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PQE WORKSHOP: What's new in Computerized System Validation, June 2008

General principles of Computer System Validation

Jakarta, July 4th 2013

Workshop Computerized System Validation and Equipment

Qualification

Author: Federico Ceccarelli

Computer System Validation

Computer System Life Cycle

Validation Effort

Client vs Supplier

Validation Responsibility

How to Maintain the Validated Status

US CFR Part 11 vs. EU cGMP Annex 11

Agenda

Agenda

Computer System Validation

Computer System Life Cycle

Validation Effort

Client vs Supplier

Validation Responsibility

How to Maintain the Validated Status

US CFR Part 11 vs. EU cGMP Annex 11

Computer System Validation is the documented

evidence that a Computerized System, while

performing its intended functions consistently and

reliably, ensures the integrity of quality product data

What is computer system validation?

The most quoted definitions of validation process of a Computerized System come from the FDA: The collection and evaluation of data, from the process design state through commercial production, which establishes scientific evidence that a process is

capable of consistently delivering quality product.

Guidance for Industry, Process Validation: General Principles and Practices, January 2011.

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 attributes.

FDA Guideline on general principles of process validation, May, 1987

Validation does not prove that a SW application

works in any condition (to be ensured by SW Vendor

through his own Quality System)

Validation shows that the system does what you say

it does and is under control

Computer system validation target

CSV allows to ensure that:

The system does what is required to do

The system is in a documented state of control

Use of the system does not introduce any

violation of the regulation

What does CSV ensure?

Validation can increase the usability and reliability

of systems

Validation can result in: decreased failure rates

fewer corrective actions

less risk to patients and users

General Principles of Software Validation; Final Guidance for Industry and FDA Staff

Jan/11/2002 - Par. 3.4

Benefits of a good software validation

Why validate (1/2)

NOT just to satisfy regulations:

To gain knowledge of the system

To achieve in-depth knowledge necessary to

Control the system

To allow safe, effective changes to the system

To Recognize system failures

To investigate thoroughly system failures

Why validate (2/2)

More than just testing:

DEFINE the system

DESIGN the system

DEMONSTRATE performance of intended

function & does not perform unintended

function

DOCUMENT the system

Do I have confidence that

my results are complete

and accurate?

Problem Statement

Comment

Users need

documentation that

explains how to use the

system and how to

confirm that results are

accurate. Testing is one of

the biggest user

concerns.

Validation: end users point of view

Did the construction and

maintenance of the system

the company uses meet

regulations?

Problem Statement

Comment

Regulatory Agencies are

most interested in Quality

System and

documentation that

proves that standard

methodology were

followed during the

building and will be

followed in the

maintenance of the

system. Regulatory

Agencies wants to know

how problems are found

and fixed after the system

is in use in order to

maintain data integrity

Validation: regulatory inspectors point of view

The Computerized System is composed by:

The controlling system

The controlled process in an operating environment

(PICS/S - Good Practices For Computerised Systems In Regulated GxP Environments).

CSV scope

Validation Process shall be applied to the Computerized

System

OPERATING ENVIRONMENT

INFRASTRUCTURE (NETWORK)

COMPUTERIZED SYSTEM

SOFTWARE

HARDWARE

Firmware

COMPUTER SYSTEM (Controlling System)

OPERATING PROCEDURES AND

PEOPLE

EQUIPMENT

CONTROLLED FUNCTION OR PROCESS

(PICS/S - Good Practices For Computerised Systems In Regulated GxP Environments).

Computerized system

Definitions (1/2)

Process:

A set of specified, ordered actions required to

achieve a defined result.

System:

A group of related objects designed to perform or

control a set of specified actions

Function:

A set of specified, ordered actions that are part of a

process.

SYSTEM

FUNCTION

MENU

FUNCTION

A

FUNCTION

B

FUNCTION

C

PROCESS

START

COMPUTER

PRESS

FUNCTION A

ON MENU

TURN OFF

COMPUTER

FUNCTION

A

FUNCTION

INPUT

DATA

PRINT

DATA

STORE

DATA

PRESS

FUNCTION C

ON MENU

Definitions (2/2)

Every Computerized System shall be assessed to

determine its GxP critical impact

GxP critical systems

A computerized system is considered GxP critical if

it impacts, or has the potential to impact, the safety,

purity, identity, efficacy, strength, or quality of a

drug or device, or if it will perform a function

specifically required by GCP, GLP, GMP or GDP

regulations.

GxP:

x = L -> Good Laboratory Practice

x = C -> Good Clinical Practice

x = M -> Good Manufacturing Practice

x = D -> Good Distribution Practice

Validation Rationale (1/2)

Computerized Systems determined to have an impact on

pharmaceutical quality and/or patient safety must be

maintained in a validated status within the whole life-

cycle (i.e. from implementation to retirement)

Validation of a Computerized System is required if it is:

Used in the manufacture or processing, packaging, holding or distribution of products

Used in the collection, analysis or storage of data from clinical trials or product release and stability

studies

Used for processes concerned with drug safety Used for distribution of information in the event of

a commercial product recall, or in patient follow-up

of clinical trials

Subject to external audits or inspections by health authorities

Validation Rationale (2/2)

Prospective validation

Prospective Validation is establishing documented

evidence that a system does what it is intended to

do based upon a pre-planned protocol,

implemented prior to distribution of either a new

product or a product made under a revised

manufacturing process, where the revisions may

affect the products characteristics.

Retrospective validation

Retrospective Validation is establishing

documented evidence that a system does what it is

intended to do whereby historical data that has been

reviewed and analyzed can be used to support the

validation

VALIDATION

Prospective vs Retrospective Validation

Prospective Validation is not an option. The

Validation process must be part of the

implementation project.

NEW

SYSTEM

NEW SYSTEM IMPLEMENTATION

DEFINITION

DESIGN

TEST

GO-LIVE

Agenda

Computer System Validation

Computer System Life Cycle

Validation Effort

Client vs Supplier

Validation Responsibility

How to Maintain the Validated Status

US CFR Part 11 vs. EU cGMP Annex 11

Validation is

a PROCESS

not an event

Requirements

System

Selection

Specify

&

Design

Build Supplier

Testing

Validation

Testing

Operation

Do

cu

me

nta

tio

n

The life cycle concept of computer validation

Software life cycle

To build a case that the software is

validated requires time and effort.

The final conclusion that the software is

validated should be based on evidence

collected from planned efforts conducted

throughout the software life cycle

General Principles of Software Validation; Final Guidance for

Industry and FDA Staff January 11, 2002; Par. 2.4

System Build

related to

related to

related to

User Requirements Specification

Performance Qualification

Functional Specification

Operational Qualification

Installation Qualification

Design Specification

RISK ANALYSIS ON PROCESS

RISK ANALYSIS ON FUNCTIONS

Validation life cycle V-cycle

GAMP 5 Guideline

GAMP 5

A Risk-Based Approach to

Compliant GxP Computerized

Systems

This Guide applies to computerized systems used in regulated activities covered

by:

Good Manufacturing Practice (GMP) (pharmaceutical, including Active Pharmaceutical Ingredient (API), veterinary, and blood)

GOOD AUTOMATED MANUFACTURING PRACTICE

GAMP 5 Approach

GAMP 5

A Risk-Based Approach to

Compliant GxP Computerized

Systems

SYSTEM RISK

ASSESSMENT

FUNCTIONAL RISK

ANALYSIS

VALIDATION

EFFORT

TESTING

EFFORT

History of GAMP (1/2)

First Draft February 1994 Distributed to UK industry for comments

Second Draft January 1995 Incorporating comments from 31

companies.

Version 1.0 March 1995 As Second Draft, but incorporating EC GMP Annex 11

Version 2.0 May 1996 Revision and new content, incorporating further comments from

Europe and the USA

Version 3.0 March 1998 Revision and new content. Separation into User and Supplier Guides.

Addition of Volume Two

GOOD AUTOMATED MANUFACTURING PRACTICE

History of GAMP (2/2)

GAMP IV December 2001 Major revision and new content in line with regulatory and technological

developments. Broadened scope to

include regulated healthcare

industries. Greater coverage

GAMP V February 2008

(USA)

April 2008

(Europe)

Major revision providing a flexible and

robust quality risk-based approach to

compliant GxP regulated

computerized systems, based on a

scaleable life cycle from concept to

retirement. New information on topics

of special interest also provided

GOOD AUTOMATED MANUFACTURING PRACTICE

GAMP 5 Guideline INDEX (1/2)