Can you talk about the items on the list in relation to PharmaCyte’s progress and what further rate limiting steps are on the path to filing the IND?
Sarah DeMare: “Documentation of work done on items (a), (b) and (c) and a significant amount of material concerning item (d) have been accumulated to date. As for item (f), publications of Phase 1/2 and Phase 2 trials that were published in scientific journals are “in-house,” as are original clinical reports of those clinical trials. The clinical trial protocol is nearing the “final” stage. Items (h), (i) and (j) will be written by Translational Drug Development (TD2), the Contract Research Organization (CRO) PharmaCyte has retained to conduct the clinical trial in the U.S. and oversee its conduct in Europe by Clinical Network Services (CNS).”
“The rate limiting step to being able to file the IND and, ultimately, begin the clinical trial is the manufacture of the combination drug product. For live cell-based products, a Master Cell Bank or ‘MCB’ first needs to be manufactured, characterized, tested and released. The speed at which the MCB can be produced is dependent on several different things. First, is the availability of starting materials. Some starting materials can have a significant lead-time when ordering, and you cannot begin manufacture until you have all your starting materials. Second, is the growth rate of the live cells. Cells grow at different rates. There isn’t much that can be done to speed up that process. Unfortunately, it is not a 1 to 2-day event. “
“Also, when working with a Contract Manufacturer Organization (CMO) to make your cell bank, some things are out of your control. For example, scheduling. CMOs typically schedule their manufacturing rooms out months in advance for their clients, so sometimes you need to wait in the queue for your turn. In addition, and perhaps most importantly, the MCB needs to be tested to ensure its quality, which is of utmost importance. These tests are also not tests that can always be done quickly. Sterility is a good example. This test is mandatory to ensure the sterility of your MCB and takes approximately 6 weeks to obtain results.”
“The purpose of creating a MCB is to provide a repository of live cells that are essentially identical to the material tested in clinical trials and throughout the development process. After creating a MCB, a Working Cell Bank or ‘WCB’ must be manufactured. Creation of a WCB is an important step, as it allows your Master Cell Bank to have a longer useful life.”
“This is an important point, and it’s worth illustrating. Let’s say you can make 300 vials in your MCB. Let’s also say that each vial of cells can produce enough drug product to treat 100 patients. That would mean you could potentially treat 30,000 patients with the entire MCB. Sounds like a lot, right? Maybe, but this MCB will need to provide cells to patients for years to come. At some point in the future, the MCB will be depleted. This would require another MCB to be produced, and in such a complex system there would be no guarantee that the original cells could be duplicated exactly. In the best case, this means extensive testing would be needed to prove that the new MCB is equivalent to the old MCB.”
“If those tests reveal differences that could affect efficacy, a new clinical study may be needed to demonstrate that the new MCB is equivalent to the old MCB. There is always the potential that it will not be equivalent. That is the situation the FDA would like to avoid, which is why a Working Cell Bank is needed. To make a WCB, you take one vial of your Master Cell Bank and grow it into more vials to become your Working Cell Bank. So, theoretically, you could get 200 vials of your Working Cell Bank from 1 vial of your Master Cell Bank. Assuming one vial of your WCB still treats 100 patients, you could treat 20,000 patients from only 1 vial of Master Cell Bank. Using this example, a 200-vial Master Cell Bank could treat up to 4 million patients. Compare that to the 30,000 patients you could treat with the entire Master Cell Bank, and you can see that having a WCB allows your MCB to go much further and last much longer.”
“Producing a Working Cell Bank is similar to the Master Cell Bank in that it takes time for the live cells to grow, and you need to test and release the live cells. Sterility testing is still required, and it still takes 6 weeks to perform.”
“Finally, with the Working Cell Bank ready, the drug product can be manufactured, tested and released. The FDA will want to see the test results that demonstrate the quality of the drug product in the IND. So, the IND cannot be filed until the testing of the drug product is completed.”
