Ann: Mesoblast Type A Meeting with FDA, page-362

Assays are highly complex. You have to measure the response in the test tube of what the T Cells in the immune system produce when the stem cells are present. Then you have to establish a mechanism of action to show that this will fight the GvHD immune response. Then you have to prove that it is delivered in the right dosage into where it is needed in the body and that you can measure the same response in the body. Different people can have different responses and different donors cells can produce different responses. They are also living cells which have to be handled carefully. Most clinics produce dead cells and rubbish, and FDA is trying to stamp them out.There are several academic papers written on the problems of biologic potency assays and the FDA has also recently issued guidance. Wahoo won't let me reference them.Just one of the FDA's points is:Sponsors developing drugs for GVHD should bear in mind that most transplant patients are on numerous concomitant medications, including antifungals and immunosuppressants. Many of these drugs are substrates, inducers, or inhibitors of cytochrome P450 (CYP) enzymes, other metabolizing enzymes, or transporters; these will affect the way other drugs are metabolized. Before any clinical trials, in vitro studies must explore all of these potential metabolic irregularities, as well as how the drugs are excreted in patients who may have impaired kidney function.

This is a good read on what the Blaster is striving to give the FDA.

Aloha.