High Containment for Lyophilization Processes
The growth of lyophilization and its complicated processes has challenged manufacturers to maintain safety for operators working with highly potent ingredients, which has created a demand to assure product quality and protection from contamination.
Ranging from small lyophilization systems used for R&D to larger production systems, the ability to handle vials and trays is often an effort to minimize ergonomic stress as well as mitigating the risks associated with exposure and potential product loss. Traditional solutions using RABS and hard wall isolators are costly and require multiple operators to work together moving trays often in very awkward positions and using unnatural motions.
All of these problems can be addressed with single use containment, which also makes it easy to retrofit isolation to existing equipment. A recent webinar by ILC Dover presented actual solutions that have been used for lyophilization containment as well as other processes to show the great depth of adaptability, safety, and performance associated with single use systems. Typical project costs of single use solutions are estimated and compared to the more costly traditional systems to show viewers the complete value proposition of using ILC Dover’s flexible systems.
Applying Single Use Systems for Cost and Ergonomic Benefits
Over the last 20 years, we have seen a surge of “increasingly potent” products that require a higher need for containment systems that are relatively low-cost and adaptable to previously installed equipment like lyophilizers. That’s where ILC Dover’s options for single use isolation technology and flexible containment systems shine.
Single use or flexible isolation technology has already been proven throughout the pharmaceutical and biopharma industries and can be easily applied to lyophilization. Because of its high costs and less-adaptable features, many companies have hesitated to purchase traditional isolation technology and continue to use PPE solutions. The PPE solutions should really be considered as a “last resort” in the safety hierarchy of containment processes. Having the ability to use single use isolation as the engineering control brings the process in line with the latest technology and best-in-class manufacturing.
As in most processes, there is not a single design to fit all lyophilization operations. From the small R&D lyophilization systems to mid-size units for clinical supply requirements, and even large commercial production systems, the attached isolators must be able to accommodate a range of needs. In addition to the loading and unloading activities with multiple trays of fragile vials, the system must consider upset events like broken vials. No matter what size of lyophilizer the production teams are operating, the reality is that vials can tip over and stoppers can be misplaced. Anyone working with lyophilizers will surely know these issues significantly increase the risk of exposure and require a hefty clean-up process. The safety features included with single use isolation assure full containment even in an upset condition.
Using Isolators to Protect Product, Operators, and Environment
In a perfect world, containment is not needed for freeze drying product, but this is hardly the case when lyophilizing highly potent powders in bulk quantities. As mentioned and especially with highly potent materials, any upset conditions during the lyophilization process such as the broken vials or the mishandling of product during the transfer process can pose significantly major risks of product cross-contamination, the operator’s health, and the environment in general. Isolation technology, whether being fixed or single use systems, mainly protects the product from cross contamination before freeze drying, as well as protects the operators and environment after freeze drying from any airborne HPAPI particles. Even though isolation technology is a must when dealing with highly potent products, there are many challenges to providing sufficient containment when working with a lyophilizer.
Some of the biggest challenges for teams when considering high containment solutions include:
- Adapting the system to the lyophilizer without requiring re-qualification/re-validation.
- Easily managing the opening and closing of lyophilizer door during operation.
- Ergonomically accessing all rows of trays and securely handling the product.
- Providing efficient and effective transfer points for products in the containment zone.
- Arranging of high containment systems for different sizes of lyophilizers.
Lyophilizer Solution Examples and Containment Designs
Let’s take a look at some of ILC Dover’s examples of flexible high containment solutions and how these isolation systems are designed for lyophilizers and their surrounding areas.
When looking at containment design for single use flexible systems during lyophilization the key features are overall safety and ergonomic capabilities during operation. Protection in these isolators during the lyophilization process mainly come from pressure controls, such as a positive pressure control during the loading stage and negative pressure in the un-loading stage. Another key feature is designing a containment system that is ergonomically friendly for the operator during long periods of operation. When looking at a fixed or hard wall isolation system, there are known to be many ergonomic issues and maintenance costs associated with their operation. Not all operators are the same size, and these poor ergonomic conditions cause process errors and costly injuries in the long term.
On the other hand, single use isolators provide multiple advantages when dealing with ergonomics such as a flexible wall at the glove interface to ease motions, and the isolator will move with the operator supplied by bungee cord restraints. For an example with flexile single use systems, the way the operators are positioned at 90-degrees to the lyophilizer promotes the highest level of ergonomics for managing trays full of potent products. Another fact is that they are actually single use with no large clean up afterwards, and process changes after install are easy to incorporate, making it a much more adaptable system for operators than hard wall isolation systems. The single use flexible wall system’s ability to change as needed and a high level of ergonomics is at a premium compared to other systems. ILC Dover has multiple flexible containment systems for use with different types and sizes of lyophilization processes. From small-scale R&D lyophilizers requiring adaptable isolation systems to large-scale cGMP operations requiring isolation coupled with a Grade A or B environment, there are cost-effective solutions for everyone. Watch the full webinar for examples, pictures, and discussion.
When thinking about the transfer technology associated with single use systems, ILC Dover has solutions to address all transfer needs, such as flexible pass box systems, rapid transfer ports (RTP) for efficiently transferring materials in/out of the flexible isolator, bag in/bag out (BIBO) systems allowing for multiple transfers of large materials, split butterfly valves for aseptic transfer of small amounts of materials, and even a BETA bag system for transferring large amounts of materials in an aseptic environment if needed.
Reduced Cleaning Validation and Cost Savings
Many teams initially think that single use isolation system would cost much more than traditional systems, but they are actually much less costly than fixed systems, as well as being more efficient and effective as a containment solution in the long term. The benefits of single use systems include:
- Reduced cleaning time/costs vs. reusable systems
- Single use meaning no cleaning required
- Cleaning SOPs and validation not required
- Integrity testing done at factory for flexible systems
- Easily moveable if needed
- No maintenance on seals/gaskets vs. hard wall systems
- 70-80% less costly than hard wall systems
- Ergonomically adaptable to all operators’ body sizes
- No cross contamination from previous production
Does your team have a need for single use flexible isolation technology in your facility? To see multiple examples of ILC Dover’s installations for any level of environment and process, watch the full webinar