One size doesn’t fit all? FDA may soften some cell therapy regs

The Pink Sheet just broke the story that the FDA may change up its oversight of the cell therapy space. This possible shift could drop the oversight bar somewhat for certain products. Most likely it’d be those with lower anticipated risks.

dr. peter marks fda, cell therapy
Dr. Peter Marks, Director of CBER at the DFA.

The Pink Sheet piece by Sue Sutter is titled US FDA To Explore New Regulatory Pathways For Some Cellular Products. She reports the news based on a talk given by CBER Director Peter Marks. Sutter also followed up with the agency.

I highly recommend the article. It goes into a lot of depth and I’m just covering some of the main points here. They have a graph on HCTP inspections over the last few years that is striking. I was very surprised.

New category for some cell therapy offerings

A key quote suggests an intermediate category for certain predicted lower-risk therapies:

“CBER Director Peter Marks Says FDA Plans To Explore Whether There Is An Intermediate Pathway Between Tissue Regulations And A Full BLA For Certain Cellular Products.”

It seems that this is more in the planning and brainstorming stage than a done deal.

The change would make many in industry happy. Getting cell therapy drugs approved is very difficult.

Plus, the move could shift many, perhaps dozens of products away from needing more intensive FDA drug oversight. In that practical sense it could be helpful for CBER staff, which has a massive workload.

Note that the title of this post could have been “two sizes don’t fit all” because the FDA has typically divided products into 351s and 361s. They are considering an intermediate classification between the two.

What products would be reclassified?

It’s going to be fascinating to see what products they have in mind here, assuming again this possible change becomes a reality.

So far there aren’t any clear hints as to what kinds of cellular products might get placed in the new category. Certain types of acellular cell therapies might be likely candidates.

“Acellular cell therapies” may sound like a contradiction in terms, but the term “cell therapy” is surprisingly broad.  The group includes things like exosomes and cell extracts as well as extracellular matrix. In that sense, things made from or secreted by cells are also cell therapies even if they have no cells in them.

Possible challenges

Picking which products could be in the intermediate category could be tricky.

Take exosomes.

The agency has been consistent in saying that exosomes are going to be regulated as drug products. Could that change? A translational challenge in the exosome space is that there is so little solid data on safety and efficacy for specific types of products for defined conditions. That will probably change over the next 5-10 years.

While acellular offerings like exosomes are generally off the shelf allogeneic products (easy to make, store, and use), one could imagine emergence of autologous exosomes, which might be more likely to present lower risks. They would be a lot more work to make and validate though.

Another broader challenge is presented by the unproven clinic industry.

With a few thousand stem cell clinics out there in the U.S., it seems like a good bet that many of these firms may scramble to claim their offerings fit into the new category even if that’s not actually the case. If in theory some clinic offerings potentially could fit into the new category, even so the clinics may use them in ways that present higher risk and trigger drug-level classification and oversight.

Sounds messy.

As Sutter reports in The Pink Sheet piece, it’s also possible a new regulatory framework with an intermediate category could spark litigation. For example, one can imagine a sponsor saying “Why is my competitor’s product in the new category and ours isn’t?” Some could turn to the courts in that kind of scenario.

Looking ahead

Such possible challenges could give the agency second thoughts about the change.

As Sutter’s piece mentions, would the possible change be statutory in nature or mediated by new guidance? I think probably the latter.

Sutter quotes Dr. Marks that things are still in the exploratory phase.

“We’re going to explore whether there is some intermediate pathway that might be appropriate there. … We are trying to lean in to those things that we regulate to find the best methods to bring them forward to the benefit of patients. Whether we’ll find a solution there I can’t say, but I think it’s worth exploring.”

However, I think this kind of change is likely to happen in some form.

If the FDA proceeds with this shift, the key is going to be proper classification of which products should go in the new lower risk category.

The criteria need to be crystal clear and logical.

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