Regulatory Updates in Taiwan

Hwei-Fang Cheng, Ph.D.

Deputy Director-General

Taiwan FDA

8th Joint Conference of Taiwan and Japan on Medical Products Regulation

Oct. 15, 2020

Outline

02

Medical Products Management01

03Collaboration with Japan

04Future Prospects

2

Response to COVID-19

3

Current Regulatory Framework for Cell and Gene Therapy in Taiwan

Medical productMedical technique

CommercializationCustomization

Cell/ gene/ tissue engineering

Cell (autologous)6 categories

IND (Clinical Trial) /NDA

Treatment Plan

Distributed by pharmaceutical

companies

Performed by registered physician in recognized

medical institute

Approved 48 Cell therapy technique

Approved 68 Cell therapy IND

Approved 13 gene therapy IND

updated to Aug. 31, 2020

Pharmaceutical Affairs Act &Regenerative Medicinal Product Act (Draft)

Regulation Governing the Application of Specific Medical Examination Technique and Medical Device

Government

Industry Academia

Guideline for bridging medical technique to medical products (Draft) Aug 28, 2020

3

4

Innovative cell therapy productsCLS2702C/CLS2702D• (Autologous) Oral Mucosal Cell

Sheet Transplantation• Esophageal cancer • Phase III ongoing

NK+NKT• non-small cell lung

cancer• Phase I ongoing

PB103 (allogeneic NK cell)• non-small cell lung cancer• Phase I/IIa ongoing

Welgenaleucel (UWC19)

• Relapsed or refractory B-cell non-hodgkin's lymphoma

• Phase I/II ongoing

Innovative CAR-T therapy products

Evolving Domestic Innovative Regenerative Medicine Products

ADCTA-SSI-G1 (Dendritic cell/tumor antigen)

• glioblastoma multiforme• Phase III ongoing

CAR-T Products under development

(Examples)

4

5

Why biosimilar is important?

MOST OF THE TOP SALES DRUGS ARE BIOLOGICS

THE PATENTS OF HIGHLY SUCCESSFUL BIOLOGICS ARE SET TO EXPIRE OVER THE NEXT 10 YEARS

「BIOSIMILAR」 HELP TO STABILIZE THE FINANCES OF NATIONAL HEALTH INSURANCE (NHI)

5

6

3

1

4

2 5

6Harmonize with International Regulations

What we had done

Transparent review considerations(provide guidance)

Provide counseling mechanism

Establish multiple communication pathways, increase public awareness

Improve review quality and review efficiency

6

7

Current status of biosimilar drugs in Taiwan

USA(28)

• Adalimumab• Bevacizumab• Infliximab• Rituximab• Trastuzumab• Etanercept• Epoetin alfa• Filgrastim• Pegfilgrastim

EU(58)

• Adalimumab• Bevacizumab• Infliximab• Rituximab• Trastuzumab• Etanercept• Enoxaparin sodium • Epoetin alfa• Epoetin zeta• Filgrastim• Follitropin alfa• Insulin aspart• Insulin glargine• Insulin lispro• Pegfilgrastim• r-Somatropin• Teriparatide

Korea(25)

• Adalimumab• Infliximab• Rituximab• Trastuzumab• Etanercept• Darbepoetin alpha• Epoetin alfa• Insulin glargine• r-Somatropin• Teriparatide

Taiwan(17)

• Adalimumab• Bevacizumab• Infliximab• Rituximab• Trastuzumab• Insulin glargine• Filgrastim• Pegfilgrastim• r-Somatropin

Developing biosimilar in Taiwan• Trastuzumab (Phase III / Phase I)• Tocilizumab (Phase I)• Omalizumab (Phase I)• Epoetinum alfa (Phase III)• Filgratim (Pre-IND)

2020.10.06 update

7

8

NCE Serious disease

Unmet medical need

children's ethnic groups /or

prevalence rate less than 5/10,000

Suitable

Review process

Priority Review ~240 days

Priority review voucher (Pediatric)

Incentives

CPPCertificate of Pharmaceutical exempt if domestic clinical trials had executed.

clinical trialsrelaxation by case.

BSENo requirement of Bridging Test Evaluation prior application.

post-marketingactual domestic consumption and estimated domestic demand for use must be report.

7 Rare disease

New Expedite Review Program: Pediatric or Rare disease Designation

Nov. 18, 2019

1 Pediatric

16 application

(Designated)

(Designated)

8

9

IND Applications in Taiwan by Local/MRCT Type

0

50

100

150

200

250

300

350

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019

2411 21

34 38 47 4633

58 57 5135

5540 36

1022

2016 9

17 1720

23 27 29

29

2935

21

86100

127

155140

129111

185

177190

222

210

214 234

229

TW single site TW multicenter MN multicenter

205

187193

174

238

258

120

133

168

274

302

274

298306

286

No.

of A

pplic

ations

MRCT :

80%

9

10

IND Applications in Taiwan by Study Phases

0

50

100

150

200

250

300

350

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019

14 12 10 11 18 18 1534 29 38 43 49 45 38 42

33 32 46 4660

44 53

6864

7493 94

87 90 9569 86

106132 95

110 90

121 138

139

137 121 141168

127

43

6

16

14 2116

1527

23

29

1025

13

22

Phase I Phase II Phase III Phase IV/Others

120133

168

205

187 193

174

238258

274 274

302 298309 286

No.

of A

pplic

ations

10

01

02

03

04

05

Real World Data/Evidence(RWD/RWE) GuidanceBasic

Consideration

Electronic Health

Record

Study design using

RWD

Relevance and

Reliability

Application and

Submission

Instruction

Basic Considerations in Supporting Drug Research and Development with Real-World Evidence

Use of Electronic Health Record Data in Clinical Trials/ Investigations Guidance (draft)

RWE study designs- considerations and key points for pragmatic clinical trial (draft)

Real World Data Quality Evaluation-Relevance and Reliability consideration (draft)

RWD/RWE application and submission guidance (drafting)

2020.04.29

2020.08.28

2020.10.13

2020.07.22

Sapropterintablets

Oral Ketoconazole, Hepatotoxicity

Case study 1 Case study 2

Alteplase

Case study 3

11

12

Generic Drug Policy

Promotion

of generic

Comprehens

ive

counseling

Approval rate

Compliance

rate

Through these efforts, our export of generic drugs has also increased. In 2019, the

export of preparations increased by about 25%

compared with 2018.

Improve the accessibility of generic drugs

Encouraging the development of “Competitive Generic” to lower drug cost than the brand drug

Promote generics through media, brochures and visits to pharmaceutical to improve the consumer's recognition

12

13

Implementing E-System13

ICH E2B(R3)

Implemented on 1st September,

2020

Adverse Event Reporting System

Track-and-Trace System

eCTD v3.2.2

Technical Document(M1~M5)

Under-Construction

E-Submission

Paperless

Efficiency

14

Establishing Medical Devices Act

Set statutory framework

2014

Complete initial draft

2015

Announce revised draft and communicate with the Legislative Yuan and industry

2016Promote legislative process

2017

Establish the Medical Devices Act to be internationally harmonized and meet domestic needs

Future

2018-2019Conduct article-by-article deliberation and inter-party negotiation

14

2020Promulgate the Act via Presidential order, develop and formulate relevant and complementary regulations and announcements

Digital Health Medical Devices

Updated Digital Health Medical Device Guidelines:

1. Guideline of Cybersecurity for the Manufacturers

2. Q&A for Intelligent Technology Medical Device Registration

3. Artificial Intelligent / Machine Learning-Based Software as a Medical Device Registration Guideline

(2019.11.21)

(2020.5.15)

(2020.9.23)

15

Approved Digital Health Medical Devices

Robotic

Exoskeleton

Diabetic Retinopathy

screening system

AI-assisted solutions for

Diabetic Retinopathy

identification.

Powered Exoskeleton

Assist people with lower

limbs weakness to walk with

stronger posture.

Diabetic retinopathy screening system

http://www.freebionics.com.tw/en/freewalk

https://www.acer-healthcare.com/veriseedr

Free Bionics Taiwan Inc.

Acer Healthcare Inc.

16

17

Response to COVID-19

Drug Supply

Database

Platform

Guidelines

Maximize

Production

Restrict

Exportation

Protect trial

recipants’

right and

safety

Emergency Use

Authorization

Fast Track

Clinical Trial

Review Process

Registration

Optimization

Measures

Consultation

Vaccine

DRUG SUPPLYSANITIZER PRODUCTS

CLINICAL TRIALSDRUG

DEVELOPMENT

17

18

Assistance for Manufacturers

Response to COVID-19

1

2

4

3

Management of Stockpiles

Offer Guidance & Consultation

Emergency Use Authorization

Relaxation of Regulations

• Announced technical guidance on 4 different medical devices

• Approved 69 applications of special manufacturing

• Approved 104 applications of special import

18

TFDA Virtual Meeting on COVID-19

Actions taken by regulatory authorities to prevent potential drug shortages or supply disruptions

Actions taken by regulatory authorities to satisfy the increasing demands for alcohol-based sanitizer products and PPE

Actions taken by regulatory authorities to fulfill the needs for COVID-19 diagnostic test kits from regulatory perspective

19

Collaboration with Japan

Progress for the Pharmaceutical Working Group

Progress for the Medical DevicesWorking Group

• Renewed the Q&A proposedby industries from both sidesand published it for thebenefit of stakeholders

• Updated the regulationsrelating to cybersecurity orartificial intelligence medicaldevices for both sides

• Sharing and comparing reviewpoints for further cooperation,including the pilot project onproduct review.

• Established the InformationSharing model and Directcontact of post-marketingsurveillance information

20

Progress for the QMS Working Group of Medical Devices

2014

2017

21

2018

2019

2020

Establishment of QMS WG 2nd Joint Conference of Japan and Taiwan on medical product regulation

Monitored audit for TUV SUD PS Japan ;MoC has been signed in November 30 ;

Start of Phase III after signing of MoC

Abbreviated mode is accepted by Taiwan and Japan authority in review of QMS

The utility of abbreviated mode is continuing and related questions and answers are gathering and sharing by Taiwan and Japanauthority in the review of QMS.

22

Taiwan Food and Drug Administration Ministry of Health and Welfare

Future Prospects

To Establish Forward-looking Legislation

To Complete Accessible Information Platform

To Establish Professional Review Team

To Optimize Quality Compliance and Management

To Enhance International Regulatory Collaboration

To Provide Efficient Communication and Services

22

Thank You