The document discusses good manufacturing practices (GMP) and good distribution practices (GDP) which govern the manufacturing and distribution of pharmaceutical products to ensure quality and safety. It explains that GMP focuses on manufacturing activities while GDP focuses on distribution activities. Key requirements for both include ensuring product quality, conforming with laws, controlling temperature, ensuring traceability, providing documentation, and staff training. Facilities, equipment, vehicles, and processes must all be qualified and validated. Personnel must be trained and there are requirements for storage premises to maintain required storage conditions and prevent contamination.

1. GDP and
the Importance
ofTemperature
Monitoring
E-BOOKLET

2. 2
GMP and GDP – Definitions and Origins
Supply chains of medicinal products and active pharmaceutical ingredients (API) are complex as a result
ofoutsourcingandthemanyplayersinvolved.Thecompletesupplychain–fromthemanufacturingofAPIs
andexcipients to themarketing of thefinishedproduct–mustbedocumented and controlled.
What is GMP?
Good manufacturing practices (GMP) are a complex set
ofregulations thatdefinerequirementsfor thesafemanu-
facturing of food and foodstuffs, pharmaceutical products,
medicaldevices–generallyallproductsconsumedor
used directly on humansoranimals. Theobjective is to
ensureeachmanufacturedproductisofhigh-quality,and
it performs as intended.
What is GDP?
Good distribution practices (GDP) refersto theregula-
tionsthatgovernthewholesaledistributionofmedicinal
productstoensurethattheirqualityandintegrityaremain-
tained throughout thesupply chain from manufacturer to
enduser.TheGDPoriginatedfromtheGMPandmaintain
their coreideasthroughoutthesupply chain.Thegoalisto
maintainproductqualitythroughoutthesupplychain.
The GDP applies not only to finished pharmaceutical pro-
ductsbutalso to theprocurement, storage, andtransport
of APIs and other components used to manufacture medi-
cines.
Both GMP and GDP intend to:
Ensure a safeproductfor consumption and/or useonthe
end user
Conformwithlawsformarketauthorization
Control healthy environmental conditions
(most importantly temperature)
Protect products from contamination, theft,
and counterfeit
Ensure traceability (detection of faulty products
and recall)
Provide detailed documentation of processes
Enhance staff training
Make effective use of a quality management system
GMP vs. GDP – What Are the Differences?
Fromtheperspectiveofthepharmaceuticalsupplychain,
thecornerstonesoftheregulatoryframeworkarethe
GMPandGDP–oroftenreferredtotogetherasGxP.While
GMPfocusesonactivitiesrelatedtomanufacturing(in-
cludingtesting,release,andstorage),GDPfocuseson
distribution(includingtransport,storage,andwholesale)
ofpharmaceuticalproducts.BothGMPandGDPaimto
improvepublichealthby ensuring productquality.

3. 3
Are GMP and GDP Universal?
GMP and GDP are the same in principle, but the rules that
apply to the sectors can vary considerably. GMP and GDP
are not global standards but are defined and enforced by
national (or, in the EU, supranational) authorities. Here are
just a few examples:
USA: Food and Drug Administration (FDA)
EU:TheEuropeanCommissiondefinesaEuropean
standardbutdelegatesenforcementtonational
authorities.ThesearesupportedbytheEuropean
MedicinesAgency(EMA)andotherauthorities.
Switzerland:Swissmedicdefinesthestandardbut
delegates enforcement to the cantonal therapeutic
products inspectorates.
Canada: Health Canada
Although country or regional authorities create and
enforceGMPandGDP,internationaleffortshavebeen
made over the pastfew decades to harmonize regulatory
requirements. The Pharmaceutical Inspection Co-opera-
tionScheme(PIC/S)wasfoundedin1995withthegoalof
harmonizingGMPandinspectionsystems,andestablishing
mutualrecognitionagreementsbetweenregulatoryagen-
cies in different countries.
Quality and Risk Management
Riskmanagementincludesallmeasuresforthesystematic
identification, assessment, monitoring, and control of risks.
Itdetermineswhichfactors,processsteps,orcomponents
couldhaveadirectorindirectinfluenceonpatientsafety.
Itisimportanttorememberthatriskassessmentisonly
onestepinriskmanagement.Riskmanagementisanon-
goingprocessthatrequiresorganizationalefforttoensure
risks to patient safety are minimized.
One of the most common methods of risk management
isfailure mode and effects analysis (FMEA). The model isa
guidetohelpusersminimizerisksassociatedwithaproduct
orsystem.Thegraphicbelowdescribeseachstepofthe
model.
FMEA Model
Aftertheriskshavebeenidentified,theycanbeevaluated.
Theevaluationalwaysreferstothedrugorpatientsafetyin
the broadersense:
Severity:Howseriouslyisthequalityofthemedicinal
productaffected? How highistherisk for thepatient?
Probability:Whatistheprobabilitythatthisriskwill
occur?
Detectability:Ifthisriskoccurs,canitbeeasilydetected?
Riskswithalowevaluationcanusuallybesolvedwith
simplemeasures.Riskswithahighevaluationmustbe
consideredinatargetedmanner:Whicheffectivemeasures
canbedefined,howaretheycommunicated,andhowis
successregularly reviewed?TheInternationalCouncilfor
Harmonisation of Technical Requirements for Pharmaceuti-
calsfor HumanUse (ICH)Quality Guideline 9 (Q9) provides
principles andtoolsto perform qualityriskmanagement.
https://www.ich.org/page/quality-guidelines

4. 4
What is a Qualification?
TheGDPguidelinesrequirethatallequipmentcriticalto
patientsafetyandproductqualitybequalified.Qualifica-
tionisdocumentedproofthataroom,asystem,aplant,a
supplier,oranemployeefulfillstheintendedpurpose.
Example of Warehouse Qualification Requirements
What is Validation?
Validationistheverification,carriedoutinaccordance
with GMPorGDPregulations,that a procedure, process,
oractivityproducestheexpectedresults.TheGxPguide-
linesstatethatallquality-relevantprocessesmustbevali-
dated.Thefirstpartofvalidationistodefinetheexpected
results;thesecondpartistoverifyanddocumentthatthe
process delivers the expected result.
Inordertodistinguishthedifferencebetweenqualification
andvalidation,rememberthatequipment,facilities,and
supplies (i.e., things you can touch) are qualified; processes
are validated. By definition, critical facilities, utilities, and
equipmentmustbefully qualified beforetheprocesscan
be validated.
Example of Warehouse Validation Requirements
What Needs to be Qualified and Validated?
Forexample,tostoreproductsinawarehouse,youobvi-
ouslyneedthe warehouse itself,butyou also need staff
qualifiedtodotheirjob,systemstosupporttheprocess,
andyoumayneedotherequipmenttoensurethatthe
product is stored according to its needs.
Validation is only possible if all elements used
are qualified in advance.
Theriskmanagementanalysisidentifieseachitemthat
needstobequalifiedinthesupplychain.Seeexamples
below:

5. 5
Room Qualification
Anywherewherethecorrespondingproductsarestored
orhandled(coldstorage,storagerooms,transshipment
points)
Equipment and Container Qualification
Refrigerators, incubators, containers, and transport boxes
used to store and transport products
Vehicle Qualification
Refrigeratedtrucks,vans,andtrolleysusedtotransport
products,exceptforequipmentusedexclusivelyfor
transportthatispartofacoldchainandusesqualified
refrigerated boxes or actively refrigerated containers such
as a cargo ship
System Qualification
Data loggers and monitoring systems used to monitor
temperatureandtrackthepositionofproducts(safety,
traceability)
Supplier Qualification
System-critical suppliers according to risk analysis
(e.g., transport service providers)
Employee Qualification
Documented training for relevant activities
The GAMP®5 V-Model
Examples of Qualification in the Supply Chain
1. User Requirement Specification (URS)
ThefirstdocumentrequiredistheURS.AURSisahigh-level
documentthatdefineswhattherequirementsarefora
system butisnotprescriptive asto how those requirements
aremet.Forarefrigerator,thiscouldbeverysimpleand
containonlyahandfulofpoints(e.g.,mustmaintain2to
8°C,mustfitunder a counter).A detailedpurchase order
ormanufacturer’stechnicalspecificationscanbeusedasa
URSforcommercialoff-the-shelfitemssuchasrefrigera-
tors.Complex,bespokesystemsgenerallyrequireamore
detailed URS.
2. Functional Specification
For complex systems, this generally encompasses
design drawings, piping and instrumentation diagrams,
and plannedlayouts.Thesearegenerallyprovidedby
third-party vendors.

6. 6
3. Design Specification
Sinceapoweroutageisacriticalrisk,youmaydefinean
uninterruptedpowersupplyinyourdesignspecification
forarefrigerator.Youmustalsodefinethemodeland
manufacturer of the refrigerator.
4. Risk Analysis
The next step is a risk analysis. In the risk analysis,
everythingthatcouldgowrongandaffectthesafetyofthe
patient is considered. In our refrigerator example, possible
riskscouldbeanopendoorandpowerfailure.Eachrisk
isassessedandevaluatedintermsofprobability,severity,
anddetectability.Measuresarethendefinedtoreducethe
risk.
5. Design Qualification
Designqualification(DQ)verifiesthatthesystemdesign
meetsuser,functional,anddesignspecificationsaswell
asdesignrequirementsdefinedinGMPandGDP.For
commercial off-the-shelf products, the manufacturer is
typicallyresponsibleforprovidingDQdocumentation.
Thismaycomeintheformofavalidationcertificate,
certificate of analysis, certificate of conformity, or other
documentation.DQforcomplexbespokesystemsgenerally
requiresamoreformaldocumentationsequencetoverify
thatthesystemmeetsuserand GxPrequirements.
6. Installation Qualification
Installationqualification(IQ)isperformedinordertoverify
thatthesystemwasinstalledaccordingtodesignspeci-
fications.IQgenerallyincludesarecordofmajorsystem
components, the place of installation, and verification steps
toensurecriticalequipmentwasinstalledaccordingtothe
manufacturer’s specifications.
7. Operational Qualification (Mapping)
Bycarryingouttheoperationalqualification(OQ),youtest
thefunctionality ofthesystemand theabilityto maintain
the specified temperature range in the refrigerator. Thermal
mappingisperformedbystrategicallyplacingdataloggers
throughoutthefacilityorcontainer(inthiscase,arefrig-
erator).Thetestistypicallycarriedoutwithoutaproduct
torepresenttheworst-casescenario.Stresstests(door
opening, power failure, etc.) are also usually carried out
during OQ.
8. Performance Qualification (Mapping)
Finally, the systems are tested in the performance qualifi-
cation(PQ)fortheirfunctionduringrealoperation,i.e.,
at full load during normal operations.
The same V-shaped principle works for all devices and rooms that
are temperature-controlled. The amount of effort required to qualify
a system should be commensurate with the level of risk posed by the
system to patient safety.
What is Calibration?
The use of calibrated measuring instruments is an im-
portantprerequisiteforanyqualification.Calibrationisa
reliable, reproducible, and documented comparison of a
sensor(testsample)withareferenceinstrumentthatis
traceabletothenationalstandard.Themeasurementseries
ofthetesteddeviceandthereferencedevicearethencom-
pared.Iftheydo notmatch, thetested device isadjusted
or,ifnecessary,replaced.Assoonasthemeasurementof
thetesteddevice iswithinthespecification, theresultis
documented in a calibration certificate.
Adjustment is no longer necessary with modern tempera-
ture sensors, and is even dangerous. Modern temperature
sensorsmeasureveryaccuratelyandarestableovertime.
Ifatemperaturesensordoesnotmeasurewithinthe
defined tolerance, it is defective and must be replaced.
Anadjustment would onlyconceal thedefect but not
eliminate it.
Calibration Procedure

7. 7
Deviations
HowdoyoudealwithdeviationsintheGDPenvironment?
Thefirst,veryimportantstepistoreportthedetecteddevi-
ationimmediately.EveryemployeeintheGDPenvironment
hastheresponsibilitytoreportthedeviationevenifthey
are not the cause.
The deviation must be carefully documented. This is
followed by root-cause analysis and an assessment of
whether – and to what extent – the deviation has an impact
onproductqualityandpatientsafety.Correctiveandpre-
ventiveactions(CAPA)arethendefined.Finally,adecision
ismadeastowhetherthe product canstill be used.
Changes
Changesaremodificationsofprocesses,equipment,or
materials without a time limit.
Justaswithdeviations,itisnecessarytocheckandevaluate
whetherthereisanimpactonproductqualityandhowto
dealwithit.Withtherisk-basedapproach,changescanbe
classifiedasminorormajor.Thetestinganddocumentation
effort is structured accordingly.
The entire change process must be described in a manual.
Phases of the CAPA Model for Excursions Phases of the CAPA Model for Changes
Howdodeviationsdifferfromchanges?Agooddistin-
guishingfeatureisthedurationoftheevent:excursionsare
always temporary,while changes are always planned and
permanent.

8. 8
Personnel
Allpersonnelinvolvedinthedistributionofpharmaceu-
ticalsshouldbetrainedandqualifiedintherequirements
of GDP.
Forthispurpose,arequirementmustbecreated
for eachfunction:
Job description: Whattask does thefunctioninvolve?
Whatresponsibilitiesandcompetenciesdoesthefunc-
tion have?
Qualification: What qualifications are required to perform
thetasksandtakeonresponsibility(training,credentials,
experience)?
Training requirements: Which processes, methods, and
tools must the employee know and regularly repeat to
ensure processquality?
Thetrainingshouldberecordedinatrainingplanandbe
based on written standard operating procedures (SOPs).
Thetrainingplanshoulddefineaone-timetrainingprogram
andalsoprovideforrepetitionandfurthertraining.The
followingaspectsshouldbegivenspecialattentionduring
training:
Knowingandadhering toGDPregulationsthatare
important in the respective workplace
Productsafetyandpreventionoferrors
(e.g.,temperature deviations)
Product identification and counterfeit detection
Preventionofcounterfeitsenteringthesupplychain
Prompt and truthful documentation
Ensuring against changes without approval
Documentandreportdeviationsanderrorsimmediately
Hygienic behavior
All training, further training measures, and qualifications should be
recorded in a “training record.” Training records are popular documents
during audits!
Responsible Person
CertainlocalGxPregulationsalsodefinetheroleofthe
“responsible person.” The holder of a wholesale license
must appoint a person with defined authority to give
instructionsandwhoisresponsibleforestablishingand
maintainingthequalitysystem.InGermany,thispersonis
calledthe“ResponsiblePerson,”inSwitzerlandthe“Tech­
nicallyResponsiblePerson.”Thispersonmustassumetheir
responsibilitypersonally.Theymaydelegatecertaintasks
but not their responsibility.
AccordingtoEUGDP guidelines, thefollowing areasof
responsibilityfortheresponsiblepersonareimportant:
Ensuring the implementation and maintenance
of a quality management system
Performance of authorized activities,
withafocusontheaccuracyandqualityofrecords
Ensuringthatinductionandtrainingprograms
are carried out regularly
Coordination and immediate implementation
of any recall of medicinal products
Ensuring that relevant customer complaints
are properly addressed
Ensuringthatsuppliersandcustomersareapproved
Authorizationofalloutsourcedactivitiesthatcouldhave
an impact on good distribution practice
Ensuringthatself-inspectionsarecarriedoutat
appropriateregularintervalsaccordingto
apredefinedprogramandthatthenecessary
corrective measures are taken
Keepingadequaterecordsofalldelegatedtasks
Decidingonthefinaldestinationofreturned,
recalled,orcounterfeitmedicinalproducts
Approvalofallreturnstomarketablestock
Ensuringthatalladditionalrequirementsfor
specificproductssetoutinnationallegislation
are met.
Requirements of a Function

9. 9
Storage and Premises
What are the basic rules for storage?
Duringthestorageofmedicinesandactiveingredients,
care should be taken to ensure that:
The required storage conditions are maintained
(avoid temperature deviations)
The products are not contaminated
(i.e., premises are maintained, in good condition,
and regularly cleaned)
Data integrity is maintained
No blocked, recalled, or contaminated goods
are delivered
Accessrestrictionmustensurethatonlyauthorizedpersons
canenter thewarehouse. Visitors mayonlyenter the ware-
house when accompanied by authorized persons.
Thewarehousemustbequalified,i.e.suitablefortheinten-
dedpurpose.Thisisachievedbycarryingoutastorage
qualification. The defined storage temperature must be
maintained atalltimes ateach location in thewarehouse
where products are stored.
Forthedistributionofthemeasuringinstrumentsinthe
storageroomunderinvestigation(mappinglayout),theen-
tirevolumeinwhichtemperature-sensitivedrugsarestored
mustbe covered three-dimensionally with themeasuring
instruments.Thedistributionofthemeasuringinstruments
must be risk-based. The ISPE guidelines areoften used for
this purpose.
Mapping Plan
Temperature Mapping
Ariskanalysisispreparedinadvance.Thecoreofthe
warehousequalificationconsistsofatemperaturedistri-
butionstudyunderrepresentativeconditions–colloquially
known as “temperature mapping.” If a warehouse has no
externalwalls, itisusuallypossible to dispensewithsea-
sonalrepetitionofthemapping.Ifthereareexteriorwalls,
influenceexertedbytheoutdoorclimatemustbeexpected
andaseasonalrepetitionofthemappingisnecessary
(summer and winter mapping).
Themappingwithinthescopeoftheoperationalqualifica-
tion(OQ)servesasproofoffunctionandisaprerequisite
forthereleaseofthewarehouse.Loadtesting(i.e.,map-
ping inemptyand full states) should encompass thescope
ofqualificationtesting. Themapping durationshouldbe
risk-based and may differ from one type of room or cham-
bertoanother.Forspaceswithexteriorwalls,windows,or
doors,adurationofatleastsevendaysisa goodguideline.
Coldroomsandwalk-infreezerswitharoom-in-room
concept (i.e., those installed in temperature-controlled
rooms) should be mapped long enough to encompass two
full cycles from each refrigeration system. Standalone units
shouldbemappedaminimumof24hoursperloadcon-
figuration.Inaddition,stresstestscanalsobecarriedout
with the same mapping structure, for example:
Temperature distribution when opening the door
Temperaturedistributionincaseofpowersupplyfailure
Functionalityofredundantairconditioningunits

10. 10
PQ Mapping
Mapping Results
Ingeneral,mosttesting requirements for warehouses,
coldrooms,andstandaloneequipmentmaybecom-
pletedduringtheOQphase.OQmappingsmay,where
appropriate, encompass all seasonal considerations,load
testing, and system challenges required for full compliance.
However, local/regional regulatory expectations or specific
organizationalrequirementsmaynecessitateaformalPQ
inadditiontotheOQ.PQmapping(s)shouldconsider
seasonalvariationforroomswithexternalwalls,worst-case
loadconditions(i.e.,fullcapacitytocapturemaximumload
andmaximumrestrictionofairflow),andnormaloperations
(i.e., personnel, equipment, worst-case heat load in the
room/chamber). The mapping duration for the PQ should
be the same as for OQ testing in order to obtain com-
parativedatafromonequalificationphasetoanother.
Asubstituteproductmaybeusedinlieuoftheactual
productifthereisconcernoverproductdamageorif
theroom/chamberisnotatfullcapacity.Anotheroption
isto fullyloada sectionofaroom whileleaving theremain-
derempty.Thiswillallowforsimultaneousloadtesting
ofbothemptyandfullstates. However,theroommustbe
symmetricalandhaveequivalentconditioningsystemsin
both the loaded and unloaded sections.
Data loggers used for mapping must meet a number
of conditions:
Suitability for the temperature range under investigation
Calibrated (ideally three-point calibration covering
the entire specification range)
Measurement accuracy better than ±0.5°C
Measuring interval of less than 10 minutes
Validated production
TheOQ orPQ report shouldcontainthefollowing points:
Device IDs and their placement in the room
Assemblyanddismantlingprotocol
Calibration certificates
Raw data and general overview
Identificationofhotandcoldspots
Evaluation of discrepancies/deviations from the plan
andanassessmentoftemperatureexcursions(ifany)
Animportantresultofthemapping isthedeterminationof
thehotandcoldspots–themeasurementpointsatwhich
thehighestandlowestvaluesweremeasuredoverthe
entiremapping. Thesepointsaretheperfectlocationsto
install the monitoring system. Thus, these critical points are
continuously monitored.

11. 11
Permanent Temperature Monitoring in Warehouses
Everyrefrigerator,coldstore,andwarehouseisequipped
withacontrolsystemthatmeasurestemperatureand
regulates the indoor climate. However, these systems
are usually not GxP-compliant because they do not
independently measure and record the temperature.
GxP-compliant temperature monitoring systems should
operate independently of the indoor climate control
andthesoftwareshouldbedevelopedandvalidated
according to GAMP® 5. Auditing the manufacturer of
the system is also recommended.
The permanent monitoring sensors must be installed
basedonthepreviousmapping.Different sensorsare
recommendeddependingontheapplication.
Theinstallationofthesystemandthesoftwaremustbe
qualified on site. During the qualification, special attention
mustbepaidtoalarms.Thetemperaturedatamustbe
readoutandstoredregularly;inmodernsystemsthis
isdoneautomatically.Alarmsanddeviationsshouldbe
acknowledgedandevaluatedpromptly.Thesystemmustbe
regularlymaintainedandthesensorsregularlycalibrated.
The Various Measuring Systems Together With the
Corresponding Sensors

12. 12
Documentation
FromGxP’spointofview,writtencommunicationisprefe-
rable to oralcommunicationbecause itavoids errorsand
is always comprehensible. However, digital communication
has created new risks.Whichversionisvalid?What
is a valid document? GMP and GDP define clear require-
mentsforgooddocumentationpracticewithrespectto
specification documents and records:
Standard Operating Procedures (SOPs)
Specificationdocuments(SOPs)describeaprocess
and the associated responsibilities. The description
must be clear and comprehensible.
Theproceduresshouldbeapproved,signed,and
dated by the person responsible.
Documents have to be tracked (i.e., provided with
a version number). Onlyapproved andcurrentlyvalid
proceduresmaybeusedintheprocess.Invalidversions
mustbeimmediatelyremovedfromtheworkplace.
WorkinstructionsshouldensurethatGDP-relevant
activities can be carried out correctly by every qualified
employee at the first attempt.
Everyemployeewhoworksaccordingtoawork
instructionmustreceivetrainingonthisinstruction
andhaveaccess toall relevant documents.
Records
Recordshavenouniversalcharacterandaretheresult
ofa process. Theymay containother rawdata
(e.g., measurement results) and are often handwritten.
The empty templates of records are also tracked
documentsandthereforepartofthequalitymanage-
ment system.
Themostcommontypeisthe“log,”whichdocuments
theexecutionofactivitiesinaccordancewiththe
respectiveinstruction.Recordsshouldbewrittenin
aclearandlegiblefontandbearthedateand
signature of the employee.
Calibration certificates are also regarded as records.
Theyrepresenttheresultsofthecalibrationandcontain,
inadditiontothecalibrationvalues,anassessmentof
theconformityoftheresults withatargetvalue.
Reportsdocumenttheexecutionofcertaintasks,
projects, or checks, such as qualification reports,
reports on excursions, or risk analyses.
Ifa changeismade toarecord, theoriginalentryshould
remainidentifiableandthechangeshouldbeindicated
with areason.
Complaints
Complaintsmustbedocumentedcompletely.Adistinction
ismadebetweencomplaintsaboutthequalityofthe
medicinalproductandcomplaintsaboutdistribution.
In the case of complaints about quality,the manufacturer
and/or marketing authorization holder must be informed
immediately.The manufacturer and/or marketing autho-
rizationholderthencontinuestoprocessthecomplaintas
partoftheirowncomplaintmanagement system.
Everycomplaintaboutdistributionorqualitymustbe
investigated thoroughly.
Returns
Returnedmedicinalproductsmustbehandled according
to a written, risk-based procedure described, for example,
inanSOP.Theproductandthespecialstorage conditions
should be taken into account (e.g., check temperature
data).Thetimeelapsedsincetheoriginalshipmentmust
alsobeevaluated.Itbecomesdifficultifitcannotbeprop-
erlydemonstrated thattheproductswerealwaysstored
and transported correctly (remaining stability budget after
deductionofalltemperaturedeviations).Returnsshould
onlybe made by the original recipient.In order to ensure
patientsafety,theworst-casescenarioshouldbeassumed
in case of doubt.
Counterfeit Medicines
A counterfeit medicine contains false information about:
Theidentity,includingitspackaging,labeling,name,or
compositioninrelationtooneormoreofitsingredients
Theorigin,includingthemanufacturer,thecountryof
manufacture,or thecountry oforiginofthemarketing
authorization holder
Thedistributionchanneldescribedinrecordsand
documents
Wholesalersmustinformthecompetentauthorityand
the marketing authorization holder immediately if they
discoverorsuspectthatamedicinalproductiscounterfeit.
Allcounterfeitmedicinalproductsmustbeimmediatelyand
physicallysegregatedandstoredinadesignatedrestricted
warehouse.

13. 13
Recalls
Itmustbepossibleto initiaterecallactionsquicklyandat
anytime. Theeffectivenessoftherecallprocedureshould
beevaluatedregularly,atleastonceayear.Thedistributor
mustfollowtheinstructionsofarecall,which,ifnecessary,
shouldbeapprovedbythecompetentauthority.Eachrecall
actionmustbedocumented atthesametimeasitiscarried
out.Theprogressoftherecallshouldberecordedforthe
purpose of a final report.
Outsourced Activities
Toensureproductqualityandpatientsafety,allGDP-
relevantactivitiesthatareoutsourcedmustbeprecisely
defined, coordinated, and controlled. It is crucial that the
clientremainsresponsiblefortheoutsourcedactivities
andthattherelationshipiscontractuallyregulated.
Inadditiontothebusinessmanagementcontent,the
contracts must also contain quality agreements. Further-
more, responsibilities and communication processes
betweenbothpartiesmustbepreciselyregulated.
Serviceprovidersmustalsobequalified.Thisappliestoall
outsourced, quality-relevant activities, e.g., temperature
monitoring, qualification/validation, storage, transport,
archiving, and IT support.
Beforethecontractisawarded,arisk-basedselectionand
evaluationmustbecarriedout,andpossiblyalsoanaudit
on-siteattheserviceprovider.Inadditiontoprofessional
competence,itmustalsobecheckedwhethertheservice
providerhasthenecessarypermits.Theperformanceof
theserviceprovidermustbecontinuouslymonitoredand
evaluated,andmeasuresforimprovementmustbetaken
ifnecessary.Thecontractormustpassonanyinformation
thatcouldhave animpactonthequalityofthe product.
A risk-based approach isrecommended for a reasonable
distributionofforces:Whatarethehigh-levelrisksduring
storage,handling,andtransport?Whichexistingcertifi-
cationsofthesupplier (e.g.,CEIV,ISO,GAMP®5) canbe
used to mitigate the risks?
Is Your Service Provider Fully Qualified?
Procurement
Wholesalersmay purchase their stocksofmedicinal prod-
uctsonly from persons orfirms which arethemselves hold-
ersofawholesale authorization orwhichare authorized to
manufacture the product concerned, i.e., other wholesalers
orthe manufacturers of the medicinal products. Respon-
sibilityisthereforeinitially“backwards”,meaningthe
wholesalerhastomakesurethatthesupplierhasavalid
wholesalelicenseormanufacturingauthorization.
Upon goods receipt, it must be checked whether the
deliveryiscorrect,i.e.,whetheritislabeledandpackaged
correctly,whetherthedeliveryisuniform,andwhetherthe
numberofcontainers,thequantity,andthetemperature
arecorrect.Incaseoftemperaturedeviations,theshipper
and/or the manufacturer must be contacted.

14. 14
Deliveries and Supplies
However, the responsibility also lies “forward”.Wholesalers,
inturn,mayonlysupplytopersonsorcompanies/bodies
whicharethemselves holdersofawholesaleauthorization
orwhich areauthorizedorempowered to supplymedicinal
products to the public. These include other wholesalers,
pharmacies,doctors,dentists,andhospitals.Here,too,the
wholesaler mustbesurethat thecustomers areentitledto
receive medicines.
Inaddition,alldeliveriesmustbeaccompaniedbyadelive-
rynotewhichcontainsatleastthefollowinginformation:
Date
Nameandpharmaceuticalformofthemedicinalproduct
Batch number (at least for medicinal products
bearing the safety characteristics)
Quantity delivered
Name and address of the supplier
Nameanddeliveryaddressoftherecipient
Otherquality-relevant information
(such as ideal storage conditions)
Recordsshouldbekeptinsuchawaythattheactualstor-
agelocationoftheproductcanbeidentified atalltimes.
Theserulesshouldalsopreventcounterfeitmedicinesfrom
entering the legal supply chain.
Self-Inspections
Regularself-inspections(internalaudits)mustbecarried
outtomonitortheimplementationofandcompliancewith
theGDPregulationsandtoinitiateanynecessarycorrective
measures.
Itisnotnecessarytochecktheentireoperationduringeach
self-inspection.Adivisionintoindividualareasispossible
andrecommended.However,care mustbetakentoensure
thateachareaiscovered,usuallyatleastonceayear.
Again,arisk-basedapproachisrecommendedtodetermine
which departments needto beinspected morefrequently
than others.
Theself-inspectionsarecarriedoutbythecompany’sin-
ternalemployees.However,itcanalsobeusefultoinvolve
externalexperts.Theself-inspectionsmustbecarriedout
accordingtoawrittenplan.Theexecutionistobedocu-
mented andsummarized inareport. Thisreport contains
the excursions as well as measures to eliminate them and
corrective and preventive measures to avoid their repeated
occurrence.
Internal Audits are Helpful in Implementing Corrective Measures
Transport Validation
Transport is understood as moving storage.
Thefollowingmustbeobservedwithregardto
temperature conditions:
Thestorageconditionsspecifiedonthepackagingfor
activeingredientsandpharmaceuticalsmustalsobe
observed duringtransport.
Temperaturedeviationsshouldberecordedandcommu-
nicatedaccordingly.Asuitableprocessforinvestigating
deviations should be defined.
Temperaturemonitoringpointsshouldbeselectedonthe
basisofrisk.Forthisreason,anappropriate riskanalysis
should be carried out as part of the transport validation
process.
Whenvalidatingtransportroutes,itmustbeproventhat
theactivesubstanceordrughasnotsufferedanyquality
degradationsduringtransport.Transportvalidationisvery
demanding.Thetransportroutesmustbepreciselydefined
beforevalidation.Seasonalchangesmustalsobetakeninto
account duringvalidation.

15. 15
Asafirst,oftenverytime-consuming step,thecomplex
processes,whichhavegrownhistoricallyovertheyears,
mustbeunderstoodasawholeanddocumentedinde-
tailed transport sections. The identified transport sections
arethenexaminedforpotentialrisksinaccordance
withICHQ9andappropriatemeasuresaredetermined.
Therisk analysisshouldprovideatleastthefollowing:
> Groupingofthetransportsectionsintoso-called“routes”
> Temperaturemonitoringrequirementsofthetransport
sections
> Qualificationrequirementsforthemeansoftransport
Theindividualtransportsectionscanbegrouped
into climatically similar routes.
Reduced testing may be limited to IQ and OQ. IQ and OQ
activitiesmaybecombinedintoasimplifiedIOQ.
Categorization of the Vehicle Fleet into Types A, B, and C
Additional Risks in Transport Validation
Transport Qualification
Ingeneral,itispossibletoensurethetemperatureduring
transport in temperature-controlled vehicles or in actively
or passively temperature-controlled transport boxes. Both
mustbequalified,andineachcasewithtemperature
mappingsundertheextremeconditionsdefinedintherisk
analysis.
Fororganizationalreasons,largevehiclefleetsmustbe
dividedintovehiclecategories,andonevehicleineach
category must be fully qualified. Testing for full qualification
shouldincludesystemclassification,riskassessment,DQ,
IQ, OQ, andPQ.Reducedtesting canthenbeperformed for
each vehicle.
Transport Monitoring
Ideally, the temperature is recorded throughout the entire
supplychain.Sincethisisnotalwayspossible,regulatory
authoritiesallowthemostcriticalpointsoftransportthat
require temperature monitoring to be defined basedon
risk.Thecriticalparametershereareproductstability,
thelengthoftimetheproductremainsinthecontainer,and
the conditions of the transport section.
Autonomousdata loggersareusedfor temperature mon-
itoringintransit,ideallyincombinationwithadatabase
connection,inordertoenablereal-timeevaluationona
global level. For particularly critical transport sections and
valuableproducts,real-timedataloggersareoftenused,
whichtransmittemperatureandpositioninrealtimeand
allow immediateintervention.
Cloud-Based Monitoring Solution

16. E-BOOKLET | GDP AND THE IMPORTANCE OF TEMPERATURE MONITORING 16
Summary
TherearemanyfacetsofGDPthatneedtobeconsidered
for your qualitysupply chain operations. As new products
enteryoursupplychain,oryoustartworkingwithnew
partners,youwillneedtoreevaluateyourGDPrequire-
ments.BeingGDP-compliantisaconstantworkinprogress.
Leveraging technology and data systems can ease the
burden and ensure robust documentation of your quality
control of the products and processes.
This E-Booklet is part of the GxP Services website
contentforsupplychainandQApractitioners.
Topicsincludethe definitionand originsof GMP
and GDP,highlighting the individual chapters
of GDP.