history of pdg
TRANSCRIPT
Fumi YamamotoDirector,Pharmaceutical Evaluation Division,Pharmaceutical Safety and Environmental Health Bureau,Ministry of Health, Labour and Welfare
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History of PDG
October 3, 2019The PDG 30th Anniversary Symposium
• What is PDG
• History of PDG
• Working Procedures of PDG
• Publication of Harmonization Status
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October 3, 2019The PDG 30th Anniversary Symposium
Today’s Topic
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October 3, 2019The PDG 30th Anniversary Symposium
Why do we need “Harmonization”?
If each country/region has own pharmaceutical regulation without harmonization….
→ When pharmaceutical products that approved in one country/region
are sold in other countries/regions, the products must meet the quality
specification of that countries/regions
- Must conduct tests based on each country/region requirement on the
product even though existence of test data
Pharmacopoeias Standardization
→ can make the test methods and the quality standards which
are valid throughout the world
Waste of resources!!
What is “PDG”?
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October 3, 2019The PDG 30th Anniversary Symposium
【Purpose of Activities】
• Standardize the test procedures and acceptance criteria that differ among pharmacopoeias
→ Standardize general chapters and excipient monographs
→ Reduce manufacturers’ burden of performing analytical procedures • Maintain an optimal level of science
PDG (Pharmacopoeial
Discussion Group)
Ph. Eur. (European Pharmacopoeia)
JP (Japanese Pharmacopoeia)
USP (United States Pharmacopeia)
Establishment :1989Observer :WHO(Since May, 2001)
Meetings :Twice every year(F2F and Video conference, hosted in turn)
Status of each Pharmacopoeia
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Ph. Eur. USP JP
Issued by • European Directorate for the Quality of Medicines and HealthCare (EDQM)
• Founded in1964• Strasbourg, France• Pharmaceutical
medical quality department within the European Council
• USP Convention • Founded in 1820• Maryland, USA• the incorporated non-
profit organization independent of regulatory authorities
the Ministry of Health, Labour and Welfare (MHLW)
Status prepared under the treaty of Council of Europe and is referenced under the order of EU
Food, Drug, and Cosmetic Act
Act on Securing Quality, Efficacy and Safety Products Including Pharmaceuticals and Medical Devices
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October 3, 2019The PDG 30th Anniversary Symposium
30 years of PDG Activities
Establishment of PDG
First sign-off(SDS-PAGE)
Participation of WHO observer
Enactment of Policy and Working Procedure
1995
ICH Q6A agreement – Specifications for new drugs
1999
Establishment of ICH Q4B –Evaluate for inter-regional regulatory acceptance
2003
Revision of Policy and Working Procedure –Change in definition of harmonization and adoption of harmonization by attribute
2003
2010Discontinue
Major activities up till September 2019General Chapters (Physico-chemical, Drug formulation, Physical methods, Microbial, Biological)
→28 out of 31 general studies (PDG work program) have been harmonizedExcipients monographs
→46 out of 60 monographs (PDG work program) have been harmonized
PDG
ICH
Singing-off of last ICH Q4B Annex
Re-examination of system
2017
Maintenance procedure of ICH Q4B Annex
Establishment of PDG
1989 May - USP Spring Conference (Virginia, USA)
Jun. - EP 25th anniversary Open Conference (Strasbourg, France)
Sep. - International conference (Tokyo, Japan)
Dr. Lee T. Grady (USP)Dr. Peter J. Schorn (EP)Dr. Mitsuru Uchiyama (JP)
1990 1st PDG Face to Face meeting
1991 Excipient International conference (Orlando, USA)→ IPEC was formed
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October 3, 2019The PDG 30th Anniversary Symposium
PDG activities in 1990 to 2000PDG Statement of Harmonization Policy
established in 1995
PDG harmonization policy in the early stages was prerequisites of reaching full harmonization of general chapters or monographs, based on objective comparability.→First sign-off in 1999 (SDS-PAGE)
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October 3, 2019The PDG 30th Anniversary Symposium
No achievement of harmonization for several years
Trial and error period
PDG activities since 2002
→ Evaluate interchangeability of harmonized pharmacopoeial text by ICH→ Establishment of ICH Q4B
Main Discussion point:
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October 3, 2019The PDG 30th Anniversary Symposium
Difference in interpretation of “Objective equivalency”
→ may cause problems in regulatory interchangeability by other regulatory authority
→ modify the definition of harmonization and adopt harmonization by attribute
Differentiate between “pharmacopoeial harmonization” that mainly PDG works for, and “regulatory interchangeability” of harmonized text that regulatory
authority guarantees as a result of pharmacopoeial harmonization.
Policy of Pharmacopoeial Harmonization
Purpose
To avoid redundant testing for different acceptance criteria in each pharmacopoeia
To contribute pubic health by maintaining an optimal level of science
Definition of harmonization
The tests should not result in disparity in the accept/reject decision of pharmaceuticals
→ Explicit description of definition in consideration of interchangeability
When full harmonization is not achievable, the approach of “harmonization by attribute” is applied. For non-harmonized attribute, using of other approaches such as “alternative method” is relied on the individual pharmacopoeia.
→ Introduction of partial harmonization10
October 3, 2019The PDG 30th Anniversary Symposium
PDG Statement of Harmonization PolicyRevision November 2003
Procedure of Pharmacopoeial Harmonization
Working Procedure
Harmonization occurs based on decisions of expert bodies of each pharmacopoeia
PDG works transparently in many ways principally including public notice and comment procedures of each pharmacopoeia.
Implementation
Implementation of harmonized document varies among pharmacopoeias (due to legal requirements, need for translation, publication schedules, etc.)
Each pharmacopoeia generally sets a period of time for transition before implementation.
Revision
Each pharmacopoeia does not revise unilaterally after publication. When necessary, revision should be conducted according to the PDG Working Procedures. 11
October 3, 2019The PDG 30th Anniversary Symposium
Working Procedure of PDGRevision version June 2010
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2010 version 2017 version
Stage 1 Identification Pre- PDG IdentificationInvestigationDevelopment of clear conceptStage 2 Investigation
Stage 3 Proposal for Expert Committee Review
Stage 1 Preparation of first draft
Stage 4 Official inquiry Stage 2 Official inquiry
Stage 5 Consensus Stage 3 Consensus
Stage 6 Regional adoption and
implementation
Stage 4 Regional adoption and
implementation
Stage 7 Inter-regional acceptance Stage 5 Inter-regional acceptance
Procedure was simplified→ harmonize more effectively in a shorter period of time
Procedure of Pharmacopoeial HarmonizationWorking Procedure of PDGRevision version September 2017
PDG Working Procedures (1)
Pre-PDG
Stage 1: Preparation of first draft
Stage 2: Official Inquiry
Stage 3: Consensus
Stage 4: Regional adoption and implementation
Stage 5: Inter-regional acceptance (for chapters previouslyevaluated by ICH Q4B for Regulatory
Interchangeability)
October 3, 2019The PDG 30th Anniversary Symposium
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Revision
Correction of a sign-off text
Correction of a sign-off cover sheet
PDG Working Procedures (2)
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October 3, 2019The PDG 30th Anniversary Symposium
PDG Work Program – General ChaptersGeneral Chapters:G-01 Analytical Sieving G-02 Bulk Density and Tapped DensityG-03 ConductivityG-04 Gas Pycnometric Density of Solids G-05 Powder FlowG-06 Tablet FriabilityG-07 Elemental Impurities*1
G-08 Inhalation*2
G-09 Optical MicroscopyG-10 Powder FinenessG-11 Specific Surface AreaG-12 Porosimetry by Mercury Intrusion*2
G-13 Laser Diffraction Measurement of Particle SizeG-14 X-Ray Powder DiffractionG-15 Water-solid InteractionG-16 Thermal AnalysisG-17 Uniformity of Delivered Dose of Inhalations*2
G-18 Microcalorimetry*2
G-19 Density of Solids*2
G-20 Chromatography*1
G-21 Dynamic Light Scattering*1
*1:First harmonization*2:Suppressed in 2017
General Methods Relevant to Q6A):Q-01 DissolutionQ-02 DisintegrationQ-03/04 Uniformity of Content/MassQ-05a Tests for Specified MicroorganismQ-05b Microbial EnumerationQ-05c Limits for Non-sterile ProductsQ-06 Bacterial EndotoxinQ-07 Color (Instrumental Method)Q-08 Extractable VolumeQ-09 Particulate ContaminationQ-10 Residue on IgnitionQ-11 Sterility TestMethods for Biotechnology Products:B-01 Amino Acid DeterminationB-02 Capillary ElectrophoresisB-03 Isoelectric FocusingB-04 Protein Determination*2
B-05 Peptide MappingB-06 Polyacrylamide Gel Electrophoresis
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PDG Work Program – Excipient MonographsE-01 AlcoholsE-02 Dehydrated AlcoholE-03 Benzyl AlcoholE-04 Calcium Disodium EdetateE-05 Calcium Phosphate DibasicE-06 Calcium Phosphate Dibasic
AnhydrousE-07 Carmellose CalciumE-08 Carmellose Sodium*1
E-09 Croscarmellose SodiumE-10 Microcrystalline CelluloseE-11 Cellulose, PowderedE-12 Cellulose Acetate (2017)*2
E-13 Cellulose Acetate Phthalate E-14 Citric Acid, AnhydrousE-15 Citric Acid, MonohydrateE-16 CrospovidoneE-17 EthylcelluloseE-18 HydroxyethylcelluloseE-19 HydroxypropylcelluloseE-20 Hydroxypropylcellulose,
Low SubstitutedE-21 HypromelloseE-22 Hypromellose Phthalate
E-23 Lactose, AnhydrousE-24 Lactose, Monohydrate E-25 Magnesium Stearate E-26 MethylcelluloseE-27 Methyl ParabenE-28 Petrolatum*1
E-29 Petrolatum, White*1
E-30 Polyethylene Glycol*1
E-31 Polysorbate 80E-32 PovidoneE-33 Saccharin (2017)*2
E-34 Saccharin, Sodium(2017)*2
E-35 Saccharin, Calcium(2017)*2
E-36 Silicon Dioxide*1
E-37 Silicon Dioxide, Colloidal*1
E-38 Sodium ChlorideE-39 Sodium Starch GlycolateE-40 Starch, CornE-41 Starch, PotatoE-42 Starch, RiceE-43 Starch, WheatE-44 Stearic AcidE-45 SucroseE-46 Talc
E-47 Titanium Dioxide(2010)*2
E-48 Ethyl ParabenE-49 Propyl ParabenE-50 Butyl ParabenE-51 Glycerin*1
E-52 CarmelloseE-53 Calcium Carbonate(2017)*2
E-54 CopovidoneE-55a Gelatin, gelling typeE-55b Gelatin, non-gelling gradeE-56 SucroseE-57 Glyceryl Monostearate(2011)*2
E-58 MannitolE-59 Propylene Glycol*1
E-60 Sodium LaurylsulfateE-61 Starch, Pregelatinized*1
E-62 Sterile Water for Injection*1
E-63 Lactose for Inhalation(2018)*2
E-64 IsomaltE-65 Isostearyl Alcohol*1
E-66 Myristyl Myristate*1
E-67 Sodium Cetyl Sulfate(2018)*2
E-68 Polysorbate 65*1
E-69 Calcium Silicate*1
*1:First harmonization, *2:Suppressed (Year)
Publication of Harmonization Status
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October 3, 2019The PDG 30th Anniversary Symposium
EP:https://www.edqm.eu/en/international-harmonisation-614.html
JP:https://www.pmda.go.jp/rs-std-jp/standards-development/jp/0005.html
USP:https://www.usp.org/harmonized-standards/pdg
Thank you for your attention‼
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October 3, 2019The PDG 30th Anniversary Symposium