LYOPHILIZ ATION

PHARMPRO.COM

Isolated Lyophilizer Loading/

Unloading Systems For
Bulk Products
Key factors, issues and solutions for containment system application in
lyophilization processes for the pharmaceutical industry

roducts processed by lyophilization are becoming

increasingly potent, necessitating strict segregation between the operator and the processing area
in order to mitigate the health risk. One practical
method by which this can be achieved is by placing a physical
barrier known as a containment isolator between product and
operator. However, separating the product and the operator
can only be achieved successfully if the process and ergonomic issues introduced by the physical barrier are properly
addressed. This article identifies the key factors which require
consideration when designing containment for a product

lyophilized in bulk and describes an equipment solution which

can be custom-configured to a range applications.

THE PROBLEM
Loading and unloading a commercial-scale lyophilizer
with a potent, bulk product in trays requires consideration
of the following factors:
1. Storage of clean, empty trays prior to filling; a commercialscale lyophilizer will require something on the order of
100 trays to accommodate a batch.
2. Filling the trays with product needs to be performed to
a specified level of accuracy
within suitable environment
conditions.
3. Transfer of the liquid-filled
trays onto the shelves of the
lyophilizer requires particular
attention. If at all possible
this should be performed
by an automated system to
assure that all motions are
smooth and consistent; any
sudden accelerations and decelerations will cause movement of the product relative
to its containing tray with the
consequent risk of spillage.
An automated system can
also help guarantee that trays
are placed with accuracy and
repeatability so that subsequent unloading is readily
facilitated. Furthermore, sliding of trays across shelves
should be avoided; in addition to particulate generation
from stainless steel surfaces
sliding against each other any
stick-slip motion will tend to
promote spillage.
4. Extraction of the trays of
Figure 1: The three-chamber mobile isolator houses the loading/unloading system which is shown attached to the front of the lyophilizer.

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MARCH 2010 | PHARMACEUTICAL PROCESSING

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Figure 2: The internal surfaces of the loading system are decontaminated

using a misting process.

dried product out of the lyophilizer chamber and transfer

of the trays to a product unloading station. The same considerations regarding particulate generation would apply.
5. Removal of the product from the trays and its transfer to
a specified container (such as an intermediate bulk container, or IBC).
6. Storage of trays contaminated with residual product following unloading.
7. Decontamination of all surfaces of trays and equipment
where product could be present to a level which is safe
for operator intervention.
THE SOLUTION
Telstar recently delivered an automated system for the
lyophilization of a bulk polypeptide which is hazardous to
operators. The system enables an OEL (Operator Exposure
Level) of 1 g/m3 to be achieved over an eight-hour shift
and is comprised of a GMP production-scale lyophilizer and
a loading unloading system housed within a three-chamber
mobile Isolator system.
The general equipment arrangement is shown in figure 1.
The central Transfer Chamber contains the mechanisms
which automatically transfer the trays of product into and out
of the process chamber of the lyophilizer through an automatic sliding door referred to as a "Pizza Door". Loading and
unloading of product trays is performed at constant level
(the lyophilizer positions each of its shelves in turn at a predefined height) and occurs without sliding of the trays across

PHARMACEUTICAL PROCESSING | MARCH 2010

LYOPHILIZ ATION

the shelves. On each side of the transfer chamber are separate Tray Storage
Chambers. The transfer chamber docks to
a flange on the front of the lyophilizer and
is made leak tight by an inflatable gasket.
The tray storage chambers are similarly
attached to the transfer chamber and once
connected the three chambers make up
the isolator system, with integrated environmental control provided to all three
chambers. Control of the entire system is
performed by integrated programmable
logic controllers and operator-interaction
is via a graphical user interface.
Implementation of this complex integrated project was achieved through
the close collaboration of three Telstar
Technology Centers: Lyophilization, based
in Terrassa, Spain; Containment, based in
Dewsbury, UK, and; Loading Systems, based
in Bristol, Pennsylvania in the USA. In addition, one of Telstars partners, the Danish
company Flexicon, provided the peristaltic
filling technology used to dispense the liquid product into stainless steel trays.
After the product has been lyophilized
the dry product is removed from the trays using a vacuum
system, which transports the product to a cyclone where it
is separated from the airstream and collected in a storage
vessel for transfer to the next step in the production process.
The required balance of safety and economics was
achieved by careful identification of which process steps
should be automated and which could be performed manually (see separate section itemizing the process steps). In order to ensure that chosen manual steps were ergonomically
acceptable a full-scale model of the system was constructed
in wood, which gave operators and process engineers the opportunity to fully assess the details of each manual task prior
to committing to a final equipment design.
Telstar was uniquely suited to provide this system; being
able to develop a process solution and then provide all of
the required equipment technology using the in-house resources of the Telstar Group.
The technology developed can be configured to operate
under both aseptic and non-aseptic environments.
THE PROCESS STEPS
1. The transfer chamber is docked to the front of the lyophilizer and in turn the two tray storage chambers are
docked to the sides of the transfer chamber. (Note: If the
product to be handled is safe in liquid form and hazardous only in dry form then it is possible to perform the
loading operation without the need for containment.)
2. The operator places trays at each of two filling stations
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LYOPHILIZ ATION

within the transfer chamber. A peristaltic

filling system automatically fills each tray
with the required volume of product. The
trays are then automatically transferred
through the pizza door and placed on the
shelf of the lyophilizer; tray movement
is performed without sliding the trays
across the surface of the shelf. This process continues until the entire lyophilizer
has been filled.
3. The pizza door is closed and the lyophilization cycle is performed. At the end of
the cycle the access doors of the isolator system are closed (if they were open
during the loading process) the environmental control is brought into operational
mode and a leak test of the isolator system is carried out.
4. The chamber of the lyophilizer is brought
to the same pressure as the isolator system, the pizza door is opened and pairs of
trays are automatically removed from the
lyophilizer and positioned in front of the
operator. Using a vacuum wand and working through glove ports, the operator removes the dry product from the trays and
then places the empty trays into storage

Figure 3: Manual cleaning operations.

racks in the tray storage chambers.

5. This process continues until all of the
trays have been removed from the lyophilizer, after which the pizza door is closed.
At this point in the process the product
has been removed and securely stored.
6. The internal surfaces of the isolator system

and the lyophilizer are potentially contaminated with

hazardous product. While all
chambers are still docked in
place and leak-tight the entire
internal surface of the equipment and the trays are decontaminated using an atomized
misting process (see Figure
2). Any gross spillage of product can be removed by the
operator using a hand-held
spray nozzle (see Figure 3).
7. The loading equipment has
now been made safe and the
elements can be undocked
for thorough manual cleaning. The lyophilizer is subjected to fully automated clean-in-place and
steam sterilization cycles.
8. The equipment is now ready for the next
production batch.

ABOUT THE COMPANY:

Telstar North America, Inc.
1504 Grundys Lane, Bristol PA 19007 (USA)
T +1 (215) 826 0770; Web: www.telstar.eu

Xcelodose S Precision Micro-Dosing System

CFS 1200 Liquid Filling & Sealing Machine

CapsuleCaddy Container

To order or for more information, call 888-783-6361

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