TRANSFER METHODS

IN THE PRODUCTION PROCESS

OF ONCOLOGY PRODUCTS

by Wulandari, S.Si., Apt.

1. BACKGROUND
• The protection of operators and the environment has always been
a priority for the pharmaceutical industry.

• “If an overall manufacturing facility consists of three components -

pharmaceutical material,
personnel,
and the environment surrounding them
- containment is the isolation of the first of these components from
the other two.” – ISPE
 2. PURPOSE
• Transfer technology provides the means to move material into and
out of an isolator without breaking the containment.
 3. PROCESS FLOW
IN WEIGHING OUT IN MIXING OUT IN FILTRATION
Raw materials, Weighed Weighed Unsterile Unsterile
weighing tools materials materials Liquid bulk Liquid bulk OUT

Sterile
liquid bulk

IN Sterile
Sterile stainless IN rubber stopper
steel tray

OUT
LYOPHILI- IN OUT FILLING & IN

ZATION STOPPERING Sterile

Sterile, & full Sterile & half Sterile & half
closed closed Liquid closed Liquid liquid bulk
Lyophilized products products
products
OUT

Sterile & full

closed Liquid
products Finished
Products-
Liquid
IN
Sterile, & full
closed Finished
IN OUT
Lyophilized
products
CAPPING Products-
Lyophilized
Example of solid materials that need to be transferred in the
production process of oncology products are:
• Raw materials
• Weighing tools
• Sterile rubber stoppers
• Sterile stainless steel trays for lyophilization process
4. TRANSFER TECHNOLOGY
FOR
SOLID MATERIALS

4.1. Transfer Chamber

4.2. Active Airlock
4.3. Split Butterfly Valve
4.4. Rapid Transfer Port
 4.1. TRANSFER CHAMBER
• THE TRANSFER CHAMBER is an enclosed chamber attached to
the isolator with a door into the isolator and one sealable opening
with another door to the outer environment. Opening only one door
at a time. The chamber is not under negative pressure

• Disadvantage:
The containment performance can be compromise if materals are
passed back out of a contaminated isolator using this route, due to
potential airborne contamination and possible surface
contamination of this passed out from the main isolator chamber

• Therefore, the use of a passive chamber is not a good practice

 4.2. ACTIVE AIRLOCK
• THE ACTIVE AIRLOCK is similar to the transfer chamber except in
this case the airlock is ventilated and under negative pressure.
• This will reduce the potential for airborne transfer from the
contaminated isolator.
• Secondary decontamination of items leaving the isolator in the
airlock is preferable where very high containment performance is
required
• Careful design, operation of this transfer system is required
• Containment performance should be verified
4.3. SPLIT BUTTERFLY VALVE
• A split-valve system is made up of an active and a passive split-valve; these seal two
different container systems independently of one another in a dust-proof manner.
• The active valve is usually to be found on the production unit; ‘active’ means that this
split-valve is actuated either manually or automatically.
• The passive part, without actuation, is usually mounted onto mobile containers by
various fixing methods.
• Example of manufacturer is GEA
• Selection of the valve type:
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Buck® TC Valve - Total Containment Valve,

produced by GEA

• The system is based on the split-valve

principle of the highly successful HC (High
Containment) docking system, but designed
to meet far more stringent requirements.
• Dust emission levels during all phases of
transfer, docking and undocking can be
measured only in nano grams. This level of
emission was previously possible only with
the aid of isolation technology.
• Dust Emmission Range :< 1mcg/m3
• Nominal Size (width) : DN 50, DN 100,
DN 150, DN 200
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Buck® split
valve technology
4.4. RAPID TRANSFER PORT
 4.4.1. RTP SYSTEM FROM
GETINGE - LA CALHẺNE
Brand name:
DPTE® System (Double Door Transfer System)

•Originally built for transporting radioactive material for the

nuclear industry (where Getinge La Calhène remains a key
supplier),
•The DPTE® System is now also used for a wide variety of
life science applications where toxic or aseptic material is
being transferred.
•The DPTE® System provides the highest bi-directional
containment without intermediate bio-decontamination.
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The Principle of DPTE system:
The system is based on the interaction of two separate units –
Alpha and Beta – each fitted with a door, a lock and a sealing
function.
The Alpha unit is mounted on the wall of the isolator, while the
Beta unit seals off the container or transfer isolator.
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DPTE® system
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i. DPTE® containers

Getinge offers DPTE® Beta flange containers:

a. autoclavable stainless steel containers

b. Plastic containers (sterilize by chemical/ETO)

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Principle of DPTE® Beta containers:
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ii. DPTE - BetaBag®
The DPTE-BetaBag® is basically an integration
of the DPTE® Beta flange and a bag for isolated
transfer of sterile products or waste material.

ii. a. Ready to Sterilize – Bag

(autoclavable or ETO)

Name: DPTE-BetaBag® RTS-

Name: DPTE-BetaBag® RTS-
iX**
PSU**
DPTE®: Stainless steel
DPTE®: PSU
Diam.: 105, 190 & 270 mm
Diam.: 105 & 190 mm
Bag: Tyvek
Bag: Tyvek®
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ii. b. Ready to Use – Bag
(Gamma Irradiated)

Name: DPTE-BetaBag® RTU*

DPTE®: Polyethylene
Diam.: 105 & 190 mm
Bag: PE base

Name: DPTE-Tubing™
DPTE®: Polyethylene
Diam.: 105, 190 & 270 mm
Folded film: PE base
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DPTE - BetaBag® system
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DPTE - BetaBag® system

Link- Animasi DPTE - BetaBag® system

4.4.2. RTP SYSTEM FROM
SARTORIUS – STEDIM
Brand Name : Biosafe Port & Biosafe  Bag

System
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Biosafe  Bag

i. Autoclavable Biosafe  Bag

ii. Gamma irradiatable Biosafe  Bag

5. TRANSFER TECHNOLOGY FOR
LIQUID MATERIALS
5.1. LIQUID TRANFER SYSTEM FROM
GETINGE - LA CALHẺNE
DPTE® System for liquid transfer

5.1.A. Inline sterilization (SIP) System

Sterilization In Place
Filling process
of tank, piping and DPTE ®
transfer container
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The detail drawing of DPTE® Beta container

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5.1.B. The tank, piping and DPTE container are

sterilized by SIP; The connection tubing is
sterilized by autoclave

Sterilization In Place Transfer of

of tank, piping and autoclaved
DPTE ® transfer connection Filling Process
container tubing
5.2. LIQUID TRANFER SYSTEM FROM
SARTORIUS STEDIM
Sartorius Aseptic Rapid Transfer (SART)
Description
The SART System™ is designed
to allow aseptic liquid transfer
between two areas with different
containment classifications. The
SART System™ consists of an
external port, an internal port and
a disposable connection device –
Gammasart ATD™

Applications
The SART System™ has been
developed to facilitate an aseptic
transfer from:
a clean room into a protected
environment (Isolator, Restricted
Access Barrier System|RABS).
a lower classified clean room or
even corridor into a class A/ISO
5 clean room
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Sartorius Aseptic Rapid Transfer (SART)

The Gammasart connector:

consists of
a SART port and
a disposable Gammasart
aseptic transfer device
(ATD) connector to
address both the quality
of the aseptic connection
and to simplify passage
(of liquid) through a
wall.
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Sartorius Aseptic Rapid Transfer (SART)
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SART connection process:
The connection process consists of the
following steps (Figure 3):
•The Gammasart ATD disposable connector is
introduced in the port and secured with two
clamping devices on the external port (Figure
3(a)).
•The internal port has a clamping system to
hold the connector cover firmly inside. The
objective is to entrap all of the connector
cover's exposed outer parts inside the port
(Figure 3(b)). The internal port is sanitized
inside this clean environment with the rest of
the main equipment, for example, with the
vapourized hydrogen peroxide cycle.
•The port is opened by rotating the internal
port (Figure 3(c)).
•The tubing (e.g., silicone) is placed in the
contained area on the connector's sterile tubing
(Figure 3(d)).
6. TECHNOLOGY USE BY THE OTHER
ONCOLOGY PRODUCTS MANUFACTER

6.1. BAXTER’S (www.baxter.com) HALLE, Germany

• Facility manufactures highly potent, sterile anticancer drugs as

liquids, crystalls, dry powders, and as lyophilized products.
• A new facility, built in 2002, was designed for isolator technology.
• At Halle: all mixing, formulation and compounding operations are
performed inside negative-pressure isolators.
• Sterile filtration and filling are performed under positive-pressure
isolation to keep out contaminants.
• Baxter relies on automatic transfer systems from several German
vendors and a manual transfer system from LaCalhene
(http://www.lacalhene.com/) to move product from one isolator to
the next.
 …… Continue (6.1. BAXTER’S)

• The LaCalhene transfer systems provide processes with a high

degree of flexibility, says Baxter’s Frank Generotzky, manager
of manufacturing for cytotoxics, and permit sterile processes
even in nonsterile Class D environments
• Baxter’s isolator, transfer, and filling systems were custom-built
for individual processes and machinery by vendors, among
them Bausch & Strobel and Metal + Plastic, both German firms.
• These days, isolators are sterilized using vaporized hydrogen
peroxide.