the regulation of complementary medicines

The regulation of complementary medicines

Yasmin Mollah

Assistant Director, Listing Operations

Angeliza Querubin

Pre-Market Assessment Section

Complementary medicines branch, TGA

Capsig NSW - Complementary medicines - revival

25/3/2015

Therapeutic Goods AdministrationWhat do we do?

• Established in 1989

• Department of Health of

Australia

• Safeguard health of

Australian public

• Regulates therapeutic

goods

– Medicines and medical

devices

TGA StructureNational Manager

Market Authorisation Division

Medicines Authorisation Branch

Complementary Medicines Branch

Devices Authorisation Branch

Scientific Evaluation and Special Product Access

Branch

Monitoring and Compliance Division

Regulatory Compliance Branch

Manufacturing Quality Branch

Laboratories Branch

Post Market Surveillance Branch

Regulatory Support Division

Regulatory Business Services Branch

Regulatory Engagement, Education and Planning

Branch

Regulatory Legal Services Branch

Regulatory knowledge and Technology Services Branch

Regulatory Business Improvement Branch

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Complementary Medicines Branch

Market Authorisation

Group

MAB

(Medicines)

CMB

(Complementary Medicines)

Regulatory Reform &

Coordination

Pre-market Assessment

Listing and Operations

Listing Compliance

DAB (Medical Devices)

SESPAB (Scientific

Evaluation)

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What are Complementary Medicines?

Capsig NSW - Complementary

medicines - revival

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The TGA does not regulate:

• Practitioners, such as naturopaths,

traditional Chinese Medicine practitioners

• Complementary medicines that are

dispensed or extemporaneously

compounded by healthcare practitioners for

individual patientsRegulated at a State/Territory level

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Risk based regulation of medicinesAustralia has a risk-based approach with a two-tiered

system for the regulation of all medicines, including

complementary medicines

Lower risk medicines

listed on the Australian Register of Therapeutic Goods

AUSTL

Higher risk medicines

registered on the ARTG

AUSTR

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Risk based approach

• Pre-market evaluation

• Medicine focussed

• May have restrictions on access

• Higher level claims

• Identified by “AUST R” number

RISK

Registered

Listed

• No restrictions on

access

• Low and medium level

claims

• May have restrictions:

quantities, dosage

form, route of admin,

plant part, etc

• Enter ARTG via the

Electronic Listing

Facility (ELF)

• Sponsor makes

certifications against

requirements

• Evidence for claims

monitored ‘post-market’

• Id. by “AUST L”

number


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Determinants of Risk

• Ingredients

• Dosage form

• Indications and claims

• Significance of side effects

• Effects of prolonged use or inappropriate self-medication


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Is it eligible for Listing?

Eligibility requirementsApproved

ingredientsPreparation

not in SUSMPQty restrictions

not exceededNot required

to be sterile

Herbal ingredients meet definition

of “herbal substance”

Indications do not refer to disease

/ condition in Appendix 6 of TGAC

Sponsor certifies medicine eligible for Listing

ELF validation can pick up some ‘ineligibility’

Listing


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Listed Medicines Regulatory Framework

Listed on ARTG

• Streamlined online application & validationprocess

• Sponsor certify meetslegislation requirements

• No premarket efficacyevaluation

Retail supply to Australian market

place

Compliance review

Unique Regulatory Framework

Evidence

sourced from

open literature

Regulatory framework

consistent with low

risk medicines

Quick & easy

market

access

Pre-approved

ingredients

Market share

established

Fully compliant Non compliant

???

Cancelledfrom ARTG


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Post-listing regulatory activities

Risk based regulatory approach includes:

• desk-based audits of listed medicines

• laboratory testing of products and ingredients

• surveillance in the marketplace

• monitoring of adverse reactions

• recalls procedure

• audit of manufacturing sites

• controls for advertising11

Type of Compliance Reviews for LMsInvestigations

• Triage of complaints into highest priority target review

Target Reviews

• Often triggered from complaint or intelligence report

• Specific information is reviewed to address concerns

• Comprehensive evidence reviews

Random Reviews

• Newly LMs are randomly selected

• Standard set of information is reviewed

Target Reviews (Narrow scope)

Random Reviews

(broad scope)

Investigations (triage)


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Compliance Review

Review

EvidenceClaims / indications:

relevance, quality

Labelling

Correct format

Presentation

Advisory statements

Manufacturing

Licence / valid clearance

Finished Product Specifications

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Listing Compliance Review Process

Medicine listed on ARTG

Compliance review

Request for information

(s31 of Act )

Assessment of information against relevant legislative

requirements

Direct cancellation

ss30(1C) or (1A)

Cancel medicine from ARTG

compliance issues identified

Propose to Cancel (P2C)

Address all non-compliance

issues of P2C

Medicine remains on ARTG

Cancellation

ss30(2)

Cancel medicine from ARTG

Fully compliantMedicine remains

on ARTG

Sponsor review listing & address issues


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Does the indication match the evidence?• Scientific indications are supported by scientific evidence

• Traditional indications are derived from a tradition of use

within a paradigm

• Format of 2 types of indications are different on the

medicine label

• According to the current Evidence Guidelines1

– Is the evidence relevant?

• Equivalent doses; plant part– Is it high quality evidence?

• Systematic reviews, methodological sound– Is it a balanced view?

• Positive evidence > equivocal/negative

1Guidelines for levels and kinds of evidence to support indications and claims (2011)

Incre

asin

gq

ualit

y

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Traditional Use – Indications & Evidence• Evidence of Traditional Use:

– well-established tradition of use for its intended purpose >75 years and includes:

how it has been used during that time

the continuity of its use; and

the geographical extent of its use.

• Example of traditional indication:

– Traditionally used in Western herbal medicine to relieve nasal congestion

• Sources include:

– National formularies

– materia medica

– official pharmacopoeias; and

– monographs


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Evidence guidelines


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Registered complementary medicines

• Higher risk than listed medicines based on the ingredients and/or

therapeutic indications

• identified on the label by ‘AUST R’ followed by a number

• Medicines must be registered on ARTG, where they:

– Don’t solely comprise ingredients permitted for use in listed

medicines

– Contain an ingredient subject to the conditions of Poisons Standard

e.g. Pharmacist Only vitamins/minerals must be registered

– Are required to be sterile

– Have indications that make higher level claims that are not allowed

in listed medicines

• Registered complementary medicines may be subject to the conditions

of a Schedule of Poisons Standard18

Registered complementary medicines

• Pre-market evaluation is undertaken to establish quality, safety and

efficacy of the medicine prior to approval for entry on the ARTG

• Data requirements and evaluation are consistent with other OTC or

prescription medicines

• Evaluation includes determining whether the medicine complies with all

applicable legislative requirements

• Application data typically follows scheme used in the Common

Technical Document (CTD), an internationally-agreed format for

approval of new drugs adopted by TGA in 2004

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Registered Medicines – Safety & Efficacy

Data Overview

• Literature search strategy

• History and pattern of human use

• International regulatory status

• Pharmacodynamics, pharmacokinetics, safety

pharmacology, drug interactions

• Toxicology: acute, chronic/subchronic, genotoxicity,

carcinogenicity, reproductive & developmental etc.

• Clinical trials

• Adverse event reports in Australia and overseas

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Registered Medicines – Quality Data

Overview

• Structural formula of the ingredient or components

• Physiochemical and other relevant properties

• Manufacturing details

• Characterisation of ingredient or components

• Control of substance: specifications, analytical procedures,

batch certificate of analysis, justification of specifications

• Reference standards

• Stability data

• Container/closure system

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The ChallengeManaging industry innovation with consumer safety

Minimal regulatory burden

Industry Consumer

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Guidance material Recently updated

• Australian Regulatory Guidelines

for Complementary Medicines

(ARGCM)

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Questions

Subscribe to Updates:

www.tga.gov.au/newsroom/subscribe.htm

Information on reforms:

www.tga.gov.au/industry/cm-reforms.htm


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http://www.tga.gov.au/newsroom/subscribe.htm

http://www.tga.gov.au/industry/cm-reforms.htm

the regulation of complementary medicines

Health & Medicine