LYOVAC® Pharma Freeze Dryer

LYOVAC^®freeze dryers can be arranged on one or multiple floors, such that the condenser is typically situated under the drying chamber and ensures both easy access to the machine parts and complete separation between the cleanroom and the technical area.

In a single-floor setup, the orientation of the condenser can be on the side or behind the drying chamber. No matter what the size or the arrangement, the unique shelf design ensures high drying rates and uniform results. In addition, all LYOVAC^®freeze dryers can be integrated with our Automatic Loading and Unloading System (ALUS^®). 

LYOVAC^® is also available using GEA’s unique Fast Track manufacturing process. Depending on the complexity of the installation and based on previously completed projects, it is possible to have a system up and running in less than a year.

Invented by GEA in 1980s, ALUS^®minimize the risk of operator/product contamination while loading and unloading a freeze dryer, offering shorter processing times, improved productivity and reduced operational costs. We were also the first company to provide an isolated ALUS in the 1990s.

Given the absolute requirements to minimize contamination, eliminate operator exposure and protect the product, further containment options include isolators, conventional cleanrooms or both active and passive Restricted Access Barrier Systems (RABS). 

Key features

• GMP equipment
• CIP/SIP with quick subprocess turnaround times
• Solvent processing capabilities
• Highly potent processing capabilities
• Refrigeration using either compressors, LN2, natural refrigerants, etc.
• State-of-the-art automation options with virtual servers
• LYOPLUS®
• LYOSPARK® controlled nucleation
• Fast track delivery system
• In-house ALUS® with integrated FATs possible
• In-house shelf manufacturing 

Process Optimization

A novel approach to simple, reliable and easily controlled nucleation during industrial freeze drying

The lyophilization process comprises three main stages: freezing (solidification), primary drying (ice sublimation) and secondary drying (moisture desorption). The nucleation of ice crystals (the initial stage of ice formation during freezing) is a naturally spontaneous and protracted process. As such, forcing ice crystals to nucleate at a specific temperature, rate and time can improve the homogeneity of the batch and reduce the cycle duration.

Historically, because of the random nature of the nucleation process, lyophilization has been difficult to control. For a typical pharmaceutical formulation filled in vials, for example, crystals might form at temperatures ranging from –5 to –20 °C). 

As the nucleation temperature has a direct impact on the developing ice structure and crystal size — as well as the appearance of the dried product cake — it can negatively influence the product’s Critical Quality Attributes (CQAs), such as residual moisture or dissolution behavior. 

A patented and proven technology from GEA, which is fully compatible with all our currently available freeze dryers, provides a novel and scalable method to control the nucleation process without having to develop new pharmaceutical formulations. 

Simultaneous Crystal Nucleation

LYOSPARK® enables the user to control the temperature at which nucleation crystals form inside the product, thereby ensuring that, at any time, every vial in the chamber is subjected to the same process conditions, irrespective of its specific location on the shelf. 

Combining LYOSPARK® technology with conventional freeze-drying processes is very simple. The vials are loaded into the freeze dryer as usual and cooled to the optimal (product dependent) nucleation/cooling temperature. As soon as the nucleation temperature is reached, the chamber is vented with gas from the freeze dryer’s condenser. 

A filter-equipped cooling trap is mounted on the chamber. Ice crystals form on the cooled surface of the trap and are entrained in the gas stream during venting. Inside the supercooled product solution, the ice crystals undergo immediate and homogenous nucleation in each vial. 

As the formation of ice crystals at higher temperatures results in larger pores, drying times can be shortened. Furthermore, LYOSPARK® offers better scalability and higher throughput speeds than conventional systems, resulting in optimized performance and productivity.

Process Optimization

LYOSPARK®, which eliminates issues such as the denaturation of active ingredients or unpredictable scale-up, also provides a number of technical advantages, including improved product quality, better vial uniformity per batch and, depending on the product, a more homogenous, aesthetically pleasing cake. It’s also recommended for highly potent applications as no toxic gas is released to the environment.

In summary, LYOSPARK® controlled nucleation technology facilitates uniform ice crystal formation in production-scale freeze dryers with a minimum degree of supercooling. This is reflected in more consistent and larger ice crystal sizes with a more open product structure. As a result, faster drying and reconstitution times can be achieved. 

QbD-compliant, GEA’s LYOSPARK® delivers a more uniform, higher quality product, reduces process times and provides a cost-effective solution to controlled nucleation.