[Scott Patterson] 25:48 – So, going on to the transfer technology, it plays a key role in containment. It’s somewhat easy to put an isolator around the process and achieve high containment, but we do need to get the product in and out, obviously, since it’s a process. So we have to rely on different technologies to manage those transfers in and out.

The different technologies could be used for different reasons, again looking at, well, what is the next process for the materials in the transfer? When we bring the materials out of the lyophilizer, where does it go to next? What is the process? Will the transfer require containment again in transferring the product? We’ve seen applications where, because it’s in liquid form, there hasn’t been a lot of emphasis on the containment. So, is the transfer going to require containment? How large are the materials in the transfer? That can be key in determining what technology is used and how the transfer is done.

Will the transfers require aseptic control? Do we have to hold a sterile condition as we’re doing a transfer in and out of the engineered isolator? Looking at that, there are different technologies. One of the most common is the rapid transfer port (RTP). Here on the left, we’re showing a simple flexible isolator, a single-use isolator, that has the RTP, if you will.

In this case, just like on a hard wall system, the alpha flange is designed to be permanently mounted to the isolator. Then, as you see on the right, the containers that move the product in and out have the beta flange to connect to that alpha flange. So it’s multi-use, allowing for multiple transfers in and out of the isolator.

Additionally, there is the beta bag, shown in the lower right picture. The beta bag combines the technology of the rapid transfer port and the benefits of that, including the ability to do aseptic transfers, with the single-use flexible technology of the beta bag. The beta bag also has good value in terms of sizes and is a little lighter for transfers, so it offers some advantages.

Another option is pass box technology, which is extremely common on hard wall isolators, as shown on the right. You see this isolator on the right has a small box where materials are passed into it in a contained way, and then the door opens to move the product out. The same technology is shown on the left, but in the flexible single-use technology. The pass box uses zippers to pass the material in and out.

This is good technology, and a lot can be done with it. However, challenges include the size of the transfer, both dimensionally and in terms of weight. As you can see on the right-hand side, particularly, the transfer box on the isolators is relatively small and may make it difficult to move larger items that are heavy. These items might only be able to be handled with one glove while inside the isolator.

Additionally, with pass box systems, we have to be careful with multiple uses of the pass box. Each time we open it to the atmosphere, there is a risk. So, a risk analysis must be conducted to evaluate the potential exposure risks.

The next technology is the bag-in-bag-out technology, which is really the single-use technology. This is extremely effective for large sizes and doesn’t take up much space with the isolator system. On the left, you can see that it is essentially an extension of the single-use isolator. It’s a flexible sleeve that’s connected to the isolator system.

The picture in the center shows a transfer—in this case, of powder—into the sleeve. Then there’s a secure seal and separate crimping process, if you will, to separate the sleeve from the containment system. Now, this material can go into the next operation or whatever needs to be done.

The beauty of this system, compared to the pass box system, is that the sleeve, as seen on the left-hand side, has never been inside the containment area. The sleeve is completely clean and can be handled by operators on the outside, then taken and transferred wherever it needs to go. Using a secure seal and separate process like the crimping system, this can be done without the risk of exposure or having the product open to the environment at all.

Lastly, we look at the split butterfly valve technology. This is an interesting technology because it combines the idea of high containment with transfer. Some of the systems available now can also be used in an aseptic process, allowing for aseptic transfers.

In this case, we’re showing the split butterfly valve connected to a plastic bottle. One of the challenges, however, with split butterfly valves is the size of the transfer. By nature, they are butterfly valves, and as they open, the wafer—in this case, a two-wafer system—sits right in the middle of the transfer.

Instead of having, say, a 6-inch diameter split butterfly valve with a true 6-inch opening, you essentially have two half-moons split by the valve wafer sitting in the middle. It’s good technology and lends itself to certain types of transfers, but because of the size limitations and the wafer in the middle, it can be somewhat restrictive.