12651 West Sunrise Blvd., Suite 104, Sunrise, Florida 33323

August 29, 2017

Food and Drug Administration

Florida District Office

555 Winderley Place, Suite 200

Maitland, FL 32751

RE: Warning letter received August 24th, 2017

 

Dear Mr. Randall Morris,

 

Please accept this letter as response to the warning letter received August 24th, 2017.  In sum, as was previously demonstrated, the US Stem Cell Clinic (USCC) is not utilizing a biological drug product and therefore the regulations of part 210 and 211 (current good manufacturing practices) do not apply.  The comments in the provided warning letter are specific to products that are produced in cGMP manufacturing facilities and classified as drugs according to the FDA.  This is not something that a medical clinic would be required to follow. USCC is not manufacturing a drug.  That being said, in an abundance of caution, US Stem Cell Clinic will immediately switch to 510(k) approved systems to process tissue in clinic such as bone marrow systems and/or fat systems.

 

Our facility has demonstrated sterile surgical techniques as required by the medical boards.  It is inappropriate and harmful to state that our clinic is not sterile as we are completely compliant with the regulations for surgical procedures including using individually wrapped disposable sterile supplies, sterile field prep, and more.  The strict regulations mentioned in the warning letter required to manufacture drugs are not applied to clinics or hospitals.  As a clinic performing a medical procedure, we have strict and appropriate protocols in place to prevent contamination and breach of sterility.  We are following the exact protocols that are utilized at surgical centers and hospitals.  As you know, these protocols are very different than what is required for GMP manufacturing facilities.  We have never had an incidence of contamination and the statements that were made in your warning letter and press release are misleading and causing irreparable harm.

 

We have previously described in detail why the FDA has wrongly defined these in clinic procedures as a drug and provided evidence.  The evidence and summary is provided below.  I would like to specifically call your attention to the fact that according to your current code of federal regulations, same surgical procedure is not subject to the rules for tissue banks which include minimal manipulation and homologous use.  We strongly believe that it is a violation of the rights of American citizens to prevent them from seeking alternative care for their conditions as long as it does not violate regulations or the law. Our clinic is not violating the law as it is currently written.  There is huge support from government officials and American citizens for stem cell treatments—again, while all laws are adhered to as we do.  Please refer to just one petition out of many regarding stem cell treatments in clinic with almost 70,000 signatures: https://www.change.org/p/fda-don-t-shut-down-our-access-to-needed-stem-cell-therapy-treatment.

 

We would also like to address the comment in your warning letter regarding our firm impairing the ability to conduct the inspection.  This statement is blatantly false and should be removed from the record.  We provided access to every room in the facility and allowed pictures on multiple occasions.  We also provided copies of all requested documents including confidential patient information.  We are an extremely small firm with only a handful of employees most of which are part time or 1099 contract.  As a small firm with limited resources, it is necessary to schedule the access that was required by the investigators in order to prevent permanent damage to our business.  We provided abundant time and availability to the inspectors and on several occasions, the inspectors canceled last minute and did not come.  At one point, the inspectors came to the office when the office was closed.  During this last inspection, we worked with the inspectors for over a month providing hundreds of copies and burned CDs.  On several occasions, I requested paper, printer ink and office supplies but did not receive what was requested.  This inspection caused undue financial harm to our small firm—yet we made our staff and resources available to the investigators at all times.  Stating that we prevented or limited access to our company is an apparent attempt to disparage our company and we deem it both unprofessional and an unfair statement.

 

Given that we are a medical clinic that does not manufacture drugs, the guidance document that you referenced does not apply to our facility. Instead, USCC is performing a medical procedure wherein tissue is removed from a patient and re-implanted during the same surgical procedure.  21 C.F.R. § 1271(b) titled “Human Cells, Tissues and Cellular Tissue-Based Products,” expressly states, “you are not required to comply with the requirements of this part if you are an establishment that removes HCT/P’s from an individual and implants such HCT/P’s into the same individual during the same surgical procedure.”

 

The procedure performed at USSC is simply the practice of medicine.  Medical practitioners have been performing similar type procedures in clinic for decades including fat, skin, tendon/ligament, vascular, hair and bone grafts, bone marrow transplantation, and blood/plasma transplantation.  Please keep in mind that many of these medical procedures may involve non-homologous use of tissue (CABG with vein graft or ileum to replace bladder) or more than minimal manipulation (skin grafts, hair transplants, or bone grafts).  But because these are completed by medical practitioners during the same surgical procedure, the practitioners per the exception clause “are not required to comply with the requirements of this part (1271)” which includes details on products under section 351 vs. 361 PHS Act.

 

Therefore, the regulatory sections of Part 1271 regarding “homologous use” or “more than minimal manipulation” are not applicable to the procedures performed by USSC.  To be clear, the purpose of stem cells inside our bodies is to maintain and repair damaged tissue, therefore any application of stem cells to patients would in fact be defined as homologous.

 

Even if USSC were somehow subject to the regulatory sections of Part 1271, the protocols utilized by USSC would be exempt from the regulations because the procedures practiced at USSC do not involve more than “minimal manipulation.” Part 1271 Regulations create a regulatory exemption from the manufacturing and labeling requirements that normally apply to drugs and biological products for any HCT/P that is no more than “minimally manipulated.” See 21C.F.R.§ 1271.10(a). “Minimal manipulation” of cells means “processing that does not alter the-relevant biological–characteristics.” Id. § 1271.3(f)(2).

 

In the procedures performed at USCC, the actual stem cells are not modified or changed in any way but instead separated via centrifugation.  Even the collagenase digestion only changes the integrity of the extracellular matrix and does not change the characteristics of the cells themselves.  These scientific facts were confirmed by several leading stem cell scientists at the September 2016 FDA hearing.

 

Medical procedures are already scrutinized and regulated by the state medical boards, legislatures, and agencies.  In addition, the doctor patient relationship is protected and physicians take a vow to protect the safety, health and welfare of patients.  They are dedicated to serving the interest of the patient and market forces, societal pressures, and administrative demands must not compromise this promise.  The FDA is responsible for protecting the public health by assuring the safety, efficacy and security of drugs.  The FDA does not regulate the practice of medicine or the bodies/tissues of individuals.

 

This same procedure is currently performed at thousands of clinics throughout the US.  Notably, throughout the stem cell field, these clinics and practitioners also maintain that the procedures performed are medical procedures, and that the regulations of part 210 and 211 (current good manufacturing practices) do not apply.

 

We are aware that many clinics have been visited by the FDA without any actions or warnings letters.  At USCC, we are following standard clinical procedures for medical facilities to ensure safety of the patients.  This is considered a medical procedure because the tissue is removed from the patient and re-implanted during the same surgical procedure to the same patient (autologous use).  The protocols used at our clinic have been well established in publications as both efficacious and safe.  Over ten thousand patients have been treated using similar protocols with a strong safety record.  Specifically, over 7000 patients have been treated using the exact same laboratory kit that we utilize at USCC.

 

Bone marrow and blood products are currently being utilized in the clinic in a similar fashion.  The only reason bone marrow products are being regulated differently is because they predate the 1976 medical device amendments allowing for a 510k process instead of IND/IDE.  There is no scientific or medical reason that fat tissue removed from a patient would be regulated differently than bone marrow or blood, when they are being used for the same purpose.  According to recent publications, cells from fat tissue are demonstrating superior clinical results than bone marrow cells.  This is most likely due to the fact that the bone marrow contains very high amounts of white blood cells (WBCs) which can cause unnecessary inflammation whereas fat has low amounts of WBCs.   Fat tissue, however, may contain up to 500 times more stem cells.  The rate of complications from taking a bone marrow aspirate is significantly higher than taking an adipose sample.  The cells that are obtained from an adipose sample are separated from the adipocytes and have not been manipulated or changed in any way prior to reintroducing into a patient.  According to reports, these therapies do not have the same negative side effects as many of the available drugs on the market.

 

We are aware that the FDA received comments on the published draft guidelines regarding adipose tissue procedures in clinic.  We are also aware that the FDA held a public hearing regarding these topics in September 2016 in which many scientists, physicians and patients expressed support for these therapies.  We are able to provide the FDA with any necessary information to demonstrate that this is a medical procedure that is safely done on an outpatient basis.  Published results of outcomes to date have been overwhelmingly positive.

 

If the federal government were to interfere with a person’s ability to obtain and utilize their own cells in their body to heal themselves, this could be a gross violation of the constitution.  According to the constitution, Americans have a fundamental right to privacy as well as protection from undue government intrusion.  Specifically, in the case of Griswold v. Connecticut 381 U.S. 479, 484-486 (1965), the Supreme Court recognized that “specific guarantees in the Bill of Rights” create “zones of privacy” to protect certain intimate activities from “means which sweep unnecessarily broadly and thereby invade the area of protected freedoms.”  Regarding bodily integrity, the court ruled that “no right is held more sacred, or is more carefully guarded…than the right of every individual to the possession and control of his own person, free from all restraint or interference from others…”    Both Roe v. Wade, 410 U.S. 113 (1973) and Planned Parenthood v. Casey 506 U.S. 833 (1992), protected rights to privacy, autonomy, and personal choice. See also A.L.A. v. West Valley City, 26 F.3d 989, 990 (10th Cir.1994) (“There is no dispute that confidential medical information is entitled to constitutional privacy protection.”); According to A. Rahman Ford, JD, PhD, “Undue infringement by the federal government upon so sacrosanct a right as the bodily integrity of private persons must be viewed as paternalistic, Victorian and an affront to the freedoms inherent in the Constitution itself.”

 

Notwithstanding the above—and again, in an abundance of caution—it is our sincerest interest to adhere to the FDA’s interpretation of the laws and have several specific questions that we would like the FDA to kindly provide answers to:

  1. Why would bone marrow in-clinic procedures be regulated differently than fat and/or stromal vascular fraction?
  2. Is fat which has been mechanically broken down (i.e. the LipoGems procedure) instead of enzyme digestion regulated differently?
  3. Will you allow clinics who are using bone marrow to continue to treat patients?
  4. Will you restrict the type of patients who are being treated using in-clinic protocols with bone marrow?
  5. Will you restrict the discretion of physicians on patient selection to treat using their own body tissue?
  6. Are you intending to limit surgical procedures which have been in practice for decades that involve more than minimal manipulation?
  7. Are you intending to limit surgical procedures which have been in practice for decades that involve non-homologous use?
  8. Are clinics using fat tissue but not using enzyme permitted to operate?
  9. Why is the FDA viewing a patient’s own body tissue used in clinic as a drug – please show specific case law justifying this violation of human rights?
  10. Why has the FDA visited similar clinics and not taken action?
  11. Why is the FDA ignoring the requests of tens of thousands of citizens to keep these therapies available?
  12. After the FDA hearing in September 2016 where scientists, physicians and patients spoke out in favor of these therapies, why has the FDA not responded?

 

Our clinic is simply providing medical treatments to consenting patients using cells from their own body during a medical procedure which does not invoke oversight by the federal government.  We would like to specifically request a meeting with the FDA commissioner to better explain the procedures that have successfully helped thousands of people.

 

We look forward to your responses to our questions above.  Feel free to contact me if additional information is required.

Sincerely,
US Stem Cell Clinic

Kristin Comella, CSO

Email: kcomella@us-stemcell.com