gamp 4/5 prospective / retrospective qualification of ... · pdf file27/03/2009 slide 2 table...

GAMP 4/5Prospective / retrospective Qualification of water treatment plants)P. Dony31.03.2008

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Table of contents

1. GAMP 4 and GAMP 5 differences

2. CHRIST prospective Qualification strategy

3. CHRIST retrospective Qualification strategy

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� Why revision of GAMP 4:

� To align with the concepts and terminology of recent regulatory and industry

developments

� such as:

- ICH Q 9 (Annex 20)

- FDA: Pharmaceutical cGMPs for the 21st Century: A Risk based Approach

� Avoid duplication of activities

� Leverage supplier activities to the maximum possible extent, while still ensuring

fitness for intended use

� Scale all life cycle activities and associated documentation according to risk,

complexity and novelty

� Recognize that most computerized systems are now based on configurable

packages, many of them networked

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� Drivers for GAMP 5

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� Overview of the significant changes GAMP 4 to GAMP 5

� GAMP 5 now describes the whole life cycle (including: concept, project,

operation, retirement)

� GAMP 5 arranges the Quality risk management as a central element in all

phases of the life cycle

� GAMP 5 was aligned with the ASTM E2500 and the ISPE Baseline-Guide

“Commissioning and Qualification” terminology

� GAMP 5 now gives the suppliers a key role in the development processes and

in the operation processes

� GAMP 5 has simplified the GAMP categories, Chapters of the GAMP 4 which

describes special types of computer systems were canceled

� BUT: The GAMP 5 remains compatible with the principles in GAMP 4

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� Life Cycle

� The general simplified Life Cycle:

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� Life Cycle Phases

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� Quality Risk Management (QMS):

� “The QMS is a systematic approach for the assessment, control,

communication and review of risks to patient safety, product quality and data

integrity. It is an iterative process applied throughout the entire system life

cycle. Section 5 describes this approach and how the activities should be

based on good science and product and process understanding.”

� Benefit of the risk based approach:

� Better knowledge about the processes and because of that a better process

control (also described in ICH Q8 (QbD), ICH Q9 (QMS), ICH Q10 (PQS))

� Safeguard patient safety, product quality, and data integrity, while also

delivering business benefit

� A central element to reducing the validation effort by concentrating on the most

critical processes

� and therewith reducing the validation costs

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� Aligned terminology

� The classical nomenclature of IQ, OQ and PQ are not longer used in GAMP 5

� Implementation of the word “verification” instead of the classical nomenclature

� Focusing of the contents of the created documents not longer of the

nomenclature. But also the classical nomenclature can be used

� Unification of the following Guidelines:

- FDA: Pharmaceutical cGMPs for the 21st Century: A Risk based Approach

- ASTM E2500

- GAMP 5

- ISPE Baseline-Guide “Commissioning and Qualification”

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� Key role of the suppliers

� Ensuring compliance and fitness for purpose is the responsibility of the

regulated company

� The supplier gets more liberties, but also more responsibilities

� The supplier gets the liberty to carry out the system development in

accordance of accepted development- and quality management methods (e.g.

ISO 9000) without consideration of specific GxP requirements

� Documentation of the suppliers can be taken directly and without changing the

format in the validation documentation of the regulated company (no

duplication)

� Services of the suppliers should be overtaken considerable as possible (in

specification and verification processes)

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� Confrontation GAMP 4 and GAMP 5 referring to the suppliers role

Appendix O 2

Establishing and Managing Support Service

Appendix O 2

Example Procedure for the Production of a Service Level Agreement

Appendix M 6

Supplier Quality and Project Planning

Appendix M 2

Supplier Assessment

Appendix M 2

Guideline for Supplier Audit

Chapter 8.3

Effective supplier participation

Chapter 8

Management System for Suppliers of IT Systems

Chapter 7.2

Supplier good practice activities

Chapter 7

Supplier activities

Chapter 7.4.3

Supplier Assessment and Education

GAMP 5GAMP 4

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� GAMP 5 Main Body Structure

� Key Concepts

� Life Cycle Approach

� Life Cycle Phases

� Concept

� Project

� Operation

� Retirement

� Science Based Quality Risk Management

� Regulated Company Activities

� Governance for Achieving Compliance

� System Specific Activities

� Supplier Activities

� Efficiency Improvements

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� Main Changes of the GAMP 5 appendices

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� GAMP Software Categories

Custom software (supplier assessments rather

than audits

Custom software5

Configured software (supplier assessments

rather than audits)

Configurable software

packages

4

Non-configured softwareStandard software3

No longer used (Firmware is no longer

functionally distinguishable)

Firmware2

Ifrastructure softwareOperating system1

GAMP 5GAMP 4Category

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� Size of verification software category 3

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� Movements and Benefits

� Reduction of validation costs (as a result of the risk based approach

and a stronger comprehension of the suppliers activities)

� A better process acknowledgement (on side of the regulated company

and on side of the suppliers)

� More flexibility of improvements (simplification of the validation

process)

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� V-Model

URS

Requirements of the User

FDS

Affirmation of the Requirements

of the supplier

Technical Specifications

Manufacturing of the Equipment

PQ

OQ

IQ

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� The CHRIST Qualification Conception

� The validation shall show that the water treatment system is installed correctly

according to the design specification and that the system works correctly.

� The validation is divided in two sections:

� FAT Factory Acceptance Test

� SAT Site Acceptance Test

� In each section (FAT and SAT), both installation inspections (IQ) and functional

inspections (OQ) are carried out.

� In order to reduce the time needed for on-site qualification, as many

inspections and tests as possible are executed during the FAT, before the

system leaves the factory.

� CHRIST has a special test bed and can, in most cases, also carry out test runs

of the system before it is dispatched.

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� DQ-Documents:

� Order Confirmation (FDS) (or optional customized FDS)

� Risk analysis (FMEA iterative)

� Quality and project plan (QPP) (optional)

� Technical Specifications

� P&ID

� List of Components

� Hardware Specifications

� Circuit Diagram

� Hardware Design Specification (HDS)

� Software Specifications

� Functional Logic (FL)

� Software Design Specification (SDS)

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� Example P&ID

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� Example of Risk analyses (iterative)

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� IQ Tests during FAT

� 1. Inspection of the Mechanical Installation and the Documentation

� P&ID: Check that the water treatment system is built according to the P&ID

� Component list: Check that all components of the system are in accordance with the list of components

� Manuals and Data Sheets: Check manuals and data sheets from the sub-supplier

� Certificates for components: Check the certificates (which are specified in the list of components) for all components

� Dead-Legs: Check that no dead-legs are present on the product side (3d or 6d rule)

� Air gap to drain: Check by visual inspection that the pipe to drain leaves an air gap to the drainage.

� Welding documentation: Check that the welding documentation for the water treatment system (including certificates for pipes and fittings) is present and complete.

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� IQ Tests during FAT

� 2. Inspection of the Electrical Hardware (Hardware Acceptance Test)

� Inspection of the switchgear cabinet: Check that the inspection record sheet for the

switchgear cabinet is completely filled out and that the document is signed and

dated.

� Line test: Check that the line test inspection sheet (external cables, digital inputs

and outputs, analogue inputs and outputs) is completely filled out and that the

document is signed and dated.

� Main switch: Check the consequence of power failure (simulation through the main

switch)

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� OQ Tests during FAT

� 1. Inspection of the Software (System Acceptance Test)

� Functional logic: Check the software and program steps together with the related

controllers, special logics and system parameters according to the functional logic.

� Alarms: Check the alarms according to the functional logics.

� Password: Check the access authority for different password levels.

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� IQ Tests during SAT� 1. Inspection of the Mechanical Installation and the Documentation

� FAT Completion: Check if the retests and the deviations from the FAT are performed

� Documentation for the water treatment system: Check that the documentation for the system is present

� P&ID: Check that the system is built according the P&ID and that the items are marked with the correct P&ID number

� List of components: Check that all components of the system are in accordance with the list of components

� Air gap to drain: Check by visual inspection that the pipe to drain leaves an air gap to the drainage.

� Dead-Legs: Check that no dead-legs are present on the product side (3d or 6d rule)

� Gradients (for distribution system): Check that the piping of the loop has been installed with the requested downward gradient

� Drainability (for distribution system): Check that the loop can be drained at its lowest points.

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� IQ Tests during SAT

� 2. Inspection of the Electrical Hardware (if not already checked during

FAT)

� Check the external cables and the analogue inputs and outputs

� Main switch: Check the consequence of power failure (simulation through the main

switch)

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� OQ Tests during SAT

� 1. Inspection of the Software (System Acceptance Test)

� Software-Version: Check the software versions of the HMI / PLC program and for

the programming tools

� Backup: Preparation of a backup of the used program (Back-up disc or CD-Rom.)

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� OQ Tests during SAT� 2. Functional Tests

� Leaks test: Check the plant connections and the components for leaks

� Operation of the Softener: Check the performance parameter of the softener, logging of the main operating data

� Operation of the RO: Check the performance parameter of the reverse osmosis

� Operation of the EDI: Check the performance parameter of the EDI

� Operation of the dosing units (wherever applicable): Check the dosing units and the regulations

� Operation of the storage and distribution system components: Check the performance parameter of the components (e.g. ozone generator, ozone measurement, UV unit)

� Function of regulation circuits (wherever applicable): Check the regulation circuits of the system

� System parameter: Logging of all actual system parameter

� Water Quality: Check the water quality (conductivity, TOC * and Microbiological situation*(* = analysis by customer))

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� PQ Plan

� First phase

� Development of the operational parameters

� Development of the cleaning / sanitization procedures and frequencies

� Sampling should be daily after each step in the purification process and at each

point of use

� The sampling procedure for point of use sampling should reflect how the water is to

be drawn (e.g. if a hose is usually attached the sample should be taken at the end

of the hose)

� Length: two to four weeks

� At the end of this phase the firm should have developed its SOPs for operation of

the water system

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� PQ Plan

� Second phase

� Demonstration that the system will consistently produce the desired water quality

when operated in conformance with the SOPs

� Same sampling as in the first phase and for the same time period

� Length: also two to four weeks

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� PQ Plan

� Third phase

� Demonstration that the water system will consistently produce the desired water

quality when operated in accordance with the SOPs over a long period of time

� Any variations in the quality of the feedwater (seasonal variations) that could affect

the operation and ultimately the water quality will be picked up

� Sampling is performed according to routine procedures and frequencies

� For WFI systems the samples should be taken daily from a minimum of one point of

use, with all points of use tested weekly

� Length: one Year

� The last part of the validation is the compilation of the data, with any conclusions

into the final report.

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� PQ Plan structure

� Introduction

� Intention of the performance qualification

� Abbreviations

� Manifestations at execution of the performance qualification

� Table of persons participating in the inspection

� Execution of the PQ

� Preface

� Point of use / sampling points

� Analyzing Parameters

� Water sampling from the system

� Arrangements

� Off-limit conditions (OOS/OOT Results)

� Summary report

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� When you have to do a retrospective Qualification

� Existing Systems which are in operation without any qualification up to

now

� Existing Systems which are in operation without an adequate

qualification up to now

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� Condition contrary to regulations

� only acceptable for well-established processes

� inappropriate where there have been recent changes in the composition of the

product, operating procedures or equipment

� should be based on historical data (which are evaluated in a protocol)

� This data could include process control charts, maintenance log books,

process capability studies, finished product data

� Basically retrospective qualifications has the same inspection scope like

prospective qualification

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� Procedure of a retrospective qualification

� Audit of the existing high purity water system

� Qualification Check

� Documentation Check

� Mechanical Check

� Electrical Check

� Functional Check

� Software Check

� Report of the audit

� Description of the System

� Description of the critical results

� Scaling of the critical results

� Further approach (required qualification documents and proposal to eliminate the critical points)

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� Qualification Check

� Has been carried out a qualification before?

� When the last qualification was carried out?

� Has been all deviations removed?

� Was the qualification risk based and adequate realized?

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� Documentation Check

� SOP’s

� Analytical studies (Monitoring of the critical batch relevant parameters)

� Electronic records

� Log books

� Drawings (R&I, Layout, circuit diagram)

� List of components

� Manuals and datasheets

� Certificates

� Operating Instructions (process descriptions)

� Welding documentation

� Staff training

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� Mechanical Check

� Design of the system and system rating

� Marked items

� Air gap’s

� Dead-Legs

� Gradients (for distribution system)

� Drain ability (for distribution system)

� Materials of the critical system components (visual check)

� Welding

� Connections

� Design of the Critical components (valves, heat exchangers, Pumps)

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� Electrical Check

� Hardware Design Specification

� Line test (AI/AO/DI/DO)

� Switchgear cabinet

� External cables

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� Functional Check

� Functional Logic

� System parameters

� Alarm parameters

� Controllers

� Calibration

� CIP/SIP/DIP Functions

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� Software Check

� Software Design Specifications (including software classification)

� Software reviews

� Password

� GAMP 4/5 conformity

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� Possible arrangements to get GxP conform status (some examples)

� If no data about the material of the critical piping and components: Non-

destructive tests

� If no, or incomplete, or inadequate welding documentation:

Try to make on critical welding seams some endoscopic photos

� If no functional logic:

Document the function (including process measuring and control technology)

� If no circuit diagram:

Draw an actual circuit diagram

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� Possible arrangements to get GxP conform status

WFI distribution System:

�No adequate GxP conform weld

seam accomplishment

�In this case cut out this area

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� Possible arrangements to get GxP conform

status

Pure Steam System:

� No GxP conform ball valves

� No adequate GxP conform weld seam

accomplishment

� No GxP conform connections

� In this case make a new POU:

Composed of:

Diaphragm Valves

GxP conform steam trap

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� Possible arrangements to get GxP conform

status

WFI Distribution System:

� Bad weld seam accomplishment

� In this case cut of both POU and make

new ones

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� Starting to write the following validation Protocols (like prospective

strategy):

� VMP

� URS (target state)

� FDS (actual state)

� RA (Risk based approach very necessary)

� RA report

� IQ

� OQ

� PQ

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� Summary

� The retrospective Qualification is a validation process which must be individual

considered (dependent of the system and it’s condition)

� Approach of a retrospective Qualification must be described by the regulated

company (SOP, SVMP)

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Thank you for your

Concentration!!!!

Any Questions????