Tofflon has been committed to the research, development, and engineering manufacturing of freeze dryers for more than 30 years. With continuous exploration, we have launched a series of new technologies like PAT tools to better assist in the research development and production of freeze-drying. We can also offer custom solutions compatible with different kinds of industry requirements and challenges which cover from R&D, pilot scale, and small production batches to industrial manufacturing. In addition to providing professional freeze-drying solution design services, Tofflon can also supply global manufacturing and after-sales service which aim to make your machine generate maximum profit value in the total life cycle.

 GB/T -150 / PED / ASME Code Pressure Vessel.

 cGMP guidelines and US-FDA recommendation.

 All chamber edges and corners are rounded to facilitate cleaning.

 Chamber dead-legs are limited to a length to diameter ratio L(length)/D(diameter) <3 and are sloped to ensure free draining.

Where the length to diameter ratio can not be achieved, cleaning action is provided with spray-nozzle.

 Chamber cooling jackets for rapid cool down after sterilization with steam.

 Condenser coils are made from polished and 316L stainless steel tubing.

 Condenser coiled piping design offers a high level of ice trapping.

 For production freeze dryers, there is optional shelf double spacing mechanism to meet requirements of different size vials.

 Optional customized shelves design for auto loading systems.

 Chamber – condenser isolation valve: mushroom valve – hydraulically driven or butterfly valve – pneumatically driven. 

 Modular design to achieve reliable and high efficiency production.

 Advanced pipeline process technology prohibits leaks.

 World-class refrigeration units ensure reliability with long service life.

 Each compressor has an independent circuit to cool shelves or condenser.

 Safety protection for compressors in high head pressure, low pressure suction, motor over-temperature, differential oil pressure,

unstable current, short circuit, lack phase and cooling water flow, etc.

 Environment friendly HFC refrigerant: free of CFC and HCFC.

 Vibration absorbers to reduce vibration and noise.

 The flow rate of refrigerant is controlled by an expansion valve to achieve the precise temperature.

 Compressor: Bitzer / Kobelco / Mycom 

 Increases lyophilizer flexibility: Achieves lower temperatures; Precise temperature control (high reproducibility); Provides faster

cooling and/or freezing.

 Improves reliability and requires minimum maintenance vs mechanical refrigeration.

 Cost competitive with mechanics.

 Smaller footprint than mechanics.

 Environmentally friendly and quiet operation.

 Nitrogen gas may be available for other uses.

 Shelf Final Temperature: -65 °C

 Condenser Final Temperature: ≤-120°C (For direct refrigeration by LN₂)

 Shelf Cooling Rate: 20°C to -40 °C≤30min (Empty Loaded)

 Condenser Cooling Rate: 20°C to -40 °C≤30min (Empty Loaded)

 Noise: 60-65dB

 Vacuum pump plus mechanical booster pump (for large scale freeze dryers) used to evacuate the complete system. (i.e. less

than 0.01mbar vacuum).

 Vacuum anti-suck back safety valve closes automatically in case of power outage to preserve system vacuum.

 Vacuum pump: Edwards

 Optional Edwards dry pump to avoid product contamination from back-streaming vacuum oil.

 Vacuum gauge: MKS capacitance manometer or Edwards APG-MP vacuum gauge

 Vacuum control: Needle valve or MKS PID control valve.

 Rotary sprayer and fixed wide-angle nozzles ensure maximum cleaning coverage.

 Pure steam sterilization minimizes contamination risks for sterile drugs.

 Ports, gaskets and viewing glasses are suitable for high temperature.

 The steam supply clean pipeline is made from polished stainless steel and is orbitally welded, tested and documented by

endoscopic inspection.

 Temperature control and monitoring are done at the coldest point of the system.

 CIP/SIP runs automatically.

 Interlocking mechanism ensures safety during sterilization process.

 External CIP System (tank and pump) as options.

 21 CFR Part 11 and cGAMP compliance.

 Access control according to authority levels.

 Audit trial recording user actions and changes to process parameter.

 Query the curve and data table record.

 Query alarm record.

 Database management and maintenance.

 Manual or automatic control available.

 Recipe management.

 PLC/Touch Screen: Siemens / AB

 Breaker / Contactor: ABB

 380V, 50Hz / 440V, 60Hz, 3-phase, 5 wires

 Cooling water for compressor (1.5≤P≤2bar, T≤25°C)

 Steam for sterilizing or defrosting (2≤P≤3bar)

 WFI for cleaning (P>=4bar, T=80°C)

 Compressed air for pneumatic system (5≤P≤8bar)

 Inert gas for vacuum release (0.5≤P≤1bar)

 Shelf temperature range: -55°C to +80°C

 Shelf cooling rate: 20°C to -40°C ≤60min

 Shelf heating rate: Approx. 1°C /min

 Condenser final temperature: ≤-75°C

 Condenser cooling rate: 20 to -40 ≤30min

 Final vacuum: ≤0.01mbar

 Evacuation rate: 1000mbar to 0.1mbar ≤30min

 Leakage rate: ≤0.03mbar.L/sec

Tofflon Airex

Tofflon Airex, a joint venture between Tofflon and Japan Airex Co.,Ltd.(the leader of Japanese barrier isolator supplier), offers safe, qualified, affordable and integrated barrier systems for pharma and biotech industry to accelerate the popular application of isolation technology in dynamic global emerging markets. 

Tofflon advanced barrier systems technology comes from our key technologies development (process understanding, ergonomics design, environment monitoring and cleaning & decontamination) and qualification expertise (construction, environment, cleaning and decontamination) in the field of isolation technology.

A scientific and risk-based lifecycle qualification and validation service can be supplied for the customer.  

Tofflon can offer a total solution proposal for the barrier systems integrated into the entire production line by fully considering the risk of contamination.  

Our products and services include barrier systems for aseptic processing line (for filling line and freeze dryer auto loading systems), for API handling (containment isolator), for laboratory sterility testing (sterility testing isolator), for VPHP decontamination (for freeze dryer, passbox, clean room and isolator), for aseptic material transfer (passbox, LAF Cart, etc) and ancillary components (glove leak tester, etc)

A. RABS and Isolator for Aseptic Processing Line

(For Filling Line and Freeze Dryer Auto Loading Systems)

B. Barrier Systems for API Handling

(For API weighing, dispensing, compounding and sampling, etc)

C． Sterility Testing Isolator

D． VPHP (Vapor Phase Hydrogen Peroxide) Decontamination

(For Freeze Dryer, Passbox, Clean Room and Isolator)

E. Aseptic Material Transfer

(Passbox, LAF Cart, etc)

F. Ancillary Equipment and Components

(Glove Leak Tester and Half-Suits, etc)

 RABS is a rigid-wall barrier, made of glass or PC, equipped with gloves, which is integrated with filling and freeze dryers for large scale aseptic process to reduce the contamination risks by physical barrier.

 A filtered unidirectional airflow (Grade A or ISO5) is designed inside RABS to protect the critical area. Pressure differential gauges are equipped to monitor the pressure across the HEPA filters.

 Anemometers are used to detect the air velocity.

 Online particle counters and microbe sampler can be equipped as options.

 Specific doors are allowed rarely opened. The intervention of opening doors should be fully validated that the operation will not introduce contamination from the background or disrupt the unidirectional airflow, and specified in the SOP. Provision for appropriate high-level disinfection of non-product contact surfaces following a door open intervention.

 Sensors mounted on doors are used to detect and record the opening, while warning or alarming will be trigged if the doors are opened.

 The temperature and relative humidity inside the RABS depend on the background cleanroom condition. 

 An absolute physical barrier between operators and the process.

 Integrated witt Vaporized Hydrogen Peroxide decontamination system to achieve a 6 log reduction of BI.

 Grade A inside with unidirectional airflow.

 Background cleanroom controlled Grade C (ISO 8 in operation).

 Temperature and relative humidity can be controlled by a dedicated HVAC system.

 RTP, SART and other transfer devices can be equipped.

 BIBO (Bag-in-Bag-out) HEPA filter or Split HEPA filter can be designed for air return ducts when both aseptic and containment required.

 Fully integrated with processing line such as filler and freeze dryer, not only mechanical but electrical as well.

 Automatic leakage test function.

 CIP and WIP function can be designed for isolator cleaning when deal with highly toxic products.

 FDA approved materials.

 Validated Grade A Unidirectional Airflow inside isolator sweep over the opened products and containers.

 Non-viable particle and viable organism are monitored online at the critical locations that determined based on risk assessment.

 Temperature and relative humidity are controlled to meet requirement of lower temperature filling or pre-cooling loading into freeze dryer.

 Vapor Phase H2O2 is introduced into isolator chamber for decontamination. Initial condition in the isolator chamber will be verified and controlled according to the cycle development to achieve a reproducible decontamination cycle.

 Mouse holes are designed between different process sections that can be decontaminated separately.

 A proper pressure differential cascade will be established differently for each working mode to achieve the optimal protection of both products and operators. 

Sterility testing isolator creates a closed and controlled environment in which to conduct pharmaceutical sterility tests. The test articles and supplies (or samples) are protected from contamination during handling by essentially eliminating direct contact between the analyst and the test articles. 

Why Isolator?

ü QC lab with Grade D and even CNC environment.

ü Minimize the possibility of “False Positive”.

ü Capable of full containment and very low bioburden.

ü Not require complicated gowning.

ü Reduction of time for labor and materials preparation.

ü Less consumption of ongoing energy cost. 

Better Understand Process to Get Even Better Isolator Design

 Unidirectional Airflow design to ensure well controlled Grade A environment.

 VPHP decontamination system is integrated.

 Environment monitoring system is integrated.

 VPHP cycle development services for the defined loading pattern.

 Customized design is also available for special package type and batches of the test.

 System with CE certification. 

Technical Highlights

A. PI-4PM, PI-4PM-S equipped with passbox. Expand the spaces of loading materials. Sliding rail design for easy transfer operations.

B. User-friendly designed HMI with functions of electronic signature, electronic records, record curve and audit tracking.

C. Integrated VPHP System, key parameters are controlled precisely to maintain a reproducible validated cycle that provides a 6-log reduction of BIs.

D. Ergonomic design for better operating experience according to procedure of sterility testing.

E. Sterility test pump and environment monitoring system are equipped. Environment monitoring data processing program is integrated with isolator control system.

F. INLS patented internal locker to control inflate or deflate the door sealing based on the mode of the isolator.

G. Online concentration monitoring both in chamber and in Your Lab.

H. Glove leakage test can test 4-6 gloves at same time in less than 20 minutes.

I. Inner frame or shelves are designed fully considered your process. Support end user to form a loading pattern making full use of space and suitable for VPHP decontamination.

J. Airflow sensor, pressure differential gauges and temperature and humidity sensor are equipped to monitor and control the chamber conditions. 

Tofflon’s toxic process isolator, designed for the safety of the operator and the production environment. Whether it is high active raw material weighing, charging or cleaning, Toflfon Isolation will provide you with a dedicated, reliable and complete containment. 

Overview

About Tofflon-Top

- Automation trend technology from Japan Top System who is specialized in designing and manufacturing of fully automatic solution preparation systems.

- Over 1000 solution preparation systems installations since 2010.

- Tofflon-Top has installed over 300 solution preparation systems across + 20 countries and regions outside China including USA, France, Spain, Turkey, Russia, Ukraine, Uzbekistan, Egypt, Algeria, Mexico, Argentina, India, Pakistan, Bangladeshi, Japan, South Korea, Hong Kong, Vietnam, Malaysia and Indonesia, etc.

- Market leader in Auto Solution Preparation Systems for complex injections (Microsphere, Liposome, Suspension, Fat Emulsions, etc.)

- Over 200 engineers specialize in process design, manufacturing, project management and service support.

- Wholly-owned pressure vessel manufacturing facility with GB-150/PED/ASME code pressure vessel compliance.

- Strength, capability and expertise to meet USFDA and EU-GMP approval

- CE and UL compliance.

- Dedicated pure steam and purified water supply facility for in-house commissioning and FAT.

Motivation for Automation

- Reproducibility

Processes and parameters are defined in recipes. It doesn’t matter who operates and his skills, final results will always be the same because of the same recipe.

- Flexibility

One system could be suitable for different products manufacturing, and recipes can be built and modified according to different product process and different batch volume.

- Easy Operation

Only push one button to launch a process. Less reliance on SOP’s.

- Data Integrity

Automation system is easy to guarantee original, accurate, contemporaneous and legible data. US FDA 21 CFR Part 11 is compliant.

- Reliability

Overall and timely monitoring. Alarm will remind operators or pause operation. Access control according to authority levels.

- Industry 4.0

Expandable automation for future DCS and MES integration. 

Features

Basic Features

Key Features

- Automatic Processing

- Filter Integrity Test in Situ after SIP

- Automatic CIP

- Automatic SIP

- Control System in compliance with USFDA 21 CFR Part 11 and GAMP 5

Key Systems

We adopt modular design and installation to save your site space and facilitate your site installation. Of course, you can choose or change different modules according to your process requirements.

Applications

Our professionals are ready to support and satisfy your various process requirements in different applications including 

- Normal chemical injectables (SVP/LVP)

- Eye drops

- Liquid orals

- Oncology / Hormone injectables

- Herbs (orals or injectables)

- Suspension injectables

- Microemulsion injectables

- Fat emulsion injectables

- Liposomal injectables

- Microsphere injectables

Oncology / Liposome / Microsphere (Three –In-One) System

Solution / Suspension (Two-In-One) System

Chemical Solution System

We believe that “Automation, Isolation, Continuous Processing and Systems Integration” are becoming main stream for aseptic processing of sterile injectables. Thanks to the above concept and European technical source, Tofflon develops aseptic filling line, incorporated with the latest design, system thinking and best practice with isolator integration to meet the increasing cGMP expectations and the latest trends in pharmaceutical and biotech industry.

Today advanced aseptic processing is growing significantly to keep operator out of the aseptic processing as far as possible. Many new technologies are developed to meet advanced aseptic processing requirements. From design concept to technology choice, Tofflon adopts the industrial latest design in aseptic filling line to minimize microbiological contamination during production for sterility assurance.

During the critical aseptic process of sterile injectables, we focus on systems thinking and practice. We study materials transfer challenges and requirements. Through mechanical integration with upstream and downstream equipment as well as complete process automation integration, we work for uninterrupted and consistent process establishment to continuously improve drug quality and production efficiency.

Today more and more oncology products come into market. Isolator Technology is becoming well-recognized technology for the processes requiring Grade A. But meanwhile Isolator Technology brings challenges for oncological production line, for example complex materials transfer and GMP quality requirements as well as safe handling of operators. In the recent years, as the isolated filling pioneer in the emerging markets, Tofflon designs and practices many advanced oncology injectables production lines in the markets which bring reputable names – KUFill and Mini KUFill. 

Our Key Features and Advantages

- Advanced Aseptic Processing Design Concept to minimize human-generated contamination in the critical process.

- Systems thinking and integration with upstream and downstream equipment so that the aseptic processing line is highly integrated, safely interlocked and reliably recorded.

- Focus on RABS or Isolator integration by design.

- Good practice in High-Speed Filling Line for Large-Scale and High-Efficiency Injectables Manufacturing.

- Advanced KUFill System for Flexible Injectables Manufacturing.

- Usage of Robotic handling for advanced aseptic processing.

- Less operator need for production and low operating cost.

- Servo Motor Control to provide a high level of automation that leads to operational accuracy as well as process reproducibility.

- Self-diagnosis and self-maintenance.

- Improving In-Process Control and reduce products loss.

- Automatically generate production batch reports in compliance with GAMP5 and 21CFR PART 11.

- Critical parameters available with control, indication, record, print and backup.

- Less change parts, fast parts change and change part with tool less.

Tofflon Aseptic Filling Line Overview

Tofflon Aseptic Filling Line includes Aseptic Vial Filling Line, Pre-Filled Syringe Filling Line, Aseptic Ampoule Filling Line and Aseptic Powder Filling Line with the series and machines available for your pharmaceutical application. On request, we will be pleased to examine the possibility of customized solutions, e.g. for similar packaging materials, specific process requirements, higher output etc.

The external washing machine is suitable to wash vials external surface under washing with PW and drying with CA with automatic continuous motion. Good performance is guaranteed for strict requirements. Washing and drying parameters of PW and CA can be real-time monitored and audited during processing so that good washing and drying can be reliably repeated. 

The tunnel is designed to sterilize and depyrogenise containers by a laminar flow of hot air with continuous process. Grade A is assured in all tunnel areas above the openings of the containers. Containers are transported through the preheating zone, heating zone and cooling zone by a conveyor belt made of stainless steel wire mesh. 

Mini-Fill Filling & Stoppering Machine for Vials is suitable for small-scale production, mainly used in R&D, Clinical Phase I and Phase II Study and other applications. Mini-Fill can meet aseptic requirements and can provide low risk, flexibility and high reliability process solutions. 

Max-Fill Filling & Stoppering Machine for Vials is suitable for small to medium scale production, mainly used for aseptic and/or toxic applications. Max-Fill can meet USFDA and EU cGMP requirements and provides low risk, flexibility and high reliability process solutions.

Industry-Fill Filling & Stoppering Machine for Liquid Vials is suitable for mass and industry scale production, mainly used for high-speed aseptic applications. Max-Fill can meet USFDA and EU cGMP requirements and provides low risk, high automation and high reliability process solutions.

Filling & Sealing Machine for Ampoules is suitable to fill liquids into ampoules and seal ampoules under Class A protection. It includes ampoules infeed, filling, pre-heating, sealing and ampoules outfeed processes. During the critical process, Class A protection is assured. Filling parameters can be managed as per the set recipe. Sealing flame intensity can be adjusted with flow meter. Real-time monitoring and traceability can be achieved during filling and sealing process so that reliable and repeatable filling and sealing process can be guaranteed.    

Filling & Stoppering Machine for Powder Vials (Mechanical Auger Type) is designed and manufactured according to cGMP requirements. It feeds powder into dosing tank with infeed screw, then accurately doses powder into vials with intermittent motion.  Auger distance, diameter and spiral shape can be changed as per filling volume demand. Powder dosing mouth is installed under powder opening and can be changed as per powder property’s influence towards dosing accuracy. Auger agitation is designed inside powder tank and can be changed as per powder property’s influence towards dosing accuracy.

Filling & Stoppering Machine for Powder Vials (Vacuum Tube Filling Type) is designed and manufactured according to cGMP requirements. It feeds powder via porous filter with vacuum, then accurately doses powder into vials with clean and dry compressed air.

Combo Mini-Fill is a series of aseptic filling machine for ready-to-use nested syringes/vials/cartridges (Three-In-One). It is designed for small batches of sterile injections for R&D or clinical trials. Combo Mini-Fill offers a low-risk, flexible and state-of-the-art filling technology. 

Combo Fill is a series of three-in-one aseptic filling machine for ready-to-use nested syringes/vials/cartridges. It is designed for commercial production of medium and high speed requirement. Combo Fill offers a low-risk, flexible and state-of-the-art filling technology. 

Overview

Blow-Fill-Seal (BFS) Machine is an advanced aseptic system which automatically delivers a finished package in a single process. Every BFS process begins with the extrusion of pharm grade PP/PE into container within the machine. The container is then instantly molded, filled, sealed and demolded in an enclosed system without any external intervention. All the filling process including the dosing system is designed with CIP/SIP functions. This machine has the advantages of advanced aseptic processing, maximum filling precision, low cross contamination risk and low production cost. It is ideal for the aseptic filling of liquids and gels which has been widely applied in eye care, injectables, respiratory therapy and other applications.

Applications

- Small Volume Applications (Range: 0.2ml ~ 20ml): Small volume injectables, eye, ear and nose drops, inhalation solutions, nestheric and other cosmetics and food applications.

- Large Volume Products (Range: 50ml ~ 1L): Large volume parenterals, large volume humidifiers and nebulizers, disinfectants, rinsing solutions, detergent,infusion and injections and other applications.

Features

BFS Typical Process

Tofflon BFS Machine Functions

Tofflon BFS Machine includes the following functions:

Tofflon BFS’ Technical Advantages

- Modular design for easy separation of gray and white system zones which not only guarantees sterility assurance of filling zone, but also much reduces space footprint than conventional filling systems to effectively save facility capital cost and operation cost.

- The extruder adopts servo motor driver with large torque and low speed to achieve higher efficiency and energy saving benefits.

- The unique parison exhaust function makes the wall thickness of the tube blank more uniform.

- The filling system adopts advanced PID control and algorithmic programming to achieve high filling precision.

- The micro damping and noise reduction technology of hydraulic system is far below the same level of vibration and noise and ensures long service life of hydraulic system.

- CUT-OFF Mechanism has its independent hydraulic system to reduce interference towards aseptic area during cut-off process, to reduce hydraulic oil leakage risk towards aseptic area and facilitate later maintenance.

- The special CUT-OFF Mechanism design ensures that the finished products are regularly delivered to the conveyor belt to offer automatic line integration possibility with the downstream process.

- We have advanced mold technology in mold design and manufacturing to provide high quality molds and later mold maintenance service.

       - Automatic execution of the cleaning and sterilization processes.

Specifications