Isolators for Cell Therapy FAQs
What are the 10 most frequently asked questions when we present our solutions?
We have collected questions received during presentations, conferences and client meetings. They concern our ATMP systems used for cell therapy and regenerative medicine in R&D departments and cell factories. Read the questions and answers below.
1. Why does Comecer believe that isolators are a superior approach to traditional clean rooms?
2. What are three factors where an isolator approach represents an advantage?
First, isolators can be installed in grade D space, sometimes in grades C depending on local regulations. Anyway, this is not grade B and we know there is a big difference in classified space and air exchange requirements between B and D/C, as it differs by a factor of 100 times in air changes/hour. Therefore, we can say there is a drastic reduction of air treatment compared to a highly classified area.
Second, it is extremely easier to clean an isolator. You can easily wipe the stainless-steel surfaces, for a line cleaning, and then decontaminate them through a hydrogen peroxide cycle, for a full cleaning. Just imagine what you have to do to clean an open environment, where people should de-gown and go out, new people with clean dressing should come in and clean everything by hand.
Third, the reduced classified space forces you to an efficient use of resources.
This has a positive impact on the global cleanliness of the space and reduces the transportation of cells in and out from the BSC to the incubator or centrifuge and vice versa.
3. What are the advantages of having integrated accessories inside the isolator?
Pollution generated by the accessories, especially by their rotating parts, is not located inside your working environment; it is outside in the technical area. The same goes for the heat generated by the devices, as it goes directly outside. In addition, having integrated accessories means they are close to your working space, they are quick to reach, and they allow you not to lose time moving cells from/to another side of the room: you have everything close to where you need it. Finally, the integrated devices usually provide centralised control and a centralised alarming system. This means that you look at a single interface on a single monitor for the majority of the integrated devices, and you do not need to go from time to time to check every single device, how it is working and whether or not it is in error.
4. How does Comecer address the manipulation through gloves, as some are worried about a lack of sensitivity?
In our experience, gloves never represent a dramatic issue. We know customers could be used to thinner gloves and more hand-fitting gloves. We found that this is mainly a question of training. Therefore, we know there is a learning curve on how to approach the use of isolator gloves in daily practice, in the daily routine of running CGT related procedures. However, what really makes a difference, the time you need to take confidence with a new way or a different way to manipulate things? We have seen that even fine manipulations, like picking and screwing the cap of a cryovial, do not significantly affect the time you need to perform a certain operation.
5. Why is it important is to have a configurable back wall in the isolator?
While CGT processes are similar and do not differ dramatically from each other, we recognize that a certain number of accessories is always necessary. We prefer to leave to customers the possibility to choose which position of the accessories fits better with their habits, circumstances, quantities of materials to be kept inside, or just accessory devices we have to consider for running the process (e.g., in and out ports, plug-in devices, peristaltic pumps et cetera).
6. How does Comecer solve the issue related to material and consumables handling within an Isolator?
The application of Isolators is not new in the pharmaceutical industry. For more than thirty years, isolators have been widely applied and see a fast-growing curve all over the world. There are currently several systems on the market that are perfectly suitable to transfer material safely IN/OUT of the isolator, both from the point of view of asepsis as well as containment. Safe connections for liquid transfer are suitable for introducing sterile liquids from the external non-aseptic area to the internal Class A area of the isolator. RTPs (Rapid Transfer Ports) are widely used to transfer solid material and consumables, like settle plates of other sterilized parts from the outside to the inside of an isolator.
Waste management is also simpler when using an isolator since it is possible to have disposable bags or waste containers for different kinds of waste. Typically, a transfer hatch, sterilizable independently from the main chamber, is also suitable for a continuous process, for entrance/exit of materials, products and consumables that are sterilizable with Hydrogen Peroxide Vapour (VHP).
7. How long is the sterilization cycle with VHP?
The total cycle time depends on several factors. It is mainly influenced by the complexity of the geometry of the isolator and by the load (the material) that is contained inside the isolator before the cycle starts. Comecer manufactures its own VHP generator, and we can assist our clients in Cycle Development, to obtain a 6LOG reduction in the worst conditions (maximum load). Furthermore, the cycle will be optimized to achieve the shortest possible time. In general, and based on our experience, most of the sterilization cycles can be completed within 2 hours. The transfer chamber, as well the different sections of the isolator can also be sterilised independently, with a significantly shorter cycle time.
8. Does the VHP Cycle need to be validated at any time?
The PQ of the sterilization cycle with VHP will be validated using chemical and biological indicators (BI & CI) which will demonstrate the lethality of the sterilization process with the given conditions. Once the cycle is validated there is no need to validate it again. The sterilization cycle runs fully automatic, and no supervision is necessary; it can be run during the night shift. If no other variables are introduced, e.g., a different material load, the VHP cycle is a standard automated process that can be repeated without failure.
9. How does the application of Isolators affect the space constraints in my facility?
The application of Isolators will minimize your floor space requirement and will optimize your capital investment. Since the Isolator is positioned in Class D (or C), there is less requirement for a changing room. Only one changing room for the personnel is necessary. Moreover, the path of material flow is simpler, when compared to a standard clean room. The classified area is reduced and is related to the isolator process area only, thus granting better efficiency. When comparing the same process in a clean room vs. within Isolators, 20% to 30% space savings become evident.
In other words, achieving the same production amount with a smaller space, fewer consumables, and lower running costs, will improve your investment efficiency.
10. How can we deal with some living materials that cannot undergo VPHP decontamination, as this will risk killing the product and not only the contaminants?
In this case, we can adopt a different decontamination strategy to address the concerns highlighted in the question.
We know that the current GMP regulations include a classification of the environments based on the count of viable and not-viable contaminants present in the area.
Basically, the VPHP decontamination is in charge of removing the viable contaminants, while the laminar flow inside the chambers is in charge of removing the particles. In the traditional approach, both goals are reached using the prechamber, where VPHP and laminar flow act together.
To replicate the same process without H2O2, we need a succession of decontamination steps similar to those we use to transfer materials in a cleanroom. This means that using a combination of biocides, laminar flows and pressure cascades, we move the objects in successive chambers with increasing classification (D → C, C → B, B → A) thereby obtaining the requested grade of cleanliness.
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