Medicines and Medical Devices Regulation – current developments and future options

John Skerritt Deputy Secretary for Regulatory Services Department of Health ARCS AGM Melbourne 26 Nov 2015

This presentation • Australia’s medicines regulatory environment – updates

– Planned medicines labelling changes – Orphan drugs and options for regulatory reform – Biosimilars – Pharmacovigilance pilot inspection program – Reviewing the URPTG (Recalls) – Clinical trial notifications go online

• Update on the Expert Panel Review on the Regulatory Framework for Medicines and Medical Devices

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Medicines labelling – why reform ? Facilitate quality use of medicines by consumers and health professionals by better labelling: • reduce risk of prescribing, dispensing and self-

selection errors • avoid consumer confusion and the inappropriate

use of medicines • assisting the appropriate selection of OTC

medicines • optimising identification and usability of necessary

information • ensuring consumers know where to go for further

information about their medicine 2

• 15 year old regulations out of step with international best practice

• Ageing population • Growth of generic and complementary medicines • Some more “powerful” medicines are now available

OTC

The process • Multiple stakeholder consultations • Several cycles of refinement • Costing of regulatory burden of the proposed changes

to industry • Drafting of TGO and guidance

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Major proposed mandatory requirements • Separate TGOs (regulations) to recognise different information requirements and

risks for prescription and OTC medicines • Text sizes for active ingredients for registered medicines > 3 mm

– smaller if 4 or more active ingredients or medicine in a small container

• Prescription medicines to have names of the medicine on at least three non-opposing sides of the carton and a machine readable code

• Certain excipients (e.g. allergens) and impurities to be declared – Information can be on label or CMI for prescription medicines

• Registered OTC medicines require a Medicines Information Panel • Required information must be in high colour contrast • Specific requirements for some types of packaging and ingredients • Warning statements related to use of medicines in pregnancy

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Medicines labelling review - current status

• Extensive Stakeholder consultations conducted on previous draft TGO during 2014

• Over 80 detailed submissions from industry, healthcare professionals, consumer groups

• TGO extensively revised during 2015

• Guidance documents on mandatory and best practice (non-mandatory) requirements developed

• More consultations during Oct-Nov 2015

• 4 year transition period proposed from 2016

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Orphan drugs program review Why review?

• The program objective is to help sponsors to market drugs used in the treatment, prevention or diagnosis of rare diseases

• Support is by waiving fees for orphan evaluation and registration – But because TGA is 100 % cost-recovered, the overall cost of NCE evaluation is

borne by other sponsors

• Change in medicines business models since 1998 – growth of highly targeted treatments rather than “blockbusters”

• Discussion paper released early 2015 6

Program coverage and viability considered • What reforms – if any – are required to ensure the program objectives are

continuing to be met ?

• Orphan drug definition, i.e. who should be targeted with an orphan drugs program ? – disease subgroups and stages – first orphan indication vs all indications

• Is the current patient threshold appropriate ?

• Program viability - are changes needed to the charging model ?

• Government will soon consider options for any reforms

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Biosimilars • A version of an already registered biological medicine

that has a demonstrable similarity in physicochemical, biological and immunological characteristics, efficacy and safety, based on comprehensive comparability studies

• The claim is “similarity in all important aspects”

• The reference product must – be registered in Australia by means of a full data

submission – have been marketed for a sufficient duration – have a volume of marketed use so that there is likely to

be a substantial body of data regarding safety and efficacy for the approved indications

Similar … but not the same..

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Biosimilars – TGA’s role in evaluation • As for all registered medicines, biosimilars must meet acceptable standards of

quality, safety and efficacy

• Additionally, TGA assesses whether the scientific and clinical data warrant a biosimilar designation

• Biosimilar naming - WHO consultation still to be concluded – In the interim, use the Australian biological name without a specific biosimilar identifier

suffix, e.g. a biosimilar to Neupogen filgrastim would be named 'TRADENAME' filgrastim

• A comprehensive Risk Management Plan developed by the sponsor – taking into account identified and potential risks for the reference product – as well as any risks associated with biosimilarity and anticipated patterns of use (including

immunogenicity in humans)

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Pharmacovigilance pilot inspection program

• Responsibilities of Sponsors are specified in the TG Act and Regulations, including: – Reporting of serious adverse drug reactions and safety issues – Notification of a staff member responsible for pharmacovigilance – Responding to TGA requests for information – Compliance with conditions of registration, such as submission of PSURS, RMPs,

updating of PI/ CMI, retention of records

• Pilot inspection program will assess compliance

• Eleven sponsors agreed to take part in pilot program – First inspection was undertaken in October 2015 – Will assess feasibility and seek feedback on value for the sponsor

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Reviewing the Uniform Recall Procedure for Therapeutic Goods

• Consultation closed 23 November

• Now drafted as interlinking webpages to enhance navigation and usability

• Includes a step-by-step guide through the recall procedure – examples of different classes of recall actions

– Sponsor’s Hazard Alert customer letter requirements

– Mandatory recall actions

• Includes requirements for recalling biologicals and greater clarity on the requirements for device/ IVD recall actions

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Reviewing the Uniform Recall Procedure for Therapeutic Goods

• Changes to recall terminologies – Product Defect Correction – Hazard Alert (implanted medical devices and biologicals) – Product Defect Alert (new terminology)

• Includes probability aspects in Classification of Recalls

• Clarifies the requirements of safety alerts (non-recall action)

• Updates publication of safety alerts (non-recall action) and publication of recall letters on a case by case basis in SARA

• Includes the outcomes of the review of recall actions 12

TGA Clinical Trial Notifications go online • From October 2015 TGA Clinical Trial Notifications

moved from a paper-based database to a new online system – reduced administrative burden – online Sponsor declaration replaces requirement for

submitting original signatures can manage and track notifications via an online dashboard

– can directly amend submitted information – online invoice generation and payment

• After December 2015, pre-July 2015 CTN data will be posted to the online system

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Expert Panel review of Medicines and Medical Devices regulation …..

• First report on medicines and medical devices, provided to government 31March and the second report on complementary medicines and advertising submitted on 31 July 2015

• Review process included submissions in response to discussion papers and interviews with key stakeholders

• Both reports now publicly released, some stakeholder workshops held and more planned

• The Report is a report from a Review panel to Government and has not yet been formally considered by Government

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Overarching principles for regulation as recommended by the Expert Panel

• Australia maintain the capacity to undertake assessments of therapeutic goods for safety, quality and efficacy

• The Australian Government retain responsibility for approving the inclusion of therapeutic goods in the ARTG

• 32 recommendations in the first report cover six main areas: – principles for regulation – pre-market approvals – post-market monitoring – access to unapproved therapeutic goods – structure/ decision making; and – broader reviews

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Some proposed initial reform bundles

• Reforms to registration of New Chemical Entities • Reforms to generics and biosimilar medicines

registration • Risk based approaches to variations of medicines

on the ARTG

• Reform to schemes for unapproved medicines and devices (i.e. the Special Access and Authorised Prescriber Schemes)

• Establish criteria and mechanisms for expedited approval of (very) novel medical devices

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Pathways proposed for registration of a new chemical entity (prescription medicine)

1. Submission of a complete dossier for full assessment by the TGA (current process)

2. Expedited approval based on submission of an un-redacted evaluation report from a comparable overseas regulator, with a copy of the dossier and an Australian-specific module one

3. Accelerated approval based on transparent criteria

4. Potential for provisional approval/ adaptive licensing, if time-limited and subject to public advice that the medicine is (only) provisionally approved

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Generic and Biosimilar medicines • The Panel recommended that there be two pathways

to seek registration of a generic medicine or biosimilar: 1. Submission of a complete dossier for full assessment by

TGA 2. Submission of an un-redacted evaluation report from a

comparable overseas regulator (together with the dossier)

• The opportunity for a range of other business process improvements for generics in the reforms is also being considered

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Other Prescription Medicine Recommendations

• Adopt a risk-based approach to management of variations: – Notification of variations where the variation does not impact the quality,

safety or efficacy

– Assessment of the variation if the variation could impact safety, quality or efficacy

• Streamline access for consumers and health professionals to medicines and medical devices that have not been approved in Australia through the Special Access Scheme

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Subsequent bundles proposed

• Comprehensive medical device reforms

• More comprehensive post-market reforms • Adaptive licensing of medicines • Further studies proposed for:

– The Medicines Scheduling Policy Framework – Schedule 3 medicine advertising Guidelines – Lower-risk goods to determine whether they may best

regulated under other frameworks or better regulated according to risk

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Post market monitoring recommendations • Better integration and timely analysis of available

datasets including matched de-identified data from PBS and MBS

• Implement an alert scheme that a medicine is newly registered and to encourage reporting of adverse events

• Electronic reporting of adverse events

• Enhanced information-sharing with overseas regulators

• Will require enhancement if accelerated and/or provisional licensing is adopted

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The Second report of the panel • Publicly released on 19 November 2015

• Focussed on options for regulation of – complementary medicines and – advertising (all categories of therapeutic goods)

• Concluded that TGA should remain the regulator for both areas – While Complementary Medicines are low risk, it is appropriate to regulate

products that make therapeutic claims within the therapeutic goods framework

– This has also underpinned the reputation of Australian Complementary Medicines in the export market

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Recommendations – Complementary Medicines

Some recommendations for reducing particular pre-market requirements are conditional on strengthening aspects of postmarket regulation and enforcement

1. Streamline transparency and predictability of regulation: – Better regulatory guidance materials – Introduce permitted indications for Complementary Medicines – Adopt/ develop evidence monographs – Allow review rights for ingredients – Establish ingredient assessment timeframes – Stakeholder input through an advisory committee

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Recommendations – Complementary Medicines

2. Increasing the transparency of evidence of efficacy for particular indications – Requirement to publish efficacy evidence – Establishment of an evidence hierarchy, with a new class of complementary

medicines proposed that would be allowed to make higher-level claims than listed medicines

– Closer linkage to advertising claims

3. Greater utilisation of overseas assessments for new ingredients

4. Increase in postmarket monitoring and compliance powers, including ability to refuse to list particular products

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Recommendations – Advertising of therapeutic goods

1. Advertising of therapeutic goods to the public continues to be regulated by TGA under a framework which includes an advertising code

2. Abolish pre-approvals of advertising, and move to a self-regulatory regime

3. Requirements for advertising to the public are made consistent for all medicines and medical devices – currently sponsors of medical devices are responsible for ensuring that advertisements are

consistent with the intended purpose for the device – but they are not subject to a pre-vetting process prior to publication

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Recommendations – Advertising of therapeutic goods

4. Advertising to the public continues to be prohibited for prescription medicines and most pharmacist only medicines

5. New mechanism for managing complaints managed through a single agency (either TGA, another government agency, or an external one)

6. Consideration be given as to whether the current range of investigation and enforcement powers around advertising should be broadened

7. TGA to run a sponsor education programme to assist in achieving compliance with advertising requirements

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A review of a number of governance arrangements were proposed by the Panel in the first report

• A comprehensive review of the legislative framework to simplify its structure

and language

• Review and enhance TGA’s funding model • Review TGA’s Decision making arrangements including the role and number of

committees

• Explore integrated collaboration with HTA assessments

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Next Steps

• Government consideration of recommendations from both reports, including those in the second report on complementary medicines and advertising

• Once Government decisions on the proposed reforms are known, implementation planning will be firmed up

• We will also consult closely with stakeholders in developing the finer detail on implementation, including assessment of regulatory impacts and fees and charges

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