FDA clarifies the definition of “same surgical procedure”

by Alexey Bersenev on October 23, 2014 · 5 comments

in regulation

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Today, FDA released a new guidance for industry document, which clarifies “same surgical procedure” definition. Please note that this is a draft document, which open for public comments. What is importance of this guidance and why FDA would clarify it?

As outlined in document’s background section, “same surgical procedure” is an exception from the regulation of cell products “as drugs” (351) and HCT/P with requirement of “FDA registration” (361). You can read more about it in section 1271.15 of CFR 21. Basically, if you transfer patient’s own cells from one place to another withing “same procedure”, you don’t need to deal with FDA, since it’s equal to “practice of medicine” as “surgery”. As FDA put it, 3 criteria must be met:

a. Remove and implant the HCT/Ps into the same individual from whom they were removed (autologous use);
b. Implant the HCT/Ps within the same surgical procedure; and
c. The HCT/Ps remain “such HCT/Ps;” they are in their original form.4 The communicable disease risks, as well as safety risks, generally would be no different from those typically associated with surgery.

But, devil in the details… And the biggest twist to me is in the phrase “HCT/Ps remain “such HCT/Ps””. Turns out that criteria of HCT/P similarity in this case are even narrower than definition of “minimal manipulation”:

… even manufacturing steps considered minimal manipulation within § 1271.10(a), will typically cause the HCT/P to no longer be “such HCT/P” under §1271.15(b), unless the HCT/P is only rinsed, cleaned, sized, or shaped.

So, to me the biggest question here – Is centrifugation falling into “rinsing, cleansing, sizing or shaping” the tissue? I don’t think so. But it could be debated. So, if centrifugation is “out of game”, pretty much none of currently used cell suspensions could be used under “same surgical procedure” exception. Of course, I’m talking about the most discussed (i) adipose tissue-derived stromal vascular fraction (SVF) and (ii) bone marrow mononuclear cells (BM MNC) – 2 types of cell products, which FDA continues to ignore in citations as examples. Isolation of both SVF and BM MNC (even in case of MNC enrichment = bone marrow concentrate) requires centrifugation – no matter what device you are using. A quote:

Processing of the autologous HCT/P raises safety concerns, such as contamination and cross-contamination, beyond those typically associated with surgery.

Here under processing they mean more than just “rinsing, cleansing, sizing and shaping” of tissue. It is not very clear to me how centrifugation will possess higher safety concerns (particularly, FDA cares about risk of microbial contamination) than rinsing cells in saline solution in the bag? How to measure which safety risks are higher?

Interestingly, HCT/P could be stored for days (!) and still be used as part of “same surgical procedure”, without FDA oversight. So, you are not limited by time of procedure as long as it’s “the same one”. But in this case, refrigerator should be in the same hospital.

Another puzzle to me is definition of “surgical procedure” itself. Is puncture of blood vessel a surgical procedure per FDA? What if I’ll make 1 cm incision to insert catheter into artery to deliver cells into heart or brain and then put 1 suture at the end? Sounds like “surgical” to me, since involves incision, but how is it different from puncture? FDA is not explicit about it.

Overall, this is very interesting document. It clarifies something, but still leaves some questions. As of now, it looks like FDA does not give any chances to adipose SVF and BM MNC to qualify for “same surgical procedure” exception. I’d encourage you to read it, discuss here and comment for FDA. I may send comments to FDA myself and ask to clarify “centrifugation” and bring SVF and BM MNC as examples.

{ 2 comments… read them below or add one }

Leeza Rodriguez October 24, 2014 at 1:30 pm

hi Alexey,

Agree that SVF is officially taken out of the equation. But for BM MNC, does it use enzymatic digestion? Can you describe the process please? As you know SVF uses not only centrifugation , but also enzymatic digestion of collagenase. Fat grafting uses only centrifugation.

IMO, it seems that centrifugation alone could be considered a ‘sizing’ mechanism. For regular fat grafting, when the fat is centrifuged it eliminates the dead stuff and yields a denser pellet of fat.

These are just my initial thoughts and of course I’m not a lawyer!

Reply

Alexey Bersenev October 28, 2014 at 2:13 pm

Yes, this guidance pretty much will close all doors for adipose SVF. If SVF isolation includes enzymes – you don’t fit in “minimal manipulation”, so you’re not 361. If your SVF isolation does not include enzymes, but considered as non-homologous and could be excepted as “same surgical procedure” – it will not work again, according to new guidance, because you will use centrifugation (it’s NO GO in guidance).
Bone marrow MNC isolation doesn’t involve enzymes – so it’s minimally manipulated, but if it’s not passing 1 criteria of 361, it could not be excepted as “same surgical procedure” again, because it’s always involves centrifugation.
That’s why, I think, clarification about centrifugation is a big deal.

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