Expertise in Synergy - Glatt

International
Times
No. 27 · March 2009
GROUP
Expertise in Synergy
ACHEMA
SPECIAL

EXPERTISE IN SYNERGY
As over fifty years ago Werner Glatt switched his production from
oven pipes to fluid bed dryers, he would never ever have dreamt
that his small company consisting of 12 employees would, within
half a century turn into a group of companies employing over
1500 staff.
Having become internationally renowned as one of the world’s
major manufacturers of fluid beds for the pharmaceutical industries,
with equipment meanwhile extended to a wide range of
processing lines, including product handling systems and related
logistics for all powder processing industries, where processes
add considerable value to the product.
List of contents
Expertise In Synergy 2
page
PAT Integration Into Process Automation 3 - 4
Test Instruments / Customer Data Base 5
About TTC 6
Extended Services: Software Hotline 7
hollomet, Innovations In Cellular Materials 8 - 9
Genzyme And Glatt 10 - 11
ADD Technologies Ltd, Reinach, Switzerland 12
Glatt Builds Sodium Cyanid Factory For Lukoil
Glatt – New Filter Design For More Flexibility
13
Of Continuous Production Plants 14
Spotlights
TTC 146
15 -16
Multiparticle Dosage Forms
TTC 150
17
Functional Filmcoating 18
TTC Program 2009 19
Glatt Group Service Range 20
Published by:
GLATT INTERNATIONAL
79589 Binzen, Germany
Ph: + 49 (0) 76 21 / 664 319
Fax: + 49 (0) 76 21 / 16 799 200
E-Mail: bianca.nowak@glatt.com
http: www.glatt.com
Editor: Klaus Eichler
Production: Bianca Nowak
Alison Russell
By Klaus Eichler, Editor
This may well be a sophisticated controlled release drug tablet or
pellet, but also a functionally coated food or feed product, or a
delivery system for a cosmetic product.
In the millennium of communication neither the equipment manufacturers,
nor their customers are reluctant to share and use the
know-how and process understanding acquired by other industries.
Nevertheless, true process understanding is only gained by
extensive own use of the processing equipment manufactured
at the various Glatt sites; warranted by our IPC division, contract
manufacturing food, feed, fine chemical and cosmetic products
24 hours a day, 7 days a week for the past 15 years.
The empirical know-how can thereby be gained and converted
into equipment specific for each project by our engineers.
In contradiction to certain contemporary statements, I believe
that quality is not achieved by design, but by continuous improvement,
as nature did for the last 4.5 billion years.
Hence, it was just a logical conclusion that we got involved in
process and product optimization, and finally the formulation of
own and contracted products, which also requires sound process
understanding if one wishes to formulate around a robust
and economical technology, presently being achieved by our
divisions ADD and Glatt Pharmaceutical Services with great
success.
No wonder we then created our division Pharmatronic, which
qualifies and validates processes; and TTC, which stages regular
international workshops on process technology.
No surprise, that there is also an industrial engineering company
in our group, having designed and built numerous processing
plants worldwide, and is currently in the process of building
a blood plasma separation plant for the Russian Health
Ministry.
It may however be surprising to find a company such as Hollomet
in our group, developing new construction materials.
The riddle is easily solved. If one considers that Hollomet’s first
new materials were based on one of our Glatt technologies,
which subsequently unite all others in the group, they can always
call on specific know-how available within the various divisions to
continuously improve their products or services, by means of a
quite easy formula: Success through Synergy.
2 International Times No. 27 · March 2009

PAT Integration Into Process Automation
Raw materials
API’s
Identification
Humidity,
Quantities
Wet Granulation
Oral Dosage Forms – typical process steps & their PAT application
By Ralf Kretzschmar, Glatt Dresden, and Thomas Hofmaier, Glatt Binzen
In recent years near-infrared spectroscopy, as well as other
online measurement systems (e.g. particle size or solid flows)
have gained growing interest within the pharmaceutical industry
for both quality control and process monitoring [1].
In order to understand the process, one main key of the PAT initiative,
online measurement is an important parameter for a successful
PAT implementation. The second, with at least similar
importance is the processing of these measurement results to
reliable rules for the process and finally the control of the process
accordingly.
Typically these online measurements not only generate one
ingle signal – such as the product temperature PT100 probe - but
generate a set of actual values in a “spectrum” which typically do
need some sort of “multi parameter interpretation” to be able to
generate some reliable algorithms for the final process control.
GLATT has integrated these systems into process automation
solutions such as MegaView or EcoView.
With an increasing number of projects, we have started to develop
and maintain standard interface modules for these PAT applications
– for example for solid flow measurements within the
Wurster tubes, particle size measurements with the PARSUM
devices or for NIR/MW systems in various process applications.
Besides our solutions customers worldwide are typically requesting
their favorite sub-supplier to be integrated. We do recognize
an increasing number of NIR or microwave system suppliers,
each of them having their strengths and weaknesses depending
on the specific application and product. Therefore, we have not
just focused on one system, but have rather added most of them
into our application library.
For example NIR/MW:
Pharmaceutical applications of near-infrared and/or Microwave
spectroscopy present both chemical and physical information in
development or production. “Nowadays NIR/MW is used in both
off and on-line applications in various pharmaceutical industrial
process control applications.
Continuous monitoring of quality is essential for PAT. The power
of NIRS for PAT is based on its speed and nondestructive nature,
which allows the analysis of intact dosage forms or intermediate
forms (e.g. granules, pellets) for chemical and physical information
[1]. Besides NIR you might see similar benefits in online
particle size measurements.
Pellets
Drying
Granulation,
Coating,
Milling
Humidity,
Endpoint of Wetting and Drying,
Pellet Agglomeration
Particle Size Control
Particle Size Distribution (Fluid Bed,
Milling)
Fluidization Control
Monitoring against Reference Batch
But how to implement them into the process controls?
Below, the 4 typical areas of integration:
1. Automation of reading cycles and management of cleaning
cycles
2. Systems setup
3. Signal processing and data interpretation
4. Implementation into process control (trip points, monitoring
and alarming)
Ad 1. Cleaning of the sensor head is essential in most cases.
This can either be achieved with liquid (the sensor is flushed in
cycles) or compressed air. Process automation manages the valves
for the cleaning media and their cleaning cycles, and reactivates
the measurement once the cleaning has been carried out.
Very often these cycle parameters are product related, and therefore
become part of the Megaview or EcoView recipe system.
Ad 2. Typically the sensor works with a set of parameters defined
during setup/calibration of the system. In some cases these parameters
for each product have to be defined individually and are
stored and maintained within the sensor device. Here the setup
of the system has to be triggered by the GLATT control system
before starting the batch. In these cases we download the actual
Fig. 1: Monitoring with NIR at a GLATT fluid bed
Photo with courtesy from Sentronic GmbH
Blending
Compressing
Homogeneity Hardness,
Compression
Rate
Coating
Coating
Thickness,
Dissolution
Profile
International Times No. 27 · March 2009
3

Fig. 2: Moisture Measurement at a GLATT fluid bed
product-ID - which is part of the standard batch-processing-data
within GLATT’s process control systems – into the local electronics
of the sensor. Standard interface technologies such as OPC
and Ethernet are the most common ways to establish communication
between the sensor and process control systems.
Ad 3. Signal processing and data interpretation only occurs
within the sensor system if accommodated with the relevant software,
if not the software must be integrated into the MegaView/
EcoView functionality. This again depends on the type of sensors.
Some suppliers can provide a signal processing software
package for the specific application, some however do not. Each
sub-supplier has their own and specific method, in some cases
exploring the definitions of the algorithms for data processing are
part of the specific project engineering. Sophisticated mathematical
processing (derivates, smoothing, baseline correction and
many more) is typically required.
Ad 4. Last but not least, the final integration of the measurement
results into the process sequence control takes place. The
Recipe-and Batch-Engine-System of MegaView does support the
PAT-application with various features:
l Freely configurable definition of a process, using “basic operations”
/ “process phases” and variable process parameters
(set values and trip-points). The customer can define a complete
process by combining basic operations. Trip-points will
switch the process from phase to phase. Here the PAT measurement
outputs can be defined as such.
l The process data with the pertinent parameters can be stored
as recipes. The control system includes recipe handling and a
recipe editor. The recipe administration (data definition) is at
the customer’s discretion.
l Freely configurable instructions, which have to be confirmed
by the operator can be added as phases to the respective
recipes. These instructions can include measurement device
procedures if required
l Real-time trends for set values and actual values
l Electronic batch reports including summaries of alarms and
deviations and graphical charts of parameters.
l Constant monitoring of the process parameter (e.g. Min/Max)
l Integrated operator guidance: the operator is guided through
the system’s preparation steps and can only activate the process
once all necessary conditions at the device are met.
Detailed messages are displayed, and inform the operator as
to why a function cannot be started and what condition has
not been met. This feature reduces possible operating errors,
and at the same time gives operators the opportunity of familiarizing
themselves with the system.
Different Levels of Integration into Process Automation
1. no integration, manual operation of the PAT device, product
parameter setup at PAT device, manual actions at GLATT control
system
2. digital and analog signals between PAT device and GLATT
control system, product parameter setup at PAT device, PAT
measurement value integrated into trip point logic of the
GLATT control system (incl. Batch Reports…)
3. digital and analog signals between PAT device and GLATT
control system, product parameter setup at GLATT control
system (as part of the recipe); data processing to generate the
actual PAT measurement value are within GLATT control system,
PAT measurement value integrated into trip point logic of
the GLATT control system (incl. batch reports…)
4. Ethernet interface (OPC) or serial/bus-interface between PAT
device & GLATT control system, product parameter setup at
PAT device, download of product information from GLATT
control system to PAT device (as part of the recipe, PAT measurement
value provided by PAT device and indicated at
GLATT control system, PAT measurement value integrated
into trip point logic of the GLATT control system (incl. batch
reports…)
Fig. 3: NIR attached to a GLATT blender
Fig.4: NIR attached to a GLATT blender
For further information please contact your GLATT sales contact
or authors
Ralf.Kretzschmar@glatt.com or Thomas.Hofmaier@glatt.com
References:
1 GLATT Times No. 23 by I Antal, A.Z. David
4 International Times No. 27 · March 2009

Test Instruments / Customer Data Base
When like us owning more than 150 test
instruments along with all required ancillaries,
relevant logistics for their use is
required. Therefore, we have developed
our own test instruments / customer data
base, in order to simplify our project management
and minimize time and cost.
Previous to now, test instrument applications
were manually logged; meaning staff
had to have a thorough knowledge of
each and every instrument, be able to
ascertain and select the most suited for
each individual application from relevant
operation instructions, which consumed a
considerable amount of time. Hence, we
decided to:
l Minimize the time for selecting instruments
l Simplify the coordination
l Improve versatility and reaction time
l Automize annual SCS calls due for certification
We achieved our target and as such set
an important milestone in our calibration
record. Since the past few months the
database has been in use, we have noticed
dramatic improvements in the motivation
of our staff. The biggest benefits
however are the acquired cost savings for
the customer, due to the above mentioned
achievements. For ourselves, we have
undoubtedly increased our competitiveness.
Fig. 1 Location schedule for test instruments
By Vito Cerone, Pharmatronic AG
Fig. 2 Customer and equipment schedule
With reference to the customer database;
annual required calibrations were in the
past coordinated by means of Excel
datasheets, in order to relieve our customers
the burden and at the same time
administrate the important calibration data
ourselves. To improve on this procedure
we were aiming to:
l Create an automatic reminder for each
piece of equipment to be calibrated or
on-site instrument
l Automatic information to the customer,
incl. a relevant offer
l Survey on the number of calibrations
l Survey on the actual calibration units
l Prevent overlapping of required instruments
to effect the calibration.
We have been using the above approach
a few years now, to the utter satisfaction
of our customers, who no longer have
to request calibration. We know the entire
scope of our required services in advance,
and are therefore able to continually
provide exact quotations and reliably
predict how long the service will take.
IMPROVEMENT BY INNOVATION
Vito Cerone is a qualified Automation Technician
specializing in Operation Management
and now works at Pharmatronic as a Service
Coordinator.
Contact: vito.cerone@pharmatronic.ch
International Times No. 27 · March 2009
5

About TTC
TTC has been created on direct
request from the industry with
respect to organize specialized
workshops on processing disciplines,
such as granulation, pelletizing
and encapsulation, for the
pharmaceutical, fine chemical,
food & feed, nutra- and phytoceutical
and the cosmetic industries.
The nomenclature “workshop”
has been preferred to “seminar”,
as our intention is not to teach but
to objectively evaluate existing
processing techniques by looking
equally at features and drawbacks,
such enabling potential
users to select the most suitable
and economical process for their
individual products.
Furthermore, we practically demonstrate
every processing option
wherever feasible or possible.
Individual exchange of experience
and a network enhancing atmosphere
is warranted by stylish social
programs in the evenings.
More than 100 reputated speakers
from the industry and industryoriented
academia lent their expertise
and vision to TTC, such
providing a treasury for information
to the attendees which also
contribute to a permanent improvement
of our program by completing
relevant questionnaires
after every workshop.
We are looking forward to welcoming
you at one of our forthcoming
workshops.
On special request we can also
offer full scale customized technology
workshops at our premises.
TTC
(Technology Training Center)
Werner-Glatt-Straße 1
79589 Binzen, Germany
Ph.: + 49 (0) 76 21 / 664 - 308
Fax: + 49 (0) 76 21 / 16 799 200
eMail: ttc@ttc-binzen.de
www.ttc-binzen.de
6 International Times No. 27 · March 2009

Extended Services: Software Hotline
During production process equipment
availability and performance is a significant
key for our clients. To provide the
best service has been the key to maintain
Glatt’s recipe for success in the past 50
years!
We measure ourselves on the success
of our customers and have
therefore extended our services
with regards to our software support
hotline, which here we would like
to explain.
Process automation has become of
increasing importance in process technology
today and is significantly defining the
performance of process equipment in
quality and output. One of the reasons for
keeping our automation and controls in
house is due our efficient after sales customer
support.
Basis for our innovative solutions and latest
technologies such as OIT/HMI (Eco-
View) and SCADA–Systems (MegaView)
are globally established and modulebased
soft and hardware.
Our control systems are installed worldwide.
As safe and reliable internet services
are nowadays state of the art within
company relations, most of our projects
are established with remote internet links
to our control systems, which are responsibly
agreed upon between the client and
GLATT, installed in save IT environments
(Firewalls, protection against malware …)
in order to establish clear procedures within
Glatt.
With these remote technologies we are
able to establish on-line diagnostics on
our systems in case of any problems or
investigation that may be requested.
The GLATT Software Hotline Support is
powered by a team of rigorously qualified
GLATT employees. Our support system is
split in 2 parts, the agreed availability level
for the support and the hotline support
service itself.
Support Levels for different customer needs
By Ralf Stanko and Thomas Hofmaier, Glatt Binzen
Typical Stand-By-Levels:
l 8 hours /5 days (8/5) typically CET –
Central European Time (Europe)
l 8 hours /7 days (8/7) typically CET –
Central European Time (Europe)
l 24 hours /7 days (24/7)
l 8 hours /5 days (8/5) local time (end
user)
l 8 hours /7 days (8/7) local time (end
user)
l or other customized Stand-By-Levels
as agreed
For the service itself, we typically agree to
a budget of man-hours per service period,
which is typically depends on the complexity
of the systems and the number of process
equipment on site. It is our policy
that service hours that have not been
used can be carried over to the next
period.
Our support consists of telephone
support and via the remote systems. Our
experience: typically more than 90% of all
support cases can be solved and closed
by instructions as to find the source of the
problem, or simply qualified answer to a
specific question.
All service requests are managed within
the GLATT help desk software system.
The predefined workflow is established
and approved by the client, GLATT and
the GLATT representatives. GLATT replies
to service requests with a qualified answer
within the agreed response time. The
scope includes activities with regards to
the clients and/or GLATT having to
change the controls, and other qualification
services for those circumstances
where setup of the system has to be
modified during the support.
Option: “Test System”:
If required so, test systems can be provided
by GLATT (typically located at
GLATT) in order to reproduce reported
performances or to test a change request
before implementing the live system on
site.
“Emergency Callout & Problem
Escalation”:
A GLATT engineer is available to come on
site and resolve the issue within the
agreed reaction time, should it not be
possible resolve an issue via remote
system.
“Preventative Maintenance Site
Visits”:
In order to maintain system reliability,
GLATT is able support the local controlsand
IT- engineers (depending on the level
of resources and qualification of the onsite
personnel): An agreed number of
regular visits can be scheduled in order to
ensure maintenance on the control system
(PC maintenance, HD clean up, PLC
and PC backups…). From our experience
these visits give operators the opportunity
to present problems that may not already
have been issued as a possible problem
during production.
The preventive maintenance typically
includes:
l On-site inspection of the systems
l Execution of data-backups on customer
requests (if required)
l Questions and Answers; Training of
personnel (if required)
l Recommendations and Consulting
(if required)
l Support for qualification activities (if
required)
Key Benefits:
GLATT Software Hotline Support program
for maximum lifetime value
GLATT Training services to empower your
team for success
GLATT Services to bring additional expertise
to your team
GLATT Software Hotline Support Resources
to help you at every problem
For further information please contact you
GLATT sales contact or the authors
ralf.stanko@glatt.com
thomas.hofmaier@glatt.com
International Times No. 27 · March 2009
7

hollomet, Innovations in Cellular Materials
Glatt, cellular materials and the hollomet GmbH
The idea of manufacturing cellular materials originated through a
close collaboration between the Glatt Systemtechnik GmbH and
a neighbouring research institute (IFAM, Fraunhofer Institute for
Manufacturing Technology and Applied Materials Research). The
most important step in producing cellular materials is the
coating, which is a core competence of the Glatt Group. After
developing this material class for more than eight years as a department
within the Glatt Systemtechnik GmbH we decided to
concentrate these activities in a new company called hollomet
GmbH launched on January 1st 2009. In this timeframe many
interesting applications have manifested from the countless possibilities,
which we together with our customers want to turn into
industrial products.
Due to being in quite similar business to IPC Dresden, with the
main difference being our focus on metallic and ceramic materials
we are its daughter company and part of the Glatt-group.
Applications of cellular materials
Here we would like to describe a few types of applications from
the different fields of industry.
- Mufflers small combustion engines
For this application the inner parts of the muffler are equipped
with globomet ® structures (material: FeCrAl). The main advantages
compared to conventional mufflers are the much simpler
setup and the mechanical strength and corrosion resistance of
this material at temperatures of up to 1.000 °C. Additionally measurements
have shown an improved sound absorption and a higher
power output / lower fuel consumption (due to a lower
backpressure of the component) compared to a conventional
component.
- Adsorbents for oxygen production
Coated carriers are ceramic spheres consisting of an inert carrier
inside and a functional coating on the surface. This functional
coating works as a catalyst (for chemical processes) or as an adsorbent
(for separations). The overall efficiency of these processes
is determined by the velocity of the process (how fast is the
process going on) and the capacity (amount of conversion per
unit volume). Whereas the velocity is increased by thinner
functional coatings (since diffusion through pores is the limiting
factor), capacity is increased by thicker coatings (more reactive
material per volume). Within our globocer ® products we can
exactly control the thickness of the functional coatings and
thereby optimize the product for maximum efficiency for each of
our customers processes.
- Oxidation catalyst for passenger cars
Conventional catalysts based on metal stripes of ceramic extrudates
have two fundamental disadvantages. Firstly the exhaust
gas is distributed unevenly concerning velocity and temperature.
This reduces the potential efficiency of the catalyst, since the
structures cannot compensate these inhomogeneities due to
their channel structure. Secondly these structures offer nearly no
possibilities for efficient construction, also due to the channel
structure. Here components based on foamet ® offer new possibilities.
Due to their morphology gas flowing through these
structures is laterally homogenized, which results in a rather even
distribution of velocity and temperature; the catalyst is used
much more efficiently. The good mechanical properties and its
morphology enable configurations with much lower backpressure
and therefore higher power output / lower fuel consumption
with the same catalytic efficiency. Additionally the amount of
precious metal needed is also significantly lower.
Technology and products
The process route for manufacturing our cellular materials
is quite easy. The first step is a coating of a polymer template
(usually Styrofoam) or a ceramic carrier (which we produce in
situ by granulation) with a mixture of ceramic or metal powder
and an organic binder. In a second step the organic compounds
are evaporated out and the powder is burnt (“sintered”) to a solid
structure, whereby the shape of the template remains. As a result
we obtain products of following types:
8 International Times No. 27 · March 2009

globomet ® are metallic hollow spheres and structures made
thereof. Their most interesting properties are sound muffling,
crash absorption, thermal insulation and high compression
strength at low density; they can withstand temperatures of over
1.000 °C and are not susceptible to pollution.
globocer ® are ceramic hollow spheres or ceramic coated carriers.
Due to the high flexibility and excellent controllability of the
Glatt coating process these structures can be ideally adapted to
the needs and requirements of our customers. Their main areas
of application are catalysts for the chemical industry and adsorbents
for gas separation and purification.
Our Team
W. Hungerbach
Managing Director
Dr. N. Reger
Operation Manager
A. Gerds
Project Engineer
globocer ®
foamet ® are metallic sponges made of highly corrosion resistant
FeCrAl. Since these structures have a very high specific surface
area, a high thermal conductivity and provide only a low drag to
passing liquids and gases, they are an ideal carrier for catalysts
and adsorbents. The mechanical properties make them well
suited for component constructions especially in mobile applications.
As it can be seen from the general properties selection the material
can be customized in wide ranges as needed by the different
applications. This is the main task to provide our customers with
the optimum solution.
Services
Besides the finished products we offer contract manufacturing on
our equipment for granulation, coating and sintering. Based on
our experience we also offer development services for the significant
process parameters as well as new and improved formulations.
G. Bingel
Project Engineer
globomet ®
P. Schmock
Project Engineer
foamet ®
International Times No. 27 · March 2009
9

Genzyme And Glatt
a winning cooperation for a new state of the art pharmaceutical plant
In 1959 just five years after having established the company
in Binzen, Werner Glatt together with just a dozen employees designed
and constructed one of the world's first fluid bed plants,
suitable for industrial application in the pharmaceutical industry.
Glatt's international activity developed due to an ever increasing
satisfied customer base and growing international demand. In
1971, Glatt AG was founded in Switzerland, followed by Glatt Air
Techniques (GAT) in Ramsey, USA in 1973. Glatt AG was instrumental
in launching a second product family onto the market: the
Glatt Coater. Today, the Glatt Corporation is a truly global company
group. It employs a workforce of over 1,300 at its various
locations and works with over 50 permanent agencies who act as
local points of contact for customers around the world.
People's ideas and expectations change the same as the economic
climate. There is however one thing that has not changed in
almost 50 years: Our focus on customer satisfaction.
In 1989 Reiner Nowak took over as Chief Executive Officer from
Werner Glatt, and made the most of the opportunities conceived
by the new development taking place in Germany. Glatt has
grown along with its customers over the past fifty years. Starting
from fluid beds, today we plan and supply complex systems specific
to the entire spectrum of solid pharmaceutical production,
exclusively using original Glatt equipment, or in cooperation with
reputable suppliers.
Three Glatt locations are together operating to successfully finalise
the new Genzyme plant on time: Glatt GmbH in Binzen (Germany),
Headquarters of the Glatt Group, with the important
automation part for the new facility; Glatt AG in Pratteln (Switzerland)
responsible for the tablet coater; and Glatt Systemtechnik
GmbH in Dresden (Germany) responsible for the high shear
mixer, the containment technology and the complete product
handling solutions. All three companies have established a single
project team, working together with PM Engineering and our
By Ralf Kretzschmar, Glatt Dresden
client Genzyme, to carry out the most efficient process solution in
time. Integrated systems are nowadays in great demand – preferably
coming from one source. With product handling, the main
criteria are primarily determined by the type of product flow,
degree of automation and level of containment.
Whether weighing, dosing, blending, sieving, storing, transporting,
docking or the necessary documentation, whether manually
or automatically controlled – Glatt together with Genzyme has
developed the optimum solution for the required application.
Something always starts with an idea, which then leads on to a
concept. Special requirements are voiced, restrictions come into
play, specifications have to be complied with and decisions to be
taken: the targeted production capacity, vertical or horizontal product
flow, manual or automatic handling, and the degree of control
integration. Open handling or total containment. WIP or CIP.
The safety concept...
There are often various different solutions which have to be
assessed. Structural circumstances on site and the type of products
being produced have to be taken into consideration.
Project management is a key factor here. Interfaces and fields of
10 International Times No. 27 · March 2009

esponsibility have to be defined, quotations obtained and costs
calculated in order to arrive at the solution that provides the best
possible cost-to-performance ratio. All these factors - and many
more - were borne in mind and bit by bit pieced together for the
new facility. After many effective meetings between Glatt, PM and
Genzyme and having been carefully coordinated, Glatt is now
supplying pharmaceutical solids production equipment, and
working in perfect harmony: A single supplier source with a
single process guarantee.
The equipment used to handle pharmaceutical solids is the allimportant
logistic and process technology link connecting individual
process steps such as weighing, mixing, blending and
tabletting on the one hand and auxiliary processes such as
homogenisation and cleaning on the other.
The type of product flow, the degree of automation and the containment
level are instrumental in determining how any complete
plant or installation is planned. The provision of the patented
Glatt SKS valve system ensures a total contained interface for the
process units and dispensing stations for the charging and
discharging of highly potent powders, hence a solution for an
application in OEB-4 areas is herewith provided.
While the weighing-in of active substances is generally performed
manually in a weighing cabin, the base carrier materials and
additives are usually measured and added into containers on
automatic weighing trucks.
Sieving and milling techniques are used to separate or reduce
the size of agglomerates in order to obtain a homogeneous grain
structure for the subsequent production process.
Even distribution of the formulation components is ensured by
dry blending using container blenders. The equipment can be
cleaned either manually or in fully automatic washing systems.
In addition to the product flow itself, factors such as preparation,
administration and reliable data transport play an ever more
important role in terms of reproduction accuracy and process
safety. Integrated systems are in great demand – preferably from
one single source. The main criteria with product handling are
primarily determined by the type of product flow, the degree of
automation and the level of containment. Whether weighing,
dosing, blending, sieving, storing, transporting, docking or the
necessary documentation, either manually or automatically controlled
– Glatt is providing the latest and proven state of the
art solution technology in close cooperation with the project
partners for the new Genzyme plant.
Schematic view of the product and data flow
in a pharmaceutical operation
Patented, contamination-free flap system
(Containment Flap)
Contamination-free
flap system: SKS
Contamination-free flap system:
Schematic diagram incl. detail
Ralf Kretzschmar is a graduated engineer in cybernetics
from the University of Ilmenau, Germany.
After ten years of sound experience in light engineering
he joined Glatt Systemtechnik Dresden as
Vice President and Sales Director.
Contact: Ralf.Kretzschmar@glatt.com
International Times No. 27 · March 2009
11

ADD Technologies Ltd
Reinach, Switzerland
ADD develops solid dosage forms (tablets and capsules)
for the pharmaceutical industry with a primary focus on
l Contract Development and Manufacturing
l Development of platform technologies
l Development of own (generic) dossiers
Drug delivery platforms:
Modified release
preparations:
Modular solutions for
delayed and extended
release multiple unit
systems
Fixed dose combination:
Platform delivery systems
for combination of different
API and/or release systems
The services of ADD include:
l Elaboration of formulation and processing
concepts
l Assessment of intellectual property rights
l Screening and selection of feasible prototypes
l Analytical characterization of raw materials,
intermediates and drug products
Members of ADD at the booth:
Armin Prasch
Chief Executive Officer
Frederic Gerber
Head Pharmaceutical Development
Burkhard Schlütermann
Chief Scientific Officer
Katrin Oppel
Project Manager Pharmaceutical Development
Taste masked products:
Effective taste masking by
film-coating of micro pellets
and APIs
Orally dispersibles:
Formulation concepts for
orally dispersible drug
products, especially ODTs
l Manufacturing of clinical trial material
l Optimization of selected product candidates
l Scale-up of a robust manufacturing process
l Technology transfer
l Regulatory services
l Commercial manufacturing
Paul Senn
Head Business Development and Licensing
Etienne Krausbauer
Project Manager Pharmaceutical Development
12 International Times No. 27 · March 2009

Glatt Builds Sodium Cyanid Factory For Lukoil
In the Glatt Times, edition 19 we reported the order received
for the above mentioned project. The complete plant was inaugurated
about a year ago.
Sodium Cyanide is used to separate precious metals such as
gold from ore, even if only contained in small quantities. The ore
is milled and turned into a slurry with water and the necessary
dressing chemicals. The cyanide (HCN) contained in the formulation
is extremely toxic and is usually produced from ammonia
and methane. It is however also produced as a by-product from
acrylnitril, which was the case for our customer OOO Saratovorgsintez
in Saratov, member of the Russian Lukoil Group, who up
to now had to thermically destroy the HCN. Due to environmental
and economical reasons it was decided to use the by-product
HCN for the production of sodium cyanide. The necessary
license for this was obtained from Dupont, the global main
supplier of this product.
By Christian Heinemann, Glatt Weimar
Glatt Weimar modified and modernized an existing building to
accommodate the new planned project, with responsibility of
design, engineering and national approval procedures; the latter
however, in cooperation with a national project institute. All
equipment was installed by our customer, however supervised
by us. The Russian operational staff was trained in parallel on
the process itself and all relevant safety aspects by Dupont in
Memphis/Tenessee.
The plant was launched in 2008 and is producing 15000 tons
per annum, which are packed and sold in steel barrels. This
quantity is however by far not sufficient to cover actual demands,
particularly when looking into separating more gold from ore with
poorer metal content.
As the main contractor we fully measured up to our customers
expectations with regards to the entire design, engineering,
equipment supply, installation, start-up and staff training. Hence
we are confident that this project will not be the only one, nor the
only Sodium Cyanide factory in Russia and elsewhere.
Christian Heiermann is a graduated process engineer
and works at Glatt since 2002 as project and sales
manager.
Contact: c.heiermann@glatt-weimar.de
International Times No. 27 · March 2009
13

Glatt – New Filter Design For More Flexibility
Of Continuous Production Plants
Plate filter design – space saving
filters on display at ACHEMA
Fluid bed equipment requires high buildings,
which are not always available.
Additional space is necessary to service
the filter on top of the already tall equipment.
Up to 2.5 meters are required
above the fluid bed contraption in order to
exchange 6m long filter bags.
Manufacturers have been offering the
possibility to place filter elements horizontally
into the filter housing for installations,
where dismantling of the filter elements to
the top is not possible. These filters are
serviced from the side, where the clean
gas also leaves the unit.
Glatt has now, for the first time integrated
such horizontal filters into the fluid bed.
The height of the equipment is decreased
by putting the clean gas chamber to the
side, resulting in no space being required
above the fluid bed unit. Doors on the
side of the clean gas chamber enable
easy access to the filter elements. Exchanging
of the filter elements is in actual
fact easier from the side compared to the
top.
New pilot plant ProCell 25 for Glatt laboratory
with highly flexible filter system at ACHEMA
By Sebastian Pfütze, Glatt Weimar
A further advantage is the possibility to
design the room at the side of the clean
gas chamber as a wash room with a solid
floor and tight connection to the fluid bed
unit. The dust-loaden filters are handled
only within this room, contaminating no
other parts of the plant with the filter dust.
Having removed the filter plates the complete
fluid bed unit can be washed in
place. With this design it is very rarely necessary
to open the fluid bed unit in the
production area.
The plate filter has been tested on a prototype
designed GF 20 in our laboratory
with the first successful application tests
being carried out in March 2008. Our new
PROCELL 25 demonstrating the plate filter
will be on display at the ACHEMA 2009.
This unit will be installed in our new laboratory
building and will be available for
tests in the fourth quarter of 2009.
WIP bag filter – no dismantling of
filter bags during wash cycle
Wash in place – bag filters have also existed
for several years. Glatt has frequently
used them for the design of continuous
fluid beds. Washing nozzles are installed
in the clean and raw gas chamber at the
top of the filter bags. During the wash
cycle they flush the filter bags from the
raw gas side and wash down all the dust
on the surface.
The quality of the washing process depends
on the product. Our experience
shows that in many applications the filters
are clean for the next product.
In order to improve the efficiency of the
WIP step and to adjust the design of the
specific granulator needs, we have now
developed our own design of spray nozzles
and filter bags. The filter has been installed
in a GFG 250 and will soon be
tested in full scale. Tests on our pilot unit
were successful in 2008.
After washing and rinsing the filter bags
are dried in the fluid or spouted bed unit,
and the next production campaign can
start. This filter has a walk-in clean gas
chamber for servicing the filter bags and
the pulse back system and is also washed
in place. Entering the clean gas chamber
is only necessary during maintenance.
Hence nobody needs to enter the processing
equipment during normal production
and cleaning cycles.
GF/ProCell 25 at ACHEMA
A new pilot unit will be installed in the laboratory
extension at GLATT, Weimar. All
commonly used filter types can be tested
with this unit:
l pleated cartridges,
l filter bags,
l metal filter cartridges,
l filter plates.
The GF/ProCell 25 is not only flexible with
regards to the filter system, but also a flexible
spraying system and the possible
change of the inlet air chamber to switch
between ProCell and Glatt fluid bed (GF)
demonstrates the state of the art design of
the pilot unit.
Additional information at::
Glatt Ingenieurtechnik GmbH
Nordstraße 12
99427 Weimar / Deutschland
Telefon +49 -3643 47-1502
Telefax +49 -3643 47-1271
eMail: redaktion@glatt-weimar.de
14 International Times No. 27 · March 2009

SPOTLIGHTS
”Yes we can“
UL Certified Automation for the US and Canada
Expectations for pharmaceutical processing
equipment are ever increasing,
particularly for very traditional processing
options such as tablet coating by
means of coating pans. The quality of
the film depends on many parameters,
such as inlet air temperature, spray rate,
process air volume etc., but also on uniform
mixing of the tablet bed, especially
when drug layering is envisaged.
GLATT process automation has extended its
portfolio in the controls and electric panel
workshop facilities. International projects with
increasing applications for the US and Canadian
market have made it possible for GLATT
to invest and offer additional services.
As our GLATT panel workshops have displayed
excellence for decades with proven
evidence according to national and European
standards, we are pleased to announce that
we have increased our portfolio.
Optimizing Tablet Coating
One expects a high homogenous film
coating, which is warranted by a uniform
statistical residence time of each
tablet in the spray area, which is a result
of tablet shape, drum design and revolution,
mixing baffles, batch size and
spreading behavior of the spray suspension
or solution.
Fig. 2, camera system
There are different approaches to evaluate
the efficiency of tablet mixing: From manual regular sampling with subsequent
analysis up to computer simulation
(the latter still being developed, see
Fig. 1).
Fig.1
In general it can be said, that so far the
evaluation of statistical exposure times
has been a rather tedious process.
Glatt AG has therefore developed an inline-tool
that can identify the motion pattern
of tablets in a dynamic process,
including the statistical analytics (Fig. 2).
This optical device can detect single colored
tablets and determine their relative
time, location and speed across the entire
tablet bed in real time.
GLATT has become a UL listed cabinet
manufacturer (UL-File E305058, Class NITW
industrial control equipment, industrial control
panels) and is therefore authorized to directly
provide UL-labels for cabinets at their manufacturing
site.
As the UL label is binding to North-American
markets (USA and Canada), having the capacity
to directly provide the UL-labels avoids
complex and cost intensive processes, no
longer applicable during the project.
A flexible camera system enables the
monitoring of the pan coaters mixing efficiency.
Even at high drum revolutions it remains
very reliable in the monitoring of tablets
(Fig. 3) and allows us to optimize
the mixing behavior and drum design,
even for individual products, in a very
short time.
A specific data analysis program using
statistical tools allows the evaluation and
qualification of the chosen coating
equipment and process parameters, allowing
the improvement of the statistical
exposure times by relevant modification
of the mixing baffles.
This tool will also be applied to future
pan coating models, aiming at the lowest
possible weight discrepancies of
layered and filmcoated tablets.
The function of this valuable tool will be
demonstrated at our Achema stand.
Fig. 3, detected tablet
International Times No. 27 · March 2009
15

SPOTLIGHTS
Latest News On
Wet Granulation, Containment Technology
& Dry Mixing
During the last ten years the Glatt-
Group has considerably extended the
realization of projects for the development
and production of pharmaceutical
solid dosage forms, particularly for wet
granulation, containment technology
and the entire product handling, mostly
by complete system integration.
Wet Granulation
Wet granulation is a major research and
development field at Glatt Dresden, with
special focus on improving handling of
the vertical granulator series (VG) with
rotor drive from below. Besides the
standard container lid fitted to a swivel
arm, we now offer a combined tilt/swivel
version of the lid for all standard and explosion
pressure shock resistant units.
We furthermore offer a pneumatic lifting
device for the rotor, which essentially
simplifies inspection and cleaning validation.
Our table top lab model is now equipped
with a multifunctional touch screen
control system, based on an industrial
PC, with the highlight option to extract
process data on a USB stick. For the
lab unit we now have interchangeable
product containers, ranging from 1-8
Liters.
Our younger series of top driven high
shear granulators (TDG) is open for further
improvement. The standard 2 bar
explosion pressure shock resistant series
has now been extended by a 12 bar
“Pro” version for all sizes. All units are
of course also available in “Super-
Clean” construction. We will be displaying
a “super-clean” TDG 600 Pro, fitted
with NIR-spectrometer for on-line end
point detection at the Achema.
Containment Technology
In order to complement the high containment
split-flap series SKS and TKS,
we have now also developed the sizes
DN 150 and DN 250, simultaneously to
improving the GMP standard for the
media flow.
For smaller productions, we have developed
the new containment transfer system
“TKS-Easy”. This new split-flap
system (patent applied) does not require
any additional docking systems or
controls, as such warranting significant
savings for the plant configuration.
During design, special attention was
given to light weight, easy handling and
easy cleaning. For the handling of small
quantities the above type, as well as
SKS 100 and TKS 100 can now be
equipped with versatile one-way bags
of different sizes.
Dry Mixing
All Glatt container mixers can now be
optionally equipped with NIR-spectrometers,
including the table top lab
mixers.
16 International Times No. 27 · March 2009

Background
More and more pharmaceutical products are reaching
the market as multiparticulate dosage forms,
mainly as pellets. The healthcare sector also frequently
selects pellets as an optimal marketable form
of functional food. As there is quite a number of existent
techniques relating to the production of pellets,
it is often very difficult for a formulator or marketing
manager to make a choice, since every technique
claims to be optimal.
This workshop is aimed at elaborating the advantages
and drawbacks of the individual techniques, focusing
on the optimal spectrum of each one, but also considering
the economical and ergonomical aspects of
manufacturing processes. On special request of various
participants, this workshop has been extended
to include lectures on the main excipients for pelletizing
and pellet coating, on functional pellet coating,
compression of pellets into tablets, capsule filling and
the most suitable capsule materials. All speakers are
specialized, experienced and renowned experts from
science and industry.
Speakers Topics
Dr. Jörg Brunemann
Syntapharm, Germany
Dr. Dominique Cadé
Pfizer, France
Dr. Pascale Gauthier
University of Clermont-Ferrand, France
Michael Jacob
Glatt Weimar, Germany
Dr. Bruno Leclercq
FMC, Belgiium
Dr. Atul Mehta
Mehta Consulting, USA
Prof. Dr. Mike Newton
The London School of Pharmacy, UK
Dr. Raphael Plüss
Encap BioSystems Inc., Switzerland
Dr. Norbert Pöllinger
Glatt Pharmaceutical Services, Germany
Prof. Dr. Agba D. Salman
Sheffield University, UK
Dr. Thilo Schmierer
Pfizer, France
Dr. Karlheinz Seyfang
Harro Höfliger, Germany
Dr. Anke Stroyer Bayer
HealthCare AG, Germany
t
Workshop no. 146
Multiparticle
Dosage
Form
l Pellets as oral multiparticulate dosage forms
l High Shear pelletizing
l Continuous fluid bed pelletization
l Preparation of pellets by extrusion / spheronization
l Pelletizing by solution, suspension and dry powder layering
l Rotor pelletization techniques
l Innovative technologies for the development and production of
controlled release pellets
l Case study: Solid state interactions between proton pump inhibitor
omeprazole and enteric coating polymers
l The main excipients for pelletizing and pellet coating
l Functional filmcoating of pellets
l Adjusting desired drug release kinetics from ethylcellulose-coated pellets
l Compatibility tests to perform with capsules
l Capsule systems today and tomorrow
l Capsule filling techniques
l Excursion to Capsugel in Colmar (France) to look at innovative
capsule technology
l Pelletizing by prilling: Theory and practise (demo)
l Process demonstrations:
direct pelletizing
suspension layering
capsule filling
Binzen, 8 -10 September 2009
To register www.ttc-binzen.de
International Times No. 27 · March 2009
17

Background
For many years the above referred to industries
have been working in the field of protecting valuable
substances for improved stability or for achieving a
defined function, without sharing their individual
experiences. Nowadays however it has been
realized that all sections of the industry have more
or less been working with the same technologies,
just using other core materials and excipients.
This workshop strives to deliver a state-of-the-art
overview on the most popular industrial techniques,
the principles of which are theoretically explained by
internationally renowned experts. During the
practical sessions the co-extrusion process and
some spray coating techniques are also
demonstrated, providing the attendees with
practice-orientated advise for future preventative
trouble-shooting.
Speakers
Dr. Jörg Brunemann
Syntapharm, Germany
Wolfgang Dejan
Glatt AG, Switzerland
Dr. Frédéric Depypere
Ghent University, Belgium
Wolf-Dieter Fischer
Glatt AG, Switzerland
Dr. David Hunkeler
Aqua+Tech, Switzerland
Dr. Karoline Kablitz
University of Düsseldorf, Germany
Jana Kell
IPC, Germany
Dr. Gabrie Meesters
DSM Food Specialties, The Netherlands
Dr. Atul Mehta
Mehta Consulting, USA
Dr. Katrin Oppel
ADD, Switzerland
Dr. Andrea Pahmeier
ticochè, Germany
Sebastian Pfütze
Glatt GmbH, Germany
Dr. Raphael Plüss
EncapBioSystems, Switzerland
Prof. Dr. Graca Rasteiro
University of Coimbra, Portugal
Dr. Frank Thielmann
Novartis, Switzerland
Wolfgang Weisbrod
Evonik, Germany
Dr. Florian Wildschek
BASF SE, Germany
t
Topics
l Pan Coating
l Fluid bed spray coating
l Dynamics of liquid sprays
l Dry powder coating
l Coacervation and interfacial polymerization
l Coating by co-extrusion, including demonstration
l Cold and hot lipid coating
Workshop no. 150
Functional
Filmcoating
barrier coating
enteric coating
controlled release
target release
l The role of material science in improving process understanding
and optimizing product quality
l Overview on the most popular coating materials for pharmceuticals,
food and feed
l Coating quality and functionality of film coatings:
Do they go hand in hand?
l Moisture protection for pharmaceutical products
l Important film coating and formulation parameters in processing
Eudragit polymer
l Process Demonstrations:
pan coating
bottom spray fluid bed coating
top spray lipid coating
l General overview of coated products on the market
l Impact of compression on film-coated micropellets -
controlled release properties/taste masking
l Health, wellness and cosmetic applications and their implications
for every day usage
l Application of Continuous Coating in the Food and Detergent Industry
Binzen, 27- 29 October 2009
To register www.ttc-binzen.de
18 International Times No. 27 · March 2009

TTC PROGRAM 2009
NO. WEEK
DATE
TOPIC
LANGUAGE LOCATION
Tue / Wed /Thu
142 17/ 09
GRANULATION + TABLETTING English Binzen, Germany
21- 23 April 2009
Tue / Wed
GLATT STEUERUNGEN
143 22 / 09
German Binzen, Germany
26- 27 May 2009
& WARTUNG
Thu / Fri
GLATT CONTROLS
144 22 / 09
English Binzen, Germany
28- 29 May 2009
& MAINTENANCE
Tue / Wed /Thu VERFAHRENSOPTIONEN
145 25 / 09
German Binzen, Germany
16- 18 June 2009 DER WIRBELSCHICHT
Tue / Wed /Thu
MULTIPARTICULATE
146 37/ 09
English Binzen, Germany
8 - 10 Sept 2009
DOSAGE FORMS
Tue / Wed
147 39 / 09
CELLETS
English Binzen, Germany
22 - 23 Sept 2009
148
40 / 09
Tue / Wed /Thu
29 Sept - 1 Oct 2009
PAN COATING
English
Binzen, Germany
Pratteln, Switzerland
Tue / Wed /Thu
149 44 / 09
FUNCTIONAL FILMCOATING English Binzen, Germany
27 - 29 Oct 2009
Tue / Wed
150 46 / 09
ROBUST DOSAGE
English Binzen, Germany
10 - 11 Nov 2009
FORM DESIGN
Info: Technology Training Center, P.O. Box 1042, 79589 Binzen, Germany
ph: +49 (0) 7621 / 664-319, Fax: +49 (0) 7621 / 16 799 200
e-mail: ttc@ttc-binzen.de, www.ttc-binzen.de
International Times No. 27 · March 2009
19

Contract
Development
GROUP Service Range
Manufacturing
Equipment
+
Contract
Manufacturing
Plant
Engineering
ACHEMA 2009
Frankfurt am Main / Germany
11. –15. 5. 2009
Please visit us
Hall 3.0 Stand O32-S42
Calibration
and Validation
20 International Times No. 27 · March 2009