Qualification vs Validation and Good Cold Chain Management Practices

7/29/2019 Qualification vs Validation and Good Cold Chain Management Practices

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Qualfication ersus alidationndGoodColdChainManagementractices

ByRafikH.Bishara, hD

Thisarticb s takenrors haPhameeükal aunachning d Pack;ng oücer,Ai|Jnn 2m5 ssle,pages102,104106.e 2fl15Sanedanid



Qualif icationersus alidationndGoodColdChainManagementracticesByRafik .Bishara,hD

$ RafikH. Bidwa is a TecfnicalAdvisoro Sensileclfnc.H€ s [rc Chair f ü|e Phannffi*icd ColdChainDiscussion lotp.Parent€ralttw Associatim. rBisharaetired rqr hisposition s Dircclor, Hlity Knowleq€ /hnagflst andTecinicalsuppo( oaEli illy adCqnpanyn tectfiber 2ü)4 afrera 35-year are€r riltr ie corpory. He eceir,€d PfiD rqn Rrü|e UnivelsiE,ndiam,USA.

Historically,he ermsqualification'and validation'have een sedinterchangeablyithinhecold hainndustry,hishas ed o a significantamount f confusionn hepharmaceuticalndustry,hich ould eavoidedbystandardisinghedefinitionsf bothqualification'and validation',

codeofrdb.l R.guldld6 (CrS (1)

Marh 2003 FDA 83 ciritimi \he shipflenrbt nd ol finßned vbls fM ore s& ro anorls is rc! ya Elidaled"ocrober oo4Fo A443 c[.rlon:"5hippir4validariswas eficienf (7)

The ParcnteralDrug Association PDA) 'Cold chainguidance or medicinalproducts naintaining thequality of temperature-sensitive edicinal Foductsthrough the transportationenvironment' 8), allows

ftrms to develop heir ovn processes nd also tomaintainalignmentwith CDER's Generalhinciples

of hocess Validation 9):

a Component ualification CQ) - establishingconfidence hat aücillary componentsare

capableof operatingwithin established imits

and tolerancesI Operationqualification (OQ) - establishing

confidence hat the process s efective and

reproduciblea Performancequalification (PQ)

establishingconfidencethough

apFopriate testing that the product

producedby a specific prccessmeetsall

release equirementsor functionality

The three qualification components are the

foundation ofqualification andvalidation. As these

two terms are frequently misuse4 it is imporiantto first understand how both qualificarion and

validation have been defined by tbe PDA

Pharmaceuticalold ChainDiscussion roup:

Qualification: a documented testing that

demonstrateswith a high degreeof assunnce hata specific process will meet its pre-determined

acceptance riteria.

Validation; a doaumcntedesting,perfomed under

highly controlled conditions,which demonstrates

processcoosistentlyproducesa resultme€tlrg pre-determinedacceptance iteria.

Eackgtou{

iLdEiE.al NaEl.e ProdßtsR.goklo., AgeEl üHnr) {1)

|||..Id lh.l{r oer.|lllid orio) (5)

u5P<1O7$ to.d Sb.4E drd

Tl"€ @renr G@d Mdrufacturing ftelico (cGMPl for finhhdd

ph€rfr &euti@ls clearly def mes:r Fe@nrel quolin@ti@s (edu@tion, Jaining,

, consutrantsqu.r if icrt ion (2r 1.34)

Th€ CGMP requlr* vdlld3um ot:j auromEric,mechanE6rand ereüonic equiprunt (211.63)

r t6nn9 aod app@alor ßjerion rorcomporunts, drug pnduct

conBineß.nd clGues (211.34.2.3)

r cmtmr of micrcbiologl@i@ntafr itunon (21 1 1 13.b)r, Iesung and el€e fordtsdhution (211r65 e)

. lnsrallät ionqualif iüt ion (|q) - üe documenred . in@ion

üEr|nefacir it l6, sFr€ß and equrpftm, as insrarßd

or mdined, @mplt q!ü tfE app.o€d design and ÜEnanufactu€ß' r€cohmndatlhs.

i operariomr qu6rin@tion oQ) rhe documentednrit icanon

üE r üp tacir it ies,sFrems and equiPment,as hstalled

or modified, pefofi a5 intend€d lhrolghout üE ant cipabd

r Psfo'lrrc qualifidrid {Po) ÜE ddumnied sfieüm

ÜEr tacirlr|es, st6$ft and €qurpnm, 6 @rEred rogets,

cd Frfom efieü@ly et ct'.ducibly b€s€d m trE appored

p@s @üEd and prDdEr +€.ifiütim.i Poc6 välidation - the dcumnted evidetue fiat

rhe pm*, opemred *lttln esr.blished paEmereE,

on pedüm eflEtüelt 6rt GpEducibly ro prodlce

a medlciml prcduct meting predecmined speclfications

and quality ätvibütes.

wand pr6edu6 for th€ shipping of drug Foducls struld

be establish€d änd valdsred slch pr@edur6 shouLd 6ke nto

&@un! ihe nätuc of tlE dtug p.oducts and desribe äny speial

Cold storag€ eilir ies are qualif iedte qualiUed.

Varidario the doclment€d act of pßving Lhat any p.dodu.e,

prc@ss, equipment, prcduci, activity or Esrsh dctually leads

whlre @mprerjr! qum@!@ 5rdl6 or 6mr ed redpdanrre

shipping pe*ag6 ärd sics6 it ls rE-gy ro lti i* rerpqa{rEpE iles ÜEr ee etp€ded ro be Dpiol for tlE rtpe of F.käqe ba.ed on

a rumber of fact6 irclldnE:' Temperaturc @nditioß 6! oBgL Sa$nal bmp€atuß (wints wßus summeD

+ I6.spon outes and nodes

r Ou€us and [email protected] of handltno and slop @r pomls

I Owrall product handring

zE

€

s3.E'tdE

sseFE

cA



Aclivity

Table1 comparison f GmdStomgpPracticesGSP)ttersröGood ransporrdion ractices GIP)

that are expected o be typical for the t ?e of packagebasedon

a number of factors, ncluding:

a Temperature onditions at origin and destination

a Seasonalemperature winter verzus summer)

a Load configurationsa Tnnsport routes and modes(ovemight air,

groun4 intemational and so on)a Total duration of transit

O Duration nd ocation fhandling

and stop-overpoints

I Product andling

By studying these va ables in multiple combinations,an

organisations able to gain a level of confidence egarding

how their packaging,processesand actions of their

conhacted service providerswill work togetherwith the

common goal of safeguardinga product during storage

and distdbution.

while quality principles ar e used to reliably qualify

the cold chain distributionprocess,t is to be acknowledged

that even a qualified process s subject to change over

time. Therefore, periodic and appropriatemonitoring is

recommended. The frequency and type of monitoring

will be based on the specific conditions of a given

distributionprocess.

USP <1079> good storage and shipping practices for

qualification of cold equipment or stores states:"Quatification procedures on a regulat basis should be

independently conducted on equipment in cold storesto guarantee suitability and proper functioning. Theprocedure should demonstrate the temperature profile

for for both air and product tempemtures when empty as

well as when loaded," Furthermore, as listed in USP<1079>, "the Presqiption Drug Marketing Act of 1987

and 2l CFR Part 203, Prescription Drug Marketing,

and Part 205, Guidelines fo r State Licensing

of Wholesale PrescriptionDrug Distdbutors, provide the

necessary egulationsand guidance or several egs of the

distribution chain for the prescription drug. The

GIP

Off-site

Handling of pmduct Static

Manufacturerconrols On-site

Environmental mpact Easier o cofnol.{essvarialrle

Documentation compreressranda'd

y?"J;jg ü.:ill';"Regulatoryequnemenrs Have €en tandard Recent xp€ctationsy

for CGMPl::uratory

asenc,esas

While qualification is used to provide a high degree of

assurancehat a processs replicable under anticipatedvariable

ranges,validation is used o describehow a systemwill perfotm

underhighlycontrolled onditions.

Based on the definitions above, it is easy to see how these

definitions are interchanged.However, the key difference is

determinedby whether or not theprocessunder review operates

under'highly controlled' onditions.

The manufacnring environment operates under cGMP-basedprocessesnd- by definition - is 'highly controlled'.Therefore,

manufacturing prccesses can be 'validated'. However, the

distribution environment s widely variable and"dependsupon a

rangeoffactors includingpointsoforigin and destination,article

and container sensitivities o col4 accidental reezing or heat,

transit mode (such as ait truclq sea" or combination), time,

weatherand season, nd carrier lpe (for example,smallpackage

carrier or integrator, teight forwarder, US Postal Service)" (6)

and thereforeoperations n the distribution environmentcannot

be validated - they can or|ly be 'qualified'. A comparisonbetweenGood StoragePractices GSP) and Good Distribution

PracticesGDP), n Table , shows$e ditrerence etweenüte $o

envüonments. igure I (seepage106)shows heproperuseofthe'quälification' and 'validation' terms as they apply to the

manufacturing, torageand distibution processes.

GOOD @LD CHAIN MANAGEMENTPRACTICESGCCMPI

Regardless f how an individual or an organisationmay define'qualification'or 'validation',ensuringhequalityofthe product

andpatient safety is the basis for good cold

chainmanagementracticesGCCMP).

As outlined n USP <1079> good storage

andshippingpractices6), while completingqualification studies of

controlled temperatureshipping packages andsystems,t is necessaryo

utilise temperatwe profiles



Highly ontDll€d_

välidaÜonManufädunnqad $o6qe pr(6s of.

phäruGü@l Fodudim d6 Pefor@in a hlohlY solled- dvlrdmenLnEra6ß, they@n he \slldated

varidble = Qualillcat ion

Th€ dHibltion Prcc6 dG not

op€rate undF a highrysfimlled'

€dronmni. The€loß lt can

dry be Qlaliaied"

f f i w -r__ \a_

CONCLUSION

The standardised soof qualification, validation aod

sood cold chain managementpractices (GCCMP)

i,rill b" b*"fi"i"l fot all involvedparties n handling'

storing and distributing cnvircüIl€ntally sensitive

pharmaceuticals.An ongoingmonitoring gogramme

will prwide data to make the quality decision for

eachshipment.O

Note

Theconceptof thßpaper waspresentedat the

3rdAnnuql Cold Chain S'orageand Dßftibution

Conference, 2-2jrd September 005' London' UK

Aclvowledgements

Theouthorwould like to rcknowledge hehelp

of HenryAmes,Ditector of Mqrketingat Seßitech'

inc ([email protected]),ndFrancisSmlderMarketingMqndgerqt Seßilech Etnope'

MiddteEa t od Afrk a ß @,t nstech' n )'

in prepafing thß article'

W f f iW

f f i f f i-

-

. , i : ' 'r,

Theauthor can becontactedal rafkbishdm2@yahoocom

Refserces

1. Co& of FederatRegulationsCFR)'21 CFR

Parts21Oand 211

2, EuropeänUnion,Gui& to Good '''anufactrringPractices'

Annex153. HealthCanada,HealthCanadtGui& 0069' Guidelines

for TemperatureContmlof DrugPrcductsDuringStorage

andTransPortationDraft). 2OO4

4. tu€dicinesandHealthcarcProduGBRegülatory

Agency,ColdChainManagement'Ensudng

Compllancewith R€gulattons ndGuid€llnes'

Presontation,April 2OO5

5, Wo d HealthOganizttion, GoodDisttibutionPractic€s

for Pharnraceutical roducts tibrking Documem

OAYo4.68 (Restricteo, 2oO4

6. <1079> GoodSto.ageand Dis{tibdion Practices'

USP28, SuPPI , 2Oo5

7. Obtainedunder he fre€domof Informätion FOl)Act'

w!flir.foiseflices.com

B. ColdChainGuidanceor MedicinalProdücts

Maintainingthe Quatityof Temperature-Sensitive

Medicinsl Ploductsthroughthe Transportation

Envirunment,TechnicalRepon 39' PDAJoJmal of

Phamaceutical Scienceand Technology'

Seotember/OctoberOO5Supplement'vol 59' no'S'3

9. FDI ProcessValidationRequirementsor Dn$ Prodlcts

and ActivePhamaceutical IngredientsSubjectto

Pre-MarketApptwal,originalty

Published

n 1987'

revised n 2OO4

manufacturers and distributors should work together to

establislr proper distribution and product-handling

,"*ir"-"* f- ,t " purposeof ensuring appropriateproduct

maintenancen transit"'

It is thenrecommende4 or the sakeof eliminating confusion'

to odopt u consistent use of tbe terms

'qualification' and

ivatidation'. tn adaition, the pmmotion anduseof GCCMP is

recommended in determiniDg and performing the prop€r

i-att , oorur" aod distribution of erwironmentally labile

frr.t-J""*i""i products. within GccMB'qualification'

iioutd b" ur"a fo, process€shat ar€replicableunder variable

"onaitiont while 'validation' should be used for those

pro""rt"t tft"t are performed under highly cootrolled

iorraltlon, (r"" nlgut" 2)' A GccMP systemwill thenmeetall

of tlle above equirements'

oNGOll{G iloltlToRlNc

Based on the above, we recommend establishing

an ongoing temperature and humidity monltonng

f.ogr"Ä" fot the shipment of environmentally sensitive

-"Ji"in".. A shipping containü that has been 'validated'

under highly controlled conditions is subject to

unt ro*o .'uinUiflty in the distribution channel and

-uy tn"r"fo"" not be sufficient to guarantee a product's

t i"gt rt ""a efficacy at the time it reaches the final

",r"io-", 1tfr" patient)' Only an ongoing monitoring

p-g."-."'it capable of generating the deta required to'sufort

appropriate quality decisions r€lated to the stomge'

;;;*; ;.d final distribution of temperature-sensitiveDharmac€uticals.

iranutacuirlng and Sbrage

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Qualification vs Validation and Good Cold Chain Management Practices