japan regulatory update - january 2017 by regarise
TRANSCRIPT
Successful product registration and latest regulatory requirements in Japan
Lamine Messaoudi, D.V.M Co-‐Founder RegArise
Confidential
Outline
! Latest regulatory requirements and updates in Japan ! Local clinical trial requirements ! Registration milestones ! Summary
Confidential
Japan Facts Summary ! Japan is the 2nd biggest pharmaceutical market after the United States ! It accounts for ~10% percent of the global pharma market: close to $150 billion
! The Japan government recognized the demand on this sector and designed a national strategy for Pharmaceutical & Biotechnology Development*.
! The generic market represents a small portion of the market size. ! PMDA is building a global infrastructure emphasizing human resources and communication.
! The Japanese pharmaceutical market is very closed and accessing KOLs is extremely difficult if there is no local partner.
* Please refer to the latest PMDA long term plan strategy outlined in June 2016.
Government bodies in Japan
! Ministry of Health and Labor Welfare (MHLW): ! Final Approvals of MAAs, CTAs, Orphan Drug Designations etc. ! Pharmaceutical Food and Safety Bureau (PFSB), part of MHLW :
! Evaluation and Licensing Division, Safety Division, Compliance and Narcotics Division, Blood and Blood Products Division (Post Marketing)
! PMDA scientific branch of MHLW
! Confidentiality agreement signed between PFSB and FDA in July 23, 2004 (Share none public information.) Similar agreement was established with the EMA in 2007.
Latest regulatory requirements in Japan • Global and Local Initiatives from PMDA:
• Added a new Branch called Hokuriku in 2016 • The Agency for Medical Research and Development (AMED) set up an office in Washington, D.C. to collaborate with LATAM countries. • Sakigake was established 2015, aiming to accelerate clinical development to market for innovative drugs with privileges in both the pre-‐application and review process. This is equivalent of the US FDA’s Breakthrough Therapy (BT) designation and the EMA’s Priority Medicines (PRIME) scheme.
Eligibility criteria: �1) being novel �2) targeting serious diseases �3) having prominent efficacy �4) being developed and planned for approval in Japan ahead of the rest of the world or simultaneously with other major markets.
Ar<cles to Relevant Submissions ! Art 268, Cases Requiring Notification of Clinical Trial on Medicinal Substances
! Art 269, Notification on Clinical Trial Plan on Medicinal Substances
! Art 38, Application for Marketing Approval of Drugs ! Art 40, Data to be Attached to Applications for Approval ! Art 43, Standards for Reliability of Application Data
Clinical Trial Procedure
PMDA Consultation -‐ Informal and
formal
CTN Application Review Response of inquiries
! CTN Approval in 30 Days/IRB 4-‐6 weeks ! “It is not a parallel review system” ! Process time 30 Days (At least 2 rounds of queries)
IRB Submission Review Approval Contract
with Hospital Study Start
IRB Process initiated after MHLW Approval
CTN Requirements ! Document stating the reason for the request for the clinical trial data ! Data showing that the clinical trial is scientifically appropriate ! Protocol ! Patient information and consent forms ! Sample case report form ! Latest version of the investigator’s brochure ! Document related to clinical trial cost estimate (including a document regarding the payment to study subjects)
! Contract agreement (if available) ! Standard operating procedures for drug control ! Check list
Understanding the Registra<on Milestones
Applicant
Pharmaceutical Affairs and Food Sanitation Council Pharmaceutical Affairs Committee 1st and 2nd
Committee on New Drugs
PMDA Office of New Drugs I-‐IV, Biologics etc. Office Of
Compliance, GCP and GLP
Response to Application
Designation of biologics drugs
Application to MHLW
MHLW Evaluation and Licensing Division, PFSP
(Management of Approval)
Inquiry
Two Types of Consulta<ons with PMDA
! Informal and formal meetings ! Schedule posted 2 months in advance by PMDA ! Start to finish the procedure takes ~3 months ! Additional follow-‐up meetings may be required
Overview of Submission/Review and Approval PMDA review the dossier
2 to 3 months after J-‐NDA first set of questions ~20-‐30. After the meeting expect ~100 questions
GCP compliance inspection and consultation with external experts
Drug Committee Meeting
Pharmaceutical Affairs Council
Understanding the Registra<on Milestones ! J-‐NDA submission, review and approval processes and their requirements are similar to those of FDA or EMA ! Important differences to be noted (e.g. language, J-‐GCP) ! Informal Meetings are crucial for foreign companies
! Easy to setup, non-‐binding, generally used from early phases to pre-‐NDA ! Formal meetings -‐ there are many of them: clinical, nonclinical, clinical, pre-‐submission meeting
Major Milestones for J-‐NDA ! The review time after filing J-‐NDA is similar to US and EU:
! 12 months for standard filing ! 9 months for the “Orphan Drug Designation” or priority review.
Two major milestones during the review: ! 2-‐3 months after filing -‐ after the Mendan meeting (face-‐to-‐face) ! After J-‐GCP compliance check conducted by PMDA inspectors
! This is a major step, set prior to the Expert Review meeting
Region-‐specific Module 1 dossier for Japan ! Table of contents ! Approval application (copy) ! Certificates ! GLP-‐ and GCP-‐related data, contracts for co-‐development, etc. ! Patent status ! Background of origin, discovery, and development ! Data related to conditions of use in foreign countries ! List of related products ! Package insert (draft) ! Documents concerning nonproprietary name ! Data for review of designation as poisons, deleterious substances, etc. ! Draft of basic protocol for post-‐marketing surveillance ! List of attached documentation
Global Study and Its Plan/Report ! Data is to be submitted in Japanese, unless stated otherwise ! Documentation requirements:
! Global CSR (acceptable in Eng.) ! J-‐CTD 2.5 Clinical Overview ! J-‐CTD 2.7.2 Summary of Clinical Pharmacology ! J-‐CTD 2.7.3 Summary of Clinical Efficacy ! J-‐CTD 2.7.4 Summary of Clinical Safety
* Note: all the tables can be submitted in English. The rest of J-‐CTD structure parallels the FDA eCTD.
Approval ! Sponsors that wish to start a marketing business for drugs must obtain a marketing business license (manufacturing/distribution approval).
The licensing requirements include: ! Appointment of a general marketing compliance officer (e.g., pharmacist) ! Compliance with the Good Quality Practice (GQP) and Good Vigilance Practice (GVP).
! The general marketing compliance officer will oversee quality assurance ! The safety management supervisor will be in charge of GVP
Summary ! Informal or formal consultation meetings on either CTN or NDA are key for the approval process
! It is essential to retain KOL for appropriate advice and for building consensus with PMDA.
! High quality translation of the documents as well as the interpreters during the meetings with PMDA is crucial.
! Always refer to ICH guidelines.
Summary ! Use CTD format -‐ English files on Modules 3 –5 can be submitted for registration purposes.
! Module 1 and Module 2 requires Japanese translation ! Bridging strategy related to ethnic differences between Caucasian and Japanese should be well vetted with the PMDA. Remember that foreign data can be used but not as pivotal data.
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Or email us for further consultation: ! [email protected]