An Easy to Understand Guide

HPLC Validation

askaboutValidation
The Validation Specialists Connecting the Life Sciences
An Easy to Understand Guide
HPLC Validation

By

Dr. David Trew

BSc (Hons), PhD, CChem MRSC

Published by Premier Validation

An Easy to Understand Guide | HPLC Validation

An Easy to Understand Guide
HPLC Validation
First Edition

© Copyright 2013 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.

An Easy to Understand Guide | HPLC Validation

So what’s this book all about?
Hey there,

I am assuming if you are reading this book you want to learn about the
validation of HPLC instruments. Validation, which when performed on
laboratory instruments is known as qualification, is about creating
documentation that demonstrates a high degree of assurance that the HPLC
consistently performs to established specifications. Unfortunately, the
relevant information on the requirements and how to perform this is
fragmented in to a large number of regulations, recommendations and
guidelines which is time consuming to correlate into a useful tool for
practical implementation.

The purpose of this book, which is based on the author's many years of
experience of working in analytical laboratories, qualifying a wide range of
laboratory instrumentation in the highly regulated environment of the
pharmaceutical industry, is to present the entire process in an easy to
understand format for practical implementation.

We begin with a review of the basic functions of the main components

of HPLC instruments and identify the key testing requirements. This is then
followed by a discussion of the principal regulations, guidelines and
recommendations. We then look at each of the qualification phases of a
typical HPLC instrument. As the creation of documentation is a key activity
in qualification, this book will use example extracts from sample documents
to illustrate the process, where appropriate.

An Easy to Understand Guide | HPLC Validation

The brains behind the operation!
Program Director: Graham O'Keeffe
Content Author: Dr. David Trew
Technical Editor: Alan Smith, Graham O'Keeffe, Peter Jacobs, Irene Kaas.
Editor: Anne-Marie Smith
Printing History: Edition: Feb 2013
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
978-1-908084-10-1

Print and bound in the United Kingdom

An Easy to Understand Guide | HPLC Validation

Table of Contents
Introduction 1
Why Should I Read This Book? 2
Purpose and Scope of Book 3
Overview of Qualification Process 5
Benefits of Qualification 6
Definitions 7
Overall Learning Objectives of This Book 10

Basic Components of a HPLC 12

Solvent Delivery System 14
Basic Functions for Testing 16
Auto Injector 16
Basic Functions for Testing 17
Column Oven 18
Basic Functions for Testing 18
Detectors 18
Basic Functions for Testing 19
Computer 19
Basic Functions for Testing 20

Regulatory Expectations, Standards and Guidelines 22

Regulatory Requirements 23
Pharmacopeias 24

An Easy to Understand Guide | HPLC Validation

 Good Automated Manufacturing Practice (GAMP) 26
21 CFR Part 11 and Annex 11 28
Consequences of Non-Compliance 30

Qualification Planning 32
Equipment Qualification Plan (EQP) 34
Suggested Contents for Each Section 36
Introduction 36
Scope 37
Users 37
Regulations, Policies, Standards and Procedures 37
Qualification Strategy 38
Roles and Responsibilities 39
Risk Assessment (RA) 39
GAMP and USP<1058> Categories 39
List of Protocols and Other Deliverables 40
Timeline 41
System Security 41
Data Backup and Recovery 42
Contingency Plan 43
Deviation Handling 43
Glossary 44

Design Qualification (DQ) 45

User Requirement Specification (URS) 47

An Easy to Understand Guide | HPLC Validation

 Functional Requirement Specification (FRS) 48
Operational Requirements 49
Clock Configuration 50
Instrument Selection 51
Vendor Qualification (VQ) 51

Qualification Risk Management 54

Risk Assessment 55
Risk Identification 56
Risk Analysis 56
Calculation of Risk Factor 58
Risk Mitigation 59

Installation Qualification (IQ) 61

Pre-installation 64
Utilities 64
Stack Configuration 65
Installation 66
Performing the Installation 68
Screen Shots, Screen Dumps, Screen Prints 69
Confirming Correct Installation of the HPLC Instrument 69
Documenting the Installation - The Installation
Qualification (IQ) Protocol 70
Pre-execution approval 72
Responsibilities 73

An Easy to Understand Guide | HPLC Validation

 Identification of Personnel Involved 73
Documentation of the Site of Installation 74
Reconciliation of deliveries 76
Documentation of the Component Modules of
the Instrument 78
Documentation of computer hardware 78
Installation, configuration and documentation of software 80
Clock Configuration 81
Installation Testing 82

Operational qualification (OQ) 84

Documenting the Operational Qualification,
the OQ Protocol 86
General Description of Operational Tests 88
Operational Qualification of HPLC Software 88
Operational Qualification of HPLC Instrument Hardware 91

Performance Qualification (PQ) 99

Performance Testing 101
Performance Checking During HPLC
Runs - System Suitability 102
Daily Lamp Checks 103
HPLC Use, Management and Responsibility 104
Systems Required for Maintaining the HPLC

An Easy to Understand Guide | HPLC Validation

 in a Qualified State 105
Instrument Logbook 105
Routine Preventative Maintenance (PM)
and Requalification (RQ) 107
Standard Operating Procedure on Chromatography Policies 108
Training 108
Change Control (CC) 109
Periodic Review 109
Documenting Performance Qualification – The PQ Protocol 111
Performance qualification scenarios 113
Instrument Logbook 114
Routine Preventative Maintenance (PM)
and Requalification (RQ) 114
Standard Operating Procedures (SOP) 115
Training 115
Change Control 116
Periodic Review 116
Decommissioning 118

Final Qualification Report 121

Deliverables 123
Functionality 123
Deviations 124
Conclusions 125

An Easy to Understand Guide | HPLC Validation