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Notice: Grant and cooperative agreement awards: Nebraska Health and Human Services, et al.
Rule: Animal drugs, feeds, and related products: North American Nutrition Companies, Inc.
Citation: 66 Food & Drug L.J.
the strong response by some members of the public to FDA's assertion of authority.
FDA regulation and polarized views on access to experimental therapies.
while adequately protecting patients from exploitation or physical harm.
I United States of America v. Loran Medical Systems, Inc., et al., 25 F. Supp. 2d 1082 (C.D. Cal.
& Christopher Thomas Scott, Stem Cell Tourism and the Power of Hope, 10(5) AM. J. Brognicrs 16 (2010).
now available in several forms.
help to repair the injury.
The process takes about 7 weeks.
to review a prospective patient's films and $250-315 for a consult.
reported to cost approximately $7000-9000,9 and is not covered by insurance.
providers suggest that two to four injection cycles will normally be needed."
they are also found in other body tissues.
conclusion about the clinical benefit of Regenexx for any condition).
physician-oriented-V6.pdf at 8 (last visited Jun. 23, 2011) [hereinafter Regenerative Sciences, Regenexx].
FAQ's, REGENExxTM, http://www.regenexx.com/common-questions/ (last visited Jun. 23, 2011).
10 FAQ's, supra note 8.
uploads/ 2009/09/Regenexx-SD-Brochure.pdf at 2 (last visited Jun. 23, 2011).
stem cell or mesenchymal stromal cell.
plications, 10(10) EXPERT OPINION ON BIOLOGICAL THERAPY 1453, 1453-54 (2010).
14 NATIONAL INsTITUTES OF HEALTH, STEM CELL BAsics, at 12-13 available at http:llstemcells.nih.
genetically reprogrammed to be pluripotent (known as induced pluripotent stem cells or iPSCs).
15 Garcia G6mez et al, supra note 13,.at 1453.
repair as well as possible applications in neurological and autoimmune disorders.
Sciences asserts that: "MSCs receive differentiation cues from their environment.
For example, stretching or pulling forces can cause MSCs to become tendon cells.
injuries and avascular necrosis among the conditions treated.
1 Two case reports have been published in medical journals.
preclinical and animal studies relating to the treatment's potential effectiveness.
including three possible complications from stem cells.
the sites where the stem cells were injected.
conditions, although there are other risks such as infection.
TIVE MED. 169, 175-79 (2008).
Mesenchymal Stromal Cells Exert their Therapeutic Benefit?, 10(8) CYTOTHERAPY 771 (2008).
" Regenerative Sciences, Regenexx, supra note 7, at 6.
which contains stories about patients treated with Regenexx).
enchymal Stein Cells, 11(3) PAIN PHYSICIAN 343.
23 Regenerative Sciences, Regenexx, supra note 7.
STEM CELL RESEARCH AND THERAPY 8 1(2010).
injecting the cells later the same day.
"Regenexx-SCP" (Stem Cell Plasma) for meniscus tears.
cells would be sufficient to have a significant therapeutic benefit.
be taken to remedy these violations.
FDA began an inspection of the Regenerative Sciences facilities.
found numerous violations of "current Good Manufacturing Practice" (cGMP)."
exxTM Stem Cell Procedure Treating Musculoskeletal Diseases in Latin America, REGENEXxTM (Oct.
29 Regenexx Procedures Family, supra note 4.
30 Regenexx-AD (Adipose Derived), REGENExxTM (Nov. 27, 2010, 1:35pm), http://www.regenexx.
" Regenexx-SCP (Stem Cell Plasma), REGENExxTM (Nov. 27, 2010., 1:55pm), http://www.
32 See Regenexx Blog, supra note 21.
11 Case Studies, supra note 21.
- Centeno et al., Regeneration of Meniscus, supra note 22, at 902-903.
1 E.g Garcia Gomez et al., supra note 13, at 1461.
n Order of Dismissal, supra note 6, at 5.
attempt to conduct unsupervised discovery, which was denied: id).
The Court agreed and dismissed the action as not ripe and fit for review.
ance with cGMP and "misbranded" because the product was not properly labelled.
pending resolution of the case.
as to any material fact, summary judgment would be appropriate.
they challenge rules made by FDA more than six years before the claims were made.
As of June 2011, no decision on these motions had yet been reported.
40 Order of Dismissal, supra note 6, at 1.
42 Plaintiff's Motion for Summary Judgment, supra note 3, at 15-16.
www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ ucm221656.htm (last updated Jun. 8.
2010) [hereinafter FDA SEEKS INJUNCTION].
" FDA SEEKS INJUNCTION, supra note 43.
content/uploads/ 2010/08/Regenerative-Science-FAQs-8.211. 10.pdf at 2-3.
47 Plaintiff's Motion for Summary Judgment, supra note 3.
9 Plaintiff's Motion for Summary Judgment, supra note 3, at 2.
~' Plaintiff's Motion to Dismiss Defendants' Counterclaims, supra note 48, at 3.
(2011) (No. 1 :10-CV-01327-RMC) (Filed Aug. 29, 2011) (U.S. Dist. Ct. D.C.), available at http://app4.
laws, such as the need for approval and compliance with cGMP, apply to Regenexx.
are also defined as drugs.
the definition of a drug.
5 21 U.S.C. §§ 321(g)(1)(B), 321(g)(1)(C).
5 REGENEXXTM. http://www.regenexx.com (last visited Jun. 23. 2011).
56 Public Health Service Act, 42 U.S.C. § 262(i) [emphasis addedl.
has been confirmed on several subsequent occasions.
assure that the biological product continues to be safe, pure, and potent."
distinct characteristics that justify a lower risk classification.
not concerned with establishing efficacy or other aspects of safety.
controls, process validation, labeling controls and record-keeping.
meet certain criteria, they are only subject to these regulations.
safety concerns with respect to the HCT/P").
* United States of America v. Loran Medical Systems, Inc., et al., 25 F. Supp. 2d 1082 (C.D. Cal.
[hereinafter FDA, GUIDANCE FOR HUMAN SOMATIC CELL THERAPY]; Dina Gould Halme & David A.
W Fink, et al., FDA Regulation of Stem Cell Based Products, 324 SCIENCE 1662 (2009).
1 42 U.S.C. § 262(a)(2)(C); see also Food and Drugs, 21 C.F.R. pts. 600, 601, 610.
6 42 U.S.C. § 264(a).
pdf [hereinafter FDA, PROPOSED APPROACH To REGULATION].
63 21 C.F.R. § 1271 subpt. B.
6 Id, at § 1271 subpt. C.
65 Id, at § 1271 subpt. D.
not appear to be challenging this claimed exemption.
67 21 C.F.R. § 1271.20.
individual) in a first- or second-degree blood relative, or for reproductive use.
expansion of MSCs in culture should be considered only minimal manipulation.
361 HCT/P but is also subject to the drug and biological product requirements.
change so they are different from the original cells in the bone marrow."
changes in the shape of the cells.""
of other forms of processing in light of evolving scientific evidence.
lations is not definitive, but it should generally be given deference by the courts.
69 Id, at § 1271.L0(a)(4).
v. Regenerative Sciences, LLC, et al, (2011) (No. 1:10-CV-01327-RMC) (Filed Jan. 7, 2011) (U.S. Dist.
at issue (see id, at 24-36) but discussion of these points is beyond the scope of this article).
tion of cells and tissues include cell expansion, encapsulation. activation, or genetic modification").
n' FDA, PROPOSED APPROACH TO REGULATION, supra note 61. at 17-It8 (regarding cell selection).
biological properties of MSCs in ways that can affect both safety and efficacy.
of which consider expansion in culture to be only minimal manipulation.
plication, or a biologics licence) and to comply with cGMP and labelling requirements.
or "after shipment in interstate commerce."
to the cultured cells, have been shipped in interstate commerce."
B. Does FDA Lack Authority to Regulate Regenexx-C?
second is that the Clinic is not manufacturing drugs but simply practicing medicine.
8 E.g Horwitz & Dominici, supra note 17, at 773; Prockop et al., supra note 27.
are listed in the Annex).
OF HUMAN CELLS, TISSUES AND ORGANS FOR TRANSPLANTATION, 15 (2009).
Framework for Biologicals, TGA (Jun. 8, 2011), http:l/www.tga.gov.aulindustry/biologicals-framework.
4 21 U.S.C. § 331(a),(b).
85 Id., at § 331(k).
86 Regenerative Sciences and FDA -FAQs, supra note 46.
possessions, or from one State or possession into any other State or possession.""
define HCT/Ps to include autologous cells and tissues are ultra vires."
this could result in the transmission of communicable disease across state boundaries.
in 2005 without providing the public with notice or an opportunity to comment.
or transfer into a human recipient,"
the required notice and comment rulemaking procedures.
(Filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.), available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.
Halme & Kessler, supra note 58, at 1732.
*' 21 C.F.R. § 1271.3(d) [emphasis added].
Interference with the Practice of Medicine?, VII J. HEALTH & BIOMED. L. 233. 253-54 (2011).
* Plaintiff's Opposition. supra note 96.
practice of medicine, which FDA does not have the authority to regulate.
ing medicine using patients' own stem cells."
the definition of a drug under a reasonable interpretation of the FDCA provisions.
As an analogy, then, this is not particularly useful.
medical practice and indirectly by the potential for malpractice litigation.
61(103) Fed. Reg. 26523-24 (1996) [hereinafter FDA, GUIDANCE ON APPLICATIONS].
101 See Chirba & Garfield, supra note 98, at 266 (note 208).
02 But see id. at 267, arguing that the change should be seen as substantive rather than procedural.
consultations on the HCT/P framework, that autologous products would be included in its scope.
'1 RSI Welcomes Opportunity to Fight, supra note 44.
106 Id; Regenerative Sciences and FDA - FA Qs, supra note 46.
OF THE CORONER'S JURY INTO THE DEATH OF ASHLEY MARIE ATKINSON, (2003), available at http:f/www.
Off- Label Scientifc and Medical Information, 10 YALE J. HEALTH PoL'Y L. & ETHICS 299. 308-12 (2010).
regulating the promotion of off-label use is also a point of contention."
about the use of those products, which fall within the domain of medical practice.
FDA is claiming authority to do in this case is the former, not the latter.
consultations on the HCT/P regulations."
cells was a drug and biological product over which FDA had regulatory authority."
regulate autologous cell therapies is a broader question which will be considered below.
Off-Label Drug Use Rethinking the Role of FDA, 358 NEW ENG. J. OF MED. 1427 (2008).
tion of Off- Label Drug Uses, 76 Gao. WASH. L. REv. 1429.
" FDA, HCT/P FINAL RULE, supra note 78, at 5452.
115 United States of America v. Loran Medical Systems, Inc., et al., 25 F Supp. 2d 1082 (C.D. Cal.
and the scope of exceptions and flexibility in the regulatory process.
efficacy of autologous medicinal products, creating an 'anything goes' atmosphere,"
other companies that use cultured autologous mesenchymal stem cells in patients).
[hereinafter Regulators Must Step Up].
119 Cyranoski, FDA Challenges, supra note 9, at 909 (quoting Christopher Centeno).
120 Id (quoting Douglas Sipp).
but this view is not unanimous.
more support for the position of Regenerative Sciences.
123 Regulators Must Step Up, supra note 117.
press: Chirba & Garfield, supra note 98.
FDA Ol.htm; FDA Stops Stem Cells in USA, POLITICOL NEWS (Aug. 7, 2010), http://www.politicolnews.
Therapy That Saved UK Boy's Life & Man's Leg, GAIA HEALTH (Aug. 14, 2010), http://www.gaia-health.
GAlA HEALTH (Jun. 12, 2009), http://www.gaia-health.com/articles51/000055-Stem-Cell-Advocacy.shtml.
127 Amy Zarzeczny et al., Stem cell Clinics in the News, 28 NATURE BIOTECHNOLOGY 1243, 1245 (2010).
128 Patient Voices, ICMS: INTERNATIONAL CELLULAR MEDICINE SOCIETY, http://cellmedicinesociety.
org/patients/ patient-voices (last visited Jun. 25, 2011); FDA Stops Stem Cells in USA, supra note 125.
& Coles, supra note 126.
cell work performed by their doctors."
to seek treatment outside the U.S.
instead to the interests of "Big Pharma."
press/?p= 5826 (citing Centeno as saying "FDA's issue has never been about the safety of the procedure.").
2010), http://www.courthousenews.com/2010/08/10/29439.htm; Wilder, supra note 125.
E Kg Patient Voices, supra note 128; Hanson, supra note 126.
11Regenerative Sciences and FDA - FA Qs, supra note 46.
136 Wilder, supra note 125; Patient Voices, supra note 128; Hanson, supra note 126.
Stem Cell Research, supra note 130.
"' Hanson, supra notc 126.
Cell Research, supra note 130.
141 Morris & Coles, supra note 126.
me, it's not the business of the federal government."
larger debates about the extent of federal government influence over medical care.
ADMIN., EXPANDED ACCESS TO INVESTIGATIONAL DRUGS FOR TREATMENT USE: FINAL RULE, 74(155) Fed.
Reg. 40900 (2009) [hereinafter FDA, EXPANDED ACCESS TO INVESTIGATIONAL DRUGs]; see also 21 C.F.R.
1"Eg Ford, supra note 130.
145 RSI Welcomes Opportunity to Fight, supra note 44.
146 Abbott, supra note 132 (quoting Christopher Centeno).
147 Minor, supra note 131 (quoting Centeno).
148 E.g Patient Voices, supra note 128; Ford, supra note 130.
149 Regenerative Sciences and FDA - FA Qs, supra note 46.
not be able to recommend fish oil to a patient with high cholesterol because it is not an approved drug).
NETDAILY (Aug. 16. 2010, 9:13 PM). http://www.wnd.com?pageld=l191177.
position is part of a "massive federalist move" and that "Obamacare" requires "a lot of infringement"
of state authority over the practice of medicine).
fundamental individual liberty of the person."
trol one's own stem cells form a prominent theme in online comments.
therapies because they involve the use of one's own biological material.
members of the public believe are at stake when regulating new medical technologies.
disadvantages of FDA regulation and alternative forms of oversight.
154 Ford, supra note 130.
55 RSI Welcomes Opportunity to Fight, supra note 44.
beings: Ford, supra note 130).
'"' E.g Minor, supra note 131; Patient Voices, supra note 128; RSI Welcomes Opportunity to Fight.
type of cell therapy to be regulated" is "local medical boards and the courts."
be sufficient in the absence of FDA regulation.
misled patients and failed to obtain informed consent.
"no substantiated medical and/or scientific value."
5 STEM CELL REVS. & REPS. 135, 137 (2009).
U.K.) (Sep. 29, 2010), available at http://www.gmc-uk.org/static/documents/content/Trossel.pdf.
162 Administrative Complaint at paras, 19-20, Department of Health v. Zannos 0. Grekos (D.O.H.
consent or negligence in providing treatments could provide a basis for liability.
which is outside the scope of IRBs whose role is to approve research protocols.
fragmentation and conflicts of interest.
a policy on stem cell treatments: see Cyranoski, Texas Prepares to Fight, supra note 116, 378.
Regenerative Medicine, (Apr. 19, 2011) (a copy of the presentation is on file with the author).
165 RSJ Welcomes Opportunity to Fight, supra note 44.
167 ICMS Board of Directors, ICMS: INTERNATIONAL CELLULAR MEDICINE SocrETY, http://www.
cellmedicine society.org/home/boards-and-councils/board-of-directors> (last visited Jun. 25, 2011).
169 StematixTM Obtains Exclusive License to RegenexxTM, supra note 28.
17 LAB PRACTICEs GUIDELINES: VERSION 1.0, supra note 166.
http://www.cell medicinesociety org/home/boards-and-councils/irb (last visited Jun. 25, 2011).
www.cell medicinesociety.org/home/faqs (last visited Jun. 25, 2011).
" Sipp, Rocky Road, supra note 122.
http://www.safestemcells.org/ (last visited Jun. 25, 2011).
cinesociety orgl home/boards-and-councils (last visited Jun. 25. 2011).
medicinesociety org/ clinics/registry (last visited Jun. 25, 2011).
The ICMS is not the only organization promoting a self-regulatory approach.
Patient Cases Trackedin Treatment Registry, ICMS: INTERNATIONAL CELLULAR MEDICINE SOCIETY (Mar.
31, 2011), http:flwww. cellmedicinesociety org/home/news/press-releases.
cellmedicinesociety org/clinics/accreditation (last visited Jun. 25, 2011).
creditation Program, ICMS: INTERNATIONAL CELLULAR MEDICINE SOCIETY (May 10, 2011), http://www.
Standards.aspx> (last visited Jun. 25, 2011).
NAT'L INSTS. OF HEALTH, http://stemcells.nih.gov/ (last modified April 29, 2011).
STEM CELL RESEARCH, http://www.closerlookatstemcells.org (last visited Jun. 25, 2011).
alinfo_lSSCRReview Process.htm (last visited Jun. 25, 2011).
CFLL RFSEARCH, http://ww~w clnserlonkatstemcells.orgSubmit aClinic.htm (last visited ,Jun. 25, 2011).
schemes without any credible means of enforcement.
and independent evaluation of the evidence cannot be overstated.
Major Principles for Responsible Translational Stem Cell Research, 3 CELL STEM CELL 607 (2008).
followed for 12 months: see Regenerative Sciences, Regenexx, supra note 7 at 21.
1" Regenerative Sciences, Regenexx, supra note 7, at 13-14, 21.
placebo treatments produce significantly more placebo analgesia than less expensive ones" id, at 1282).
therapies - many of them autologous - are moving toward clinical applications.
produced drugs" that could "make many patients ill in 50 states."
ing one patient's tissue at a time.
periods of over- and under-regulation."
sionals in the field, it may seem very odd to use the language of "manufacturing"
that are appropriate to products composed of living cells.
200 Centeno, FDA Slippery Slope, supra note 151.
202 Regenerative Sciences and FDA - FAQs, supra note 46.
with Nanotechnology Regulation?, 27(11) TRENDS IN BIOTECHNOLOGY 615, 615 (2009).
on Best Practices and the Need for Harmonization, 7(4) CELL STEM CELL 451, 451 (2010); Sebastian C.
Sethe, The Implicationsof "Advanced Therapies" Regulation, 13 REJUVENATION RESEARCH 327,327 (2010).
206 Fink et al., supra note 58, at 1662.
200 Preti, supra note 207, at 802.
ficult for cell therapies than conventional pharmaceuticals.
explore and address outstanding issues.
were intended to be applied to autologous as well as allogeneic cell therapies.
are equally relevant to autologous as to allogeneic products.
regulatory challenges that apply to autologous or other individualized therapies.
and How to Meet Them, 9 NATURE REVS. DRUG DEV. 195, 197 (2010).
[hereinafter FDA, GUIDANCE ON POTENCY TESTS]; U.S. DEP'T OF HEALTH AND HUMAN SERVICES, U.S.
HUMAN SOMATIC CELL THERAPY, supra note 58.
211 Fink et al., supra note 58, at 1663.
ON APPLICATIONS, supra note 100.
213 21 C.F.R. § 1271.90(a)(1).
generative Medicine, 4(6) REGENERATIVE MED. 835 (2009).
to "one-on-many," as Centeno has suggested.
administered within a short time so that it may be impractical to wait for test results.
requirements to autologous therapies where the usual requirements are not feasible.
and could be treated as a separate product by regulatory authorities.
215 Centeno, FDA Slippery Slope, supra note 151.
216 Ward, supra note 92, at 232.
Financial Challenges of Personalised Cell Therapies, 4(22) PHARMACEUTICAL TECH. EUROPE 30 (2010).
Transplants, 43 TRANSPLANTATION PROCEEDINGs 338, 339 (2011).
219 Mason & Dunnill, supra note 214, at 845; Carpenter & Couture, supra note 118, at 570.
220 Condic & Rao, supra note 118, at 2755-56.
221 Mason & Dunnill, supra note 214, at 844.
222 Amy Zarzeczy et al., iPS, supra note 118, at 1036.
time stem cells are taken and grown for use on that same person.").
224 FDA, GUIDANCE ON POTENCY TESTS, supra note 210, at 3.
ApprovedProducts/ucm 171702.htm; April 29, 2010 Approval Letter from U.S. FOOD AND DRUG ADMIN.
final product from patient to patient.
to satisfy these concerns could be a significant obstacle.
by FDA less relevant or inappropriate, provided that it is applied in a flexible way.
autologous stem cell therapies - in the way FDA has attempted to do with Regenexx.
D. Is There a Need for Greater Flexibility?
used (in this case without prior approval) where there is an "urgent medical need,"
even if the usual standards for donor eligibility have not been satisfied.
where the approved product is unsuitable for an individual patient.
of approved drugs or are listed on an appropriate pharmacopoeia or equivalent.
nipulated, contains an additional exemption known as the "hospitals exemption."
Products, MESOBLAST (Jul. 21, 2010), http://www.mesoblast.com/download/l78/.
228 Carpenter & Couture, supra note 118, at 577.
23o 21 C.FXR. Pt. 312. subpt. I; FDA, EXPANDED ACCESS TO INVESTIGATIONAL DRUGs, supra note 143.
2 21 U.S.C. § 353a.
(EC) 726/2004. 2007 0.J. (L324), art. 28.
for a custom-made product for an individual patient."
standards equivalent to those imposed on other ATMPs.
where centralized marketing authorization operates alongside national regulation.
life-threatening or other serious conditions and no other viable treatment options.
safety and efficacy of which have not been assessed, on the other.
distinction in a reasonable way.
2" Id, at art. 28(2).
23 ISSCR GUIDELINES, supra note 194, at 4-5.
tive treatment can occur outside clinical trials); von Tigerstrom, supra note 158, at 136-37.
* Centeno, FDA Slippery Slope, supra note 151.
240 Eg. 1SSCR GUIDELINES. supra note 194. at 5.
position and challenge its authority in this matter are flawed in important respects.
the adequacy of alternative forms of oversight such as voluntary organizations (e.g.
to be accepted as credible.
in "clinician-centered activity in hospitals and clinics,"
lenging the traditional model of multi-phase clinical trials and regulatory approvals.
and unwise to dispense with this form of regulation, despite its difficulties.
regulation of autologous stem cell therapies will remain a work in progress.
New Therapies that Face Increasing FDA Scrutiny, 2010(6) UPDATE 16, 19 (2010).
24 Mason & Dunnill, supra note 214, at 848.
tion in Trials of Innovative Therapies. 328 SCIENCE 829 (2010).
supra note 207, at 803.

References: v. 
 § 262
 v. 
 § 262
 § 264
 § 1271
 § 1271
 § 1271
 § 1271
 § 1271

v. 
 § 331
 § 331
 § 1271
 v. 
 v. 
 § 1271
 § 353
 art. 28
 art. 28