Why Perform Batch Control of the Freeze Drying Process?
Almost half of all biological products produced within the pharmaceutical industry are freeze dried using vials as containers. An incredible scope that ensures millions of life-saving and quality-of-life drugs across the globe – making it immensely crucial to get the freeze drying process right.
To ensure these drugs are safe for consumption, it is advised to perform batch control and monitoring of samples during the freeze drying process. Monitoring and controlling the process through batch control by measuring the product temperature has two crucial purposes:
Saving the batch if something unexpected happens – thereby ensuring the integrity of extremely expensive products
Defining the end of the primary drying and optimizing the drying speed without jeopardizing the product
Measuring the product temperature therefore provides important information about the status of the product during the freeze drying process:
Pre-freezing: Stabilizes the structure of the sample through freezing. The freezing speed is controlled to form the appropriate ice structure and crystals for sublimation.
Primary Drying: Through establishing a vacuum, ice will be converted directly into vapor without melting. This is also known as sublimation. This part of the process requires energy to be added to the product in order to compensate for the energy used by the sublimation process itself.
Secondary Drying: As not all of the water within the product is frozen initially (intercellular water, bound water) and removed by sublimation, the secondary drying phase, also known as desorption, will remove this excess water.
How Costly is the Loss of a Freeze Drying Batch?
Not only are the drugs that undergo freeze drying highly crucial for consumers, but the costs and impact of not properly monitoring and controlling the process correctly can be detrimental.
Some freeze drying systems can operate with more than 100,000 vials at a time – all containing expensive and important biopharmaceutical drugs. A single batch can easily reach a worth of several million Euro or US Dollars – often greater than the cost of the freeze dryer itself.
To reduce the risk of batch loss, accurately monitoring and controlling the process from start to finish ought to be in focus. There are two critical variables that affect the heat transfer, process efficiency and product quality, namely: chamber pressure and product temperature.
By monitoring and controlling these parameters, the process can be optimized and adjusted to ensure a high quality batch. In this paper, we will be focusing on how to use product temperature to perform batch control.
Monitoring the status of the product during the freeze drying process is also highly useful for:
Scaling up a process
Performing laboratory level validation cycles from a pilot to industrial plan
Performing successful freeze drying cycles that avoid shrinkage, collapse, eutetic melt, excessive moisture levels in the final product, extended reconstitution time or ultimately loss of activity in the Active Pharmaceutical Ingredients (API)
What are the Temperature Measurements for?
Temperature sensors are used to collect information about the product temperature as a function of the chamber pressure and shelf temperature – serving as an indirect method of determining when sublimation is complete. Additionally, live temperature measurements allow operators to act and adjust the temperature or vacuum on the fly to avoid the loss of batch.
With products as important as life-saving and quality of life drugs, there is little room for error. The loss of batch is not an option, and the quality and safety of the drugs can never be compromised. Which is why Ellab developed TrackSense® LyoPro to solve all the usual headaches associated with batch control, while also providing industry-leading accuracy and secure data collection.
LyoPro – Qualification, Validation, Monitoring and Batch Control all in one
The TrackSense LyoPro wireless data logger is as versatile as high-end measuring equipment comes. LyoPro comes equipped with an ultra-thin replaceable thermocouple sensor that can be placed in the vials for the product temperature – or stuck on the shelves or put in contact pucks to measure shelf temperature.
These thin sensors have next to no impact on the product temperature and therefore provide highly accurate measurements – unlike thicker stainless-steel sensors or transmitters that have an increased impact on the sample and therefore less reliable readings.
Uniquely Designed for Freeze Drying
Having been designed specifically for the freeze drying process, LyoPro comes with a wide range of features that makes using it within the crucial process a whole lot easier:
LyoPro comes equipped with special stoppers that keep the sensor fixed at the desired measuring point throughout the entire process. These stoppers also make future measurements easily repeatable and keeps the thermocouples from being damaged during stoppering
The ultra-thin replaceable thermocouple has next to no impact on sampling
An optional buffer vial can be placed between the sample vial and LyoPro to eliminate any potential heat conduction from the logger
LyoPro transmits real time data throughout the entire process, but also stores all samples on its large internal battery operated memory.
Over 100 LyoPro data loggers can be used simultaneously for a single study – eliminating data gaps
Just to name a few…