Validation Terminology

ACME LABORATORIES LTD

29th MAY 2008

ACME LABORATORIES LTD GMP TRAINING 1

Validation of Pharmaceutical
Processes

Terminology and
definitions

ACME LABORATORIES LTD GMP TRAINING 2

 Objectives:

By the end of this session you should

Know about how various document types

used in validation fit together
The overall terminology you will come across.

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 Validation Definitions

What is it ??
What isnt it ??

No idea !
Havent a clue

Search me !!

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 Definition of Validation

Making Valid
Ratifying
Confirming
Substantiating
Corroborating
to give legal force or
official confirmation to.
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Validation Definitions

US Pharmaceutical
Manufacturers Association
...a formal programme to
demonstrate that a
specific product can be
reliably manufactured by
the designed process.

ACME LABORATORIES LTD GMP TRAINING 7

 Validation Definitions

EC Guide.........
...qualification is the action of proving that any
equipment works correctly and actually leads to the
expected results.
The word Validation is sometimes widened to
incorporate the concept of qualification.

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 Validation vs. ISO 9000

ISO 9000 series standards ensure products are

consistently manufactured to the requirements of
the customer
Validation ensures products are consistently
manufactured to the requirements of cGMP

ACME LABORATORIES LTD GMP TRAINING 9

 Validation Definitions

...Generally....

Validation should be carried

out throughout a project..
and not just at the end. If it
is added as an after thought
it could cost 10x as much.

ACME LABORATORIES LTD GMP TRAINING 10

Validation Flowchart
Change Control

Validation Master Plan

User Review and
Requirements Approval
Design
Qualification
Pre Commissioning Review and
Approval
Equipment Logs
Installation
Qualification Review and
Approval
Calibration
Commissioning
Operation
SOPs & Training Qualification
Review and
Manufacturing Approval
Instructions Experimental work
Performance
Packing Instructions Qualification
Review and
Approval
Summary
Validation
Report Validation &
Product Review
ACME LABORATORIES
System LTD GMP TRAINING
Normal Production 11
Change Revalidation
 Validation V model and Life Cycle
Product Reviews

Performance
Review Final
Yes Routine Use/ Validation
Changes required Report
??? Manufacture

No PV
Process Protocol
Validation PQ
User Requirement
Specification Performance Protocol/
Qualification Report
Testing
Validation OQ
Master Protocol/
Functional Functional
Plan Report
Specification Testing

Commissioning IQ
Protocol/
Design Installation Report
Specification Testing

DQ
Protocol/ Build/
Report
Install

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Definitions

VMP
URS PQ
FS Calibration
DS Commissioning
DQ SOP
IQ ....etc......etc.
OQ

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 Validation Master Plan (VMP)

A VMP is a structured, detailed plan of work which

provides information about how all of the validation
work on a project is going to be controlled

ACME LABORATORIES LTD GMP TRAINING 14

 User Requirement Specification (URS)

Detailed statements, approved by the

customer department, which define what is
required by the project
These should be sufficiently detailed to
enable a specification to be drawn up.

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 Functional Specification (FS)

Description of the system/equipment to be supplied

in terms of the functions it will perform and facilities
required in order to meet the requirements as
defined in the URS

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 Design Specification D(D)S

The Design Specification or Detailed Design Specification

defines the physical attributes of a system (required to
meet the functional specification) in sufficient detail to
enable something to be built

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 Design Qualification (DQ)

The first element of the validation of new

facilities, systems or equipment
Compliance of the design with GMP
- UK Orange Guide

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 Design Qualification (DQ)

the documented verification that the proposed

design of the facilities, systems and equipment is
suitable for the intended purpose
-EC Guide

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 Installation Qualification (IQ)

should be performed on new or modified

facilities
Should include;
Equipment, piping, services and instruments
Supplier operating and maintenance
instructions
Calibration
Materials of construction
UK Orange guide

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 Installation Qualification (IQ)

Documented verification that the facilities,

systems and equipment, as installed or modified,
comply with the approved design and the
manufacturers recommendations
- EC Guide.

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 Installation Qualification (IQ)

Basically..
At static completion
. Youve got what you asked for and were
told what you would get!

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 IQ Examples

Room data sheets

Equipment data sheets
As built drawings
Operation and Maintenance manuals.

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 Calibration

Demonstrating that a measuring

device produces results within
specified limits of those
produced by a reference
standard over an appropriate
range of measurements.

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 Calibration
The set of operations which establish, under
specified conditions, the relationship between values
indicated by a measuring instrument or measuring
system, or values represented by a material measure,
and the corresponding known values of a reference
standard.
- EC Guide

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 Calibration

List of critical instruments

Summary of test method
Record of results which will
eventually determine the
maximum time between checks

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 Commissioning

A well planned,
documented and managed
engineering approach to
the start-up and turnover of
facilities, systems and
equipment to the End-User
that results in the safe and
functional environment that
meets established design
requirements and stake-
holder expectations - ISPE

ACME LABORATORIES LTD GMP TRAINING 27

 Commissioning

Important -
This work should produce documentation of a
quality suitable for use during the FDA/MCA
inspections.....
Who does the work......??
General Systems
Specialist Systems
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 Operational Qualification (OQ)

Performed after IQ
Include;
Tests developed from knowledge or process and
equipment
Encompass lower and upper operating conditions
and worst case.
UK orange guide

ACME LABORATORIES LTD GMP TRAINING 29

 Operational Qualification (OQ)

The documented verification that the facilities,

systems and equipment, as installed or
modified, perform as intended throughout the
anticipated operating ranges
-EC Guide

ACME LABORATORIES LTD GMP TRAINING 30

 Operational Qualification (OQ)

Protocols and reports designed to show that a

system or sub-system performs as intended
throughout the anticipated operating ranges.

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 OQ Examples

Manufacturing
Services:
equipment
HVAC Granulators
Water(s) Mixers
Gases, Tablet presses
Filling machines

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 Commissioning vs. OQ

Both relate to Dynamic

Completion
Overlaps ?
Gaps?
Commissioning &
Validation Guide ISPE

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 Standard Operating Procedures (SOPs)

Written approved instructions which govern all

production operations
They are the details of the who, what, when
and how of general policies.

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 SOPs - Style

Governed by one group

Imperative style
Short, simple paragraphs
NOT PROSE
Beware of JARGON... explanations necessary.

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 Training Requirements

All relevant persons

Written, approved programmes
At start and continuing
Assessment
Records.

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 Analytical Method Validation

Analytical Methods must be demonstrated to be

consistently capable of meeting the required
precision, accuracy and reproducibility. Linked to
product specification and required level detection.

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 Cleaning Validation

Cleaning validation is documented evidence that an

approved cleaning procedure will provide
equipment, which is suitable for processing
medicinal products.
- EC Guide

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 Performance Qualification (PQ)

Protocols and reports intended to produce

documented evidence that a system
satisfies its intended purpose

..... Product related work .....

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 Performance Qualification (PQ)

the documented verification that the

facilities, systems and equipment, as
connected together, can perform effectively
and be replicated, based on approved
process method and product specification
- EC Guide

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 You may have noticed..

We havent mentioned
..The Product !!!

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 Experimental / Trial Work

Use the Planned Change Procedure if trials for

a change in:
Product reformulations
Process parameters
Equipment
Components
Procedures

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 Process Validation

The documented evidence that the process,

operated within established parameters, can
perform effectively and reproducibly to produce a
medicinal product meeting its predetermined
specifications and quality attributes
- EC guide

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 Process Validation

establishing documented evidence which

provides a high degree of assurance that a specific
process will consistently produce a product meeting
its pre-determined specifications and quality
characteristics
- FDA Guidelines 1987 (re-printed 1993)

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 What do you do about it??

You put the information into.

a Validation Master Plan

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From OQ to beneficial production

Operational Qualification May comprise OQ1 and OQ2

Analytical Methods Validation For methods used in PQ, CV and PV

Performance Qualification Applies to utilities only

Experimental Work To optimise the process

Process Validation Applies to utilities only

Cleaning Validation Once the process is proven to work

Process Validation Remaining batches

Beneficial Production
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Terminology
URS Specification
DQ Design Qualification
IQ Handover checking
OQ Static checking
Experiments Pilot, Scale-up batches
Calibration Instrument checking
Protocol Method statement; programme
Snag list Deficiency report; punch list

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 Summary

In this presentation we have discussed:

Terminology used within validation work

How all the aspects of validation work fit
together.

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