Scale-Up and Manufacturing of Regenerative Medicine

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William Fodor

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 Q&A interview, William Fodor, Director of Translational Sciences, Cell Therapy Group, gives some great insights into the commercial manufacturing scale-up process of cell therapies.

Pharma IQ: Can you give some advice on the best way for a company to develop standards for commercialisation to improve safety?

W Fodor: Well, 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 he regulatory process is pretty well outlined by the FDA and the CBER Division and cell therapy products are regulated by the ofice of Cell Tissue and Gene Therapy Division. So, it’s not that you need to develop standards for commercialisation to improve safety. You just need to follow the regulations involved 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 then potency are all assays that need to be developed within the manufacturing process for your particular cellula product.
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Pharma IQ: And what are some approval processes and pitfalls to be aware of within the scale-up process?

W Fodor: So as you are scaling up, you absolutely need to maintain current good manufacturing practices ? it’s known as cGMPs. 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 manufctured under good cGMP.

Pharma IQ: What are some technology transfer and patent protection concerns to be cognizant of?

W Fodor: Well, 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 manufacured 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 propery 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, whenever you do manufacture, whatever scale it is, you have to ensure safety, and that’s sterility, tests for microplasma, or other adventitious agents; things like bioburden and endotoxins, so all those tests need to be performed.

You need to have an identity test to make sure that your cell product ,whatever scale your manufacturing is, 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, and again, 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 ovr 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 and you can also do PCRto 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 quantitate your active cell 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 uring the manufacturing process.

And then typically, what you do is you archive. You archive samples from during your manufacturing process. You cryopreserve those so you can always go back to ensure that that a particular batch was consistent with other batches thatwere manufactured.

Join us in Philadelphia, December 12th and 13th 2011 for the IQPC Commercialization of Regenerative Medicine Summit.