Celltex responds in press release: FDA problems result of their Texas lab being run by Koreans, not Texans

Celltex has issued a press release (PR), entitled “Company Pioneering Regenerative Medicine Services Invited FDA to Inspect Lab” on their FDA audit in response to the reaction in the media and stem cell community about it.

I view this PR as a step in the right direction–more openness!

There is a lot of info in this PR that is quite interesting and new.

Celltex describes the issues they faced with the FDA as largely the result of a “language barrier” because as it turns out their Texas lab is apparently almost entirely run by Korean nationals employed by its partner, RNL, out of Seoul, Korea.

Here in my mind I imagined all this time that Celltex was staffed and operated entirely by Texans!

Somehow this is just not quite the same.

I wonder if Governor Perry knew this before he received his stem cell transplant via Celltex?

The relationship between RNL and Celltex has been known for some time, but the fact that RNL is actually apparently running the Celltex Lab in Texas is news to me and probably others. Note that I have nothing against Korea and in fact I believe some of the world’s best scientists are from Korea.

In another surprising disclosure, Celltex indicated that most of its procedures and documentation were not in English, but rather in Korean.

The PR also says “Celltex continues to strengthen its documentation and laboratory operations and has added to its staff Celltex personnel experienced in U.S. FDA compliance.”

I think that’s a smart move.

They also noted “We have an open line of communication with the FDA and expect to maintain that in our cooperative relationship. ”

Also a good sign.

Two puzzling aspects of the PR (emphasis mine), however, are the statements from Celltex that

1) “Celltex’s process for reproducing adult mesenchymal stem cells is legal, and there is no requirement that the cells be approved or licensed.”

2) “Celltex is registered with the FDA as a facility that multiplies human cells and cellular products (HCT/Ps); in particular, adult mesenchymal stem cells. The FDA does not require a company to obtain FDA approval prior to distribution of its HCT/Ps. 21 CFR Part 1271.”

These statements are particularly notable because to my knowledge according to current FDA guidelines any growth or multiplication of stem cells in culture or storage (or addition of storage or freezing media) by definition makes those products “more than minimally manipulated” and hence effectively biological drugs subject to far more thorough FDA vetting and pre-approval PRIOR to administration to any patients.

Yet Celltex-produced stem cells have reportedly (perhaps this is incorrect?) been given to more than 80 patients already.

Thus, it will be intriguing to see how this plays out and whether the FDA is indeed fully giving the “kosher” stamp to how Celltex is producing its MSC product in that they are storing and growing stem cells before the product is given to patients.

Perhaps the FDA is OK with it, but perhaps not. I don’t know.

But I think we’ll find out which it is fairly soon.

In this regard it is also critical to note that on the FDA 483 inspection report that Celltex is described as a “Biological Drug Manufacturer” and one view is that the FDA has defined the Celltex MSC product as a “351 biological drug”. To my knowledge, such a drug would in fact require FDA pre-approval and licensing prior to administration to patients. Again, perhaps I’m wrong.

Since I’m not a lawyer nor someone who routinely thinks about the minute, technical details of these legal rules and regulations, I’ve reached out to various people in the adult stem cell field, particularly those in the for-profit sector.

Only one person would go on the record about what he thought and that was Dr. Chris Centeno of Regenerative Sciences, Inc., who is currently in litigation with the feds over stem cell regulatory issues. He is someone that I often do not see eye to eye with, but I recently did a tandem interview of sorts with Dr. Centeno and Doug Sipp on stem cell regulation that was extremely popular with readers. The reaction of some of my academic colleagues was “why do you talk to him and publish his views on your blog if you disagree with him on key things?” The answer is because if we never talk to anyone but those who agree with us then we are doomed to group think and to only a narrow perspective on important issues. Call me naive after two decades in academia in one role or another, but I still find it kinda surprising how closed minded academic scientists can be to the point that they believe you shouldn’t even talk to someone at all with whom you disagree.

It is clear that Dr. Centeno and I do not agree on how much regulatory oversight is appropriate for stem cell-based treatments, but that’s OK and I still find his perspectives interesting for a variety of reasons as do the readers of this blog.

Here’s his take on Celltex’s FDA report, which I have reproduced verbatim:

“Which authority has regulatory control over CellTex (Texas or FDA) will eventually likely be decided by the courts. Having said that, this 483 is placing a square peg into a round hole. What’s interesting is that the FDA called CellTex’s MSCs a drug (351 biologic). By doing that, even though CellTex processes only autologous samples and the process is similar to IVF blastocyst culture (something that’s performed outside of FDA authority under the practice of medicine), FDA applied cGMP manufacturing guidelines which were designed to keep millions of drug doses safe. Several big players have commented that they think applying cGMP to autologous cell culture makes no common sense; see https://www.box.com/s/k1s1kxgrn3gj3boab1t1, https://www.box.com/s/oa9d02pnmbk7g2a2sluh, andhttps://www.box.com/s/3tb6ccqh6gep8y3hld3g . So realize that the best U.S. Fertility clinic safely transplanting cultured embryos would fail a cGMP inspection, but pass a CAP inspection with flying colors (College of American Pathologists). The bottom line is that cGMP is a drug mass manufacture standard.”

Frankly, I disagree with  Centeno on a lot of this, but I do agree that the FDA calling the Celltex product a “drug” and Celltex itself a “Drug manufacturer” has enormous implications.

I sincerely wish Celltex the best and hope that under the current and future guidance of the FDA that they can make a mark in the regenerative medicine field helping patients through safe and effective stem cell-based regenerative medicine treatments. It’s a challenging and very important new area of medicine. My offer to Celltex to do a friendly, non-confrontational interview on my blog is still open and in fact I will put up any statement they have verbatim on this blog.*

Call me!

*assuming it conforms to the rules of this blog (e.g. no personal attacks, obscenities, etc, which I doubt would be a problem in this case).

 

12 Comments


  1. Dr. Knoepfler,
    We at Biolife in Dallas Texas are huge fans not only of you as a premier scientist and researcher in the field, but for also providing an excellent platform for a non descriminatory exchange of ideas and opinions.
    As the person in charge of the 1st and largest Adipose Tissue and Stem Cell Bank in Texas, I wanted to clarify your comment that Cryogenic freezing of cells or adipose tissue were considered more than minimal manipulation.
    As you will see below under current “Federal GUIDLINES” the use of cryopreseratives such as DMSO, are exempt from the rule.
    And of course in Texas ( a more than minimally friendly stem cell state) new legislation was proposed last week by the Health & Human Services Commission (HHSC) as it relates to what a Stem Cell Bank can store, and soon it appears the language to be adopted will read that “Autologous Adult Stem Cells are cells taken from a person to be transplanted into the same person”.
    The following is provided for your edification.
    Legislation: 21 CFR 1271; HCT/P
    (“HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS”) • BioLife’s HCT/P’s are regulated solely under the regulations in 21 CFR 1271 and under section 361 of the PHS Act, according to 21 CFR 1271.10(a). All of the following criteria are satisfied: o The HCT/P is minimall ymanipulated.


    • Thank you very much for the comment and education! I love this kind of comment because it is so important for experts such as yourself to teach the rest of us. Also, when I’m wrong I actually want to know and to be corrected. I did not realize that DMSO was exempted.
      Thank you also for the kind words!
      I have two questions.
      1) Is there a restriction on the length of time of storage before something becomes more than minimal manipulated?
      2) Is growth of the cells prior to transplanted mean the cells are no longer minimally manipulated?


  2. I was cut short on the last post…
    Legislation:21 CFR 1271; HCT/P (“HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS”)
    • BioLife’s HCT/P’s are regulated solely under the regulations in 21 CFR 1271 and under section 361 of the PHS Act, according to 21 CFR 1271.10(a). All of the following criteria are satisfied:
    o The HCT/P is minimally manipulated.
     From FDA Docket No. 97N-484R, minimal manipulation include (1) density gradient separation; (2) selective removal of B-cells, T-cells, malignant cells, red blood cells, or platelets; (3) centrifugation; (4) cutting, grinding, or shaping; (5) soaking in antibiotic solution; (6) sterilization by ethylene oxide treatment or irradiation; (7) cell separation; (8) lyophilization; (9) cryopreservation; or (10) freezing.
    o The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent.
     Retrieval and distribution of stored samples are labeled for “Autologous and Homologous Use Only,” according to BioLife’s SOP.
    o The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P.
     The use of cryoprotectants for preserving and storage is exempt as noted above.
     From FDA Docket No. 97N-484R, examples of substances that would generally be acceptable include: (1) Cryoprotectants (e.g., DMSO).
    o The HCT/P has a systematic effect or is dependent upon the metabolic activity of living cells for its primary function, and is for autologous use.
     Retrieval and distribution of stored samples are labeled for “Autologous Use Only,” according to BioLife’s SOP.
    • BioLife is exempt from the determination of donor eligibility, according to 21 CFR 1271.90(a).
    o From 21 CFR 1271.90(a), BioLife is not required to make a donor-eligibility determination or to perform donor screening or testing as (1) cells and tissues are for autologous use.
    o According to BioLife’s SOP, samples contain the required labeling in 21 CFR 1271.90(b):
     (1) “FOR AUTOLOGOUS USE ONLY”
     (2) “NOT EVALUATED FOR INFECTIOUS SUBSTANCES”
    • BioLife is FDA-registered as a HCT/P establishment as outlined in Subpart B of 21 CFR 1271.
    • BioLife is compliant with Current Good Tissue Practice as required in Subpart D of 21 CFR 1271.


    • (1) I could find not any FDA mention of a storage time limit before cryopreserved tissues/cells are classified as beyond minimally manipulated. As stated in Docket No. 97N-484R, freezing with DMSO [with no mention of storage time] is considered minimally manipulated.
      (2) Yes, any growth of cells is no longer minimally manipulated as stated in Docket No. 97N-484R.


  3. @BioLife Cell Bank
    Is enzymatic digestion during the autologous fat tissue processing considered by FDA as minimal manipulation? As far as I’m concern the answer is no. Therefore, if “stem cell bank” do primary adipose tissue processing before storage, they not fit in definition of “minimal manipulation” because the use of enzymes.

    The problems with CellTex, which FDA should be notice is that they do enzymatic digestion of the tissue, they do culture cells and they sell cells for non-homologous application. Therefore, they can’t fit in 21 CFR 1271.

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