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| Quality in Each and Every Tablet
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 download Reference Project
(pdf, 2.3 MB)
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| Bayer Relies on Werum's PAS-X for Managing its Production Processes
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| Since 1999, Bayer HealthCare in Leverkusen, Germany, has been operating its
manufacturing plant for pharmaceutical solids with the production management
system PAS-X by Werum. The well-proven system supports paperless production
and enables electronic execution workflows, documentation and approval of
batch records. Due to mobile RF terminals the operators can freely move in
the whole plant while being safely guided through the entire production
process. Just by a click of a button operators can acquire relevant
order and batch data and execute them.
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| Bayer HealthCare |
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Bayer HealthCare, a subgroup of Bayer AG, is one of the world's
leading companies in the health care and medical products industry,
combining the global activities of its Animal Health, Biologicals
Products, Consumer Care, Diagnostics and Pharmaceuticals divisions.
More than 34,000 employees work for Bayer HealthCare worldwide.
Bayer HealthCare's Pharmaceuticals Division develops innovative and highly
effective drug products. The research program covers life-threatening
conditions but also disorders that markedly impair quality of life and
life expectancy. The division has a promising early product pipeline,
in particular for the indications cancer, cardiovascular, metabolic
disorders, anti-infectives.
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Production of Pharmaceutical Solids in Leverkusen |
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Each year several billions of tablets leave Bayer's manufacturing facilities for
pharmaceutical solids in Leverkusen. Among them are such successful
pharmaceuticals as Ciprobay®, Avelox®, and Levitra®
as well as
Adalat®, one of Bayer's most well-known products for cardiovascular
treatment with Nifedipine as active ingredient. Of particular interest
in the solids plant is the production of the OROS tablet, a double-layer
Nifedipine tablet with a semi-permeable coating, which delivers its
active ingredient using the patented oral osmotic principle. A laser
gun shoots a 0.6 millimeter small orifice into the coating from
which the ingredient is later released. When the drug is administered,
the osmotic layer expands to provide a precisely dosed delivery of the
active ingredient for up to 24 hours.
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Such highly sophisticated technologies demand software-based support
during all phases of production to ensure that patients get a drug of
stable quality. Prior to 1999, Bayer had employed a Manufacturing
Execution System (MES) developed by its own in-house software experts
and optimally tailored to suit the requirements of solids production.
"We were not sure whether the system would be able to cope with the
year 2000 conversion," explains Wolfgang Malburg, Plant Manager at
Bayer's Solids Production Facility. |
Due to this problem and other new requirements, Bayer
started looking for a manufacturing execution system that
offered the "customary comfort", met today's and tomorrow's
GMP compliance requirements and was apt to support optimal
material flow control, reliable user guidance and paperless
production with electronic signatures.
"At first, we were undecided whether to use in-house development
or purchase a market software package. On the one hand, a
self-developed system provides a tailor-made solution. On
the other hand, with a purchased software package you can
indirectly benefit from the experience of other users. In
the end, this was the deciding factor," Malburg summarizes
the decision process.
The project team studied the market and tested the products of
several suppliers. Ultimately, the production management system
PAS-X, a pharma-specific solution by the software provider Werum,
seemed best suited to meet Bayer's requirements. Malburg explains,
"We need software that we can configure in a simple way, that
enables us to create recipes easily and which has a flexible
structure." This is essential since the manufacturing of solid
pharmaceuticals is characterized by a large number of recipe
variants. Up to twelve different active ingredients and auxiliary
substances are weighed, ground, blended, granulated, compressed
into tablets and then coated. With several hundred recipes, the
administration and creation of Master Batch Records with all
relevant order and batch data is one the system's core functions.
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| A Focus on Flexible Processes |
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With the objective to obtain high throughput and productivity the recipes are
structured so that they may be executed on different machines. It must be
possible to switch between different equipment without any problem. For
example, Bayer operates with different tablet presses in order to have an
alternative option in case the dedicated machine fails. The Manufacturing
Execution System is required to map this flexibility and provide for the
verification of receptacles to assure a correct material flow. "It was no
easy task to achieve this," Malburg recalls. These requirements primarily
have an effect on the design of the recipes. Even if the product stays the
same, machine-dependent parameters will change and this has to be mapped
for every single case. A change of equipment required while the process
is running is a real challenge, and fortunately only happens rarely.
Any modification of the batch record needs to be visible in the
documentation, but any impact on the Master Batch Record has to
be avoided. To ensure this, the process is stopped and a special
function is activated to change the recipe status allowing it to
be edited. Now, the operator may perform the necessary modifications.
Next, an authorized user has to approve the altered recipe by entering
an electronic signature. Then the process is resumed. Also during "normal"
batch record execution the collected data are continuously compared to the
stored recipe. The next step can only be initiated if all the data match.
Such verifications are automatically performed by the system. The entire
workflow with all the associated deviations is electronically documented,
and then finally evaluated. "This way safety procedures are integrated
into the process, and we can rely on correct workflows," says Malburg.
Transparency was also requested for the mapping and control of the complex
material flow. "It was one of our primary goals to enable an easier and
safe way of identifying the products across the entire production process,"
explains Malburg. For the operator the chosen solution is both comfortable
and reliable. All input materials, containers, and machines are provided
with barcode labels and are automatically identified with barcode scanners.
This avoids mistakes and increases pharmaceutical safety. The mobile
RF terminals for barcode scanning give the personnel the necessary
freedom of movement and users no longer depend on the PC station,
since they can get the required information on the progress of the
manufacturing process directly on the shop floor. Only the barcode
labels are still printed at the PC. Moreover, all the weighing stations
are consistently integrated. A weighing robot is supplied with data
directly from the electronic batch records and is connected to the system.
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| The Reality of Electronic Documentation |
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Meanwhile, a fourth partial goal has been achieved. Apart
from a few forms, paper has completely disappeared from production.
All documents only exist in electronic form. Also all the signatures
required for the approval of individual production steps are performed
electronically. Safety first - a hierarchically structured user concept
regulates the authorizations to sign. Bayer was consistent in
implementing the double-check principle. If a signature is required
at a critical process step, the employee responsible needs to
re-identify with user ID and password. It is checked whether the
inputs are plausible and it is possible to change entries, if
necessary. The system logs all data corrections and changes and
documents them together with the associated electronic signature.
Since signatures are actually database entries, they cannot be
deleted and it is thus ensured that it is not possible to copy
a signature or remove it from a document. Malburg comments:
"From our point of view such a database-oriented system is the
optimal approach. It is easy to handle and guarantees that
documentation and signatures are 21 CFR Part 11-compliant."
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Fully Integrated Systems
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The Manufacturing Execution System is integrated into a comprehensive IT
framework concept. At the level above, there is a Unix-based system
supporting materials planning, order creation and the entire supervisory
control planning. Below the MES, there is the machine level to which the
MES offers standard integration modules. A standard interface has been
implemented to SAP. It ensures that all pharmaceutically relevant data
remain in the Manufacturing Execution System. Material inventories are
administered in SAP. Another important feature: the Manufacturing
Execution System provides an automatic master data interface to the
SAP system. In case recipes are changed in the MES the interface
makes sure that the master data are automatically reconciled between MES and SAP.
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Optimum Efficiency |
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Looking back on more than four years of practical experience with the Manufacturing
Execution System Wolfgang Malburg strikes a positive balance. Following an
initial phase of familiarization, the user satisfaction was complete.
"The use of mobile RF terminals has proven a real success." Malburg
underlines, "The operators truly welcome the high degree of mobility
and the safe guidance guaranteed during the execution of orders."
In using PAS-X, Bayer has been able to further optimize pharmaceutical
safety, to substantially increase the transparency of the material flow,
and to implement measures for boosting efficiency of the manufacturing process.
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| Your direct link to Bayer
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 www.bayerpharma.com
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