Drug Labeling Packing Rules 1986

An Easy to Understand
Guide to Equipment
Qualiﬁcation
By Joginder Mittal
An Easy to Understand Guide
Risk Based Equipment
Qualification
Published by Premier Validation
An Easy to Understand Guide | Risk Based Equipment Qualification

Equipment Qualification
First Edition
© Copyright 2011 Premier Validation
All rights reserved. No part of the content or the design of this book maybe
reproduced or transmitted in any form or by any means without the express
written permission of Premier Validation.
The advice and guidelines in this book are based on the experience of the
authors, after more than a decade within the Life Science industry, and as
such is either a direct reflection of the “predicate rules” (the legislation
governing the industry) or are best practices used within the industry.
The author takes no responsibility for how this advice is implemented.
Visit Premier Validation on the web at www.premiervalidation.com or visit

our forum at www.askaboutvalidation.com.

So what’s this book all about?
Hey there,
If you're reading this, I'm going to assume you're here to learn about
how to perform risk based Equipment Qualification activities and how they
are applied within any compliance based environment.
Equipment Qualification activities are the foundations upon which

process validation is built and these activities play a critical role in delivering
operationally effective, safe and efficient facilities, utilities and equipment.
So it is important to ensure that a comprehensive and systematic approach is
undertaken during the qualification process.
What & How to qualify? This is still a big & confusing question for the
industry professionals!!
This Book explains how to find out the level of Equipment Qualification
required, fulfilling the regulatory requirements along with eliminating the
duplication & cumbersome documentation efforts.
So, if you want to learn about the systematic way of risk based
Equipment Qualification approach, this is the book for you. Don't worry this
isn't the usual boring scientific book or white paper that you've seen a
thousand times, our books are an easy read and get straight to the point.
Enjoy!

The brains behind the operation!
Program Director: Graham O'Keeffe
Content Author: Joginder Mittal
Technical Editor: Dr Shahid Ali, Graham O'Keeffe, Peter Thompson, Mo Acton.
Editor: Anne-Marie Smith
Printing History: Edition: Oct 2011
Cover and Graphic Design: Those Concepts
Notes of Rights
All rights reserved. No part of this book may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means, without the prior
written permission of the copyright holder, except in the case of brief quotations
embedded in critical articles or reviews.
Notes of Liability
The author and publisher have made every effort to ensure the accuracy of
the information herein. However, the information contained in this book is sold
without warranty, either express or implied. Neither the authors and Premier
Validation Ltd, nor its dealers or distributors will be held liable for any damages
to be caused either directly or indirectly by the instructions contained in this
book.
The Validation Specialists
Published by Premier Validation Ltd

Web: www.premiervalidation.com
Forum: www.askaboutvalidation.com
Email: query@premiervalidation.com
ISBN 978-1-908084-08-8
Print and bound in the United Kingdom

Table of Contents
The Starting Line 1
Why Should I Read This Book? 2
Learning Objectives 4
Terms Explained 5
Qualification versus Validation 6
What are the Benefits of Equipment Qualification? 7
Equipment Qualification Process 9

Qualification Planning 10
Risk Based Impact Assessment - Qualification
Need Assessment 13
Qualification Phases 23
User Requirement Specification (URS) 24
Risk Assessment 25
What is FAT/SAT? 44
Equipment Design Qualification (DQ) 45
Equipment Installation qualification (IQ) 48
Equipment Operational Qualification (OQ) 51
Equipment Performance Qualification (PQ) 55
Requalification 59
Change Control 61
REFERENCES 65

The Starting Line
Why Should I Read This Book?
Learning Objectives
Terms Explained
Qualification versus Validation
What are the Benefits of Equipment Qualification?
1
Why Should I Read
This Book?
This book describes how to perform the qualification assessment

depending upon the impact of individual equipment on product quality. The
risk based qualification assessment describes the qualification steps (RA,
DQ, IQ, OQ, PQ etc.) required to qualify the equipment.
This approach eliminates the duplication of effort and costly practices

such as:
· Repeating qualification steps;

· Equipment which do not require complex qualification approach;
· Generation of unsatisfactory and unnecessary documentation.
After gauging the impact-based requirement of qualification steps at

equipment or system level, this book describes the assessment of risk of
failure modes at component level of the equipment or system.
It also describes how to mitigate the associated risk with each failure
mode by taking necessary steps at different qualification steps (DQ, IQ, OQ
and PQ).
Following the instructions in this book will ensure that you will develop
2
and document your equipment qualification protocols/reports in a
consistent, understandable and traceable manner.
The rules and guidelines in this book are either a direct reflection of
the“predicate rules” (the legislation governing the industry) or are best
practices used within the industry.
Although written primarily with the pharmaceutical and biotechnology

industries in mind (two of the most highly regulated industries), these
guidelines and good practices can be deployed anywhere.
3
Learning Objectives
Upon the completion of this book you will be able to:
· Understand the basic difference between Validation &

Qualification Terms;
· Discuss the principles of Equipment Qualification;
· Understand regulatory Requirements and Expectations;
· Understand Equipment Qualification Requirements;
· Understand Impact Based Qualification Need Assessment
Approach;
· Understand Risk Based Equipment Qualification Approach;
· Understand Risk Management Approach;
· Understand Equipment Qualification Phases;
· Understand Equipment Qualification Documentation;
· Determine Equipment Qualification Acceptance Criteria;
· Develop Equipment Qualification Protocols;
· Create Equipment Qualification Reports;
· Understand the need to maintain a Validated Status.
4
Terms Explained
Validation
“Documented evidence that provides a high degree of assurance that a
specific process, equipment or system will consistently produce a product
meeting its predetermined specifications and quality attributes.”
Qualification
Action of proving and documenting that any premises, systems and
equipment are properly installed, and/or work correctly and lead to the
expected results.
Commissioning
A process that will ensure installed equipment or systems perform in
conformity with their intended design.
Equipment Qualification
Equipment Qualification is used as an umbrella term covering the steps
that ensure an instrument or equipment is appropriate for its intended use.
Qualification involves testing equipment to demonstrate that it does

what it is supposed to do.
5
Qualification versus
Validation
General saying
“We qualify a system and/or equipment and validate a process”
A system and/or equipment must be qualified to operate in a validated

process.
For Example
“You qualify an autoclave, whereas you validate a sterilization process”
· Validation and qualification are essential components of the same

concept.
· The term qualification is normally used for equipment, utilities and
systems, and validation for processes.
· In this sense, qualification is part of validation.
6
What are the Benefits of
Equipment Qualification?
There are three reasons why the pharmaceutical industry is concerned

about Equipment Qualification:
Safety Aspects
· Patient – Assurance of quality;
· Operator – Temporary or permanent injury, death;
· Environment- Environmental hazards, damage to people outside
the facility.
Business Aspects
· Increased throughput;
· Reduction in rejections and reworks;
· Reduction in utility costs;
· Avoidance of capital expenditures;
· Fewer complaints about process related failures;
· Reduced testing in process and finished goods.
7
Regulatory Compliance Aspects
The requirements for validation/qualification are now explicitly stated
in both the US and European regulations (US Code of Federal Regulations US
CFR Part 211,subpart L, 211.220 and 211.222 and within the EU 'Rules
Governing Medicinal Products in The European Community' VoI IV, Part
5.21, 5.22, 5.23, 5.24).
In CFR 211.220 it says:
'The manufacturer shall validate all drug product manufacturing

processes ... '
and:
' . . . validation protocols that identify the product and product

specifications and specify the procedure and acceptance criteria for the tests
to be conducted and the data to be collected during process validation shall
be developed and approved
and:
' . . . the manufacturer shall design or select equipment and processes to

ensure that product specifications are consistently achieved. The
manufacturer's determination of equipment suitability shall include testing
to verify that the equipment is operating satisfactorily
Similar requirements are stated in the EU Rules.
8
Equipment Qualification Process
· Validation Master Plan
Qualification
Planning
· Risk Based Impact Assessment
· Direct Impact
Qualification
· Indirect Impact
Need
· No Impact
Assessment
· User Requirement Specification (URS)
· Risk Assessment (RA)
· Design qualification (DQ)
Qualification · Commissioning (Factory Acceptance Test (FAT),

Site Acceptance Test (SAT))
Phases
· Installation qualification (IQ)
· Operational qualification (OQ)
· Performance qualification (PQ)
· Equipment Re-Qualification
· Change Control
GMP · Calibration
Procedures · Preventive Maintenance Program
and Program · Standard Operating Procedures (SOPs)
9
Qualification Planning
The first step of Equipment Qualification is to generate a Validation

Master Plan (VMP).
What is a Validation Master Plan

The VMP is the basic document for all validation activities. It assures
that the validation activities are performed in a structured and GMP-
compliant manner according to the current national/international
regulations.
A Validation Master Plan (VMP) is a comprehensive document

describing the applicable validation requirements for the
Facility/System/Equipment, and thus providing a plan for meeting those
requirements.
The Validation Master Plan defines

· The Validation Concept / the Corporate Validation
Policy/Philosophy;
· The Project for which it is established;
· The Structure of the Validation Project Team;
10
· The Responsibilities;
· Listing of Equipment's, Control and Systems;
· System Impact Assessment Philosophy/ Methodology
· Computer System Validation
· Cleaning Validation Aspects
· Process Validation Aspects
· The extent of the Qualification Work in a Qualification Matrix;
· The Layout and Structure of Qualification and Validation
Documents;
· The Change Control/ Deviation Concept;
· Requalification/ Revalidation Concept;
· Maintenance Planning and Implementation Concept;
· Calibration Concept;
· The Documentation System;
· Times Schedule for Validation/Qualification Activities - The Matrix.
· Training Requirements
How?
Relevant SOPs
By whom?
Responsibilities
What?
premises, systems
Why? and equipment
The processes
Validation products
Where?
Policy
The Plant
Location
11
Master Validation Plan
VMP Helps
· Management
· Validation Team Members
· Project Leaders
· GMP Inspectors
12
Risk Based Impact
Assessment - Qualification
Need Assessment
Impact assessment is the process by which the impact of equipment on

the product quality is evaluated, and the critical components of equipment/
system are identified.
Critical components could be operation, contact, data, control, alarm or

failure.
Or
Process of evaluating the impact of the operating, controlling, alarming

or failure conditions of a system on the quality of a product.
Classification
The impact should be evaluated by using three different levels of critical
state as criterion of assessment.
Indirect
Impact
Direct
No Impact
Impact
Impact
Assessment
13
These being defined by the terms:
Direct impact
Any system whose failure could affect product quality.
· Subject to qualification.
· Any equipment or system that is part of a validated manufacturing
process will normally be a direct impact system.
Example:
Process Equipment's/System
Autoclave Failure will have direct impact on sterilization process

& hence product quality
Filling Machine Failure will have direct impact on product quality
CIP/SIP System Failure will have direct impact on Cleaning/Sterilization

process & hence product quality
Laboratory Equipment's/System
HPLC Failure will have direct impact on the test results &
hence product quality
Immunoassay- Failure will have direct impact on the test results &
System hence product quality
14
Utility Equipment's/System
Water For Failure will have direct impact on the test results &
Injection System hence product quality
Pure Steam Failure will have direct impact on the sterilization

process & hence product quality
Building Automation/ Computerized System:

Building Failure will have direct impact on the monitoring &
Management control of associated systems like HVAC & hence
System (BMS) product quality
Laboratory Failure will have direct on the monitoring, control &

Information report generation system of associated laboratory
Management equipment's like HPLC, GC etc. & hence product
System (LIMS) quality
Note:
All computerised systems/Applications influences the product quality
and computerised systems/Applications which will support analytical
procedures and the batch release shall be categorised according the
determined parameters based on the GAMP 5 approaches.
For further reading please refer: ISPE GAMP 5: A Risk-Based Approach

to Compliant GxP Computerized Systems.
Indirect impact
A system not expected to have a direct impact on product quality, but
15
typically will support a Direct Impact System.
· Designed and commissioned following Good Engineering Practice

only.
· Indirect impact systems can affect the performance or operation of
a direct impact system; interfaces need to be carefully assessed.
Example:
Process Equipments/System
Refrigerator/ Failure will have indirect impact on product quality
Freezer for
Chemical
Storage
Acid/ Alkali Failure will have indirect impact on product quality

Vessels for
CIP/SIP System
Laboratory Equipment's/Systems
pH-Meter Failure will have indirect impact on product quality
Water Bath Failure will have indirect impact on product quality
Utility Failure will have indirect impact on product quality

Equipments/Sys
tem: Chilled
Water for Air
Conditioning
16
No impact
A system which does not have any impact, either directly or indirectly,
on product quality.
Example:
Process Failure will have no impact on product quality

Equipments/System:
Lifting Device,
Trolleys etc
Laboratory Failure will have no impact on product quality

Equipments/System:
Laboratory stirrer /
agitator
Animal Cage Failure will have no impact on product quality
Utility Failure will have no impact on product quality

Equipments/System:
Feed water for Failure will have no impact on product quality

Industrial Steam
All facility areas, utilities and process equipment should be classified as

direct impact, indirect impact or no impact following an analysis of their
impact on the identity, strength, quality, purity or safety of products
manufactured at the facility and also the safety of the operators &
environment.
Impact Assessment is performed in accordance with the following
17
procedure.
Identify Equipment
Does the
equipment have a YES
direct impact on
the product
quality?
Is the equipment
YES
linked to a Direct
Impact System?
No
Indirect Impact Direct Impact

No Impact System
System System
Just so you know...

The impact classification for facility areas, utilities and process
equipment within the scope of this exercise should be
presented in the Validation Master Plan (VMP).
18
Impact Assessment Objectives
GMP Compliance Objective
The objective is to evaluate the impact on the GMP Compliance, which a

possible failure of the functionality of equipment could cause.
Level Description
Low (L) The failure has no impact on the product quality;
Medium (M) The failure has an indirect impact on the product quality;
High (H) The failure has a direct impact on the product quality.
Business Objective
The objective is to evaluate the impact on the business that a possible

failure of the functionality of equipment could cause.
As business objective it is intended that a loss in the equipment function

could cause production to stop and/or loss of product.
Level Description
High (H) The failure has ahigh impact on company business.
Low (L) The failure has a low impact on company business.
19
Overall Impact
GMP
LOW MEDIUM HIGH
Business HIGH Indirect impact Direct impact Direct impact
LOW No impact Indirect impact Direct impact
Example:
GMP IMPACT BUSINESS OVERALLIMPACT

IMPACT
Equipment Use
High Medium Low High Low
Impact
H M L H L
Depyrogenation Depyrogenation
Direct Impact
Tunnel of Glass Vials
CIP Vessel Storage of

Acid/Base Indirect Impact
Pallet Lifting Lifting of Pallets No Impact

Truck
Equipment can be assessed only on the basis of GMP objective, but

not without them!!!
Impact Assessment Results
Impact Assessment will determine the level of qualification activities

required for each equipment.
20
Impact Based Qualification Activities
Impact Based
Qualification
Activites
No Impact Indirect Impact Direct Impact
No Basic Complete
Qualification Qualification Equipment
Activites Only Qualification
Qualification Documentation Depending On The Impact Assessment
Direct Impact

· Risk Analysis (RA)
· Design Qualification (DQ)
· Installation Qualification (IQ)
· Operational Qualification (OQ)
· PQ Performance Qualification
· Training
· Requalification
· Standard Operating Procedures
· Maintenance
· Change Control
21
Indirect Impact
· Basic Specification
· Basic Designing and Commissioning protocol/report following Good
Engineering Practice
· Maintenance
· Change Control
· Not subject to qualification if the Direct Impact system can detect or prevent
failure to product.
Example:
Equipment Impact Qualification Activites
Basic Qualification
Basic Specification
Control/Deviation
Re-qualification
Indirect Impact
Direct Impact
Maintenance
Calibration/
No Impact
Training
FAT/SAT
Change
URS
OQ
DQ
PQ
RA
IQ
Depyrogenation
Tunnel
CIP Vessel
Pallet Lifting
Truck
22
Qualification Phases
User Requirement Specification (URS)
Risk Assessment
What is FAT/SAT?
Equipment Design Qualification (DQ)
Equipment Installation qualification (IQ)
Equipment Operational Qualification (OQ)
Equipment Performance Qualification (PQ)
23
User Requirement
Specification (URS)
Depending upon the results of Impact Assessment of each process

equipment, either a URS or Basic Specification Sheets should be designed.
A URS should typically include specific, but non-detailed information

relating to, for example, quantity, quality, compatibility, performance,
environment and finishes in terms of:
· Materials of Construction;
· Clean ability Requirements;
· Maintenance Requirements;
· Operator Interface Requirements;
· Performance Criteria;
· Critical Parameters;
· Essential Design Criteria;
· Requirements of Computerized/Automation System;
· Training and Documentation Requirements.
It should make reference to relevant in-house standards and regulatory

documents.
24
Risk Assessment
“Production equipment should not present any hazard to the

products.”
Example:
¡ A polyurethane scraper was used to scrap down the sides of a

dryer to dislodge dried product. The scraper was corroded and
damaged when inspected… (doubt over product quality)
¡ A risk assessment approach could have identified the need to

qualify or validate the use of this ancillary equipment during
either the Performance Qualification (PQ) of the dryer, or the
process validation of the drying and discharging process (PV).
¡ Thus, a risk assessment approach here could have helped

determine the extent of Qualification or Validation.
25
What is risk?
Combination of the probability of occurrence of harm and the severity
of that harm (ICH Q9: Quality Risk Management).
· It is widely accepted that the concept of risk has two components –
Chance & Consequences:
¡ How likely is the scenario to happen?

¡ If it does happen, what are the consequences?
Key Considerations:
¡ The probability of occurrence of harm, (chance, possibility,
uncertainty, etc.)
¡ The consequences or severity of that harm, (injury, cost, supply
issues, etc.)
What is Risk Management?

¡ The combination of Risk Assessment & Risk Control, with
mechanisms for Periodic Review and Risk Communication.
§ Periodic Review uses new info (e.g. market surveillance, deviations,

processexperience, etc.), to increase knowledge about hazards,
and to improve the Risk Assessment.
¡ Risk Management should be viewed as an on-going Quality

Management process
26
Initiate
Risk Management Process
Risk Assessment
Risk Identification
Risk Analysis
Risk Evaluation
Risk Management tools
Risk Control
Risk Reduction unacceptable
Risk Acceptance
Risk Communication Risk Review

Risk Communication acceptable Risk Acceptance
Output/Results of the
Review Events
Risk Management Process
ICH Q9: Quality Risk Management
27
Risk Identification
Possible Risk to Critical Components, Process, and Functions
Risk Assessment
Risk Analysis
Probability of Occurrence (O) Severity (S) Probability of Detection (D)
Risk Evaluation
Low Medium High
Risk Acceptance
RISK MANAGEMENT
Acceptable Unacceptable Intolerable
Periodic
Risk Control Review
Acceptable No actions or new measures are required
Actions must be taken during

Unacceptable qualification/ validation to reduced
the risk to an acceptable level
Actions must be taken during qualification/

Intolerable validation to eliminate the risk
Risk Knowledge Communication
28
HACCP - Hazard Analysis and Critical Control
Points
HACCP (reference WHO Technical Report Series No 908, 2003 Annex 7)
is a structured approach that applies technical and scientific principles to
analyze, evaluate, prevent, and control the risk or the adverse
consequence(s) of hazard(s) due to the design, development, production,
and use of products.
HACCP consists of the following seven steps:

(1) conduct a hazard analysis and identify preventive measures for
the process;
(2) Determine the critical control points;
(3) establish critical limits;
(4) establish a system to monitor the critical control points;
(5) establish the corrective action to be taken when monitoring
indicates that the critical control points are not in a state of control;
(6) establish system to verify that HACCP system is working
effectively;
(7) establish a record-keeping system.
Potential Areas of Use(s)

Although used extensively by Food Industry, the process can be applied
to pharmaceutical or biotechnology manufacturing with the focus being on
patient safety and product quality. HACCP is most useful when product and
29
process understanding is sufficiently comprehensive to support
identification of critical control points.
HAZOP – Hazard Operability Analysis

HAZOP (reference IEC 61882) has origins in the bulk chemical industry
and was introduced in mid 1970s. It is based on a theory that assumes that
risk events are caused by deviations from the design or operating intentions.
It is a systematic brainstorming technique for identifying hazards using so-
called “guide-words”. “Guide-words” (e.g., No, More, Other Than, Part of,
etc.) are applied to relevant parameters (e.g., contamination, temperature)
to help identify potential deviations from normal use or design intentions. It
often uses a team of people with expertise covering the design of process or
product and its application.
HAZOP can be applied to manufacturing processes, equipment and

facilities for drug substances and drug (medicinal) products. It has also been
used primarily in the pharmaceutical industry for evaluating process safety
hazards.
FTA – Fault Tree Analysis

The FTA method (reference IEC 61025) is an approach that assumes
failure of the
functionality of a product or process. FTA is a method of analysis to
30
identify all root causes of an assumed failure or problem. This method
evaluates system (or sub-system) failures one at a time but can combine
multiple causes of failure by identifying causal chains. The results are
represented pictorially in the form of a tree of fault modes. At each level in
the tree, combinations of fault modes are described with logical operators
(AND, OR, etc.). FTA relies on process understanding of the experts to
identify causal factors.
The method can be used to establish the pathway to the root cause
of the failure. The use of FTA can be applied while investigating complaints
or deviations to fully understand their root cause and to ensure that
intended improvements will fully resolve the issue and not lead to other
issues (i.e. solve one problem yet cause a different problem).
PHA - Preliminary Hazard Analysis

PHA is a method of analysis based on applying prior experience or
knowledge of a hazard or failure to identify future hazards, hazardous
situations and events that might cause harm, as well as in estimating their
probability of occurrence for a given activity, facility, product or system. The
method consists of:
1) The identification of the possibilities that the risk event happens,

2) The qualitative evaluation of the extent of possible injury or
damage to health that could result and
31
3) The identification of possible remedial measures.

PHA is most commonly used early in the development of a project when
there is little information on design details or operating procedures; thus, it
will often be a precursor to further studies. Typically, hazards identified in
the PHA are further assessed with other risk management tools such as
those in this section.
But the most widely used Risk Assessment tool in Pharmaceutical

Industry is Failure Mode Effects Analysis (FMEA)!!
FMEA – Failure Mode & Effects Analysis
32
ICH Q9: Quality Risk Management
Failure Mode Effects Analysis (FMEA)
FMEA (IEC 60812) provides for an evaluation of potential failure modes

for processes and the likely effect on outcomes and/or product
performance. Once failure modes are established, risk reduction can be
used to eliminate, reduce or control the potential failures. It relies on
product and process understanding. FMEA methodically breaks down the
analysis of complex processes into manageable steps. It is a powerful tool for
summarizing the important modes of failure, factors causing these failures
and the likely effects of these failures.
FMEA can be used to prioritize risks and monitor the effectiveness of

risk control activities.
FMEA can be applied to equipment and facilities, and might be used to

analyze a manufacturing process to identify high-risk steps or critical
parameters. The output of an FMEA is a relative risk “score” for each failure
mode that is used to rank these modes on a risk basis.
33
What is expected during regulatory Inspections!!
¡ Inspectors may ask to see evidence of how Risk Assessment was

used when determining what qualification & validation work was
carried out on a certain process, piece of equipment, etc.
¡ Inspectors may ask to see evidence of how Risk Assessment was

used when designing qualification & validation protocols, and in
Change Controls.
¡ Inspectors will not require any specific Risk Assessment tool used.
¡ Inspectors will look for evidence that hazards were adequately

identified and that risks were adequately assessed & managed.
¡ Inspectors will ask to see how risk acceptability criteria were

chosen.
34
Risk Assessment - Failure Mode Effects Analysis
(FMEA) - Explained
Step 1: Risk Detection/Identification
Identification of different failure modes of Equipment's Critical
Components and Functions.
Step 2: Risk Analysis

Estimation of the possible risk to the Product Quality; Operator and
environment safety; if those components and functions fail.
Probability of Occurrence (O)

Occurrence (O) refers to the probability that a specific cause will result
in a specific failure mode.
The Probability of Occurrence is evaluated and graded as high (will

probably occur), medium (may occur at some time) or low (unlikely to occur
in most circumstances).
Severity (S)
Severity is the measurement of the possible consequences of failure.
The Severity is evaluated and graded either as high (very significant

non-compliance with GMP or injury to patients), medium (significant non-
compliance with GMP or impact on patients) or low (minor infringement of
GMP and no impact on patients).
Probability of Detection (D)

Probability of Detection is the ability to discover or determine the
35
existence, presence, or fact of a failure.
The Risk Level is evaluated and graded as high (unlikely to be detected in
most circumstances), medium (may be detected at some time) or low (will
probably be detected).
Step 3: Risk Evaluation

Depending on the Probability of Occurrence (O), Severity (S) and
Probability of Detection (D) overall risk can be graded as low, medium or high
level.
The risk must be defined as acceptable, unacceptable or intolerable in

accordance to the most critical evaluation of the different risk levels for the
parameters Probability of Occurrence, Severity and Probability of Detection.
Risk Evaluation Methods

Quantitative Method
Under the Quantitative Method the occurrence, severity and detection
are rated as 1-10 depending on their probability/ chance, impact and
easiness/ hardness respectively and scores are multiplied to get a Risk
Priority Number (RPN).
Risk Priority Number (RPN) formula = Ox SxD
Scale 1-10 Risk Priority Risk Acceptance

Number
Probability of Occurrence (O) x < 70 Acceptable
Severity (S) x Probability of Detection (D) 71-99 Unacceptable
≥ 100 Intolerable
36
Qualitative Method
In Qualitative method Score of about 1 to 4 is considered as low, a score
of about 5 to 6 is considered as medium and a score of about 7 to 10 is
considered as high.
Factors Quantitative Equivalent Definition Equivalent

Score Risk Level Risk Evaluation
/Acceptance
Probability of 1-4 Low Unlikely to occur in most Acceptable

Occurrence (O) circumstances
5-6 Medium May occur at some time Unacceptable

7-10 High Will probably occur Intolerable
Severity (S) 1-4 Low Minor infringement of GMP and Acceptable
no impact on patients
5-6 Medium Significant non-compliance with Unacceptable

GMP or impact on patients
7-10 High Very significant non-compliance Intolerable

with GMP or injury to patients
Probability of 1-4 Low Will probably be detected Acceptable

Detection (D)
5-6 Medium May be detected at some time Unacceptable
7-10 High Unlikely to be detected in most Intolerable

circumstances
Probability Detectability
Medium
Medium
High
High
Low
Low
Risk Class1 High Risk Priority

High High
Risk Class
Severity
Medium Risk Class2 Medium Medium Risk Priority
Low Risk Class3 Low Low Risk Priority
Severity = Impact on Patient Safety, Product Quality Detectability = Likelihood that the fault will be
and Data Integrity (or other harm) noted before harm occurs
Probability = Likelihood of the fault occurring Risk Priority = Risk Class x Detectability
Risk Class = Severity x Probability
Source: Figure M3.5, GAMP5: A Risk-Based Approach to Compliant GxP Computerized Systems, © Copyright ISPE 2008. All rights reserved. www.ISPE.org.
37
Hybrid method:
It may not be adequate to rely solely on qualitative or quantitative
information and leveraging both types of rating systems may be useful.
Risk – Should we Quantify or Qualify?
Most Risk Assessment methods require to determine the Probability of

Occurrence of a failure mode or hazard, but accurate Probability of
Occurrence info can often be very difficult to establish!
Reasons:
¡ Probability relates not to the effects of the failure, but to the
probability of occurrence of the failure mode itself or to its cause,
and this can be difficult to determine accurately
¡ Some hazards occur because of systematic errors, as opposed to
random errors…. & systematic errors are difficult to quantify
§ e.g. errors of commission or omission which, under some set of
circumstances, result in a hazardous situation
Severity & Probability are 'ordinal' scales

¡ Their magnitude is not meaningful.
¡ A Probability of Occurrence of 4 is higher but not necessarily twice
as likely as a Probability of 2.
¡ It is not mathematically permissible to multiply 'ordinal' scales.
¡ Numerical operations such as (Risk = 3 x 4) or (Risk = 3 x 4 x 2) have
questionable validity.
38
Word descriptors (e.g. high, medium, low) may be more valid than
numerical descriptors, and are preferable, because we will not then be
tempted to multiply categories.
More recent publications, e.g. ISO 14971 – Application of Risk

Management to Medical Devices – do not actively promote numerical
operations in risk determination.
Inadvisable to place too much faith in risk quantitation.
Just so you know…

A good qualitative estimation is better than a poor quantitative
estimation!
Risk Control
¡ A process in which risks are reduced or maintained within specified
levels. It occurs after Risk Assessment.
¡ Determine what detection or other controls are in place to

maintain the risk within specified levels.
¡ Determine whether these controls give assurance that the risk is

adequately controlled & no further controls required.
¡ Determine what additional actions or controls are needed to

reduce the risk or maintain it within specified levels.
39
Additional Controls could include:
l Eliminating the hazard… by designing it out of the process.
l Designing in Redundancy
l Building in new & improved Detection Mechanisms.
l Improving Preventative Maintenance Activities.
l Training Operators to better detect the effects of the failure mode
l Risk Control work also determine Critical Control Points, (or Critical
Process Parameters), how they will be monitored, and what level of
Qualification & Validation are required.
The following risk control actions are to be undertaken in accordance to

the risk:
Risk Risk control actions

Acceptable No actions or new measures are required
Actions or new measures are required and the risk must
Unacceptable be reduced to an acceptable level by taking appropriate
measure at specific qualification phase.
Actions or new measures are required and the risk must
Intolerable be eliminated by taking appropriate measure at specific
qualification phase.
Risk Assessment Table

The results of any risk analysis should be well documented as they
40
become the key input into the qualification and validation process. They are
the basis for defining tests in the IQ, OQ, and PQ phases.
The table consists of the following items:

· Name of the component or process-step
· Description of the component or process-step
· Possible failure modes, for example: not working, wrong reading,
incorrect operation or malfunction.
· Possible Consequences
A short description of the possible consequences and effects on
the product in the case of the given failure.
· Probability of Occurrence (O)
· Severity (S)
· Probability of Detection (D)
· Risk
· Measures
· Qualification steps in which the tests must be carried out
41
Example:
Autoclave Risk Assessment
No. Test Items Failure Mode Risk and Risk Risk Evaluation/ Risk Control/ Qualification Risk after
Function conceivable Analysis Steps
Acceptance Actions for control
/ Process/ malfunction/
Correction measures
Components/ Consequence
Risk Risk
O S D Overall DQ IQ OQ PQ
Risk Accepted? Accepted?
Yes
Temperature value does Containers are Calibration
not comply with processed in
specification: a) correct an inadequate
1 Sensors value - wrong indication manner L H L H No
Guarantee
b) wrong value - correct
alarm
indication.
function
The containers are not Containers are The heating Yes

2 Depyrogenation heated not L H L H No elements are
Process sufficiently/Temperatur depyrogenated checked
e too low (heating when
elements defective). machine is
switched on
Check of
alarm
function
Process
Validation
Risk Communication
ICH Q9 defines Risk communication as an interactive process of
exchange of information and opinion on risk among risk assessors, risk
managers, and others.
This might include communication among many interested parties;

e.g., regulators and industry, industry and the patient, workers and
42
management within a company, industry or regulatory authority, etc.
The main aim in understanding and communicating risk is to identify

and prioritize risks, and take appropriate actions to minimize them.
The included information might relate to the existence, nature, form,

probability, severity, acceptability, treatment, detect ability or other aspects
of risks to quality.
Risk Review
ICH Q9 states the output/results of the risk management process
should be reviewed to take into account new knowledge and experience.
Once a quality risk management process has been initiated, that

process should continue to be utilized for events that might impact the
original quality risk management decision whether these are planned (e.g.,
results of product review, inspections, audits, change control) or unplanned
(e.g., root cause from failure investigations, recall).
ICH Q9 also states that Risk Management should be an ongoing part of

quality management process and a mechanism to perform periodic review
of events should be implemented.
The frequency of the review should be based upon the level of risk. Risk
review might include reconsideration of risk acceptance decisions.
43
What is FAT/SAT?
FAT (Factory Acceptance Testing)

FAT is performed on the site of the vendor usually before the
equipment/application is purchased, to ensure that the product has all of
the required functionality from a URS perspective. This testing should be
quite rigorous as there is little point in purchasing a piece of equipment if it
doesn't do what you want it to do.
SAT (Site Acceptance Testing)

SAT is testing performed on site to ensure that the equipment works as
intended. Some companies perform a SAT before going into main validation
testing, whereas other incorporate this testing into their IQ/OQ testing.
44
Equipment Design
Qualification (DQ)
DQ is providing documented evidence that quality is built into the

equipment design.
Applies to the Equipments identified in the risk based impact

assessment.
Example:
Equipment Impact Qualification Activities

Basic Qualification
Basic Specification
Control/Deviation
Re-qualification
Indirect impact
direct impact
Maintenance
Calibration/
No impact
Training
Change
URS
FAT
OQ
DQ
PQ
RA
IQ
Depyrogenation X X
Tunnel
The purpose of design qualification is to ensure that the equipment

final design:
· Is according with all relevant specifications and design intentions

mentioned in URS or Basic Specifications;
· Meets the requirements of the process, product and user;
· Adequately specifies all necessary supporting documentation;
45
· Complies with the requirements and principles of GMP/ GEP;
· Complies with the test points mentioned in the Risk Assessment
Protocol.
DQ Review Documents
· Functional Specification (FS)
· Equipment Impact Assessment
· Equipment Risk Assessment
· Factory Acceptance Testing (FAT).
· Tender Specifications, P&ID's and Drawings
· Vendor Quality procedures and documents
· Purchase Specification
Example: Depyrogenation Tunnel

Table Of Contents
1.0 PURPOSE
2.0 DESCRIPTION
3.0 REFERENCES
4.0 RESPONSIBILITIES
5.0 IDENTIFICATION OF PERSONNEL
6.0 DESIGN QUALIFICATION
7.0 DQ ACCEPTANCE CRITERIA
8.0 MODIFICATIONS/CHANGE CONTROL AND REVALIDATION
46
9.0 DEVIATIONS AND CORRECTIVE ACTIONS
10.0 DQ ATTACHMENTS
1A. Design Basis – Project Documentation
1B. Design Basis – Codes & Guidelines
2. Quality-Critical Systems
3. Specification Verification – FDS & P&ID Verification
4A. Specification Verification of Packaged System – Process
4B. Specification Verification of Packaged System – Control
5. Specification Verification – Utilities
6. Authority Approval
7. Supplier Qualification & Bid Evaluation
8. History of Design Changes
9. Reference List
10. Design Qualification Summary
11. Approval of Design Qualification Report
12A. Deviations – List
12B. Deviations – Corrective Actions
13. Identification of Personnel
47
Equipment Installation
qualification (IQ)
Installation qualification is the documented evaluation of the

equipment to establish that it has been installed in accordance with design
specifications, cGMP requirements and manufacturers recommendations.
Verify Static Attributes

assessment.
Example:

Basic Qualification
Basic Specification
Control/Deviation
Re-qualification
Indirect impact
direct impact
Maintenance
Calibration/
No impact
Training
Change
URS
FAT
OQ
DQ
PQ
RA
IQ
Depyrogenation X X
Tunnel
IQ Review Documents
· Equipment Impact Assessment
48
· Equipment Risk Assessment
· Factory Acceptance Testing (FAT).
· Tender Specifications, P&ID's and Drawings
· Vendor Quality procedures and documents
· Purchase Specification
Pre-conditions for IQ execution:
· DQ-reports must be approved

· IQ-protocols must be approved
· Installation of the equipment has to be completed
· Technical documentation has to be available
· Pre-conditions defined in VMP and IQ documents have to be
fulfilled (e.g. calibration, etc.)
The results of the IQ performance will be summarised in an IQ-report.

Table Of Contents
1.0 PURPOSE
2.0 DESCRIPTION
3.0 REFERENCES
6.0 INSTALLATION QUALIFICATION
7.0 IQ ACCEPTANCE CRITERIA
49
8.0 MODIFICATION/CHANGE CONTROL AND REVALIDATION
10.0 IQ ATTACHMENTS
1. Equipment Identification
2A. Connections Checkout – Piping
2B. Connections Checkout – Electrical
2C. Connections Checkout – Instrumentation
3. Materials of Construction in Product Contact
4. Spare Parts List
5A. Instrument Calibration: Quality-Critical Instruments
5B. Instrument Calibration: Reference Instruments
6. Documentation
7. Drawings
8A. Utility Check-Out: Electrical
8B. Utility Check-Out: Other Utilities
9. Calibration of Validation Test Instruments
10. Lubricant List
11. Preventive Maintenance Schedules Verification
12. Control System Software and 21 CFR Part 11Verification
13. Installation Qualification Summary
14. Approval of Installation Qualification Report
50
Equipment Operational
Qualification (OQ)
Operational qualification is the documented evaluation of the

equipment to show that it operates as intended throughout the anticipated
operating ranges.

assessment.
Example:

Basic Qualification
Basic Specification
Control/Deviation
Re-qualification
Indirect impact
direct impact
Maintenance
Calibration/
No impact
Training
Change
URS
FAT
OQ
DQ
PQ
RA
IQ
Depyrogenation X X
Tunnel
Typically it will consist of various functional checks on the equipment,

generally performed using inert materials such as water or compressed air
and in the absence of real product.
Tests should be designed to show that the equipment would perform as
51
intended and to specification. The tests should encompass upper and lower
processing limits and circumstances, including those within normal
operating conditions, which pose the greatest chance of process or product
failure compared to ideal conditions. These conditions are widely known as
'worst case' or 'most appropriate challenge' conditions.
OQ and Commissioning
OQs demonstrate the functionality of the installed system and are often
carried out as part of commissioning. Engineering commissioning is
normally undertaken by a 'system' vendor and is geared to starting up the
'system.' OQ work is more concerned with the operating parameters of the
'system' and with the identification and independent measurement of
operating variables over their normal operating ranges.
However, depending on how contracts are let and the responsibilities

for the 'system' testing are specified, the vendor or installer may be
requested to carry out certain OQ activities as part of commissioning work.
For instance, in the case of the commissioning of a HVAC system, it may fall
within the scope of the engineering activities to stimulate certain 'worst
case' conditions such as the effects on the air pressure regime of a power
dip.
The OQ protocol should require verification of the satisfactory

completion of all such commissioning activities.
Pre-conditions for OQ execution:
52
· IQ-reports must be approved
§ OQ-protocols must be approved
§ Equipment / system has to be officially released for OQ
§ Pre-conditions defined in VMP and OQ documents have to be
fulfilled (e.g. SOP's, training of personnel, etc.)
The results of the OQ performance will be summarised in an OQ-report.

Table Of Contents
1.0 PURPOSE
2.0 DESCRIPTION
3.0 REFERENCES
6.0 OPERATIONAL QUALIFICATION
7.0 OQ ACCEPTANCE CRITERIA
10.0 OQ ATTACHMENTS
2. Alarm and Interlock Test
3. Control Panel Test
4A. Verification of Differential Pressure between Fill Room and
Tunnel Cooling Zone
53
4B. HEPA Filter Integrity Verification
4C. Cleanliness Class Verification
4D. Particulate on Glass Containers Verification
4E. Air Flow Direction Verification
4F. Air Velocity Verification
4G. Heat Distribution Study
4H. Glass Temperature Exiting Tunnel Verification
5. Safety Performance Verification Checklist
6A. Probe Placement Worksheet
6B. Thermocouple Calibration Worksheet
7. SOP's & Personnel Training
8. Operational Qualification Summary
9. Approval of Operational Qualification Report
54
Equipment Performance
Qualification (PQ)
Performance qualification is the documented evaluation of the system

to show that the system operates as intended throughout the anticipated
operating ranges, under conditions as close as possible to normal
production.

assessment.
Example:

Basic Qualification
Basic Specification
Control/Deviation
Re-qualification
Indirect impact
direct impact
Maintenance
Calibration/
No impact
Training
Change
URS
FAT
OQ
DQ
PQ
RA
IQ
Depyrogenation X X
Tunnel
Typically it will consist of various functional checks on the equipment,

generally performed using actual product.
PQ work should be performed on systems whose performance or
55
process parameters are critical and could affect the quality of the product.
Examples of the systems requiring PQ work are pieces of process

equipment such as a production sterilizer and critical utilities such as a WFI
system.
As with an OQ, the critical parameters and acceptance criteria of the

system under consideration should be defined. Once these have been
defined, the test that is required to show the parameters are met can be
designed. To successfully complete PQ work it is necessary to examine a
number of consecutive batches or runs. One should also consider the
variability to be expected to show that it does not affect product quality —
i.e. 'worst case' conditions.
Normally any samples taken during PQ testing work will be taken by the
user's personnel, not by vendors or outside contractors responsible for
installing and commissioning of the system.
Pre-conditions for PQ execution:
· OQ-reports must be approved

· PQ-protocols must be approved
· equipment / system has to be officially released for PQ
· Pre-conditions defined in VMP and PQ documents have to be
fulfilled (e.g. SOP's, start up of system, etc.)
The results of the PQ performance will be summarised in the PQ-report.
56
Table Of Contents
1.0 PURPOSE
2.0 DESCRIPTION
3.0 REFERENCES
6.0 PERFORMANCE QUALIFICATION
7.0 PQ ACCEPTANCE CRITERIA
10.0 PQ ATTACHMENTS
2A. Determination of Slowest Heating Zone (SHZ) for
Maximum Loading Configuration – Probe Placement
Worksheet
2B. Determination of Slowest Heating Zone (SHZ) for
Maximum Loading Configuration – Thermocouple
Calibration Worksheet
2C. Determination of Slowest Heating Zone (SHZ) for
Maximum Loading Configuration – Heat Distribution /
Penetration Worksheet
57
3A. Determination of Heat Distribution across the width of the
belt – Probe Placement Worksheet
3B. Determination of Heat Distribution across the width of the
belt – Thermocouple Calibration Worksheet
3C. Determination of Heat Distribution across the width of the
belt – Heat Distribution/Penetration Worksheet
4A. Performance Consistency & Biological Challenges for
Maximum Loading Configurations – Probe Placement
Worksheet
4B. Performance Consistency & Biological Challenges for
Maximum Loading Configurations – Thermocouple
Calibration Worksheet
4C. Performance Consistency & Biological Challenges for
Maximum Loading Configurations – Heat Distribution /
Penetration Worksheet
4D. Performance Consistency & Biological Challenges for
Maximum Loading Configurations – Biological Indicator
Test Results
5. Performance Qualification Summary
6. Approval of Performance Qualification Report
7A. Deviations - List
58
Requalification
In order to maintain the equipment, once initially qualified, in a state of

qualified throughout their lifecyclethere should be continuous review of the
need for requalification andimplementation of requalification whenever it is
agreed to be necessary.
Requalification requirements should be defined based on a technical

reviewof the initial qualiflcation(s), change control data and documentation
supportingthe performance of the item subject to qualification.
Requalification will beundertaken if a change is likely to affect the

validated status or if theperformance of the validated system is seen to have
deteriorated.
Requalificationexercises should be built into the Validation Master

Plan.
The need for requalification may be identified via several mechanisms:
· through a change control procedure;

· by regular review of the performance of a validated item to a
predeterminedschedule;
59
· by the use of a plant certification system;
· through annual product reviews;
· through internal audits.
Critical items of the plant are frequently covered by a routine

certificationand re-certification programme. Requalification intervals and
the test to beconducted are normally specified at the time of certification.
· Not required if PQ or alternative modes in place to verify qualified

state
· Required for
· Repairs;
· Relocation;
· Change in application/ user requirement;
· Extent of Requalification – Decided on case to case- can be

limited to module.
60
Change Control
Change control is defined in the PIC/S document PI 006 as follows: “A

formal system by which qualified representatives of appropriate disciplines
review proposed or actual changes that might affect a validated status. The
intent is to determine the need for action that would ensure and document
that the system is maintained in a validated state.”
Change control is a lifetime monitoring approach. The implementation

of a change control system is an important and necessary step in the
validation approach for equipment and facilities.
Planning for well executed Change Control Management should

include the following aspects:
· Workable documentation system;

· Defined responsibilities and job descriptions;
· Defined review procedures;
· Well-trained staff;
· Identification of the entity being changed.
· A description of Impact based Change Classification- Crirtical,
Major and Minor;
61
· A description of Likelihood based Change Classification– Planned or
Unplanned;
· Identification of the affected documents;
· Signature of the approving individual(s);
· The approval date;
· When the change becomes effective;
· Traceability.
It is not only good practice but also essential that a requested change
isonly implemented after the appropriate change control procedures and
approvals have been followed.
Change Process
· Identify the change and assess the impact of the change

Identification
· Qualify/ validate the change and document the results

Qualification
· Approve the change documentation and implement the change

Implementation
62
Glossary
DQ Design Qualification
di Direct Impact
FAT Factory Acceptance Test
FMEA Failure Mode and Effects Analysis
FS Functional Specifications
FTA Fault Tree Analysis
GAMP Good Automated Manufacturing Practice
GEP Good Engineering Practice
GMP Good Manufacturing Practice
ii Indirect Impact
IQ Installation Qualification
ni No Impact
OQ Operational Qualification
63
PQ Performance Qualification
QbD Quality by Design
SAT Site Acceptance Test
SOP Standard Operating Procedure
URS User Requirements Specification
WFI Water for Injection
64
References
- ICH Quality Risk Management Q9, International Conference on

Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use, guidance for industry, June 2006.
- ICH Pharmaceutical Quality System Q10, International Conference

on Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use, guidance for industry, April 2009.
- ISO 14791:2000 (Application of Risk Management to Medical

Devices).
- ISO 31000: Risk Management – Principles and Guidelines, 2009.
- ISO 31010: Risk Assessment Techniques, 2009.
- EU GMP Annex 15: Validation and Qualification 2010.
- Failure Mode and Effect Analysis, FMEA from Theory to Execution,

2nd Edition 2003, D. H. Stamatis, ISBN 0873895983.
- Guidelines for Failure Modes and Effects Analysis (FMEA) for

Medical Devices, 2003 Dyadem Press, ISBN 0849319102.
- ISPE Baseline Pharmaceutical Engineering Guide, Volume 5 -
65
Commissioning and Qualification, International Society for
Pharmaceutical Engineering (ISPE), First Edition, March 2001.
- ISPE Baseline Pharmaceutical Engineering Guide, Volume 7 – Risk

Based Manufacture of Pharmaceutical Products, International
Society for Pharmaceutical Engineering (ISPE), First Edition,
September 2010.
- A White Paper on Risk-Based Qualification for the 21st Century,

ISPE, 9 March 2005.
- IEC 61882 - Hazard Operability Analysis (HAZOP).
- IEC 61025 - Fault Tree Analysis (FTA).
- IEC 60812 Analysis Techniques for system reliability—Procedures

for failure mode and effects analysis (FMEA).
- ISPE GAMP 5: A Risk-Based Approach to Compliant GxP

computerized Systems, International Society for Pharmaceutical
Engineering (ISPE), 2008.
- ISPE Guide: Science and Risk-Based Approach for the Delivery of

Facilities, Systems, and Equipment, June 2011.
- PI – 006 – 2 (Recommendation on Validation Master Plan:

Installation- and Operational Qualification, Non-Sterile Process
Validation, Cleaning Validation).
- The Basics of FMEA, Robin McDermott, Raymond J. Mikulak,
66
Michael R. Beauregard 1996, ISBN 0527763209.
- US FDA - Code of Federal Regulations, Title 21, Part 210: Current

Good Manufacturing Practice in Manufacturing, Processing,
Packaging, or Holding of Drugs; General.
- US FDA - Code of Federal Regulations, Title 21, Part 211: Current

Good Manufacturing Practice for Finished Pharmaceuticals.
- WHO Technical Report Series No 908, 2003, Annex 7 Application of

Hazard Analysis and Critical Control Point (HACCP) methodology to
pharmaceuticals.
67
Quiz
1. We qualify a ______________ and validate a ___________”
2. What is Impact assessment?
3. What are different levels of Impact assessment?
4. What are the qualification documentation are required for equipment

having direct Impact on product quality?
5. What is Risk Management?
6. What is ICH Q9?
68
7. Which is the most widely used Risk Assessment tool in Pharmaceutical
Industry?
8. What are the major steps in Failure Mode Effects Analysis (FMEA)?
9. What is RPN in Failure Mode Effects Analysis (FMEA)?
10. Identify the Impact Class and Qualification activities required for the
Filling Machine in your facility?
69
Answers
1. We qualify a system and/or equipment and validate a process”
2. Impact assessment is the process by which the impact of equipment on

the product quality is evaluated, and the critical components of
equipment/ system are identified.
3. The impact should be evaluated by using three different levels of critical

state as criterion of assessment:
Direct Impact
Indirect Impact
No impact
4. · User Requirement Specification (URS)

· Risk Analysis (RA)
· Design Qualification (DQ)
· Installation Qualification (IQ)
· Operational Qualification (OQ)
· PQ Performance Qualification
· Training
· Requalification
· Standard Operating Procedures
70
· Maintenance
· Change Control
5. The combination of Risk Assessment & Risk Control, with mechanisms

for Periodic Review and Risk Communication.
6. ICH Quality Risk Management Q9, International Conference on

Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use, guidance for industry, June 2006.
7. The most widely used Risk Assessment tool in Pharmaceutical Industry is

Failure Mode Effects Analysis (FMEA)!!
8. Step 1: Risk Detection/Identification

Step 2: Risk Analysis
Step 3: Risk Evaluation
9. Risk Priority Number (RPN).
10.

Basic Qualification
Basic Specification
Control/Deviation
Re-qualification
Indirect impact
direct impact
Maintenance
Calibration/
No impact
Training
Change
URS
FAT
OQ
DQ
PQ
RA
IQ
Filling Machine X X
71
SCORE
True False
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Your score
72

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An Easy to Understand

Published by Premier Validation

An Easy to Understand Guide | Risk Based Equipment Qualification

© Copyright 2011 Premier Validation

The author takes no responsibility for how this advice is implemented.

Visit Premier Validation on the web at www.premiervalidation.com or visit

An Easy to Understand Guide | Risk Based Equipment Qualification

Equipment Qualification activities are the foundations upon which

An Easy to Understand Guide | Risk Based Equipment Qualification

The Validation Specialists

Published by Premier Validation Ltd

Print and bound in the United Kingdom

An Easy to Understand Guide | Risk Based Equipment Qualification

Equipment Qualification Process 9

An Easy to Understand Guide | Risk Based Equipment Qualification

This book describes how to perform the qualification assessment

This approach eliminates the duplication of effort and costly practices

· Repeating qualification steps;

After gauging the impact-based requirement of qualification steps at

Although written primarily with the pharmaceutical and biotechnology

Upon the completion of this book you will be able to:

· Understand the basic difference between Validation &

Qualification involves testing equipment to demonstrate that it does

A system and/or equipment must be qualified to operate in a validated

· Validation and qualification are essential components of the same

There are three reasons why the pharmaceutical industry is concerned

In CFR 211.220 it says:

'The manufacturer shall validate all drug product manufacturing

' . . . validation protocols that identify the product and product

' . . . the manufacturer shall design or select equipment and processes to

Similar requirements are stated in the EU Rules.

Qualification · Commissioning (Factory Acceptance Test (FAT),

The first step of Equipment Qualification is to generate a Validation

What is a Validation Master Plan

A Validation Master Plan (VMP) is a comprehensive document

The Validation Master Plan defines

Impact assessment is the process by which the impact of equipment on

Critical components could be operation, contact, data, control, alarm or

Process of evaluating the impact of the operating, controlling, alarming

Autoclave Failure will have direct impact on sterilization process

Filling Machine Failure will have direct impact on product quality

CIP/SIP System Failure will have direct impact on Cleaning/Sterilization

Pure Steam Failure will have direct impact on the sterilization

Building Automation/ Computerized System:

Laboratory Failure will have direct on the monitoring, control &

For further reading please refer: ISPE GAMP 5: A Risk-Based Approach

· Designed and commissioned following Good Engineering Practice

Acid/ Alkali Failure will have indirect impact on product quality

pH-Meter Failure will have indirect impact on product quality

Water Bath Failure will have indirect impact on product quality

Utility Failure will have indirect impact on product quality

Process Failure will have no impact on product quality

Laboratory Failure will have no impact on product quality

Animal Cage Failure will have no impact on product quality

Utility Failure will have no impact on product quality

Feed water for Failure will have no impact on product quality

All facility areas, utilities and process equipment should be classified as

Impact Assessment is performed in accordance with the following

Indirect Impact Direct Impact

Just so you know...

The objective is to evaluate the impact on the GMP Compliance, which a

The objective is to evaluate the impact on the business that a possible

As business objective it is intended that a loss in the equipment function

Low (L) The failure has a low impact on company business.