Enhancing Review Efficiency(Pharmaceuticals)
Naoto KatoOffice of Review Management
Review Planning Div.Pharmaceuticals and Medical Devices Agency ( PMDA )
September 10th, 2015The 2nd Brazil-Japan Seminar on Regulations on
Pharmaceuticals and Medical Devices
Pharmaceuticals and Medical Devices Agency1
3rd 5‐year mid‐term plan of PMDA (FY2014‐2018)
Globalization
Shortening the time from Shortening the time from early development to
approval“Zero” review time lag Support for elimination of development time lag
High quality review/consultation
services
Accelerated review process(Improvement of approval predictability) Enhancement of
regulatory science research and human resource development Development of advanced
review/consultation framework using innovativeassessment techniquesCross‐products analysis of accumulated large data sets by PMDA using innovative techniques
Utilization of Science Board(cooperation with the academia)
Appropriately accommodate the most advanced technologies including personalized medicine and regenerative medicine
Prerequisites:US/EU‐equivalent system and human resources with excellent skills
Enhancing safety
measures
Major challenges
Specific measures
Goal
Activation of the industry
Extending health and life
span of Japanese people
Contribution to global medicine
Utilization ofmedical
information database
Drastic improvement of consultation service
Active involvement from the early development phase
Improvement of pharmaceutical affairs consultation service on R&D strategy
Improvement of clinical trial consultation service
Improvement of prior assessment
(substantial acceleration of approval review process)
Enhanced overseas inspection system
Readinessfor introduction
of risk management
plan
Development of Japan’s original innovative drugs and medical devices
Marketing of cellular and tissue‐based products
Responding to social needs such as Japan Reconstruction Strategy
and Health/Medical Care Strategy
Pharmaceuticals and Medical Devices Agency2
1,065
256291
605521
426341319
753
648678 708
Improvement of Infrastructure(Staff Size)
Pharmaceuticals and Medical Devices Agency
820
Others
3
PMDA’s business structure
Relief
１６５staffs
５３２staffs
３６staffs（As of April 1, 2015）
Pharmaceuticals and Medical Devices Agency
Review
Advanced Review with Electronic Data Promotion Group, Office of Review Administration, Office of Review Management, Kansai Branch(Division of Pharmaceutical Affairs Consultation)
Office of New DrugⅠ - Ⅴ
Office of OTC/Quasi-Drugs, Office of Generic Drugs
Office of Medical DevicesⅠ - Ⅲ, Office of In Vitro Diagnostics
Office of Non-clinical and ClinicalCompliance
Office of Cellular and Tissue-based Products, Office of Vaccines and Blood Products
Office of Standards and Guidelines Development
Office of International Programs
Office of Relief Funds
Office of Safety Ⅰ, Ⅱ
Kansai Branch (Division of Manufacturing/Quality and Compliance)
Office of Manufacturing/Quality and Compliance
Safety
Office of Medical Infomatics andEpidemiology
4
Review Categories of New DrugsOffice Review Category Products
Office of New Drug Ⅰ Team1Team6‐2
Gastrointestinal drugs, Dermatologic drugsHormone drugs, Drugs for metabolic disorders
Office of New Drug Ⅱ
Team2
Team5RadiopharmaceuticalsIn vivo diagnostics
Cardiovascular drugs, Antiparkinsonian drugs, Antithrombotics,Anti‐Alzheimer’s drugsReproductive system drugs, Drugs for urogenital system, combination drugsRadiopharmaceuticalsContrast media
Office of New Drug ⅢTeam3‐1Team3‐2
Central/peripheral Nervous system drugs(excluding anesthetic drugs)Anesthetic drugs, Sensory organ drugs(excluding drugs for inflammatory diseases),Narcotics
Office of New Drug ⅣTeam4Anti‐AIDS drugsTeam6‐1
Antibacterial drugs, vermifuge, Antifungal drugs, Antiviral drugs(excluding AIDS drugs)Anti‐HIV agentsRespiratory tract drugs, Anti‐allergy drugs(excluding dermatologic drugs),Sensory organ drugs for inflammatory diseases
Office of New Drug Ⅴ Oncology drugs Antineoplastic drugs
Office of Cellular and Tissue‐based Products
Bio‐CMCCellular and tissue‐basedproducts, Gene therapy products
Quality of biologics, BiosimilarsCellular and tissue‐based productsQuality and safety of gene therapy products
Office of Vaccines and Blood Products
VaccinesBlood products
Vaccines, Antitoxic serumGlobullin, Blood coagulation factor products 5
Team Reviewing at the PMDA
Office Director
Review Director
Team Leader
Risk Manager
Reviewers are required to have a high level of expertise
Pharmacology
BiostatisticsToxicology
ADMECMC
Clinical
Pharmaceuticals and Medical Devices Agency6
The Standard Review Timeline for New Drug ApplicationsTo achieve the target of 12 months (standard review products) for the total review time from receipt of an application to approval
after FY2014, the priority review timeline indicating the timeframes(the total of the times allowed for the regulatory authorities andthe applicant) for each review stage, based on past performance in regulatory review, is shown below. This timeline is applicable whenthere are no particular concerns in the course of review.
Applican
tPM
DA
MHLW
Subm
issi
on o
f app
licat
ion
for m
arke
ting
appr
oval
Initi
al m
eetin
g
Inqu
iries
on
impo
rtan
t iss
ues
Com
plet
e pr
epar
atio
n of
revi
ew re
port
Mar
ketin
g ap
prov
al
Expe
rt
disc
ussi
on
GLP/GCP & data integrity assessment
GMP inspections
2.3 ‐ 2.4 ‐ 2.8months
0.5 ‐ 0.6 ‐ 0.7months 5.1 ‐ 5.7 ‐ 6.8months
0.7 ‐ 0.9 ‐ 1.6months
1.2 ‐ 1.5 ‐ 2.0months
Note: “Inquiries on important issues” means inquiries made by PMDA after the initial meeting.
Dru
g C
omm
ittee
sR
evie
ws
byD
rug
Com
mitt
ees
25th percentile ‐median ‐ 75th percentile
Pharmaceuticals and Medical Devices Agency7
The Priority Review Timeline for New Drug ApplicationsTo achieve the target of 9 months (priority review products) for the total review time from receipt of an application to approval after
FY2014, the standard review timeline indicating the timeframes(the total of the times allowed for the regulatory authorities and theapplicant) for each review stage, based on past performance in regulatory review, is shown below. This timeline is applicable whenthere are no particular concerns in the course of review.
1.6 ‐ 1.9 ‐ 2.0months
0.2 ‐ 0.3 ‐ 0.7months 4.2 ‐ 4.4 ‐ 5.6months
0.8 ‐ 0.8 ‐ 1.1months
1.1 ‐ 1.3 ‐ 1.5months
25th percentile ‐median ‐ 75th percentile
Note: “Inquiries on important issues” means inquiries made by PMDA after the initial meeting.
Applican
tPM
DA
MHLW
Subm
issi
on o
f app
licat
ion
for m
arke
ting
appr
oval
Initi
al m
eetin
g
Inqu
iries
on
impo
rtan
t iss
ues
Com
plet
e pr
epar
atio
n of
revi
ew re
port
Mar
ketin
g ap
prov
al
Expe
rt
disc
ussi
on
GLP/GCP & data integrity assessment
GMP inspections
Dru
g C
omm
ittee
sR
evie
ws
byD
rug
Com
mitt
ees
Pharmaceuticals and Medical Devices Agency8
77 107 112 130 134 138 117
15.4
11.9
9.26.5
6.1 7.2
8.8
22.0
19.2
14.7
11.5
10.3
11.3 11.9
0
20
40
60
80
100
120
140
0
5
10
15
20
25
FY2008 FY2009 FY2010 FY2011 FY2012 FY2013 FY2014Number of approved applicationsPriority Review ProductsStandard Review Products
（Month）
（Number of approvedapplications）
Number of Approvals and Review Time
New Drugs
～FY2013: 50th percentile
FY2014～:60th percentile
9
1.Review time for new drug (priority review products)Fiscal year Percentile Review timeFY 2014 60% 9 monthsFY 2015 60% 9 monthsFY 2016 70% 9 monthsFY 2017 70% 9 monthsFY 2018 80% 9 months
2.Review time for new drug (standard review products)
審査等業務
Fiscal year Percentile Review timeFY 2014 60% 12 monthsFY 2015 70% 12 monthsFY 2016 70% 12 monthsFY 2017 80% 12 monthsFY 2018 80% 12 months
New target review times for new drugsIn order to further shorten review times, PMDA plans to sequentially increase the target values by 2018 as follows, which were also stated in the Third Mid-term Plan implemented from 2014.
8.8 months(Result)
11.9 months(Result)
Pharmaceuticals and Medical Devices Agency10
PMDA’s performance highly evaluated globally Comparison of review time in 6 regulatory agencies from 2004 to 2013
“PMDA and Health Canada may have had the most notable improvements over the past decade.” Regulatory Affairs Professionals Society 14 January 2015
Reference: The impact of the changing regulatory environment on the approval of new medicines across six major authorities 2004‐2013. CIRS (Centre for Innovation in Regulatory Science) R&D 55 http://cirsci.org/node/73
Pharmaceuticals and Medical Devices Agency11
Implementation of prior assessment consultations
Development Approval application Review
Quality
phase I study
phase II study phase III study Application
preparation
Non-clinical（Toxicity, Pharmacology, ＡＤＭＥ）
Drug Stability
Carcinogenicity StudyCre
atio
n S
eeds
of
new
dru
g/ m
edic
al d
evi
ces
Prior Assessment （Quality）
Prior Assessment （Non-clinical）
Prior Assessment （Clinical）
de facto review before application due to prior
assessment consultations
（Standards and Stability of Drug and Drug Substance ）
Results
Assess study results in order coming out, instead of waiting for all results
Results
Results
Pharmaceuticals and Medical Devices Agency12
Implementation status of prior assessment consultation
Fiscal year Total of the ingredientNumber of prior assessment consultation
Number of approved ingredient
2009 7 33 7
2010 9 30 9
2011First half 3 9
8Second half 7 24
2012First half 5 17
6Second half 2 2
2013First half 5 14
2Second half 6 18
2014First half 7 25
0Second half 2 7
Pharmaceuticals and Medical Devices Agency13
Timing of clinical trial consultation
IND
Clinical NDA
Non‐Clinical Review Post‐Market
PhaseⅢ PhaseⅣ
PhaseⅡ
PhaseⅠ
P-II data Assessment
Non-ClinicalAssessment
QualityAssessment
（Synthesis)（Preparation）
（Pharmacology）
（Toxicology)etc
Clinical trial consultations Clinical trial
consultations
Prior assessment consultations
Prior assessment consultations
P-I data Assessment
Qualification priority review
R&D strategic consultations R&D strategic consultations
Quality and safety of cellular and
tissue-based products
Regulatory affairs development plans
BeforeNon‐Clinical
Pharmaceuticals and Medical Devices candidates
R&D strategy (Drugs/ Medical devices/Cellular and tissue-based products)
Medically Necessary Unapproved Drugs,
etc.
P-II/III data Assessment
14
Pharmaceutical Affairs Consultation on R&D Strategy
Practical Use
Innovative Products
Basic ResearchPharmaceuticals and
Medical Devices candidates
Non-Clinical Study
Quality Study
Clinical Trial
Valley of Death -Shortage of funds, Knowledge on Regulation and developmental strategy
（Up to POC studies）
* Further studies are handled by the Regular Consultation
Consultation on quality and battery of pre‐clinical, including examining tumorigenicity,
biological ingredient safety
Consultation on endpoints or sample
size of early clinical trial
Strategic Consultation
Introductory Consultation(775)
Pre‐Consultation(937)
Face‐to‐Face Consultation(236)
Flow of Strategy
Consultation(7/1/2011 – 10/31/2014)Pharmaceuticals and Medical Devices Agency
15
153
254
346325
0
50
100
150
200
250
300
350
FY2011(from july)
FY2012 FY2013 FY2014
Pre‐consultation
3140
123
85
0
20
40
60
80
100
120
140
FY2011(from july)
FY2012 FY2013 FY2014
(Face‐to‐face) Consultation
Number of R&D Strategic Consultation
Pharmaceuticals and Medical Devices Agency16
General Timeframe of SAKIGAKE
Pharmaceuticals and Medical Devices Agency17
Pharmaceuticals and Medical Devices Agency18
Thank you for your attention !
Pharmaceuticals and Medical Devices Agency19
