iso tc276 wg4 strategies and plans for developing bioprocessing

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ISO TC276 WG4 strategies and plans for developing bioprocessing standards

Convenor: ISO/TC 276/WG 4 (Bioprocessing)Chair: ISO/TC 276 (Biotechnology) Japan Mirror Committee

Chair: FIRM Standardization Committee

Fujifilm Co. Tatsuo Heki

Secretary, ISO/TC 276/WG 4 (Bioprocessing)Vice Chair: ISO/TC 276 (Biotechnology) Japan Mirror Committee

Vice Chair: FIRM Standardization Committee

Astellas Pharma Inc.Yutaka Yanagita

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Content

• Scope / Business plan of ISO/TC 276 (Biotechnology) and ISO/TC 276/WG 4 (Bio-processing)

• How Bio-processing standards are different from regulations (e.g. GMP)

• Technology space in bio-process to be focused for standardization

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ISO/TC276 Scope

• Standardization in the field of biotechnology processesthat includes the following topics:– Terms and definitions; – biobanks and bioresources; – analytical methods; – bioprocessing; – data processing including annotation, analysis, validation,

comparability and integration;– metrology.

– ISO/TC 276 Biotechnology will work closely with related committees in order to identify standardization needs and gaps, and collaborate with other organisations to avoid duplications and overlapping standardization activities.

– The committee will not pursue subjects within the scope of other TCs including but not limited to ISO/TC 212 and ISO/TC 34/SC 16.

ISO/TC 276 (Biotechnology) focuses on processes, NOT the final product

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ISO/TC276 Scope

• Standardization in the field of biotechnology processesthat includes the following topics:– Terms and definitions; – biobanks and bioresources; – analytical methods; – bioprocessing; – data processing including annotation, analysis, validation,

comparability and integration;– metrology.

– ISO/TC 276 Biotechnology will work closely with related committees in order to identify standardization needs and gaps, and collaborate with other organisations to avoid duplications and overlapping standardization activities.

– The committee will not pursue subjects within the scope of other TCs including but not limited to ISO/TC 212 and ISO/TC 34/SC 16.

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Previous efforts - ISO/TC 276/WG 4 Business Plan

ISO/TC 276/WG 4 goal is Consistency (NOT safety)

TG4, in collaboration with other TGs, will develop international standards and guidelines to give confidence to suppliers when developing or operating bioprocesses and to users when products are placed on the market or into a supply chain. The standards will

– - ensure a supply of products, having• - consistent and reproducible quality, and• - appropriate level of safety, depending on use

– - ensure that biotechnology processes operate to the specified degree of control (i.e. adequate process capability)

– - tracking biotechnology processes, to ensure the maintenance of chain of custody throughout the process lifecycle

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Previous efforts - ISO/TC 276/WG 4 Business Plan

ISO/TC 276/WG 4 goal is Consistency (NOT safety)

TG4, in collaboration with other TGs, will develop international standards and guidelines to give confidence to suppliers when developing or operating bioprocesses and to users when products are placed on the market or into a supply chain. The standards will

– - ensure a supply of products, having• - consistent and reproducible quality, and• - appropriate level of safety, depending on use

– - ensure that biotechnology processes operate to the specified degree of control (i.e. adequate process capability)

– - tracking biotechnology processes, to ensure the maintenance of chain of custody throughout the process lifecycle

ISO/TC 276/WG 4 (Bioprocessing) focuses on consistency, NOT safety

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Content


• How Bio-processing standards are different from regulations (e.g. GMP)


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Start point ISO/TC276/WG4 Standardization Needs and Gap Survey,

March 2014• JP#001 Assurance of appropriate handling of cells and tissues during transportation• JP#002 Requirements containers for transportation• UK#001 Logistics for delivery of and assurance of appropriate handling of cells and tissues at points of receipt at the clinic/pharmacy • Luxembourg#001 Validation of biospecimen processing methods. This issue is not currently being addressed. Biobanks process materials based on

protocols communicated by colleagues or previously published but without any formal validation relative to the fitness-for-purpose in the scope of downstream biotechnological applications

• Korea#2 Quality of blood and tissues when they are collected from donor or patient.• JP#003 Quality assessment of additives (meaning reagents?)• US#2 Lot to lot consistency of non-chemically defined raw materials. Such as human derived products, plant derived products and animal derived products• US#5 Raw materials selection in the design of human cell therapy manufacturing processes for clinical applications• US#12 Cell Culture media consistency requirements and control strategies• US#8a End to end tracking and genealogy of clinical supplies from raw materials, cell banks and seeds to vial at the clinic• JP#004 Characteristics of materials that may contact with cell during culturing processes• US#9 Quality and control strategies for Plastic Resins used to fabricate Single Use (SU) Equipment • US#10 Expand on USP Class 6 plastics requirements for Single Use technology and SU Bioreactors • US#11 Requirements for Single Use Equipment Documentation, tracking, Sterilization records, resin supplies, C of A etc• US#14 SU Equipment Supplier Audit Standards• US#15 SU Sensor accuracy and reproducibility • US#16 Class III biological safety cabinets or isolators• US#3 Interchangeability of disposables• US#7 Standardize connectors of disposables • US#6 Best practices to manage multi-production lines in a single facility• US#8 End to end tracking for autologous cell therapy work flow• JP#005 Traceability of bio-processed materials, starting from production until disposal.• JP#006 Monitoring of cell culture process• UK#003 Use of surrogate samples• JP#007 Requirements of apparatus where multiple types of cells is processed• JP#008 Requirements for automated cell culturing• JP#009 Assessment of cell culturing capability• Canada#001 Standards for manufacture of Microbial-based Products (MBP) such as cleaners, or consortiums for bioremediation of contaminated

sites• Korea#1 Quality assurance of Bioprocessing technology transfer from R&D at laboratory to production at plant for pharmaceutical products.• UK#002 Requirements for environmental control and monitoring• JP#010 Environmental impact of materials and apparatus used for bioprocessing• US#4 Specifications for extractable, leachable• US#13 Virus Testing and clearance for MaB

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Start point ISO/TC276/WG4 Standardization Needs and Gap Survey,

March 2014• JP#001 Assurance of appropriate handling of cells and tissues during transportation• JP#002 Requirements containers for transportation• UK#001 Logistics for delivery of and assurance of appropriate handling of cells and tissues at points of receipt at the clinic/pharmacy • Luxembourg#001 Validation of biospecimen processing methods. This issue is not currently being addressed. Biobanks process materials based on

protocols communicated by colleagues or previously published but without any formal validation relative to the fitness-for-purpose in the scope of downstream biotechnological applications

• Korea#2 Quality of blood and tissues when they are collected from donor or patient.• JP#003 Quality assessment of additives (meaning reagents?)• US#2 Lot to lot consistency of non-chemically defined raw materials. Such as human derived products, plant derived products and animal derived products• US#5 Raw materials selection in the design of human cell therapy manufacturing processes for clinical applications• US#12 Cell Culture media consistency requirements and control strategies• US#8a End to end tracking and genealogy of clinical supplies from raw materials, cell banks and seeds to vial at the clinic• JP#004 Characteristics of materials that may contact with cell during culturing processes• US#9 Quality and control strategies for Plastic Resins used to fabricate Single Use (SU) Equipment • US#10 Expand on USP Class 6 plastics requirements for Single Use technology and SU Bioreactors • US#11 Requirements for Single Use Equipment Documentation, tracking, Sterilization records, resin supplies, C of A etc• US#14 SU Equipment Supplier Audit Standards• US#15 SU Sensor accuracy and reproducibility • US#16 Class III biological safety cabinets or isolators• US#3 Interchangeability of disposables• US#7 Standardize connectors of disposables • US#6 Best practices to manage multi-production lines in a single facility• US#8 End to end tracking for autologous cell therapy work flow• JP#005 Traceability of bio-processed materials, starting from production until disposal.• JP#006 Monitoring of cell culture process• UK#003 Use of surrogate samples• JP#007 Requirements of apparatus where multiple types of cells is processed• JP#008 Requirements for automated cell culturing• JP#009 Assessment of cell culturing capability• Canada#001 Standards for manufacture of Microbial-based Products (MBP) such as cleaners, or consortiums for bioremediation of contaminated

sites• Korea#1 Quality assurance of Bioprocessing technology transfer from R&D at laboratory to production at plant for pharmaceutical products.• UK#002 Requirements for environmental control and monitoring• JP#010 Environmental impact of materials and apparatus used for bioprocessing• US#4 Specifications for extractable, leachable• US#13 Virus Testing and clearance for MaB

There are many standardization needs in bio-processing

How Bio-processing standards are different from regulations (e.g. GMP)

• One Cell Therapy product is made of plural Materials and Processes.• One Material and/or one Process is used for plural Cell Therapy products.• In contrast, GMP assure one Cell Therapy Product and its Materials.

Plural Materials Plural Processes

Materials and Processes for plural use

Cell Therapy Product A

Cell Therapy Product B


• It is not rational to start from zero– to investigate all of its raw materials and processes for one Cell

Therapy Products (by Cell Therapy product manufacturers)– to investigate its raw material and process against various

requirements from users making different Cell Therapy products (by Raw Material Suppliers)

• Now is the time to start international standardization,– Bio-pharma industry is making standards for Single-Use

Systems such as standards on extractables and leachables.– Cell therapy bio-process is likely to be more complicated.– Bio-process is in progress and still accumulating experiences.

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General Structure – Two distinct worlds with its common language (standards)

Manufacturer Regulator

Raw data/record with traceability

Tox

StudiesCMC

Ps

Clinical

Trial

#1

Clinical

Trial

#2

ADME

Studies

GXPs (GMP, GCP, GCTP, etc.)

Regulator

Applicant

FINAL product

Materials/processes/services

specific to individual product

IS #1 IS #2 TS #1 TS #2PAS

General requirements

User/manufacturer

Product IN GENERAL

Interest towards ONE FINAL productInterest towards PLURAL products

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General Structure – Two distinct worlds with its common language (standards)



Tox

StudiesCMC

Ps

Clinical

Trial

#1

Clinical

Trial

#2

ADME

Studies


Regulator

Applicant

FINAL product





User/manufacturer

Product IN GENERAL

Interest towards ONE FINAL productInterest towards PLURAL products

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Common language (standards) among users/manufacturers and suppliers/providers

Common language (standards) among regulators and applicants

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#1: ONE FINAL product as seen from manufacturer



Tox

StudiesCMC

Ps

Clinical

Trial

#1

Clinical

Trial

#2

ADME

Studies


Regulator

Applicant

FINAL product

PLURAL Materials and Processesleads to ONE FINAL Product.

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#2: PLURAL productｓ as seen from manufacturer

Manufacturer’s world Regulator’s world





User/manufacturer

Product IN GENERAL

Ps

Ps

Ps

Ps

ONE Material and Process may lead to PLURAL Products

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Cell Therapy Product BP

s

Ps




Cell Therapy Product BP

s

Ps


Individual materials/processes/services



User/manufacturer

Product in general

Raw data/record/with treceability

Tox CMCP

sClinical

Trial

#1

Clinical

Trial

#2

ADME


Regulator

Applicant

FINAL product

Compliance to the Rules (standards) are investigated for PLURAL PRODUCTS Compliance to the Rules (regulation) are

investigated for ONE FINAL PRODUCT

ISO/TC 276/WG 4 Direction

• Standards in bio-processing are needed in the industry– As a “common language” among the users

and suppliers in the industry.• Do not aim to make a standard at this moment

– As the standards endorsed by regulators.– When the standards are useful, they may be

recognized by regulators.

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Content


• How Bio-processing standards are different from regulatory (GMP)


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Don

or

Pat

ient

Substance

Apparatus

Operation Operation

Substance

Substance

Operation

Substance

Operation

Apparatus

Apparatus

ApparatusApparatus Apparatus

OperationOperation

#1component material control

Medium, additives

Cells, tissues

Substance

Operation

Apparatus


#4 handling, transportation & storage

#2 bioreactor processes

#3 collection, separation, purification and formulation


#x pre-processes

Technology spaces of bio-processing covered by WG4.Material from Berlin WG 4 Meeting (2014-12)

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Needs/gaps survey and PWI and proposals concentrates in certain areas

Group #1 Group #2 Group #3 Group #4 Group #5

Ishikawa Method “5M”

component material controlCells, tissues

component material controlMedium, additives

bioreactor processes

collection, separation, purification and formulation

handling, transportation & storage

Material Korea#02 PWI#2,PWI#3JP#03、US#02、US#05、US#12

NA NA NA

Method NA PWI#1 PWI proposal(Korea)US#06, JP#06, UK#03, JP#08, JP#09, Canada#01, Korea#01, UK#02, US#13

JP#01

Machine NA PWI prposal(US)JP#04, US#09, #11, #14, #15,#04, US#16, US#03, #07, JP#07

JP#02

Man

Measure WG3 WG3 WG3 WG3 WG3

Don

or

Pat

ient

Substance

Apparatus

Operation Operation

Substance

Substance

Operation

Substance

Operation

Apparatus

Apparatus

ApparatusApparatus Apparatus

Operation Operation


Medium, additives

Cells, tissues

Substance

Operation

Apparatus

#1 component material control


#2bioreactor processes

#3 collection, separation, purification and formulation #4 handling,

transportation & storage

#x pre-processes

Cause Effect

Problem

Ishikawa (fishbone) Diagram

The 5 Ms (used in manufacturing industry)

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Needs/gaps survey and PWI and proposals concentrates in certain areas

Group #1 Group #2 Group #3 Group #4 Group #5

Ishikawa Method “5M”

component material controlCells, tissues

component material controlMedium, additives

bioreactor processes

collection, separation, purification and formulation

handling, transportation & storage

Material Korea#02 PWI#2,PWI#3JP#03、US#02、US#05、US#12

NA NA NA

Method NA PWI#1 PWI proposal(Korea)US#06, JP#06, UK#03, JP#08, JP#09, Canada#01, Korea#01, UK#02, US#13

JP#01

Machine NA PWI prposal(US)JP#04, US#09, #11, #14, #15,#04, US#16, US#03, #07, JP#07

JP#02

Man

Measure WG3 WG3 WG3 WG3 WG3

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Summary• ISO/TC276 Biotechnology focus on “process”.

ISO/TC 276/WG 4 Bioprocessing focus on consistency.

• ISO/TC 276/WG 4 will work on “common language” among the manufacturers

• ISO/TC 276/WG 4 will start from Raw materials, method/apparatus of bioreactor processes.

Thank you

iso tc276 wg4 strategies and plans for developing bioprocessing

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