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Rolling Reviews in SAKIGAKE and Breakthrough Therapy Designation

Toshiyoshi TOMINAGA, Ph.D.

Associate Executive Director

Pharmaceuticals and Medical Devices Agency

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Prior Assessment Consultation as Japan’s Rolling Review

Summary• PMDA reviews data piecemeal as they become ready during developmentAim• Issues are found and addressed early to streamline review and decreaser

burden on the applicant

Doc. Submission

Pre-meeting Response

Draft Evaluation report

FinalE. report

40 days 30 days 35 days 15 days

Inquiry

Total:120 work. days

(6 calendar mo.s)Applicant’s Action

PMDA’s Action

NDA Submi-ssion

2011 2012 2013 2014 2015 Approx. Cost (US$)

Phase I study 3 5 2 5 0 36,000

Phase II study 1 1 0 1 0 46,000

Phase II / III study 1 2 3 6 1 72,000

Pre-clinical: toxicity 4 9 2 7 2 21,000

Pre-C: pharmacology5 7 2 8 2 21,000

Pre-C: pharmacokinetics4 9 3 6 2 21,000

Quality 6 8 3 11 1 31,000

TOTAL 24 41 15 44 8180,000-210,000

Pr. Rev. Consultations made and Cost for each category

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1. This is “Consultation”; not formal submission or review.

When done, formal submission of ALL data required

2. About 50% of Applications accepted, depending on

Human-resources available in the relevant Review

Team

Whether there are more suitable categories of

consultation

3. Does not ensure quicker review; target review time of 9

months (prioritized) or 12 months (regular) is set

independently.

On Prior Assessment Consultation

Survey Results on Applicants completing Prior Review Consultation and formal review (2009-2010 Pilot)

Q4 Fee for Consultation appropriate?Very Cheap 0

Somewhat Cheap 1

Neutral 5

Somewhat Expensive 5

Very expensive 5

Q1 review time shortened?Very much shortened 2

Shortened 3

Neutral 1

Extended 0

Very much extended 0

Q2 Review became efficient?

Made very much efficient 2

Made somewhat efficient 4

Neutral 0

Made somewhat inefficient 0

Made very much inefficient 0

No duplicated review was conducted

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Partly duplicated 0

Almost all duplicated 0

Q3 Duplicated review avoided?

Rolling Review in SAKIGAKE (Pioneer) Designation Program

【SAKIGAKE Designation Product】

【Ordinary Review】

Non-clinical

Clinical Research

Phase I/II Consul-tation

Phase III Review

Consultation

12 months

2months

Phase I/II Phase III

Consultation Prior ReviewDesignation as SAKIGAKE

6months

1 month

Review

Approval

Non-clinical

Clinical Research

Expedited PathwaysUS JAPAN

Accelerated Approval

- Approval on a surrogate or intermediate clinical end point

(usual practice)

Priority Review - 6-month review- Designation required

- 9-month review period- Designation required

SAKIGAKE/Breakthrough Therapy

- Rolling Review & 6-month review period

- Designation required

- Rolling Review (SAKIGAKE Compre-hensive Consultation)& 6-month review period

- Designation required

Fast Track - Rolling Review & 6-month review period

- Designation required－

Jinsoku (Rapid) Review

－- Specially designated by MHLW

Breakthrough Therapy vs. SAKIGAKE 1Breakthrough Therapy SAKIGAKE

Launch July 2012 April 2015

Criteria - Unmet Needs, Serious or Life-

threatening Conditions- Substantial improvement in

efficacy

- New Mechanism/Action- Unmet Needs, Serious or Life-

threatening Conditions- Substantial improvement in

efficacy

Project Manager - Cross-disciplinary project lead- Senior manager involved

- Review Partner (Concierge)

Priority Review - Not automatically designated - Review within 6 months (shorter than Priority’s 9 months target)

Rolling Review Eligible Eligible (SAKIGAKE Comprehensive Evaluation Consultation

Breakthrough Therapy vs. SAKIGAKE 2

Breakthrough Therapy SAKIGAKE

First NDA in the world

- Intent to develop and file NDA first in Japan (simultaneously in other countries)

Preferably• First-in-human study in Japan• Proof of Concept Study in Japan

Re-examination period

- Maximum 10 years (standard 8 years)

# of Designated Items

Total 130 items111 (CDER), 19 (CBER)

Total 11 items6 Drugs, 3 Regenerative Products, 2 Medical Devices

Approved items 43 (about a quarter of novel drugs approved)

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SAKIGAKE Comprehensive Evaluation Consultations (simplified)

ApprovalNDA

Submission

Review

1. CMC

2. Non-Clinical

3. Clinical

4. GCP/GLP Compliance

5. GMP Compliance

ca. 4 months

First submission

I/A

(on-site Inspection)Preparation

On-site InspectionP 3

PreparationOn-site Inspection

(on-site inspection)

= Permission to submit

I/A

Inquiry/Answer

6 months

Monthly Consul.with Concierge

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1. Mandatory for Sakigake-designated products

2. 5 Tracks as 1 package, basically no separate deals

3. Cost: about $ 200, 000

4. Currently (June 2016), monthly consultation going-on,

not yet reached the initiation of the Sakigake

Consultation.

On SAKIGAKE Consultations’ Operation

Rolling Review in Breakthrough Therapy Designation

ApprovalNDA

Submission

In case designated as Priority Review Products

Review

1. CMC

2. Non-clinical

3. Clinical

Cross-Disciplinary Project Lead

6 months

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1. All-Hands-on-Deck for applicants and reviewer/inspectors

2. Rolling review (or Sakigake comprehensive consultation) is an

essential mechanism to start review/inspection as early as

possible to achieve the ambitious goal.

3. Enabling partnership between applicant and regulator to deliver

drugs to patients.

4. Strain on data obtained in the late stage of development (e.g.

product quality in scaled-up production). Applicants’ efforts

expected.

Findings

Thank You

Dr. Peter Honig

Mr. Jerry Stewart

PMDA SAKIGAKE Team