update on regulatory landscape of regenerative …pharmaceuticals and medical devices agency 1...

1Pharmaceuticals and Medical Devices Agency

Update on Regulatory Landscape of

Regenerative Medicine in Japan

DISCLAIMER : The contents of this presentation represent the view of this

presenter only, and do not represent the views and/or policies of the PMDA

4th India - Japan Medical Products Regulation Symposium 2019

5 February 2020

Yoshiaki Maruyama, Ph.D.Review Director,

Office of Cellular and Tissue-based Products

PMDA, Japan


Regenerative Medicine

All medical technologies using

processed cells which 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


Medical Care or

Academic Research Purpose

Commercial Product

Marketing Authorization Purpose

Enacted on

25 November 2014

Two Acts Regulating Regenerative Medical Technology & Product



Technology excluded by Cabinet OrderYes

Out of the scope of application of the Act

YesNo

Cells to which gene was introducedYes

No

Class I

Class I

YesStem cells are used

No

Allogeneic cellsYes

No

Class I

No

Xenogeneic cellsYes

Class I

No

Purpose is reconstruction, repair or formation

of human body structure of function

No

Yes

Homologous use Class IINo

Yes

Human embryotic stem cells, iPS cells, cells similar to iPS cells

Class III

Class IICell cultureYes

No


YesClass III

Class IICell cultureYes

No


Yes

Class III

Risk Classification Regenerative Medical Technology

Note:In vivo gene therapy is currently out of scope



MHLW

Health Science CouncilHospitals / Clinics

submission evaluation

MHLW

submission

opinion

Provision (Within

90 days)

Change order (Within 90 days)

Certified special committee for regenerative medicine

Plan

High Risk (class I)

Middle Risk (class II)

Low Risk (class III)

Hospitals / Clinics

Plan

evaluation

submissionProvision

Hospitals / Clinics

Plan

submission

submission evaluation

submission

MHLW

Provision

Certified special committee for regenerative medicine

Certified committee for regenerative medicine

Special committee = 57

Committee = 96

Plans (3,785)

Clinical

research

Medical

care

0 19

443 70

3,342 64

(As of 30 November 2019)

Rules for Hospitals and Clinics

Safety Act



Medical institutionCorporate factory. etc

Collection

Transplant

Processing, storage

Outside hospital Within hospital

Processing, storage

Notified = 2,711 sites Licensed (Local)

= 66 sites

Accreditation (Overseas) = 6 site (Korea) = 1sites (China) = 2 sites (Taiwan)

Cell Processing Facility

(As of 30 November 2019)

Safety Act



Organizations and Authorities in Japan

Health Policy Bureau

Pharmaceutical Safety and Environmental Health Bureau

R&D Division

Site Inspections

Product Review

Approval Decision, License Execution

Office of Safety II

HospitalsCPFsManufacturing

SitesMAHs

Certified committees

MHLW

PMDA

Office of Cellular and Tissue based Products

Office of Manufacturing Quality and Compliance

Safety Act

Medical Device Evaluation Division

PMD Act4th India - Japan Medical Products Regulation Symposium 2019


Approved Plans (iPS)

2019-

Under The Act on the Safety of




Feb/2019

Safety Act



Aug/2019Mar/2019 Safety Act



Jan/2020Safety Act




All medical technologies using

processed cells which 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


Medical Care or

Academic Research Purpose

Commercial Product

Marketing Authorization Purpose

Enacted on

25 November 2014

Two Acts Regulating Regenerative Medical Technology & Product



Consultation and Review Pathway

Regulatory Science Strategy

Consultations

After completion of

exploratory study meeting

Consultations on quality assurance

Etc.

Quality

Non-clinical

Clinical trial

Development

Consultation

Application for

Marketing

Authorization

Review of Clinical Trial Protocol

(30 days-IND review)

* To prevent the occurrence or spread of

hazard to the public.



Face-to-face consultations

on R&D strategyFY2014 FY2015 FY2016 FY2017 FY2018 Total

Regenerative medical products#1 2 11 14 13 5 45

Quality and safety of regenerative

medical products#2 18 [44] 29 [55] 26 [64] 29 [71] 25 [54] 158 [340]

Total 46 66 78 84 59 385

Number of INDs#4 FY2014 FY2015 FY2016 FY2017 FY2018 Total

First Notification 3 [1] 10 [2] 16 [7] 13 [8] 18 [8] 60 [26]

Others 1 [1] 3 [2] 5 [0] 14 [10] 17 [3] 40 [16]

Face-to-face consultations for INDs#3 6 18 28 38 47 137

PMD Act

#1: This consultation category was introduced on November 25, 2014.#2: Some consultations were divided into multiple sessions over several days, to confirm the quality and safety of regenerative medical products before the submission of clinical trial notifications. The figures in brackets indicate the total number of sessions.#3: For prior assessment consultations for regenerative medical products, the number of consultation categories was summed. (Set categories: quality/safety/efficacy, exploratory trial, confirmatory trial)#4: Timing: The first notifications; 31 days before, Others; 2 weeks before. The figures in brackets indicate the Investigator -initiated Clinical Trials.

Number of Consultations and INDs



Today Approved Regenerative Medical Products

Maruyama et al., Cell & Gene Therapy Insights 2019; 5(6), 561–568


https://www.novartis.co.jp/news/media-releases/prkk20180423-1

Press release in Japanese)

Mar/2019

Indication:

ALL

DLBCL



Desirable development model of regenerative medical products for conditional and time-limited approval

Maruyama et al., Cell & Gene Therapy Insights 2019; 5(6), 561–568


https://www.anges.co.jp/en/pdf.php?pdf=100990.pdf

https://www.anges.co.jp/en/project/proj_develop.html

Indication:

Ulcer healing for CLI patient

Conditional &

Time-Limited

Approval

Mar/2019



Assigned SAKIGAKE

Designation4th round, announced by 8th April 2019



Lead the world in the practical application of innovative medical products

Accelerate R&D through supporting each stage

The Strategy of SAKIGAKE covers from basic research to clinical

research/trials, approval reviews, safety measures, insurance coverage,

improvement of infrastructure and the environment for corporate activities,

and global expansion.

Strengthen the structure of PMDA

（consultation, review, safety measures in terms of quality and quantity)

Promotion of Regulatory Science

(Developing guidelines/assessment for the state-of-the-art technology)

Strategy of SAKIGAKE



4th Round

2019



Thank you foryour attention!

Please visit the PMDA website http://www.pmda.go.jp

http://www.pmda.go.jp/english/index.html

2020

Thank you for your attention!


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