Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
CMC Challenges in JapanYoshihiro Matsuda, Ph.D., PMDASession 10
CMC Workshop 2015April 13-15 | Bethesda, MD
Disclaimer
The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to 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. DIA and the DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners.
© 2015 DIA, Inc. All rights reserved.
Agenda
Introduction of PMDARevised Pharmaceutical Affairs ActRevised Japanese PharmacopoeiaCollaboration with external organizationsCMC Challenges
© 2015 DIA, Inc. All rights reserved.
Introduction of PMDA
Name : Pharmaceuticals and Medical Devices AgencyDate of Establishment : In April 2004Established as an Incorporated Administrative Agency
© 2015 DIA, Inc. All rights reserved.
http://www.pmda.go.jp/en/index.html
PMDA Organization
© 2015 DIA, Inc. All rights reserved.
PMDA
Office of Regulatory
Science
Office of Standards and
Guidelines Development
Office of Relief Funds
Office of Safety
Office of Generic Drugs
Office of GMP/QMS Inspection
Office of New Drug
Office of International
Programs
Office of Medical Devices
Office of Conformity
Audit
Office of Cellular and
Tissue-based
Products
Office of Vaccines and
Blood Products
The revision of Pharmaceutical Affairs Act (PAA)
The revised PAA was enforced on November 25, 2014.Name of PAA was changed to “the Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics”
PMD Act
© 2015 DIA, Inc. All rights reserved.
Safety Measures & Medical Devices
New Regulations for Safety Measures• Pharmaceutical companies should notify the Ministry
of Health, Labour and Welfare (MHLW) / PMDA about the contents of package inserts at the time of approval and revision.
• Package inserts notified will be uploaded in a PMDA web-site.
New Regulations for Medical Devices• Standalone Medical Device Software (SMDS) will be
regulated as well as in US and EU.• Scope of third party certification will be expanded.
© 2015 DIA, Inc. All rights reserved.
Overview of Medical Device Regulation
© 2015 DIA, Inc. All rights reserved.
Classification Class I Class II Class III Class IVExtremely
low riskLow risk Medium risk High risk
Example X-Ray film MRI Dialyzer,Artificial bone
Pacemaker, Artificial heart valve
Category General MDs Controlled MDs
Specially controlled MDs
Review regulation Self-declaration
Third partycertification
Post-market safety vigilance/surveillance
PMDA and MHLWRe-examination or Use-results survey for Brand New MDs, Re-evaluation, AE
reporting, Researches, etc.
Minister’s approval(PMDA’s review)
Regenerative Medicines
New Regulations for Regenerative Medicines• Approval system for earlier commercialization of
regenerative medicine products: Introduction of Tentative Approval with conditional / term-limited authorization. This is because regenerative medicines generally have characteristics that the qualities are not homogeneous. Efficacy and safety will be further confirmed after tentative approval.
© 2015 DIA, Inc. All rights reserved.
Expedited approval system under PMD Act
© 2015 DIA, Inc. All rights reserved.
Phased clinical trials(confirmation of efficacy and safety)
Clinical study
Post-marketing safety measures must be taken, including prior informed consent of risk to patients
Marketing(Further confirmationof efficacy and safety)
Conditional/term-limited authorization
Clinical study
Marketing authorization
or Revocation
Marketing
Marketing continues
Clinical trials(likely to
predict efficacy, confirming
safety)
Traditional approval process
Marketing authorization
New scheme for regenerative medicines
The Japanese Pharmacopoeia (JP)
Under the Article 41-1 of PMD Act, the Minister of Health, Labour and Welfare (MHLW) establishes and publishes the JP.JP is a book of official pharmaceutical standards in Japan, prepared by the JP secretariat in PMDA and established by the MHLW.JP has been revised periodically.The 17th edition will be published in February, 2016.
© 2015 DIA, Inc. All rights reserved.
Overview of the 17th JP
Improving quality by positive introduction of latest science and technology• Introduce the new sections in JP by referring to
European Pharmacopoeia (EP)Promoting internationalization of JP• Introduce the philosophy of ICH guidelines into JP as
well as EP and United States Pharmacopeia (USP)
© 2015 DIA, Inc. All rights reserved.
New sections
Production:• Statements under the heading Production draw
attention to particular aspects of the manufacturing process.
• They relate to source materials; to the manufacturing process itself and its validation and control; to in-process testing etc..
© 2015 DIA, Inc. All rights reserved.
We expect that “Production” section can facilitate to carry biotech products and products developed by QbD in JP
New sections (continued)
Potential Adulteration:• Information of fraudulent activities and cases of
adulteration.• A method for the detection of potential adulterants
and relevant limits are included in this section of monographs.
© 2015 DIA, Inc. All rights reserved.
The JP can take account of cases of adulteration such as Over Sulfated Chondroitin Sulfate (OSCS) in Heparin
Sodium quickly and appropriately.
Introduction of ICH guidelines into JP
The philosophy of ICH Q6A/B was introduced into the general information in JP.ICH Q9 was introduced into the general information in JP.ICH Q3C was introduced into Residual Solvents Test in JP.
© 2015 DIA, Inc. All rights reserved.
We expect that there will no longer be difference of control strategy between New Drugs and Drugs in JP in the near future.
Collaboration with external organizations
The EMA-FDA pilot program of QbD• PMDA participates the program as an observer
MHLW-sponsored Health Science studies• Sakura Bloom Tablets P2 Mock
• CTD P.2 section for a drug product that had been developed by using the QbD methodology presented in ICH Q8,Q9,Q10 and Q11.
• http://www.nihs.go.jp/drug/DrugDiv-J.html• Discussion of Analytical QbD
• A mock will be posted for public review and comment this summer.
Joint MHLW/EMA reflection paper• Reflection paper on the development of block copolymer micelle
medicinal products• http://www.pmda.go.jp/files/000157408.pdf
© 2015 DIA, Inc. All rights reserved.
Current Works in CMC area
MHLW Nanomedicine Study Group(included Industries):Drafting a guideline for development of Liposome Drug Products• The draft guideline written in Japanese will be posted for public
review and comment soon.
Drafting a reflection paper for Drug Products carried small interference RNA (siRNA).
© 2015 DIA, Inc. All rights reserved.
NIHS
Personnel Exchange
Develop Guidelines
Cultivate Human
Resource
Medical Institutions
Universities and research institutions
PMDA and the World
© 2015 DIA, Inc. All rights reserved.
PMDA, JapanFDA, US CFDA,
China
Confidentiality Arrangement Resident Staff Joint symposium
Health Canada, Canada
ANVISA, Brazil
EMA(EU)
TGA, Australia
NADFC, Indonesia
TFDA, ThailandHPRA, Ireland
MHRA, UK
ANSM, France Swiss medic, Switzerland
AIFA, Italy
HSA, Singapore
Taiwan FDA, Taiwan
CBG-MEB,Netherlands
OECD, France
NPCB, Malaysia
CMC Challenges
Matters related to ICH Q12• Knowledge management• Control Strategy• Post-approval change management plans and
protocolsFuture ICH topics• Enhanced Approaches for Development and
Utilization of Analytical Procedures• Continuous Manufacturing of Pharmaceuticals
© 2015 DIA, Inc. All rights reserved.
SAKIGAKE Designation System
SAKIGAKE is a system to put into practice innovative medicines/medical devices/ regenerative medicines initially developed by Japan.Designation CriteriaMedical products for diseases in dire need of innovative therapy and satisfies the following two conditions:1. Having developed firstly in Japan and anticipating an application
for approvals (desirable to have PMDA consultation from the beginning of R&D)
2. Prominent effectiveness (i.e. radical improvement compared to existing therapy), can be expected based on the data of mechanism of action from non-clinical study and early phase of clinical trials (phase I to II)
© 2015 DIA, Inc. All rights reserved.
Not limited to life-threatening and regenerative medicine
General Timeframe of SAKIGAKE
© 2015 DIA, Inc. All rights reserved.
Non clinical studies, Clinical studies
Clinical trials Phase I/II
2 m. 12 m.
1 m.
6 m.
③ Priority Review②Prior assessment
① Priority Consultations
④Review Partner System
⑤ Strengthening post‐marketing safety
【Standard】
【SAKIGAKE】
Consultation on Clinical
trialsClinical trial Phase III Review reimburs
ement
Post‐Mar‐keting
Pharmaceutical affairs
consultation for R&D strategy
Non clinical studies, Clinical studies
Clinical trials Phase
I/II
Consul‐tationon
Clinical trials
Clinical trial Phase III
SAKIGAKEassign‐ment
Prior Review(rolling submission) Review
Post‐Mar‐keting
reimbursement
Pharmaceutical affairs
consultation for R&D strategy
※May accept Phase III data during review, depending on conditions
• Shorten review time, using rolling submission of data as “prior review” during P-III• Similar to breakthrough therapy designation of US FDA• Come Into effect in early 2015
CMC Challenges (continued)
Accelerated programs
© 2015 DIA, Inc. All rights reserved.
In US : Breakthrough therapy & Fast Track designationIn EU : Pilot Project on Adaptive Licensing
What can CMC Area do?Risk based assessment is needed to facilitate the
accelerated programs.
A product lifecycle strategy with QbD
AskAsk
Thank you for your attentionThank you for your attention