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MASCHINEN • SYSTEME • IDEEN
Exceeding Expectations
Made in Germany
REPORT
1 / 2008
Flexible Disposable Containment Technology
applied in an existing multi purpose
API facility – OEL (Occupational Exposure
Level) < 1µg/m 3
Richard Denk
Director Pharma-Department
r.denk@hecht.eu

REPORT 1 / 2008
Closed System Solutions for Highly Hazardous Substances
„Made in Germany“
American Pharmaceutical Manufacturer uses Closed
Systems for the benefit of Operator Safety and for preventing
Cross-Contamination.
As a result of the growing number of products which are
classified hazardous and highly hazardous for employees
in the active substance (API)- and pharmaceutical industries,
the demand for product and operator safety is
constantly increasing. In the United States, the Food and
Drug Administration (FDA) monitors and regulates the
producers of Active Pharmaceutical Ingredients and
pharmaceuticals. The FDA is also acting outside the U.S.
when a manufacturer plans to launch a pharmaceutical
product into the American market.
For some years now, the FDA has been requesting
stronger integration of Closed Systems in the U.S. for
the handling of hazardous and highly hazardous substances.
The risk of cross contamination cannot be excluded in
clean rooms either. Clean rooms and lock systems are
merely secondary resources. Cross contamination,
which originates from carrying objects to the production
area or from employees, cannot be prevented. Especially
in the manufacturing process of substances such as cytotoxic
beta-lactham, teratogenic substances as well as
antibiotics in multipurpose plants, the regulatory authorities
have highest concerns if products are temporarily
handled in open condition.
Customer Requirements OEB5, OEL < 1µg/m³
2

Flexible Containment Solutions
as Product and Operator Safety
Reactor Charging
Transfer System
Sampling
Warehouse
Centrifuge
Discharge
Dryer
Filling
Reactor
Reactor
Centrifuge
To be able to produce highly hazardous substances
which require a very low containment level of 1µg/m³ (the
average OEL measured over a period of 8 hours), an existing
manufacturing facility processing active substances
required a complete redesign of their powder transfer
equipment. The containment requirement included the
equipment processing the starting material up to the finished
substance API (Active Pharmaceutical Ingredient).
For the integration of a suitable closed system, the existing
structure of the building and the customized demands
concerning raw-materials, intermediates and final products
were taken into consideration. The basic materials
are acquired from all over the world and there are no
standard packaging norms. The possibility could not be
ruled out that the operator gets in contact with a substance
when opening the packaging material which, for
example, were filled improperly by a supplier. Some
products compact in the packaging material and require
delumping before entering the manufacturing process.
Another focus was the cleaning of the facility in order to
minimize the set-up- and down-times when changing the
product. For planning, the customer placed an order for
detailengineering first and then decided to appoint us
general contractor.
Dryer
The product brief included the
following Containment solutions:
Dryer
Discharge
and Filling
in Drums
the sampling of starting materials,
the transfer from drums to FIBCs,
the charging of reactors,
the discharge of centrifuges,
the filling of dryers,
the discharge of dryers into small quantity
receptacles.
3

REPORT 1 / 2008
Closed Sampling of
the Starting Materials
As solution for the sampling from drums with inner
liners, a flexible protective liner technology was chosen.
This protective liner system is a primary Containmentsystem.
The protective liner technology protects the
product from contamination originating from the environment
and the operator from hazardous substances.
The protective liner for sampling is fitted with two
gloves, a sampling liner sleeve and a connection to the
small dust filter cartridge. Inside the protective liner
there is a bag for tools required for sampling.
The protective liner is
designed as one-way
system and therefore
needs no cleaning. A
validation of cleaning, as
customary in the pharmaceutical
or API trade,
is not necessary.
The protective liner is fixed in a sampling unit. After
opening the drum, the outer liner (not the product liner)
is turned inside out over the edge of the drum and fixed.
The end of the protective liner is joined with the outer
liner of the drum by adhesive tape. The dust filter cartridge
is connected to a larger external dust filter system.
By using the gloves, the operator opens the product liner
and starts the sampling. After sampling is completed,
the liner sleeve is clamped twice with special closures
and cut in the center between the closures. If there is no
further sampling necessary, the product liner is closed
again. The protective liner is evacuated and removed, together
with the outer liner, from the edge of the drum.
The outer liner is closed now with two special closures
and cut in the centre between the closures. The drum is
sealed with the drum lid.
The outer liner is opened and
turned inside out over the
edge of the drum.
The protective liner is turned
inside out over the drum and
fixed at the outer liner.
Using the gloves, open the
inner liner of the drum and
take a product sample.
Comparison of Protection Technologies for product sampling
Consumables
25.000 $
20.000 $
15.000 $
10.000 $
5.000 $
0 $
Protective
Liner
Technology
Isolator with
Decontamination
Unit
Laminar Flow Unit
with PPE and
Decontamination
Unit
0 $ 100.000 $ 200.000 $ 300.000 $ Investment
The part with the product sample
is cut off at the end of the
liner.
The operator closes the inner
liner via the gloves.
After closing and cutting the
protective liner twice, the protective
liner system can be removed.
4

Dispensing Unit for Starting Materials
and Intermediates from Drums into FIBCs
For the purpose of transfer and process-related weighing,
the starting materials (raw-materials) or intermediates
are taken to a transfer room. For containment of
the products in the transfer area, a drum/sack transferisolator
is provided for the various size drums used in
the facility. All products are emptied in the isolator by
force of gravity.
An hygienic lump breaker breaks up any product agglomerates
to a size suitable for weighing and metering
into the intermediate FIBC. Between the lump breaker
and the metering system there is a safety screen to sieve
any large agglomerates which may have passed through
the delumper.
Lump Breaker
The operator opens the drum and connects the protective
liner system and the drum with a liner tube. With the
gloves of the transfer isolator, the operator pulls the
residual liner into the isolator and disposes it in a waste
bag. Subsequently, the drum is pushed into the isolator
via the tipping device until the operator, still wearing the
gloves, is able to reach and open the drum and inner
liner.
Once the discharge is completed, the drum is closed
and removed from the isolator, the protective liner is
clamped twice and cut off in the centre between the closures.
The one half of the protective liner serves as closure
at the isolator; the other half of the protective liner
serves as closure at the drum. The discharged product is
prepared by the lump breaker and the safety screen in
order to be weighed-in into the FIBC by means of the
Q-Dos, a hygienic metering system. The Q-Dos consists
of a flexible tube which is opened and closed externally
by two variably controlled pneumatic cylinders. For precision
metering, the cross-section is narrowed on one side
and thus the metering flow reduced. For finest precision
metering, the cross-section of the Q-Dos is narrowed further
and completely closed after the desired product
quantity is transferred to the intermediate receptacle.
Protective Liner System for the Discharge of Drums
Transfer Isolator, Lump Breaker, Q-Dos Metering
System, LBK, Weighing System for the FIBC
At the back of the isolator there is a protective liner connecting
system which is closed with the residual liner of
the previous protecting liner. By means of a drum liftingand
tipping device, the drum is positioned directly in
front of the protective liner connecting system.
Q-Dos Metering System
open
closed
5

REPORT 1 / 2008
LBK
Liner Filling Head
For the closed filling of FIBCs in the dispensing unit and
for the discharge of the centrifuges.
For intermediate packaging, FIBCs with inner liners were
selected because they are most suitable for filling, discharge
and storage of the various types of products. The
purchasing price is low in contrast to other systems,
such as IBCs. There is no cleaning required for each FIBC
is only used once.
For the safe connection of the FIBC, the Liner Filling
Head (LBK) was integrated. The inliner of the FIBC is
connected to the Liner Filling Head with a tension ring.
After filling, the operator
closes the liner inlet
twice at a short distance
and cuts it off in
the centre between the
closures. A residual
liner remains at the
Liner Filling Head. The
Liner Filling Head and
the FIBC are sealed
from the surrounding
Closure Toolkit
environment. The next
FIBC is connected with a new tension ring over the residual
liner. Subsequently, the residual liner is isolated
and disposed of via a side hand access opening.
Connecting the Liner.
Connecting the Removal Bag for the Residual Liner.
Removing the Residual Liner from the
Hand Access Opening.
Removing the Residual Liner from the Product Pipe.
Securing and Filling.
Closing and Cutting the Liner.
6

FIBCs as In-Plant
Packaging Handling-System
Sequence of
Operation LAS
The filled FIBC is taken from the dispensing unit to the
stand-by room. Depending on the requirement, the FIBC
is identified by a bar-code system and carried into the
corresponding room for reactor charging. A containment
discharge system consisting of lifting column and Liner
Connecting System (LAS) is installed in each reactor
room. The lifting column picks up the FIBC and positions
it at the discharge system. Moreover, the lifting column
is needed to balance the stretching of the FIBC during
the discharging process.
The inliner of the FIBC is connected to the Liner Connecting
System (LAS) with a tension ring. A mechanical agitation
unit optimizes the product flow. When the FIBC is
empty, it is evacuated. The operator closes the liner outlet
twice at a short distance and cuts it off in the centre
between the closures. A residual liner remains at the
Liner Connecting System (LAS). The Liner Connecting
System and the empty FIBC thus are sealed off from the
surrounding environment. The next FIBC is connected
below the previous residual liner with a new tension
ring. The residual liner is isolated and disposed of
through a side hand access opening.
Fix the inner liner of the FIBC with a
new tension ring in the lower groove.
+
Remove the residual liner with the liner bag.
Pull out the residual liner and the
tension ring with the removal bag.
Secure and FIBC discharge.
Lifting column, FIBC Upper transport frame,
FIBC, Mechanical agitation, LAS,
Lower Transport frame for the FIBC, Reactor
After discharge, close the liner twice and
cut it off in the centre between the closures.
7

REPORT 1 / 2008
Centrifuge-Discharge and
Dryer-Filling in one Unit
Dryer Discharge with
Endless Liner-Technology
Special requirements existed for discharging product
from the centrifuge directly into the dryer below or alternately
into a separate FIBC.
Centrifuge Discharge, LBK for FIBC Filling, Lifting
column, FIBC Upper transport frame, FIBC,
Mechanical agitation, LAS for FIBC Discharge,
Dryer Filling, Lower Transport frame for the FIBC
After drying, the produced API is to be weighed-in into a
fibre-drum. For this purpose, an endless liner system
with Q-Dos metering system was chosen. Before entering
the metering system, the product is first sampled via
small bags (endless liner) and fed through an inline turbulent
sieving machine. For maintenance purposes, the
metering system, sieving machine and sampler can be
adjusted to operating height with an integrated post
hoist. The endless liner system is fitted with a liner cartridge
which includes up to 80 meters (240 feet) of liner.
The closed liner end is pulled into the fiber drum by the
operator and is inflated with nitrogen in order to prepare
an optimal filling of the drum. After filling with the
Q-Dos system, the operator pulls a clean liner from the
liner cartridge. A bag sealer closes the filled bag at the
same time, creates a new bag bottom and separates the
bags from each other. Now, the operator again pulls a
sufficient quantity of liner from the liner cartridge into
the drum and the filling procedure can start again.
The discharge of the centrifuge into the dryer is carried
out via an empty FIBC which is connected with the Liner
Filling Head (LBK) at the inlet and with the Liner Connecting
System (LAS) at the outlet. The empty FIBC
serves as buffer if the dryer cannot be filled directly. By
means of a mechanical agitation unit even moist product
which tends to bridge can be loaded into the dryer. The
option also exists to only fill the FIBC and discharge the
product into another dryer. This solution provides the
pharmaceutical manufacturer with optimum flexibility
of operation.
Turbulent seeving machine, Q-Dos metering
System, Lifting column, Endless Liner System,
Bag sealer, Weighing System
8

Endless Liner Filling
with Tensioning Bands
Cleaning the
Containment Systems
Basic position
Pull liner to the bottom of the drum.
Inflate and make the atmosphere inert.
Filling
Close twice with the clamping tool.
Cut off in the center between the closures.
Special concepts were developed to ensure a contamination-free
cleaning and maintenance. The cleaning is done
with WIP-screens which can be attached in a closed manner.
Through a specific WIP/CIP study, the cleaning nozzles
were placed at the most appropriate positions. After
the cleaning, filtered air is provided via the cleaning units
to dry the systems. After cleaning and drying, the systems
are opened for wipe tests and maintenance.
All from one Source reduces the
Planning- and Manufacturing Costs
Working with one supplier for the design engineering
and equipment supply for the Containment solution not
only substantially reduced the costs of the project but
also the installation and start-up of the equipment were
accomplished earlier than planned. The direct contact
between the supplier and the customer resulted in a
timely flow of information during the project, and
allowed the supplier to scrutinize every aspect of the
installation in detail. In doing so, weak points in other
areas were identified and corrected as necessary.
As a result, the estimated planning- and implementation
costs could be reduced by approx. 30 %.
Comparison of the total investment and life cycle cost
Investment
9.000.000 $
8.000.000 $
7.000.000 $
6.000.000 $
IBC Ridget Containment
5.000.000 $
4.000.000 $
3.000.000 $
2.000.000 $
Flexible Containment (FIBC)
1.000.000 $
0 $
0 year 1 year 2 year 3 year 4 year 5 year 6 year 7 year 8 year 9 year 10 year Life cycle cost
9

REPORT 1 / 2008
Excerpt from our
range of products
LBK filling head
for closed filling of Big Bags as well as
drums and boxes with liners installed.
LAS connecting system
for the contained discharge from Big Bags
and plastic containers.
SAS protective liner
connecting system
for filling and discharge of Big Bags as well
as other containers. Containment is ensured
by using protective liner.
Sack and drum discharge
using a discharge station with gloves and
protective liner entry system. All containers
can be brought in and discharged without
locking system.
Drum filling
with glove box for safe filling. The station
is complete including integrated screening
machine and sampler.
Isolator technology
for the highest containment for filling and
discharge of Big Bags.
10

Process technology and engineering
for the basic handling of raw materials and bulk solids as well
as special designed production processes involving active products.
We have many custom designed systems in operation
throughout the world.
Service
Preventative maintenance, repair, assembly, commissioning
and training are done by our service technicians. Of course, we
are pleased to support you in checking and modernizing older
stations.
The clean system
in bulk solid handling
ProClean ® is the quality sign for customer-specific solutions
for high value tasks in the pharmaceutical, chemical
and nutrition industries. The highest requirements
for hygiene, personnel and product safety, consistent
production and exceptional equipment quality are standards
when developing the HECHT ProClean ® systems.
Engineering – high value from a single source
During the past 30 years HECHT has consistently supplied high value technology based on professional engineering.
Our long term experience in process engineering has made us specialists in the areas of material logistics and process
engineering. Our flexibility, speed and efficiency are the keys for your company’s success!
Whatever your material handling need, you can count on us.
11

MASCHINEN • SYSTEME • IDEEN
FLEXIBLE
CONTAINMENT TECHNOLOGY
CLOSED
SYSTEMS
FLEXIBLE
CONTAINER HANDLING
HIGH
CONTAINMENT
OPTIMAL
SOLUTIONS
FLEXIBLE
AND SAVE
08-0020 | E | design©www.adverma.de
Containment solutions
for sacks and drums
■ Filling station for drums with continuous liner.
■ For clean and exact filling of drums, bags and boxes
in manual or fully automatic mode.
For further information please visit our website under www.hecht.eu/proclean
HECHT Technologie GmbH
Schirmbeckstraße 17
85276 Pfaffenhofen/Ilm · Germany
Phone +49 84 41-89 56-0
Fax +49 84 41-895656
E-Mail
Internet
info@hecht.eu
www.hecht.eu