Current Status of Global Change Control Management

Tetsuya Kawakami, Chugai Pharmaceutical Co., Ltd., Japan

CMC Strategy Forum Japan 2015(Nov. 8-9, 2015)

Contents

1. Change Control Management in Japan2. Global Change Control Management3. Variation of Regulatory Actions (Examples)

2

1. CHANGE CONTROL MANAGEMENT IN JAPAN

3

Change Control Management in Japan (Simplified Flow)

Preliminary regulatory assessment

Chugai change control committee

PCA management meeting : (Supply risk management)

CMC-RA

PCA submission

Dossier preparation according to reference data

PCA approval

MCN

Q&A with PMDA

MCN is submitted by collaboration with supply chain group

PCA/MCN management system

Labeling preparation meeting

Input (All)

List of PCA/MCN related to labeling change (PI)

Input (PCA/MCN)

Submit within 30 day after first product release.

Change Information at Local site

4

Change Control Committee in Chugai

• Monthly meeting• Attendees

– QA, Subject Matter Experts (drug substance, formulation, analytical), CMC project leader (Supply chain leader), CMC-RA (Regulatory)

• Scope– Products after NDA/BLA submission

• Discussion– Scientific rationale for the change– Regulatory action (PCA, MCN, None)– Impact for package insert– Change implementation plan (if needed)

5

PCA/MCN Management System in Chugai(PCA Master)

• QA and CMC-RA input necessary information of each MCN/PCA into the system.

• Input item– Name of change and change ID No.– PCA submission date (Plan & Actual)

• Plan: Under negotiation(of target receipt date of reference data)Input planed submission date after agreement of target receipt date of reference data

• Actual: PCA submitted date

– Expected PCA approval date– Necessity of GMP inspection

6

PCA/MCN Management System Example(PCA Master)

Chugai Change ID No.

Change request

dep.

Product name

Title of change

Chugai CC

status

Chugai CC assessment

date

PCA date(Plan)

PCA date(Actual)

Expected PCA

approval date

GMP inspectionnecessity

7

PCA Management Meeting• Quarterly meeting

• Attendees

– QA, CMC-RA, supply chain department, CMC coordination department

• Discussion

– Supply risk management based on expected PCA approval date

• Sustainability of product supply with addition/replacement of manufacture site

• Product switch after approval manufactured/tested with new approved conditions

– GMP inspection readiness check in accordance with progress of PCA dossier review

– Progress check of regulatory action

• Readiness of reference data and PCA dossier

• Proper actions to review queries

• Responsibility

– QA : GMP inspection status (site or paper)

– CMC-RA : PCA status including dossier readiness and Q&A

– Supply chain :

• Supply plan for the change

• Stock strategy 8

GLOBAL CHANGE CONTROL MANAGEMENT IN CHUGAI

9

Global Change Control Management in Chugai (Simplified Process)

Status of HAs Review

Information of Approval

License Holders

outside JapanChugai

QA

Chugai Manufacture

Site (MS)

Regulatory & Quality

Impact Evaluation

Change Control

CMC-Leader

MS

Supply Chain

&

Oversee Business

Shipping Arrangement

Global HAs

CMC-Regulatory

CMC-Leader

MS

Supply Chain

Oversee

Business Dep.

Planning & Filing

Technical Regulatory

at

License Holders

Dossier Updates

Supply Chain at

License Holders

“Green light” to GO

10

VARIATION OF REGULATORY ACTIONS

11

No Description US EU

1 Change of bioreactor in seed culture CBE30 type Ib

2Change of infusion solution for dilution of product

solution in addition to the current infusion solutionCBE30 type II

3 Change standard procedure of dilution of testing Annual report type Ia

4 Change of campaign numbering rule Annual report -

5 Change of manufacturing process of DSPrior Approval

submission (PAS)type II

6 Introduction a new product at manufacturing site CBE30 -

7Use of different type of spinner in seed culture at

manufacturing siteCBE30 -

8A infusion solution for dilution of product in addition to

the current infusion solution CBE30 -

9 New vial supplier Annual report type IA

10 Replacement of bioassay with new bioassay PAS type II

11 Transfer of visual inspection site to new site CBE30 type Ib

Regulatory Actions for US and EU (Example)There are various regulatory actions to change control based on the CTD M3 document

12

Regulatory Actions for EU and other countries(Example)There are different various kinds of regulatory actions depending

on regulatory impacts

PACMP: Post approval change management protocol13

Japan Taiwan Korea China ThailandAustralia/

NewZealandEU

1 Deletion of ID test item

Change

post

approval

Change

prior to

approval

2 Layout change in the filling site

3 Layout change at gowing room in the packging room

4 Addition of inspection room

5Discontinuation of environmetal monitoring by settle plate

in ISO8 and ISO8 at rest area

6 Renewal of manufacturing equipment for purified water

7 Inspection site addition

8 New building installation for QC testing

9 Renewal of Raw material storage place

10 Change of Reference standard test methods

11 ID test method change

12 Addition of filling line in the same manufacturing sitePACMP &

type 1b

Regulatory Actions

Change Items

No

Summary

• Introduced Global Change Control Management System in Chugai

• For the regulatory compliance, it is necessary to have a change control management system

• Different regulatory actions based on different binding information for a change may burden the management system

• Expectation to the globally unified established conditions and its simplified regulatory actions for better regulatory compliance

14

- Innovation all for the patients -

15