FDA’s position on adult stem cells
FDA’s position on adult stem cells is contained in multiple places and can be tough to decipher. The basic starting place is: http://edocket.access.gpo.gov/cfr_2005/aprqtr/21cfr1271.3.htm.
The basic rule is that if the cellular therapy is covered within the CFR 1271 regulations, than it’s governed within this public health act (like a tissue transplant), if the cell therapy falls outside, it’s considered a drug that must go through an Investigational New Drug request (IND). The 1271 CFR PHS act basically says:
1. Stem cells can be regulated by FDA as drugs (outside of 1271) if:
a. They are used non-homologous. Pretty vague for adult stem cells, as they all have a function to repair or maintain tissue. When we have contacted FDA, the interpretation example given to us was that a fat derived MSC could not be used to repair cartilage in a joint, since that was not its function in the body. However even this is vague, as there are MSC’s in the pre-patellar fat of the knee that can theoretically participate in normal physiologic maintenance of the joint. In addition, MSC’s are discovered in places in the body every month, so this definition is seriously flawed.
b. There is more than “minimal manipulation”. This appears to say that if the stem cells are frozen or if solutions are used to maintain normal osmolarity, then they are not drugs. This doesn’t discuss how long they can be manipulated nor does it cover if they can be incubated for any period. In addition, bringing cells out of cryo typically involves a period of recovery incubation in at least basal media, so this would appear to say that you can freeze cells, you just can’t properly recover them as using growth media (more than minimal manipulation).
So when are stem cells a drug? Confused? Here are minor clarifications:
“Minimal manipulation” as used in the determination of whether HCT/Ps are “HCT/Ps regulated solely under section 361 of the PHS Act” means that any processing does not alter the relevant characteristics of the tissue for its intended use. Examples of minimal manipulation include: density gradient separation, selective removal of certain cells, centrifugation, grinding, lyophilization, freezing, and certain sterilization steps. Specifically excluded are any cellular expansion techniques. 21 C.F.R. § 1271.3(f)”
Still no clarification on the basal media issue. So this says that if you grow cells in culture than they are drugs? Does this include short periods of incubation? What about fertility clinics that grow allogeneic cells every day? That would be excluded?
For more guidance on these issues, http://www.fda.gov/cber/gdlns/pbsc.htm is illustrative. Basically, it says that if cells are processed for more than a few hours outside the body or outside of the same surgical procedure or at different site, than they fall out of 1271 and would be by default drugs.
Bottom line, while it’s OK for fertility clinics to culture expand allogeneic cells without new drug oversight, minimal periods of incubation or culture expansion of autologous adult cells (which would involve at a minimum a basal growth media, likely be performed at a separate site from a clinic, and not during the same surgical procedure where the cells are harvested) makes them drugs per the FDA’s current regulatory framework. This is despite the fact that you may not be altering the function of the cell in any way shape or form. This has been directly stated to us by FDA as well.
That’s why we put this organization together, the regulations should say at a minimum that mimicking processes that occur within the body so that autologous cells can be incubated without changing the cell phenotype does not create a drug, it’s processing human tissue.
Chris Centeno, M.D.
Founding Member, The American Stem Cell Therapy Association, ASCTA
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