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BnAn@nnepharmaplan.com
Direct telephone: +4530751381
Agendaen
Fra indbydelsen:
• På mødet vil Brian Andreasen fra NNE Pharmaplan
fortælle om hans erfaringer med at implementere
standarden hos Pfizer globalt.
Slide 2
NNE Pharmaplan, my workplace
• Over 80 years of experience in the pharma and biotech industries
Slide 3
Global reach - local knowledge
Slide 4
Where is the best Quality?
u e
Faster project execution
tr
Focus on patient safety
l y
ab
Significantly reduces documentation
Enhanced process understanding
o b
Saves time and resources
pr
Higher production yield (OEE)
Improved quality at less costs - better use of expertise
n d
Compliance with Health Authorities expectations
a
to risk based approach
…
Thus, improved quality, major cost reduction (above 40%), faster to market and
longer time to take the right decisions for investments.
Slide 6
The Pfizer case
Slide 7
ASTM!!!!
What is that….?
• Large voluntary standards development
organization
• Not-for-profit organization
• Established in 1898
• HQ in Philadelphia,
• Sub-offices in London, Mexico City &
Beijing
Slide 8
ASTM Committee E55
Slide 9
Issued Standards (Pharma) :
• E2363-06a Standard Terminology Relating to Process Analytical
Technology in the Pharmaceutical Industry
Slide 10
Work Items in Progress (E55.01)
• WK5930 Standard Practice for Risk Assessment and Risk Control as it Impacts the
Design, Development, and Operation of PAT Processes for Pharmaceutical
Manufacture (Gawayne Mahboubian Jones)
• WK9191 Standard Guide for Multivariate Data Analysis Related to Process Analytical
Technology (Chun Cai)
• WK15778 Guide for Science-based and Risk-based Cleaning Process Development and
Validation (Andrew Walsh)
Slide 12
Important Terms
Critical Quality Attributes (CQA)
A Critical Quality Attribute is defined as a
physical, chemical, biological, or
microbiological property or characteristic that
should be within an appropriate limit, range or
distribution to ensure the desired product
quality (ICH Q8)
Dissolution
Disintegration
Apperance
Hardness
Content Slide 13
uniformity
Important Terms
Critical Process Parameters
Pressure
Velocity
Pressure
Flow
pH
Dissolution Time
Disintegration
Apperance
Hardness
Content Slide 14
uniformity
Important Terms
Critical Aspects Critical Aspects are defined as
functions, features, abilities, and
performance or characteristics
necessary for the manufacturing
process and systems to ensure
consistent product quality and patient
Sanitary safety (ASTM E-2500-07)
design
Slide 16
The SME role & responsibilities
From E2500
Slide 17
Risk Based Approach
The old way
Indirect Impact
Slide 18
Risk Based Approach
The new way
Quality Risk Management – Risk 1 ..
…
Slide 19
Risk Based Approach
The new way
Quality Risk Management – Risk 1 ..
…
Slide 20
Quality Risk Management
Determination of Critical Aspects
Risk 1 ..
…
Critical Aspects must be identified during the risk
Management process.
Critical Aspects are derived directly from CQA and the
general GMP compliance issues.
Critical Aspects are subject to risk assessment and
risk mitigation; if possible and Verification testing.
Slide 21
Quality Risk Management
Identifying potential Risk
Customized
Manual
Equipment Slide 22
Quality Risk Management
Risk Mitigation – Safe design solutions & Control strategy
Sanitary issue:
Removal of pumps,
by using gravity
PAT PAT
Monitoring Monitoring
Risk 1 ..
Equipment …
Monitoring Manual
Monitoring
Slide
Slide 23
23
Quality Risk Management
Risk Mitigation - Vendor Assessment Risk 1 ..
…
Interfaces
to other disciplines
Custom made
or vendors ?
or bulk?
New Technology?
Documentation?
Experienced
employee? Slide 24
Quality Risk Management
Risk Mitigation -Design Review (DR)
The DR is an important part of the risk management
process, and DR must be focused on the risk
aspects:
Slide 25
Quality Risk Management
Use of Vendors test results etc
Slide 26
Quality Risk Management
Test- planning
Mapping
CQA & CPP
Critical Aspects
&
Risk Assessment
Risk
Mitigation
Planning
Verification
Slide 28
Quality Risk Management Process
Risk
Mitigation Design
CQA Critical Risk + Vendor SME
+ Verification
CPP aspects Ranking DER issues Involve-
New
ranking issues ment
Link to
illustration
Slide 29
Risk Mitigation
Slide 30
Quality activities commensurate with the
level of risk.
Slide 31
Pfizer ASTM E2500 Transformation
Pfizer Case
ASTM E2500 Transformation
• Transformation from C&Q to
Verification based on ASTM
E2500
• 2 project phases:
• Gap mapping & Scope
Setting
• Document writing, review
and approval
• Pilot implementation ongoing Pfizer Verification
Slide 33
Pfizer Case
ASTM E2500 Transformation - 2
• Combines E2500 with Quality by
Design principles and Lean
methods
• Integrates
• Engineering
• Automation
• Quality
• Maintenance etc.
Slide 34
Quality by Design in NNE Pharmaplan:
Transform C&Q to ASTM Verification
Client
• Pfizer Client Case 2008
• Global Engineering - for global use on all
manufacturing sites
Service
• Transformation of Pfizer C&Q program to
the ASTM E2500 standard for
Verification, for use globally
• Combined with a Pfizer Lean Program to
streamline current practices and get
more value of investments – both on
money and time
• 3 months delivery time Dissolution
Disintegration
• 5 consultants in NP Consulting Denmark Apperance
and USA plus global roll-out assistance Hardness
Content uniformity
Deliverables
• Full update of existing procedures to
ensure the harvesting of benefits of the Customer Quote:
Verification approach instead of the ”We selected NNE Pharmaplan for the work
traditional validation approach of
Commissioning and Qualification because these guys really understands
the QbD principles in practice.
What’s in it You guys really got it!”
• Faster and more cost-effective
verification compared to traditional ASTM E2500 Standard Guide
’validation’ for Specification, Design, and
Verification of Pharmaceutical
and Biopharmaceutical
Manufacturing Systems and
Equipment
Slide 35
C&Q vs Verification Opportunities
Verification Cost
Slide 36
1st Generation – and the next:
Face the Learning Curve
• Every new paradigm has its learning curve
• 1st Generation is not always right
• Example: From the Horse Cap to the 1st Generation Taxi
Slide 37
BnAn@nnepharmaplan.com
Direct telephone: +4530751381
Slide 38
Back up slides
Slide 39
A Brief Validation History
First FDA Validation Guideline
1987
• “Process validation is
establishing
documented
evidence which provides
a high degree of assurance
that a specific process will
consistently produce a
product meeting its pre-
determined
specifications and
quality
characteristics” GUIDELINE ON GENERAL PRINCIPLES OF
PROCESS VALIDATION
MAY, 1987 FDA CDER, CBER, CDRH
Slide 41
ISPE C&Q Baseline Guide 2001
QA Change Control
IQ & OQ
New Verification
Design
Risk Based Approach Development
ASTM E2500
Design Review Commissioning PT Process
Validation
Performance
Testing
Slide 44
Verification overview
From ISPE’s draft of coming new Verification guideline
Slide 45
Planning Verification
From E-2500:
Slide 46
Graphic model
NNE Pharmaplans model
Slide 47
NNE Pharmaplan is involved in the
new Pharma Standard Settings
• NNE Pharmaplan is closely involved in the
setting of the new standards of the
pharmaceutical industry
• ASTM Committee E55 on Manufacture of
Pharmaceutical Products
• ISPE
• PDA
• We have participated in setting the new
standards of the pharmaceutical industry
in ISA, GAMP, ISPE, PDA and ASTM for 20
years
Slide 48