TITOLO SLIDE Testo Slide General principles of Computer System Validation Testo Slide Testo Slide

Workshop Computerized System Validation and Equipment Qualification

Jakarta, July 4th 2013

Author: Federico Ceccarelli

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

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

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

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

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

Computer system validation target

Validation shows that the system does what you say it does and is under control

Validation does not prove that a SW application works in any condition (to be ensured by SW Vendor through his own Quality System)

What does CSV ensure?

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

Benefits of a good software validation

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

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

Validation: end users point of view

Problem Statement Do I have confidence that my results are complete and accurate?

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: regulatory inspectors point of view

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

Problem Statement

Did the construction and maintenance of the system the company uses meet regulations?

Comment

CSV scope

Validation Process shall be applied to the Computerized System

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).

Computerized system

SOFTWARE

OPERATING PROCEDURES AND PEOPLE EQUIPMENT CONTROLLED FUNCTION OR PROCESS

HARDWARE Firmware COMPUTER SYSTEM (Controlling System)

INFRASTRUCTURE (NETWORK)

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

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.

Definitions (2/2)
PROCESS START COMPUTER PRESS FUNCTION A ON MENU PRESS FUNCTION C ON MENU TURN OFF COMPUTER

SYSTEM FUNCTION MENU FUNCTION A FUNCTION B FUNCTION C

FUNCTION FUNCTION A INPUT DATA PRINT DATA STORE DATA

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.
Every Computerized System shall be assessed to determine its GxP critical impact 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 lifecycle (i.e. from implementation to retirement)

Validation Rationale (2/2)

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

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

Prospective vs Retrospective Validation

Prospective Validation is not an option. The Validation process must be part of the implementation project.
NEW SYSTEM IMPLEMENTATION DEFINITION NEW SYSTEM DESIGN VALIDATION 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

The life cycle concept of computer validation

Requirements

System
Selection

Documentation

Validation is a PROCESS

Operation Specify & Design

not an event
Validation Testing

Supplier
Testing

Build

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

Validation life cycle V-cycle

User Requirements Specification

RISK ANALYSIS ON PROCESS

related to

Performance Qualification

Functional Specification

RISK ANALYSIS ON FUNCTIONS

related to

Operational Qualification

Design Specification

related to System Build

Installation Qualification

GAMP 5 Guideline

GAMP 5 A Risk-Based Approach to Compliant GxP Computerized Systems

GOOD AUTOMATED MANUFACTURING PRACTICE
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)

GAMP 5 Approach

GAMP 5 A Risk-Based Approach to Compliant GxP Computerized Systems

SYSTEM RISK ASSESSMENT VALIDATION EFFORT

FUNCTIONAL RISK ANALYSIS TESTING EFFORT

History of GAMP (1/2)

GOOD AUTOMATED MANUFACTURING PRACTICE

First Draft Second Draft Version 1.0 Version 2.0

February 1994 January 1995 March 1995 May 1996

Distributed comments Incorporating companies.

to

UK

industry from

for 31

comments

As Second Draft, but incorporating EC GMP Annex 11 Revision and new content, incorporating further comments from Europe and the USA Revision and new content. Separation into User and Supplier Guides. Addition of Volume Two

Version 3.0

March 1998

History of GAMP (2/2)

GOOD AUTOMATED MANUFACTURING PRACTICE

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

GAMP 5 Guideline INDEX (1/2)