When introducing a regenerative medicine cell based product to a commercial setting, there are a number of things to take into consideration to ensure a commercially viable and safe product for patient use.
In this QandA interview by Pharma IQ,
William Fodor, Director of Translational Sciences,
Cell Therapy Group, gives a few insights into the commercial manufacturing scale‐up process of cell therapies.
Listen to the podcast here (registration required) or read the transcript below:
Pharma IQ: Can you give some advice on the best way for a company to develop standards for commercialization to improve safety?
W Fodor: As with any biological product, you have to do all the appropriate testing and there’s really no standards necessarily to be developed by the company because the regulatory process is pretty well outlined by the FDA and CBER. Cell therapy products are regulated by the office of Cell Tissue and Gene Therapy Division. So, it’s not that you need to develop standards for commercialization you just need to follow the regulations by demonstrating to the FDA that your product is safe, and maintains the identity, in other words, your product doesn’t change during your regular manufacturing process. Purity and potency are all assays that need to be developed within the manufacturing process for your particular cellular product.
Pharma IQ: And what are some approval processes and pitfalls to be aware of within the scale-up process?
W Fodor: As you are scaling up your process to meet clinical trial requirements and eventually commercialization, you absolutely need to maintain current good manufacturing practices, cGMP. Typically, during a phase one, you can get away with certain reagents that may not be fully GMPs. Or in other words, if you use a growth factor or a certain media that doesn’t have or isn’t manufactured under full GMPs, as long as you test that particular reagent or media that you are using to ensure safety and sterility, you can typically get away with that in the phase one clinical trial process. But when you move to a phase two, you need to make sure that all your reagents and medias and any compounds that come in contact with your product are all manufactured under cGMP.
Pharma IQ: What are some technology transfer and patent protection concerns to be cognizant of?
W Fodor: With any cellular-based product, if there’s a technology that is out there that a company wishes to pursue, to improve yield, or the manufacturing process, you need to demonstrate that that technology fits within your manufacturing process. So typically, what is done is you’ll do validation runs to ensure that that new technology satisfies the regulatory process for your manufactured product.
With respect to patent protection, again, that company needs to maintain their IP portfolio and needs to make sure that they’re not infringing other intellectual property and that’s just standard for the industry.
Pharma IQ: And do you have any tips for ensuring quality and consistency no matter how little or how much one is producing?
W Fodor: Yes, when you manufacture a cell-based product, it’s not that much different than any other biologic product. And so, during your manufacturing runs, whatever scale it is, you have to ensure safety, such as sterility tests for microplasma, or other adventitious agents; as well as bioburden and endotoxin. These are all tests that need to be performed.
You need to have an identity test to make sure that your cell product, at whatever scale you are manufacturing, that at the end of that manufacturing run, the product hasn’t changed. Again, no matter what scale you’re at, you need to make sure the identity of the product is consistent from batch to batch.
For identity, you can do a number of things for a cell-based product, if you want to look at cell surface antigens to ensure that the cell surface proteins on your cellular product don’t change over time or through your manufacturing process. And typically, what you like to do is keep it relatively simple. You don’t want to test for a hundred things because you’re just asking for the potential for something within those hundred tings to change. So typically, what you do is maybe three to four cell surface antigens to ensure your product identity is consistent. You can also run PCR tests to determine that an intracellular protein of interest doesn’t change during your manufacturing process.
You also need to ensure for purity, so you want to quantify the purity of your active cell type or your tissue type. And then potency; you need to demonstrate the product has a consistent potency and the biological activity of that final product doesn’t change during the manufacturing process.
And then typically, what you do is you archive. You archive samples from your manufacturing process. You cryopreserve those so you can always go back to ensure that that a particular batch was consistent with other batches that were manufactured.
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