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2-2 Current KGMP 2007 0910 - ICH
Transcript of 2-2 Current KGMP 2007 0910 - ICH
KGMP의 현재와 미래
식품의약품안전청의약품평가부
김동섭Dong Sup Kim, Ph.D.
Director, Drug Evaluation Dep.
Pharmaceutical Headquarter
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
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
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
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 다[email protected]
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 다[email protected]
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