CGMP Complete

8/18/2019 CGMP Complete

1/128

The Institute of

Quality Assurance

PharmaceuticalQuality Group

A Guide to the GMP requirementsof PS 9000:2001 Pharmaceuticalpackaging materials


2/128

The Institute of Quality Assurance

Pharmaceutical Quality Group

PS 9004

A Guide to the GMP requirements

of PS 9000:2001 Pharmaceutical packaging materials

September 2004

i


3/128

ii


4/128

P S

9 0 0 4

g u i d

e P S 9 0 0

4 g u i d e

PS 9004 guide

ISO 9000

+

GMP

for Pharmaceuticalpackaging materials

=PS 9000

Figure 1. Model of PS 9004: a Guide to the GMP requirements of PS 9000

iii

The symbol is used in Part 1 to identify risk areas.


5/128

iviv

ISBN 0-906810-79-5

PS 9004: 2004

For further information about the Pharmaceutical Quality Group (PQG) and

any additional information or updates on PS 9000 or PS 9004 visit the PQG

website on: www.pqg.org

PS 9004 is available from:

IQA Information Service

12 Grosvenor Crescent

London SW1X 7EE

Tel: + 44 (0)20 7245 6722

Fax: + 44 (0)20 7245 6788

e-mail: [email protected]

website: www.iqa.org


6/128

v

COPYRIGHT

PS 9004 copyright

© 2004 Institute of Quality Assurance (IQA)

This PS 9004 guide is copyright protected by IQA/Pharmaceutical Quality

Group(PQG). However in pursuit of their objectives to promote quality

throughout the pharmaceutical manufacturing and supply industries,

permission is given to use the contents for quality system improvement

in education, training, auditing or for certification purposes, provided

acknowledgement of the source of the material (PS 9004 IQA/PQG Copyright)

is given. Reproduction,storage in a retrieval system,transmission in any form

or by any means,electronic, photocopying, recording or otherwise FOR ANY

OTHER PURPOSE without prior permission being secured is prohibited.

Requests for permission to reproduce should be addressed to the IQA at the

address below:

IQA Information Service

12 Grosvenor Crescent

London SW1X 7EE

Tel: + 44 (0)20 7245 6722

Fax: + 44 (0)20 7245 6788

e-mail: [email protected]

Reproduction may be subject to royalty payments or a licensing agreement.

Violators may be prosecuted.

v


7/128

vi


8/128

vii

MHRA FOREWORD

The EU Guide to Good Manufacturing Practice (GMP) emphasizes the need for

pharmaceutical manufacturers and assemblers to ensure that the packaging

materials that they use are of the appropriate quality. Not only is this in the

interests of patient safety, but also in the pharmaceutical industry where

the increasing use of automated packaging processes relies heavily on the

consistent quality of packaging components.

Each year the Medicines and Healthcare products Regulatory Agency

(MHRA) receives and investigates a number of reports of quality defects

concerning medicinal products. A significant proportion of these concern

packaging errors, some of which are attributable to the use of packaging

materials not of the desired quality. The introduction of PS 9000 in 2001 by

the Pharmaceutical Quality Group of the Institute of Quality Assurance was

a key step in promoting the understanding of GMPs relevant to the suppliers

of packaging materials to the pharmaceutical industry. PS 9000 focused on

the development and implementation, by suppliers, of a quality management

system designed to provide assurance of the quality of their products and to

enhance customer satisfaction. Its contribution was welcomed by both industry

and the Regulator. PS 9004 is aimed at increasing the awareness of the quality

management system requirements embodied in PS 9000. This comprehensive

and easy to follow guide explains further the GMP requirements of PS 9000.

It adopts a risk assessment approach to the identification and implementation

of preventive action and uses case studies to illustrate areas of GMP risk.

The MHRA encourages the introduction of PS 9004 designed to improve

product and service quality in the supply of packaging materials for medicinal

products, for the benefit of patients and the pharmaceutical industry as a

whole.

John Taylor Quality and Systems Manager

Inspection and Enforcement Division, MHRA


9/128

viii


10/128

ix

GENERAL INTRODUCTION

What is PS 9004?

This guide aims to assist suppliers of pharmaceutical packaging materials to

understand and implement the Quality Management System (QMS) of ISO

9001 and the application standard of PS 9000. It supplements the following

documents:

• ISO 9001 which specifies the requirements of the international QMS

standard

• ISO 9004 gives guidance on ISO 9001

• PS 9000 is an application standard written by the PQG for suppliers of

pharmaceutical packaging materials that integrates ISO 9001 and ISO

9004 together with additional Good Manufacturing Practices (GMP)

requirements particular to these suppliers

Companies complying with PS 9000 will comply with ISO 9001 and also the

additional GMP requirements endorsed by the highly regulated pharmaceutical

industry.

This guide is constructed around the clause structure of PS 9000 (and therefore

ISO 9001) to:

• clearly explain the GMP requirements of PS 9000

• list many of the risk areas associated with packaging processes and identify

relevant ISO 9001 and PS 9000 clauses

• provide examples of process inputs and process outputs typical of suppliers

of pharmaceutical packaging materials, and relate these to the QMS

requirements of ISO 9001 and the additional GMP requirements of PS

9000

• give examples of actual case histories of problems arising from the supply of

defective pharmaceutical packaging materials and where the consequences

would have been avoided by correct application of the GMP requirements

of PS 9000. These case histories help to explain the requirements and

provide a valuable training resource


11/128

x

How to use this Guide

PS 9004 has been organized in the following way:

• Part 1 consists of a selection of process schematics, illustrating typical

operations of a packaging supplier, and giving examples of some of the

more significant risks caused by inadequate manufacturing practices

• Part 2 gives guidance on the clauses of PS 9000, by taking the user through

each major section and providing examples to illustrate suggested process

inputs and outputs

• Annex A gives expanded explanatory notes on several key concepts used in

PS 9000

• Annex B gives a listing of other external regulatory references, which are

the background to pharmaceutical GMP and which are directly relevant to

PS 9000 requirements

• the text is primarily black but blue is used for PS 9000 related GMP text

• red text is used to highlight the ‘Risk Areas’

The user can cross refer between the schematics in Part 1 and the process

information in Part 2. In addition, the user can move from Part 2 to the additional

explanations in the annexes.

The annexes contained within this Guide are a stand-alone explanation of key

concepts and external GMP references. The PS 9000 cross-references are for

illustrative purposes and are not a definitive list of clauses or references.

The How to use section, which follows the contents list, shows the user how to

navigate between the different sections of the Guide.

As the range of organizations that may implement PS 9000 is great, both in

terms of size and type of business, the guidance given here is illustrative and

advisory.

Why was the PS 9004 Guide written?

There are three main reasons:

• to guide professional quality specialists towards the implementation and

inspection of a Quality Management System (QMS) in accordance with PS

9000

• to support the training of all the various stakeholders in the PS 9000 process

(top management, quality professionals, staff at all levels of packaging


12/128

xi

material suppliers and their customers)

• to provide those people who are not quality specialists with a better

understanding of the aims, objectives and implementation of PS 9000

How was the PS 9004 Guide written?

A group of experienced quality professionals selected from the packaging supply

industry and pharmaceutical customers was recruited by the Pharmaceutical

Quality Group Partners Team and given the task of preparing this Guide.

Many of the people who contributed to the writing of PS 9000 also participated

in the creation of this Guide.

Specific acknowledgements are given for the contributions of the

following people:

Roy Evans PS 9004 Team Leader

David Abraham Supplier

Ian Harwood Pharmaceutical

Jill Jenkins Pharmaceutical

Daniel Peek Supplier

Richard Rowlett Supplier

Mike Shorten Pharmaceutical

Steve Taylor Pharmaceutical

Additional contributions:

Caroline Fowler Pharmaceutical

Peter Gough Pharmaceutical

Ian Holloway Regulator

Steve Merrit Pharmaceutical

Ashley McCraight Consultant

Jeff Monk Training

Dominic Parry Training

Steve Pike Accredited certification

Norman Randall Consultant

Trevor Stabb Consultant

Paul Stockbridge Consultant

QA review:

Tony Harper Consultant and accredited certification

Afshin Hosseiny Consultant


13/128

xii

QA review (con’t):

Jean Lanet Consultant

Iain Moore Supplier

Steve Moss Pharmaceutical

Ashok Chand Pharmaceutical

John Turner Consultant

The PQG Partners Team and Steering Committee:

Roy Evans

Tony Harper

Femi Ibironke

Jill Jenkins

Ashley McCraight (PT Chairman)

Steve Moss

Norman Randall (SC Chairman)

Ian Richardson

In addition, the PQG is appreciative of the management of Patheon UK

Limited. for the use of their resources and facilities.


14/128

xiii

CONTENTS

Section Page

How to use this guide xv

Part 1 – Process schematics and case studies 1

Overview of business processes 2

Schematic 1 Top level business processes 2

Schematic 2 From the customer 4

Schematic 3 Planning 6

Schematic 3 (a) Warehouse (purchased materials and in-process) 8

Schematic 4 Preparation 10

Schematic 4 (a) Print impression media controls 12

Schematic 5 Production 14

Schematic 6 Checking and final release 16

Schematic 7 Distribution 18

Case studies 21

Part 2 – Guidance on PS 9000 GMP clauses 35

Clause 4 Quality management system 37

Clause 5 Management responsibility 39

Clause 6 Resource management 45

Clause 7 Product realization 49

Clause 8 Measurement, analysis and improvement 59

Clause 9 Contamination control 66

Clause 10 Printed materials 68

Clause 11 Origination/artwork 70

Clause 12 Print impression media 72

Clause 13 Print and conversion processes 74


15/128


16/128

xv

HOW TO USE THIS GUIDE

STEP 1

Choose a schematic from the ‘Overview of business process’ diagram in Part 1 of

this guide. (e.g. Schematic 3(a) is illustrative)

STEP 2

From your schematic, choose a particular stage of the process to examine, e.g.

Store material (see below).

SCHEMATIC 3 (a) - WAREHOUSE

STEP 3

Consider the Risk Areas shown in red and the real life case study (if shown) - these

are detailed at the end of Part 1, following the schematics.

Deliverychecks

• Document errors

• Missing

documents

7.4.3

7.5.3

Qualityinspection

• Labelling errors

• Incorrect goods

7.4

7.4.3

Storematerial

• Pest

Infestation

Case study G

7.5.5:

Preservationof product

9:

Contamina-

tion control

Issuematerial

• Incorrect

materials

7.5.3

See Part 2

for more

details

Risk areas


17/128

xvi

STEP 4

Using the references shown in the schematic, move to the corresponding section

in Part 2, entitled ‘Guidance on PS 9000 GMP clauses’. This gives reasons for the

‘extra’ GMPs and shows examples of processes, inputs and outputs.

General synopsis: Clause 9 Contamination control

The capability of facilities and equipment, achieved through their design, location,

etc.

Reasons for the ‘extra’ GMP requirements

The highest priority of the pharmaceutical industry is... etc.

Process inputs Processes Process outputs

and evidence

Cross refer to

Schematic/Annex

Specification

for design of

new facilities,

processes, or

environment

Specialistsupport for

pest control

Standards for

environmental

conditions

Processes which

identify/control:

• operating areas

• pest control

• cleaning proce-

dures

Records of:

• processing

• cleaning

schedules

• material disposal

• incidents/audit

reports

Schematic 3(a)

Schematic 4(a)

Schematic 5

Annex A - all parts

STEP 5

Use the cross references to move back to a relevant process schematic, alterna-

tively refer to Annex A or B for further guidance.

ANNEX A

Additional Explanation of Key Concepts

ANNEX B

Other external GMP references.


18/128

1



PS 9004



PART 1 - PROCESS SCHEMATICS

PS 9000 GMP references are reproduced in blue

Risk areas are reproduced in red


19/128

2

OVERVIEW OF BUSINESS PROCESSES

Schematic 1: Top level business processes

Schematic 2:From the customer

Schematic 3:Planning

Schematic 4:Preparation

Schematic 3 (a):Warehouse

Schematic 4 (a):Print impressionmedia controls

SCHEMATIC 1: TOP LEVEL BUSINESS PROCESSES

Quality management system

Managementcommitment

• Inadequate

incorporationof PS 9000

requirements

• QMS not

communicated

and/or

supported

by senior

management

4 QMS

5.1 Management

commitment

5.5

Responsibility,

authority andcommunication

Objectives

• Unclear

businesstargets/goals

• No clear

direction as

objectives not

published

5.3 Quality

Policy

5.4 Planning

Resourceallocation

• Too few people

for qualitycompliant

operation

• Wrong/

inadequate

equipment

• Inadequate

premises

• Inadequate

training

6.1 Provision of

resources

6.2 Human

resources

Refer to the hypothetical examples which

are located after the schematics.

See Part 2

for more

details

Risk areas


20/128

3

Schematic 5:Production

Schematic 6:Checking and finalrelease

Schematic 7:Distribution

This diagram shows the main business processes from customerrequirements through to delivery of final product and provides an indexto the schematics

Audit andmeasurement

• Inadequate

performancemeasures

• Poorly controlled

processes

• Unreliable

information for

management

decisions

• Poor compliance to

internally established

processes/ procedures

• Insufficient proof

of continuous

improvement

8.1 Measurement,

analysis and

improvement -

general

Managementreview

• Quality System

measures notreviewed

• Lack of senior

management

involvement/

leadership

• No continual

process

improvement

5.1 Management

commitment

5.6 Management

review

8.5 Improvement

Quality management system

Feedback/communication


21/128

4

SCHEMATIC 2: FROM THE CUSTOMER

Organization Customerrequest/ requirements

• Requirements

unclear

• Requirements

incorrectly

specified

• Requirementsmisunderstood

• Requirements

incorrectly

accepted

See case study A

5.2 Customer

focus

7.2 Customer-

related processes

Supplyrequirements(what, how,when)

• Unclearly

specified

• Failure to meet

customer

expectation• Rejection by

customer

Customerdesign

• Poor design

• Inadequate detail

• Failure tofunction

• Poor

performance at

customers site

• Rejection by

customer

• Potential risk to

patient

• Inadequate

testing/validationSee case studies

A and B

Feedback

7.2 Customer-related processes

7.3 Design and development

See Part 2

for more

details

Risk areas

Refer to the case studies

which are located after

the schematics.


22/128

5

Assessmentof capability

• Incorrect

assessment

of capability

e.g. resource,

technology,

systems,

environment• Fail to meet

delivery/quality

6.1 Provision of

resources

6.3 Infrastructure

6.4 Work

environment

7.1 Planning

of product

realization

Agreedcontract/ agreementand confirmedorder

• Lack of formal

contract/

agreement

• Failure toagree contract

requirements

• Poor

communication

7.2.3 Customer-

related processes

Planning


23/128

6

SCHEMATIC 3: PLANNING

Receive orderfrom customer

Order review andcustomer feedback(where required)

• Incorrect specification

chosen

• Inadequate

communication with

customer

• Order details incorrect• Supply incorrect product

• Supply error (quantity/

schedule)

• Proof approval error

• Specification not

approved

See case studies

C and D

5.2 Customer focus

7.2 Customer-related

processes

7.3 Design and

development

Availability checkson documentation,materials, toolingand equipment

• Incorrect material checked

or issued (e.g. wrong foil

gauge)

• Wrong print media

(version or item)• Non-availability of

equipment (e.g.

maintenance/validation

status)

• Unapproved production

process (e.g. not

approved by customer)

• Unsuitable/unapproved

material/changes

• Missing/incorrect

documentation (e.g.

missing mould inspection

record)

7.4 Purchasing

7.5 Production and service

provision

11 Origination/artwork

12 Print impression media

See Part 2

for more

details

Risk areas



the schematics.


24/128

7

Purchasing and printmedia provision

• Inadequate supplier

control

• Nonconforming

purchased materials or

service

• Inability to obtain raw

material• Inadequate security (e.g.

printing plates)

• Insecure data links (e.g.

validation of ISDN link)

• Incorrectly identified

materials (e.g.

mislabelling of stock

from supplier)

See case study E

4.2 Documentation

requirements

7.4 Purchasing

8.3 Control of

nonconforming product



Production scheduleand feedback fromproduction

• Inadequately defined

plan/schedule (e.g.

insufficient time for

line clearance or

maintenance)

• Inadequate programmetime to follow procedures

• Problems in production

7.1 Planning of product

realization


provision

8 Measurement, analysis

and improvement

Preparation for start of production

Feedback


25/128

8

SCHEMATIC 3 (a): WAREHOUSE (purchased materials and in-process)

Delivery from supplier/sub-contractor

Deliverydocumentation andoff-loading checks

• Errors not identified

between delivery

documentation &

purchase order

• Missing delivery/QC

documentation• Transit damage or wet

boxes not identified

before off-loading

• Incorrect goods

7.4.3 Verification of

purchased product

7.5.3 Identification and

traceability

Goods checks andquality inspection

• Inadequate checks

performed

• Labelling errors not

identified

• Incorrect goods sent

• Rogue box within delivery

• Inadequate batch coding• Non representative sample

taken or provided

• Transit/water damage not

detected

• Inadequate packaging/

sealing not detected

• Incorrect quality status

input to system

See case study F

7.4 Purchasing

7.4.3 Verification of

purchased product

See Part 2

for more

details

Risk areas



the schematics.


26/128


27/128

10

SCHEMATIC 4: PREPARATION

Production

plan

Preparation/

pre-productionchecks ofpurchased rawmaterials

• Error in checking

raw material

• Quality status

incorrect

• Availability status

incorrect

Materials

management

Errors in:

• Co-ordination

of all required

resources

• Combining/

assembly/ Bills

of Material

• Timing/change

management

• Machine

allocation

7.1 Planning

of product

realization

7.2 Customer

related

processes

Preparation/ pre-productionchecks oftooling andequipment

• Error in checking

tooling/equipment

• Change controlerror

• Validation status

error

• Maintenance

omission/ error

• Availability status

incorrect

See case study H

7.4 Purchasing

7.5 Production and service provision

10 Printed materials



13 Print and conversion process

See Part 2

for more

details

Risk areas



the schematics.


28/128

11

Issue of tooling

• Issue incorrect tool

• Issued with incorrect

status

• Issue in poor

condition

• Issue printing plates

in insecure manner

See case studies

I, J and K

7.5 Production and

service provision

12 Print impression

media

Issue of

materialsanddocumentation

• Issue incorrect

materials

• Incorrect quantity

issued

• Issued with incorrect

status

• Issue incorrect

documentation

• Unapproved

documentation

4.2 Documentation

requirements

7.5 Production and

service provision


12 Print impression

media

Production


29/128

12

SCHEMATIC 4 (a): PRINT IMPRESSION MEDIA CONTROLS

Customer supplieddesign text

New printmedia design

• Errors in media

undetected by

checks

• Individual plate

incorrectly coded

• Set of plates

incorrectly coded

• Failure to secure

customer proofapproval

• Failure to log

customer

approval

See case study L

11 Origination/

artwork

12.1 General

12.2 Matched

plates

Securestorage andcontrolledissue ofplates

• Mix-up with

plates from

another product

• Uncontrolled

access of

personnel• Physical

damage to

plates

• Inadequate

records of issue

introducing

admixture risk

in production

Controlsover partialre-designsand obsoletedesigns

• Incorrect plates

retained

• Insecure disposal

• Superseded platesnot rendered

unusable

• Incorrect plate

identification

• Error in

replacement plate/

matching set

• Documentation

errors

• Customerapproval error

See case study M

12.2 Matched plates

12.3 Copy / design change

12.5 Quarantine and destruction

13.2 Changeover systems See Part 2

for moredetails

Risk areas



the schematics.


30/128

13

Line use ofplates

Failure to :

• Check design

• Clear line of

previous plates

• Perform start-up

printing checks

• Record checks

• Keep samples

See case

study N

9.1.7 Line

clearance

12.4 Verification

13.1 Print

machine set-up

(make-ready)13.2 Changeover

systems

13.3 Retained

samples

Controls overreplacementplate (samedesign)

• A new first off

check is not

performed or

recorded (e.g.plate made

from existing

approved

source)

• New origination

& new batch

checks not

performed or

recorded (e.g.

plate createdfrom a new

source)

13.4 Replacement

print media

Line clearanceand controlledreturn ofplates to store

• Plate left on

machine in error

• Inadequate

records of return

to store

9.1.7 Line

clearance

12.1 General

Production


31/128

14

SCHEMATIC 5: PRODUCTION

Preparation Line clearcheck

• Admixture from

previous batch

• Erroneous use

of previous

documents

• Use of a plate

from previous job

7.5 Production

and service

provision

9.1.7 Line

clearance

10 Printed

materials11 Origination/

artwork

Documents/ materials/ tooling to line

• Use of incorrect

documents/

materials

• Failure to use

documents

correctly• Incorrect

quantities

• Defective moulds/

equipment/plates

See case study O

4.2 Documentation

requirements

7.5 Production and

service provision

Set upchecks andproductionstart

• Errors in

data input to

machine, e.g.

settings

• Setting errorundetected

• Start up waste

inadequately

segregated

from main

batch

• Unauthorized

start up

5.5 Respon-

sibility,

authority and

communication

7.6 Control of

monitoring

and measuringdevices

9 Contamination

controls

10 Printed

materials

12 Print

impression

media

See Part 2for more

details

Risk areas



the schematics.


32/128

15

Production/inprocess control

• Quality variation due

to environment e.g.

temperature, humidity

• Contamination e.g.

insects, dust

• Defective / out of spec

or wrong materials• Visual defects not

detected

• Inadequate IPC of transit

packaging

• Labelling errors

• IPC errors

• Material usage error

• Failure to identify/

segregate non

conforming product

• Recording error

See case studies P, Q

6.4 Work environment

7.5 Production and

service provision

8.2 Monitoring and

measurement

8.3 Control ofnonconforming product


Production completionand line clearance

Risk to next job due to:

• lack of GMP training

• failure to clear line

• inadequate waste disposal

• documentation not signed

off therefore status unclear

• clearance of electronicfiles/settings

See case study R

6.2.2 Competence,

awareness and training

8.2 Monitoring and

measurement

9 Contamination controls


13 Print and conversionprocesses

Checking andfinal release

Feedback


33/128

16

SCHEMATIC 6: CHECKING AND FINAL RELEASE

Production End product

QC testing

• Inadequate training

• Test method not

validated

• Out of Specification

results not investigated

• Inadequate procedures

• Release decision

contradicts data

• Inconsistent sampling/ risk

• Equipment/test

equipment inadequate

• Calibration errors/

omissions

See case study S

6.2.2 Competence,awareness and training

7.6 Control of monitoring

and measuring devices

8 Measurement, analysis

and improvement

8.4 Analysis of data

Review of batch

documents and QCtesting

• Missing/incorrect

document

• Missing/incorrect sample

• Signature omissions,

unauthorized check

signature

• Errors of information/data

entry• Checks out of sequence

• Abnormal events not

reviewed

See case study T

5.5 Responsibility, authorityand communication

6.2 Human resources

4.2 Documentation

requirements

13 Print and conversion

process

See Part 2

for more

details

Risk areas



the schematics.


34/128

17

Create certificate of

test or conformance

• Errors / omissions

• Signature invalid

• Inappropriate data

supplied

• Incorrect specifications/

tolerances

• Incorrect release decision

• Certificate text differsfrom batch details

See case study U

8.2 Monitoring andmeasurement

8.3 Control of

nonconforming product

Check box labels

against batchinformation

• Incorrect/missing label

• Label data error/

omission

• Label reconciliation

• Incorrect QC status label

See case studies V and W

7.5 Production and serviceprovision

Distribution


35/128

18

SCHEMATIC 7 - DISTRIBUTION

Checking and

final release

Receipt of product

into storage/holding(goods outwarehouse)

• Error in system

transaction (receipt)

• Inadequate segregation

from other goods

• Storage damage


provision


Order preparation

(picking and transitpackaging)

• Picking wrong product

• Damage to product due

to inappropriate transit

packaging

• Pallets not suitable for

customer handling

• Error in transaction (issue)

See case study X


provision

See Part 2

for more

details

Risk areas

Refer to the case studieswhich are located after

the schematics.


36/128

19

Dispatch area/

goods check anddocumentation

• Errors of quantity

• Incorrect labelling

• Error in dispatch note

• Admixture of boxes

See case study Y

Transport to the

customer

• Transit damage e.g. poor

pallet stacking, poor

weather protection

• Contamination in transit

• Inadequate control of

hauliers

See case study Z

The customer

7.5 Production and service provision


37/128

20


38/128

21



PS 9004



PART 1 - CASE STUDIES


39/128

22


40/128

23

Part 1 – Examples and Case studies

These examples and ‘real life’ case studies should be used with the

relevant Schematic, to illustrate specific GMP risk areas and the

appropriate QMS processes involved.

HYPOTHETICAL EXAMPLE FOR SCHEMATIC 1 –

TOP LEVEL BUSINESS PROCESSES

The senior management of a booklet printing company believes that PS

9000 certification will aid company profitability and smooth throughput

because of consistent demand from the pharmaceutical industry, which

is not adversely affected by recessions. The company has an enthusiastic

Quality Manager who has produced a comprehensive manual with up to

date and relevant procedures. However, the Quality Manager is beginning

to feel like a ‘voice in the wilderness’ as there is little evidence that senior

management is driving the whole organization to become aligned to the

requirements of the standard. The lack of senior management commitment

to the continual improvement philosophy and the Good Manufacturing

Practices of the pharmaceutical industry means that only superficial actions

are taken in areas considered highly visible to visiting auditors. Key individu-

als are unclear about the standards required of them. The level of customer

complaints remains high, some of these complaints being serious mix-ups.

Productivity stays unchanged with a high level of wastage. Workforce moral

is low and many staff are demotivated.

The company is then purchased by another company that already supplies

cartons to the pharmaceutical industry - allowing them to offer a better

product range to the customer. The corporate re-organization results in key

changes in senior management at the booklet factory. The new managers

know their prime objective is to encourage each and every employee to

understand the particular needs of their pharmaceutical customers. They

understand the value of PS 9000 in a competitive market, but know that the

real benefits are much deeper than merely achieving the ‘badge’. The Qual-

ity Manager begins to feel encouraged and genuinely part of the team. The

frequency of management review meetings is increased with the emphasis

changed to progressing preventive actions for nonconformities and review-


41/128

24

ing clear measures of performance for key parameters such as complaint

rates. The senior management commitment begins to permeate throughout

the staff and becomes evident in many areas such as resourcing, training,

customer service, and improved product quality. The board of directors

soon recognises that the PS 9000 implementation process is enabling them

to profitably expand their business, improve relationships with their custom-

ers, whilst still significantly reducing their cost of quality.

CASE STUDIES FOR SCHEMATIC 2 – FROM THE CUSTOMER

A Focus - Customer request/requirements

Bar coded product labels could not be read by customer’s electronic read-

ers due to shading of background colour, caused by inadequate testing

and validation. The packing orders at the pharmaceutical company were

delayed which threatened the availability of the medicinal products to the

end customers. The labels had to be destroyed, incurring the direct expense

of replacement. The product was redesigned with solid background, and all

graphics designers were made aware of the issue and to consider the pos-

sible need for trials on change of design or introduction of a new design.

B Focus – Customer design

A market need for a needle protection mechanism was specified, but

translation of this into a final design was lengthy and complicated. The

component did not perform reliably due to limited experimental validation.

The problems were addressed through increased communication with the

supplier to make the design more robust, involving revalidation and testing.

This extended work caused a delay in providing the improved safety prod-

uct to the patient. An organizational review followed to ensure that in future,

adequate resource is devoted at the design and testing stages of product

development.

CASE STUDIES FOR SCHEMATIC 3 – PLANNING

C Focus – Order review and customer feedback

The wrong material was ordered by the supplier’s UK sales office from their

own factory. Normally, orders were placed for 40 micron PVDC coated PVC


42/128

25

(for tablet blister packing), but on this occasion a new order for 60 micron

coated film was incorrectly notified by the sales office to the factory in Ger-

many as 40 micron; the incorrect material was delivered and used causing

a regulatory noncompliance and potentially inadequately protecting the

tablets from moisture. Significant work was necessary by the pharmaceuti-

cal company to assess stability data to determine the acceptability of the

packed tablet batches. The root cause was established through customer

audit of the ordering system at the sales office. An independent check of

order details was implemented to prevent repetition.

D Focus – Order review and customer feedback

The printer’s proof was incorrectly read by the supplier as ‘approved’ when

it was actually ‘rejected’; also the wrong file was used to make replace-

ment printing plates. Cartons for a heart condition medicinal product were

printed and used showing on one end flap 14 tablets instead of 28. The

consequence of this was that stock had to be recalled from the distribu-

tion centres to enable a rework. This delayed the critical medicinal product

reaching the market. Working together, customer and organization, the

complete sequence of events was reconstructed. In addition to awareness

training, the rules regarding issuing artworks and file management between

organization and platemaker were made more robust.

E Focus – Purchasing and print media provision

Leaflets with a different paper weight were supplied, due to problems with

availability of normal paper. This caused insertion difficulties on the phar-

maceutical packing line, high wastage of components and loss of some

pharmaceutical product. The supplier was advised of the existing change

control clause in the quality agreement/contract and procedures were

revised. The supplier managed to obtain further supplies of normal paper.

CASE STUDIES FOR SCHEMATIC 3 (a) –

WAREHOUSE (PURCHASED MATERIALS & IN-PROCESS)

F Focus – Goods checks and quality inspection

Self-adhesive labels were failing to stick to glass vials at the customer’s

premises because a different adhesive had been used. This had been

caused by the supplier switching their source of unprinted label material.


43/128

26

The raw material was thought to be of equivalent quality and no extra qual-

ity checks were performed at goods-inwards. The change was introduced

without informing the customer therefore no formal change control or a

risk assessment could be performed. The problem caused chaos on the

customer’s packing line and it was not certain how well the labels were

affixed to ‘apparently’ satisfactory packed vials. The label printing company

pursued the quality issue with its supplier and proper trials of alternatives

were subsequently conducted with the pharmaceutical company. In addi-

tion, revisions were made to the change control system.

G Focus – Store material

Two dead mice were found inside the pallet wrapping of a consignment of

plastic bottles to be used for an antiseptic liquid product. This caused major

disruption to the output of the pharmaceutical filling plant. All the stock of

bottles had to be manually inspected for contamination. It was necessary to

audit the supplier and its remote warehouse. Immediate action involved the

relocation of bottle storage back into the main factory. The root cause was

inadequate warehouse pest controls at the supplier’s remote warehouse. It

prompted an extensive programme of work to improve the standards at the

site. The product was a low margin item for the pharmaceutical company

and it has since been sold off to another company. Although many other

factors were involved, this episode only added to the reasons to sell this

part of the business.

CASE STUDIES FOR SCHEMATIC 4 – PREPARATION

H Focus – Preparation/pre-production checks of tooling and

equipment

Mould tool used to produce parts for a syringe was used in production

when the validation documentation had not been fully approved and signed

off. This contributed to high variability in functional performance of the

assembled syringe with some batches of parts rejected, and it necessitated

ongoing improvement work. It also delayed the launch of the pharmaceuti-

cal product which in this case was a life saving cancer product. The opera-

tional procedures were revised and the operators were retrained.


44/128

27

I Focus – Issue of tooling

Syringe labels were printed correctly, but were cut with corners of the wrong

profile/shape due to the issue of an incorrect cutter to the press. The labels

were rejected by the pharmaceutical company at the expense of the print-

ers. The time needed to replace the labels meant rescheduling of packing

was necessary at the pharmaceutical company. The cutter identification

process was reviewed & storage standards were improved.

J Focus – Issue of tooling

Cartons were produced with a varnish free area in the wrong position due

to the issue of an incorrect varnish plate. The purpose of a varnish free area

is to ensure the printing of variable data (e.g. lot & expiry) is clear and per-

manent. This error was identified at the pharmaceutical company. The risk

existed that variable data applied by the pharmaceutical company could

be easily smudged or erased when in the market and this would clearly be

a critical problem. The supplier reviewed the varnish plate issuing process

and made improvements to the system which linked varnish plate usage to

print plate usage.

K Focus – Issue of tooling

Mould tool for a syringe plunger rod was issued to production despite

being overdue for refurbishment. This resulted in minor plastic ‘flash’ being

present on the mouldings. If this problem became more serious then loose

particles of plastic could break off and contaminate the pharmaceutical

syringe pack. The supplier applied for a concession from the customer and

this was granted for a limited period because of the extent of the problem.

The case highlighted the need for proper planned preventive maintenance

and sufficient resources allocated to facilitate it.

CASE STUDIES FOR SCHEMATIC 4 (a) –

PRINT IMPRESSION MEDIA CONTROLS

L Focus – New print media design

Artwork supplier made a “cut & paste” error which resulted in cards being

part printed with Polish text in the main body of Portuguese text. The cards

were for an anti-cancer injection. Fortunately the error was noticed dur-

ing in-process checks of printing. The error had the potential to become


45/128

28

a product recall if it had reached the end user. An extensive review of the

artwork supplier’s procedures was completed and a further proof-reading

check was introduced.

M Focus – Controls over partial redesigns & obsolete designs

The printed foil for tablet blister strips (used to treat a heart condition) was

incorrectly printed with two different identifying codes on the foil (different

by one digit). The error occurred during the ‘step and repeat’ process to

generate a single replacement cylinder. The error was only found on inspec-

tion at the pharmaceutical company. In this case, no packed stock was lost,

but the error could have been more serious. The supplier took the issue up

with its cylinder manufacturer and reviewed its inspection procedure for first

off sample inspection following cylinder replacement.

N Focus – Line use of plates

A printing plate was left on the leaflet press by the operator after leaving the

area to retrieve a spare part. Upon return the operator continued printing,

but against the job documentation for the next job. The item was visually

very similar and all subsequent checks by operators and QC failed to spot

the admixture that had been created. The problem was found on goods

inwards checks by the customer, and resulted in a detailed audit of proce-

dures by the customer. Line clearance checks were reviewed, procedures

around bar code scanning at the suppliers were enhanced and refresher

training was delivered.

CASE STUDIES FOR SCHEMATIC 5 – PRODUCTION

O Focus – Documents/materials/tooling to line

During the folding stage of leaflet production two orders were mixed up. Job

A was folded, scanned, labelled and released against Job B documenta-

tion, and Job B documentation was folded, scanned, labelled and released

against Job A documentation. The mixed-up orders were then delivered to

the pharmaceutical company where the error was discovered. The potential

for incorrect leaflets to be packed into pharmaceutical packs was increased.

The supplier’s investigation identified the root cause as human failure to fol-

low established procedures. In addition the codes for the bar code scanner

are now input from an independent source (a PS 9000:2001 requirement).


46/128

29

P Focus – Production/in-process control

A delivery of poorly printed foil, used for tablet blister strips, was caused

by inadequate ‘flagging’ of defective material during printing. The ‘flagged’

material is removed during later stages of slitting and rewinding. The defec-

tive material was detected on the customer’s packing line and lead to the

scrapping of some packed pharmaceutical product. The supplier’s printers

and the operators responsible for removal of the ‘flagged’ material were

given refresher training to ensure all defective material is removed, up to

and around the ‘flagged’ point in the reel.

Q Focus – Production/in-process control

Plastic tablet bottles were manufactured with a wall thickness that was

below specification. This was caused by poor appreciation of the cus-

tomer’s requirements, inadequate in-process monitoring and an inability to

segregate product that was out of specification. Packed pharmaceutical

product had to be quarantined until all aspects of the problem had been

assessed by the pharmaceutical company’s QA Department. The issue was

resolved through improved specification regarding the criticality of certain

dimensions, increased in-process measuring regime and enhanced segre-

gation procedures.

R Focus – Production completion & line clearance

On a reel of label/leaflet combinations, six ‘rogue’ components (of similar

appearance) were found at intermittent points in the reel, by the pharmaceu-

tical customer. This was despite a scanning operation being in place at the

supplier. The root cause was human error involving inadequate line clear-

ance and replacing incorrect labels back onto the web during rewinding/

scanning. Although the rule existed which forbade this practice, the

operator had recently been transferred from a department supplying non-

pharmaceutical customers where this rule was not in place. The supplier

commenced a fundamental review of procedures and operator retraining.

CASE STUDIES FOR SCHEMATIC 6 – CHECKING & FINAL RELEASE

S Focus – End product QC testing

An out of specification result on a test machine record was transcribed

incorrectly as satisfactory on the summary sheet, causing an incorrect


47/128

30

release decision of a batch of syringes. Although, in this case no harm was

caused, it highlighted a risk area, should the error have occurred on another

safety related function of the syringe. Refresher training was delivered to the

operator concerned.

T Focus – Review of Batch documents & QC testing

Carton barcode scanner was switched off during the night shift without

QA authorization and not noticed upon review of documentation. This

meant that the product had been made without the safeguards required

by, and contractually agreed with the customer. The product was therefore

inadequately checked for the absence of rogue components. The affected

order was rejected and scrapped. A detailed audit was performed by the

pharmaceutical company and numerous significant procedural enhance-

ments were made.

U Focus – Create Certificate of Test or Conformance

Irradiated syringes were released for use despite radiation dose figures

being omitted from the certificate of test. In this case the dosage was

actually satisfactory, however the omission / error had the potential to

threaten the sterility of the syringes thus endangering the patient, and to

compromise the pharmaceutical sterile filling facility. The certificates are

now double checked before release from the irradiation contractor.

V Focus – Check box labels against batch information

A box of shampoo closures was delivered amongst a consignment of tablet

bottle closures, caused by box labelling error & poor segregation practices.

This resulted in admixture on the filling line at the pharmaceutical company,

line downtime, and some lost product. The supplier had been audited on

numerous occasions but lack of commitment to eliminate such problems

ultimately lead to a change of supplier for the component.

W Focus – Check box labels against batch information

A keying-in error of leaflet product identity code to outer box label printer

caused rejection upon delivery to customer. Apart from the disruption

caused by the rejection, there was a risk that the material could have been

received into stock as a different item, i.e. admixture. The preventive action

eventually implemented was to link the box label printer to the mainframe


48/128

31

computer thus removing the necessity to manually key the data into a

standalone label printer.

CASE STUDIES FOR SCHEMATIC 7 – DISTRIBUTION

X Focus – Order preparation (picking & transit packaging)

An admixture of boxes of labels was found on receipt by the customer

caused by a picking error made due to poor warehouse lighting and lack

of a double check. In another incident an admixture of batch of cartons

occurred, caused by a picking error due to poor batch segregation in

the warehouse. Both batch defectives were found during the customer’s

receipt checking, but they caused disruption to the product scheduling

programmes because of the need to return the material to the supplier for

sorting/replacement. The corrective and preventive actions, in both cases,

involved a fundamental review of the conditions (and checks made) in the

warehouse and implementation of improved lighting and segregation mea-

sures.

Y Focus – Despatch area/goods check & documentation

Despatch note details accompanying the delivery differed from physical

quantity delivered. This resulted in delays in product release and schedul-

ing disruption while the supplier was contacted. The supplier’s despatch

checking procedures were reviewed, no fundamental weaknesses were

found. In this case, a one-off error had occurred and the issue was dis-

cussed with the individual concerned.

Z Focus – Transport to the customer

Goods were damaged in transit due to movement of the load and inade-

quate control while the vehicle was being loaded. In another incident, goods

were damaged by water penetration due to a poorly closed and maintained

“curtain” of a flexible sided vehicle. Both examples resulted in the need for

product inspection at the customer, and the return of damaged material to

the supplier leaving too few components to meet requirements. In the first

case, the checks made on loading were increased and in the second exam-

ple the company decided it was feasible to switch to hard sided vehicles to

eliminate the risk of water penetration.


49/128

32

Using the Case Studies - Guidance for Trainers

Introduction

The case studies that have been described here can be used as valuable aides to

training programmes, for use either by a supplier or a pharmaceutical company. It

is recommended that you select one or more of the case studies that are appro-

priate to your business and design an activity that will encourage your trainees to

discuss the particular subject you would like them to understand. An example of a

training exercise protocol is provided below based on a case study selected from

Schematic No. 3. Developing a short set of questions similar to those illustrated

below should help improve understanding. It will probably be beneficial if such Q &

A sets were developed jointly after discussion between pharmaceutical customers

and their suppliers.

It will certainly be helpful to provide explanations and visual aides relevant to the

case study. For example in the example illustrated below it would be helpful if:

i) For a laminate that you use or manufacture explain which illness(es) the tablets,

that are packed within it, are used to treat.

ii) A copy of an analogous page of a Product Authorisation (Licence) was shown

and the legal basis of such licences explained.

iii) The function of PVDC in the laminate was explained.

Training Exercise

Case study No. C

Title: Mix-up in the weight of PVDC on a PVC based blister film

In this case study, the wrong material was ordered from the factory.

Nomally, orders were placed for 40 micron PVDC coated PVC (for tablet

blister packing) - and etc.

Training objectives

Discuss the case study in groups and decide your answers to the following ques-

tions:

Q 1. Which requirement(s) of PS 9000 do you consider had not been effectively

implemented?

State the clause numbers and your reasons.


50/128

33

Q 2. Why do you think that the thickness of the PVDC could affect the stability of

the tablets that were to be packed in the laminate?

Q 3. If this mistake had not been detected what do you think the implications

might have been to:

i) The manufacturer of the laminate film?

ii) The pharmaceutical customer?


51/128

34


52/128

35



PS 9004



PART 2 - GUIDANCE ON PS 9000 GMP CLAUSES

PS 9000 GMP related text is reproduced in blue


53/128

36


54/128

37

G e n e r a l s y n o p s i s - C l a u

s e 4 Q u a l i t y m a n a g e m e n t s y s t e m

A Q M S p r o v i d e s a b a s i s f o

r c o n t i n u o u s i m p r o v e m e n t o f t h e o r g a n i z a t i o n ’ s e f f e c t i v e n e s s a n d e f f i c i e n c

y , w h i l s t s t i l l c o n s i d e r i n g

t h e v a r i o u s n e e d s o f a l l s t

a k e h o l d e r s ( e . g . c u s t o m e r s , s u p p l i e r s , i n v e s t o r s , e m p l o y e e s ) .

C l a u s e 4 . 1 G e n e r a

l r e q u i r e m e n t s

D e t a i l e d c o n s i d e r a t i o n i s r e q u i r e d o f t h e n e e d s o f s t a k e h o l d e r s ,

t h e p

r o c e s s e s t o m e e t t h o s e n e e d s a n d t o m e

a s u r e p e r f o r m a n c e .

T h e r e a r e n o ‘ e x t r a ’ P S 9 0 0

0 G M P s w i t h i n t h i s c l a u s e .

T h e r e a r e i m p o r t a n t G M P p r i n c i p l e s i n t h i s a r e a ,

b u t t h e

y a r e a d e q u a t e l y

e x p r e s s e d i n I S O 9 0 0 1 a n d

I S O 9 0 0 4 .

P r o c e s s i n p u t s

P r o c e s s e s

P r o c e s s o u t p u t s a n d

e v i d e n c e

C r o s s r e f e r t o

S c h e m a t i c / A n n e x

•

I d e n t i f i e d p r o c e s s e s

t h a t m e e t o r g a n i z a t i o n

s t r a t e g i c o b j e c t i v e s

•

C u s t o m e r r e q u i r e m e n t s

•

R e g u l a t o r y

r e q u i r e m e n t s

P r o c e s s e s w h i c h :

•

d e f i n e ,

i m p l e m e n t a n d m a i n t a i n Q M S

p r o c e s s e s ( i n c l u d i n g m a n a g e m e n t

a n d

o p e r a t i o n a l a c t i v i t i e s )

•

d e t e r m i n e p e r s o n n e l r e q u i r e d t o c a r r y o u t

p r o c e s s e s a n d t r a i n i n g n e e d s

•

p r o v i d e p r e m i s e s a n d e q u i p m e n t f

o r t h e

p r o c e s s e s

•

d e f i n e a n d i m p l e m e n t c o n t r o l s t o m e a s u r e

p e r f o r m a n c e o f Q M S p r o c e s s e s i n

c l u d i n g

o u t s o u r c i n g

•

W r i t t e n p r o c e d u r e s

e s s e n t i a l t o

Q u a l i t y S y s t e m

•

O r g a n i z a t i o n s t r u c t u r e

t h a t s u p p o r t s Q M S

•

A d e q u a t e p r e m i s e s

a n d e q u i p m e n t

•

D a t a f r o m p r o c e s s e s

a n d m e a s u r e m e n t

s y s t e m s

S c h e m a t i c 1


55/128

38

C l a u s e 4 . 2 D o c u m e n t a t i o n r e q u i r e m e n t s

D o c u m e n t a t i o n i s a f u n d a m e n t a l p a r t o f t h e Q M S t h a t d e f i n e s w h a t t h e o r g a n i z a t i o n d o e s , p r o v i d e s t r a c e a b i l i t y a n d e v i d e n c e o f i t s

a c t i v i t i e s .

R e a s o n s f o r t h e ‘ e x t r a ’ G M

P r e q u i r e m e n t s ( r e f e r t o P S 9 0 0 0 c l a u

s e s 4 . 2 . 2 ; 4 . 2 . 3 ; 4 . 2 . 4 )

P h a r m a c e u t i c a l c o m p a n i e s

h a v e , o n o c c a s i o n s , e x p e r i e n c e d p r o b l e m

s i n t h e r e t r i e v a l o f a c c u r a t e h i s t o r i c a l d a t a f r o m s u p p l i e r s a n d

t h e s e h a v e b e e n a t t r i b u t e d t o i n a d e q u a t e d a t a s y s t e m v a l i d a t i o n a n d

d a t a c o n t r o l s .

T h e p r o c e s s r e f e r e n c e s a b

o v e a r e p a r t o f a s y s t e m

o f d a t a t r a c e a b i l i t y t h a t c a n

p r o v i d e a c o m p l e t e h i s t o r y o f t h e c o m p o n e n t ’ s m a n u f a c t u r e .

T h i s c a n b e v i t a l l y i m

p o r t a n t i f t h e r e i s a

p r o b l e m i n t h e u s e o f t h e p h

a r m a c e u t i c a l p r o d u c t i n t h e m a r k e t p l a c e .

T h e p h a r m a c e u t i c a l c o m p a n y h a s a r e g u l a t o r y o b l i g a t i o n t o r e t a i n p r o d u c t i o n a n d p a c k i n g d a t a f o r o n e y e a r b e y o n d t h e s h e l f - l i f e o f

t h e p r o d u c t . T h e r e i s t h e r e f o r e a c o r r e s p o n d i n g r e s p o n s i b i l i t y ( s e e A n

n e x B ) u p o n t h e c o m p o n e n t s u p p l i e r t o e

s t a b l i s h a n d m a i n t a i n

a c c u r a t e a n d s e c u r e d a t a c o n t r o l a n d r e t e n t i o n s y s t e m s .


P r o c e s s e s


e v i d e n c e



•

D o c u m e n t s t h a t n e e d

t o b e c o n t r o l l e d

•

S t a n d a r d s a n d

r e g u l a t o r y r e q u i r e m e n t s

•

C u s t o m e r r e q u i r e m e n t s

( s p e c i f i e d a n d

u n s p e c i f i e d )

•

R e s p o n s i b i l i t i e s f o r

d o c u m e n t s ( e . g .

a u t h o r s , a p p r o v e r s ,

e t c . )

•

P r o c e s s m a p s


•

c o n t r o l t h e d o c u m e n t a n d d a t a m a

n a g e m e n t

f o r a n y m e d i a t y p e t o c o v e r l i f e - c y

c l e

•

e n s u r e t h e s e c u r i t y o f e l e c t r o n i c d o c u m e n t s i s

e q u a l t o t h a t o f p a p e r d o c u m e n t s

•

p r o v i d e a u d i t t r a i l f o r e l e c t r o n i c d o

c u m e n t s a n d

d a t a

•

c o n t r o l b a c k u p a n d r e c o v e r y o f d a

t a

•

c o n t r o l v a l i d a t i o n o f h a r d w a r e / s o f t w a r e u s e d

f o r d o c u m e n t a n d d a t a m a n a g e m e

n t

•

c o n t r o l a r c h i v i n g / r e t e n t i o n o f d o c u

m e n t s a n d

d a t a

•

d e f i n e t h e e x t e n t t o w h i c h P S 9 0 0 0 a p p l i e s

w i t h i n t h e Q M S

•

Q u a l i t y m a n u a l

•

P r o c e d u r e s t h a t

s u p p o r t t h e d o c u m e n t

a n d d a t a m a n a g e m e n t

s y s t e m

•

C l e a r a c c o u n t a b i l i t i e s

a n d r e s p o n s i b i l i t i e s

R e c o r d s o f :

•

d o c u m e n t a t i o n

c h a n g e s

•

t r a i n i n g

•

v a l i d a t i o n

S c h e m a t i c 3

S c h e m a t i c 4

S c h e m a t i c 5

S c h e m a t i c 6

A n n e x B


56/128

39

G e n e r a l S y n o p s i s - C l a u

s e 5 M a n a g e m e n t r e s p o n s i b i l i t y

M a n a g e m e n t ’ s r e s p o n s i b i l i t y t o e n s u r e a n e f f e c t i v e Q M S w h i c

h r e c o g n i s e s t h e n e e d s o f t h e o r g a n i z a t i o n , c u s t o m e r s a n d

o t h e r k e y s t a k e h o l d e r s .

C l a u s e 5 . 1 M a n a g e m

e n t c o m m i t m e n t

T o p m a n a g e m e n t d e f i n e s t h

e o r g a n i z a t i o n ’ s s t r a t e g y a n d i s r e s p o n s i b

l e f o r d e m o n s t r a t i n g c o m m i t m e n t t o t h e Q M S .

C o n t i n u a l

i m p r o v e m e n t o f t h e s y s t e m

a n d i t s p r o c e s s e s a r e n e c e s s a r y t o e n s u r e c u s t o m e r a n d r e g u l a t o r y n e e d s a r e f u l l y

s a t i s f i e d .

T h e r e a r e n o ‘ e x t r a ’ P S 9 0 0

0 G M P ’ s w i t h i n t h i s c l a u s e .

T h e r e a r e i m p

o r t a n t G M P p r i n c i p l e s i n t h i s a r e a ,

b u t t h e y a r e a d e q u a t e l y

e x p r e s s e d i n I S O 9 0 0 1 a n d

I S O 9 0 0 4 .


P r o c e s s e s


e v i d e n c e



•

C o m p a n y s t r a t e g y /

p u r p o s e

•

A d e q u a t e r e s o u r c e s t o

m e e t r e q u i r e m e n t s


•

e s t a b l i s h q u a l i t y p o l i c y

•

e s t a b l i s h q u a l i t y o b j e c t i v e s

•

r e q u i r e a M a n a g e m e n t R e v i e w a s a m e a n s o f

c o n t i n u a l i m p r o v e m e n t

•

e n s u r e s t h e c o m m u n i c a t i o n w i t h s t a f f t o h e l p

t h e m u n d e r s t a n d a n d c o n t r i b u t e t o

Q M S

i m p l e m e n t a t i o n ( e . g . c o n t i n u o u s i m

p r o v e m e n t

o b j e c t i v e s , c u s t o m e r s a t i s f a c t i o n t a r g e t s , e t c . )

•

E v i d e n c e o f s t a f f

u n d e r s t a n d i n g a n d

c o m m i t m e n t

•

C u s t o m e r s a t i s f a c t i o

n

m e a s u r e s

C l e a r l y d o c u m e n t e d :

•

q u a l i t y p o l i c y

•

q u a l i t y o b j e c t i v e s

•

i m p r o v e m e n t p l a n s

S c h e m a t i c 1


57/128

40

C l a u s e 5 . 2 C u s t o m e r f o c u s

A k e y r e q u i r e m e n t t o p r o v i d

e s u i t a b l e p r e m i s e s , p e o p l e , a n d p r o c e s s e s ,

i n o r d e r t o e n h a n c e c u s t o m e r s a t i s f a c

t i o n .

R e a s o n s f o r t h e ‘ e x t r a ’ G M

P r e q u i r e m e n t s

P h a r m a c e u t i c a l I n d u s t r y e x p e r i e n c e s h o w s t h a t f r o m t h e p r o d u c t d e v

e l o p m e n t s t a g e o n w a r d s , c o m p l i a n t p h a r

m a c e u t i c a l q u a l i t y

r e q u i r e s f a c i l i t i e s a n d s t a f f t o b e ‘ f i t f o r p u r p o s e ’ , i . e .

‘ s u i t a b l e f a c i l i t i e s a n d c o m p e t e n t s t a f f ’ , a n d t h a t t h i s G M P

r e q u i r e m e n t i s e q u a l l y

a p p l i c a b l e t o t h e s u p p l i e r o f p h a r m a c e u t i c a l p a c k a g i n g c o m p o n e n t s .

P r o d u c t s e c u r i t y a n d t h e a v o i d a n c e o f c r o s s c o n t a m i n a t i o n u n d e r p i n s a l l p h a r m a c e u t i c a l q u a l i t y , s i n c e t h e s e a r e b a s i c i s s u e s t h a t c a n

l e a d t o p e o p l e t a k i n g t h e w r o n g m e d i c i n e ,

d a m a g i n g t h e p h a r m a c e u t i c a l c o m p a n y ’ s b u s i n e s s , a n d p u b l i c c o n f i d e n c e i n i t .

( S e e a l s o

A n n e x A ,

‘ C o u n t e r f e i t ’ t h a t c o v e r s i n d e t a i l t h e n e e d s f o r c o n t r o l s i n a

r e a s i n v o l v i n g d i s p o s a l o f a r t w o r k , p r o c e s s d e f e c t i v e s a n d w a s t e

m a t e r i a l s , e t c . ) .

B e g i n n�