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Latest Trend of Pharmaceutical and Medical Device Regulation in Japan
Takao Yamori, Ph.D.Executive Director
Pharmaceuticals and Medical Devices Agency (PMDA)
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Regulatory Authority in JAPAN
Scientific Review for Drugs & Medical Devices
GCP, GMP Inspection
Consultation on Clinical Trials etc.
Final Authorisation of applications
Administering laws, publishing legislations
Publishing Guidelines
Advisory committee
Supervising PMDA Activities
PMDAMHLW – PSEH BureauPharmaceutical Safety and Environmental Health Bureau,
Ministry of Health Labour and WelfarePharmaceuticals and Medical Devices Agency
Today’s topics
1. Review Process
2. International Collaboration
3. Summary
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New active substance (NAS) median approval time for six regulatory authorities in 2008-2017 (Pharmaceuticals)
Centre for Innovation in Regulatory Science (CIRS) , 2018, R&D Briefing 67
PMDA
333
EMA
419
FDA
243
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NAS median approval time by review type for six regulatory authorities in 2013-1017
Centre for Innovation in Regulatory Science (CIRS) , 2018, R&D Briefing 67
PMDA was the agency with the smallest difference
between expedited review median approval time and standard review median approval time in 2017.
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Reform to rational and efficient structure based on Regulatory Science
Lead the World in Regulatory Innovation
Stage Agendas for MHLW/PMDA Activity
Development Support for promising seeds to forward the
development
Regulatory Sceince Consultation(from July 2011)
Review Approaches to cutting-edge technologies
(including iPS Cells by collaboration with Academia)
Encourage Japan-first development and approvals
Improve efficiency of development and review process by utilizing electric data
Science Board(from June 2012)
SAKIGAKE Designation System(from 2015)
Conditional Early Approval System for Pharmaceuticals(from October 2017)
Post-marketing
○ Utilize medical information database to develop more
sophisticated safety measures
○ Predictability & Transparency in post-marketing change
control
MIHARI project (from 2009)
MID-NET project (from April 2018)
PACMP pilot (from April 2018)
Establishment of Regulatory Science Center (from April 2018)
*PACMP: Post-Approval Change Management Protocol
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SAKIGAKE Designation System
ConsultationClinical
Trial PhIII
Clinical Trial
Ph I/II
【Ordinal Review】
【SAKIGAKE 】
Review
Clinical
Trial PhIII
Clinical Trial
Ph I/IIPrior
Review
Priority Consultation
2 months
12 months
Priority Review
6 months
1 month
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Name of product
(Applicant)Summary of product Product indications
XOFLUZA Tablets 10mg/20mg
(baloxavir marboxil)
by Shionogi & Co., Ltd.
- an antiviral drug indicated for influenza
- novel mechanism
(suppresses influenza viral replication via inhibition of cap-
independent endonuclease enzymes required for viral mRNA
synthesis in host cells)
Influenza
Types A and B
図2 塩野義製薬株式会社プレスリリース資料から引用、一部改変
< Timeline of SAKIGAKE-designation >
Oct. 2015: Designated for SAKIGAKE
Novel mechanism of action developed in Japan (Shionogi & Co., Ltd)
Influenza Virus
Figure Excerpted with partial revisions from Shionogi’s original press release
Attachment
Released
from cell
Particle formation
Invasion
Membrane fusion Duplication of genome RNA
mRNA elongation
Polymerase inhibitor
(favipiravir)
Start of mRNA synthesis
(Cap endonuclease)
Neuraminidase inhibitor
(e.g. oseltamivir, laninamivir,
peramivir)
Cap-dependent endonuclease inhibitor
(baloxavir marboxil)
Viral genome
RNA
Feb. 2018: Regulatory approval
4 months
Oct. 2017: Submission
for marketing approval
Details of the product approved with SAKIGAKE-designation (Drug)
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Name of product
(Applicant)Summary of product Product indications
TITANBRIDGETM
(device for thyroid cartilage
fixation)
by Nobelpharma Co., Ltd.
- A medical device to be used for the treatment of adductor
spasmodic dysphonia
- novel mechanism
(preventing excessively tight closure of the glottis and maintaining
the glottis opening)
Type Ⅱ thyroplasty
< Timeline of SAKIGAKE-designation >
Feb. 2016: Designated for SAKIGAKE
Dec. 15, 2017: Regulatory approval
6 months
Jun. 30, 2017: Submission
for marketing approval
Novel mechanism of action developed in Japan
(Nobelpharma Co., Ltd)
Developed by Dr. Nobuhiko Isshiki, Prof. of Kyoto Univ.
Kumamoto Univ.
etc., cooperated to
conduct research
Manufactured by
Wakayoshi
Seisakusho Co.,
Ltd. (Fukui pref.)
Nobelpharma,
venture capital,
led them to
practical use
*There AMED research funding support of MHLW
Improvement of
dysphonia
Over-closing
prevention of glottis
Details of the product approved with SAKIGAKE-designation (MD)
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<Implemented on 20 Oct, 2017>
To realize early access to innovative treatments that are:
For severe diseases with limited choice of treatments
Difficult to conduct confirmatory clinical trials due to small number of patients or prolonged follow-up period
Conditional Early Approval System for Pharmaceuticals
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Accepted Pharmaceuticals for Conditional Early Approval scheme
Product Expected indication Marketing Authorization Applicant
Granted Date
Lorlatinib The treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on 1 or more ALK tyrosine kinases inhibitors (TKIs).
Pfizer 8 June 2018
Pembrolizumab(KEYTRUDA)
The treatment of patients with unresectable or metastatic, microsatellite instability-high(MSI-H) Cancer
MSD 22 June 2018
https://www.pfizer.co.jp/pfizer/company/press/2018/2018_06_12.htmlhttp://www.msd.co.jp/newsroom/msd-archive/2018/product_news_0627.xhtml
All medical technologies using processed cells
whose safety and efficacy have not yet been
established
The Act on Pharmaceuticals and
Medical Devices (PMD Act)
Production and marketing of regenerative
and cellular therapeutic products by firms
The Act on the Safety of
Regenerative Medicine
Commercial IND and
product approval
MHLW process PMDA process
At hospital
Regenerative
Medicine Products
Two acts regulating cellular-, tissue- and gene therapies(Regenerative medicine products)
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Clinical Trial Clinical research
Mar
keti
ng
Approval
Clinical Trial
First Approval
Marketing&
Clinical Trial
Permanent Approval
or Revocation
Clinical Research
↑Re-application
Conventional Pathway
E.g. Autologous skeletal myoblast
New scheme
Conditional & time-limited approval for cellular-, tissue-,
and gene-therapy products (Regenerative medicine products)
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Today’s topics
1. Review Process
2. International Collaboration
3. Summary
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:Cooperative Arrangement has been signed between the Interchange Association of Japan and East Asia Relations of Taiwan
1
PMDA staff stationed at the agency
Joint symposium held Cooperative Arrangement signed
As of 23 Oct. 2017
Health Canada,Canada
FDA, the United
StatesUSP, the United
States
ANVISA, Brazil
Japan
Taiwan FDA,Taiwan
NPRA,Malaysia
NADFC,Indonesia
TGA,Australia
HSA,Singapore
Thai FDA,Thailand
CDSCO,India
ChP,China
MFDS,Korea
CFDA,China
MHRA,the UnitedKingdom
CBG-MDB,the Netherlands
Swissmedic,SwitzerlandAIF
A,Italy
ANSM,France
HPRA,Ireland
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MPA,Sweden
EMA, the European Union
EDQM, the Council of
EuropeWHO
EC, the European Union
URPL, Poland
Bilateral cooperation
Cooperative Arrangement on cooperation of pharmacopoeia signed
Confidentiality Arrangement signed
DKMA,Denmark
1 15
FY 2018 Planned symposium
Month Country Contents (Location)
Feb. Thailand The 4th Joint Symposium (Bangkok)
Apr. India The 2nd Joint Symposium (Tokyo)
May. Korea The 2nd Joint Symposium (Seoul)
May. Indonesia The 3rd Joint Symposium (Jakarta)
Dec. Taiwan The 5th Joint Conference (Taipei)
FY 2017 Completed symposium (As of August, 2018)
Bilateral Symposium
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Month Country Contents (Location)
Apr. Thailand The 5th Joint Symposium (Bangkok)
Jul. Korea The 3nd Joint Symposium (Tokyo)
Aug. India The 3nd Joint Symposium (India)
Oct. Taiwan The 6rd Joint Symposium (Tokyo)
Dec. Brazil The 4th Joint Conference (Tokyo)
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Bilateral cooperation with India
11th April,2018; PMDA(Tokyo)
Information sharing on the
latest issues
Discussions toward the 3rd
India-Japan Symposium
Bilateral Meeting between PMDA/MHLW and MHFW/CDSCO
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Asian sites
PMDA Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs(ATC)
Japan
APEC
(1)Help raise the level of regulations in Asia as a whole
(2)Training seminar at PMDA, local prefectures in Japan and Asian with manufacturing site
visits
(3)APEC Center of Excellence (COE) for Training (Multi-Regional Clinical Trials and Pharmacovigilance)
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International Reputation of Asia Training Center
Attendance (FY 2017)
Nine training seminars and 235 attendees from 27countries/regions
More than 70% of attendees rated as “Very good” according to the
questionnaire
Official certificate of APEC LSIF RHSC Training Centers of
Excellence for Regulatory Science from APEC
Area: Global clinical trials/GCP inspection, pharmacovigilance
Stipulate utilization of ATC in the Joint Statement of ASEAN-
JAPAN Health Ministers (July 15th in 2017)
PMDA contributes to mutual understanding and cooperation in Asia 19
Contents Date Location
1 Pediatric Review June 11-14, 2018 Tokyo (PMDA)
2 Pharmaceuticals Review June 18-22, 2018 Tokyo (PMDA) and Toyama Prefecture
3 Good Registration Management(GRM)*
September 26-28, 2018
Taipei
4 Pharmaceuticals Review October 15-16, 2018 Naypyidaw, Myanmar
5 Medical Devices Review November 12-16, 2018 Tokyo (PMDA)
6 Good Manufacturing Practice(GMP) **
November 26-30, 2018 Utsunomiya, Tochigi Prefecture
7 Pharmaceuticals Review December 10-13, 2018 Jakarta, Indonesia
8 Multi-Regional Clinical Trial (MRCT)* January 21-24, 2019 Tokyo (PMDA)
9 Pharmacovigilance* February 4-7, 2019 Tokyo (PMDA)*APEC-LSIF-RHSC CoE Workshop **With the support of PIC/S
Asia Training Center: Training Seminar 2018
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Today’s topics
1. Review Process
2. International Collaboration
3. Summary
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Summary 1
1. Adapt for innovative science technology
Through innovative science and technology, it will become possible to treat hard-to-treat diseases.
It will become necessary to be more cautious in development/approval/post-marketing safety measures
To start the new initiative, it will be necessary to improve and make existing work more efficient.
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Summary 2
2. Cooperation between reliable regulatory agencies
Using the review results and the outcomes of reliable regulatory authorities
Using the resources freed through operational streamlining for adapting to new technology such as regenerative medicine.
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Summary 3
3. International harmonization activities
International harmonization is important
Active participation in international harmonization activities such as ICH and PIC/S.
Thank you for your attention25
Work Together for patients!!