How to sell validatable equipment to pharmaceutical manufacturers

360 Pages·2000·9.359 MB·English

by  Erik Kopp

How to Sell
Validatable
Equipment
to Pharmaceutical
Manufacturers
Erik Kopp
informa
healthcare
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 1999 by Taylor & Francis Group, LLC
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Version Date: 20130325
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DEDICATION
With special thanks to the following individuals:
My best friend, my wife, Carla,
who believed that I could really do this.
My little helper, my son, Devin,
who showed me that to achieve anything worthwhile in life
you have to keep working at it and working at it and working at it,
until you get it just right.
My friend and colleague Dan Meshnick,
who took a chance on bringing me into this industry
and taught me most of what I know about this stuff.
iii
CONTENTS
INTRODUCTION x
1. The Basics: The Regulations in Plain Language 1
Pharmaceutical Terminology 1
How the Regulations Affect the Pharmaceutical Industry 18
Summary 20
Notes 20
2. A (Very) Simple Validation Example 21
Equipment Qualification 22
IQ/OQ/PQ 22
Documentation 25
Process Validation 26
Additional Validation Requirements 29
Summary 33
3. Why Is Validation So Confusing? 35
Why the GMPs Are Vague 35
The PDAs Role in Enforcing the GMPs 36
The Pharmaceutical Industry's Role in Interpreting the GMPs 37
Who Is Qualified to Perform Validation? 43
Summary 46
Notes 46
v
vi How to Sell Validatable Equipment to Pharmaceutical Manufacturers
4. What to Be Aware of Before Working on a Job
for the Pharmaceutical Industry 47
Things the Equipment Supplier Can Do More Easily
than the Pharmaceutical Company 51
Things Either Group (the Equipment Suppliers
or the Pharmaceutical Companies) Can Do 52
Things the Pharmaceutical Company Can Do More Easily
Than the Equipment Supplier 53
Summary 55
Notes 55
5. Providing Validatable Equipment: The Role of the Equipment Supplier 57
How the Equipment Supplier Can Help
with Equipment Qualification 58
Design and Construct Equipment According to GMP
and Company Requirements 59
Provide Documentation to Support Equipment Qualification 60
How the Equipment Supplier Affects the Cost
of Validatable Equipment 62
The Extent of the Equipment Supplier's Involvement 65
Summary 66
Note 66
6. Pharmaceutical Industry Requirements for Process Equipment
Design and Construction 67
Contact Surfaces 70
Materials of Construction 72
Common Materials Used 73
Materials to Avoid 75
Design and Construction of Pharmaceutical Process Equipment 75
Cleaning and Sanitization Considerations 76
Methods of Attachment 79
Contour 80
Valves 81
Elimination of Dead Legs in Water Distribution Systems 82
Penetrations into the Equipment (Ports) 83
Filters 84
Instrumentation (Measuring Devices) 85
Computerized and Automated Systems 86
Security of Control Systems 86
Separation of Process and Utility Streams 86
Drainage 87
Special Considerations for Cleanroom Equipment 88
Exterior Surfaces 89
Summary 89
Notes 90
Contents vii
7. Validatable Computer Systems 91
Types of Computer Systems 96
Solid State Controllers 96
Programmable Logic Controllers 97
Personal Computers 98
Functions of Computers in the Pharmaceutical Industry 98
Scope of Validation Needed for Computer Systems 98
How Much Validation Needs to Be Done? 100
Level of Confidence in Computer Systems 100
Importance of Computer Systems Applications 102
Requirements for Completing Computer Systems Validation 102
General Computer Systems Validation Practices 103
Step 1: Define What the System Is Supposed to Do 105
Step 2: Describe How the System Will Accomplish What It Is
Supposed to Do 107
Step 3: Select or Construct Appropriate Hardware That
Will Satisfy the Requirements and Specifications Defined
in Steps 1 and 2 109
Step 4: Develop Software That Will Satisfy the Requirements Defined
in Steps 1 and 2 109
Step 5: Install the System 119
Step 6: Release the System to the Pharmaceutical Company
and Let It Test It 122
Step 7: Provide Support As Needed to Keep the System
Running Properly 122
Key Points 124
Validatable Hardware 127
Validatable Software 126
Categorization of Software 129
Customized Software 129
Widely Distributed Software 130
Configurable Software 130
Specialized Software 131
Validation Requirements for Suppliers
of Computerized Equipment 133
Summary 136
Notes 136
8. Documentation: The Foundation of Good Manufacturing Practices 137
Rule #1 All Entries Must Be Made in Permanent Ink 138
Rule #2 Never Obliterate Data 138
Rule #3 All Documentation Must Be Signed 139
Rule #4 Original Records Are the Most Important 140
Rule #5 Use Templates and Forms 142
Rule #6 Leave No Missing Information 142
viii How to Sell Validatable Equipment to Pharmaceutical Manufacturers
Rule #7 Reference Procedures and Standards Whenever Possible 143
Rule #8 Drawings Should Be an Accurate Representation of the
Equipment Being Supplied to the Pharmaceutical Company 144
Rule #9 Provide All the Manuals with the Equipment 145
Rule #10 Provide All the Documentation in One Package 146
General Comments 147
Summary 147
Notes: 148
9. The Turnover Package 149
Elements of a Good Turnover Package: Contents 150
Elements of a Good Turnover Package—Purpose Behind the Information 152
Manuals 152
Parts Lists 153
Bill of Materials 154
Technical Specifications 154
Inspection Certificates 155
Passivation Records 156
Calibration Certificates 156
Mill Certificates 158
As-Built Drawings 159
Computer Systems Documentation 160
Test Records 162
Procedures 163
Summary 164
10. Providing Added Value Without a Lot of Extra Work 165
Step 1: Ask Customers Exactly What They Expect 165
Step 2: Be Up-Front about What You Know
and What You Can Do 168
Step 3: Get All the Facts You Need to Give Customers
What They Need 169
Step 4: Factor in Any Extra Work Required 170
Step 5: Have Written Procedures for Handling
Quality-Related Jobs 170
Step 6: Keep Good Records 171
Step 7: Use Standard Forms Whenever Possible 172
Step 8: Keep the Drawings Current 172
Step 9: Maintain Copies of Current Manuals
and Technical Information 173
Step 10: Follow Good Quality Practices for Design
and Development of Computer Programs 173
Step 11: Let the Pharmaceutical Companies Come in and See
What a Good Job You Are Doing 174
Contents ix
Step 12: Follow Up on All the Details (Even If They Don't Seem
to Be Important or Make Sense) 175
Step 13: Treat the Documentation with the Level
of Importance It Deserves 175
Step 14: Communicate Throughout the Project 176
Step 15: If You Provide Services to the Pharmaceutical Industry,
You Need to Follow Its Rules 176
Summary 177
11. Validation Hang-Ups: What to Watch Out for and How
to Avoid Them 179
Validation Hang-Up #1 Not Recognizing
the Need for Validation 180
Validation Hang-Up #2 Not Wanting to Confront Regulations 181
Validation Hang-Up #3 Raising Expectations beyond
What Can Be Delivered 182
Validation Hang-Up #4 Not Providing All the Documentation
in a Timely Manner 183
Validation Hang-Up #5 Not Providing Technical
Follow-Up Support 183
Summary 184
12. Validation Services Performed by Equipment Suppliers 185
How to Validate Pharmaceutical Process Equipment: Step-by-Step
Instructions for Preparing Validation Documents 187
Step 1: Write the Protocol 187
Step 2: Get the Protocol Approved by the Pharmaceutical Company 189
Step 3: Perform the Work According to the Protocol
and Document the Results 189
Step 4: Prepare the Report 190
Step 5: Get the Report Approved by the Pharmaceutical Company 191
How to Validate Pharmaceutical Process Equipment: Step-by-Step
Instructions for Conducting Equipment Qualification Studies 192
Conducting Installation Qualifications 193
Installation Qualification Documentation 197
Requirements for Operation Qualification 197
Functional Testing 198
Operational Testing 199
Eventful Testing 201
Documentation of Operation Qualification 202
Pointers for Conducting IQ and OQ 202
Summary 203
13. Conclusion 205
x How to Sell Validatable Equipment to Pharmaceutical Manufacturers
Attachments
1. Current Good Manufacturing Practices (cGMPs) 209
2. Documentation Examples 245
3. Example Procedure (SOP) 257
4. Project Planning Questionnaire 261
5. Example Turnover Package 267
6. Example IQ Protocol 301
7. Example OQ Protocol 321
References 341
Index 343
INTRODUCTION
If you are supplying or planning to supply manufacturing equipment to
pharmaceutical companies, it is important to have a good understanding of
what your customers need from you to meet government regulations. The
pharmaceutical industry is strictly regulated by the Food and Drug Admin
istration (FDA) to ensure the products they produce are safe and effective.
As part of these regulations, the processes and equipment used to produce
drug products must be validated before they can be produced for human
use. Validation is an essential step in assuring the quality of drug products.
This means the equipment must be validated before it is used to produce
any salable products. If it cannot be validated, it cannot be used.
What is validation? Who does validation? How is validation accom
plished? How much of this does an equipment supplier need to know? Don't
pharmaceutical companies handle validation? These are the questions that
will be covered in the chapters that follow.
Validation has been my occupation for almost 10 years. Since I started
in validation, I've held positions at pharmaceutical, medical device, and con
sumer products/over-the-counter companies. I've been involved in many
equipment purchase and start-up projects. Some went smoothly and some
were troublesome. A lot of the troubles were the result of validation issues.
Many times, validation issues were not considered as part of the pro
ject from the start. As a result, after the equipment was delivered and
installed, it couldn't be used because the validation was inadequate. In
these situations, a lot of time and money was spent trying to get everything
in order. At this point, validation can seem like a lot of extra work and
expense. I've been in heated discussions with equipment suppliers in which
the following statements were made, "Why do you need this? The equip
ment works doesn't it?" and "This is just extra paperwork to keep you
busy!" and "Isn't that your job—to validate this?"
xi