Keep it simple – keep it flexible

Content

Discover VarioSys®

Benefits

Fields of application

Three partners – one system

Isolator

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Types of processing

Semi-automatic processing 10

Dosing machines EDM 12

Closing machine SVP 14

Closing machine HVM 15

Nest processing 16

Module for tray/tub opening and denesting 18

Module for tub opening and denesting 19

Module for RTU containers 20

Processing vials in bulk 22

Module for filling and closing vials 24

Automatic vial processing with freeze drying 26

Freeze Dryer 28

Module for closing vials 30

Processing vials containing highly potent substances 32

External cleaning machine 34

Add-ons 36

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Discover VarioSys®

The innovative and highly flexible VarioSys® production system for biotech and pharmaceuticals is essentially a combination of two elements: an isolator made by SKAN and machine modules made by Bausch+Ströbel. The system has been designed to provide utmost flexibility in the production of medications by exchanging modules. The machine modules are simply slotted into place on the “lock-and-key” principle and plugged in. Pharma- ceutical production can be extended by adding a suitable freeze-dryer made by GEA.

VarioSys® is suitable for a wide range of applications that the manufacturing of clinical samples as well as the production of batches is possible in one installation. All FDA requirements for pharmaceutical production are met.

Discover more on our website www.variosys.com

Benefits

Adaptable to various packaging materials

Extendable modular design

Modular design of the processing line

Standardization of subassemblies

Space saving Time efficient Processing highly potent medications

Lock & key

Plug & PlayGMP and FDA conforming machine design

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Filling personalized medicines

Fields of application

Start-up / Scale-up

Flexible contract

manufacturing

Small batch

manufacturing

Product development

Process development

Commercial manufacturing

Clinical filling

Maximum flexibility for small batch aseptic manufacturing and laboratory applications in the isolator

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Three partners – one system

GEA is an expert in freeze drying technology – a partner that knows the requirements of the pharmaceutical and biotech industries and builds them into every plant it creates. With over 75 years of experience, GEA is one of the leading manufacturers of freeze dryers worldwide. The product range includes pilot plants for R+D as well as production plants for industrial batches and complete production systems containing multiple freeze dryers and Automatic Loading and Unloading Systems (ALUS™).

Providing the best technical and economical answers to the challenges presented by the world market. With this clearly defined company goal in mind, Bausch+Ströbel designs, builds and sells packaging and production systems for the pharma- ceutical and allied industries. From modest beginnings more than 55 years ago – with only four people – Bausch+Ströbel has developed into an international enterprise. It is now one of the leading manufacturers in pharmaceutical packaging.

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Founded in 1968, SKAN AG today holds a leading position in the field of isolator technology for the pharmaceutical industry worldwide. Their major products include: various safety glove isolators and filling isolators for aseptic and/or highly active products, as well as complete validation/qualifi- cation documentation and service execution. For 20 years SKAN has been the leading manufactu- rer of isolator systems in the pharmaceutical sector.

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SKAN VarioSys Isolator (PSI-L 2.0)

Efficient air- handling concept

The pre-filters, the HEPA filters of filter class H13 / H14 and the catalysts are components of the efficient air treatment concept. Different pressure cascades can also be implemented between the individual modules. The isolator can also be operated at overpressure or underpressure. The filtered air is returned via the catalysts and discharged into the room or can be exhausted externally.

The isolator provides an aseptic environment for the VarioSys® system and thus reliably protects the operating personnel and the product. This solution is suitable for processing aseptic and/or highly active substances. The new version of the isolator impresses with the patented SKANFOG® Flow System, a cleaning-friendly design and a revised air processing concept. Highest process reliability is ensured by reliable cycles with lower consumption and, above all, a significantly reduced cycle time.

Great variety of possible combinations

The individual isolator modules can be combined as required depending on the process. Depending on the production process, the system can be loaded and unloaded via a mousehole, the SARA-XL fast airlock or a sterilization tunnel. For the connection to upstream and downstream machines, various interface modules are available to cover the entire process safely.

• �Isolator with quick and easy interchangeable modules

• �Aseptic production due to H2O2 decontamination of the isolator

• �Toxic processes can be realized as well

• �Robot safety for risk mini- mization on the part of the operator and the process

• �Fast H2O2 decontamination of the material lock with SKANFOG technology

• �Excellent operator pro- tection with safely replaceable FIPA return air filters

• �Suitable for many different sizes and types of presterilized (RTU) packaging materials

Features

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SARA-XL Airlock

The newly designed SARA-XL with integrated SKANFOG® Flow technology is a safe and fast airlock for a short and gentle bio-decontamination process. The upgraded stainless-steel construction is also easy to clean. Due to its modular design, the airlock can be attached to any isolator configuration. Even when loaded, very short cycle times are possible. In addition, the principle of the single flow chamber in conjunction with the double HEPA filtered exhaust air ensure the highest level of process reliability.

SKANFOG® H2O2

micro-nebulization

Controlling the microbial load within A/B cleanroom classes is a daily challenge. Surface decontamination of the equipment is a time-consuming procedure, and validation is often complex. SKANFOG® is a decontamination technology based on the micro-nebuli- zation of hydrogen peroxide (H2O2 ). Compared with con- ventional decontamination, it simplifies and enhances both process flow and validation. Moreover, nebulized H2O2 in moderate concentrations can be used without concern for toxicity, corrosion and persis- tence. Scientific studies have shown that a total kill of a 106 population of the test organism Geobacillus stearothermophilus can be achieved and reprodu- ced. SKAN are experts in H2O2 decontamination processes and provide support in all phases of cycle development and microbiological validation.

�• Total kill of a 106 population of G. stearthermophilus

��• Can be validated and is reproducible

�• Unidirectional Airflow

�• � Catalytic converter and powerful fan for fast decontamination in a One-Trough System

�• Ultra-short cycle times

�• � Suitable for H2O2 resistant and ready-to- use (RTU) packaging material

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Semi-automatic processing

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VarioSys® provides an ideal production environment – whether in galenics, in the lab in small batch manufacturing. Equipped with semi-automatic machines, it can be used to fill a wide range of different containers with liquid and powder products very flexibly and efficiently. The system can easily be upgraded to a fully func- tional production line at any time.

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1 Quick decontamination SARA for material transfer

2 Bench-top machine for simple and precise filling of all kinds of containers EDM

3 Bench-top machine for closing vials with crimp or screw caps HVM

4 Bench-top machine for closing cartridges and syringes SVP

5 Isolator PSI-L

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Features • Rotary piston pump

• �Patented single-hose peristaltic pump

• �ViscoTec rotary displace- ment pump for dosing highly viscous (up to 5.000.000 mPas), shear sensitive and abrasive products

• �Dosing with ADVANCEDfill technology

• Filling needle movement

• Vacuum-assisted dosing

• �Automatic feedback adjustment of the dose

• In-Process Control 1 – 100 %

Dosing machines EDM

Bench-top machines for simple and precise filling of all kinds of containers. Unstable containers such as cartridges, syringes barrels and test tubes can also be processed easily using transport stands.

With this self-priming and run empty function without product loss, only the last container may need to be rejected.

Technical Specifications

Dosing range > 0.02 ml

Vial, Syringe, Cartridge Ø 6.85 – 68 mm h 35 – 160 mm

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EDM with rotary piston pumpEDM with single-hose peristaltic pump

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Closing machine SVP

Bench-top machine to close cartridges and syringes with plunger stoppers (type SVP). The stopper insertion depth and insertion speed can be freely selected.

• �Gas-flushing during stopper insertion (option)

• �Stopper insertion by vacuum (option)

Technical Specifications

Plunger stoppers Ø 5 – 30 mm h 6 – 15 mm

Syringe Ø 6.85 – 35 mm h 45 – 160 mm

Cartridge Ø 8.55 – 35 mm h 35 – 106 mm

SVP for closing cartridges and syringes

Features

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Closing machine HVM

Bench-top machine for closing vials and cartridges with crimp caps or flip-off caps. Crimping speed and pressure as well as crimping tool lift are freely adjustable.

• �Rotation of containers during closing

• �Central crimping pressure adjustment

• �Single crimping disc with servo controlled movement

HVM for closing vials

Technical Specifications

Crimp caps Ø 7.5 – 34 mm h 4.8 – 19 mm

Flip-off caps Ø 13.5 – 36.5 mm h 7 – 19 mm

Containers Ø 8.55 – 68 mm h 35 – 136 mm

Closing vials with crimp caps

Features

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Nest processing

Pharmaceuticals manufactur- ers are increasingly using RTU containers, particularly in processes such as small batch manufacturing. This eliminates the need for cleaning and steriliing syringes, vials and cart- ridges; the nested containers are delivered directly to the dosing process in special packaging. VarioSys® can be used in combination with handling, filling and closing modules to guarantee efficient processing and compliance with all regulations applicable to aseptic production.

Vial nest processing – filling in bulk

Photo: SCHOTT AG

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Syringe / Cartridge nest processing 1 Quick decontam-

ination SARA for material transfer

2 Tub debagging TUM 9030

3 VarioSys® module DDM 9105 for tub opening and denesting

4 VarioSys® module KSF 5105 for filling and stoppering vials

5 VarioSys® module SFM 5205 for filling and closing RTU containers

6 Isolator PSI-L

65631

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Module for tray/tub opening and denesting TDM 9105 (manual/semi-automatic)

• �No movement above the open containers

• �Simple and safe mode of operation

• �Automatic denesting of the vials

• �Denesting prior to filling allows the processing of potent/ toxic products in bulk

Technical Specifications

Output/h 60 trays/tubs

Tub processing

After the RTU tubs have been loaded, the foil and liner are removed. The next processing step depends on what down- stream module is used. After opening, the tub is either transferred to the module downstream by a conveyor, or the nest is removed from the tub with a handling tool and positioned for automatic denesting of the containers.

Tray processing

After loading, the tray is opened manually and then placed in the inversion unit. Once the tray is inverted, it is removed and the vials are transferred manually to the next module.

TDM 9105 - semi automatic tub opening and vial denesting

TDM 9105

Features

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Module for tub opening and denesting DDM 9105 (fully automatic)

The tubs are opened fully automatically using a heating frame. For that purpose, the tubs are transferred to the relevant positions by a clean room robot. After the tub has been opened, the subsequent process flow will depend on the type of filling machine used: The tub can be transferred in its entirety to the next machine. Vials can be denested and transferred to the next machine. Syringes and cartridges can be denested, transferred to the next machine, and renested after the filling process.

• �Nest transport by clean room robot

• �Automatic opening of the tubs

• �Automatic removal of the containers

• �Particle generation is minimized through heating at lid removal

• �Denesting prior to filling allows the processing of potent/toxic products in bulk

• Renesting of RTU containers

Technical Specifications

Output/h 60 tubs

DDM 9105 – fully automatic tub opening and denesting

DDM 9105

Features

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Module for RTU containers SFM 5205

Fully automatic module for filling and closing RTU containers (syringes or cartridges with crimp caps) at an output of up to 4,500 containers/h.

• Individual container transport

• Various dosing systems: piston pump, peristaltic pump or multi dosing unit

• �100 % In-Process Control at full speed

• Dosing with ADVANCEDfill technology

• �Camera for 100 % plunger stopper position inspection

• �Container-oriented reject discharge

• �Zero reject principle

Technical Specifications

Output/h 4,500

Dosing range 0.02 – 10 ml

Syringe size 0.5 – 10 ml

Cartridge size 1 – 10 ml

SFM 5205

Features

With this self-priming and run empty function without product loss, only the last container may need to be rejected.

Zero reject principle Maximizing efficiency and ensuring highest product quality

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Precise closure without preassure

100 % In-Process Control

Nest-to-bulk infeed and discharge

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1 Fully automatic cleaning machi- ne for vials and bottles FAW 1005

2 Sterilizing tunnel DHT 2431

3 Quick decontamination SARA for material transfer

4 VarioSys® module KSF 5105 for fil- ling, stoppering and crimping vials

5 Isolator PSI-L

Processing vials in bulk

VarioSys® reflects in its design the combined expertise and experience of our partners in the construction of machines for high-end pharmaceuticals production. The system is, as a result, an ideal solution for small-scale production runs with vials. Applications range from cleaning and sterilization, as well as gentle and precise dosing of liquid and powder products, to the closing of the containers.

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Module for filling and closing vials KSF 5105

Fully automatic module for filling and closing vials at an output of up to 3,600 containers/h.

• �Various dosing system for liquid and powder products with the ADVANCEDfill technology

• �Gas flushing after filling and during closing

• �100 % In-Process Control at full speed

• �Up to 2 closing stations – stoppers or similar inserts (e.g. press-fit caps), crimp caps

• Zero reject principle

Technical Specifications

Output/h 3,600

Dosing range (KSF 5105) 0.02 – 100ml

Vial size Ø 14.25 – 52 mm h 30 – 105 mm

KSF 5105

Features

With this self-priming and run empty function without product loss, only the last container may need to be rejected.

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Fully automatic vial filling and closing with press-fit caps

Filling and closing with stopper and crimp capZero reject principle

Maximizing efficiency and ensuring highest product quality

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Automatic vial processing with freeze drying

VarioSys® reflects in its design the combined expertise and experience of our partners in the construction of machines for high-end pharmaceuticals production. The system is, as a result, an ideal solution for small- scale production runs with vials and ampoules. Applications range from cleaning and sterilization, as well as gentle and precise dosing of liquid and powder products, to the closing of the containers. The concept also lends itself to processing complex and sensitive products such as biotech medicines.

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1 Fully automatic cleaning machine for vials and bottles FAW 1005

2 Sterilizing tunnel DHT 2431

3 Quick decontamination SARA for material transfer

4 VarioSys® module KSF 5105 for filling and stoppering vials

5 Isolator PSI-L

6 Freeze dryer for product lyophilization process

7 VarioSys® module KS 4105 for vial capping

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Freeze Dryer

If freeze drying is required, then the vials are transferred from the vial filler into the next isolator segment which contains a fully Automatic Loading and Unloading System ALUS®. The vials are then loaded without frames fully automatically into the freeze dryer. The bridge plate movement to dock onto the shelves, the shelf indexing and pizza door operation are all imple- mented in an automated sequence. When the freeze drying cycle is complete, the stoppered vials are then unloaded automatically and transferred into the following PSI-L isolator and onto the capper.

Ballroom design

The VarioSys® range of freeze dryers are available with a complete Grade C enclosure. You can walk right around the installation and never leave the cleanroom.

• �LYOPLUS® mass spectrometer - PAT tool for online silicone oil and end point detection

• LYOSPARK® controlled nucleation - Increased product uniformity

Features

Available in 3 different sizes:

FCM 25-I 1.5 m² * 25 kg **

FCM 75-I 4.7 m² * 75 kg **

FCM 150-I 9.9 m² * 150 kg **

• Compact footprint due to belly condenser design • Fast turnaround through defrosting/CIP/SIP, also coordinated with the VHP cycle

• Potent / toxic processing • Redundancy of components possible

* usable shelf area ** sublimation performance in 24hrs @ 0.2 mbar

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Technical Specifications

FCM25-I 5+1 shelves @ 350 x 900mm 1.5 m² / 17 ft² Shelf interdistance = 120 mm

Vial size Diameter Total vials

2/4 R 16 6520

6/8 R 22 3385

10/15 R 24 2825

20/30 R 30 1775

50 R 40 965

FCM150-I 7+1 shelves @ 1050 x 1350 mm 9.9 m² / 106 ft² Shelf interdistance = 120 mm

Vial size Diameter Total vials

2/4 R 16 42,406

6/8 R 22 22,295

10/15 R 24 18,697

20/30 R 30 11,900

50 R 40 6,622

LYOVAC® FCM 150-I

FCM75-I 5+1 shelves @ 700 x 1350 mm 4.7 m² / 50 ft² Shelf interdistance = 120 mm

Vial size Diameter Total vials

2/4 R 16 20,039

6/8 R 22 10,506

10/15 R 24 8,802

20/30 R 30 5,583

50 R 40 3,094

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Module for closing vials KS 4105

Fully automatic module for closing vials at an output of up to 3,600 containers/h.

• Stopper gap detection

• �Closing station for crimp caps

• �Re-capping – all containers are closed

• �Check station „no container - no closure“

• Zero reject principle

Technical Specifications

Output/h 3,600

Vial size Ø 14.25 – 52 mm h 30 – 105 mm

KS 4105

Features

Zero reject principle Maximizing efficiency and ensuring highest product quality

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Fully automatic closing vials

Reliable positioning of crimp caps using pick-and-place technology

Closing station for crimp caps

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Processing vials containing highly potent substances

VarioSys®  was designed and developed drawing on the expertise and practical experience of all partners in the high-end production of drugs. This means that this system is also able to process highly active substances (OEB5/BSL2) safely and efficiently. VarioSys® modules can be used to build a complete production line with applications from cleaning and sterilization to the exact dosing of liquids and powders, freeze-drying, sealing and comprehensive external cleaning containers. VarioSys® includes a host of features to enhance operator and product safety.

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1 Fully automatic cleaning machine for vials and bottles FAW 1005

2 Sterilizing tunnel DHT 2431

3 SARA rapid airlock for material transfer

4 VarioSys® module KSF 5105 for filling and closing vials

5 Isolator PSI-L

6 Freeze-dryer for product lyophilization

7 VarioSys® module KS 4105 for closing vials

8 External cleaning machine ARM 10600

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External cleaning machine ARM 10600

The exterior cleaning and drying machine is designed for gentle and thorough cleaning of vials. This guarantees the safety of operators and users as well as trouble-free processing of filled and sealed containers.

• �360° cleaning thanks to special ring jets

• �High-precision adjustment of cleaning parameters

• �Low or high pressure cleaning

• �Sealing or shielding of the crimp cap

ARM 10600

• �Integrated drying process

• �Validated cleaning results

• Hygienic design

• �Magnetic transport system

• Easy size changes

Features

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360° cleaning thanks to special ring jets

Discharge

Infeed and transfer to magnetic transport system

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Basic L-flange

The L-flange can be supplied without fittings for flexible use or fully adapted for customer processes. The back wall, base frame and work bench can be fitted with laboratory equipment such as scales, incubators, mixers, sensors, piping, WFI and electrical connections. Large items of process equipment - such as vessels, RTP ports and hot air ovens - can be interfaced with pressure-tight flanges.

Add ons

Flexible use of the empty flange

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• �Wireless transmission to PC

• �Specific test recipes for different types of gloves

• �Safe recognition of the tested glove port by RFID

• �Detects holes larger than 100 μm

• Cleanroom compliant

• �Test pressure up to 3000 Pa

• �In situ testing without removal of the gloves

• Reduced turnaround time

• Reliable test results on a scientific basis

WirelessGT

WirelessGT is the most advanced and fully automated GAMP-com- pliant glove leak testing system with pressure decay measurement for isolators and RABS in the pharmaceutical industry. Operation is simple and fast, without tubes and wires. All the necessary functions for performing a reliable glove test are integrated in the battery-powered test cover. The test monitors the pressure loss of the glove/sleeve assembly over a defined period of time.

Features

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Tub handling (semi-automatic) Debagging machine for tubs TUM 9030

• �Pharmaceutical transfer of tubs

• �Manual tub alignment

• Automatic bag opening

• �Automatic discharge of tubs

The unit opens the bags for removal of the tubs in accordance with pharmaceutical standards. The bag is opened inside the unit and the tub is pushed out of the bag and transferred through an airlock to the machine down- stream without any direct contact.

Features

Add ons

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• �Pharmaceutical transfer of tubs or trays

• Manual tub alignment

• �Tub discharge without direct contact (NTT principle)

• �Processing tubs and trays on one machine

• �Processing RTU packaging materials in double bags

Tub/tray handling (semi-automatic) Debagging machine for tubs and trays TUM 90100

Built for absolute reliability and compliance with pharmaceutical industry standards, this system makes sterile and ready-to-use tubs and trays available for further processing. The bags are opened inside the unit, and the tubs or trays are transferred through an airlock to the unit down- stream without any direct contact.

Features

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Cleaning machine Cleaning machine FAW 1005

• �Cleaning with ECOwash solution

• �Washing inside and outside by intensive rinsing and spraying

• �Blow-drying inside and outside

• �Silicone coating of the inner glass wall

• Processing of vials

The first step in the industrial processing of the containers for pharmaceutical purposes is to rinse the containers thoroughly. They can then proceed through further automated processing steps.

Features

Add ons

An ideal and cost-effi- cient solution for cleaning containers of any type

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• No seals are required for the HEPA filters

• �B+S stainless steel filters

• High energy efficiency

• Processing vials

Sterilizing tunnel Sterilizing tunnel DHT 2431

Sterile glass containers free of pyrogens are a prerequisite for industrial pharmaceutical production. A low-turbulence vertical air flow is used for drying, sterilization and depyrogenation of glass containers. The controlled flow of ultra-pure air allows optimal heat transfer and temperature distribution.

Features

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Sterile closure transfer BZV

• �No glove intervention with RTP with outside operation

• �Highest process reliability with loading on demand

• �Eliminates process risk of operator overfilling bowl

• �Reduces number of operators (cost savings!)

• �Fewer parts need to be sterilized

The BZV 8110 hopper system automates the feeding of presterili- zed components via a Rapid Transfer Port (RTP). The bin and feed unit is a portable system designed to store and supply ready-to-use or ready-to-sterilize component bags. It is automated by using a vibrating system to dispense the components into the bowls for processing. This prevents machine stoppages at the VarioSys® module due to a shortage of closures. The supply bin is mounted on an electrical- ly controlled telescopic column which can be lowered for filling.

• �Fully automatic closure bag unloading

• �Electrical telescopic column for ergonomic handling

• �Low particle generation for ISO 6/7 compliance

• �Touch screen HMI with memory buttons

• �Two BZV units cover all VarioSys® flexible filling line applications

Features

Add ons

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• �Robust containment due to segregated air

• �Clonable, facilitating duplicate installations

• �Fast lead times, easily installed, relocatable

Cleanroom G-Con PODs® Unique cleanroom infrastructures

The standard POD cleanroom unit is comprised of classified space (shown center), personnel and material airlocks (left) and a mechanical space (right). The mechanical space typically contains an air handling unit, the fire suppression system, and control/access points for utilities. Ductwork from the air handler to the clean space, integrated process piping, and fire suppres- sion piping is contained inside the POD ceiling plenum for efficiency and compactness.

Features

variosys.comBausch + Ströbel SE + Co. KG Parkstraße 1 74532 llshofen Germany T +49 7904 701-0 F +49 7904 701-222 info@bausch-stroebel.de www.bausch-stroebel.com

SKAN AG Kreuzstrasse 5 4123 Allschwil Switzerland T +41 61 485 44 44 F +41 61 485 44 45 info@skan.com www.skan.com

GEA Lyophil GmbH Siemensstraße 9 50189 Elsdorf Germany T +49 2274 9380990 glde_empfang@gea.com www.gea.com

Changes may be made as a result of technical progress or improvements in the services offered.

Please contact:

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Cleanroom machine ARM 10600 External cleaning highly potent and toxic substances Processing vials containing vials KS 4105 Module for closing Freeze Dryer Automatic vial processing Module for filling and closing vials KSF 5105 Processing vials in bulk SFM 5105 Module for RTU containers (fully automatic) and denesting DDM 9105 Module for tub opening (manual/semi-automatic) and denesting TDM 9105 Module for tray/tub opening Nest processing Closing machine HVM Closing machine SVP Dosing machines EDM Semi-automatic processing with freeze drying