The Art and Science of Lyophilization
Let us share how pharmaceutical “pharma” experts use lyophilization technology to create lyophilized drugs, proteins and biologics. Learn about lyophilization (freeze drying) and how it may be the answer to advancing your drug candidate quickly to Phase I clinical trials and beyond.
SCIENCE-DRIVEN LYOPHILIZATION SERVICES
Lyophilization of drugs, proteins and biologics in vials ranging from 3mL to 50mL
Developing an effective lyophilization cycle is both art and science. Our skilled, experienced team of formulation scientists and professionals, using in-house Millrock lyophilization technology, can provide cycle development for your compound. Critical synergies between the development lab and larger GMP production scale, for CTM through commercial, ensures outcomes are met with the highest quality and with minimal timeline delays.
Lyophilization Cycle Development and Optimization: How to develop your drug, biologic or protein injectable in the appropriate container closure vial. Here are some common reasons why you should select an experienced R&D team for your lyophilization program:
- Expertise to develop and/or optimize your lyophilization cycle with consistency from lab to scale-up and GMP production
- Flexible R&D development-scale lyophilization equipment that is suitable for a range of batch sizes and available API quantities
- Customized process evaluation capabilities to augment your lyo development project, including developing early-stage, phase-appropriate analytical methods, manufacturing toxicology supplies, small-scale CTM, and supporting stability studies and testing
- Integrated software features of the Millrock technology provide process control and monitoring that enable real-time analysis and optimization to expedite getting to your clinicals faster
- Unparalleled ability to understand thermal events during the freezing and primary drying for continuous process protocol improvement and transfer
- Concept-to-clinic to commercial for small-volume products ranging from 3ml to 50ml vials
Based on the stage of your lyophilization project, our scientists will quickly and efficiently help you determine whether your lyophilization cycle is robust or requires development to proceed to clinical-stage applications. Our team can provide required phase-appropriate analytical methods and stability testing. We can formulate and scale up a product with limited API to progress your program faster into clinical stages.
Our team, led by Bryan Braxton, Ph.D, understands how to apply the integrated software of Millrock technology in the early stages to ensure future process control and monitoring, leading to faster timelines from concept-to-clinic-to-commercial production.
The 3 Stages of Lyophilization: How The Process Works
Freeze drying works by freezing a material, then reducing the pressure and adding heat to allow the frozen water in the material to change directly to a vapor (sublimate). Freeze drying occurs in three phases: freezing; primary drying (sublimation); and secondary drying (adsorption). Note that proper freeze drying can reduce drying times by 30%.1
Freezing Phase
Freezing is the most critical phase of freeze drying. Freezing can be done in a freezer, a chilled bath (shell freezer) or on a shelf in the freeze dryer. Cooling the material below its triple point ensures that sublimation, rather than melting, will occur. This preserves its physical form. Freeze drying is easiest to accomplish using large ice crystals, which can be produced by slow freezing or annealing. However, with biological materials, when crystals are too large they may break the cell walls, and that leads to less-than-ideal freeze drying results. To prevent this, the freezing is done rapidly. For materials that tend to precipitate, annealing can be used. This process involves fast freezing, then raising the product temperature to allow the crystals to grow.
Primary Drying (Sublimation) Phase
At this stage, the pressure is lowered and heat is added to the material in order for the water to sublimate. The vacuum speeds sublimation. The cold condenser provides a surface for the water vapor to adhere and solidify. The condenser also protects the vacuum pump from the water vapor. About 95% of the water in the material is removed in this phase. Primary drying can be a slow process. Too much heat can alter the structure of the material.
Secondary Drying (Adsorption) Phase
Here, ionically-bound water molecules are removed. By raising the temperature higher than in the primary drying phase, the bonds are broken between the material and the water molecules. Freeze dried materials retain a porous structure. After the freeze drying process is complete, the vacuum can be broken with an inert gas before the material is sealed. Most materials can be dried to 1-5% residual moisture.
Request a Consultation with Our Lyophilization Scientists
Effective Lyophilization Cycle
SPECIALIZED LYOPHILIZATION TECHNOLOGY
In order to provide the best possible transfer between the development-scale process and the production-scale process, Pii uses Millrock lyophilization technology in the lab and in the production unit. This allows for the synergy of technology and engineering factors critical for scale-up and transfer activities.
CAPACITY: Our development-scale lyophilizer has a chamber suitable to produce a range of different batch sizes for evaluating process parameters or producing pre-clinical and clinical supplies for various studies. The supporting services include, but aren’t limited to, the development of phase appropriate analytical methods, provision of non-pivotal toxicological materials, and evaluation of short-term and long-term stability.
ADVANCED SOFTWARE: The AccuFlux™ and AutoDry™ features for our development scale unit are powerful, innovative tools that offer process control and monitoring for both the freezing and primary drying steps, enabling analysis and process optimization. This software is an upgrade from older technologies used in the industry.
AccuFlux™ is a patented method of process monitoring and control that provides a direct measurement of heat flux. AccuFlux provides a new and valuable tool to understand the thermal events occurring during the freezing and primary drying steps. With direct and continuous measurement, AccuFlux provides a continuous stream of your critical process parameters, for use in protocol improvement and transfer.
AutoDry™ is a patented method to control primary drying based on the product temperature. Optimize your cycle early for the highest throughput in the lab and in manufacturing.
Pii has the skilled and experienced professionals, smart technology, and Pharmaceutics KnowHow TM to serve your lyophilization project from concept-to clinic-to-commercialization.
