HOF FTU Englisch 2025

HOF – knowledge Knowledge and experience you can rely on With over 35 years’ experience, HOF Sonderanlagenbau GmbH is the leading specialist in the manufacture of individual freeze drying systems, loading and unloading systems, as well as freeze thaw units for the pharmaceutical and biotechnological industry. At the company’s sites in Lohra and Mornshausen, near Marburg, more than 350 highly motivated and qualiﬁed employees work on the company’s own production area of 15,500 square meters. These employees also include the HOF service team, which is responsible for close contact with customers – both nationally and internationally. 2

HOF Freeze-Thaw Solutions - Continuous innovation since the 1990s HOF – company Optimal freezing and thawing processes for pharmaceutical industry Especially during the COVID-19 pandemic, topics such as cryogenic storage and transportation have increasingly come into focus. However, just as important as storage and transportation is the actual freezing process, in which products are frozen to extremely low temperatures. The focus here is on fast and high cooling rates as well as uni- form and controlled heat transfer into the product. With its extensive experience, HOF Sonderanlagenbau is the leading expert in the provision of freeze-thaw solutions for single-use processes in the pharmaceutical and biotechno- logy industries. Technological excellence for the highest product requirements Since the early 1990s, HOF Sonderanlagenbau has been developing and manufacturing solutions for freezing and thawing, the so called Freeze-Thaw Units (FTUs), which were initially designed speciﬁcally for the rapid freezing of blood plasma. Initial development of the Freeze-Thaw Systems in the early 1990s Today`s Freeze-Thaw Unit design: modern and reliable This early innovation quickly attracted the interest of the pharmaceutical and biotechnology industries. In order to meet the speciﬁc requirements of these markets, both the machine design and the technical equipment have been continuously developed. Today, HOF‘s freezing and thaw- ing solutions are widely used to produce a variety of diffe- rent products. HOF Freeze-Thaw Units reliable, efﬁcient and innovative Today‘s Freeze-Thaw Unit design: modern and reliable Through continuous development in all technological areas, HOF ensures that its Freeze-Thaw solutions always meet the latest technical standards and fulﬁll the highest product re- quirements. With innovative solutions and pioneering de- sign, HOF successfully supports its customers in achieving their ambitious goals. 3

HOF – technology Optimal process control for safe production In the pharmaceutical industry, processing in single-use bag systems is essential. The freezing and thawing plays a critical role and require fast, efﬁcient and precisely controlled pro- cesses. From the preparation of cell lines, through upstream and downstream processing, to the ﬁnal Fill and Finish, HOF systems ensure optimal handling. They enable stable and safe product transfer between the individual process steps. 1 2 3 Product preparation Filling Load/Unload - Freezing Preparation includes the creation of cell lines required for the fermen- tation process, followed by their cultivation and multiplication up to the respective production scale in the bioreactor. This upstream pro- cessing step leads to downstream processing, which deals with the pu- riﬁcation and concentration of the products. Once ﬁltration is completed, the ﬁnal formulation and ﬁlling steps follow. In general, the products are ﬁlled into bag or bottle systems using single use technology, which are used both for storage and for in- termediate buffering step. The ﬁlled product is transfered from the ﬁlling machine to the Free- ze-Thaw Unit. The loading and un- loading equipment ensures that the product is transported efﬁciently from the ﬁlling process to the Free- ze-Thaw Unit and towards the sto- rage room afterwards. The freezing process is essential in order to make the product long term stable, as the probability of unintended reactions or contamination is much reduced. Versatility of product applications HOF‘s Freeze-Thaw Units are speciﬁcally designed to process a wide range of biotechnological and phar- maceutical products. Controlled processes are critical for handling these sensitive products to ensure quality and efﬁciency throughout the production cycle. The systems are designed to effectively process speciﬁc for- mulations for different applications. Monoclonal antibodies (MABs) Messenger RNA (mRNA) Bioconjugates Vaccines Cell and Gene Therapy First steps in product development 4

HOF – technology 4 5 6 Storage and shipping Load/Unload - Thawing Fill and Finish After freezing, the products can eit- her be stored or prepared for ship- ping to the drug product site until the thawing process begins and preparations for ﬁnal ﬁnishing and ﬁlling start. Once the product is to be reactivated and prepared for the ﬁnal Fill and Finish, the frozen product will be transfered via the loading and un- loading equipment from the storage room to the Freeze-Thaw Unit. Wit- hin the same device as for freezing purposes, the thawing process can be executed and allow for controlled rate thawing of the product. After thawing and ﬁnal preparation of the product, the ﬁnal phase of the production process takes place. Here, the ﬁnal product is ﬁlled into the appropriate packaging material, labeled, packaged and undergoes a ﬁnal quality check before being re- leased for use. These steps are cruci- al to ensure that the product reaches the patient safely and effectively. Each of these products requires precise control during free- zing and thawing to preserve the integrity and functionali- ty of the active biological components. HOF‘s sophisticated technology enables these demanding requirements to be met with the utmost accuracy, making the systems an in- dispensable part of the production of modern biopharma- ceutical products. Final Fill and Finish of pharmaceutical products 5

HOF – technology Technological precision for maximum ﬂexibility The HOF Freeze-Thaw Units are speciﬁcally designed for the controlled rate freezing and thawing of biopharmaceu- tical products and enable temperature control from +40 °C to -90 °C. The machines are designed for the highest de- gree of ﬂexibility and are compatible with all common sing- le-use bag systems on the market. Depending on the machine conﬁguration selected, up to 300 liters of product can be processed per batch. The innovative design of the HOF FTU guarantees that the entire product volume is treated evenly, regardless of bag size, resulting in consistent freezing and thawing results. HOF Freeze-Thaw Unit Pharma with suitable packaging material Loading process of the HOF FTU Pharma with bag systems HOF Freeze-Thaw Unit Pharma with © Sartorius AG FFTp Bags Reliable control and comprehensive quality assurance HOF‘s Freeze-Thaw Units ensure reliable control of all pro- cess parameters, which is essential to maintain the integrity and quality of pharmaceutical and biotechnological pro- ducts. The systems offer adjustable freezing and thawing rates that can be customized to the speciﬁc requirements of each product. This ﬂexibility allows for both process ty- pes, freezing and thawing with maximum speed or control- led process to be carried out in several stages at different temperature rates to ensure uniform and controlled heat 6 transfer. The HOF Freeze-Thaw systems therefore meet all the requirements of professional users in the industry. Whether for sensitive biotechnological products or stan- dardized pharmaceutical applications, HOF equipment provides the necessary process control to achieve optimal results and maintain the highest quality standards.

Individual adaptions for for speciﬁc production requirements HOF – technology The HOF Freeze-Thaw Units are characterized by their ﬂe- xibility, allowing them to process different bag and shell combinations. This versatility helps customers efﬁciently handle multiple products in the same machine, processing up to 300 liters of product per batch. The compact design of the FTUs optimizes space requirements and integrates all process-relevant and electrical components within the machine housing. In addition, the units offer alternative conﬁguration options to meet speciﬁc installation requirements, including inte- gration into clean rooms up to class C and the option of a split installation, where the machinery skid is positioned in a separate technical area. HOF FTU Pharma with ©Entegris Life Science Aramus Bags and plate freezer shell FFTp Bags ©Sartorius AG Celsius Pak ©Sartorius AG Sterile room integration of the HOF FTUs Aramus Bag with Plate Freezer Shell ©Entegris Life Science Inc. Aramus Bags ©Entegris Life Science Inc. RoSS Shell ©SingleUse Support GmbH Splitted machinery design of the HOF FTUs Exemplary Freezing-Thawing Cycle within a HOF Freeze-Thaw Unit 7

HOF – technology HOF Freeze-Viewer Professional – Customization in interfaces Advanced process control and GMP-Compliant audit trails The HOF Freeze-Thaw Units are equipped with the HOF Freeze-Viewer Professional (FVP), an advanced visualiza- tion system that provides comprehensive process control, program management and audit trails in accordance with strict GMP requirements. The system also complies with FDA guidelines according to 21 CFR Part 11, ensuring the highest standards in pharmaceutical production. Seamless integration into customer networks The software specially developed by HOF enables seamless integration of the FTUs into existing customer networks. Thanks to Active Directory support, the customer‘s exi- sting and global user administration can easily be used for system login. In addition, the Freeze-Viewer Professional offers the ability to automatically store batch reports and backups either locally or on network drives, providing ad- ditional security and traceability. Integrated HMI for simpliﬁed operator handling Integration with supervisory systems for maximum control The FTU‘s programmable logic controller (PLC) can also be connected to a higher-level system to receive all rele- vant process data and alarms in real time. Equipped with a Manufacturing Execution System (MES), the higher-level system can take full control of starting and stopping pro- grams on the line. Flexible and simple recipe management Easy calibration with IO-Link technology The recipe management within the Freeze-Viewer Profes- sional allows programs to be created for a variety of pro- ducts. These programs can be conﬁgured quickly and ea- sily, whether fast temperature changes, slow temperature ramps or long holding times are required. Another highlight is the usage of IO-Link sensors and actu- ators, which facilitates the replacement of components as well as the calibration of the machine. As communication with the sensors is digital, probes can easily be unplugged for calibration or even sent to HOF to perform calibration without compromising operational efﬁciency. HOF Freeze-Viewer Professional Overview 8

HOF – technology Innovative refrigeration technology for sustainable production HOF relies on advanced refrigeration systems that use both synthetic and natural refrigerants to meet the latest env- ironmental guidelines. These systems provide efﬁcient, reliable and environmen- tally friendly solutions for ultra-low temperature processing while ensuring the required precision and safety. For precise temperature control during the freezing and thawing process, HOF uses an advanced heat transfer medium that is pumped through the shelves of the Free- ze-Thaw Units. This medium is cooled by an integrated and reliable refrigeration system that uses either synthetic refrigerants or environmentally friendly, natural solutions, depending on the design standard. Schematic overview on the HOF refrigeration and heat transfer system Synthetic refrigeration skid for HOF FTU Sustainability as a key component FTU CAR6 (hydrocarbons): Nowadays, sustainability is a key factor in the development of process machines for the ultra-low temperature range. The European Union‘s F-Gases Regulation and other cli- mate protection directives have severely restricted the usa- ge of synthetic refrigerants, and their use will be further regulated in the coming years. To meet these challenges, HOF offers a variety of alternative, natural refrigerant so- lutions that both protect the environment and ensure the long-term reliability of the systems. The two-stage CAR6 cascade system uses natural hydrocarbons such as ethane and propene to achieve low temperatures efﬁ- ciently and safely. These environ- mentally friendly refrigerants offer high efﬁciency with maximum ﬂexibility and make the system fu- ture-proof. Refrigerant options of HOF FTUs FTU Air-Line (air as refrigerant): FTU LN2 (liquid nitrogen): This technology provides instant cooling performance by using -196 °C cold liquid nitrogen sup- plied directly from external tanks. This solution is future-proof, as it is not affected by legal regulati- ons, and impresses with low main- tenance costs and high tempera- ture ﬂexibility. The HOF FTU Air-Line is the next generation of Freeze-Thaw Units with a completely natural refrige- ration system while keeping the compact machinery design. This solution uses air as refrige- rant and offers an environmental friendly alternative with a global warming potential (GWP) of 0. The compact design as well as the performance of the machine enable an easy inte- gration into existing process and represent a sustainable development of previous FTUs. 9

HOF – technology HOF Pharma Blast Freezer - The versatile solution for comprehensive applications Versatile processing of pharmaceutical and biotechnological products HOF Pharma Blast Freezer with suitable packaging material The HOF Pharma Blast Freezer offers a ﬂexible and efﬁcient solution for processing pharmaceutical and biotechnologi- cal products. This system is distinguished by its ability to efﬁciently process products in both bag and bottle systems. This allows products in all common packaging materials to be frozen safely and accurately, making it a valuable additi- on to production lines with varying requirements. Flexible temperature range for tailored applications With a ﬂexible adjustable temperature range from +40 °C to -110 °C, the Pharma Blast Freezer offers customers the opportunity to adapt it to the speciﬁc requirements of their products. This means that different products with different requirements can be frozen in a targeted and precise man- ner, ensuring a high degree of ﬂexibility in production. Hygienic design and easy installation in any environment The interior of the system is made entirely of stainless steel, which not only makes it easy to clean, but also meets the high hygienic requirements in pharmaceutical and biotech- nological environments. Thanks to its compact design, the Pharma Blast Freezer can be easily installed in non-classi- ﬁed rooms as well as in sterile areas. The control panel mounted directly on the system ensures simple and intui- tive handling by the operator. HOF Pharma Blast Freezer with product HOF Pharma Blast Freezer (technical area) 1010 FFT Bags ©Sartorius AG Aramus Bag in Blast Freezer Shell ©Entegris Life Science Inc. Nalgene Bottle ©ThermoFisher Schientiﬁc Future-Proof and eco-friendly cooling system To meet current legal and regulatory requirements while offering a future-proof design, the system uses an inno- vative Mirai Intex chiller with only air as refrigerant. This environmentally friendly refrigerant meets all the require- ments of the F-Gases Regulation and requires no additional safety measures as only air is used. The advanced technolo- gy makes it possible to achieve a wide temperature range with high cooling capacity, while the compact design of the system enables easy installation and integration into existing processes.

Service is part of it - HOF Service+ HOF‘s Freeze-Thaw Units (FTUs) are always state of the art and meet the highest safety standards. In addition to pro- duction, HOF offers comprehensive project support, which accompanies the entire project - from system planning and production through to commissioning - by a specialized project team on site. HOF also assists its customers with the transportation and installation of the systems and of- fers comprehensive training as well as annual service and maintenance units. HOF – service Our service for you - as individual as our solutions At HOF, only our own employees look after your system, even long after these systems have left our factory. The- se employees take care of the transportation, installation, commissioning and qualiﬁcation of the systems. This all- round service minimizes interfaces and effectively avoids potential problems. HOF offers a comprehensive service that covers the entire life cycle of your system. Our 24-hour emergency service and our own spare parts warehouse with over 65,000 available items help to keep downtimes to a minimum and ensure the smooth operation of your systems. Advantages at a glance Maximum process reliability: Precise control of freezing and thawing processes to ensure Ease of use: Easy integration into existing networks and cleanrooms up product quality and integrity. This includes ﬂexible adaption to class C, as well as intuitive operation through advanced to different product requirements and the use of advanced software solutions such as the HOF Freeze-Viewer Profes- software solutions for process control. sional. This enables seamless integration and simpliﬁes the operation and maintenance of the systems. Flexibility: Processing of all common single-use bag systems as well as bottle systems, with adaptability to different product Compact design: Space-saving installation and ﬂexible arrangement options requirements. This includes ﬂexible production in different that allow easy adaption to different production environ- machine sizes and conﬁgurations to meet speciﬁc customer ments. The compact design supports installation in non-clas- needs. siﬁed rooms as well as into sterile conditions. Sustainability: Use of natural refrigerants and environmentally friendly Innovative technology: State-of-the-art refrigeration technology and digital process technologies that are future-proof and legally compliant. control ensure maximum efﬁciency and reliability. The HOF HOF offers a variety of alternative refrigeration systems to systems combine innovative cooling technologies with preci- protect the environment and ensure long-term reliability. se digital control to ensure optimum production conditions. 11