Small test efforts for large production plants
Sanofi uses filling and closing machines from Syntegon Technology to determine ideal manufacturing parameters for development and life cycle management products.

The cards are constantly reshuffled in pharmaceutical development.
Especially the production of clinical samples and the technology transfer to existing commercial equipment require manufacturers to adapt
processes continuously to meet the needs of new preparations. Sanofi, for example, relies on the MRD 1010 filling and closing machinefrom Syntegon Technology to define suitable manufacturing processes
for synthetic and biologic drugs, such as peptides, oligonucleotides, orantibodies. The company tests filling and closing parameters of cartridges and vials on a small scale, before they are transferred to larger
equipment for clinical samples and commercial products.
The French pharmaceutical company Sanofi arose out of the mergerof Sanofi-Synthélabo and Aventis in 2004. Today, over 100,000 employees in more than 100 countries contribute to medical progress;
about 8,000 of them in Germany. At the site in Frankfurt-Höchst, they
develop different active ingredients in indications such as immunology,inflammation, and rare diseases and are constantly facing new challenges. Clinical samples for antibodies and other synthetic and biolo-

commercial and clinical sample production from Syntegon,” Wagner

gic modalities are administered in different ways, for example with theexplains. “So the idea of purchasing another filling and closing machi-

help of injection devices such as pens. Primary packaging materials

ne for R&D test purposes seemed obvious.”vary depending on the drug. The same accounts for the requirements
on filling and closing processes, which must constantly be redefined

Tests on a small scaleby pharmaceutical manufacturers like Sanofi. Ideally, this is done as

Sanofi and Syntegon Technology developed a special filling line,flexibly and cost-effectively as possible, and without interrupting com-which is used to carry out small-scale test series on a pilot plant,mercial production.

before transferring the defined parameters for each preparation tocommercial equipment. Sanofi selected the standard MRD 1010 filling

Securing medicine supply

and closing machine. The platform was then specially adapted by the“Process adjustments for different preparations require long test pha-experts from Syntegon Technology to meet Sanofi‘s requirements forses, which are difficult to realize on commercial equipment in terms

the planned applications. The focus was on flexibility: the entire line isof time and logistics,” explains Dr. Daniel Wagner, Head of the Drugsuited for small-batch filling of up to 50 liters and covers different car-Product development department for peptides, oligonucleotides andtridge and vial sizes.

large synthetic molecules at Sanofi. „Our large commercial filling lines
are operating continuously in shift models with minimized stop times.

Its three filling systems are another special feature of the MRD line.

Stopping commercial production for test purposes would interrupt theIn addition to the time-pressure filling system, the versatile platform is

supply of vital drugs to patients. Moreover, process adaptations would

equipped with a peristaltic pump and a rotary valve piston pump. Theychange the complex GMP configurations and would lead to further

make it possible to fill and close up to 30 different types of vials andcosts, for instance for revalidation efforts.“ Hence, Sanofi was looking

cartridges – a crucial prerequisite for Sanofi’s wide range of develop-for an additional solution to test parameters for robust development

ment and commercial products. Thanks to an intermittent rotary starprocesses, while the commercial lines could continue to run without

wheel which features an inclined infeed chute, the system also saves

interruption.

space, is easy to clean and simple to operate.

The pharmaceutical company turned to Syntegon for support. The twocompanies look back on a long-standing partnership. “We already use
several filling and closing machines for cartridges and vials inSuccessful test operations
Sanofi started test operations for small batches in autumn 2017. „The
small machine has proven to be the right choice. We can flexibly test
process parameters during filling, stoppering and capping of cartridges and vials,“ says Dr. Mandy Mohnicke, who was involved in planning and commissioning of the plant. Amongst others, Sanofi tests
the influence of filling speed, filling pressure and contact pressure on
product quality during capping, as well as the influence of the piston
stopper position in cartridges regarding its functionality in injection
devices. Only if all the critical parameters are correct, the scale-up tocommercial equipment can begin. „The flexible MRD helps us to thoroughly check relevant process parameters so that we can later manufacture our products with robust processes,“ says Mandy Mohnicke.
Patient safety has top priority
The correct speed and exact position are particularly important wheninserting the stoppers: they must neither be placed too high nor too
low inside the cartridge to enable patients to dose their medications
correctly. Otherwise, the pressure in the container might be too high or
too low. This would lead to an undesired leakage of drug product when
the needle is positioned, or to an insufficient dosage. In the interestof patient safety, Sanofi also pays great attention to optimum capping
parameters such as height and contact pressure. These parameters
are crucial for leakproof and sterile injection products.
A specially integrated data logger helps to record the parameters. It
bundles the data of different pressure and temperature sensors of
the MRD 1010 filling line. Operators have full transparency of the line
and can improve processes in a more targeted manner. “The customer-specific data collection and the fact that the equipment is suited
for a great number of different containers ensures a high degree offlexibility. Personal discussions with colleagues from other pharmaceutical companies reveal that not every pharmaceutical manufacturer
is able to work with such a special pilot line in the development area,”
Dr. Daniel Wagner explains.
Valuable advice
Sanofi was not only satisfied with the advice and support provided during the acquisition and installation phase of the MRD 1010 pilot line,
Syntegon Technology also offered the operators competent on-site
introductions regarding functions and controls of the line. “The cooperation between Syntegon Technology and Sanofi was exemplary, fromordering to start-up and subsequent service support. We can definitely
imagine continuing our cooperation in future projects,” Wagner says.
The pilot plant in Sanofi’s R&D department is paving the way for thedrug products of tomorrow.

Get in touch with us!

AuthorSebastian Lauterbach
Area Sales Manager
Syntegon Technology
E-Mail: sebastian.lauterbach@syntegon.com
Tel: +49 7951 402-268
www.syntegon.com