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94 INTERNATIONAL PHARMACEUTICAL INDUSTRY Winter 2014 Volume 6
Issue 4
Manufacturing
Lawmakers and regulators around the world are demanding
serialisation for drug products. It is their belief that this
process, where the result is a clear identification of drug
products, is a major step in the struggle against counterfeiting.
While some countries have already embraced certain guidelines,
others will be doing so in the coming years. Whatever their
timeframe, all drug companies, along with their suppliers, are
facing the challenge of implementing appropriate solutions.
Counterfeit drugs have become an enormous problem both for
developing nations and the industrialised world as a whole.
Counterfeit drugs jeopardise the health of patients and, in some
cases, have resulted in deaths. They have also had a major negative
economic impact on a global basis. According to the WHO,
counterfeit drugs have cost nations an estimated $75 billion1 a
year combined.
Typically, due to their high costs of development and
manufacture, counterfeiters have focused on complex medications
such as cytostatic and virostatic drugs, as well as antibiotics and
hormones. Therefore, as a means of managing this problem, lawmakers
and industry representatives have turned their attention to the
tracking of these products beginning with the production line, on
through to the pharmacy. The process is called ‘serialisation’, and
it entails clear identification of the smallest packaging unit with
a unique identification number.
While there has been some debate about this approach, it is
clear that serialisation is quickly being embraced on a global
basis. For every stakeholder in the supply chain, the rapid rise of
serialisation means there has to be an appropriate response. And,
it is essential that this solution meets the requirements as
defined by official agencies while offering greater security for
the patient. An economic solution is important, allowing for the
optimisation of production and distribution processes. The question
for companies then is ‘how can the interested parties be brought
together to implement
a form of serialisation that meets future needs?’
A Variety of ChallengesThe subject of serialisation and
track-and-trace has been on the industry's agenda for quite some
time. Several of the major drug manufacturers have, in fact, made
considerable inroads into implementing solutions. Others have
waited for the regulatory standards to be in force before
addressing the issue. Regardless of the approach taken, the
industry as a whole is keenly aware of the need for serialisation
and is working hard toward developing appropriate solutions.
However, serialisation is not a simple process. Therefore, in
order for it to be effective, it is backed by some important
technological transformations in both the IT and engineering areas.
For those companies seeking a suitable partner and supplier, there
exists a bottleneck since only a limited number of specialists are
available to design and implement the required IT system,
applications and plant engineering. Alternatives are difficult to
find since there is some risk involved to consider suppliers
unfamiliar with the industry. Packaging processes that meet
stringent regulatory standards or supply chain structuring requires
considerable pharmaceutical expertise.
Also complicating the issue is the fact that there exist
important differences in the plants and the IT landscapes of large
companies that have several locations. Each individual subsidiary
usually has its own history. Thus, the plants have usually been
built by a variety of suppliers and are often run by several
different IT systems. The rule of thumb is the larger the company,
the more extensive the challenge. Thus, the effort needed to
retrofit ten lines is significantly different from the effort
required for retrofitting 100 lines. Finally, the same product is
often manufactured on various lines and has to go to a variety of
markets that are all regulated differently.
Another set of challenges is faced by smaller or virtual
companies, which usually lack in-house production facilities,
and also have to exchange serialisation data directly with
officials. This entails a great deal of learning about in-line and
distribution processes and packaging. And, there is also the cost
factor ultimately forcing the question, “Do we make it or buy it?”
It is clear: companies are facing a large number of multifaceted
challenges and need to have a comprehensive knowledge of the
subject.
Questions AnsweredHow then, can companies best address the tasks
at hand? The first step is to get a good understanding of the
extent and demands of a serialisation solution that best fits their
specific needs. Those in key positions to implement serialisation,
along with experts in this area, should first identify and develop
the most important parameters, determine what they can put into
practice themselves, and what can be outsourced to a service
provider. The following questionnaire can provide some help:
• Which regulatory authorities’ serialisation rules have to be
met?
• What firm guidelines do the individual agencies offer for
structure and presentation?
• How should the serialisation data be shared with the
regulating agencies?
• How, and in what form, should companies administer and manage
the serial numbers?
• What solutions are in place to deal with the serial numbers on
the manufacturing level?
• What kind of systems and transmission systems will be used in
advance of the packaging line?
• How will the serialisation solution be integrated into the
existing enterprise resource planning (ERP)?
• What interfaces and transfer protocols are required?
• What are the key processes demanded by warehouse
management?
• How can in-process controls and quality management be
integrated into the serialisation solution?
These questions are critical since they determine the tasks that
a company
Implementing Serialisation
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96 INTERNATIONAL PHARMACEUTICAL INDUSTRY Winter 2014 Volume 6
Issue 4
Manufacturing
implementing serialisation has to be aware of. Each task is
analysed in detail in order to produce a list of precise
specifications a candidate supplier will need to meet. Clearly,
companies without actual packaging lines will have to direct
greater attention to a management solution. However, drug companies
with their own production facilities will also have to make sure
their equipment is up to the task of serialisation. Ultimately,
there are two clear areas that need to be attended to. First,
companies will need to implement an IT solution covering both
hardware and software, and second, they will need an engineering
project to retrofit the lines.
Solving the IT IssueKnowing the requirements that are expected
to be met is central to implementing both hardware and software
solutions. Companies that deliver products to various markets face
the challenge of having to meet a variety of standards for
serialisation. In such cases, the guidelines will be determined by
the following:
• Code type • Serial number characteristics• Serialisation
level• Reporting requirements
What is most needed is a flexible serialisation solution that
can meet all regulatory requirements. Companies will have to make
every effort to be sure of various aggregation depths,
as some official agencies demand aggregation from the sales
packaging unit to the shipping carton, on through to the
transportation pallet. Therefore, the following elements will have
to be taken into account when implementing the solution:
• Integration into ERP• An IT solution for the management of
serialisation data from aggregation through sample
withdrawal
• Interfaces and data transmission
The IT solution should then link order data with the
corresponding serialisation data. This will allow the serial
numbers to be monitored prior to delivery and generation of the
subsequent data reporting, including the aggregation data.
Basically there are two options to solve the IT issue: either you
implement and develop an IT solution in-house, or you go with a
cloud or hosted solution. Each solution has its advantages
depending on your company’s IT strategy. Going with an in-house
solution will take more time, but it gives your organisation more
control of your data and is easier to integrate with your internal
IT systems. If you have a short timeframe and don‘t have the budget
for high investments upfront, a cloud solution could be the
answer.
Engineering SolutionThe guidelines for serialisation demand
clear identification of the smallest packaging units, i.e. the
folding boxes
that the drugs are to be packaged in. Even a cursory glance at
the secondary packaging such as an injectable, will reveal what
system will be needed for implementation on the lines. After
filling and visual inspection, the syringes are blistered and then
packed into the folding boxes on the packaging line. Afterwards,
the boxes are packed into shipping cartons and loaded onto pallets.
Variable data are already printed onto the folding boxes, including
batch numbers and expiration dates. The shipping carton and the
transportation pallet also carry product information. Printing the
serial numbers at the same time as the production data is
recommended for serialisation.
A plant can be both retrofitted and connected to printers that
can print in either number or some machine-readable form such as
bar codes or 2D data matrix codes. Networked camera systems are
also needed for monitoring in addition to scanners that are
necessary for the in-process controls and rejects which allow for
rebooking. A mobile machine might be a good start since it allows
companies the flexibility to do serialisation on various lines. The
fact that the machine can be qualified separately and offline also
means that you are able to gain experiences without influencing
your existing packaging lines. It also avoids down time and allows
those in charge to collect important information on the process
itself without risk of breakdowns.
Once the ‘know-how’ has been gathered and integrated, a
stationary serialisation unit can be commissioned. The on-line
systems will still need to be rounded off with a label printer and
a camera unit for manual aggregation of the individual boxes with
the shipping carton. The same principle applies to the manual
aggregation of the shipping carton with the transportation pallet.
The systems for each packaging line are connected via a line
controller, which is controlled by means of a site server directly
connected to the central IT platform.
Software and HardwareIt should be clear to the reader at this
point that serialisation can only work effectively if implemented
with an IT system, combined with a well-conceived engineering
project. The two sides of serialisation implementation are
carefully meshed with all existing integration
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98 INTERNATIONAL PHARMACEUTICAL INDUSTRY Winter 2014 Volume 6
Issue 4
systems and communicate with them as well, which requires an
on-site server to control production. Integration can be performed
using SAP process integration (PI) for example, with standard
interfaces like EPCIS and reports using XML in EPCIS design.
The IT solution has several other tasks to perform, including
recording and documenting events along the entire supply chain, and
then generating full documentation as well as reports. A link-up
with ERP is also vital to initiate orders and to generate,
administer, and share print information and key materials, such as
serial numbers. And, because the serialisation solution involves
many different layers, the IT solution is important to support the
work across different systems to generate and disseminate
commissioning reports for the serial numbers, aggregation reports,
etc. In-process controls can be used for sampling during
production, while a
handheld solution could allow exception handling at the
warehouse. Relabelling will then need to be completed at the
warehouse as well.
Key DetailsThe official guidelines for serialisation solutions
require certain fundamental elements. All sales packaging units
will bear a clear set of serial numbers and other identifying
features. These numbers can be in 1D linear code or 2D data matrix
code, as well as the information being in text form so they can be
read by humans and robots alike. The 2D data matrix code has the
advantage of providing more data, i.e., expiration date and batch
number, in addition to the number of folding boxes in the shipping
carton. This information needs to meet the GS1 standard.
There are, of course, national differences. China, for example,
demands very special guidelines, including 1D linear codes as well
as aggregation with shipping boxes. For the exchange of data such
as serial numbers, and reports which contain integrated photos of
serialised
shipments, Chinese authorities also require a manual interface
with the drug company, to enable the transition of the serial
numbers and reports. South Korea follows at least for 2015 another
concept, serialisation on item level. They will meet the GS1
recommendations depending on data matrix code information like
GTIN, expiry date, batch/lot and serial numbers using a 2D data
matrix.
Toward a Safe FutureIn summation, serialisation involves the
clear tagging of the smallest packaging unit with a unique
identification number. The rationale behind this new approach is to
provide greater safety throughout the entire supply chain.
Combatting counterfeit drugs through serialisation protects
patients as well as companies whose reputation can be
adversely affected if their products are counterfeited.
Serialisation combined with Track & Trace also offer potential
for process optimisation, since clear mapping of distribution
channels allows for easy tracking and tracing. Thanks to powerful
IT systems with simple and efficient interfaces, caregivers can
quickly check the origin and integrity of the drugs they are
administering to patients. The fakes will be immediately identified
and removed from circulation.
References1. Source: WHO http://
w w w . w h o . i n t / b u l l e t i n
/volumes/88/4/10-020410/en/
Manufacturing
Alexander Ulbrich is project manager within the IT department
responsible for the Serialization Project at Vetter. He began his
career at Vetter in 2003 and since 2013 he is
team leader responsible for a team of SAP application
consultants. Prior to Vetter, Alexander was with the technology
group of Acterna (now JDSU) as system administrator member of the
global Lotus Notes Core Team. After he finished his studies at the
FH Reutlingen he began his working career in 1999 at Wavetek Wandel
und Goltermann as a qualified engineer (FH) of Electronics.
Example of a software and hardware solution