Copyright © 2006 The International Pharmaceutical Excipients Council

TheIPECGood DistributionPractices Guide

FORPHARMACEUTICALEXCIPIENTS

2006

IPEC Good Distribution Practices Guide for Pharmaceutical Excipients

This document has been written to provide guidance for those companies involved in the supply chain ofpharmaceutical excipients. Examples based on practical experience are provided to facilitate the applica-tion of GDP. However, alternative approaches may be acceptable.

This guide provides additional explanatory notes to:

“GOOD TRADE AND DISTRIBUTION PRACTICES FOR PHARMACEUTICAL STARTING MATERIALS” [1]World Health Organization, WHO Technical Report Series, No. 917, 2003

The explanatory notes in this guide are the views of The International Pharmaceutical Excipients Council(IPEC) and not necessarily those of WHO.

World Health Organization:

“We are pleased to see that IPEC is using the recommendations from WHO’s technical report on GoodTrade and Distribution Practices for Pharmaceutical Starting Materials. We hope that this will help tomake those recommendations more widely known and allow for their intended implementation. We lookforward to our continued collaboration aiming at providing quality medicines to patients.”

(Dr. Lembit Rägo, Dr. Sabine Kopp; December 2005)

Table of contents PagesI. Introductory Note .......................................................................................................................2II. Scope ..........................................................................................................................................2III. Pharmaceutical Grade Excipients...............................................................................................2IV. Acknowledgements ....................................................................................................................2Table 1 Matrix of Applicability...............................................................................................................4Table 2 Applicability for Supply Chain Activities..................................................................................51. Quality Management ..................................................................................................................62. Organization and Personnel........................................................................................................73. Premises......................................................................................................................................84. Warehousing and Storage...........................................................................................................95. Equipment ................................................................................................................................116. Documentation .........................................................................................................................137. Repackaging and Relabeling....................................................................................................148. Complaints................................................................................................................................199. Recalls ......................................................................................................................................1910. Returned goods.........................................................................................................................2011. Handling of non-conforming materials ....................................................................................2112. Dispatch and Transport.............................................................................................................2113. Contract activities.....................................................................................................................22Appendix A Glossary................................................................................................................................24Appendix B Bibliography.........................................................................................................................30

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 1

I. Introductory NoteThe International Pharmaceutical Excipients Council (IPEC) first published a GMP Audit Guideline forDistributors of Bulk Pharmaceutical Excipients in 2000. This Guideline was designed as a tool to assist in evaluating the practices and quality systems of distributors who store excipients in their warehouses and those who both repackage and store excipients. During 2001, and again in 2006, IPEC revised its GMP Guidelines for manufacturers of excipients and decided to publish a complementary document fordistributors of excipients.

In the meantime WHO published its guideline on Good Trade and Distribution Practice forPharmaceutical Starting Materials (GTDP) [1] the scope of which extends to active pharmaceutical ingredients and excipients. As a result, IPEC is publishing its Good Distribution Practices Guide forPharmaceutical Excipients based on the WHO GTDP guideline [1] as an explanatory document.

The WHO GTDP document provides the general principles of good practices in the pharmaceutical start-ing materials supply chain. This IPEC document should provide the practical approach with examples thatprovide guidance on the application of WHO GTDP principles. In addition, extracts have been taken fromIPEC PQG GMP Guide 2006 [2] to clarify certain requirements and maintain consistency.

For the purpose of this guide “distributors” includes those parties involved in trade and distribution,(re)processors, (re)packagers, transport and warehousing companies, forwarding agents, brokers, traders,and suppliers other than the original manufacturer.

II. ScopeThis document is based on the WHO Good Trade and Distribution Practice for Pharmaceutical StartingMaterials (GTDP) guideline [1], and therefore it follows the same structure.

It applies to steps in the distribution/supply chain starting from the point at which an excipient is trans-ferred outside the control of the original manufacturer’s material management system. Some sectionsand/or sub-sections in this document may not apply to all involved parties. This document is meant to provide guidance in the application of the GTDP; however, alternative approaches may be acceptable.

To help the user to identify the sections applicable to the activities, see table 1 - Matrix of Applicabilityand table 2 - Applicability for supply chain activities.

The matrix differentiates between activities involving warehousing and distribution from those involvingfurther processing such as distributor bulk storage, repackaging, sampling, or labeling activities withexcipients, reflecting different levels of control. For definitions, please refer to Annex A.

Further processing activities, such as blending, mixing, milling, micronization or any other physicalmanipulation of pharmaceutical excipients, should also refer to relevant aspects of the IPEC PQG GMPGuide 2006 [2].

In addition to this text Introductory Note, Scope, General Considerations and the Glossary of WHO GTDPguideline [1] should be referenced.

III. Pharmaceutical Grade ExcipientsParties involved in the supply chain should be aware that an excipient can only be pharmaceutical gradewhen it is in compliance with pharmacopoeial specification and/or appropriate regulatory requirements (ifexisting for the specific excipient) and is manufactured, repackaged, and handled in accordance withexcipient GMPs (e.g. IPEC PQG GMP [2], WHO Excipient GMP [6]). Upgrading technical or industrialgrade material to pharmaceutical grade quality only on the basis of analytical results found in conformancewith the requirements of a pharmacopoeial monograph is an unacceptable practice.

IV. Acknowledgements

The International Pharmaceutical Excipients Council (IPEC) prepared this document. IPEC is an interna-tional industry association with a distinguished worldwide membership of chemical, pharmaceutical and

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 2

food firms that develop, manufacture, distribute, sell and use pharmaceutical excipients. IPEC was formedin 1991 to address prevalent industry concerns related to the harmonization of international excipient stan-dards, the introduction of useful new excipients to the marketplace, and the development of good manu-facturing practices for excipients. IPEC is an umbrella organization comprised of three regionalpharmaceutical excipient industry associations in the United States, Europe, and Japan. The objective ofthe three organizations, which are known respectively as IPEC Americas, IPEC-Europe and JPEC, is topromote the safety and efficacy of finished dosage forms worldwide.

IPEC would like to acknowledge the World Health Organization (WHO) for their extensive efforts in devel-oping the guidelines “GOOD TRADE AND DISTRIBUTION PRACTICES FOR PHARMACEUTICALSTARTING MATERIALS” [1], which are valued by IPEC as a significant step forward in the development oftools for the improvement of safety and quality of starting materials and finished pharmaceuticals.

This document is the result of significant collaboration between IPEC-Europe and IPEC-Americas. IPECgreatly appreciates the many hours of hard work by the following individuals devoted to developing thisguide and the generous support provided by their employers:

IPEC-EUROPE

Dr. Mathias Brenken Dow Deutschland GmbH & Co. OHGReiner Gellrich Cognis Deutschland GmbH & Co. KGDr. Andreas Lekebusch Biesterfeld Spezialchemie GmbHGeorge Mansveld Hercules International Ltd.Dr. Frank Milek Aug. Hedinger GmbH & Co. KG – ChairmanDr. Alexander Schoch Palatinit GmbHDr. Najib Sehat Merck KGaAAllan Whiston sanofi-aventis

IPEC-AMERICAS

Dr. Sidney Goode The Dow Chemical CompanyDr. Rodney Gray Hercules IncorporatedAnn Perry The Dow Chemical CompanyDavid B. Klug sanofi-aventisJack Tully Hercules IncorporatedJames Slagle Hercules IncorporatedRobert Wiens Eli Lilly and CompanyRick Green CP KelcoDale Carter ADMKristin Moore ADMDon Ewert EMD ChemicalsRobert Zega Chr. Hansen Inc.Priscilla Zawislak FMC BiopolymerDr. Philip Merrell Tyco Healthcare/MallinckrodtDavid Schoneker ColorconVictoria Shaheen Mutchler, Inc.Laura Horne Mutchler, Inc.Dennis Walker Proctor & GambleFrank Murphy The Dow Chemical CompanyAmanda Martin National Starch & Chemical CompanyKatherine Ulman Dow CorningDr. Arthur Falk IPEC-AmericasDr. R Christian Moreton Idenix Pharmaceuticals, Inc.Dr. Irwin B. Silverstein IBS Consulting in Quality (committee consultant)

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 3

War

ehou

sing

/ D

istr

ibut

ion

(pac

ked

exci

pien

ts)

Add

itio

nal P

roce

ssin

g A

ctiv

itie

s

Bro

king

,T

rans

port

atio

n W

areh

ousi

ng

Tra

ding

,Sa

mpl

ing,

of p

acke

d (s

tora

ge o

f pa

cked

R

esel

ling

pack

ed

Rep

acka

ging

,Te

stin

g an

d B

ulk

hand

ling,

Tra

nspo

rtat

ion

of

exci

pien

tsex

cipi

ents

)ex

cipi

ents

Proc

essi

ng

Re-

test

ing

Rel

abel

ing

bulk

sto

rage

bulk

exc

ipie

nts

1.Q

ualit

y M

anag

emen

tX

+X

X+

XX

XX

X+

2.O

rgan

izat

ion

and

Pers

onne

lX

+X

+X

+X

XX

XX

3.P

rem

ises

X+

XX

XX

4.W

areh

ousi

ng a

nd S

tora

geX

+X

X+

X

5.E

quip

men

tX

X+

XX

6.D

ocum

enta

tion

X+

X+

X+

XX

+X

X+

X+

7.R

epac

kagi

ng a

nd

Rel

abel

ing

XX

+X

+X

+

8.C

ompl

aint

sX

XX

XX

+X

XX

9.R

ecal

ls*

X+

XX

X

10.R

etur

ned

good

sX

XX

X

11.H

andl

ing

of

non-

conf

orm

ingm

ater

ials

X+

XX

X

12.D

ispa

tch

and

Tra

nspo

rtX

+X

13.C

ontr

act

activ

itie

sX

XX

XX

XX

X

X =

app

licab

le +

= o

nly

part

ly a

pplic

able

* In

the

USA

the

term

rec

all h

as s

peci

fic

regu

lato

ry im

plic

atio

ns th

at d

o no

t dir

ectly

app

ly to

exc

ipie

nts;

ther

efor

e th

e te

rm r

etri

eval

is ty

pica

lly u

sed

in th

e U

SA.

Cop

yrig

ht ©

2006

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erna

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Tabl

e 1:

Mat

rix

of A

pplic

abili

ty

Act

ivit

y:

Sect

ion:

Table 2: Applicability for Supply Chain Activities

A supply chain participant, who exclusively carries out a specific activity, should apply the sections of thedocument mentioned under an activity. If a company carries out different activities all sections mentionedunder all conducted activities should be applied.

1. Activities including direct contact with excipients

1.1 Repackaging, Processing

Applicable sections:1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 13.

1.2 Sampling, Testing, Re-testing

Applicable sections:1., 2., 3., 5. (except 5.2 and 5.6); 6. (except 6.7, 6.8), 7. (except 7.1, 7.2, 7.3, 7.4, 7.6, 7.7, 7.8,7.9, 7.10, 7.11, 7.15), 8. (except 8.4 and 8.5), 13.

1.3 Relabeling

Applicable sections:1., 2., 3., 4 (except 4.9), , 6., 7. (except 7.13. and 7.14), 8., 9., 10., 11., 13.

1.4 Bulk handling and bulk storage

Applicable sections:1., 2., 3., 4., 5., 6. (except 6.8), 7. (except 7.5, 7.6, 7.9, 7.10), 8., 9., 10., 11., 13.

1.5 Transportation of bulk excipients

Applicable sections:1. (except 1.7), 2., 5., 6. (except 6.3, 6.4, 6.7, 6.8, 6.9), 8., 12., 13.

2. Activities including non-direct contact with excipients (handling of packaged excipients)

2.1 Transportation of packed excipients

Applicable sections:1. (except 1.7), 2. (except 2.6), 6. (except 6.3, 6.4, 6.7, 6.8, 6.9), 8., 12. (except 12.4 and 12.7), 13.

2.2 Warehousing (storage of packed excipients)

Applicable sections :1., 2. (except 2.6), 3. (except 3.5), 4. (except 4.9), 6. (except 6.3, 6.4, 6.7, 6.8), 8., 10., 11. (except 11.2 and 11.4), 13.

2.3 Broking, Trading, Reselling originally packed excipients

Applicable sections:1. (except 1.7), 2. (except 2.5 and 2.6), 6. (except 6.1, 6.7, 6.8), 8., 9. (except 9.4), 13.

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 5

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

1.Q

ualit

y M

anag

emen

t

1.1

With

in a

n or

gani

zatio

n qu

ality

ass

uran

ce s

erve

s as

a m

anag

emen

t too

l. In

con

-tr

actu

al s

ituat

ions

qua

lity

assu

ranc

e al

so s

erve

s to

gen

erat

e co

nfid

ence

in th

esu

pplie

r. T

here

sho

uld

be a

doc

umen

ted

qual

ity p

olic

y de

scri

bing

the

over

all

inte

ntio

ns a

nd d

irec

tion

of th

e su

pplie

r re

gard

ing

qual

ity,a

s fo

rmal

ly e

xpre

ssed

and

auth

oriz

ed b

y m

anag

emen

t.

1.2

Qua

lity

man

agem

ent s

houl

d in

clud

e:•

an a

ppro

pria

te in

fras

truc

ture

or

“qua

lity

syst

em”,

enco

mpa

ssin

g th

e or

gani

-za

tiona

l str

uctu

re,p

roce

dure

s,pr

oces

ses,

and

reso

urce

s;•

syst

emat

ic a

ctio

ns n

eces

sary

to e

nsur

e ad

equa

te c

onfi

denc

e th

at a

mat

eria

l(o

r se

rvic

e) a

nd r

elev

ant d

ocum

enta

tion

will

sat

isfy

giv

en r

equi

rem

ents

for

qual

ity. T

he to

talit

y of

thes

e ac

tions

is te

rmed

(qu

ality

ass

uran

ce);

and

•a

clea

r pr

oced

ure

for

appr

ovin

g su

pplie

rs o

f ph

arm

aceu

tical

sta

rtin

g m

ater

i-al

s an

d se

rvic

es (

for

deta

ils s

ee G

MP)

.

1.3

The

sys

tem

sho

uld

cove

r qu

ality

ass

uran

ce p

rinc

iple

s.

1.4

All

part

ies

invo

lved

in th

e m

anuf

actu

re a

nd s

uppl

y ch

ain

mus

t sha

re r

espo

nsi-

bilit

y fo

r th

e qu

ality

and

saf

ety

of th

e m

ater

ials

and

pro

duct

s to

ens

ure

that

they

are

fit f

or th

eir

inte

nded

use

.

1.5

The

res

pons

ibili

ties

plac

ed o

n an

y on

e in

divi

dual

sho

uld

not b

e so

ext

ensi

ve a

sto

pre

sent

any

ris

k to

qua

lity.

In

the

even

t of

a su

pplie

r ha

ving

a li

mite

d nu

mbe

rof

sta

ff,s

ome

dutie

s m

ay b

e de

lega

ted

or c

ontr

acte

d ou

t to

desi

gnat

ed p

erso

ns

Part

ies

invo

lved

in th

e ex

cipi

ent s

uppl

y ch

ain

shou

ld e

stab

lish

a Q

ualit

yM

anag

emen

t Sys

tem

to m

anag

e th

e qu

ality

of

thei

r pr

oduc

ts a

nd s

ervi

ces,

inor

der

to m

aint

ain

the

orig

inal

qua

lity

of th

e ex

cipi

ents

. Thi

s is

impo

rtan

t whe

nop

enin

g th

e or

igin

al m

anuf

actu

rer

seal

ed c

onta

iner

s,pe

rfor

min

g:bu

lk h

andl

ing,

sam

plin

g,te

stin

g,pr

oces

sing

(ph

ysic

al a

nd c

hem

ical

man

ipul

atio

n),r

epac

kag-

ing,

or r

elab

elin

g ac

tiviti

es. A

s an

ess

entia

l pre

requ

isite

for

any

Qua

lity

Man

agem

ent S

yste

m,t

he to

p m

anag

emen

t sho

uld

elab

orat

e a

corp

orat

e qu

ality

philo

soph

y (Q

ualit

y Po

licy)

.

A s

yste

m s

houl

d be

in p

lace

to c

ontr

ol d

ocum

ents

and

dat

a th

at r

elat

e to

the

requ

irem

ents

of

the

appl

icab

le Q

ualit

y Sy

stem

. It i

s su

gges

ted

to p

repa

re a

Qua

lity

Man

ual s

tatin

g th

e co

rpor

ate

Qua

lity

Polic

y an

d de

scri

bing

the

Qua

lity

Man

agem

ent S

yste

m. T

his

Qua

lity

Man

ual i

s th

e do

cum

ente

d ba

sis

for

the

Qua

lity

Syst

em. I

t des

crib

es th

e co

mm

itmen

t of

the

part

icip

ant i

nvol

ved

in th

eex

cipi

ent d

istr

ibut

ion

chai

n to

the

appr

opri

ate

qual

ity s

tand

ards

men

tione

d in

this

doc

umen

t. T

he Q

ualit

y M

anua

l sho

uld

incl

ude

at a

min

imum

the

follo

win

g el

emen

ts:

•sc

ope

of th

e Q

ualit

y M

anag

emen

t Sys

tem

,•

orga

niza

tiona

l str

uctu

re,

•w

ritte

n pr

oced

ures

,pro

cess

es a

nd r

esou

rces

or

refe

renc

e to

them

,and

•a

desc

ript

ion

of th

e se

quen

ce a

nd in

tera

ctio

n be

twee

n th

e pr

oced

ures

and

depa

rtm

enta

l fun

ctio

ns.

The

Qua

lity

Man

agem

ent S

yste

m s

houl

d al

so in

clud

e a

proc

edur

e to

ver

ify

that

any

supp

lier

of e

xcip

ient

s,pa

ckag

ing

mat

eria

ls o

r se

rvic

es h

as th

e ca

pabi

lity

toco

nsis

tent

ly m

eet p

revi

ousl

y ag

reed

req

uire

men

ts. T

his

may

incl

ude

peri

odic

audi

ts o

f th

e ve

ndor

’s m

anuf

actu

ring

fac

ility

if d

eem

ed n

eces

sary

.

See

1.2

Part

ies

invo

lved

sho

uld

shar

e re

spon

sibi

lity

for

assu

ring

that

the

exci

pien

t pro

-vi

ded

by th

e di

stri

buto

r co

nfor

ms

to th

e m

utua

lly a

gree

d sp

ecif

icat

ion

requ

ire-

men

ts o

f th

e ph

arm

aceu

tical

man

ufac

ture

r an

d/or

is s

uita

ble

for

the

inte

nded

use

of th

e ex

cipi

ent.

The

re s

houl

d be

an

adeq

uate

num

ber

of q

ualif

ied

pers

onne

l ava

ilabl

e ei

ther

in-

hous

e or

con

trac

tors

to c

arry

out

all

oper

atio

ns in

com

plia

nce

with

this

gui

de(r

efer

to 2

.2.)

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

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al E

xcip

ient

s C

ounc

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Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 7

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

who

are

app

ropr

iate

ly q

ualif

ied.

The

re s

houl

d,ho

wev

er,b

e no

gap

s or

une

x-pl

aine

d ov

erla

ps r

elat

ed to

the

appl

icat

ion

of G

TD

P

1.6

Whe

re e

lect

roni

c co

mm

erce

(e-

com

mer

ce)

is u

sed

defi

ned

proc

edur

es a

nd a

de-

quat

e sy

stem

s sh

ould

be

in p

lace

to e

nsur

e tr

acea

bilit

y an

d co

nfid

ence

in th

equ

ality

of

the

mat

eria

l.

1.7

Aut

hori

zed

rele

ase

proc

edur

es s

houl

d be

in p

lace

to e

nsur

e th

at m

ater

ial o

f an

appr

opri

ate

qual

ity is

sou

rced

fro

m a

ppro

ved

supp

liers

and

rel

ease

d fo

r its

inte

nded

pur

pose

.

1.8

Insp

ectio

n an

d ce

rtif

icat

ion

of c

ompl

ianc

e w

ith a

qua

lity

syst

em (

such

as

appl

i-ca

ble

Inte

rnat

iona

l Sta

ndar

ds O

rgan

izat

ion

(ISO

) se

ries

and

haz

ard

anal

ysis

and

criti

cal c

ontr

ol p

oint

(H

AC

CP)

) by

ext

erna

l bod

ies

is r

ecom

men

ded.

How

ever

,th

is s

houl

d no

t be

seen

as

a su

bstit

ute

for

the

impl

emen

tatio

n of

thes

e gu

ide-

lines

or

for

conf

orm

ing

with

pha

rmac

eutic

al G

MP

requ

irem

ents

,as

appl

icab

le.

1.9

A s

yste

m s

houl

d be

in p

lace

for

the

perf

orm

ance

of

regu

lar

inte

rnal

aud

its w

ithth

e ai

m o

f co

ntin

uous

impr

ovem

ent.

The

fin

ding

s of

the

audi

t and

any

cor

rec-

tive

actio

ns ta

ken

shou

ld b

e do

cum

ente

d an

d br

ough

t to

the

atte

ntio

n of

the

resp

onsi

ble

man

agem

ent.

2O

rgan

izat

ion

and

Per

sonn

el

2.1

The

re s

houl

d be

an

adeq

uate

org

aniz

atio

nal s

truc

ture

and

suf

fici

ent p

erso

nnel

shou

ld b

e em

ploy

ed to

car

ry o

ut a

ll th

e ta

sks

for

whi

ch th

e su

pplie

r is

res

pons

i-bl

e.

2.2

Indi

vidu

al r

espo

nsib

ilitie

s sh

ould

be

clea

rly

defi

ned,

unde

rsto

od b

y th

e in

divi

d-ua

ls c

once

rned

and

rec

orde

d in

wri

ting

(as

job

desc

ript

ions

or

in a

con

trac

t).

Cer

tain

act

iviti

es,s

uch

as s

uper

visi

on o

ver

perf

orm

ance

of

activ

ities

in a

ccor

-da

nce

with

loca

l leg

isla

tion,

may

req

uire

spe

cial

atte

ntio

n. P

erso

nnel

sho

uld

besu

itabl

y qu

alif

ied

and

auth

oriz

ed to

und

erta

ke th

eir

dutie

s an

d re

spon

sibi

litie

s.

2.3

All

pers

onne

l sho

uld

be a

war

e of

the

prin

cipl

es o

f G

TD

P.

See

6.10

.

If a

n ex

cipi

ent i

s pr

ovid

ed o

nly

in o

rigi

nally

sea

led

cont

aine

rs f

rom

the

man

u-fa

ctur

er,n

o ad

ditio

nal t

estin

g an

d ba

tch

rele

ase

are

requ

ired

. Ins

pect

ion

of th

ein

tegr

ity o

f th

e pa

ckag

ing

(inc

ludi

ng la

belin

g) a

nd s

eals

sho

uld

be c

arri

ed o

ut. A

copy

of

the

man

ufac

ture

r’s

qual

ity d

ocum

ents

(su

ch a

s C

OA

or

CO

C)

shou

ld b

epr

ovid

ed f

or e

ach

deliv

ery.

ISO

or

HA

CC

P ce

rtif

icat

ion

is n

ot a

man

dato

ry r

equi

rem

ent f

or e

xcip

ient

man

u-fa

ctur

ers

and

othe

r co

mpa

nies

invo

lved

in th

e su

pply

cha

in. T

hese

sta

ndar

dssh

ould

pro

vide

ass

uran

ce th

at th

e ex

cipi

ent w

as p

rodu

ced

and

hand

led

in c

onfo

r-m

ance

with

an

appr

opri

ate

qual

ity m

anag

emen

t sys

tem

(IP

EC

PQ

G G

MP

Gui

de[2

] is

rec

omm

ende

d).

Inte

rnal

aud

its s

houl

d be

car

ried

out

at a

fre

quen

cy b

ased

on

the

stat

us a

ndim

port

ance

of

the

Qua

lity

Man

agem

ent S

yste

m a

ctiv

ity. A

udits

and

fol

low

up

actio

ns s

houl

d be

car

ried

out

in a

ccor

danc

e w

ith d

ocum

ente

d pr

oced

ures

. Aud

itre

sults

sho

uld

be d

ocum

ente

d an

d di

scus

sed

with

man

agem

ent p

erso

nnel

hav

ing

resp

onsi

bilit

y in

the

area

aud

ited.

Fur

ther

mor

e,co

rrec

tive

actio

n an

d pr

even

tive

actio

n sh

ould

be

unde

rtak

en o

n th

e no

n-co

nfor

miti

es f

ound

.

Self

exp

lana

tory

Pers

onne

l per

form

ing

wor

k af

fect

ing

the

exci

pien

t qua

lity,

incl

udin

g th

ird

par-

ties,

shou

ld h

ave

an a

dequ

ate

com

bina

tion

of tr

aini

ng,e

duca

tion,

and

expe

rien

ceto

car

ry o

ut th

at w

ork.

Lev

els

of a

utho

riza

tion

shou

ld b

e cl

earl

y de

fine

d in

job

desc

ript

ions

. Rec

ords

sho

uld

be m

aint

aine

d lis

ting

the

nam

e,ad

dres

s,an

d qu

ali-

fica

tions

of

any

cont

ract

ed s

ervi

ce p

rovi

der

and

the

type

of

serv

ice

they

pro

vide

.

Aw

aren

ess

of th

e pr

inci

ples

incl

udes

this

IPE

C G

DP

Gui

de.

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 8

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

2.4

Pers

onne

l sho

uld

rece

ive

initi

al a

nd c

ontin

uing

trai

ning

rel

evan

t to

thei

r ta

sks.

All

pers

onne

l sho

uld

be m

otiv

ated

to s

uppo

rt th

e es

tabl

ishm

ent a

nd m

aint

e-na

nce

of q

ualit

y st

anda

rds.

2.5

Pers

onne

l dea

ling

with

haz

ardo

us m

ater

ials

(su

ch a

s hi

ghly

act

ive,

toxi

c,in

fec-

tious

or

sens

itisi

ng m

ater

ials

) sh

ould

be

give

n sp

ecif

ic tr

aini

ng a

nd s

houl

d be

prov

ided

with

the

nece

ssar

y pr

otec

tive

equi

pmen

t.

2.6

Pers

onne

l who

may

be

expo

sed

to m

ater

ials

fro

m o

pen

cont

aine

rs s

houl

d m

ain-

tain

goo

d hy

gien

e,ha

ve n

o op

en w

ound

s an

d be

equ

ippe

d w

ith a

n ap

prop

riat

epr

otec

tive

outf

it,su

ch a

s gl

oves

,mas

ks a

nd g

oggl

es.

3P

rem

ises

3.1

Prem

ises

mus

t be

loca

ted,

desi

gned

,con

stru

cted

,ada

pted

and

mai

ntai

ned

tosu

it th

e op

erat

ions

to b

e ca

rrie

d ou

t. T

heir

layo

ut a

nd d

esig

n m

ust a

im to

min

i-m

ize

the

risk

of

erro

rs a

nd p

erm

it ef

fect

ive

clea

ning

and

mai

nten

ance

in o

rder

to a

void

cro

ss-c

onta

min

atio

n,m

ix-u

ps,b

uild

-up

of d

ust o

r di

rt a

nd,i

n ge

nera

l,an

y ad

vers

e ef

fect

on

the

qual

ity o

f m

ater

ials

.

Qua

lity

stan

dard

s ap

plie

d sh

ould

be

part

of

a re

gula

r tr

aini

ng p

rogr

am p

rovi

ded

by q

ualif

ied

indi

vidu

als

and

the

trai

ning

sho

uld

be d

ocum

ente

d. T

he e

xten

t of

trai

ning

sho

uld

be d

epen

dent

upo

n th

e co

mpa

ny’s

act

iviti

es. A

ll pe

rson

nel

shou

ld r

ecei

ve in

itial

and

reg

ular

fol

low

-up

trai

ning

acc

ordi

ng to

the

pote

ntia

lim

pact

of

the

activ

ities

on

the

exci

pien

t.

Self

exp

lana

tory

To p

rote

ct e

xcip

ient

s fr

om c

onta

min

atio

n by

per

sonn

el a

ctiv

ities

suc

h as

han

-dl

ing

of u

npac

ked

exci

pien

t whi

le p

erfo

rmin

g op

erat

ions

like

exc

ipie

nt s

am-

plin

g,bu

lk h

andl

ing

and,

repa

ckag

ing

pers

onne

l sho

uld:

•w

ear

clea

n pr

otec

tive

appa

rel s

uch

as h

ead,

face

,han

d,an

d ar

m c

over

ings

,as

nece

ssar

y;•

rem

ove

or c

over

jew

elry

and

oth

er lo

ose

item

s;•

stor

e an

d co

nsum

e fo

od,d

rink

,tob

acco

pro

duct

s an

d si

mila

r ite

ms

only

ince

rtai

n de

sign

ated

are

as;

•re

ceiv

e an

ade

quat

e an

d co

ntin

ued

pers

onal

hyg

iene

trai

ning

to p

ract

ice

good

sani

tatio

n an

d he

alth

hab

its;

•be

inst

ruct

ed to

rep

ort t

o su

perv

isor

y pe

rson

nel a

ny h

ealth

con

ditio

ns th

atm

ay h

ave

an a

dver

se e

ffec

t on

exci

pien

ts.

Ext

ract

fro

m I

PEC

PQ

G G

MP

Gui

de 2

006

[2],

chap

ter

6.3.

1:(F

or th

e w

ord

“man

ufac

turi

ng”

read

“ha

ndlin

g”.)

Bui

ldin

gs a

nd F

acil

itie

sT

he p

reve

ntio

n of

con

tam

inat

ion

shou

ld b

e co

nsid

ered

in

the

desi

gn o

f th

e m

an-

ufac

turi

ng p

roce

sses

and

fac

ilit

ies,

part

icul

arly

whe

re t

he e

xcip

ient

is

expo

sed.

Bui

ldin

gs a

nd f

acil

itie

s us

ed i

n th

e pr

oduc

tion

,pro

cess

ing,

pack

agin

g,te

stin

g,or

sto

rage

of

an e

xcip

ient

sho

uld

be m

aint

aine

d in

a g

ood

stat

e of

rep

air

and

shou

ld b

e of

sui

tabl

e si

ze,c

onst

ruct

ion,

and

loca

tion

to

faci

lita

te c

lean

ing,

mai

nten

ance

,and

cor

rect

ope

rati

on,a

ppro

pria

te t

o th

e ty

pe o

f pr

oces

sing

.M

anuf

actu

ring

pro

cess

es a

ssoc

iate

d w

ith

the

prod

ucti

on o

f hi

ghly

sen

siti

zing

or

toxi

c pr

oduc

ts (

e.g.

her

bici

des,

pest

icid

es e

tc.)

sho

uld

be l

ocat

ed i

n de

dica

ted

faci

liti

es o

r eq

uipm

ent

sepa

rate

fro

m t

hat

used

for

exc

ipie

nt m

anuf

actu

re. I

f th

isis

not

pos

sibl

e,th

en a

ppro

pria

te m

easu

res

(e.g

. cle

anin

g,in

acti

vati

on)

shou

ld b

e

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 9

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

3.2

Mea

sure

s sh

ould

be

in p

lace

to p

reve

nt u

naut

hori

zed

pers

ons

from

ent

erin

g th

epr

emis

es.

3.3

Prem

ises

sho

uld

be d

esig

ned

and

equi

pped

so

as to

aff

ord

max

imum

pro

tect

ion

agai

nst t

he e

ntry

of

inse

cts,

rode

nts

or o

ther

ani

mal

s.

3.4

Suita

ble

supp

ortin

g fa

cilit

ies

and

utili

ties

(suc

h as

air

con

trol

,lig

htin

g an

d ve

n-til

atio

n) s

houl

d be

in p

lace

and

app

ropr

iate

to th

e ac

tiviti

es p

erfo

rmed

.

3.5

The

re s

houl

d no

rmal

ly b

e a

sepa

rate

sam

plin

g ar

ea f

or p

harm

aceu

tical

sta

rtin

gm

ater

ials

in a

con

trol

led

envi

ronm

ent.

If s

ampl

ing

is p

erfo

rmed

in th

e st

orag

ear

ea,i

t sho

uld

be c

ondu

cted

in s

uch

a w

ay a

s to

pre

vent

con

tam

inat

ion

orcr

oss-

cont

amin

atio

n. A

dequ

ate

clea

ning

pro

cedu

res

shou

ld b

e in

pla

ce f

or th

esa

mpl

ing

area

s.

4W

areh

ousi

ng a

nd S

tora

ge

GSP

is a

pplic

able

in a

ll ci

rcum

stan

ces

in w

hich

and

all

area

s w

here

mat

eria

lsar

e st

ored

.

4.1

The

re s

houl

d be

aut

hori

zed

proc

edur

es d

escr

ibin

g th

e ac

tiviti

es r

elat

ing

to th

ere

ceip

t,st

orag

e an

d di

stri

butio

n of

mat

eria

ls.

impl

emen

ted

to a

void

cro

ss-c

onta

min

atio

n an

d th

e ef

fect

iven

ess

of t

hese

mea

s-ur

es s

houl

d be

dem

onst

rate

d.T

here

sho

uld

be a

dequ

ate

faci

liti

es f

or t

he t

esti

ng o

f ra

w m

ater

ials

,pac

kagi

ngco

mpo

nent

s,in

term

edia

tes,

and

finis

hed

exci

pien

ts.

Self

exp

lana

tory

Ext

ract

fro

m I

PEC

PQ

G G

MP

Gui

de 2

006

[2],

chap

ter

6.4.

4:

Pest

Con

trol

Bui

ldin

gs s

houl

d be

free

from

infe

stat

ion

by r

oden

ts,b

irds

,ins

ects

,and

oth

er v

erm

in.

Som

e ra

w m

ater

ials

,par

ticul

arly

bot

anic

als,

may

con

tain

som

e un

avoi

dabl

e co

n-ta

min

atio

n,su

ch a

s ro

dent

or

othe

r an

imal

filth

or

infe

stat

ion.

The

man

ufac

ture

rsh

ould

hav

e su

ffici

ent c

ontr

ol m

etho

ds to

pre

vent

the

incr

ease

of s

uch

cont

amin

atio

nor

infe

stat

ion

in h

oldi

ng a

reas

or

its s

prea

d to

oth

er a

reas

of t

he p

lant

.

Self

exp

lana

tory

Self

exp

lana

tory

GSP

– G

ood

Stor

age

Prac

tice

[3]

Wri

tten

proc

edur

es s

houl

d de

scri

be r

ecei

pt o

f th

e ex

cipi

ent,

its s

tora

ge a

nd

furt

her

disp

atch

.So

me

cons

ider

atio

ns (

that

may

not

be

appl

icab

le in

all

situ

atio

ns)

are:

•R

ecei

pt:v

isua

l ins

pect

ion

of th

e co

ntai

ner

(pac

kage

d or

bul

k) in

tegr

ity,c

on-

firm

atio

n of

mat

eria

l ide

ntity

fro

m th

e la

bel a

gain

st d

ocum

enta

tion,

evid

ence

of in

fest

atio

n;

•St

orag

e:cl

eanl

ines

s of

exc

ipie

nt s

tora

ge a

rea,

accu

racy

of

the

inve

ntor

y lo

cato

r sy

stem

;

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

0

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

4.2

Stor

age

area

s sh

ould

be

of s

uffi

cien

t cap

acity

to a

llow

ord

erly

sto

rage

of

the

vari

ous

cate

gori

es o

f m

ater

ials

.

4.3

Rec

eipt

and

dis

patc

h ba

ys s

houl

d be

equ

ippe

d w

ith th

e m

eans

to p

rote

ct m

ater

i-al

s fr

om th

e w

eath

er. R

ecep

tion

area

s sh

ould

be

desi

gned

and

equ

ippe

d to

allo

wco

ntai

ners

of

inco

min

g m

ater

ials

to b

e cl

eane

d be

fore

sto

rage

if n

eces

sary

.

4.4

Segr

egat

ed a

reas

sho

uld

be p

rovi

ded

for

the

stor

age

of r

ejec

ted,

reca

lled

and

retu

rned

mat

eria

l,in

clud

ing

thos

e w

ith d

amag

ed p

acka

ging

.

4.5

Segr

egat

ed a

reas

and

mat

eria

ls s

houl

d be

app

ropr

iate

ly id

entif

ied.

4.6

The

req

uire

d st

orag

e co

nditi

ons

as s

peci

fied

for

the

prod

uct s

houl

d be

mai

n-ta

ined

with

in a

ccep

tabl

e lim

its. T

he s

tora

ge a

reas

sho

uld

be k

ept c

lean

and

dry

.

4.7

Whe

re s

peci

al s

tora

ge c

ondi

tions

are

req

uire

d (e

.g. p

artic

ular

req

uire

men

ts f

orte

mpe

ratu

re o

r hu

mid

ity)

thes

e sh

ould

be

prov

ided

,mon

itore

d an

d re

cord

ed.

4.8

Hig

hly

activ

e m

ater

ials

,nar

cotic

s,ot

her

dang

erou

s dr

ugs

and

subs

tanc

es

pres

entin

g sp

ecia

l ris

ks o

f ab

use,

fire

or

expl

osio

n sh

ould

be

stor

ed in

saf

e,de

dica

ted

and

secu

re a

reas

. In

addi

tion

inte

rnat

iona

l con

vent

ions

and

nat

iona

lle

gisl

atio

n m

ay a

pply

.

4.9

Spec

ial a

ttent

ion

shou

ld b

e gi

ven

to th

e de

sign

,use

,cle

anin

g an

d m

aint

enan

ceof

all

equi

pmen

t for

bul

k ha

ndlin

g an

d st

orag

e,su

ch a

s ta

nks

and

silo

s.

4.10

Spill

ages

sho

uld

be c

lean

ed a

s so

on a

s po

ssib

le to

pre

vent

pos

sibl

e cr

oss-

cont

amin

atio

n an

d ha

zard

•D

ispa

tch:

truc

k cl

eanl

ines

s,tr

acki

ng r

ecor

ds,v

erif

icat

ion

of c

orre

ct m

ater

ial

by m

atch

ing

exci

pien

t lab

el a

gain

st d

ispa

tch

docu

men

tatio

n,cl

eanl

ines

s of

cont

aine

rs,a

nd tr

ansp

ort e

quip

men

t.

Exc

ipie

nts

shou

ld b

e st

ored

in a

man

ner

to p

rote

ct th

eir

qual

ity a

s w

ell a

s th

eir

pack

agin

g an

d la

belin

g. T

he f

acili

ty s

houl

d be

org

aniz

ed in

a m

anne

r to

fac

ilita

tese

lect

ion

of d

esig

nate

d m

ater

ials

. Exc

ipie

nts

shou

ld b

e st

ored

in c

onfo

rman

ce w

ithsa

fety

req

uire

men

ts.

Prot

ectio

n fr

om a

dver

se e

nvir

onm

enta

l con

ditio

ns s

houl

d be

con

side

red

as a

min

imum

req

uire

men

t (e.

g. r

oof

or s

helte

r) b

ut s

peci

fied

sto

rage

con

ditio

nssh

ould

be

met

whe

n re

quir

ed.

See

4.2

Segr

egat

ion

can

be a

chie

ved

thro

ugh

phys

ical

or

com

pute

r co

ntro

l with

ap

prop

riat

e sy

stem

s in

pla

ce.

See

4.2

An

asse

ssm

ent s

houl

d be

con

duct

ed to

con

firm

that

des

igna

ted

cond

ition

s co

uld

be m

et. R

ecor

ds s

houl

d de

mon

stra

te o

n-go

ing

conf

orm

ance

to s

peci

fied

con

di-

tions

. In

such

cas

es r

ecor

ders

sho

uld

be in

stal

led.

Sep

arat

e ai

r-co

nditi

oned

are

assh

ould

be

cons

ider

ed w

here

nec

essa

ry.

Self

exp

lana

tory

See

5.1

Self

exp

lana

tory

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

1

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

4.11

Prov

isio

n sh

ould

be

mad

e fo

r th

e pr

oper

and

saf

e st

orag

e of

was

te m

ater

ials

awai

ting

disp

osal

. Tox

ic s

ubst

ance

s an

d fl

amm

able

mat

eria

ls s

houl

d be

sto

red

in s

uita

bly

desi

gned

,sep

arat

e,cl

osed

con

tain

ers

in e

nclo

sed

area

s,ta

king

into

acco

unt t

he r

elev

ant n

atio

nal l

egis

latio

n

4.12

A s

yste

m s

houl

d be

in p

lace

to e

nsur

e th

at th

ose

mat

eria

ls d

ue to

exp

ire

firs

tar

e so

ld o

r di

stri

bute

d fi

rst (

Ear

liest

Exp

iry/

Firs

t Out

(E

EFO

)). W

here

no

expi

ry d

ates

are

spe

cifi

ed f

or th

e m

ater

ials

,the

Fir

st I

n/Fi

rst O

ut (

FIFO

) pr

inci

ple

shou

ld b

e ap

plie

d

4.13

Stor

age

area

s sh

ould

be

clea

n an

d fr

ee f

rom

acc

umul

ated

was

te a

nd f

rom

ver

-m

in. A

wri

tten

sani

tatio

n pr

ogra

mm

e sh

ould

be

avai

labl

e,in

dica

ting

the

fre-

quen

cy o

f cl

eani

ng a

nd th

e m

etho

ds to

be

used

to c

lean

the

prem

ises

and

stor

age

area

s. T

here

sho

uld

also

be

a w

ritte

n pr

ogra

mm

e fo

r pe

st c

ontr

ol.

5E

quip

men

t

5.1

Equ

ipm

ent m

ust b

e lo

cate

d,de

sign

ed,c

onst

ruct

ed,a

dapt

ed,u

sed

and

mai

n-ta

ined

to s

uit t

he o

pera

tions

to b

e ca

rrie

d ou

t. D

efec

tive

equi

pmen

t sho

uld

not

be u

sed,

and

shou

ld e

ither

be

rem

oved

or

labe

led

as d

efec

tive.

Equ

ipm

ent

shou

ld b

e di

spos

ed o

f in

suc

h a

way

as

to p

reve

nt a

ny m

isus

e.

See

sect

ions

4.4

,4.5

and

4.8

.

Self

exp

lana

tory

The

re s

houl

d be

rec

ords

to s

how

whe

n in

spec

tions

wer

e m

ade

incl

udin

g ob

ser-

vatio

ns o

f th

e fi

ndin

gs f

or v

erm

in a

nd a

ll pe

st c

ontr

ol a

ctiv

ities

. Mat

eria

ls u

sed

for

cont

rol o

f ve

rmin

sho

uld

not a

dver

sely

aff

ect t

he E

xcip

ient

(se

e al

so 3

.3).

Ext

ract

fro

m I

PEC

PQ

G G

MP

Gui

de 2

006

[2],

chap

ter

6.3.

2:

Equ

ipm

ent

Equ

ipm

ent u

sed

in th

e pr

oduc

tion,

proc

essi

ng,p

acka

ging

,tes

ting,

or s

tora

ge o

f an

exci

pien

t sho

uld

be m

aint

aine

d in

a g

ood

stat

e of

rep

air

and

shou

ld b

e of

sui

tabl

esi

ze,c

onst

ruct

ion,

and

loca

tion

to fa

cilit

ate

clea

ning

,mai

nten

ance

,and

cor

rect

oper

atio

n,de

pend

ing

on th

e ty

pe o

f pro

cess

ing

(e.g

. bat

ch v

s. c

ontin

uous

).E

quip

men

t sho

uld

be c

omm

issi

oned

bef

ore

use

to e

nsur

e th

at it

is fu

nctio

ning

as

inte

nded

.W

here

equ

ipm

ent i

s lo

cate

d ou

tdoo

rs th

ere

shou

ld b

e su

itabl

e co

ntro

l to

min

imiz

e th

eri

sk to

exc

ipie

nt q

ualit

y fr

om th

e en

viro

nmen

t (e.

g. p

roce

ssin

g w

ithin

a c

lose

d sy

stem

).

Equ

ipm

ent

Con

stru

ctio

n P

roce

ss e

quip

men

t sh

ould

be

cons

truc

ted

so t

hat

cont

act

surf

aces

wil

l no

t be

reac

tive

,add

itiv

e,or

abs

orpt

ive

and

thus

not

alt

er t

he q

uali

ty o

f th

e ex

cipi

ent.

Subs

tanc

es r

equi

red

for

oper

atio

n,su

ch a

s lu

bric

ants

or

cool

ants

,sho

uld

pref

er-

ably

not

com

e in

to c

onta

ct w

ith

raw

mat

eria

ls,p

acka

ging

mat

eria

ls,i

nter

med

i-at

es,o

r fin

ishe

d ex

cipi

ents

. Whe

re c

onta

ct i

s po

ssib

le,s

ubst

ance

s su

itab

le f

orus

e in

foo

d ap

plic

atio

ns s

houl

d be

uti

lize

d.E

quip

men

t sh

ould

be

desi

gned

to

min

imiz

e th

e po

ssib

ilit

y of

con

tam

inat

ion

caus

ed b

y di

rect

ope

rato

r co

ntac

t in

suc

h ac

tivi

ties

as

the

unlo

adin

g of

cen

-tr

ifug

e ba

gs,u

se o

f tr

ansf

er h

oses

(pa

rtic

ular

ly t

hose

use

d to

tra

nsfe

r po

wde

rs),

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

2

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

5.2

The

layo

ut,d

esig

n an

d us

e of

equ

ipm

ent m

ust a

im to

min

imiz

e th

e ri

sk o

f er

rors

and

to p

erm

it ef

fect

ive

clea

ning

and

mai

nten

ance

to a

void

cro

ss-c

onta

min

atio

n,bu

ild-u

p of

dus

t or

dirt

and

any

adv

erse

eff

ect o

n th

e qu

ality

of

mat

eria

ls

5.3

Fixe

d pi

pew

ork

shou

ld b

e cl

earl

y la

belle

d to

indi

cate

the

cont

ents

and

,whe

reap

plic

able

,the

dir

ectio

n of

flo

w.

5.4

All

serv

ices

,pip

ing

and

devi

ces

shou

ld b

e ad

equa

tely

mar

ked

and

spec

ial a

tten-

tion

paid

to th

e pr

ovis

ion

of n

on-i

nter

chan

geab

le c

onne

ctio

ns o

r ad

apto

rs f

orda

nger

ous

gase

s,liq

uids

and

oth

er m

ater

ials

.

5.5

Bal

ance

s an

d ot

her

mea

suri

ng e

quip

men

t of

an a

ppro

pria

te r

ange

and

pre

cisi

onsh

ould

be

avai

labl

e an

d sh

ould

be

calib

rate

d on

a s

ched

uled

bas

is.

5.6

Proc

edur

es s

houl

d be

in p

lace

for

the

oper

atio

n an

d m

aint

enan

ce o

f eq

uipm

ent.

Lub

rica

nts

and

othe

r m

ater

ials

use

d on

sur

face

s th

at c

ome

into

dir

ect c

onta

ctw

ith th

e m

ater

ials

sho

uld

be o

f th

e ap

prop

riat

e gr

ade,

e.g.

foo

d-gr

ade

oil.

5.7

Was

hing

and

cle

anin

g eq

uipm

ent s

houl

d be

cho

sen

and

used

suc

h th

at it

can

not

be a

sou

rce

of c

onta

min

atio

n.

5.8

Ded

icat

ed e

quip

men

t sho

uld

be u

sed

whe

re p

ossi

ble

whe

n ha

ndlin

g an

d/or

pro

-ce

ssin

g ph

arm

aceu

tical

sta

rtin

g m

ater

ials

. Whe

re n

on-d

edic

ated

equ

ipm

ent i

sus

ed c

lean

ing

valid

atio

n sh

ould

be

perf

orm

ed.

and

the

oper

atio

n of

dry

ing

equi

pmen

t an

d pu

mps

. The

san

itar

y de

sign

of

tran

s-fe

r an

d pr

oces

sing

equ

ipm

ent

shou

ld b

e ev

alua

ted.

Equ

ipm

ent

wit

h m

ovin

g pa

rts

shou

ld b

e as

sess

ed i

n re

gard

to

the

inte

grit

y of

sea

ls a

nd p

acki

ng m

ater

ials

to

cont

rol

the

risk

of

cont

amin

atio

n.

Equ

ipm

ent

Mai

nten

ance

D

ocum

ente

d pr

oced

ures

sho

uld

be e

stab

lish

ed a

nd f

ollo

wed

for

mai

nten

ance

of

crit

ical

equ

ipm

ent

used

in

the

prod

ucti

on,p

roce

ssin

g,pa

ckag

ing,

test

ing,

orho

ldin

g of

the

exc

ipie

nt. T

here

sho

uld

be r

ecor

ds o

f qu

alit

y cr

itic

al e

quip

men

tus

e an

d m

aint

enan

ce. T

hese

rec

ords

can

be

in t

he f

orm

of

a lo

g,co

mpu

ter

data

-ba

se,o

r ot

her

appr

opri

ate

docu

men

tati

on.

Self

exp

lana

tory

Self

exp

lana

tory

Self

exp

lana

tory

The

re s

houl

d be

pro

cedu

res

in p

lace

for

cal

ibra

tion

and

mea

ns to

ver

ify

calib

ratio

nst

atus

. Cal

ibra

tion

reco

rds

shou

ld b

e m

aint

aine

d.

See

5.1.

Self

exp

lana

tory

Whe

n no

n-de

dica

ted

equi

pmen

t com

ing

in d

irec

t con

tact

with

the

prod

uct i

sus

ed f

or e

xcip

ient

han

dlin

g (e

.g. s

tora

ge ta

nks,

bulk

truc

ks,p

ipes

and

hos

es,

repa

ckag

ing

equi

pmen

t etc

.; se

e al

so 7

.7),

appr

opri

ate

clea

ning

pro

cedu

res

and

effe

ctiv

e cl

eani

ng s

ched

ules

sho

uld

be m

aint

aine

d an

d re

cord

ed.

Mul

ti-pu

rpos

eeq

uipm

ent s

houl

d on

ly b

e us

ed a

gain

aft

er v

erif

icat

ion

of th

e cl

eani

ng e

ffic

ienc

y.C

lean

ing

effi

cien

cy s

houl

d be

ver

ifie

d by

e.g

.:

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

3

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

6D

ocum

enta

tion

6.1

Doc

umen

ts,i

n pa

rtic

ular

inst

ruct

ions

and

pro

cedu

res

rela

ting

to a

ny a

ctiv

ityth

at m

ight

hav

e an

impa

ct o

n th

e qu

ality

of

mat

eria

ls,s

houl

d be

des

igne

d,co

m-

plet

ed,r

evie

wed

and

dis

trib

uted

with

car

e. D

ocum

ents

sho

uld

be c

ompl

eted

,ap

prov

ed,s

igne

d an

d da

ted

by a

ppro

pria

te a

utho

rize

d pe

rson

s an

d sh

ould

not

be c

hang

ed w

ithou

t aut

hori

zatio

n.

6.2

Doc

umen

ts s

houl

d ha

ve u

nam

bigu

ous

cont

ents

:the

ir ti

tle,n

atur

e an

d pu

rpos

esh

ould

be

clea

rly

stat

ed. T

hey

shou

ld b

e la

id o

ut in

an

orde

rly

man

ner

and

beea

sy to

che

ck.

6.3

Ori

gina

l Cer

tific

ates

of A

naly

sis

(CO

As)

sho

uld

acco

mpa

ny m

ater

ials

sup

plie

dby

man

ufac

ture

rs to

sup

plie

rs. C

OA

s is

sued

by

the

man

ufac

ture

r sh

ould

indi

-ca

te w

hich

res

ults

wer

e ob

tain

ed b

y te

stin

g th

e or

igin

al m

ater

ial a

nd w

hich

resu

lts c

ame

from

ski

p lo

t tes

ting.

The

use

of

the

Mod

el C

OA

as

adop

ted

byth

e W

HO

Exp

ert C

omm

ittee

on

Spec

ific

atio

ns f

or P

harm

aceu

tical

Pre

para

tions

is r

ecom

men

ded

[5].

6.4

Bef

ore

any

mat

eria

l is

sold

or

dist

ribu

ted,

the

supp

lier

shou

ld e

nsur

e th

at th

eC

OA

s an

d re

sults

are

ava

ilabl

e an

d th

at th

e re

sults

are

with

in th

e re

quir

ed s

pec-

ific

atio

ns. A

ltern

ativ

ely

the

cust

omer

sho

uld

be in

form

ed w

ithou

t del

ay o

f th

ere

sults

as

soon

as

thes

e be

com

e av

aila

ble.

For

eac

h sh

ipm

ent t

he C

OA

sho

uld

be f

orw

arde

d to

the

phar

mac

eutic

al p

rodu

ct m

anuf

actu

rer.

•te

stin

g th

e fi

nal r

inse

aft

er c

lean

ing

for

resi

dues

of

the

prev

ious

pro

duct

or,

•ch

ecki

ng th

e eq

uipm

ent a

fter

cle

anin

g fo

r re

sidu

es o

f th

e pr

evio

us p

rodu

ct

or a

ltern

ativ

ely,

•by

test

ing

each

bat

ch f

or r

esid

ues

of th

e pr

evio

us p

rodu

ct h

andl

ed w

ith th

esa

me

equi

pmen

t•

in o

rder

to a

void

con

tam

inat

ion

and

carr

y-ov

er o

f pre

viou

sly

proc

esse

d pr

oduc

ts.

Self

exp

lana

tory

A r

evis

ion

hist

ory

of d

ocum

ents

sho

uld

be r

eadi

ly a

vaila

ble.

A d

istr

ibut

or s

houl

d no

t cha

nge

the

orig

inal

title

and

dat

a of

the

CO

A o

r ot

her

qual

ity d

ocum

ents

. Whe

neve

r po

ssib

le,t

he o

rigi

nal m

anuf

actu

rer’

s do

cum

enta

-tio

n sh

ould

be

used

,or

tran

scri

ptio

n of

dat

a sh

ould

be

veri

fied

. The

ori

gina

lm

anuf

actu

ring

site

sho

uld

be id

entif

ied

by n

ame

or u

niqu

e id

entif

ier

on th

e C

OA

or a

ny o

ther

doc

umen

t agr

eed

upon

with

the

cust

omer

.A

dditi

onal

dat

a re

sulti

ng f

rom

ana

lyse

s co

nduc

ted

by th

e di

stri

buto

r sh

ould

be

prov

ided

with

cle

ar in

dica

tion

of th

e so

urce

of

data

. Qua

lity

docu

men

ts s

houl

dal

low

trac

eabi

lity

back

to th

e m

anuf

actu

rer,

alon

g w

ith a

con

tact

ref

eren

ce.

If a

ny lo

t mix

ing

is c

arri

ed o

ut,C

OA

s fr

om m

anuf

actu

rers

are

no

long

er v

alid

and

the

dist

ribu

tor

shou

ld p

erfo

rm a

naly

ses

in it

s ow

n la

bora

tory

or

at a

nam

edan

d qu

alif

ied

cont

ract

labo

rato

ry.

Oth

erw

ise

the

dist

ribu

tor

can

supp

ly a

cer

tifi-

cate

of

com

plia

nce

(CO

C),

prov

ided

that

all

othe

r re

pack

agin

g an

d st

orag

e ac

tiv-

ities

are

car

ried

out

acc

ordi

ng to

thes

e gu

idel

ines

.

Self

exp

lana

tory

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

4

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

6.5

The

ori

gina

l man

ufac

ture

r an

d in

term

edia

ries

han

dlin

g th

e m

ater

ial s

houl

dal

way

s be

trac

eabl

e an

d th

e in

form

atio

n av

aila

ble

to a

utho

ritie

s an

d en

d-us

ers,

dow

nstr

eam

and

ups

trea

m.

6.6

Mec

hani

sms

shou

ld e

xist

to a

llow

for

tran

sfer

of

info

rmat

ion,

incl

udin

g th

etr

ansf

er o

f qu

ality

or

regu

lato

ry in

form

atio

n be

twee

n a

man

ufac

ture

r an

d a

cust

omer

,and

of

info

rmat

ion

to th

e re

gula

tory

aut

hori

ty u

pon

requ

est.

6.7

Lab

els

appl

ied

to c

onta

iner

s sh

ould

be

clea

r,un

ambi

guou

s,pe

rman

ently

fix

edan

d in

the

com

pany

’s a

gree

d fo

rmat

. The

info

rmat

ion

on th

e la

bel s

houl

d be

inde

lible

.

6.8

Eac

h co

ntai

ner

shou

ld b

e id

entif

ied

by la

belli

ng b

eari

ng a

t lea

st th

e fo

llow

ing

info

rmat

ion:

•th

e na

me

of th

e ph

arm

aceu

tical

sta

rtin

g m

ater

ial,

incl

udin

g gr

ade

and

refe

renc

e to

pha

rmac

opoe

ias,

whe

re r

elev

ant;

•if

app

licab

le,w

ith th

e In

tern

atio

nal N

onpr

opri

etar

y N

ames

(IN

Ns)

;•

the

amou

nt (

wei

ght o

r vo

lum

e);

•th

e ba

tch

num

ber

assi

gned

by

the

orig

inal

man

ufac

ture

r or

the

batc

h nu

mbe

ras

sign

ed b

y th

e re

pack

er,i

f th

e m

ater

ial h

as b

een

repa

cked

and

rel

abel

led;

•th

e re

test

dat

e or

exp

iry

date

(w

here

app

licab

le);

•an

y sp

ecia

l sto

rage

con

ditio

ns;

•ha

ndlin

g pr

ecau

tions

,whe

re n

eces

sary

;•

iden

tific

atio

n of

the

orig

inal

man

ufac

turi

ng s

ite; a

nd•

nam

e an

d co

ntac

t det

ails

of

the

supp

lier.

6.9

Rel

evan

t sto

rage

,han

dlin

g an

d sa

fety

dat

a sh

eets

sho

uld

be a

vaila

ble.

6.10

Rec

ords

mus

t be

kept

and

mus

t be

read

ily a

vaila

ble

upon

req

uest

in a

ccor

danc

ew

ith G

SP [

3].

7R

epac

kagi

ng a

nd R

elab

ellin

g

7.1

Ope

ratio

ns,s

uch

as c

ombi

ning

into

a h

omog

eneo

us b

atch

,rep

acka

ging

and

/or

rela

belli

ng,a

re m

anuf

actu

ring

pro

cess

es a

nd th

eir

perf

orm

ance

sho

uld

ther

efor

efo

llow

GM

P.

Self

exp

lana

tory

Self

exp

lana

tory

Self

exp

lana

tory

Lab

el g

ener

atin

g sy

stem

s an

d pr

oced

ures

sho

uld

be c

ontr

olle

d an

d do

cum

ente

d.A

ppro

pria

te v

erif

icat

ion

and

reco

rds

shou

ld b

e m

aint

aine

d.

If a

gree

d up

on w

ith th

e ph

arm

aceu

tical

cus

tom

er in

form

atio

n ab

out t

he o

rigi

nal

man

ufac

turi

ng s

ite m

ay a

lso

be p

rovi

ded

in o

ther

way

s or

on

othe

r do

cum

ents

.

Self

exp

lana

tory

The

sec

urity

and

met

hods

of

arch

ivin

g an

d re

trie

val o

f su

ch r

ecor

ds s

houl

d be

con

side

red.

Proc

esse

s w

here

exc

ipie

nts

are

expo

sed

to th

e en

viro

nmen

t suc

h as

tran

sfer

ring

exci

pien

t fro

m o

ne c

onta

iner

to a

noth

er,e

.g. f

rom

bul

k eq

uipm

ent t

o st

orag

eta

nks/

silo

s or

fro

m s

tora

ge ta

nks/

silo

s in

to c

onta

iner

s,ar

e cr

itica

l for

pro

duct

qual

ity. U

nder

thes

e co

nditi

ons

exci

pien

ts m

ay b

e co

ntam

inat

ed w

ith o

ther

pro

d-uc

ts,l

ubri

cant

s,cl

eane

rs o

r an

y ot

her

fore

ign

mat

ters

. To

min

imiz

e th

ese

risk

sIP

EC

PQ

G G

MP

prin

cipl

es s

houl

d be

app

lied.

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

5

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

7.2

Spec

ial a

ttent

ion

shou

ld b

e gi

ven

to th

e fo

llow

ing

poin

ts:

•pr

even

tion

of c

onta

min

atio

n,cr

oss-

cont

amin

atio

n an

d m

ix-u

ps;

•se

curi

ty o

f st

ocks

of

labe

ls,l

ine

clea

ranc

e ch

ecks

,on-

line

insp

ectio

ns,

dest

ruct

ion

of e

xces

s ba

tch-

prin

ted

labe

ls;

•go

od s

anita

tion

and

hygi

ene

prac

tices

;

•m

aint

aini

ng b

atch

inte

grity

(no

rmal

ly m

ixin

g of

dif

fere

nt b

atch

es o

f th

esa

me

solid

mat

eria

l sho

uld

not b

e do

ne);

•as

par

t of

batc

h re

cord

s al

l lab

els

that

wer

e re

mov

ed f

rom

the

orig

inal

con

-ta

iner

dur

ing

oper

atio

ns,a

nd a

sam

ple

of th

e ne

w la

bel,

shou

ld b

e ke

pt;

Spec

ial a

ttent

ion

shou

ld b

e gi

ven

to th

e fo

llow

ing

poin

ts:

•C

onta

min

atio

n,cr

oss-

cont

amin

atio

n an

d m

ix-u

ps s

houl

d be

avo

ided

by

usin

g su

itabl

e eq

uipm

ent a

nd c

lean

ing

proc

edur

es a

ccor

ding

to th

e re

com

-m

enda

tions

of

chap

ter

5 of

this

doc

umen

t and

with

ade

quat

e la

belin

g.E

nvir

onm

enta

l con

ditio

ns a

nd r

epac

kagi

ng p

roce

dure

s sh

ould

be

desi

gned

toav

oid

cont

amin

atio

n an

d cr

oss-

cont

amin

atio

n du

ring

rep

acka

ging

and

rel

a-be

ling

oper

atio

ns. F

ilter

ed a

ir in

the

repa

ckag

ing

area

sho

uld

be c

onsi

dere

dw

here

nec

essa

ry f

or th

e pr

oduc

t. Pr

otec

tive

clot

hing

for

the

oper

ator

s sh

ould

be c

lear

ly d

efin

ed.

•L

abel

s sh

ould

be

prin

ted

with

a c

ontr

olle

d sy

stem

ens

urin

g th

at a

ll ne

cess

ary

info

rmat

ion

is c

orre

ct (

see

6.8)

.Suf

fici

ent c

ross

chec

ks s

houl

d be

inst

alle

d to

ensu

re p

rope

r da

ta tr

ansf

er. A

pro

cedu

re s

houl

d be

inst

alle

d to

avo

id m

is-

labe

ling.

The

refo

re p

rint

ing

and

usag

e of

labe

ls s

houl

d be

a r

estr

icte

dpr

oces

s. A

ll la

belin

g op

erat

ions

(e.

g. g

ener

atin

g,pr

intin

g,st

orag

e,us

age,

dest

ruct

ion)

sho

uld

alw

ays

been

rec

orde

d. L

abel

ed c

onta

iner

s sh

ould

be

insp

ecte

d an

d su

rplu

s la

bels

sho

uld

be d

estr

oyed

to a

void

any

mis

use.

If

labe

ls w

ill n

ot b

e pr

inte

d ju

st in

–tim

e,se

curi

ty s

tock

sho

uld

be c

ontr

olle

dan

d lim

ited

acce

ss s

houl

d be

def

ined

.

•R

epac

kagi

ng a

nd r

elab

elin

g pr

oces

ses

shou

ld b

e ca

rrie

d ou

t in

an e

nvir

on-

men

t cle

an e

noug

h to

avo

id c

onta

min

atio

n. I

t sho

uld

be c

lear

ly d

efin

edw

here

and

how

an

exci

pien

t will

be

repa

ckag

ed a

nd r

elab

eled

. Per

sonn

elin

volv

ed in

rep

acka

ging

pro

cess

es s

houl

d w

ear

clea

n pr

otec

tive

appa

rel s

uch

as h

ead,

face

,han

d,an

d ar

m c

over

ings

,if

nece

ssar

y an

d pr

actic

e ap

prop

riat

epe

rson

nel h

ygie

ne (

e.g.

han

d di

sinf

ectio

n,fo

llow

ing

heal

th r

equi

rem

ents

,he

alth

mon

itori

ng,c

over

ing

expo

sed

jew

elry

). P

erso

nnel

sho

uld

be tr

aine

d on

spec

ial h

ygie

ne r

equi

rem

ents

. Tra

inin

g sh

ould

be

reco

rded

. Rep

acka

ging

area

s sh

ould

be

regu

larl

y cl

eane

d an

d sa

nitiz

ed.

•W

here

new

bat

ch n

umbe

rs a

re a

ssig

ned,

trac

eabi

lity

to o

rigi

nal b

atch

num

-be

rs s

houl

d be

ens

ured

by

prop

er d

ocum

enta

tion.

Ass

igni

ng o

ne b

atch

num

-be

r to

con

tain

ers

of d

iffe

rent

bat

ches

com

plyi

ng w

ith th

e sa

me

spec

ific

atio

nis

an

unac

cept

able

pra

ctic

e (s

ee a

lso

7.3

and

7.4)

.

•Se

lf e

xpla

nato

ry

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

6

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

•if

mor

e th

an o

ne b

atch

of

labe

l is

used

in o

ne o

pera

tion,

sam

ples

of

each

batc

h sh

ould

be

kept

; and

•m

aint

aini

ng p

rodu

ct id

entit

y an

d in

tegr

ity.

7.3

Whe

n di

ffer

ent b

atch

es o

f a

mat

eria

l fro

m th

e sa

me

orig

inal

man

ufac

turi

ng

site

are

rec

eive

d by

a d

istr

ibut

or a

nd c

ombi

ned

into

a h

omog

enou

s ba

tch,

the

conf

orm

ity o

f ea

ch b

atch

with

its

spec

ific

atio

n sh

ould

be

conf

irm

ed b

efor

e it

is a

dded

.

7.4

Onl

y m

ater

ials

fro

m th

e sa

me

man

ufac

turi

ng s

ite r

ecei

ved

by a

dis

trib

utor

and

conf

orm

ing

to th

e sa

me

spec

ific

atio

ns c

an b

e m

ixed

. If

diff

eren

t bat

ches

of

the

sam

e m

ater

ial a

re m

ixed

to f

orm

a h

omog

eneo

us b

atch

it s

houl

d be

def

ined

as

ane

w b

atch

,tes

ted

and

supp

lied

with

a b

atch

cer

tific

ate

of a

naly

sis.

In

such

case

s th

e cu

stom

er s

houl

d be

info

rmed

that

the

mat

eria

l sup

plie

d is

a m

ixtu

reof

man

ufac

ture

rs’b

atch

es. T

he s

uppl

ied

mat

eria

l mus

t hav

e a

cert

ific

ate

of c

on-

form

ity to

a s

peci

fica

tion

at d

ate

of s

uppl

y.

7.5

In a

ll ca

ses

the

orig

inal

CO

A o

f th

e or

igin

al m

anuf

actu

rer

shou

ld b

e pr

ovid

ed.

If r

etes

ting

is d

one,

both

the

orig

inal

and

the

new

CO

A s

houl

d be

pro

vide

d.T

he b

atch

ref

erre

d to

on

the

new

CO

A s

houl

d be

trac

eabl

e to

the

orig

inal

CO

A.

7.6

Rep

acka

ging

of

mat

eria

ls s

houl

d be

car

ried

out

with

pri

mar

y pa

ckag

ing

mat

eri-

als

for

whi

ch th

e qu

ality

and

sui

tabi

lity

have

bee

n es

tabl

ishe

d to

be

equa

l to

orbe

tter

than

thos

e of

the

orig

inal

con

tain

er. T

he a

ppro

val o

f th

e su

pplie

r is

nec

-es

sary

for

the

pack

agin

g m

ater

ial u

sed

for

the

repa

ckag

ing.

•Se

lf e

xpla

nato

ry

•A

ll re

pack

agin

g an

d re

labe

ling

proc

esse

s sh

ould

be

desi

gned

and

car

ried

out

to a

void

com

min

glin

g an

d ca

rry-

over

and

to e

nsur

e fu

ll tr

acea

bilit

y of

the

exci

pien

ts b

ack

to th

e or

igin

al m

anuf

actu

rer

and

trac

eabi

lity

dow

nstr

eam

toth

e fi

nal c

usto

mer

. Eve

ry s

tep

shou

ld b

e su

ffic

ient

ly r

ecor

ded

by r

espo

nsib

lepe

rson

nel.

Nam

e of

ope

rato

r,da

te a

nd ti

me

of e

very

ste

p sh

ould

als

o be

reco

rded

. Thi

s sh

ould

als

o be

ens

ured

if c

ompu

teri

zed

syst

ems

are

used

.

All

repa

ckag

ing

and

rela

belin

g re

quir

emen

ts s

houl

d be

def

ined

in

wri

tten

proc

edur

es.

Ble

ndin

g of

bat

ches

or

lots

of

exci

pien

ts th

at in

divi

dual

ly d

o no

t con

form

tosp

ecif

icat

ions

,with

oth

er lo

ts th

at d

o co

nfor

m (

in a

n at

tem

pt to

sal

vage

,or

hide

adul

tera

ted

mat

eria

l) is

not

an

acce

ptab

le p

ract

ice.

A b

atch

can

onl

y be

hom

ogen

ous

whe

n co

nfor

min

g m

ater

ial i

s th

orou

ghly

mix

ed. M

ixin

g to

for

m a

hom

ogen

eous

bat

ch is

a m

anuf

actu

ring

ste

p an

d sh

ould

be d

efin

ed in

a w

ritte

n pr

oced

ure.

Mix

ing

shou

ld a

lway

s be

con

trol

led

and

hom

ogen

eity

sho

uld

be v

erif

ied

and

docu

men

ted.

See

also

7.1

The

ble

ndin

g pr

oces

s sh

ould

be

veri

fied

to e

nsur

e th

at it

will

not

impa

ct th

equ

ality

of

the

exci

pien

t. T

he b

lend

ed e

xcip

ient

sho

uld

be te

sted

to e

nsur

e co

n-fo

rman

ce to

the

spec

ific

atio

n an

d to

pro

vide

dat

a fo

r th

e C

ertif

icat

e of

Ana

lysi

s(C

OA

). A

Cer

tific

ate

of C

onfo

rmity

(C

OC

) m

ay b

e ap

prop

riat

e un

der

cert

ain

circ

umst

ance

s w

ith a

ppro

pria

te c

ontr

ols

in p

lace

.

Qua

lity

docu

men

ts a

ccom

pany

ing

deliv

erie

s sh

ould

be

subj

ect t

o an

agr

eem

ent

betw

een

dist

ribu

tor

and

fina

l cus

tom

er.

In c

ase

of r

etes

ting,

anal

ytic

al m

etho

ds o

f th

e or

igin

al m

anuf

actu

rer

and/

or

phar

mac

opoe

ia m

etho

ds s

houl

d be

app

lied.

Whe

re o

ther

met

hods

are

app

lied,

thes

e sh

ould

be

agre

ed u

pon

betw

een

both

par

ties.

Prim

ary

pack

agin

g m

ater

ial s

peci

fica

tions

sho

uld

be e

stab

lishe

d an

d a

wri

tten

proc

edur

e sh

ould

cle

arly

def

ine

prim

ary

pack

agin

g m

ater

ials

for

eac

h in

divi

dual

exci

pien

t bas

ed u

pon

the

exci

pien

t’s s

tabi

lity.

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

7

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

7.7

The

re-

use

of c

onta

iner

s sh

ould

be

disc

oura

ged

unle

ss th

ey h

ave

been

cle

aned

usin

g a

valid

ated

pro

cedu

re. R

ecyc

led

cont

aine

rs s

houl

d no

t be

used

unl

ess

ther

e is

evi

denc

e th

at th

e qu

ality

of

the

mat

eria

l pac

ked

will

not

be

adve

rsel

yaf

fect

ed.

7.8

Mat

eria

ls s

houl

d be

rep

acka

ged

only

if e

ffic

ient

env

iron

men

tal c

ontr

ol e

xist

s to

ens

ure

that

ther

e is

no

poss

ibili

ty o

f co

ntam

inat

ion,

cros

s-co

ntam

inat

ion,

degr

adat

ion,

phys

iCO

Che

mic

al c

hang

es a

nd/o

r m

ix-u

ps. T

he q

ualit

y of

air

sup

-pl

ied

to th

e ar

ea s

houl

d be

sui

tabl

e fo

r th

e ac

tiviti

es p

erfo

rmed

,e.g

. eff

icie

ntfi

ltrat

ion.

7.9

Suita

ble

proc

edur

es s

houl

d be

fol

low

ed to

ens

ure

prop

er la

bel c

ontr

ol.

If th

e sa

me

type

of

pack

agin

g m

ater

ial i

s us

ed f

or r

epac

kagi

ng th

en it

sho

uld

beeq

uiva

lent

to th

at u

sed

by th

e or

igin

al m

anuf

actu

rer.

In s

uch

case

s th

e re

-pac

k-ag

er a

nd d

istr

ibut

or m

ay r

ely

on th

e m

anuf

actu

rer’

s st

abili

ty e

valu

atio

n an

das

sign

the

sam

e sh

elf

life

for

the

exci

pien

t.W

hen

prim

ary

pack

agin

g m

ater

ial d

iffe

rs f

rom

the

orig

inal

man

ufac

ture

r’s

pri-

mar

y pa

ckag

ing

mat

eria

l or

if th

e he

ad s

pace

incr

ease

s si

gnif

ican

tly,a

n ev

alua

-tio

n of

the

cont

aine

r an

d its

clo

sure

sys

tem

sho

uld

dem

onst

rate

that

it is

adeq

uate

to p

rote

ct th

e ex

cipi

ent f

rom

det

erio

ratio

n an

d co

ntam

inat

ion

beyo

ndits

est

ablis

hed

spec

ific

atio

n fo

r th

e sh

elf

life

(re-

test

or

expi

ratio

n pe

riod

)de

fine

d by

the

exci

pien

t man

ufac

ture

r. O

ther

wis

e th

e sh

elf

life

defi

ned

by th

em

anuf

actu

rer

cann

ot b

e tr

ansf

erre

d to

the

repa

ckag

ed m

ater

ial.

The

nee

d fo

r st

abili

ty s

tudi

es s

houl

d be

con

firm

ed.

Stor

age

and

hand

ling

proc

edur

es s

houl

d be

inst

alle

d w

hich

pro

tect

con

tain

ers

and

clos

ures

and

min

imiz

e th

e ri

sk o

f co

ntam

inat

ion,

dam

age

or d

eter

iora

tion,

and

whi

ch w

ill a

void

mix

-ups

(e.

g. b

etw

een

cont

aine

rs th

at h

ave

diff

eren

t sp

ecif

icat

ions

but

are

sim

ilar

in a

ppea

ranc

e)

Ret

urne

d co

ntai

ners

may

hav

e un

know

n re

sidu

es f

rom

oth

er th

an th

e in

tend

ed u

se.

The

refo

re,u

se o

f ne

w c

onta

iner

s is

rec

omm

ende

d fo

r ex

cipi

ents

. How

ever

,if

con-

tain

ers

are

reus

ed,a

pro

cedu

re s

houl

d de

mon

stra

te a

rat

iona

le f

or c

lean

ing

proc

e-du

res

for

spec

ific

exc

ipie

nts

and

thei

r di

ffer

ent t

ypes

of

cont

aine

r (s

ee a

lso

5.8)

.T

here

sho

uld

be a

n ag

reem

ent d

efin

ing

the

spec

ific

con

ditio

ns (

e.g.

han

dlin

g,se

al-

ing,

clea

ning

) of

reu

se b

etw

een

dist

ribu

tor

and

cust

omer

. If

retu

rnab

le e

xcip

ient

cont

aine

rs a

re r

euse

d,al

l pre

viou

s la

belin

g sh

ould

be

rem

oved

or

defa

ced.

Env

iron

men

tal c

ontr

ols

shou

ld e

nsur

e th

at te

mpe

ratu

re,h

umid

ity a

nd c

lean

lines

sof

air

and

equ

ipm

ent a

re a

ppro

pria

te to

avo

id a

ny c

onta

min

atio

n or

det

erio

ratio

nof

the

exci

pien

t. It

is r

ecom

men

ded

to d

efin

e th

e ne

cess

ary

envi

ronm

enta

l co

nditi

ons

for

the

repa

ckag

ing

of e

ach

exci

pien

t. E

nvir

onm

enta

l con

trol

is a

spe

cial

ist s

ubje

ct a

nd e

xper

ts s

houl

d be

con

sulte

d.(s

ee a

lso

sect

ion

2.6)

.

Proc

edur

es s

houl

d be

impl

emen

ted

to e

nsur

e th

at th

e co

rrec

t qua

ntity

of

labe

lsar

e pr

inte

d an

d is

sued

and

that

labe

ls c

onta

in th

e ne

cess

ary

info

rmat

ion.

The

proc

edur

e sh

ould

als

o de

fine

that

labe

ls a

re r

econ

cile

d an

d an

y ex

cess

labe

lsim

med

iate

ly d

estr

oyed

or

retu

rned

to c

ontr

olle

d st

orag

e an

d ap

prop

riat

ely

reco

rded

. Rep

acka

ging

and

rel

abel

ing

faci

litie

s sh

ould

be

insp

ecte

d im

med

iate

lypr

ior

to u

se,e

nsur

ing

that

all

mat

eria

ls th

at a

re n

ot r

equi

red

for

the

next

re

pack

agin

g op

erat

ion

have

bee

n re

mov

ed.

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

8

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

7.10

Con

tain

ers

of r

epac

kage

d m

ater

ial a

nd r

elab

elle

d co

ntai

ners

sho

uld

bear

bot

h th

ena

me

of th

e or

igin

al m

anuf

actu

ring

site

and

the

nam

e of

the

dist

ribu

tor/

repa

cker

.

7.11

Proc

edur

es s

houl

d be

in p

lace

to e

nsur

e m

aint

enan

ce o

f th

e id

entit

y an

d qu

ality

of

the

mat

eria

l by

appr

opri

ate

mea

ns,b

oth

befo

re a

nd a

fter

rep

acka

ging

ope

ratio

ns.

7.12

Bat

ch r

elea

se p

roce

dure

s sh

ould

be

in p

lace

in a

ccor

danc

e w

ith G

MP.

7.13

Onl

y of

fici

al p

harm

acop

oeia

l met

hods

or

valid

ated

ana

lytic

al te

st m

etho

dssh

ould

be

used

for

the

anal

ysis

.

7.14

Sam

ples

of A

PIs

and

exci

pien

ts o

f ap

prop

riat

e qu

antit

ies

shou

ld b

e ke

pt f

or a

tle

ast 1

yea

r af

ter

the

expi

ry o

r re

test

dat

e,or

for

1 y

ear

afte

r di

stri

butio

n is

com

plet

e.

7.15

The

rep

acke

r an

d re

labe

ller

shou

ld e

nsur

e th

at th

e st

abili

ty o

f th

e m

ater

ial i

sno

t adv

erse

ly a

ffec

ted

by th

e re

pack

agin

g or

rel

abel

ing.

Sta

bilit

y st

udie

s to

jus-

tify

assi

gned

exp

iry

or r

etes

t dat

es s

houl

d be

con

duct

ed if

the

phar

mac

eutic

alst

artin

g m

ater

ial i

s re

pack

aged

in a

con

tain

er d

iffe

rent

fro

m th

at u

sed

by th

eor

igin

al m

anuf

actu

rer.

It is

rec

ogni

zed

that

som

e ex

cipi

ents

may

not

nee

d

If a

gree

d up

on w

ith th

e ph

arm

aceu

tical

cus

tom

er,i

nfor

mat

ion

abou

t the

ori

gina

lm

anuf

actu

ring

site

may

als

o be

pro

vide

d in

oth

er w

ays

or o

n ot

her

docu

men

ts.

The

se p

roce

dure

s sh

ould

incl

ude

docu

men

ted

trac

eabi

lity

dow

nstr

eam

and

up

-str

eam

.

App

ropr

iate

test

ing

of r

epac

kage

d m

ater

ials

sho

uld

be p

erfo

rmed

to d

emon

stra

teco

nsis

tenc

y of

exc

ipie

nt q

ualit

y. T

estin

g of

the

com

plet

e sp

ecif

icat

ion

is n

ot n

ec-

essa

ry in

suc

h ca

ses

but s

ome

defi

ned

key

qual

ity p

aram

eter

s,w

hich

may

be

affe

cted

by

the

repa

ckag

ing

proc

ess,

shou

ld b

e te

sted

. Unt

il th

ese

test

s ha

vebe

en p

erfo

rmed

,the

rep

acka

ged

mat

eria

ls s

houl

d be

kep

t und

er q

uara

ntin

e an

did

entif

ied

as s

uch.

The

mat

eria

ls s

houl

d co

mpl

y w

ith th

e de

fine

d sp

ecif

icat

ions

befo

re th

ey c

an b

e re

leas

ed f

or d

istr

ibut

ion.

Exc

ipie

nt te

stin

g an

d re

leas

e sh

ould

be

perf

orm

ed b

y th

e Q

ualit

y U

nit a

nd c

on-

form

to w

ritte

n sp

ecif

icat

ions

and

ana

lytic

al te

st m

etho

ds. T

here

sho

uld

be a

proc

edur

e to

ens

ure

that

test

dat

a ar

e re

cord

ed a

nd e

valu

ated

pri

or to

rel

ease

of

the

repa

ckag

ed o

r tr

ansf

erre

d ex

cipi

ent.

For

cont

rol o

f ke

y pa

ram

eter

s du

ring

rep

acka

ging

and

or

full

rete

stin

g of

ex

cipi

ents

,off

icia

l pha

rmac

opoe

ia m

etho

ds o

r m

etho

ds v

alid

ated

aga

inst

the

phar

mac

opoe

ia m

etho

ds s

houl

d be

use

d. O

ther

wis

e th

e or

igin

al m

anuf

actu

rer’

san

alyt

ical

met

hods

are

rec

omm

ende

d.

The

met

hods

use

d sh

ould

be

liste

d on

the

Cer

tific

ate

of A

naly

sis

acco

mpa

nyin

gth

e ex

cipi

ent o

r m

ade

avai

labl

e to

the

cust

omer

by

othe

r do

cum

ents

. The

se d

ocu-

men

ts s

houl

d al

so r

efer

ence

any

con

trac

t lab

orat

ory

that

is u

sed

to p

erfo

rm a

naly

-se

s. T

he C

ertif

icat

e of

Ana

lysi

s sh

ould

iden

tify

whi

ch te

sts

have

bee

n pe

rfor

med

on th

e in

divi

dual

bat

ch a

nd w

hich

test

s ha

ve b

een

perf

orm

ed v

ia s

kip

lot t

estin

g.

If e

xcip

ient

s ar

e re

pack

aged

,pro

cess

ed o

r pa

ckag

ed f

rom

bul

k,re

tain

ed s

ampl

esre

pres

enta

tive

of th

e ex

cipi

ent b

atch

sho

uld

be k

ept f

or o

ne y

ear

afte

r th

e ex

pira

-tio

n or

re-

eval

uatio

n da

te o

r fo

r on

e ye

ar a

fter

dis

trib

utio

n is

com

plet

e. T

he s

ampl

esi

ze s

houl

d be

the

amou

nt r

equi

red

to p

erfo

rm tw

o co

mpl

ete

anal

yses

. Sto

rage

cond

ition

s of

the

sam

ples

sho

uld

avoi

d an

y co

ntam

inat

ion

and

dete

rior

atio

n.

Stab

ility

and

exp

irat

ion

datin

g of

exc

ipie

nts

are

prim

arily

the

resp

onsi

bilit

y of

the

exci

pien

t man

ufac

ture

r. If

an

exci

pien

t is

tran

sfer

red

to a

noth

er c

onta

iner

or

repa

ckag

ed b

y th

e di

stri

buto

r,st

abili

ty a

nd s

helf

life

(re

test

or

expi

ry p

erio

d) c

onsi

dera

tions

hav

e to

be

take

n in

toac

coun

t. T

he ty

pe o

f co

ntai

ner,

prim

ary

pack

agin

g m

ater

ials

and

sto

rage

con

ditio

ns

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 1

9

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

orig

inal

man

ufac

ture

r. It

is r

ecog

nize

d th

at s

ome

exci

pien

ts m

ay n

ot n

eed

addi

tiona

l sta

bilit

y st

udie

s.

8C

ompl

aint

s

8.1

All

com

plai

nts

and

othe

r in

form

atio

n co

ncer

ning

pot

entia

lly d

efec

tive

mat

eria

lsm

ust b

e ca

refu

lly r

evie

wed

acc

ordi

ng to

wri

tten

proc

edur

es th

at d

escr

ibe

the

actio

n to

be

take

n,an

d in

clud

ing

the

crite

ria

on w

hich

a d

ecis

ion

to r

ecal

l apr

oduc

t sho

uld

be b

ased

.

8.2

Any

com

plai

nt c

once

rnin

g a

mat

eria

l def

ect s

houl

d be

rec

orde

d an

d th

orou

ghly

inve

stig

ated

to id

entif

y th

e or

igin

or

reas

on f

or th

e co

mpl

aint

(e.

g. th

e re

pack

-ag

ing

proc

edur

e,th

e or

igin

al m

anuf

actu

ring

pro

cess

,etc

.).

8.3

If a

def

ect i

n a

phar

mac

eutic

al s

tart

ing

mat

eria

l is

disc

over

ed o

r su

spec

ted,

cons

ider

atio

n sh

ould

be

give

n as

to w

heth

er o

ther

bat

ches

sho

uld

be c

heck

ed.

8.4

Whe

re n

eces

sary

,app

ropr

iate

fol

low

-up

actio

n,po

ssib

ly in

clud

ing

a re

call,

shou

ld b

e ta

ken

afte

r in

vest

igat

ion

and

eval

uatio

n of

the

com

plai

nt.

8.5

The

man

ufac

ture

r an

d cu

stom

ers

shou

ld b

e in

form

ed if

act

ion

is n

eede

d fo

llow

ing

poss

ible

fau

lty m

anuf

actu

ring

,pac

kagi

ng,d

eter

iora

tion,

or a

ny o

ther

seri

ous

qual

ity p

robl

ems

with

a p

harm

aceu

tical

sta

rtin

g m

ater

ial.

9R

ecal

ls

used

by

the

repa

ckag

ing

site

has

to b

e ta

ken

into

acc

ount

whe

n sh

elf

life

(ret

est o

rex

piry

per

iod)

is d

efin

ed f

or e

xcip

ient

s. T

he r

ecom

men

ded

expi

ratio

n da

te p

rovi

ded

by th

e or

igin

al m

anuf

actu

rer

shou

ld n

ot b

e ex

tend

ed w

ithou

t dem

onst

ratin

g st

abil-

ity to

just

ify

an e

xten

ded

shel

f lif

e (r

etes

t or

expi

ry p

erio

d). I

n su

ch a

cas

e th

e ty

peof

con

tain

er a

nd s

tora

ge c

ondi

tions

sho

uld

be c

lear

ly d

efin

ed.

If th

e ne

ed f

or s

peci

al s

tora

ge c

ondi

tions

exi

sts

(e.g

. pro

tect

ion

from

ligh

t,he

at,

etc.

),su

ch r

estr

ictio

ns s

houl

d be

indi

cate

d on

the

labe

ling.

Cus

tom

er c

ompl

aint

s an

d in

form

atio

n ab

out p

ossi

ble

defe

cts

shou

ld b

e sy

stem

-at

ical

ly d

ocum

ente

d an

d in

vest

igat

ed,b

ased

on

a w

ritte

n pr

oced

ure

with

assi

gned

res

pons

ibili

ties.

Inve

stig

atio

ns s

houl

d be

for

mal

ly c

ondu

cted

and

wri

tten

up in

a ti

mel

y m

anne

rto

est

ablis

h if

the

com

plai

nt is

just

ifie

d,to

iden

tify

root

cau

se(s

),to

def

ine

any

initi

al a

nd/o

r fo

llow

up

actio

n(s)

,and

the

met

hod

of c

omm

unic

atio

n,e.

g. to

the

cust

omer

,ori

gina

l man

ufac

ture

r,au

thor

ities

etc

.C

ompl

aint

rec

ords

sho

uld

be r

etai

ned

and

regu

larl

y ev

alua

ted

for

tren

ds,f

re-

quen

cy a

nd c

ritic

ality

in o

rder

to id

entif

y po

ssib

le a

dditi

onal

nee

ds f

or c

orre

ctiv

eor

pre

vent

ive

actio

ns.

Inve

stig

atio

ns s

houl

d id

entif

y w

heth

er th

e re

port

ed d

efec

t is

limite

d to

a s

ingl

eba

tch

of m

ater

ial,

or if

oth

er b

atch

es n

eed

to b

e co

nsid

ered

as

part

of

the

inve

sti-

gatio

n. A

ny a

dditi

onal

bat

ches

impl

icat

ed s

houl

d be

iden

tifie

d an

d la

bele

d (e

.g.

“und

er q

uara

ntin

e”)

acco

rdin

gly.

For

prod

uct r

ecal

ls s

ee s

ectio

n 9.

Con

firm

ed s

erio

us p

robl

ems

rela

ted

to p

rodu

ct q

ualit

y sh

ould

be

com

mun

icat

edup

stre

am to

the

man

ufac

ture

r an

d al

so d

owns

trea

m to

the

cust

omer

(s)

in c

ase

they

may

hav

e re

ceiv

ed m

ater

ial w

ith th

e sa

me

batc

h nu

mbe

r.

In th

e U

SA th

e te

rm r

ecal

l has

spe

cifi

c re

gula

tory

impl

icat

ions

that

do

not d

irec

tlyap

ply

to e

xcip

ient

s; th

eref

ore

the

term

ret

riev

al is

typi

cally

use

d in

the

USA

.

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 2

0

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

9.1

The

re s

houl

d be

a s

yste

m f

or r

ecal

ling

prom

ptly

and

eff

ectiv

ely

from

the

mar

ket,

mat

eria

ls k

now

n or

sus

pect

ed to

be

defe

ctiv

e.

9.2

The

ori

gina

l man

ufac

ture

r sh

ould

be

info

rmed

in th

e ev

ent o

f a

reca

ll.

9.3

The

re s

houl

d be

est

ablis

hed

wri

tten

proc

edur

es f

or th

e or

gani

zatio

n of

any

reca

ll ac

tivity

; the

se s

houl

d be

reg

ular

ly c

heck

ed a

nd u

pdat

ed.

9.4

All

reca

lled

mat

eria

ls s

houl

d be

sto

red

in a

sec

ure,

segr

egat

ed a

rea

whi

le th

eir

fate

is d

ecid

ed.

9.5

In th

e ev

ent o

f se

riou

s or

pot

entia

lly li

fe-t

hrea

teni

ng s

ituat

ions

all

cust

omer

san

d co

mpe

tent

aut

hori

ties

in a

ll co

untr

ies

to w

hich

a g

iven

mat

eria

l may

ha

ve b

een

dist

ribu

ted

shou

ld b

e pr

ompt

ly in

form

ed o

f an

y in

tent

ion

to r

ecal

lth

e m

ater

ial.

9.6

All

reco

rds

shou

ld b

e re

adily

ava

ilabl

e to

the

desi

gnat

ed p

erso

n(s)

res

pons

ible

for

reca

lls. T

hese

rec

ords

sho

uld

cont

ain

suff

icie

nt in

form

atio

n on

mat

eria

lssu

pplie

d to

cus

tom

ers

(inc

ludi

ng e

xpor

ted

mat

eria

ls).

9.7

The

eff

ectiv

enes

s of

the

arra

ngem

ents

for

rec

alls

sho

uld

be e

valu

ated

at r

egul

arin

terv

als.

10R

etur

ned

good

s

10.1

Goo

ds r

etur

ned

to th

e su

pplie

r sh

ould

be

appr

opri

atel

y id

entif

ied

and

hand

led

in a

ccor

danc

e w

ith a

pro

cedu

re a

ddre

ssin

g at

leas

t the

kee

ping

of

the

mat

eria

lin

qua

rant

ine

in a

ded

icat

ed a

rea,

and

its a

sses

smen

t and

dis

posi

tion

by a

des

ig-

nate

d pe

rson

. Whe

re a

ny d

oubt

ari

ses

over

the

qual

ity o

f th

e m

ater

ials

,the

ysh

ould

not

be

cons

ider

ed s

uita

ble

for

reis

sue

or r

euse

.

Func

tions

invo

lved

in th

e su

pply

cha

in s

houl

d im

plem

ent w

ritte

n pr

oced

ures

tom

anag

e ex

cipi

ent r

ecal

l (re

trie

val)

pro

mpt

ly a

nd e

ffec

tivel

y. T

he p

roce

dure

sho

uld:

•de

scri

be h

ow th

e pr

oces

s of

rec

all (

retr

ieva

l) s

houl

d be

man

aged

,bas

ed o

nth

e ri

sk in

volv

ed,

•de

scri

be a

dec

isio

n m

akin

g pr

oces

s w

ith d

efin

ed r

espo

nsib

ilitie

s,•

defi

ne th

e fu

nctio

ns in

volv

ed in

the

proc

ess

(e.g

. Qua

lity

Ass

uran

ce,s

ales

,lo

gist

ics,

com

pete

nt a

utho

ritie

s et

c.)

•de

fine

the

com

mun

icat

ion

proc

ess

and

docu

men

tatio

n,an

d•

defi

ne th

e st

eps

need

ed to

ret

riev

e th

e m

ater

ial.

Self

exp

lana

tory

Self

exp

lana

tory

Self

exp

lana

tory

See

sect

ion

9.1

See

sect

ion

9.1

Self

exp

lana

tory

Ret

urne

d ex

cipi

ents

sho

uld

be id

entif

ied

as s

uch

and

held

pen

ding

res

olut

ion.

Proc

edur

es f

or h

oldi

ng,l

abel

ing,

test

ing,

and

any

proc

essi

ng o

f th

e re

turn

edex

cipi

ent s

houl

d be

in a

ccor

danc

e w

ith w

ritte

n pr

oced

ures

. Rec

ords

of

retu

rned

prod

ucts

sho

uld

be m

aint

aine

d an

d sh

ould

incl

ude

the

nam

e of

the

exci

pien

t and

the

lot n

umbe

r (o

r ba

tch

num

ber)

,rea

son

for

the

retu

rn,q

uant

ity r

etur

ned,

date

of d

ispo

sitio

n,an

d ul

timat

e fa

te o

f th

e re

turn

ed e

xcip

ient

.

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 2

1

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

11H

andl

ing

of n

on-c

onfo

rmin

g m

ater

ials

11.1

Non

-con

form

ing

mat

eria

ls s

houl

d be

han

dled

in a

ccor

danc

e w

ith a

pro

cedu

reth

at w

ill p

reve

nt th

eir

intr

oduc

tion

or r

eint

rodu

ctio

n in

to th

e m

arke

t. R

ecor

dsco

veri

ng a

ll ac

tiviti

es,i

nclu

ding

des

truc

tion,

disp

osal

,ret

urn

and

recl

assi

fica

-tio

n,sh

ould

be

mai

ntai

ned.

11.2

An

inve

stig

atio

n sh

ould

be

perf

orm

ed to

est

ablis

h w

heth

er a

ny o

ther

bat

ches

are

also

aff

ecte

d. C

orre

ctiv

e m

easu

res

shou

ld b

e ta

ken

whe

re n

eces

sary

.

11.3

The

dis

posi

tion

of th

e m

ater

ial,

incl

udin

g do

wng

radi

ng to

oth

er s

uita

ble

pur-

pose

s sh

ould

be

docu

men

ted.

11.4

Non

-con

form

ing

mat

eria

ls s

houl

d ne

ver

be b

lend

ed w

ith m

ater

ials

that

do

com

-pl

y w

ith s

peci

fica

tions

.

12D

ispa

tch

and

Tra

nspo

rt

12.1

Mat

eria

ls s

houl

d be

tran

spor

ted

in a

man

ner

that

will

ens

ure

the

mai

nten

ance

of

cont

rolle

d co

nditi

ons

whe

re a

pplic

able

(e.

g. te

mpe

ratu

re,p

rote

ctio

n fr

om th

een

viro

nmen

t). T

he tr

ansp

ort p

roce

ss s

houl

d no

t adv

erse

ly a

ffec

t the

mat

eria

ls.

12.2

Req

uire

men

ts f

or s

peci

al tr

ansp

ort a

nd/o

r st

orag

e co

nditi

ons

shou

ld b

e st

ated

on

the

labe

l. If

the

phar

mac

eutic

al s

tart

ing

mat

eria

l is

inte

nded

to b

e tr

ansf

erre

d ou

t-si

de th

e co

ntro

l of

the

man

ufac

ture

r’s

mat

eria

ls m

anag

emen

t sys

tem

,the

nam

ean

d ad

dres

s of

the

man

ufac

ture

r,qu

ality

of

cont

ents

,spe

cial

tran

spor

t con

ditio

nsan

d an

y sp

ecia

l leg

al r

equi

rem

ents

sho

uld

also

be

incl

uded

on

the

labe

l.

12.3

The

sup

plie

r of

the

mat

eria

ls s

houl

d en

sure

that

the

cont

ract

acc

epto

r fo

r tr

ans-

port

atio

n of

the

mat

eria

ls is

aw

are

of a

nd p

rovi

des

the

appr

opri

ate

stor

age

and

tran

spor

t con

ditio

ns.

12.4

Proc

edur

es s

houl

d be

in p

lace

to e

nsur

e pr

oper

cle

anin

g an

d pr

even

tion

ofcr

oss-

cont

amin

atio

n w

hen

liqui

ds (

tank

s) a

nd b

ulk

or p

acke

d m

ater

ials

ar

e tr

ansp

orte

d.

Self

exp

lana

tory

The

inve

stig

atio

n sh

ould

be

docu

men

ted

as w

ell a

s ac

tions

take

n to

pre

vent

recu

rren

ce o

f th

e pr

oble

m.

Self

exp

lana

tory

Self

exp

lana

tory

Tra

nspo

rt c

ondi

tions

and

the

equi

pmen

t to

be u

sed

shou

ld b

e de

fine

d ac

cord

ing

to th

e ch

arac

teri

stic

s of

the

prod

ucts

. Any

spe

cial

tran

spor

t con

ditio

ns s

houl

d be

mon

itore

d an

d re

cord

ed.

Doc

umen

ts a

ccom

pany

ing

a de

liver

y sh

ould

als

o lis

t any

spe

cial

req

uire

men

tsfo

r st

orag

e an

d tr

ansp

orta

tion.

If a

gree

d up

on w

ith th

e ph

arm

aceu

tical

cus

tom

er,i

nfor

mat

ion

abou

t the

ori

gina

lm

anuf

actu

rer

may

als

o be

pro

vide

d in

oth

er w

ays

or o

n ot

her

docu

men

ts th

anth

e la

bels

.

The

sup

plie

r sh

ould

pro

vide

the

cont

ract

acc

epto

r w

ith in

form

atio

n ab

out a

nysp

ecia

l req

uire

men

ts f

or a

ppro

pria

te tr

ansp

ort a

nd s

tora

ge c

ondi

tions

. The

abi

lity

of th

e co

ntra

ct a

ccep

tor

to c

ompl

y w

ith th

ese

requ

irem

ents

sho

uld

be e

valu

ated

.

Bes

t pra

ctic

e fo

r bu

lk tr

ansp

ort i

s to

use

ded

icat

ed e

quip

men

t and

def

ined

han

-dl

ing

proc

esse

s. I

f th

is is

not

pos

sibl

e,th

e ty

pe o

f tr

ansp

ort e

quip

men

t and

su

itabl

e su

pplie

s (e

.g. s

eals

,fitt

ings

,hos

es,p

umps

) sh

ould

be

spec

ifie

d. T

hem

ater

ials

use

d sh

ould

be

com

patib

le w

ith th

e tr

ansp

orte

d ex

cipi

ents

. Pos

sibl

ein

com

patib

ilitie

s be

twee

n se

alin

g m

ater

ials

or

hose

s an

d th

e pr

oduc

t tra

nspo

rted

shou

ld b

e ta

ken

into

acc

ount

esp

ecia

lly f

or s

olve

nts.

Cle

anin

g pr

oced

ures

with

docu

men

ted

evid

ence

of

thei

r ef

fici

ency

sho

uld

be u

sed

betw

een

load

ings

of

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 2

2

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

12.5

The

bul

k tr

ansp

ort o

f ph

arm

aceu

tical

sta

rtin

g m

ater

ials

req

uire

s nu

mer

ous

pre-

caut

ions

to a

void

con

tam

inat

ion

and

cros

s-co

ntam

inat

ion.

The

bes

t pra

ctic

e is

to u

se d

edic

ated

equ

ipm

ent,

tank

s or

con

tain

ers.

12.6

Pack

agin

g m

ater

ials

and

tran

spor

tatio

n co

ntai

ners

sho

uld

be s

uita

ble

to p

reve

ntda

mag

e to

the

phar

mac

eutic

al s

tart

ing

mat

eria

ls d

urin

g tr

ansp

ort.

12.7

For

bulk

tran

spor

t,va

lidat

ed c

lean

ing

proc

edur

es s

houl

d be

use

d be

twee

n lo

ad-

ings

,and

a li

st o

f re

stri

cted

pre

viou

s ca

rgoe

s m

ust b

e su

pplie

d to

the

tran

spor

tco

mpa

nies

.

12.8

Step

s sh

ould

be

take

n to

pre

vent

una

utho

rize

d ac

cess

to th

e m

ater

ials

bei

ngtr

ansp

orte

d.

12.9

Gen

eral

inte

rnat

iona

l req

uire

men

ts r

egar

ding

saf

ety

aspe

cts

(e.g

. pre

vent

ion

ofex

plos

ion

and

of c

onta

min

atio

n of

the

envi

ronm

ent,

etc.

) sh

ould

be

obse

rved

.

13C

ontr

act

acti

viti

es

13.1

Any

act

ivity

per

form

ed,a

s re

fere

nced

in th

e G

MP

and

GT

DP

guid

elin

es,d

ele-

gate

d to

ano

ther

par

ty,s

houl

d be

agr

eed

upon

in a

wri

tten

cont

ract

.

13.2

The

con

trac

t giv

er s

houl

d ev

alua

te th

e pr

opos

ed c

ontr

act a

ccep

tor’

s co

mpl

ianc

ew

ith G

TD

P be

fore

ent

erin

g in

to a

n ag

reem

ent.

13.3

All

cont

ract

acc

epto

rs s

houl

d co

mpl

y w

ith th

e re

quir

emen

ts in

thes

e gu

idel

ines

.Sp

ecia

l con

side

ratio

n sh

ould

be

give

n to

the

prev

entio

n of

cro

ss-c

onta

min

atio

nan

d to

mai

ntai

ning

trac

eabi

lity.

docu

men

ted

evid

ence

of

thei

r ef

fici

ency

sho

uld

be u

sed

betw

een

load

ings

of

diff

eren

t mat

eria

ls.

Con

side

ratio

n ha

s to

be

give

n to

pre

viou

s ca

rgoe

s. A

list

of

rest

rict

ed o

r ac

cept

-ab

le p

revi

ous

carg

oes

shou

ld b

e co

mm

unic

ated

to a

nd a

gree

d up

on w

ith th

etr

ansp

ort c

ompa

nies

. Cha

nges

to b

ulk

tran

spor

t equ

ipm

ent a

nd s

uppl

ies

shou

ldbe

wel

l con

trol

led,

eval

uate

d an

d fi

nally

app

rove

d by

the

cont

ract

giv

er.

See

sect

ion

12.4

.

Self

exp

lana

tory

See

sect

ion

12.4

.

Con

side

ratio

n sh

ould

be

give

n to

sec

urity

asp

ects

. For

exa

mpl

e,tr

ansp

orta

tion

ofbu

lk e

xcip

ient

s sh

ould

hav

e a

seal

ing

syst

em in

pla

ce. C

onta

iner

s sh

ould

bea

rta

mpe

r ev

iden

t sea

ls.

Self

exp

lana

tory

Res

pons

ibili

ties

for

such

act

iviti

es s

houl

d be

ref

eren

ced

in a

con

trac

t and

/or

tech

nica

l agr

eem

ent.

The

eva

luat

ion

shou

ld in

clud

e an

aud

it of

the

cont

ract

acc

epto

r’s

prem

ises

and

qual

ity s

yste

m.

See

12.4

Cop

yrig

ht ©

2006

The

Int

erna

tiona

l Pha

rmac

eutic

al E

xcip

ient

s C

ounc

ilPa

ge 2

3

Goo

d tr

ade

and

dist

ribu

tion

prac

tices

for

pha

rmac

eutic

al s

tart

ing

mat

eria

ls

IPE

C G

ood

Dis

trib

utio

n P

ract

ices

Gui

de f

or P

harm

aceu

tical

Exc

ipie

nts

2006

(GT

DP

),W

HO

Tec

hnic

al R

epor

t Se

ries

,No.

917

,200

3

13.4

The

re s

houl

d be

a w

ritte

n an

d ap

prov

ed c

ontr

act o

r fo

rmal

agr

eem

ent b

etw

een

the

cont

ract

giv

er a

nd c

ontr

act a

ccep

tor

that

add

ress

es a

nd d

efin

es in

det

ail

the

resp

onsi

bilit

ies,

GT

DP

and

whi

ch p

arty

is r

espo

nsib

le f

or w

hich

qua

lity

mea

sure

s.

13.5

Subc

ontr

actin

g m

ay b

e pe

rmis

sibl

e un

der

cert

ain

cond

ition

s,su

bjec

t to

appr

oval

by

the

cont

ract

giv

er,e

spec

ially

for

act

iviti

es s

uch

as s

ampl

ing,

anal

ysis

,rep

acki

ng a

nd r

elab

ellin

g.

Self

exp

lana

tory

Self

exp

lana

tory

Appendix A Glossary

Acceptance CriteriaNumerical limits, ranges, or other suitable measures of acceptance for test results. [4]

Active Pharmaceutical Ingredient (API)Any substance or mixture of substances intended for use in the manufacture of a drug (medicinal) productand that, when used in the production of a drug, becomes an active ingredient of the drug product. Suchsubstances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure,mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of manor animals. [4]

AgreementArrangement undertaken by and legally binding on parties. [1]

Batch (Lot)A specific quantity of material produced in a process or series of processes so that it can be expected to behomogeneous. In the case of continuous processes, a batch may correspond to a defined fraction of the production. The batch size can be defined either by a fixed quantity or by the amount produced in a fixedtime interval. [2]

Batch Number (Lot Number) A unique combination of numbers, letters and/or symbols that identifies a batch (or lot) and from whichthe production and distribution history can be determined. [4]

Batch ProcessA process that produces the excipient from a discrete supply of raw materials that is present before thecompletion of the reaction. [2]

Batch Record Documents that provide a history of the manufacture of a batch of excipient. [2]

Broker / BrokingBrokers resell excipients without conducting physical handling of the product such as warehousing,transport, repackaging etc.

Bulk excipientExcipient in any transportation or storage equipment (tanks, silos, ISO-Containers, tank/silo trucks etc.) tobe filled/repackaged into others (tanks, silos, drums, bags, containers etc.).

CalibrationThe demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements. [4]

Certificate of Analysis (COA)A document listing the test methods, specification and results of testing a representative sample from thebatch to be delivered. [2]

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 24

Certificate of Conformity (COC)A document, which confirms that the product shipped to the customer, complies with a specific set ofrequirements or specifications. It does not contain actual test results.

ComminglingUnintended blending of traces of carryover material from one batch with another.

ConsignmentThe quantity of a pharmaceutical starting material made by one manufacturer and supplied at one time in response to a particular request or order. A consignment may comprise one or more packages or containers and may include material belonging to more than one batch. [1]

ContaminationThe undesired introduction of impurities of a chemical or microbiological nature, or foreign matter, intoor onto a raw material, intermediate, or excipient during production, sampling, packaging, or repackaging,storage or transport. [2]

Continuous ProcessA process that continually produces material from a continuing supply of raw material. [2]

ContractBusiness agreement for supply of goods or performance of work at a specified price. [1]

CriticalA process step, process condition, test requirement or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the excipient meets its specification. [2]

Cross-Contamination Contamination of a material or product with another material or product. [4]

CustomerThe organization receiving the excipient once it has left the control of the excipient manufacturer; includesbrokers, agents and users. [2]

DeviationDeparture from an approved instruction or established standard. [4]

Drug (Medicinal) ProductThe dosage form in the final immediate packaging intended for marketing. [4]

Earliest expiry/first out principle concept (EEFO)A distribution procedure to ensure that the stock with the earliest expiry date is distributed and/or utilizedbefore an identical stock item with a later expiry date is distributed and/or utilized. [1]

ExcipientSubstances other than the API which have been appropriately evaluated for safety and are intentionallyincluded in a drug delivery system. [2]

Expiry (Expiration) DateThe date designating the time during which the excipient is expected to remain within specifications andafter which it should not be used. [2]

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 25

First in/first out principle concept (FIFO)A distribution procedure to ensure that the oldest stock is distributed and/or utilized before a newer andidentical stock item is distributed and/or utilized. [1]

Good Manufacturing Practices (GMP)That part of quality assurance which ensures that products are consistently produced and controlled to thequality standards appropriate to their intended use. Current Good Manufacturing Practices (cGMP) is theapplicable term in the United States. For purposes of this guide the terms GMP and cGMP are equivalent.

Homogeneous materialMaterial of uniform consistency and composition throughout a batch. [1]

ImpurityA component of an excipient that is not intended to be present but arises as a consequence of the raw materials used or the manufacturing process. [2]

In-process Control / TestingChecks performed in production to monitor and, if appropriate, to adjust the process and or to ensure thatthe intermediate or excipient conforms to its specification. [2]

IntermediateMaterial that must undergo further manufacturing steps before it becomes an excipient. [2]

LabelingThe action involving the selection of the correct label, with the required information, followed by line-clearance and application of the label. [1]

LotSee Batch.

Manufacture / Manufacturing ProcessAll operations of receipt of materials, production, packaging, repackaging, labeling, relabeling, qualitycontrol, release, storage, and distribution of excipients and related controls. [2]

MaterialA general term used to denote raw materials (starting materials, reagents, and solvents), process aids,intermediates, excipients and packaging and labeling materials. [4]

Non-conforming MaterialMaterial that does not meet the manufacturer’s specifications or has not been manufactured according toapplicable GMPs.

Original ManufacturerPerson or company manufacturing a material to the stage at which it is designated as a pharmaceuticalstarting material. [1]

Packaging MaterialA material intended to protect an intermediate or excipient during storage and transport. [2]

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 26

Pharmaceutical Starting MaterialA pharmaceutical starting material is an active pharmaceutical ingredient (API) or an excipient intendedor designated for use in the production of a pharmaceutical product. [1]

ProcedureWritten, authorized instruction for performing specified operations.

ProcessingOperations to change product characteristics by mainly physical treatment through e.g. milling, sieving,distilling, filtration, blending.

ProductionOperations involved in the preparation of an excipient from receipt of materials through processing andpackaging of the excipient. [2]

Quality Assurance The sum total of the organised arrangements made with the object of ensuring that all excipients are of thequality required for their intended use and that quality systems are maintained. [2]

Quality ControlChecking or testing that specifications are met. [4]

Quality CriticalDescribes a material, process step or process condition, test requirement or any other relevant parameterthat directly influences the quality attributes of the excipient and which must be controlled within predetermined criteria. [2]

QuarantineThe status of materials isolated physically or by other effective means pending a decision on their subsequent approval or rejection. [4]

Raw MaterialA general term used to denote starting materials, reagents and solvents intended for the use in the production of intermediates or excipients. [2]

Recall (USA: see Retrieval)A process for withdrawing or removing a pharmaceutical material from the distribution chain because of defects in the materials or complaints of a serious nature. The recall might be initiated by the manufacturer/importer/distributor or a responsible agency. [1]

RecordDocuments stating results achieved and/or providing evidence of activities performed. The medium maybe paper, magnetic, electronic or optical, photography etc. or a combination thereof . [2]

Re-evaluation Date (Retest Date)The date when the material should be re-examined to ensure that it is still suitable for use. [4]

RelabelingThe process of putting a new label on the material (see also labeling). [1]

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 27

RepackagingThe action of changing the packaging of the material. [1]

Retained SampleRepresentative sample of a batch/delivery that is of sufficient quantity to perform at least 2 full quality control analyses and will be kept for a defined period of time.

Retest DateThe date when a material should be re-examined to ensure that it is still suitable for use. [1]

Retrieval (especially in the USA)Process for the removal of an excipient from the distribution chain. [2]

SamplingOperations designed to obtain a representative portion of a pharmaceutical starting material based on an appropriate statistical procedure, for a defined purpose, e.g. acceptance of consignments, batch release, etc. [1]

Skip Lot (periodic) TestingThe performance of specified tests at release on pre selected batches and/or at predetermined intervals,rather than on a batch-to-batch basis, with the understanding that those batches not tested must still meetall the acceptance criteria established for that product. This represents a less than full schedule of testingand should therefore be justified, presented to, and approved by, the regulatory authority before imple-mentation. When tested, any failure of the starting material to meet the acceptance criteria established forthe periodic (skip lot) test should be handled by proper notification of the appropriate regulatory authority(authorities). If these data demonstrate a need to restore routine testing, then batch-by-batch release testing should be reinstated. [1]

Specification A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numericallimits, ranges or other criteria for the tests described for a material. [2]

StabilityContinued conformance of the excipient to its specifications. [2]

SupplierPerson or company providing pharmaceutical starting materials on request. Suppliers may be distributors,manufacturers, traders, etc. [1]

Supply ChainFor the purpose of this guideline supply chain is defined as all steps in the entire chain of distribution start-ing from the point at which an excipient is transferred outside the control of the original manufacturer’smaterial management system downstream to the final user of the excipient.

Top ManagementPerson or group of people who direct and control an organization at the highest level. The highest levelcan either be at the site or corporate level and will depend on the way that the quality management systemis organized. [2]

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 28

TraceabilityAbility to determine the history, application or location that is under consideration, for example, origin ofmaterials and parts, processing history or distribution of the product after delivery. [2]

Trader / TradingSee Broker/Broking.

ValidationA documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria. [4]

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 29

Appendix B Bibliography

[1] Good Trade and Distribution Practices for Pharmaceutical Starting Materials World Health Organization, WHO Technical Report Series, No. 917, 2003

[2] The Joint IPEC – PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients The International Pharmaceutical Excipients Council and Pharmaceutical Quality Group, 2006

[3] Guide to Good Storage Practices for PharmaceuticalsWorld Health Organization, WHO Technical Report Series, No. 908, 2003

[4] Good Manufacturing Practice for Active Pharmaceutical Ingredients (ICH Q7a) International Conference on Harmonisation, 2000

[5] Model Certificate of Analysis World Health Organization, WHO Technical Report Series, No. 902, 2002

[6] Good Manufacturing Practices: Supplementary Guidelines for the Manufacture of Pharmaceutical Excipients World Health Organization, WHO Technical Report Series, No. 885, 1999

Copyright © 2006 The International Pharmaceutical Excipients CouncilPage 30

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