Updates from the Prescription Medicine Authorisation Branch Prescription medicine reforms

Adrian Bootes, Kaylene Raynes, Mark McDonald, Prescription Medicines Authorisation Branch Health Products and Regulation Group, Department of Health ARCS Annual Conference 2018, Sydney, NSW 22 August 2018

Session overview

Three parts:

I. Options for new medicines: Priority, Provisional, Orphans and COR

II. International work-sharing initiatives

III. Scheduling Policy Framework and PI/CMI initiatives

1

2

Prescription Medicines Authorisation Branch (PMAB) Structure

• Branch is comprised of 6 Clinical Evaluation Units (CEU) and 4 business sections • ~85 staff across 4 cities (Canberra, Sydney, Melbourne, Brisbane)

Branch Head (Assistant Secretary)

Adrian Bootes

Transparency, Reforms and

Evaluation Support Mark McDonald

Business Systems, Review and Reporting

Kaylene Raynes

Application Entry, Support and Export

Melissa Quinn

Clinical Evaluation Units (1–6)

Nitin Bagul Ting Lu Jason Ferla Michael Coory Monique Stone Neil Everest (a/g)

Application and Advisory

Management

Kaylene Raynes

Medical adviser

John McEwen

Prescription Medicines Registration

Medical Devices & Product Quality Division

Medicines Regulation Division

Pharmaceutical Benefits Division

PM Registration Processes

Prescription Medicines

Authorisation Branch

Scientific Evaluation Branch

Pharmacovigilance and Special Access

Branch

Laboratories Branch

Manufacturing Quality Branch

Regulatory Practice & Support Division

Scheduling & Committee

Support Section

Product Billing & Industry Assistance

Section

5

RegistrationDesignation

MS2

MS7

0 220 2550 20

orphan,priority,

provisional( if

required)

−40

legislatedtimef rame

(except for

COR)

applicationsubmitted

MS1(optional)

dossiersubmitted

TGA clock

in

working days

for decision

timing ('Milestone

7')

f or the

dif f erent pathways

120 150 175STOP-CLOCK,s.31

questions

to sponsor

TGA clock

STARTS

MS3 MS4Round

1

evaluationMS5

Round 2

evaluation

ACMexpert

advice(optional)

TGA clock

STOPS

MS6

155

COR

- A

prio

r ity

COR

- B

gene

r ic

prov

is iona

l

non

- gene

r ic an

d

• Multiple submission pathways ranging from 120-220 target days to grant market approvals

Submission Pathways – Overview

Options for new medicines

International perspective NCEs*

Country 2017 - New active substances

EU 30

US 50

Canada 33

Japan 22

Switzerland 29

TGA 24

Australian perspective • Aim to increase options for Australian patients • Limit regulatory burden on sponsors and the

regulator • Benefit for EOIs in addition to NCEs (reduces

target timeframe from 220 to 150 work days)

New actives substances approved by all 5 regulators*

*CIRS R&D Briefing 67 Bujar M, McAuslane N, Liberti L. 2018. R&D Briefing 67: New drug approvals in six major authorities 2008 – 2017: Focus on the availability of medicines and company size. Centre for Innovation in Regulatory Science. London, UK

TGA: NCEs & NBEs (past 5 years)

Biosimilars:

expected ↑

TGA: EOIs (past 5 years)

Considerations • Expecting increasing number of

medicines with same resources • Necessity to work smarter & more

flexibly while avoiding lack of clarity or transparency

Options for new medicines – expedited pathways Priority Review

• Implemented on 1 July 2017 • Determination eligibility criteria • Dossier - substantial evidence • Expedited through flexible business process • Exit criteria to standard pathway • Target time frame – 150 working days • Full registration on ARTG • Satisfactory quality, safety & efficacy

for the intended use

Provisional Approval • Implemented on 20 March 2018 • Determination eligibility criteria • Dossier – preliminary clinical data • Expedited through accepting early data where

the benefit of availability outweighs the risk • Target time frame – 220 working days • Time limited registration, full registration if

approved after evaluation of confirmatory data • Confirmatory safety and efficacy data required

Medicine and Medical Devices Review (MMDR)

reforms

Determination/designation: Process • Only medicines likely to provide the most benefit

are eligible • A designation/determination must be in force to

access pathways and/or fee waiver • Designation/determination in force for 6 months • 6 months extension if registration application not

submitted (1 month prior expiry not for priority) • Sponsor may re-apply for orphan designation once

lapsed, but criteria must be met (e.g. show benefit against self)

• Orphan designation applicable to all 5 pathways (standard, priority, provisional, COR A & B)

• Consistent & transparent process

10

Determinations/designations: applications

0

5

10

15

20

25

priority provisional orphan

Num

ber o

f App

licat

ions

Number of determination and designation applications (1 July 2017 - 31 July 2018)

withdrawn

rejected

approved

Application type * New orphan drug program (applications received from 1 July 2017)

• Approved applications (to 31 July 2018)

Priority, 14/23 (61%) determined Provisional, 2/2 (100%) determined Orphan, 12/24 (50%) designated

• Average time to priority and provisional determination : 19 working days

• Average time to orphan designation: New program: 25 working days Previous program: 60 working days

Designations/determinations: therapeutic area

8%

Approved orphan designations

Metabolic disorders

Immunology

Ophthalmology

Oncology

Haematology

Respiratory diseases

Neurological disorders

Endocrinology

9%

9%

8%

8%

42%

8%

8%

n=12

64%

29%

7%

Approved priority determinations

Oncology

Haematology

Neurological disorders

n=14

12

Designation/determination: Tips for success Main rejection reasons: • Comparison against registered

therapeutic goods

• Major therapeutic advance

Orphan drug considerations: • Prevalence: calculated differently for

diagnosis, prevention or treatment

• Subgrouping: ‒ compare against standard of care in the

absence of a registered treatment ‒ line of therapy or disease stage are not a

valid subgroup

Compare against standard of care if there is no registered treatment

?

Improved safety or efficacy

Medicine combinations

Major therapeutic

advance

Provide comparison against all registered treatments /prophylaxis

Separate applications for each active ingredient if not a fixed dose

Provide justification of why the supporting evidence is substantial: e.g. progression free survival vs overall survival

Updates to guidance documents

Orphan Drug Program • Subsetting of conditions with the

use of biomarkers generally not acceptable. Additional clarification has been included.

• The designation must been in force when the application and evaluation fees are payable (Regulation 45(12).

Provisional Approval • Confirmatory trial data may be in a clinical

setting. • Provisional applications will be included in the

PPF batching process.

Priority Review • Designation replaced by determination.

Guidance updates: - comparison excludes provisional - clarification - rewording - restructure

Priority review registrations

Excerpt from CIRS R&D Briefing 67

Regulator 2017 median approval time (accelerated NAS) Calendar

days Estimated

Working days* EMA 235 168 FDA 240 171 PMDA 275 196 Health Canada 209 149 Swiss Medic 272 194

*overseas regulators: excludes weekends but includes public holidays, includes sponsor time; TGA: additionally excludes holidays and sponsor time

98

104

124

96

96

140

119

80

0 20 40 60 80 100 120 140 160

Alectinib

Emicizumab

Nivolumab

Dabrafenib

Trametinib

Nivolumab

Osimertinib

Apalutamide

TGA Priority approval times 2017/18

Working Days

NCE/NBE EOI

Median approval time for NAS and EOIs

101 working days*

Priority /Orphan: considerations Priority Review

• No applications for the COR A/B • Most applications were for EOIs, in comparison

less new medicines (4/14) • Applications on the basis of benefit in a sub-

group of patients & major therapeutic advance

New medicine

EOI

TGA 4 /14 10 /14

& EMA accelerated 75% (3/4) 10% (1/10)

& FDA priority 100% (4/4) 90% (9/10)

Orphan drug • No applications for new dosage form medicines • None on the basis of lack of financial viability • No applications that used the COR A/B pathway • Most applications for NCEs/NBEs (9/12) • Applications on the basis of rare diseases New

medicine EOI

TGA 9 /12 2 /12

also EMA orphan 89% (8/9) 50% (1/2)

also FDA orphan 78% (7/9) 100% (2/2) 16

Options for new medicines - COR A and B • For medicines with full marketing approval from

a comparable overseas regulator following a de novo evaluation.

• Six overseas regulators identified as CORs. Unredacted COR evaluation reports must be provided by the applicant.

• Two approaches*:

COR-A – 120 working days

COR-B – 175 working days

*depending on extent of TGA evaluation required.

Experience (from 2 January) • Only few applications received to date • COR A- identical medicine and manufacturing overseas MA < 1 year ago critical review of the COR assessment evaluation of label PI & RMP, no additional

data evaluated • COR B No limit to currency of overseas MA Critical review of COR assessment reports additional data analysis required (e.g.

updated stability data, or pivotal study data)

17

Considerations for Implementation of provisional approval in Australia

‘immediate availability of new drugs

offers patients a benefit that outweighs the risks of limited clinical

information’

• What is the minimum evidence acceptable at the time of early approval?

• Will post-marketing commitments improve the evidence (bridge the gap)?

18

Provisional Pathway

Risk-Benefit of provisional registration *32% of New Active Substance Applications (NAS) had post market safety events *Accelerated applications were associated with higher rates

*Medicines approved through expedited pathways are associated with increased safety related label changes after approval particularly for the types of changes representing the highest risk warnings

20

Safety Issues? TGA approach

• New powers under the Act for provisionally registered medicines to:

– reduce the class of persons for whom the medicine is suitable

– change the directions for use – add a warning or precaution – change the Product Information related to the medicine

• Enhanced Pharmacovigilance framework (e.g. black triangle, pharmacovigilance inspections)

21

Confirmatory trials I *After 5 to 6 years, 20% of postapproval studies had not been started, 25% were delayed or ongoing, ~half completed. *15% of incomplete postapproval studies were ‘released ‘ *Crucial to ensure that open questions at registration are quickly resolved

*Products marketed prior to completion of confirmatory trials accelerated approvals ↑ over time *Only a small portion of indications have failed to verify clinical benefit

Accelerated approval – 25 years FDA experience

Presentation title 23

Confirmatory trials II EMA: Conditional MA report on 10 years experience

OPINION: *’ confirmatory studies should include both overall survival and quality of life ’ *’randomized control design of post-market studies can be lost due to the crossover from the control to treatment group or vice versa, raising questions about the true treatment effect ‘ * most drugs retain FDA approval and remain on the market when post-market studies show no clinically meaningful benefit compared with placebo

OPINION: *’ Conditional approvals share some parallels with the early termination of clinical trials, which are known to overestimate treatment benefits and underestimate harms’ *It is hard to believe that a few more trials—mostly phase II, open label,…..., possibly against inappropriate comparators—can fill the knowledge gap at the time of conditional approval.’

Confirmatory trials III

TGA approach • Provisional intended only for those

medicines where further confirmatory data can be collected

• Confirmatory data can be in a different clinical setting (by agreement)

• Evidence of a plan to submit comprehensive clinical data within 6 years required at the ‘early’ determination stage

• 2 year checkpoints to assess progress on clinical trial plan

Which endpoints are appropriate

Over the past 25 years more than one third of new oncology indications received accelerated approval Debate - appropriate endpoints for oncology: - not feasible to use OS as primary endpoint - For most advanced cancers progression of

disease can trigger changes in clinical management

26 …that were the primary basis for approval for accelerated or traditional pathways

Public & Healthcare professionals

“Some prescription medicines can now be approved faster”

“Not everything about a medicine is known

when it is first approved”

“We will watch medicines that have been approved for a short period of time more

closely”

“Report side effects to your health professional or call

1300 134 237”

“ Some prescription medicines will be approved for a short period of time

while more information about them is collected

Health Professionals

& Patients

Videos

Facebook

Webinars

Blogs

Journal articles

TGA website

Twitter

Immediate future… TGA

• Continued benchmarking against international regulators

• Continuing to seek feedback from all stakeholders

• Continuing refinement of guidelines and processes

• Document & share lessons learned

• Continue working with other regulators and establish processes

Industry • Convert to full registration as

soon as possible • Submit progress reports with

extensions • Ethical promotion of priority

and provisionally approved medicines

• Ongoing supply to patients, where appropriate, if provisional does not progress to full registration

Patients & Health Professionals

• Earlier access to promising new treatments

• PI/CMI statements re. provisional status

• Active participation in treatment decisions

• Co-design & co-development of communication material to inform these groups

28

Part II International Work Sharing Initiatives Dr. Kaylene Raynes Director, Applications & Advisory Management Director, Business Systems Review & Reporting

29

International Work-sharing for new Prescription Medicines – Government priority

– ACSS Consortium

– General model for WS

– What does work-sharing process look like for PMs?

examples

Overview & benefits for industry

– Common questions

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Government priorities

Health Portfolio Budget Statements

Outcomes 1 & 5 Department of Health & TGA

1: Health system policy, design & Innovation

5: Regulation, Safety & Protection

Outcome 1.5 International Policy - Engaging

on health issues

Outcome 5.1 Protect the Health and Safety of the

Community through Regulation

Delivery Dept engaged in several international

fora (WHO, OECD etc) to integrate evidence-based international Stds

Develop & forge new bilateral relationships with target countries

Protection of Health & Safety of Australian community…...through regulation of therapeutic

goods using International best practice Participate in International Engagement & Work-

sharing activities with CORs

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Regulatory Engagement Activities

• International Pharmaceutical Regulators Forum (IPRF) • International Generic Drugs Regulators Programme (IGDRP) • International Coalition of Medicines Regulatory Authorities (ICMRA) • The Australia Canada Singapore Switzerland (ACSS) Consortium

ACSS Consortium

Market Authorisation

TGA

HC

HSA

Swiss medic

• Promotes greater regulatory collaboration between international regulators across multiple areas: Therapeutic Goods Administration (TGA) Health Canada (HC) Singapore Health Sciences Authority (HSA) Switzerland’s Therapeutic Products Agency (Swissmedic)

• ACSS explores opportunities for work-sharing through various WGs:

• Generic medicines • NCEs = New prescription medicines • Complementary Health products • Pharmacovigilance • IT architecture

• Supported by confidentiality agreements & existing MOUs • Work-sharing of evaluation phase only with sovereign decision relating

to market authorization • Both NCE & Generic Medicines WGs have had successful pilots

International work - sharing - general model General NCE model

Market Authorisation

Quality Assessment

Toxicology Evaluation

Clinical Evaluation

TGA

HC

HC

TGA

Separate Sovereign Decisions

Confidence Building – a prelude to formal WS • Undertook confidence building exercises at different levels:

Understanding regulatory framework (process, stop clock, Qs, prescreen, timeframes)

Sharing of evaluation reports across all areas

Retrospective analysis of decisions to date

ACSS NCE pilot – General NCE WS model

• Across 3 evaluation areas – more complicated

• TGA & HC to WS with Singapore & Swissmedic to observe

• Leverage success of Generic WS trial – Quality assessment

• HC: Quality assessment & TGA: Non-clinical evaluation

• HC & TGA: Parallel clinical evaluation

• WS evaluations phase - separate sovereign decisions

Familiarity with International work-sharing

Australian Context

Market Authorisation

Quality Assessment

Toxicology Evaluation

Clinical Evaluation

TGA

HC TGA

X TGA

Retrospective analysis of previous PM decisions (HC:TGA) • Sovereign decisions potential for opposing decisions

• Decisions were aligned, slight differences in indications, dosages or registration conditions

• Risk of opposing decisions was low

Compound ‘X’ - becoming familiar • Identified during retrospective analysis. HC had approved

• When identified, TGA clinical & non-clinical evaluations were complete

• EMA & FDA had approved prior to HC & TGA; the TGA evaluators had access to the EMA & FDA review.

• TGA leveraged HC quality assessment reducing evaluation effort (15 working days)

• Facilitated confidence building between jurisdictions & allowed for systems to be built to support greater collaboration

• Undertook high level review of clinical evaluations

Compound X – A comparison study • Dossiers were identical, and X has received orphan status in Australia • High-level review of clinical reports – slight differences in analytical process & conclusions. Differences

included: a) Details reported for some evaluations of Phase 1 studies b) Level of importance placed on some studies over others – same data, interpreted differently c) Number of Q’s: HC = 39 & TGA = 22; with ~5 common Q’s

• Despite differences - both regulators found (consistent with FDA and EMA): ‒ an overall favorable R/B balance ‒ Approved identical indication & dosage

• TGA: in decision phase • HC: approved conditionally, requiring confirmatory evidence from the 2 further clinical trials being conducted

by Sponsor, aligning with FDA and EU post-marketing requirements.

35

Recent work-sharing initiative for PM Apalutamide (ERLYAND/ERLEADA)

Approved in 80 WD

Market Authorisation

Quality Assessment

Toxicology Evaluation

(+impurities)

Clinical Evaluation

(-BE, PopPK)

Clinical Evaluation

(+BE, PopPK)

TGA

HC

TGA

HC

Separate Sovereign Decisions

TGA ERLYAND ERLEADA HC

• First work-sharing initiative for PM between HC/TGA; HSA & Swissmedic were observers

• Designated priority in HC (Dec 2017); TGA priority designated in February 2018

• ↓ TGA timelines/milestones = HC timelines – priority pathway

• Important to deliver a proof of concept for Work-sharing

• Negotiated timelines/milestones with Janssen-Cilag (Australian /Canadian) – rolling Q’s

• TGA – Partial clinical evaluation (-clinical pharmacology, BE studies & popPK) and Full toxicology assessment + impurities

• HC – Full clinical & quality evaluation

• Integrated clinical evaluations between HC & TGA

• During evaluation - multiple TCs between agencies to discuss issues, rolling Q’s & the subsequent responses to Q’s shared (clarifaxes/TGA’s rolling Q’s)

• Separate PI/PM negotiations with local sponsors

• Sovereign Decisions for market approval – 4th July 2018

Apalutamide – Proof of concept

Janssen-cilag feedback: • Positive, smooth & predictable process with flexibility • Level of transparency, communication & coordination between Janssen and affiliates was fantastic • Would recommend work-sharing initiative to other industry members

“…….congratulate the TGA and Department of Health for their commitment to ongoing reforms to policy and process in ensuring better health outcomes for Australians. The collaboration between the Australian and Canadian health authorities in achieving such an expedited approval of this important medicine for men with prostate cancer is indicative of the Government’s genuine commitment to …. approval of new, innovative therapies,” - Mr Bruce Goodwin, Managing Director Janssen Australia and New Zealand.”

37

Work-sharing – Process overview

- 3-6months

• Contact TGA with EOI in work sharing (https://www.tga.gov.au/acss-nce-work-sharing-pilot) • Give thought as to the best regulatory pathway (priority, standard, orphan) for your submission • TGA will reach out to nominated CORs to canvass possibilities on your behalf

- 3 months

• Establish pre-submission meetings (multi-way between regulators is an option) • Clarify any differences in dossiers, synchronize submission dates & willingness to share reports with CORs • Draft timeline/process is developed cognisant of pathway & available resources – shared with Sponsor

submission

• Pre-screening & negotiations with sponsor (Q’s, batching/rolling, timelines), timelines/milestone are confirmed • Sponsor communication plan developed • Communication strategy between participating jurisdictions established

Evaluation

• Share evaluation reports; Evaluators/Delegates discuss data • Consolidated questions & Sponsor responses shared across all parties

Sovereign decisions

• Simultaneous market authorisation across all jurisdictions • National PI/PM negotiations & RMP

38

Work-sharing – Benefits for all

Industry

Potential for simultaneous market authorisation in all jurisdictions

Flexible milestone approach with transparency & coordination

Vision to decrease workload through single window service

Regulators Improved efficacy with potential to reduce regulatory effort

Best of both worlds - Sovereign decisions & harmonisation

Maintain & share expertise across regulators

39

Work-sharing – some common questions • Does an application need to be submitted to all regulators involved with WS ?

Yes and on a similar date, and preferably with the same dossier (or minor local specific modifications)

• How are clarification Q’s handled during work-share review? Priority review - Q’s raised during the evaluation will be sent to the respective local affiliate for a response, then shared with partnering regulators (& affiliate to support complete eCTD) Standard review - consolidated Q’s will be sent to both local affiliates simultaneously based upon the review milestones established jointly by partnering regulators.

• Will the labelling be part of the joint review process? No. While there may be discussions between regulators about product labelling, it is understood that different laws and frameworks exist between the countries that will affect decisions on the final text and product labelling.

• Is the work-sharing initiative available for all applications? No. This initiative is currently available for only specific applications and under certain conditions.

40

41

Scheduling Policy Framework (SPF): Reform Outcomes

•Created a new appendix to enable additional controls for newly down-scheduled (prescription to OTC) substances

•Streamlined and aligned the scheduling consideration and market authorisation process for substances moving from prescription to OTC.

• Increased time available for interim decision consultation.

•Piloting applicants making presentations to the scheduling committees

•Provided guidance for using risk-benefit analysis

•January 2018: the revised PF and Scheduling Handbook were published

•February and March 2018: 2 meetings were held with stakeholders to discuss further evolution of scheduling reforms

Governance Decision Making

Tools Process Improvements

42

Reforms to Schedule 3 advertising • Advertising of medicines containing Pharmacist Only

(Schedule 3) substances direct to consumers (DTC) should be permitted unless actually deemed unsuitable by the Scheduling Delegate

• Factors the Delegate will consider when deciding if a substance is not suitable for advertising: 1. The potential impact on public health

a) Is there potential for inappropriate use, abuse, diversion that may be exacerbated by advertising?

b) Are there potential interactions with the substances (drug-drug, drug-food) that require increased patient education to ensure safe use?

c) Are there additional risks associated with the dosage form that may impact on safe use?

d) Any other information that may be relevant, for example the substance has sedating properties, or there are safer alternatives available

Mandatory Requirements • Advertisements for therapeutic goods must comply with

the Therapeutic Goods Advertising Code (the Code) • The revised Code is due to take effect on January 2019 • There is a specific requirement in the draft revised Code

for Schedule 3 substances:

“Ask your pharmacist – they must decide if this product is right for you”

43

Reforms to Schedule 3 advertising • Public consultation to determine which Schedule 3

substances should be added to Appendix H was closed on 9 July.

• The current Schedule 3 substances were classified into two lists: those that can be advertised (added to Appendix H), those that are not suitable for advertising.

• Following consideration of the consultation feedback, together with feedback from stakeholder meetings, the Delegate will do one or more of the following for each substance:

1. Make a decision to add a substance to Appendix H 2. Decide not to add a substance to Appendix H 3. Reconsider the initial proposal and seek further

comment on an alternative proposal 4. Refer the substance to the ACMS for further advice.

• 20 submissions were received as part of the public consultation.

• The delegate is currently considering the feedback received from stakeholders.

• It is anticipated that most of the substances proposed to be added to Appendix H in the consultation paper will be added to Appendix H.

• There are some substances that will be referred to the ACMS for further advice.

• It is anticipated that this work will be largely completed by the end of 2018.

44

Low Risk Products Review Outcomes of this review have been published on the website

• What is not changing (maintaining the status quo) – Regulation of vitamins and minerals – Sunscreens regulation.

• Products that will be excluded (not a therapeutic good for the purposed of the Act, and over which we have no regulatory control) – Antiperspirants – Ear candles

• Products that will be exempted from specified regulatory requirements – Tampons and menstrual cups – Nappy rash creams – Some hard surface disinfectants

• Other regulatory activities flowing from this review include: – A clean up of class I medical devices that should not be

included on the ARTG – Further reform and streamlining of the regulatory framework

for hard surface disinfectants – Further improvements to the way sunscreens are regulated

• Rehydration/sports drinks which were identified for further reform consideration are now being considered as part of a broader project addressing the food-medicine interface.

• Government is yet to decide on the preferred regulatory approach for aromatherapy and homeopathy products.

45

Transparency Initiatives

0102030405060708090

100

2009 2010 2011 2012 2013 2014 2015 2016 2017

Num

ber

TGA: Number of published Australian Public Assessment Reports (AusPAR) for Prescription

Medicines :2009-2017

Calendar Year

• First Australian Public Assessment Report (AusPAR) for prescription medicine published in 2009

• Modelled under the EMA “EPAR” (see publication)

• Over 900 AusPARs published • Business rules - ‘major submissions” that are

referred to an advisory committee (ACV/ACM) • +tive, -tive decisions, and some withdrawals • TGA discretion

46

Proposed transparency reforms • AusPARs

• Review of business rules & AusPAR document

• Subject to consultation

• Reduce volume of documents

• Shorten sponsor negotiation

• AusPARs for all new chemical/biological entities

• Promotion of AusPARs to health professionals

• Publication of submissions under evaluation

• Subject to consultation

Outline of current AusPAR document

Also includes two attachments 1. The approved Product Information as at the time the AusPAR was

prepared and first published 2. Extract from the clinical evaluation report containing more details of

the clinical findings 47

PI/CMI initiatives

Priority areas of work

Status Requires external consultation?

1.Boxed warning guidance 2. Mandate safety changes for significant safety issues 3.xml searchability for PI and CMI

Consultation phase Planning phase Planning phase

Yes Yes Yes

Boxed Warning

Teratogenic effects: Thalidomide has caused severe birth defects when taken during pregnancy. Thalidomide should never be used by women who are pregnant or who could become pregnant whilst taking the medicine or could become pregnant within 4 weeks after stopping the medicine. Even a single dose can cause birth defects

48

Public Consultation on Boxed Warning Guidance • A mechanism used to highlight special

warning statements in the Product Information to the prescriber.

• Concerns prominent safety issues with a potential for major impact on public health.

• Have been used for more than 25 years in Australia and are also used in other jurisdictions.

• Currently no TGA guidance, we are seeking to standardise the approach.

• Three week consultation period closing 31 August 2018

49

Boxed Warning Guidance

Boxed Warning in the PI

Format

Content

Applies prospectively, unless new information

becomes available Required evidence base

When a boxed warning is proposed

CMI and Promotional material

Stakeholder feedback Process

Summary

• Multiple pathways for prescription medicines registration available

• Working with stakeholders is key in ensuring expedited access to life saving medicines

• Opportunities for additional reforms

51

TGA continues working to integrate new systems & increase efficiencies • Improve internal business processes • Recruitment • Improve IT systems • Increase alignment with overseas regulators