ASTM E2500

A New Approach to Validation

Peter K. Watler, Ph.D.,

Principal Consultant and CTO,
Hyde Engineering + Consulting, Inc.

Where you can find it

Only 5 pages
http://www.astm.org/Standards/E2500.htm
$36.00
-Page 1-

ASTM E 2500 07, What is it?

A risk-based and science-based approach to the specification,
design, and verification of manufacturing systems and equipment that
have the potential to affect product quality and patient safety.
The overall objective is to provide manufacturing capability to support
defined and controlled processes that can consistently produce
product meeting defined quality requirements.

Approved June 1, 2007

A voluntary consensus standard
It has legal relevance

Stresses expert analysis of critical element that affect product quality

quality, (not Quality Assurance or Quality Unit) appears 44 times

expert appears 21 times
critical appears 20 times

-Page 2-

The National Technology Transfer Act of 1995

Public Law 104-113
The Congress finds the following:
(1) Bringing technology and industrial innovation to themarketplace
is central to the economic, environmental, and social well-being of
the people of the United States.
(2) The Federal Government can help United States business
to speed the development of new products and processes

Provision (12(d)) - Utilization of Consensus Technical

Standards by Federal Agencies;

all Federal agencies and departments shall use technical

standards that are developed or adopted by voluntary consensus
standards bodies, using such technical standards as a means to
carry out policy objectives or activities deemed by the agencies and
departments.

-Page 3-

What the Law Looks Like

http://www.nist.gov/director/ocla/Public_Laws/PL104-113.pdf

-Page 4-

What ASTM E 2500 Applies To

Pharmaceutical and biopharmaceutical

manufacturing systems:

Facility equipment
Process equipment
Supporting utilities
Process monitoring systems
Process control systems
Automation

Systems that have the potential to affect

product quality
patient safety
-Page 5-

ASTM E 2500-07 Highlights

The ASTM standard focuses on

Specification
Design
Verification
Lifecycle

Alternative to ISPE Baseline Guide Vol 5 Commissioning &

Qualification

complexity, cost, time

Replaces Design Qualification with a Design Review by Subject Matter

Experts

Risk Assessments by Subject Matter Experts (SMEs)

Eliminate Impact Assessment

Replaces sequential Commissioning and Qualification with Verification

Fit for intended use - Not bound by the formal IQ, OQ PQ phases

Lifecycle Change

Continuous process improvements and real-time monitoring (PAT)

-Page 6-

Why is it needed now?

It is estimated that validation

can add up to 25% of the
total installation cost for new
facilities.

I know Nothing!

M Guyader, LBP

E 2500 puts focus on

Critical areas that affect

Product Quality
Patient Safety
Lets Validate
Everything!
-Page 7-

Whats Driving us to Consider new Validation

Approaches

Pharmaceutical manufacturing operations are

inefficient and costly.

s
e
t
s
a
W
y
r
t
Pharmaceutical manufacturing
will
need to ient
s
u
c
d
i
f
n
f
I
employ innovation,
cutting
edge
scientific
&
e
l
n
a
I
c
i
o
If
FDA
could
change
the
way
it
t
t
u
e
e
engineering
knowledge.
u
c
a
D
r
m
r
a
a

e
regulated
h
g
Y
n
P
i
a

r
n
u
Source:
PAT
Team
&
Manufacturing
Science
Working Group Report, 2004
t
o
i
c
l
l
a
i
f
B
u
n
0
$5
Ma
the industry
could save
o
orget
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esea
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tical
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arma

rsity,
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2006
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o
Oct

"if we change the way both manufacturers and

10regulators
to P50%
of thethecost
of could
goods
h
operate,
industry
savesold.
an
Pharmaceutical Manufacturing Research Project Benchmarking Study, Georgetown University, October 2006
average of 15 per cent of manufacturing costs".

-Page 8-

They Have!

FDA 2004: Pharmaceutical cGMPs for the 21st Century A Risk

Based Approach
Encourage implementation of risk-based approaches

FDA 2004: PAT A Framework for Innovative Pharmaceutical

Development, Manufacturing, and Quality Assurance
encourage the voluntary development and implementation of
Process Analytical Technology

FDA 2006: A Regulatory Paradigm to Encourage Innovation. Keith

Webber, CDER/OPS, FDA

FDA 2006: Guidance for Industry Q9 Quality Risk Management

FDA 2007: Pharmaceutical Quality for the 21st Century A RiskBased Approach Progress Report

FDA 2009: Guidance for Industry Q8(R1) Pharmaceutical

Development

science- and risk-based submissions QbD

-Page 9-

Focus on Criticality, Ongoing Verification

3
-Page 10-

Why Now?

Industry and Regulatory Agencies are striving to

be more efficient, reduce costs and improve
quality and safety
Decades of pharma & bio manufacturing
experience
More knowledge of systems
Solid understanding of operations
Less anything can happen philosophy
-Page 11-

Implementing ASTM E 2500

Some will wrongly interpret this as simply shifting validation
responsibilities:

This new approach will significantly shift the current qualification

responsibilities and activities associated with facility qualification,
equipment qualification, and utility qualification to the companys
corporate engineering group

Some will wrongly interpret this as simply changing the

terminology:

Out goes the Design Qualification (DQ) with a Design Review (DR).
Also for those that do them, Impact Assessments are out. Commissioning and
Qualification are replaced by Verification,
the qualification phases (IQ, OQ, PQ) are obsolete.

ASTM E 2500 is a new Concept, requiring new Approaches

Its more than simply re-naming documents

Its more than a re-org of shifting responsibilities from one group

-Page 12-

Implementing ASTM E 2500

To implement the concepts of E 2500

Approach has to change

Expertise (of the people involved) has to change
Tools have to change

Otherwise there will be no real change

-Page 13-

Is ASTM E 2500 About This?

OLD

NEW?
-Page 14-

GAMP Validation V Model

-Page 15-

ASTM E 2500 Is:

A standard approach for validating equipment,

facilities, processes

Streamlined process
Risk based reduce costs
QbD develop then employ best practices
More consistent qualification
Supports current regulatory guidance (FDA, ICH)
Knowledge (expert) based
Risk based

-Page 16-

ASTM E 2500 Process Map

-Page 17-

E2500 System Lifecycle and Validation Approach

Planning
& Documentation

Identify
Subject Matter
Experts

User
Requirements
Specification

Risk
Assessment

Functional
Specifications
and Design

Verification Plan
Traceability
Matrix
Factory
Acceptance
Tests
Vendor
Documentation

Site
Acceptance
Tests

Installation/
Operational
Qualification
Tests

Performance
Qualification
Tests

Verification Summary Report

ETOP

GMP Operation and

Change Management
-Page 18-

The New Standard is About Fundamental Change!

To more efficiently and better, design and implement
manufacturing systems
ASTM E 2500 embraces, leverages and brings together the
cutting edge concepts of:

RiskBased Approach
Science Based Approach
Quality by Design (QbD)
Process Analytical
Technologies (PAT)
Design Space
Critical Parameters
Critical Quality Attributes (CQA)

Knowledge & Understanding

Subject Matter Experts (SMEs)
Good Engineering Practice,
(GEP)
Lifecycle concepts
Change implementation
Continuous process
improvement
Vendor documentation
-Page 19-

E 2500 Key Concepts for Design &

Implementation of Manufacturing Systems

Methodologies
1. Requirements
2. Specification & Design
3. Verification

Toolbox
1. Design Review
2. Subject Matter Experts
3. Risk Management
Process
4. Change Management
Plan

-Page 20-

Benefits of Implementing E 2500

LEANer manufacturing systems

Remove waste

Elevate our industry to more knowledge, better

understanding of our manufacturing systems

Data, PAT, Design Space

Focus on whats important (Critical)

More is not better

Better technical understanding (Subject Matter Experts)

Less waste & repetition

Use vendor docs

-Page 21-

Implementing ASTM E 2500

1. Planning and Documentation:

VMP
Verification Team and Responsibilities
Document Matrix (planning, design & verification)
Eligible vendor documentation

Document Matrix

prepared by:

Phase 1 Planning and Definition

HYDE
Task
002

Title

Doc. #

FMECA RISK
ASSESSMENT SOP
COMMISSIONING PLAN

TEC-005

VERIFICATION PLAN
PROTOCOL TEMPLATE
HVAC SYSTEM- AIR
HANDLERS

APPROVED
04AUG09
URS-50058- APPROVED
66
29SEP09

COM-001

002
002

Status

Doc. #

Status

Date: 20-Oct-09

Phase 2 Design & Development

Doc. #

Status

Doc. #

Status

FAT

SAT

Validation
IOQ

PQ

Enhanced
Comm

IOQ

PQ

Summary
Reports

APPROVED
19MAY09
APPROVED
24JUL09

RSK-50058- DRAFT
66

003
AUTOCLAVE (2 DOOR)

URS-50043

BAS- BUILDING
AUTOMATION SYSTEM

URS-50054

CHILLER SYSTEM

URS-50050

APPROVED
02JUL09

CLEAN DRY AIR SYSTEM URS-50049

APPROVED
25JUN09

COOLING TOWER
SYSTEM

URS-50056

APPROVED
09JUL09

URS-50053

APPROVED
03AUG09

004
005

APPROVED
13MAY09
APPROVED
08AUG09

RSK-50043
RSK-50054

APPROVED
25JUN09
DRAFT

006
007

RSK-50049

APPROVED
18SEP09

RSK-50053

APPROVED
03AUG09

008
009

ELECTRICAL/ LIGHTING
SYSTEM
EMERGENCY
GENERATORS

010

-Page 22-

Implementing ASTM E 2500

2. Identify Subject Matter Experts:

(6.7) SMEs have primary responsibility for specification, design and
verification of the manufacturing systems
individuals with specific expertise and responsibility in a particular
area or field (for example, quality unit, engineering, automation,
development, operations.
CFR21 211.34 Consultants advising on the manufacture,
processing, packing, or holding of drug products shall have sufficient
education, training, and experience, or any combination thereof, to
advise on the subject for which they are retained.
Who are they?
Where do you find them?

-Page 23-

SME Qualifications
Experience
>10 y experience
Designed & implemented systems or practices
Process/System Expertise
Knowledge of GMP, compliance, design elements, risk factors
Applies engineering equations, principles to the design, sizing & scaling
of systems.
In-depth knowledge of the subject
Methodology Expertise
Proficient in standard methodologies for design and implementation,
such as ICH Quality Guidelines (Q8, Q9, Q10), FDA Guidance, CFRs,
ASME Standards (BPE, E 2500), ISPE Guides (GAMP, Baseline)
Completed formal training courses
Recognized Competence
Recognized by peers and professional associations, published, teaches
topic
Professional credentials, license
-Page 24-

Implementing ASTM E 2500

3. Requirements Specification:

SME

Identify specific requirements

Basis for specification, design,
and verification of the system (7.2)
SMEs

product and process knowledge

and understanding
based on scientific data (QbD,
Design Space).

This knowledge is the basis of scientific understanding for the system

FDA 2009: Guidance for Industry Q8(R1) Pharmaceutical Development

What is critical

-Page 25-

Implementing ASTM E 2500

4. Risk Management Process

FDA 2006: Guidance for Industry [ICH] Q9
Quality Risk Management

Perform risk assessments at appropriate stages to

evaluate the risks to product quality and patient safety

Performed by an appropriate SME

Identify controls and verification techniques to
manage risk to an acceptable level

-Page 26-

Implementing ASTM E 2500

5. Specification and Design :

Leverage qualified equipment vendor expertise (SME)
to identify & document elements which affect critical quality
attributes
Communicate the factors that impact product quality to the
system (e.g. equipment) designer.
Strive to mitigate product quality & patient safety risks
through the design
Functional Specifications provide acceptance criteria for
functional tests specified in the Verification Plan.

-Page 27-

Potential Design Requirements

Requirements Definition:
Temperature
Shear
Flow rate
Membrane Area

-Page 28-

Implementing ASTM E 2500

6. Verification Plan (5.1, 7.4)
Verify the critical aspects of the manufacturing system

Design
Properly installed
Operating correctly
Meets performance requirements
Fit for intended use

Identifies all required testing & documentation

Extent of verification and documentation should be based on risk to

product quality and patient safety
Criticality, risk factors identified in the URS, FMECA Risk Analysis, and
detailed design
Testing occurs from FAT to PQ

Acceptance criteria:

Developed and approved by subject matter experts

Critical aspects approved by the quality unit

A Traceability Matrix summarizes required testing and when it occurs

-Page 29-

Verification Plan Traceability Matrix

Identifies required test

functions
Identifies when testing
will be executed
FAT, SAT, IQ, OQ, PQ

-Page 30-

Implementing ASTM E 2500

7. Verification Plan Execution:
Subject matter experts perform or oversee activities, and
document results (7.4.3.1)
Vendor verification documentation may be used (7.4.3.2)
Leverage FAT/SAT testing rather than repeating vendor
activities and replicating vendor documentation (6.8.2)
Testing occurs across FAT, SAT, IQ, OQ, PQ

The more critical testing or additional testing may occur during IQ/OQ
to mitigate risk

-Page 31-

The Role of System Vendors

The key to a competitive parts supply system is the way the
assembler works with its suppliers Womack, The Story of Lean Production

-Page 32-

Implementing ASTM E 2500

8. Verification Summary Report
Approved FAT, SAT, ETOP, IOQ and PQ Reports collectively provide
documented verification that the manufacturing system is fit for
intended use (E 2500 7.5.1)
Summary Report provides an overview of test results and nonconformances with acceptance criteria (7.5.2)
Completed verification documentation reviewed by qualified and
independent subject matter expert(s) (7.4.4.1)
SME reviews overview of results and any nonconformance with
critical acceptance criteria
Systems with critical aspects should be approved by the quality unit.
SME confirms manufacturing system is fit for intended us (7.5.3)
Approved by SME and Quality Assurance (7.5.4).
-Page 33-

Implementing ASTM E 2500

9. GMP Operation Acceptance, Release & Change
Management:
After Verification Summary Report approval,
Quality Assurance issues authorization to release the system for GMP
operational use (7.5.5).
As part of the system life-cycle, equipment, and procedures are
periodically reviewed.

Modifications are controlled via Change Management throughout the

system lifecycle (E 2500 8.4.3).
Changes are approved by system subject matter experts.
Changes to critical aspects or to aspects that affect system requirements
relative to product quality and patient safety are additionally approved by
Quality Assurance (8.4.2, 8.4.3)

-Page 34-

The Role of QA in ASTM E 2500

7.4.1.3 Acceptance criteria of critical aspects (that is, critical to product
quality and patient safety) should be approved by the quality unit.
7.4.2.3 The verification plan should be developed and approved by
t
h
g
i
subject matter experts. Verification plans for systems containing
rs critical
e
v
aspects should be approved by the quality unit.
O
l
a
n
7.5.4 Such documentation should be prepared and
by
oapproved
i
t
i
dd systems with critical
subject matter experts. Such documentationAfor
h
aspects should be approved by the quality
wit unit.

is
R
te

8.4.2 Before acceptance,ig

change
management should be applied. This
a
t
i
process should be managed
by, and changes approved by, subject
M
matter experts. Changes affecting critical aspects of manufacturing
systems should be communicated to the quality unit.
8.4.3 After acceptance, prior to manufacturing for commercial use,
operational change management should be applied. Under operational
change management, all changes related to specific requirements
relative to product quality and patient safety require prior approval by
the quality unit, unless predefined arrangements are established
covering
-Page 35-

What Else is Needed?

Risk Management Process

ICH Q9
Perform risk assessments at appropriate stages to
evaluate the risks to product quality and patient safety

Performed by an appropriate SME

Identify controls and verification techniques to
manage risk to an acceptable level

-Page 36-

Risk Management Program

ICH Published 09 Nov 2005

FDA Published Federal
Register, June 2, 2006

Although there are some examples of the use of quality

risk management in the pharmaceutical industry today,
they are limited and do not represent the full contributions
that risk management has to offer.

Risk Based Quality Systems

Risk Based Validation
Risk Based Process Monitoring
Risk Based Documentation
-Page 37-

ICH Q9 Describes Several Risk Assessment Tools

Basic Risk Management Facilitation Methods
(Flowcharts, Check Sheets Etc.)
Failure Mode Effects Analysis (FMEA)
Failure Mode, Effects and Criticality Analysis (FMECA)
Fault Tree Analysis (FTA)
Hazard Analysis And Critical Control Points (HACCP)
Hazard Operability Analysis (HAZOP)
Preliminary Hazard Analysis (PHA)
Risk Ranking and Filtering
Supporting Statistical Tools

-Page 38-

Risk Management - FMEA Method

Severity

addresses the impact on a process in the event a parameter is

out of range.

Occurrence

assesses the likelihood a parameter will be out of range.

Detection

addresses the ability of detecting a defect if a parameter is out

of range.

Risk Priority Number

RPN = Severity x Occurrence x Detection

-Page 39-

FMEA Risk Assessment - Identifying Criticality

Assemble multidisciplinary team

Manufacturing, Process Development, Manufacturing Sciences,

Engineering and Quality Assurance

Prepare FMEA Data Sheet

All operating inputs and proposed operating ranges
What are the potential failure modes (process, equipment,
operators)
Typical sources of failure in systems
What are causes of these failures

Scoring based upon

Knowledge, known equipment capability, maintenance
Previous experience and expertise

-Page 40-

Risk Assessment SOP

-Page 41-

FMEA Worksheet
Severity x Occurrence x Detection = RPN
Failure Modes and Effects Analysis
Process

Healgen

Unit Operation

TFF

Leader

John Smith

Participants

Robert S, Bill E, Fred J, Mary S, Jill R

Operational Parameter

Current Range

Failure Mode

Cause(s)

Preparation
Verify TFF-08207 is within cleaning
expiration date

30 days

Out of date

Operator error / Process delay

Incorrect dip tube orientation

Operator error / Incorrect

alignment of alignment pin

Install dip tubes

Perform pre-use visual inspection

Clean

Set-up TFF for processing per MO173

Not cleaned

Faulty cleaning cycle

System set-up incorrectly

Operator error / Incorrect SOP

revision

Incorrect system hose

connections
Incorrect connection / utilities
failure
Incorrect connection / utilities
failure
Incorrect connection / utilities
failure

System hose connections

Connect chilled water supply
Conncect AWFI
Conncect CDA
Drain the system per MO173

System not drained

Verify Hydraulic Pressure Unit is in the run

setting
Open and download file "Automated TFF
Method VER01"

Incorrect pressure on
membranes

Buffer Manifold Flush

System AWFI flush

> 1150 psig

Wrong file downloaded

Flush valves for > 2
min

Valves not flushed for

sufficient tim
System not adequately
flushed with AWFI

Potential Effect(s)

Severity

Occurrence

Detection

RPN

Expired equipment used in

process
Foaming / Over concentration /
Yield loss
Dirty equipment used in
process
Production delay / Product loss

Inadequate flushing of system /

Operator error
Product loss
Temperature spike / Product
Utilities failure / Operator error
loss
Inadequate flushing of system /
Utilities failure / Operator error
Product loss
System will not operate / valves
Utilities failure / Operator error
will not toggle
System not flushed of storage
Operator error / Equipment failure
solution
Wrong setting selected / Faulty
Membranes not sealed /
Hydraulic Pressure Unit
Product loss
Operator error

Product Loss

Incorrect flow rate / Valve failure

System not flushed of storage

solution

Incorrect system connections /

Insufficient volume / Incorrect flow
path

System not flushed of storage

solution / Product loss

-Page 42-

FMEA Worksheet
Severity x Occurrence x Detection = RPN

System/Process
Failure Mode, Effects and Criticality Analysis
(FMECA)
Compiled by:

Team:

Reference Drawings

System Owner:

Primary SME:

URS

Original Date:

System or Process Name:

Revision Date:
Revised Conditions

Existing Conditions
Component Description
& Function

Potential Failure Mode

Potential Failure Effects

Potential Failure Causes

Compensating Provisions

S
E
V

O
C
C

D
E
T

R
P
N

Recommended
Actions

Resp.

Actions Taken

S
E
V

O
C
C

D
E
T

R
P
N

-Page 43-

FMECA Worksheet
Component Description
& Function
3

WFI Distribution System

Potential Failure Mode

WFI distribution pipe

Contamination

Potential Failure Effects

WFI water quality out of spec

Potential Failure Causes

Compensating Provisions

S
E
V

O
C
C

D
E
T

R
P
N

200

Check design, commissioning,

Dead leg, Non-turbulent flow,
wrong surface finishing and/or validation, PM & EM program
incompatible material (MOC) for
WFI piping

Res
Recommended Actions

Commissioning & Qualification Testing (RPN=200

Undesirable)
1. Verify no dead leg L/D >2.0
2. Verify surface finish
3. Verify MOC (elastomers, SS grade)
4. Verify Reynolds number (circulation
flowrate)
5. Verify Design Review

p
.

Actions
Taken

O
E
V

D
C
C

R
E
T

P
N

Particle Test
Program
-Yearly
by
Intarcia?

-Page 44-

Criticality Ranking

100
80
70
High Risk
60
50
42
36
Risk Score
30
24 Moderate Risk
16
12
9
Low Risk
6
1
Number of
RISK CRITICALITY
RPN's in Range
Intolerable
343-1000
37
Undesirable 189-336
26
Tolerable
72-180
23
Negligible
1-70
34

1
Certain
100
80
70
60
50
42
36
30
24
16
12
9
6
1

2
Very High
200
160
140
120
100
84
72
60
48
32
24
18
12
2

Detection Rank
4
6
Moderate
Low
400
600
320
480
280
420
240
360
200
300
168
252
144
216
120
180
96
144
64
96
48
72
36
54
24
36
4
6

8
Remote
800
640
560
480
400
336
288
240
192
128
96
72
48
8

10
Uncertain
1000
800
700
600
500
420
360
300
240
160
120
90
60
10

ACTION
Design modification required to mitigate risk
Qualification testing or design modification required to mitigate risk
Qualification testing may be required to mitigate risk
Commission
-Page 45-

Manufacturing FMEA
RPNs can range from 1 to 1,000

RPN 100 indication may be a high risk item

Manufacturing:
Nine unit operations analyzed
FMEA evaluated 445 operational inputs
RPNs ranged from 3 to 158

Only 6 operational inputs received RPN scores 100

Indicates robustness, procedural controls and equipment
capabilities have minimized the risk of failure
Fewer parameters to validate
More Targeted Validation
Better understanding, better quality, lower cost

-Page 46-

FMEA Results
Unit Operation

Parameter

RPN

Production Fermentation

Raw Material Addition

111

Production Fermentation

Sampling for Culture Purity Analysis

102

SEC

Elution Buffer (BT018) pH

158

SEC

Elution Buffer (BT018) Conductivity

155

SEC

Load Volume

144

SEC

Remove Bioburden, LAL Samples

113

Validate only CRITICAL & KEY Parameters

From FMEA
From Severity
From Knowledgebase

-Page 47-

FMECA Risk Analysis Report

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-Page 48-

E 2500 Implementation Gaps

ASTM E 2500 lays out a standard roadmap for the overall
approach
It is not a how to guide,

Firms should develop appropriate mechanisms to communicate

requirement inputs, including product quality considerations, to
those responsible for design

Firms will need to develop

Processes
Tools & templates suited to their operations

Not one size fits all needs to address corporate risk,

nature of business, expertise of staff, organization
resources

-Page 49-

What Else is Needed?

Design Review Process

Planned and systematic reviews throughout the system lifecycle:

Specifications
Design
Design development
Continuous improvement changes

Ensure product and process requirements are satisfied by

the design
Unacceptable risks are mitigated by design or other means
Design is performed by appropriate SMEs
-Page 50-

What Else is Needed?

Change Management Process
Develop a change management plan before releasing the system
Change is good, is expected
Managed by, changes approved by SMEs
Changes affecting critical aspects communicated to the quality unit

Changes related to product quality and patient safety

require prior approval by the quality unit, unless predefined
plan
PAT provides scientific data to support changes and
manage risk

-Page 51-

ASTM E 2500 The Role of Vendors

The key to a competitive parts supply system is the way
the assembler works with its suppliers

(Womack et al., 1990)

Partner with a supplier (LEAN)

vs
Bid them against each other (MASS)
Preferred Suppliers

Few in number, single sourced?

Share information needs, specifications
Supplier becomes the solution provider

Encourages use good vendor documentation and testing

to support qualification
-Page 52-

Implementation Gaps
Gaps

How do you do a risk assessment eg. FMEA SOP?

How often, at what points in the process?
How do you qualify to be an SME?
How many QA staff will be needed? What expertise will they need?
Where will you find them?
How do you manage changes during design & implementation?
How do you manage change to enable improvements to be
implemented?
How do you efficiently address deviations from the Verification
Plan?
How do you determine the Critical aspects of the manufacturing
system
How to define & document the verification approach
-Page 53-

E 2500 Implementation Gaps

ASTM E 2500 lays out a standard roadmap for the overall
approach
It is not a how to guide,

Firms should develop appropriate mechanisms to communicate

requirement inputs, including product quality considerations, to
those responsible for design

Firms will need to develop

Processes
Tools & templates suited to their operations

Not one size fits all needs to address corporate risk,

nature of business, expertise of staff, organization
resources

-Page 54-

E 2500 Efficiency & Cost Savings

The extent of verification and the level of detail of

documentation should be based on risk, including
those associated with product quality and patient
safety, and the complexity.
Only companies that achieve a high level of
process understanding will have the opportunity
to justify a more flexible regulatory path.

FDA 2004

-Page 55-

Yes, ASTM E 2500 is Being Implemented

Hyde Client, Commercial Device Facility

E2500 Based facility and systems commissioning and qualification

Amgen, Thousand Oaks Clinical Mfg

50-70% reduction in IQ/OQ for chromatography skid

Phil Bowles, ISPE Tampa 2009

Bristol-Myers Squibb Biologics

Applying ASTM E2500 to a Greenfield Site

E Bramhall, Director Validation, ISPE 2008 Annual Meeting

Perkin Elmer

Best Practices for Qualification of Laboratory Equipment

Utilizing ASTM E2500

Major East Bay Pharmaceutical Company

Risk based commissioning & qualification

Major Bay Area Biotech Company

Risk based validation for new facility commissioning

-Page 56-

FDA Guidance

Guidance for Industry Process Validation:

General Principles and Practices - FDA Nov 18
2008 Guidance
In keeping with the spirit of ASTM E 2500
Standard, the document uses the term verify
rather than validate when referring to facility
systems.
IQ, OQ, DQ, PQ are industry terms and standards,
not FDA mandated.
-Page 57-

Summary

ASTM E 2500-07 provides a cutting edge

framework for planning and execution of riskbased
approach to designing and implementing reliable
manufacturing systems
ASTM E 2500 has many parallels to existing
approaches, but relies on more risk management
and higher expertise
The challenge is to address the implementation
gaps and develop the custom tools
-Page 58-

Contact Info

Peter K Watler, PhD

Principal Consultant and
Chief Technology Officer
Hyde Engineering + Consulting, Inc.
peter.watler@hyde-ec.com
415-235-1911

-Page 59-