer to the;
• prevention
• alleviation,
• cure or
• management
of a serious form of a
disease, ailment, defect or
injury (restricted reps)
Must not refer to a prohibited representation 6

8. Proposed approaches to establishing efficacy
1. Sponsors all medicines must meet minimum evidence requirements
2. Existing approaches to establish efficacy for listed and registered
complementary medicines will be retained
3. For the new pathway:
• The evidence requirements can be met in two ways (Method 1 or Method 2)
• Sponsor will self-assess the safety and quality
(permitted ingredients, compliance with quality standards and GMP)
Complementary Medicines: Regulatory Obligation Seminar 7

9. Proposed Categories of Evidence
Category A Category B Category C Category D
Traditional Reference text Non-systematic,
generalised reviews -
including databases
Observational studies e.g.
cohort and case control
studies
Double blind randomised
controlled trials (including
cross-over trials)
Herbal Monograph Publicised international
Regulatory Authority
Articles
Comparative studies
(non-control)
Systematic reviews
Herbal Pharmacopoeia Evidence based
reference text - scientific
Materia Medica Scientific Monographs
Publicised International
Regulatory Authority
Articles – Traditional only
Pharmacopoeias
Complementary Medicines: Regulatory Obligation Seminar 8

10. Proposed minimum literature requirements
Listed medicines New Pathway Registered medicines
Indication Traditional Low Level Scientific Intermediate Level Indications Non-prohibited Indications
Evidence
Category
Required
evidence
Minimum of two
independent sources from
Category A
OR
A minimum of one from
Category B
Minimum of two
independent sources from
Category B
PLUS (where required)
A minimum of one from
Category C
Primary indication
Minimum of one from Category D
OR
Minimum of 2 independent
sources from Category B, AND a
minimum of one from Category C
Primary indication
Minimum of one from
Category D
Evidence
Category
Supplementary
evidence
Minimum 1 from Category
A to support specific
therapeutic claims (where
relevant)
Minimum of 1 from
Category B to support
specific therapeutic claims
(where relevant)
Secondary indications
One from Category D
OR
Minimum of 2 independent
sources from Category B, AND a
minimum of one from Category C
Secondary indications
One from Category D
OR
Minimum of 2 independent
sources from Category B,
AND a minimum of one from
Category C
Complementary Medicines: Regulatory Obligation Seminar 9

11. Options for submission of efficacy evidence
Method 1:
• Clinical Trial data on the finished product that supports the specific indication
– Potential 3 years data protection.
Method 2:
• A data package containing:
– evidence for efficacy of all ingredients; AND
– evidence for efficacy of the product formulation;
(e.g. bioavailability data and/or dissolution testing) AND
– justification of the combination of ingredients.
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12. Proposed evidence dossier requirements for New Pathway
Data Type Method 1 Method 2
Primary
indication
A minimum of one randomised controlled
clinical trial (including cross-over trial) or
systematic review on the product.
A minimum of one randomised controlled
clinical trial (including cross-over trial) or
systematic review on each active ingredient.
Body of
scientific
information
Full literature search report on the
product or formulation.
Full literature search report on all active
ingredients and formulation.
Non-clinical data N/A Dissolution data and bioequivalence data on
the product.
Formulation N/A Justification of the use of the particular
combination of ingredients, including potential
interactions.
Quality Evidence of GMP. Evidence of GMP.
Complementary Medicines: Regulatory Obligation Seminar 11

13. Examples of products and evidence packages suitable for
the New Pathway
Product Type Example of products
Standard product
(e.g. multiple active ingredients)
Method 1
A sponsor proposes to list a product consisting of 1000 IU of Vitamin D
(cholecalciferol 25 micrograms) and 1200 mg calcium indicated for reducing the
risk of fractures associated with osteoporosis. The sponsor has evidence from
multiple clinical trials and a systematic review of the literature indicating that
daily supplementation with the product reduces the risk of fractures associated
with osteoporosis.
Single ingredient active
(immediate release only) with
established bioavailability
Method 2
A product contains 450 micrograms of folic acid. The sponsor wishes to use the
restricted representation ‘prevents neural tube defects when used during the first
trimester of pregnancy’. The sponsor can provide dissolution studies indicating
that the product results in appropriate release of the active, and full literature
search supporting the indication.
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14. Initial outcomes of public consultation
New Pathway
• Broad support for the introduction of the new pathway
Efficacy evidence
• General support for the proposed evidence hierarchy
• Significant concerns around excluding traditional medicines
from the new pathway
• Some industry stakeholders feel there is too much
emphasis on the finished product
Complementary Medicines: Regulatory Obligation Seminar 13

15. Recommendation 45: Claimers for assessment of efficacy
Panel Recommendation:
Where a medicinal product is listed in the ARTG following an assessment by the
TGA of an application under Option Two, the sponsor is able to indicate on all
promotional materials and on the product label, that the efficacy of the product
has been independently assessed for the approved indications.
Government response:
Accepts-in-principle Recommendation 45, noting that the design and use of the
promotional statements will require careful consideration by the TGA and further
consultation with stakeholders.
Complementary Medicines: Regulatory Obligation Seminar 14

16. Features of the claimer
• The use of a claimer is optional
• Must be supported by the appropriate level of scientific evidence for all
indications made for the medicine
• Must not imply superiority of the product over other medicines that have been
pre-market assessed (e.g. OTC, prescription)
• Must comply with advertising requirements
• Must not be more prominent or detract from the label information mandatorily
required by the current Labelling Order
Complementary Medicines: Regulatory Obligation Seminar 15

17. Who can use the claimer?
• A claimer can be used by medicines that have had TGA
pre-market assessment:
– Complementary medicines assessed via the new
pathway
– Registered complementary medicines
• A claimer cannot be used by medicines that have not had
a pre-market assessment:
– Listed medicines – including those that have been subject
to a post market compliance review
– “Grandfathered” medicines
Complementary Medicines: Regulatory Obligation Seminar 16

18. Possible presentation of claimers
Option 1: The claimer as a statement
• ‘The efficacy of the product has been independently assessed
for the approved indication’
• ‘Evidence has been reviewed by the TGA’
Option 2: A visual identifier as well as statement
Implementation and design
Claimers will be:
• standardised and easily recognisable by consumers
• appropriately placed on label and promotional material to not
detract from essential product information
Complementary Medicines: Regulatory Obligation Seminar 17

19. Initial outcomes of public consultation
Claimer on promotional material
• Generally well supported by consumer groups,
industry and healthcare professionals
• Strong support for an appropriate education
campaign to accompany the introduction of a
claimer
Complementary Medicines: Regulatory Obligation Seminar 18

20. Questions?
Complementary Medicines: Regulatory Obligation Seminar 19