KGMP의 현재와 미래

식품의약품안전청의약품평가부

김동섭Dong Sup Kim, Ph.D.

Director, Drug Evaluation Dep.

Pharmaceutical Headquarter

KGMP Overview1

Considerable Issues2

Revision of KGMP Regulation3

Perspective4

Contents

KGMP Overview

Guarantee on Policy IntegrityㆍPublic Satisfaction Guarantee on Policy IntegrityㆍPublic Satisfaction

Elevating the

Standard of

Living

Elevating the

Standard of

Living

Quality

Assurance

Quality

Assurance

Scientific

Progress

Scientific

Progress

Enhance

Health

Concept

Enhance

Health

Concept

• Introduce Validation System

• Introduce International Standard

<Policy Quality Management Manual>

Harmonized GMP RulesConstitution of Institutional Base for Quality Control

Quality Management SystemGMP Steering Committee

Milestone of KGMP

KGMP was required by the law(mandatory)

Recommendedby WHO

2000

1992

1977

1969

Established &Notified KGMP

Established KGMP for Biologics

TOTAL : 359

Drug Product : 232

Drug Substance : 127

KGMP KGMP companiescompanies

(August 2007 )(August 2007 )

Authorization of GMP facility & operation systemby document review &inspection

GMP managementby formulation

(Not by product)

No Validation

Lack of GMP rulesfor clinical trial medicine

Optional GMP education

for manufacturer(Not mandatory)

Lack of GMP rules for herbal medicine

CurrentStatus

OOOOOContamination Control

XOXOOSelf Inspection

XOOOOAutomatic Equipment

Control

XOOOOOut Of Specification

XXOOOAnnual Product Review

OOOOOStability

XOOOOChange Control

XOOOOQualification

XOOOOValidation

KoreaIndiaUSAEU, Japan,Singapore

WHO,PIC/S

RegulationRegulation

Considerable Issues

LOGIC TREE

Backwardnessof

pharmaceuticalIndustry

BackwardnessBackwardnessof of

pharmaceuticalpharmaceuticalIndustryIndustry

WhatWhat WhyWhyIssue CategoryIssue Category

SmallmarketSmallSmall

marketmarket

SmallscaleSmallSmallscalescale

IndustryIndustryIndustry

Too many items in a companyToo many items in a company

Lack of distribution systemLack of distribution system

Bottleneck of M&ABottleneck of M&A

Lack of developmenton product to profit

items

Lack of developmenton product to profit

items

Be short of expertsfor new drug development

Be short of expertsfor new drug development

TechnologyTechnologyTechnology

Lack of advanced GMP rules

Lack of advanced Lack of advanced GMP rulesGMP rules

PolicyPolicyPolicy No product-based pre-approval GMPNo product-based pre-approval GMP

Bottleneck ofAccession to PIC/S

& MRA planning

Bottleneck ofBottleneck ofAccession to PIC/S Accession to PIC/S

& MRA planning& MRA planning

No validationNo validation

Lack of herbal & IND (clinical)GMP rules

Lack of herbal & IND (clinical)GMP rules

Lack of education for manufacturerLack of education for manufacturer

Lack of AdvancedGMP Rules

Lack of AdvancedGMP Rules

InsufficientGMP Inspection

System

InsufficientGMP Inspection

System

IssuesIssues SolutionsSolutions

Formulation based GMP

management

No validation

Low level GMP

Lack of GMP rules for

herbal & clinical trial medicine

Lack of the wholly

responsible structure for

Inspection

Be short of Professional

inspectors

Adoption of product-based

pre-approval GMP System

Phase in Validation

Harmonized with international

GMP rules

Establish GMP rules for herbal

& clinical trial medicine

Accession to PIC/S

Enhancement of education

for inspectors & authorized

manufacturers

Build a GMP inspection

division

Revision of KGMP Regulation

Conduct study on the advanced model of KGMP for assuring International competition

SeptemberSeptember 20072007

October 2006October 2006

JulyJuly 20062006

2003 ~ 20052003 ~ 2005

Revision of Enforcement Ordinance of Pharmaceutical Affair Act

Notify the pharmaceutical industries regarding KGMP international harmonization through civil affair explanation meetings

The Presidential Commission Body decided to push ahead KGMP international harmonization

Revision ProcessRevision ProcessRevision Process

1 Adoption of product based pre-approval KGMP

Mandatory validation by law2

3 Adoption of change control

Adoption of annual product review4

5 Control on Out of specification / Deviation

NewNew

January 2010

July 2009

July 2008

July 2007

•• Drug SubstanceDrug Substance•• QuasiQuasi--Drug (Oral Drug (Oral SoildSoild & Liquid Preparation)& Liquid Preparation)

•• NonNon--prescription Drugprescription Drug

•• Prescription DrugPrescription Drug

•• New DrugNew Drug

On-going BE products since July 2006: as a Study conducted by The Presidential Commission on Healthcare Industry Innovation

Pre-approval KGMP( Product-based )

PrePre--approval KGMPapproval KGMP( Product-based )

Pre-approval KGMP( Product-based )

PrePre--approval KGMPapproval KGMP( Product-based )

July 2007

July 2008

July 2009

January 2010

New Drug

ProcessValidation

ValidationValidationValidation

Prescription Drug

ProcessValidation

Non-prescription Drug

ProcessValidation

Drug SubstanceQuasi-Drug

Process ValidationCleaningValidationValidation of AnalyticalMethods

Support SystemValidationComputervalidation

OptionalQualificationMandatory

Not availableQuantity3 Lot

OptionalValidationMandatory

Not LimitedRange of quality unitLimited to Contract Unit

Pharmacist or Non-pharmacist

Authorized manufacturerpharmacist

IND-KGMPGeneral-KGMP

IND-KGMP GuidelineINDIND--KGMP GuidelineKGMP Guideline

KGMP Rules for Herbal MedicineKGMP Rules for Herbal MedicineKGMP Rules for Herbal Medicine

OptionalQualificationMandatory

OptionalCompatibilityMandatory

OptionalAnnual Product ReviewMandatory

OptionalValidationMandatory

A, B, C, . .Contamination controlA, B, C, . .

Herbal-KGMPGeneral-KGMP

Set up Facility Standard (Preprocessing/Storage Area etc) for Herbal Medicinal Materials

Set up Manufacture & QC Standard for Extract and Powders of Herbal Medicinal Product

KGMP EducationKGMP EducationKGMP Education

RecipientRecipient MandatoryMandatory ExceptionException

All who first desired to become an authorized

manufacturer for KFDA’s approval

or declaration (including any change of the manufacturer )

Should complete the education designated by KFDA

More than 16 hrs biennially

Anyone who have completed

the same education

designated by KFDA within 2

years

Approval

Review report

KFDA

Report on review result

External experts

Interview Applicant Inquiry and conformation from KFDAPresentation from applicant and Response

Reviewersand

Applicant

Manufacturing site

KFDA

Discussion of main issues and conclusionDocument-based discussion possible

Expert discussionon review

Reviewers External expertsand

GMP audit

GMP audit result

Compliance review

GMP Review Rangein case of site changes within the same location of the facility

GMP Review RangeGMP Review Rangein case of site changes within the same location of the facility

Filing Report

Change Control

DocumentO

Change of environmental

conditionsTransfer of major instrument/equipment,

workroom

Filing Report

Change Control

DocumentOAir/Water System Change within the

existing facility

Filing Report

Change Control

DocumentXStorage/Laboratory change

Filing Report-X

Same environmental

conditions

Filing Report

Change Control

DocumentOExtension / Remodeling

LicenseGMP ApplicationONew Building

ClassDocumentGMP ReviewChange

Reinforcement on herbal medicineReinforcement on herbal medicineReinforcement on herbal medicine

Quality control on manufacturing the herbal powders & extracts in separated working area and their batch records Quality control on manufacturing the herbal powders & extracts in separated working area and their batch records

Storage of the records on chemicals and fumigants used for the prevention of insects and mold proliferation on the crude herbal medicine

Storage of the records on chemicals and fumigants used for the prevention of insects and mold proliferation on the crude herbal medicine

Obligation of detail quality control standards on the crude herbal medicine and control on the species and specimen of the herbal medicine

Obligation of detail quality control standards on the crude herbal medicine and control on the species and specimen of the herbal medicine

Selection, discrimination, and cleaning of the herbal medicine should be proceeded at the separated preparation working area and stored in a separated storage facility

Selection, discrimination, and cleaning of the herbal medicine should be proceeded at the separated preparation working area and stored in a separated storage facility

Main Reinforcement Main Reinforcement Main Reinforcement

Sanitation by performing regular medical examination of the personnel and retaining the records of the cleaning, and the use record of the equipment and facilities

Sanitation by performing regular medical examination of the personnel and retaining the records of the cleaning, and the use record of the equipment and facilities

Response to complaints such as investigating the content, finding the reason and corrective actions, etc.Response to complaints such as investigating the content, finding the reason and corrective actions, etc.

Mandatory stability test for the first three commercial batches (long-term storage) Mandatory stability test for the first three commercial batches (long-term storage)

Review process of intermediate inspector beyond the person who performed the test and the authorized person in the quality control

Review process of intermediate inspector beyond the person who performed the test and the authorized person in the quality control

Main ReinforcementMain ReinforcementMain Reinforcement

Separation of the facility which manufacture the medicine including cephalosporin & cytotoxic anticancer materialsSeparation of the facility which manufacture the medicine including cephalosporin & cytotoxic anticancer materials

In case of contract manufacture or quality control, the contract giver should perform self audit on the contract accepter sites

In case of contract manufacture or quality control, the contract giver should perform self audit on the contract accepter sites

Recommendation on the verification of suitability of all the testing methods in quality control Recommendation on the verification of suitability of all the testing methods in quality control

Perform regular internal audits by the manufacturer in order to verify the manufacture and quality control Perform regular internal audits by the manufacturer in order to verify the manufacture and quality control

Main ReinforcementMain ReinforcementMain Reinforcement

Self audit by the manufacturing and quality control supervisor on the critical deviations or the failure in the standards of the manufacturing and quality control

Self audit by the manufacturing and quality control supervisor on the critical deviations or the failure in the standards of the manufacturing and quality control

Clarify the standard of detailed general laboratory facility Clarify the standard of detailed general laboratory facility

Quality management on the verification of the manufacturing and quality control of the annual manufactured products, and cause of rejected materials etc.

Quality management on the verification of the manufacturing and quality control of the annual manufactured products, and cause of rejected materials etc.

Detailed storage sample rules of the retaining samples for two or more tests for each unit of batch or lot numberDetailed storage sample rules of the retaining samples for two or more tests for each unit of batch or lot number

Perspective

Future ActivitiesFuture Activities

Establishment of GMP inspection guideline Establishment of GMP inspection guideline

Better coordination between pre-market review and inspection and surveillance programsBetter coordination between pre-market review and inspection and surveillance programs

Accession to PIC/SAccession to PIC/S

Establishment of detailed education program for manufacturersEstablishment of detailed education program for manufacturers

Comprehensive Understanding of

Manufacturing Process and

Product Knowledge

Improvement of PharmaceuticalQuality System

Facilitation Science-based

Quality Assessment

Internationally Harmonized Quality SystemInternationally Harmonized Quality System

감 사 합 니 다dskeem@kfda.go.kr

ありがとうございます谢谢

Merci

Thank you

Muchas Gracias

Gratia

stib

i

Tack, Tack så mycket Danke schön

te agradezcoMaine Pyar Kiya

Terima Kasih

ขอบคุณ/ใจ

감 사 합 니 다dskeem@kfda.go.kr

ありがとうございます谢谢

Merci

Thank you

Muchas Gracias

Gratia

stib

i

Tack, Tack så mycket Danke schön

te agradezcoMaine Pyar Kiya

Terima Kasih

ขอบคุณ/ใจ