Post on 20-Mar-2018
transcript
Advancing Roles of Japan on Global Drug Development
Ethnic factors consideration with a view to International Harmonization
1
Dr Yoshiaki UyamaPharmaceuticals & Medical Devices Agency
(PMDA)Visiting Professor, Graduate School of Medicine, Chiba UniversityVisiting Professor, Graduate School of Medicine, Nagoya University
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
2
Disclaimer• The views and opinions expressed in the following PowerPoint
slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Communities or affiliates, or any organization with which the presenter is employed or affiliated.
• These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, Drug Information Association Inc., DIA and DIA logo are registered trademarks. All other trademarks are the property of their respective owners.
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Japanese:http://www.pmda.go.jp/operations/notice/2007/file/0928010.pdfEnglish:http://www.pmda.go.jp/operations/notice/2007/file/0928010-e.pdf
2007 GuidelineBasic Principles on MRCTs
3Japanese:http://www.pmda.go.jp/regulatory/file/guideline/new_drug/GCT_jirei.pdf
English:http://www.pmda.go.jp/regulatory/file/english_guideline/new_drug/GCT-jirei_en.pdf
2012 Guideline
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
FY2007 FY2008 FY2009 FY2010 FY2011 FY2012 FY2013 FY2014
0
5
10
15
20
25
30
% o
f GC
T % of GCT % of Bridging
Total 81 79 107 114 130 134 133 35MRCT 1 0 4 7 12 18 21 9Bridging 4 2 3 6 2 3 1 1
(Year)
As of July
Development strategies for drug approval in Japan
4
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
MRCTs have contributed to decreasing “Drug Lag”
5
Clinical development strategy
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000
Lag
in d
rug
deve
lopm
ent
(day
s)
1111 days
Local
trial
(n = 69)
Local and
foreign trials
(n = 59)
Bridging
study
(n = 19)
Global
clinical
trial
(n = 18)
Foreign
trial
(n = 13)
No
efficacy/safety
trial (n = 5)
***
**
Ueno T et al, Clin Pharmacol Ther, 95, 533-41 (2014)
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Regulatory Perspective: PMDA and FDA
Clin Pharmacol Ther. 2013;94:230-42. Clin Pharmacol Ther. 2013;94:195-8.
US FDA PMDA
6
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
US FDA Perspective: Points consider in reviewing global clinical trial data
Points shown here are similar to those in Japanese guideline
7
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Activities toward International Harmonization
8
012 | Tokyo, Japan
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
ICH E17 Guideline
9
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
ICH E17 Guideline: MRCTs
In June 2014, the Steering Committee approved the establishment of the new expert working group (E17 EWG), focusing on “General principle on planning/designing Multi‐Regional Clinical Trials” with MHLW/PMDA as the Rapporteur.
This guideline provide common points to consider in planning/designing MRCTs and minimize conflicting opinions from regulatory bodies.
10
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Accomplishment in Lisbon
• Sharing regional perspectives as to what topics should be covered in this guideline.
• Reaching a consensus on a table of contents of E17 guideline
• Initiating to draft concrete sentences of some sections in the guideline
• Confirmed that E17 guideline is really important to improve current situation of global drug developemnt and promote simultaneous regulatory submission in multiple countries/regions
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Current table of contents (E17)
1. INTRODUCTION1.1 Objective(s) of the Guideline1.2 Background1.3 Scope of the Guideline1.4 General Principles
2. General recommendations in planning/designing MRCT2.1 Strategy-related points
2.1.1 The value of MRCTs in drug development and regulatory approval
2.1.2 The basic requirements to conduct a MRCT2.1.3 Scientific consultation meeting with regulatory
agencies
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Current table of contents (E17)
2. General recommendations in planning/designing MRCT2.2 Clinical trial design and protocol-related points
2.2.1 Pre-consideration of regional variability on efficacy/safety2.2.2 Subject selection2.2.3 Selection of doses in MRCTs2.2.4 Choice of endpoint/index2.2.5 Estimation of a sample size and a proportion of each regional
subjects in an MRCT2.2.6 Collecting and handling efficacy/safety information in MRCTs2.2.7 Statistical analysis plans that specifically address the features
of MRCTs2.2.8 Selection of comparator (where applicable)2.2.9 Handling concomitant medications or therapies in a MRCT
3. GLOSSARY
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Current Timeline of the E17 guideline
14
• First face-to-face EWG Meeting in November 2014 in Lisbon
• Discussion by e-mail and web-based conference: 4Q 2014 -1Q 2015
• Second F2F EWG Meeting in 2Q 2015 for coordinating opinions of all parties and delivering Step 1 document
• Third F2F EWG meeting in 4Q 2015 for adaption of Step 2document
• Public consultation: 4Q 2015 - 2Q 2016
• Revision of the guideline based on comments: 2Q 2016 - 4Q 2016 (depending on contents of comments recieved)
• Fourth face-to-face EWG Meeting for adaption of Step 4 document in 4Q 2016 or 2Q 2017
012 | Tokyo, Japan
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
ICH E6 Discussion Group
15
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
16
Training for GCP Inspector
2009.06 Establishment of E6 Discussion Group under the Regulator Forum Regulator Forum=the International Pharmaceutical Regulator Forum
Since then, web‐meeting was regularly held Sharing regulatory experiences on GCP implementation and inspection
Identifying tasks for proper implementation of ICH‐GCP
2011.08 Start to prepare a document regarding general principles of GCP inspector education and training
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Members
17
as of Feb 26, 2014
Japan PMDA Yoshiaki Uyama, Group Leader Tomoko Osawa Mari Shirotani Hideaki Ui
Australia TGA Anthony Gill Katherine Clark
Chinese Taipei FDA/CDE Horng-I Yeh Wen-Ting Liu
Korea KFDA Mee-Ryung Ahn Tea-Kyun Nam Hojin Oh
Russia Roszdravnadzor Evgeny Rogov
Singapore HSA Foo Yang Tang
EU Ana Rodriguez (EMA) Alexander Hönel (Austria AGES)
ASEAN Yuppadee Javroongrit (Thai FDA) Akanid Wapeewuttikorn(Thai FDA) Endang Woro (Indonesia BPOM) Ega Febrina (Indonesia BPOM) Farida Anwar (Indonesia BPM) Tan Ann Ling (Malaysia DRA) Joyce Cirunay (Philippines DRA)
GCC Khaled Alshahwan(Saudi FDA) Khalid Almowaizri (Saudi FDA) Ahmad M. Al-Ghamdi (Saudi FDA) Abdullah H AL-Hatareshah (Saudi FDA) Haitham A.Al-Hassan (Saudi FDA)
PANDRH Ileana Herrera Gallegos (Costa Rica DRA)
SADC Joseph Mthetwa (SADC Secretariat) Fortunate Fakudze (MoH Swaziland)
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake 18
• 15 page document• Introduction• Purpose• General steps for
training GCP inspector– step 1- step4
• Appendix 1- Appendix 3
General Principles for Training/Education of GCP Inspectors FINAL (May 23, 2013)
Uyama, Y. et al. Therapeutic Innovation & Regulatory Science, (2014)
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
19
Possible strategies of future drug development
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
20
Case 1:phase I study in Japanese population before initiating MRCTs
Is there any cases that conduct of phase I study in Japanese population is not necessary before joining a MRCT?
Japan
US/EUJ/WGCT
J/WGCT
Too late for joining
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
21
• 3rd guideline specifically focusing on MRCTs
• Provides several cases for which phase I study is required or not required.
• Useful for planning an early phase of global drug development
Just Published:Basic principles on conduct of phase I study in Japanese
population before initiating MRCTs(October 27th 2014)
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
PMDA Workshop on MRCTs
22http://www.pmda.go.jp/operations/shonin/info/report/workshop20141215.html
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
23
Case 2: Asia-leading drug development
• In some therapeutic area whose prevalence is higher in Asia (e.g.; gastric cancer, hepatitis etc.), can early phase of drug development (PI, POC, ePII etc.) be initiated in Asia?
• If yes, can later phase clinical trials be conducted globally, based on a hypothesis established by Asian data?
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Japan
Other Asia
US/EU
PK, Safety
Exploratory, Dose‐Finding ConfirmatoryPOC
Japan only
West only
W/J/EGCT
W/J/EGCTAsian
GCT
24
Case 2: Asia-leading drug development
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
25
• PROS:
– More appropriately design a confirmatory trial based on Asian data
• Dose selection, Target population etc.– Provide more scientific evidences in Asian population
• CONS (Challenges)– Uncertainty about effects of extrinsic ethnic factors– How to define Asia? How much Japanese data are
required?– Acceptability of a hypothesis based on Asian data in
non-Asian countries
Case 2: Asia-leading drug development
Pros/Cons
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
26
Case 3: Genome-defined population
Can we define a population based on a specific genotype relating to drug responses rather than an ethnicity/race?
e.g.; molecular-target drug EGFR (+)
EGFR (-)Gefitinib
Calboplastin+Paclitaxel
Calboplastin+Paclitaxel
Gefitinib
Calboplastin+Paclitaxel
Gefitinib
Gefitinib: IPASS study
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Case 3: Genome-defined population
27
• PROS:
– Maybe not necessary to consider strictly about subject number from a country in a clinical trial
– Can select more objectively a target population based on genomic test results
• CONS (Challenges):– Need to develop CDx simultaneously– Uncertainty about effects of extrinsic ethnic factors– How much Japanese data are required?
Pros/Cons
11th Annual Meeting DIA JAPAN 2014 | November 16-18 | Tokyo Big Sight | Ariake
Conclusion
28
• Prepare for various strategies of drug development
• More scientific data and experiences facilitate activities of the international harmonization
More MRCTs with more international cooperation for providing more drugs earlier to patients