Efforts on the Japanese side Session 1: Enhancing Review Efficiency of Pharmaceuticals and
Medical Devices
Naoyuki Yasuda
Office Director
Office of International Programs
Pharmaceuticals and Medical Devices Agency
4 October, 2016
1. Introduction
2. Promotion of Regulatory Science to the Global Level
3. Promotion of Developing Innovative Products
Today’s Content
1. Introduction
Today’s Content
As at 2006, new drug marketing in Japan lagged on average 4 years behind the initial
global launch, a gap of around 2.5 years over the US, the country with the smallest lag. *
1,417 days(=approx. 4 years)
915days
757days
620 days 583 days 538 days 512 days
505 days
(=approx. 1.5 years)
Japan France Denmark Germany Sweden Switzer- land UK US
* The average of the number of days until marketing in the respective country following initial launch of the global top 100 products. Since the number of the top 100 products available varies with the country, the marketing lag has been calculated using only the number of products marketed in the respective country. For example, for the US where all drugs are available it was calculated using 88 of the 100 best-selling drugs after deduction of duplicate ingredients and those launched prior to 1981. Source: OPIR Research Paper No. 31 (May 2006)
Gap between Japan and the US Approx. 2.5 years
Drug Lag – What did PMDA solve??
4
319
256
648
521
678
605
753
341
426
291
708
1065
PMDA Staff Size
820
0
200
400
600
800
1000
1200
2004.4 2005.4 2006.4 2007.4 2008.4 2009.4 2010.4 2011.4 2012.4 2013.4 2014.4 2015.4 2018
Administrative part Safety Department
Review Department Planned
Enhancement of Consultation from earlier stage
© 2015 DIA, Inc. All rights reserved.
Exploratory Research
Optimization Research
Non-clinical
trial
Development Research Research with specific objectives (disease treatment, etc.) aiming at practical use
Applied Research
Basic Research
Clinical Trial
Application
Review
-> Approval
[Old Model]
Consultation
[New Model]
Consultation
LATER SATGE
EARLIER SATGE
Accelerate the application & approval period
Utilization to Int’ Guideline (e.g. ICH/GL)
© 2014 DIA, Inc. All rights reserved.
http://www.cirsci.org/wp-content/uploads/2016/05/CIRS_RD_-Briefing_59_23052016.pdf
PMDA achieved shorting approval time of new drug
R&D Briefing 59, May 2016, © Centre for Innovation in Regulatory Science, Ltd.
2. Promote Regulatory Science to the Global Level
Today’s Content
Science Board Established in May 2012; to discuss how PMDA can better cope with products with advanced science & technology, in each developmental stage (basic research, development support, product review, and PMS).
Pharmaceutical consultation on R&D
Strategy
Basic Research
Seeds of new
drug / medical devices
Non-clinical tests
Clinical Trial
Quality Tests Practical use
Innovative medical products
Offices of Review (Drugs & Medical Devices), Office of Safety
Clinical Trial Consultation
Review
Review Approve Post Marketing
Post Marketing Safety Measure
Board members
Academia (Knowledge of the Latest Innovative Technologies)
Science Board
9 Communication
Outcome of the Science Board
Summary of discussion on the assessment of the current status of personalized medicine related to development and regulatory review (2014)
Summary of discussion on non-clinical pharmacological studies on anticancer drugs (2013)
Current perspective on evaluation of tumorigenicity of cellular and tissue-based products derived from induced pluripotent stem cells (iPSCs) and iPSCs as their starting materials (2013)
1st term (FY2012 - 2013)
2nd term (FY2014 - 2015)
Discussion on Evaluation of Medical Devices in Pediatric Use (2015) Proposal on Basic Principle to Quality Assurance of Cell Therapy (CT) Products (2015) Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs
(2016) Current Status and Perspectives of Placebo-Controlled Studies (2016) Report on the Use of Numerical Analysis for Evaluating the Strength of Orthopedic
Implants (2016)
3rd term (FY2016 - 2017)
Topics are now in discussion (rare diseases, bottle neck of medical development, and artificial intelligence)
Harmonization to International Guideline/Standards
[Pharmaceutical area]
• Participation to ICH
• Participation to PIC/S
• Bilateral talking with US/Europe on each area & GCP inspection
[Medical Devices area]
• Participation to IMDRF (GHTF)
• Participation to ISO/IEC standard setting (horizontal)
11
Can avoid duplicative works and seek common data utilization
Under the harmonization
3. Promotion of Developing Innovative Products
- Pharmaceutical Affairs Consultation on R&D Strategy
- SAKIGAKE Designation
- Conditional and Time-limited Authorization of Regenerative Medical Products
- Utilization to International Standards on Medical Devices
Today’s Content
(1) Pharmaceutical Affairs Consultation on R&D Strategy
© 2015 DIA, Inc. All rights reserved.
Exploratory Research
Optimization Research
Non-clinical
trial
Development Research Research with specific objectives (disease treatment, etc.) aiming at practical use
Applied Research
Basic Research
Clinical Trial
Application
Review
-> Approval
[Old Model]
Consultation
[New Model]
Consultation
LATER SATGE
EARLIER SATGE
Communication from the early development
Seamless Activity from Research to Approval - Collaboration PMDA & AMED -
© 2015 DIA, Inc. All rights reserved.
Exploratory Research
Optimization Research
Non-clinical
trial
Development Research Research with specific objectives (disease treatment, etc.) aiming at practical use
Applied Research
Basic Research
Clinical Trial
Application
Review
-> Approval
Drug Discovery Support Network
AMED*
Pharmaceutical Affairs Consultation
On R&D Strategy (Scientific Advice)
PMDA
Close Collaboration • Japan Agency for Medical
Research and Development
1.Utilizing Pharmaceutical Affairs Consultations on R&D
Strategy
3. Mutual cooperation to improve clinical research
infrastructures
4. Sharing information
2. Support AMED to evaluate projects
Partnership Agreement with AMED (August 19, 2015)
1. Research and Development on Medical issues
2. Foundation of Clinical Study
3. Support towards commercialization
4. Promotion of International Strategy
Japan Agency for Medical Research and Development (AMED) was established on 1 April, 2015, with following missions
Collaboration with other Organizations
Comprehensive Partnership Agreements since FY 2015
NCC (National Cancer Center) (February 2, 2016)
Hiroshima University (March 4, 2016)
Keio University (March 11, 2016)
• Joint Research
• Human Resources Development
• Information Dissemination
Joint Graduate School Agreement (December 2009- )
with 19 graduate schools in medicine: Personnel Exchanges
Expansion and
Improvement
University of Tsukuba (March 30, 2016)
National Center of Neurology and Psychiatry (July 11, 2016)
Designation Criteria
- New mechanisms compared to existing approved products
- Medical products for diseases in dire need of innovative therapy
- Applied for approval firstly or simultaneously in Japan
- Prominent effectiveness can be expected based on non-clinical study and early
phase of clinical trials
Advantage for Designated Products
Prioritized Consultation
[Waiting time:
2 →1 month]
Review Partner
[PMDA manager
as concierge]
Post Market Measures
[Extension of re-examination
period considered]
Prior-Review
Consul.
(Rolling Review)
Prioritized Review
[12 → 6 months]
(2) SAKIGAKE Designation
SAKIGAKE - General Timeframe
18
Designated:
6 Pharmaceuticals, 2Medical Devices, 3 Regenerative Products
Progress of SAKIGAKE Designation System Comprehensive Evaluation Consultations in SAKIGAKE System
Approval NDA
Submission
Review
1. CMC
2. Non-Clinical
3. Clinical
4. GCP/GLP
Compliance
5. GMP
Compliance
ca. 4 months
First
submission
I/A
(on-site Inspection) Preparation
On-site Inspection Phase
III
Preparation
On-site Inspection (on-site inspection)
= Permission to
submit
I/A
Inquiry/Answer
6 months
Monthly
Consultation
with Concierge
SAKIGAKE Designated Products (Drugs, as of Oct. 2015)
Name of drug Proposed indication Name of applicant
Sirolimus (NPC-12G) Angiofibroma associated with tuberous sclerosis Nobelpharma Co., Ltd.
NS-065/NCNP-01 Duchenne muscular dystrophy (DMD) Nippon Shinyaku Co., Ltd
S-033188 Influenza A or B virus infection Shionogi & Co., Ltd.
BCX7353 Management of angioedema attacks in patients with hereditary angioedema (HAE)
Integrated Development Associates Co., Ltd.
ASP2215 First-relapsed or treatment-resistant FLT3 mutation-positive acute myeloid leukaemia Astellas Pharma Inc.
Pembrolizumab (genetical recombination)
Unresectable, advanced and recurrent gastric cancer MSD K.K.
SAKIGAKE Designated Products (Medical Devices and Regenerative Medical Products, as of Feb. 2016)
Name of medical products Proposed indication Name of applicant
Titanium Bridge
(Hinge-type plate with titanium) Adduction-type spasmodic dysphonia Nobelpharma Co., Ltd.
Bioresorbable adhesion barrier
(THN-01: Trehalose solution) Postoperative adhesion prevention
Otsuka Pharmaceutical Factory,
Inc.
STR01
(Autologous bone marrow-derived
mesenchymal stem cell)
Nerve syndrome and dysfunction caused by spinal
cord injury NIPRO Medical Co., Ltd.
G47△
(Growth-controlled oncolytic
herpes simplex virus type 1)
Malignant glioma Daiichi Sankyo Co., Ltd. The University of Tokyo, Institute of Medical Sciences
Autologous cardiac
progenitor/stem cells
Pediatric congenital heart disease (single ventricle physiology)
Japan Regenerative Medicine Co.,
Ltd.
(3) Conditional and Time-limited Authorization of Regenerative Medical Products
Re-Application (or Expiration) within max. 7yrs
Conventional Regulatory Approval Process
Clinical trial (likely to
predict efficacy,
confirmation of
safety)
Marketing further confirmation of efficacy
and Safety
Clinical
research
Marketing
Authorization or
Revocation of the
conditional approval
Conditional
and time-
limited
authorization
Continued
marketing
Clinical trial (Confirmation of efficacy and safety)
Clinical
research
Mark
eti
ng
Approval
Regulatory System that Facilitate Early Patient Access
Regenerative Medical Products Approval
HeartSheet ® for serious heart failure due to ischemic heart disease
(conditional and time-limited authorization – 5 years, conducting post-
marketing efficacy studies)
1 Product approved on 18 September 2015 Note: application in September/in October 2014
Conditional approval requirement (part)
I. Confirmation of efficacy (survival) with 60 HeartSheet
cases vs 120 existing treatment cases
II. Time limitation of approval: 5 years
・ Target: Serious heart failure due to Ischemic Heart Disease
・ Product: Autologous skeletal myoblast
・ Manufacturing Process - Biopsy from Quadriceps -> manufactured at company CPF -> sheet culture in hospital CPF
[Conditional and time-limited authorization(HeartSheet ®)]
Conditional approval requirement (part)
I. Confirmation of efficacy (survival) with 60 HeartSheet cases vs 120 existing treatment cases
II. Time limitation of approval: 5 years
Figures quoted from the company
press release docs
Demonstrating Conformity Assessment
25
Essentia
l Prin
cip
les
Test1
Test5 Test4
Test3
Test2
Test1 Test4
(Standards) Test3
Test2
Test1
Test2
(Standards) Test3
(Standards)
Merits of Standards
Enhance transparency
Reduce duplication
Reduce Oversight
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Time saving
Cost saving
Enhancing Safety and Efficacy
Technologies beyond Standards
27
Exis
ting t
echnolo
gie
s
MD1 MD2 MD3
Innovative T
echnolo
gie
s
Sta
ndard
s
Com
pete
ncy o
f Revie
ws
IMDRF Strategic Priority
The MC will select further New Work Items (NWIs) to improve
the effectiveness and efficiency of premarket review. These may
include assuring the reliability of data submitted to regulatory
bodies, improving quantity and quality of clinical data, developing
Good Review Practices for premarket reviews/evaluations which
includes competence and training for pre-market reviewers,
developing guidance on benefit-risk determinations, and
improving the suitability of international standards for
regulatory authorities and effective regulatory authority
involvement at each stage in standards development.
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Thank you for your attention!!
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