HOF lyophilization solutions and principles

HOF Sonderanlagenbau GmbH has more than three decades of experience in designing and engineering  high quality just-in-time freeze drying lyophilization equipment.

HOF specializes in lab scale, pilot scale and industrial scale lyophilization solutions, freeze-thaw units and handling systems that can be tailored to life science and pharma applications.

What is lyophilization?  

Lyophilization is the technical term for freeze drying: a preservation process based on removal of ice or other frozen solvents from a material through the process of sublimation and the removal of bound water molecules through desorption.

Freeze drying and lyophilization are synonymous terms that only vary according to application or  industry.

The essential freeze drying principle is that ‘sublimation’: changing solid (ice) directly to vapor without it becoming liquid first. This demands precise control over heat and pressure inside the lyophilization plant.

When carried out correctly, lyophilization keeps product temperature sufficiently low and stable to  preserve its essential properties. This makes it an ideal process  for preserving  heat-sensitive pharmaceutical products, based on proteins, microbes, pharmaceuticals, tissues, plasma, etc. .

As well as extending shelf-life, a successfully lyophilized  product  should be capable of simple and rapid reconstitution with essential potency and other properties preserved intact.

The freeze drying process

The essential sublimation process involves freezing the product, then placing it in deep vacuum to move it below the ‘triple point’ where  the solid, liquid, and gas transition curves of water meet, and finally adding heat energy to cause the ice to sublime into vapor, thus drying the product .

In practice,  lyophilizing a product is considerably more complex with an industrial process that involves:

• Pretreatment: Formulating or preparing the product for lyophilization
• Loading : Preparing and handling batches of primary packaged product for the process
• Freezing: Refrigeration at atmospheric pressure
• Sublimation: the primary drying process carried out under vacuum
• Desorption: the secondary drying process carried out under vacuum
• Unloading: removal of lyophilized product from freeze dryer

In addition it may be necessary to carry out backfill and stoppering of products in containers.

This process needs to be 100% repeatable with defined temperature, pressure and time parameters for each step..

It should be noted that because of highly specialized nature of lyophilization equipment, loading/unloading also becomes a distinct process that demands specialized solutions.

HOF Freeze Drying Solutions

A lyophilizer incorporates five core component systems

• Product Chamber: the place where products are kept for lyophilization usually taking the form either of an insulated shelved cabinet or a manifold with attached flasks.
• Condenser: Accepts the vapors being sublimed off of the product and turns them back into solid ice for removal at the end of the cycle.
• Vacuum System: a separate vacuum pump connected to the airtight condenser and product chamber.
• Refrigeration System: used both to cool the ice condenser inside the freeze dryer and also to cool  the product chamber itself and powerful enough to maintain condenser temperature  substantially below that of cabinet and product.
• Control System: must include temperature and pressure control but may also allow programming of a complete lyophilization ‘recipe’ of defined and sequenced process steps with defined parameters, durations, etc., as well as real-time monitoring

Within these basic requirements, HOF can precisely tailor its freeze drying solutions to individual application and production requirements to the point that every such system is unique. These customized solutions also include cleaning and sterilization facilities to suit  different types of refrigeration and vacuum systems.

HOF also maintains a range of off-the-shelf LYOPOOL equipment in a very wide range of sizes, designs and configurations, ranging from small (approx. 1m²) to large (75m²) systems, including freeze dryers, laboratory freeze dryers  for research or product & scale up process development and freeze-thaw units. The LyoPool range keeps lyophilizer price low and availability high.

HOF Lyophilization Technologies

HOF systems incorporate advanced design and the latest technologies, such as PAT process analytical technology) sensor systems, and recipe control over shelf position, along with proprietary HOF operating system software to make process operation more user-friendly, with overview of all functions, ability to create product-specific recipes and specific load documentation.

HOF has also developed SynchroFreeze as an advanced controlled nucleation system, combining a conditioning phase in which dissolved gases are withdrawn from the liquid product under partial vacuum with supercooling of the largely degassed liquid and further pressure drop to trigger nucleation at the desired freezing point. This advanced process allows synchronized freezing for individual vials or product containers, offering conditioned product structure, improved product homogeneity, reduced drying times and more energy-efficient lyophilization.

HOF’s lyophilization offer includes 100% reliable loading/unloading systems for the safe, optimal and integrated handling of pharmaceutical products.

Resources

Click on HOF Freeze Drying Systems for further detail.
Click on HOF LYOPOOL for information on off-the-shelf products.