Essentials

of Successful
Transport Validation
by Mojmir Vavrecka

MV Life Science Consulting GmbH

Management Summary
Usually transport validation projects encom- data analysis, a final concept should be agreed
pass a complex matrix of products, shipping on e.g. in a Master Transport Validation Plan or
sites, destinations, transport categories and a guideline, and a scalable project plan with cost
transport modes. This complexity makes a estimate produced. The approved plan then is
transport validation project difficult to master. the basis for the validation project.
But with well-structured project phases and
few essential decisions such a project can be
mastered effectively.
„Apart from a well-structured
One key is to analyze transport data and produ-
ce a concept how to group all lanes in few clus- project there are two keys to
ters and validate all lanes in few validations. master the complexity of a trans-
The second key is automation supported by tem- port validation project:
plates and a well instructed team. Based on the clusters of transport lanes
derived from historical data
1
A transport-lane, or simply a lane, is defined by its starting
point, destination, route, transport means (road, sea, air), and automation.“
and transport category (e.g. 2-8°C, 15-25°C, 2-25°C).
Benefits of a Transport Validation Project
Generally, the driving force for a company to perform a More controlled and reliable transports causing less or no
transport validation project is the necessity to comply with deviations are the result of a validation project. Conse-
the EU GDP Guideline [1] because of an internal upgrade quently, the company can possibly reduce the monitoring
of the systems, or the launch of a new product, or an expec- of the transports, based on sound scientific reasoning.
ted EMA / FDA audit. Compli-
ance and successful audits are
the resulting benefits. If the
project was performed with an „This validation concept covers the whole transport
effective approach this comes
process end to end, the temperature controlling pa-
at a reasonable cost.
ckaging and containers are just one link in the whole
The validation concept de-
chain. Adequate storage along the entire lane and the
scribed in this paper covers
the whole transport process appropriate handling of the cargo at every hub are
end to end, in contrast to the
often seen validations of only
equally important.“
the temperature controlling
packaging or device. In this
concept the temperature controlling packaging is just one The worldwide distribution of pharmaceutical products is
link in the whole chain. The availability and correct use of a complex, sometimes extremely complex process2. A sys-
adequate storage facilities along the entire lane, the appro- tematic and structured validation project will bring trans-
priate handling of the cargo during the transport and at all parency into the complexity and make simplification, stan-
hubs, so that the chosen packaging can protect the product dardization, improvement, and savings possible.

Because a product transport is a very frequent process, it

is important to achieve the product protection in high qua-
lity but also cost-effectively. Otherwise huge unnecessary
costs can accumulate through the big number of repeti-
tions. An effective validation project achieves the quality
to reasonable cost.
© Stefano Grau / Fotolia

adequately, are equally important and in the focus of this

2
concept. The resulting benefit is a more controlled and
reliable end to end transport, so that matching protective
measures can be applied, not more. In summary, in a one off
exercise an optimization of the quality and cost is elabora-
ted that then can be applied thousandfold.
Some companies distribute thousands of products, within
several temperature classes, from tens of sites, to hundreds
of destinations, with various passive or active temperature
control systems, by truck, train, ship, airplane, or courier ser-
vices, with numerous companies participating in each trans-
port, in ten thousands outbound deliveries, which can lead to
millions of theoretically possible data points.

2
Keys to an Effective Approach
There are two essentials for significant savings in a trans-
port validation project: automation and clustering.
Automation: validation is a repetitive process. Although it
can be complex, at the end it is „always the same“. There-
fore, savings can be achieved through “automation” and in
our case automation means:
Clustering means grouping of the lanes into clusters of
comparable criticality. The worst case lanes of the clusters
then can be validated as representatives of all other lanes
of each cluster. This way even the most complex project
can be broken down to some 5 – 20 clusters and 5 – 30 va-
lidations covering all the transports of a company. Cluste-
ring process:

1) Assign a group of spe- 1) The project should start

cialists to the validation
work for the duration of
the project (the validati-
on team). There is a huge
learning curve and the
team usually improves
their effectiveness sig-
nificantly after few vali-
dations.
with the analysis of historic
„There are two essentials transports. Usually a compa-
ny commands a big amount
for significant savings in a
of data from past transports,
transport validation project: providing information about
lanes, the critical points, etc.
automation and clustering.“
This data is the base for im-
provement on one hand and
for clustering on the other.

2) Produce a flow chart for a validation which the people, 2) Based on the analysis of the historic data, the lanes can
who do the work, can follow through the project and be grouped into clusters (e.g. the same mode of trans-
repetitively in each validation. port, the same transport category, and to the same cli-
mate zone) and the worst case lane per cluster can be
3) Produce templates that can be used 50 – 70% un- identified in a risk assessment.
changed for each validation for all documents and that
represent the best state of the art standard. This saves
a lot of work3 , and delivers consistent final documents
of high quality4.

3
The nominal time saving is 50–70% as many
times as a validation is completed. However,
the real time saving is higher, because the
team needs to fill in for each validation the
„same” into a simple format.

4
The quality is high, because a lot of expert
effort and know-how can be put into the
production of only few high quality templa-
© stockphoto mania / Fotolia

tes (usually three), which then can be used

repeatedly.

3
 Some Additional Considerations
An often encountered issue during transport validation
projects is that manufacturers don’t really know their rou-
tes, especially in air transports, and worst of all, don’t know
that they do not know. Although the lane is known, the ex-
act route can vary significantly, which can be relevant for
the transport reliability and ability of the transport process
to be validated.
© BESTGREENSCREEN/Fotolia
Another issue in today’s industry is still that the logistic
department of a pharmaceutical company or wholesaler
often doesn’t really feel responsible for the transport con-
ditions of the products once they left the door. Indeed, it
is very difficult to influence how the material is treated at
a random airport, port, or another hub around the globe.
However, who else should feel responsible and at the end
is accountable for the product than the company that owns
it? Also, in the logistic industry the understanding for GDP
requirements is often unsatisfactory, be it in forwarder,
„Manufacturers don’t really know the transport routes
their products take, especially in air transports, and
worst of all, they don’t know that they do not know.“
ground handling, or carrier companies. Therefore, there
is an urgent need in the industry for a culture change to a
culture that recognizes the GDP requirements as its core
competence – and not only bringing the material from A
to B as quickly and cheaply as possible. Until this culture
change happens, we need to count this fact into our trans-
port qualification and validation projects.
4
At present, road and sea transports can be validated with
a reasonable effort, but air transports generally speaking
cannot be validated, except when a big extra effort is made,
because there is usually not sufficient GDP relevant con-
trol over the hand-over processes at the airports. So, al
though improvements can be put in place and a qualification
of the lanes may be possible in air transports, usually a full
monitoring of the air transports will be necessary, unless ex-
tensive temperature protection measures are put in place.
In any case there is a trade-off between possible control
of the processes along the route and the need for protec-
tion of the products through passive or active temperature
control devices. The more control of the processes along
the route we have, the less protection measures are nee-
ded. As both of these parameters are cost drivers, we need
to find an optimum for each individual solution.
Because the GDP culture
is not yet fully installed
in the industry, it can be-
come difficult to improve
the transports to a satis-
factory level before qua-
lification or validation.
Attention must be turned
to the engendering the proper understanding and culture
for GDP within the own team first, and then in the external
teams of forwarders, ground handlers and carriers.
Overall Concept for Transport Validation
The overall concept for transport validation should usually
follow three stages [2], [3]:
1) Stage 1 – Process Design: The optimal transport pro-
cess is defined during this stage based on knowledge
gained through monitoring of past transports (evalua-
tion, improvement).
2) Stage 2 – Process Qualification: During this stage, the
process design is evaluated to determine if the process
is capable of reproducible transports (validation runs).
3) Stage 3 – Continued Process Verification: Ongoing
assurance is gained during routine transports that the
process remains in a state of control (ongoing trans-
port monitoring).
© TTStudio / Fotolia
This FDA validation concept is robust, simple, well-tried,
and accepted by all agencies and experts. Depending on
the specific company situation, the focus in transport va-
Project Execution in Practice
Based on the considerations above, a transport validation
project usually is structured in three stages, as follows:
Stage 1: includes data analysis, concept, project plan, and
cost estimate5:
• Assess the situation and define the target.
• Collect data about your company’s specific transports
and lanes for further analysis. This can for example hap-
pen by extracting data from the previous year from SAP.
• Analyze the data, group lanes to clusters.
• Define the parameters that influence the risk of a
lane and the way how to take these parameters into
account. Perform a risk analysis of the lanes and iden-
tify the worst case lanes. Then finalize the clusters and
identify the weak points of the transportation system.
• Setup the final concept for the transport qualification
and validation project, project plan and cost estimate
as base for further decisions through the management.
• Get the project plan and cost estimate or parts of it ap-
proved through the management, if necessary adapt
the plan.
5
lidation can be put more on stages 1 and 2 (definition and
improvement of the lanes in advance, then validation runs),
or more on stage 3 (tight monitoring of the transports and
ongoing improvement). However, we recommend to bene-
fit of phase 1, and improve the transports based on experi-
ence at the beginning of the project.
Stage 2: perform the practical transport qualification &
validation project:
• Elaborate the written, detailed concept for the per-
formance of the validation project and layout the plan
with time schedule. This usually includes the Master
Transport Validation Plan with templates for qualifi-
cation of the system, validation protocols and reports,
sometimes also SOPs or guidelines, depending on your
needs.
• Setup the project: identify, recruit and train the valida-
tion team members.
• Remediate the gaps identified during the data analysis
and qualify the entire transport system of the company.
• It has proven effective to validate the lanes with real
5
At this point in time an accurate cost estimate is possible for
phase 1. Often a reasonable cost estimate for the whole pro-
ject is possible too, if everything goes the way you assume.
However, it is still better to readjust the cost estimate for
phase 2 after phase 1.
 transports. The validation team chooses the worst
case transports that will be the validation runs, pre-
pares the validation protocol and informs the logistic
operations, which transports are going to be the vali-
dation runs. This way the operations have no additio-
nal work, except maybe to support the validation team
with data collection.
• Collect the data of the validation runs, investigate de-
viations and changes.
• Write the validation reports, the final Master Transport
Validation Report, and if necessary a guideline or SOP
for the implementation of the results of the project.
Stage 3: Perform a continuous process verification
• Based on the results of the qualification and validation
project, a suitable monitoring pattern, KPIs and their
target ranges for the desired performance should be
derived for each cluster, and laid down in writing e.g. in
the Master Transport Validation Report or a separate
guideline.
• Suitable data collection (e.g. electronic data base) and
statistical evaluation tools (e.g. ongoing evaluation of
the deviation rates) should be put in place for monito-
ring of the KPIs.
• The KPIs should be used for the improvement of the
performance of the transports along the whole lanes
end to end – not only in the area under own control,
because this is the least critical area. To these ends re-
gular discussions of the performance against the KPIs
with the forwarders should be used (and possibly with
Bibliography
[1] Guidelines on Good Distribution Practice of Medici-
nal Products for Human Use, European Commission
Health and Consumers Directorate - General, Public
Health and Risk Assessment, Pharmaceuticals, Brussels,
2013/C 343/01; http://eur-lex.europa.eu/LexUriServ/
LexUriServ.do?uri=OJ:C:2013:343:0001:0014:EN:PDF
[2] Guidance for Industry, Process Validation: General
Principles and Practices, FDA, January 2011; http://
other stakeholders). In these discussions the impro-
vement of the performance should be requested and
assessed. If the improvement is not satisfactory, coun-
termeasures should be taken (e.g. change forwarder).
• Based on the results of the validation project, also a
concept how to maintain the validated status of the
transports (validated and new transports) should be
defined in writing (e.g. in the Master Validation Report
or a separate guideline or SOP).
Performing your transport validation project in the descri-
bed structured way should lead to a high quality, robust
transport validation at the lowest possible cost. If you
would like to discuss your project with an expert or should
you need support with your implementation, don‘t hesitate
to contact us.
MV Life Science Consulting GmbH
Schwirtenstrasse 11
4414 Füllinsdorf
Switzerland
PhD Mojmir Vavrecka, MBA
phone: +41 (0)79 360 20 58
e-mail: m.vavrecka@mvlsc.ch
www.fda.gov/ucm/groups/fdagov-public/@fdagov-
drugs-gen/documents/document/ucm070336.pdf
[3] EU Guidelines for Good Manufacturing Practice for
Medicinal Products for Human and Veterinary Use,
Annex 15: Qualification and Validation, March 2015;
http://ec.europa.eu/health/files/eudralex/vol-4/2015-
10_annex15.pdf