December 13, 2012 Dr.

Celia Witten, MD, PhD Director, Office of Cellular, Tissue and Gene Therapies Center for Biologics Evaluation and Research Food and Drug Administration 1401 Rockville Pike Rockville, MD, 20852 Re: Precision StemCells Marketing & Administration of Stem Cell Procedures to Individuals with Amyotrophic Lateral Sclerosis, Spinal Cord Injuries & Other Diseases & Injuries Dear Dr. Witten: I am contacting you because I am concerned about autologous stem cell interventions marketed by Precision StemCell and provided to patients by Dr. Jason R. Williams.1 Dr. Williams, the owner of Precision StemCell and apparently the only physician working at this clinic, is a radiologist who promotes and administers stem cell interventions for wide range of diseases and medical conditions. Precision StemCell is located in Gulf Shores, Alabama. Many individuals have undergone adipose-derived stem cell interventions at Precision StemCell. It is imperative that such purported stem cell-based interventions are confirmed to be safe, efficacious, and in compliance with federal regulations before they enter the commercial marketplace and are used to treat patients. I am therefore hoping that you will investigate the regulatory status of stem cells administered to patients at Precision StemCell. Given that adipose-derived stem cells are being provided to individuals with Amyotrophic lateral sclerosis (ALS), spinal cord injuries, and other diseases and injuries I am concerned that autologous stem cells are being used in a nonhomologous manner. If this assessment is accurate then Precision StemCell appears to be operating in violation of 21 Code of Federal Regulations Part 1271. It also appears as though processing of adipose-derived stem cells at Precision StemCell might involve more-than-minimal manipulation as well as use of medical devices that are not intended for use in extracting, processing, and transplanting autologous stem cells. According to one account, Dr. Williams performed liposuction on a five-year-old child with optic nerve hypoplasia. Dr. Williams then reportedly processed stem cells obtained from adipose tissue before

The website for Precision StemCell is available at http://precisionstemcell.com

2 injecting the stem cells into the childs back.2 The Precision StemCell website does not provide scientific, clinical, ethical, or legal rationale for this act. A second stem cell recipient is a 74-year-old male diagnosed with ALS.3 This individual underwent what Precision StemCell describes as a stem cell reprogramming technique. A press release apparently distributed by Precision StemCell states, The technique performedis InVivo reprogramming, which reprograms adult stem cells into neural stem cells. The procedure involves harvesting adult stem cells from the patients own fat, which Dr. Williams obtains via minimally invasive liposuction, and then using image-guided therapy to insert the stem cells into the patients spine. For three to five days after the procedure, Dr. Williams places the patient on an oral medication that, as laboratory research has shown, causes stem cells to reprogram, converting them into neural stem cells.4 The press release does not state what medication Dr. Williams administered to this individual or what evidence supports the claim that adipose-derived stem cells are reprogrammed into neural cells. Additional individuals with ALS have had stem cells administered to them at Precision StemCell. Friends and family members of one man held a fundraiser to raise $15,000 for a stem cell procedure.5 Yet another patient underwent stem cell procedure at Precision StemCell and now seeks donations to cover the cost of future stem cell interventions.6 These reports suggest that paying for stem cell interventions provided at Precision StemCell is considerable financial burden for some patients and their loved ones. The list of illnesses and injuries for which stem cell interventions are available at Precision StemCell includes both neurodegenerative diseases and Nerve injury/Paralysis. The website states that two individuals with spinal cord injuries underwent neural reprogramming of mesenchymal stem cells.7
2

Andrews C (2012) Caydens second chance: 5-year-old has stem cell injection that may help his vision. AL.com. July 30. Available at: http://blog.al.com/live/2012/07/caydens_second_chance_at_sight.html
3

Andrews C (2012) Former Auburn coach getting stem cell treatments for Lou Gehrigs disease. AL.com. June 29. Available at: http://blog.al.com/live/2012/06/former_auburn_coach_getting_st.html
4

Hubbard B. (2012) Precision StemCells Revolutionary InVivo Adult Stem Cell Reprogramming Procedure Show Potential for Treating ALS. July 26. Available at: http://www.ereleases.com/pr/precision-stemcells-revolutionary-invivo-adult-stem-cell-reprogrammingprocedure-shows-potential-treating-als-83418
5

Smith J. (2012) Fundraiser for Mr. Hot Dog. Rockdale News. August 3. Available at: http://www.rockdalenews.com/archives/12225/
6

SCOTT JOHNSONS ALS TREATMENT FUND. (2012) September 7. Available at: http://www.cybertrout.com
7

Precision StemCell. See NEURODEGENERATIVE DISEASES/NERVE INJURY. Available at: http://www.precisionstemcell.com/Neurodegenerative.cfm

3 Precision StemCell also markets adipose-derived stem cell procedures for numerous orthopedic and sports-related injuries. Both coaches and athletes from college and professional ranks have had autologous stem cells administered to them at Precision StemCell. At least two NFL players have had stem cell procedures at Precision Stem Cell.8 Finally, a Twitter account labeled @jasonwilliamsmd describes the account holder as a Medical doctor in Alabama performing image guided stem cell procedures.9 The Twitter stream mentions stem cell interventions involving twelve patients with ALS, a five-year-old child, a paraplegic, and a patient with Alzheimers disease. The tweets suggest that the total number of individuals who have received stem cells at Precision StemCell exceeds the limited number of cases mentioned in local news media reports. The FDA registry, Human Cell, Tissues and Cellular and Tissue-Based Products (HCT/P) List of Registered Establishments, does not list Precision StemCell, Precision Stem Cell, or Dr. Jason Williams. Likewise, searches reveal that the FDA website contains no information concerning New Drug Applications (NDA), Biologics License Applications (BLA), or Investigational New Drug (IND) Applications associated with Precision StemCell or Dr. Williams. In addition, I have not found in the Clinicaltrials.gov database any stem cell-related (or other) clinical studies conducted by Dr. Jason Williams or Precision StemCell. Given that Dr. Williams and his clinic do not appear to have an IND, NDA, or BLA for any of the stem cell interventions provided at this facility I am writing to urge you to contact Precision StemCell and determine whether or not it is in compliance with federal regulations governing human cell, tissues, and cellular and tissue-based products (HCT/P). Though there appears to be no record of Precision StemCell registering with the FDA, I was able to locate on FDA website reference to the medical devices used by Dr. Williams. These pieces of equipment are manufactured by Medi-Khan. The US company Medi-Khan is located in Los Angeles, California. The parent company Medikan Korea Co. Ltd or Medikan International is based in Pusan, South Korea. Shipments from this company typically enter the U.S. via the port in Long Beach, California. One of the devices reportedly used at Precision StemCell is the Medi-Khan Lipokit.10 This device is classified as Class II; it appears that in October 2008 Medi-Khan submitted to FDA 510(k) notification

Andrews C. (2012). Former Alabama football players get stem cell injections from Gulf Shores doctor. AL.com. April 22. Available at: http://blog.al.com/live/2012/04/stem_cell_injections_offered_b.html
9

https://twitter.com/jasonwilliamsmd

10

Andrews C. (2012). Former Alabama football players get stem cell injections from Gulf Shores doctor. AL.com. April 22. Available at: http://blog.al.com/live/2012/04/stem_cell_injections_offered_b.html. The article states, As he (Williams) pored over ways to deliver stem cells to patients, he said, he became interested in the company Medi-Khan, with roots in Korea, because it offered a patented enclosed system for harvesting the adipose tissue. Williams said that Medi-Khan staff members came to his office and taught him how

4 of intent to market this device. According to the 510(k) summary, The Lipokit is used in the tumescent injection, aspiration, harvesting, filtering and transferring of autologous fat tissue.11 The summary also states, The Lipokit is indicated for use when harvesting of highly concentrated pure fatty tissues for aesthetic body and facial contouring is desired. There is no mention of stem cell procedures or stem cell processing in information concerning device classification, use, or intended use. The second medical device that Precision StemCell uses is the Medi-Khan Maxstem. This device is listed on FDA website as a Class I device.12 The classification name is container, specimen mailer and storage, temperature controlled, non-sterile. It appears that at Precision StemCell this device is used as an incubator.13 In photos the Maxstem medical device is somewhat reminiscent of a hotel mini-bar fridge.14 It is unclear what role this equipment plays in processing adipose-derived mesenchymal stem cells prior to injecting them into individuals with ALS or other diseases. While FDA website lists this device, the information describing its intended use makes no reference to processing and administration of autologous stem cells in clinical setting. I am therefore concerned with how Precision StemCell is using these devices to process adipose-derived stem cells before administering them to patients. Whatever documents were provided to FDA concerning the Lipokit and Maxstem, I should note that Medikan, the South Korean manufacturer of the Lipokit and Maxstem, appears to market these devices as a system capable of functioning as an incubator, isolating adipose-derived stem cells using an to use the system. In addition, please note that an earlier version of Precision StemCells website stated, Our Medikahn Lipokit and Maxstem stem System allows for closed harvesting, processing and re-introduction to the patient. This means that the cells are harvested and processed without exposure to the outside environment. this (sic) reduces chances of introducing infection. We combine the stem cells which (sic) platelet rich plasma (obtained from the patients blood. This contains growth factors that promote healing and stem cell growth.
11

Medi-Khan (USA) Inc. (2008) 510(k) Summary (21 CFR 807.92(c)) October 23. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf8/K083455.pdf
12

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/LDetails.cfm?LID=312258

13

The current version of Precision Stemcells website states, We use advanced stem cell processing and incubation system to harvest large numbers of stem cells from the patients own body (adult autologous). Available at: http://precisionstemcell.com/About-Precision-StemCell.cfm
14

For example, see Medikan Internationals website, http://www.medikanint.com/maxstem_detail.html as well as the MaxStem listing on the website for EquipForSkin. http://www.equipforskin.com/product/product_view.php?product_id=33. Please note that EquipForSkins website lists the MaxStem medical device as a FDA-certified incubator. The accompanying text states, MaxStem is a specially designed, FDA registered incubator. Maxstem is a specially designed medical incubator designed to effectively mix and culture the cell or tissue culturing solution within the inner containers completely separated from the outside environment within a certain temperature range.

5 enzyme/collagenizer solution, and processing autologous stem cells in less than ninety minutes.15 In short, there are some important unanswered questions concerning the gap between how these two pieces of equipment are in practice being used as point-of-care autologous stem cell processing devices and how they entered the marketplace as body and facial contouring device and non-sterile specimen container. Given the stem cell-based interventions marketed by Precision StemCell and provided to patients at this clinic, as well as the liposuction kit and specimen container that are being used to process adiposederived stem cells before administering them to patients, there are reasonable grounds for concern about safety and efficacy of stem cell interventions administered to individuals with ALS, spinal cord injuries, and other diseases and medical conditions. I am also greatly concerned that a five-year-old child with optic nerve hypoplasia had liposuction and stem cell procedure performed by a radiologist. I hope that you will contact Dr. Williams and address whether or not Precision StemCell is operating in compliance with federal regulations governing administration of stem cells and stem cell-based products. Thank you for considering this request. Please note that I am not writing on behalf of the institution of the University of Minnesota. Rather, I am contacting you as an individual faculty member, advocate for patient safety, and someone concerned with ethical and legal issues raised by domestic proliferation of clinics marketing stem cell interventions for ALS, Parkinsons disease, MS, Alzheimers, and other diseases and injuries. Yours sincerely,

Leigh Turner, PhD Associate Professor Center for Bioethics University of Minnesota N520 Boynton, 410 Church Street SE Minneapolis, Minnesota, 55455 Phone: 612.626.4830 Email: turne462@umn.edu cc: Lorrie Harrison McNeill, Director, Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, Food and Drug Administration Richard D. McFarland, MD, Associate Director for Policy, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration Theodore R. Stevens, MS, Associate Director for Information Management, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration

15

http://www.medikanint.com/maxstem_detail.html