The Food and Drug Administration, regenerative sciences, and the regulation of autologous stem cell therapies

Food and Drug Law Journal

Volumn 66, Issue 4, 2011, Pages

  Von Tigerstrom, Barbara ^a  

^a UNIVERSITY OF SASKATCHEWAN   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL PRODUCT;

AUTOLOGOUS STEM CELL TRANSPLANTATION; CELL EXPANSION; CELL SEPARATION; CENTRIFUGATION; ENCAPSULATION; FERTILIZATION IN VITRO; FOOD AND DRUG ADMINISTRATION; FREEZING; HUMAN; MESENCHYMAL STEM CELL; REGENERATIVE MEDICINE; REVIEW;

AUTOGRAFTS; HUMANS; REGENERATIVE MEDICINE; STEM CELL TRANSPLANTATION; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84861752533     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (296)

1. United States of America v. Loran Medical Systems, Inc., et al., 25 F. Supp. 2d 1082 (C.D. Cal. 1997);
2. Letter from MARY A. MALARKEY, OFFICE OF COMPLIANCE AND BIOLOGICS QUALITY, U.S. FOOD AND DRUG ADMIN., to Stem Cell Pharma Inc., (Nov. 22, 2006), available at http://www.fda.gov/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/ComplianceActivities/Enforcement/ UntitledLetters/ucm091930.htm.
3. E.g. COMMITTEE FOR ADVANCED THERAPIES AND CAT SCIENTIFIC SECRETARIAT, Use of Unregulated Stem-Cell Based Medicinal Products, 376 LANCET 514 (2010) [hereinafter CAT, Use of Unregulated Stem-Cell];
4. Jane Qiu, Trading on Hope, 27 NATURE BIOTECHNOLOGY 790 (2009);
5. Ole Lindvall & Insoo Hyun, Medical Innovation Versus Stem Cell Tourism, 324 SCIENCE 1664 (2009);
6. Darren Lau et al., Stem Cell Clinics Online: The Direct-to-Consumer Portrayal of Stem Cell Medicine, 3 CELL STEM CELL 591 (2008);
7. Charles E. Murdoch & Christopher Thomas Scott, Stem Cell Tourism and the Power of Hope, 10(5) AM. J. BIOETHICS 16 (2010).
8. Plaintiff's Motion for Summary Judgment at 19, United States of America v. Regenerative Sciences, LLC, et al (2011) (No. 1:10-CV-01327-RMC) (filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.), available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.com/pdf/ I%2019%20Plaintiff's%20Motion%20for%20Summary%20Judgment%20010711.pdf.
9. Regenexx Procedures Family of Stem Cell and Platelet Procedures, REGENEXX™, http://www.regenexx.com/regenexx-procedures-family/ (last visited Jun. 23, 2011) [hereinafter Regenexx Procedures Family]. (Regenerative Sciences and the Clinic refer to the "Regenexx procedure" while the Food and Drug Administration refers to it as a product, reflecting the difference of views between them. This article will use "treatment" or "therapy" as neutral terms, although this is not meant to imply any conclusion about the clinical benefit of Regenexx for any condition).
10. This description is summarized from court documents, including: Order of Dismissal, Regenerative Sciences, Inc. v. United States Food and Drug Administration, et al., (Mar. 26, 2010) (No. 09-cv-00411-WYD-BNB) 2WL 1258010 (U.S. Dist. Ct, D. Colo.) and Plaintiff's Motion for Summary Judgment, supra note 3, at 10-12.
11. Regenerative Sciences, LLC, Regenexx Procedure: Imaging Case Reports and Medical Provider Information, REGENEXX™, available at http://www.regenexx. com/wp-content/uploads/2008/12/Regenexx-physician-oriented-V6.pdf at 8 (last visited Jun. 23, 2011) [hereinafter Regenerative Sciences, Regenexx].
12. FAQ's, REGENEXX™, http://www.regenexx.com/common-questions/ (last visited Jun. 23, 2011).
13. David Cyranoski, FDA Challenges Stem-Cell Clinic, 466 NATURE 909, 909 (2010) [hereinafter Cyranoski, FDA Challenges].
14. FAQ's, supra note 8.
15. Regenexx-SD Procedure, REGENEXX™, available at http://www.regenexx. com/wp-content/uploads/2009/09/Regenexx-SD-Brochure.pdf at 2 (last visited Jun. 23, 2011).
16. The terminology has been the subject of some debate, and other names have also been proposed: see Arnold I. Caplan, What's in a Name?, 16(8) TISSUE ENGINEERING: PART A 2415 (2010);
17. Paolo Bianco, Pamela Gehron Robey & Paul J. Simmons, Mesenchymal Stem Cells: Revisiting History, Concepts, and Assays 2(4) CELL STEM CELL 313, 314 (2008). In all of its literature, Regenerative Sciences uses the term "mesenchymal stem cell." This article will use the acronym MSC which can refer to either mesenchymal stem cell or mesenchymal stromal cell.
18. Ignacio García Gómez et al., Mesenchymal Stem Cells: Biological Properties and Clinical Applications, 10(10) EXPERT OPINION ON BIOLOGICAL THERAPY 1453, 1453-54 (2010).
19. NATIONAL INSTITUTES OF HEALTH, STEM CELL BASICS, at 12-13 available at http://stemcells.nih.gov/staticresources/info/basics/SCprimer2009.pdf (last visited Jun. 24, 2011) This is unless they are genetically reprogrammed to be pluripotent (known as induced pluripotent stem cells or iPSCs).
20. García Gómez et al, supra note 13, at 1453.
21. E.g. id. at 1457-58; Ivan Martin et al., A Survey on Cellular and Engineered Tissue Therapies in Europe in 2008, 16(8) TISSUE ENGINEERING: PART A 2419, 2420-21 (2010);
22. Stefan Bajada et al., Updates on Stem Cells and their Applications in Regenerative Medicine, 2 J. TISSUE ENGINEERING AND REGENERATIVE MED. 169, 175-79 (2008).
23. E.g. García Gómez et al., supra note 13, at 1462-63; Em Horwitz & M Dominici, How do Mesenchymal Stromal Cells Exert their Therapeutic Benefit?, 10(8) CYTOTHERAPY 771 (2008).
24. Regenerative Sciences, Regenexx, supra note 7, at 6.
25. Conditions Treated, REGENEXX™ http://www.regenexx.com/the-regenexx- procedures/ (last visited Jun. 23, 2011).
26. Regenexx-SD Procedure, supra note 11.
27. Case Studies, REGENNEX™, http://www.regenexx.com/the-regenexx- procedures/case-studies/ (last visited Jun. 23, 2011);
28. see also Regenexx Blog, REGENEXX™, http://www.regenexx.com/global- navigation/regenexx-blog/ (last updated Jun. 24, 2011) (This is a blog found on the Regenexx website, which contains stories about patients treated with Regenexx).
29. Christopher J. Centeno et al., Partial Regeneration of the Human Hip via Autologous Bone Marrow Nucleated Cell Transfer: A Case Study, 9 PAIN PHYSICIAN 253 (2006);
30. Christopher J. Centeno et al., Regeneration of Meniscus Cartilage in a Knee Treated with Percutaneously Implanted Autologous Mesenchyman Stem Cells, 71 MEDICAL HYPOTHESES 900 (2008);
31. Christopher J. Centeno et al., Increased Knee Cartilage Volume in Degenerative Joint Disease using Percutaneously Implanted, Autologous Mesenchymal Stem Cells, 11(3) PAIN PHYSICIAN 343.
32. Regenerative Sciences, Regenexx, supra note 7.
33. Id., at 14, 21.
34. Christopher J. Centeno et al., Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique, 5(1) CURRENT STEM CELL RESEARCH AND THERAPY 81 (2010).
35. Darwin J. Prockop et al., Defining the Risks of Mesenchymal Stromal Cell Therapy, 12(5) CYTOTHERAPY 576, 578 (2010).
36. Regenexx Procedures Family, supra note 4;
37. Stematix™ Obtains Exclusive License to Regenexx™ Stem Cell Procedure Treating Musculoskeletal Diseases in Latin America, REGENEXX™ (Oct. 23, 2009), http://www.regenexx.com/2009/10/stematix%E2%84%A2-obtains- exclusive-license-to-regenexx%E2%84%A2-stem-cell-procedure-treating- musculoskeletal-diseases-in-latin-america/ [hereinafter Stematix™ Obtains Exclusive License to Regenexx™];
38. Local Chinese Government Authorities Approve Pricing and Reimbursement for Neostem's Licensed Adult Stem Cell Treatments for Orthopedic Applications in China, NEOSTEM (Nov. 2, 2010), http://www.neostem.com/news/ocal-chinese- government-authorities-approve-pricing-and-reimbursement-for-neostem-s-licensed- adult-stem-cell-treatments-for-orthopedic-applications-in-china.html;
39. Centeno-Schultz Clinic Opening a State of the Art Stem Cell Culture Lab in the Cayman Islands, REGENEXX™ (Aug. 17, 2011), http://www.regenexx.com/ 2011/08/centeno-schultz-clinic-opening-a-state-of-the-art-stem-cell-culture-lab- in-the-cayman-islands/.
40. Regenexx Procedures Family, supra note 4.
41. Regenexx-AD (Adipose Derived), REGENEXX™ (Nov. 27, 2010, 1:35pm), http://www.regenexx.com/2010/11/regenexx-ad-adipose-derived/.
42. Regenexx-SCP (Stem Cell Plasma), REGENEXX™ (Nov. 27, 2010, 1:55pm), http://www.regenexx.com/2010/11/regenexx-scp-stem-cell-plasma/.
43. See Regenexx Blog, supra note 21.
44. Case Studies, supra note 21.
45. Centeno et al., Regeneration of Meniscus, supra note 22, at 902-903.
46. E.g. García Gómez et al., supra note 13, at 1461.
47. Letter from MARY A. MALARKEY, OFFICE OF COMPLIANCE AND BIOLOGICS QUALITY, U.S. FOOD AND DRUG ADMIN., to Regenerative Sciences, Inc., (Jul. 25, 2008), available at http://www.fda.gov/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/ComplianceActivities/Enforcement/ UntitledLetters/ucm091991.htm.
48. Order of Dismissal, supra note 6, at 5.
49. Id. (Regenerative Sciences also sought a protective order alleging that FDA's inspection was an attempt to conduct unsupervised discovery, which was denied: id.).
50. Plaintiff's Motion for Summary Judgment at 14-15, United States of America v. Regenerative Sciences, LLC, et al (2011) (No. 1:10-CV-01327-RMC) (filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.) available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.com/pdf/ I%2019%20Plaintiff's%20Motion%20for%20Summary%20Judement%20010711.pdf.
51. Order of Dismissal, supra note 6, at 1.
52. Id., at 15.
53. Plaintiff's Motion for Summary Judgment, supra note 3, at 15-16.
54. U.S. DEP'T OF HEALTH & HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., News & Events: FDA Seeks Injunction Against Colorado Manufacturer of Cultured Cell Product, F.D.A. (Jun. 6, 2010), http://www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm221656.htm (last updated Jun. 8, 2010) [hereinafter FDA SEEKS INJUNCTION].
55. Regenerative Sciences, Inc., Colorado Medical Clinic Welcomes Opportunity to Fight FDA in Court, PR NEWSWIRE (Aug. 9, 2010), http://www.prnewswire.com/ news-releases/colorado-medical-clinic-welcomes-opportunity-to-fight-fda-in- court-100247969.html [hereinafter RSI Welcomes Opportunity to Fight].
56. FDA SEEKS INJUNCTION, supra note 43.
57. Regenerative Sciences and FDA - FAQs, REGENEXX™ (2010), http://www.regenexx.com/wp-content/uploads/2010/08/Regenerative-Science-FAQs-8. 21.10.pdf at 2-3.
58. Plaintiff's Motion for Summary Judgment, supra note 3.
59. Plaintiff's Motion to Dismiss Defendants' Counterclaims, United States of America v. Regenerative Sciences, LLC, et al, (2011) (No. 1:10-CV-01327-RMC) (Filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.), available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.com/pdf/ I%2020%20Plaintiff's%20Motion%20to%20Dismiss%20Defs'%20Counterclaims%20010711. pdf.
60. Plaintiff's Motion for Summary Judgment, supra note 3, at 2.
61. Id., at 2-3.
62. Plaintiff's Motion to Dismiss Defendants' Counterclaims, supra note 48, at 3.
63. At the end of August 2011, the District Court issued an Order to Show Cause, asking for submissions from the U.S. on the interpretation of the definition of "drug" in 21 U.S.C. §§ 321(g)(1)(B)&(C): Order to Show Cause, United States of America v. Regenerative Sciences, LLC, et al, (2011) (No. 1:10-CV-01327-RMC) (Filed Aug. 29, 2011) (U.S. Dist. Ct. D.C.), available at http://app4.websitetonight.com/projects2/7/0/7/5/815707/uploads/ 2011-09-USAvsRSI-OrderToShowCause.pdf. The Order compares the definition of "drug" with the definition of "device" in 21 U.S.C. §§ 321(h), which includes an article that "does not achieve its primary intended purposes through chemical action ... and which is not dependent upon being metabolized for the achievement of its primary intended purposes." The Order states that the definitions "immediately raise the question of why the Court should not interpret the meaning of the word 'drug' to include not only an article for use in diagnosis, etc., and intended to affect the structure or function of a patient, but also an article that 'achieve[s] its primary intended purposes through chemical action' and which is 'dependent upon being metabolized for the achievement of its primary intended purposes.'" The United States therefore is ordered to show cause why the definition of "device" should not inform and restrict the definition of "drug." This line of questioning raises broader questions about whether cell therapies, and indeed all biologics, fall within the definition of a "drug."
64. This is an unexpected approach to the dispute with potentially "far reaching implications" which are not yet clear: Suzan Onel, Michael H. Hinckle & Karl M. Nobert, Culture Stem Cells for Autologous Use: Practice of Medicine or FDA Regulated Drug and Biological Product? (Sep. 19, 2011), http://www.klgates.com/cultured-stem-cells-for-autologous-use-09-19-2011.
65. 21 U.S.C. §§ 321(g)(1)(B), 321(g)(1)(C).
66. Id., at § 321(g)(1)(D).
67. REGENEXX™, http://www.regenexx.com (last visited Jun. 23, 2011).
68. Public Health Service Act, 42 U.S.C. § 262(i) [emphasis added].
69. U.S. DEP'T OF HEALTH AND HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., APPLICATION OF CURRENT STATUTORY AUTHORITIES TO HUMAN SOMATIC CELL THERAPY PRODUCTS AND GENE THERAPY PRODUCTS, 58(197) Fed. Reg. 53248-51, 53249 (1993) [hereinafter FDA, APPLICATION OF CURRENT STATUTORY AUTHORITIES].
70. United States of America v. Loran Medical Systems, Inc., et al., 25 F. Supp. 2d 1082 (C.D. Cal. 1997);
71. U.S. DEP'T OF HEALTH AND HUMAN SERVICES, FOOD AND DRUG ADMIN., CENTER FOR BIOLOGICS EVALUATION AND RESEARCH, GUIDANCE FOR INDUSTRY: GUIDANCE FOR HUMAN SOMATIC CELL THERAPY AND GENE THERAPY (Mar. 1998), available at http://www.fda.gov/downloads/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/ ucm081670.pdf [hereinafter FDA, GUIDANCE FOR HUMAN SOMATIC CELL THERAPY];
72. Dina Gould Halme & David A. Kessler, FDA Regulation of Stem-Cell-Based Therapies, 355(16) NEW ENG. J. MED. 1730 (2006);
73. Donald W. Fink, et al., FDA Regulation of Stem Cell Based Products, 324 SCIENCE 1662 (2009).
74. 42 U.S.C. § 262(a)(2)(C); see also Food and Drugs, 21 C.F.R. pts. 600, 601, 610.
75. 42 U.S.C. § 264(a).
76. U.S. FOOD AND DRUG ADMIN., PROPOSED APPROACH TO REGULATION OF CELLULAR AND TISSUE-BASED PRODUCTS, 62 Fed. Reg. 9721, (Feb. 28, 1997), available at http://www.fda.gov/downloads/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/Guidances/Tissue/UCM062601.pdf [hereinafter FDA, PROPOSED APPROACH TO REGULATION].
77. 21 C.F.R. § 1271 subpt. B.
78. Id., at § 1271 subpt. C.
79. Id., at § 1271 subpt. D.
80. HCT/Ps are exempt from these regulations if they are removed from an individual and implanted "into the same individual during the same surgical procedure": id. at § 1271.15(b). Regenerative Sciences asserts that the same-day version of the Regenexx treatment, Regenexx-SD, is exempt from regulation under this provision: FAQ's, supra note 8. This seems to be stretching the plain meaning of "same surgical procedure" given that the process involves harvesting the sample in the morning, taking the sample to the lab for processing, then the patient returning to the Clinic in the afternoon for the injection procedure: Regenexx-SD Procedure, supra note 11. For the time being, however, FDA does not appear to be challenging this claimed exemption.
81. 21 C.F.R. § 1271.20.
82. Id., at §§ 1271.10(a)(1)-1271.10(a)(3).
83. Id., at § 1271.10(a)(4).
84. Id., at § 1271.3(f)(2).
85. See Plaintiff's Motion to Dismiss Defendants' Counterclaims at 24, United States of America v. Regenerative Sciences, LLC, et al, (2011) (No. 1:10-CV-01327-RMC) (Filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.), available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.com/pdf/ I%2020%20Plaintiff's%20Motion%20to%20Dismiss%20Defs'%20Counterclaims%20010711. pdf (The legal status of FDA's interpretive statements and the effect of the statute of limitations on this counterclaim are also at issue (see id., at 24-36) but discussion of these points is beyond the scope of this article).
86. Plaintiff's Motion for Summary Judgment at 21-22, United States of America v. Regenerative Sciences, LLC, et al (2011) (No. 1:10-CV-01327-RMC) (filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.) available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.com/pdf/ I%2019%20Plaintiff's%20Motion%20for%20Summary%20Judgment%20010711.pdf.
87. Id., at 22.
88. Id., at 21-22.
89. Id., at 22.
90. A Gee, Mesenchymal Stem-Cell Therapy in a Regulated Environment, 3(5) CYTOTHERAPY 397, 397 (2001);
91. e.g. FDA, APPLICATION OF CURRENT STATUTORY AUTHORITIES, supra note 57, at 53249 (somatic cell therapy products to be regulated as biological products include "cells that have been propagated, expanded, selected, pharmacologically treated, or otherwise altered in biological characteristics");
92. FDA, PROPOSED APPROACH TO REGULATION, supra note 61, at 17 ("Examples of more-than-minimal manipulation of cells and tissues include cell expansion, encapsulation, activation, or genetic modification").
93. FDA, PROPOSED APPROACH TO REGULATION, supra note 61, at 17-18 (regarding cell selection).
94. Id., at 17; DEP'T OF HEALTH AND HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., HUMAN CELLS, TISSUE, AND CELLULAR AND TISSUE-BASED PRODUCTS; ESTABLISHMENT REGISTRATION AND LISTING (FINAL RULE) 66 Fed. Reg. 5447, 5457 (Jan. 19, 2001) (to be codified at 21 C.F.R. pt. 1271) [hereinafter FDA, HCT/P FINAL RULE].
95. For example, see the cases cited in Plaintiff's Motion for Summary Judgment, supra note 3, at 22, n. 20.
96. E.g. Horwitz & Dominici, supra note 17, at 773; Prockop et al., supra note 27.
97. Regulation (EC) 1394/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products and Amending Directive 2001/83/EC and Regulation (EC) 726/2004, 2007 O.J. (L324), 132 (Annex I) (Due to the way the Regulation is drafted, forms of manipulation equivalent to minimal manipulation (manipulation not considered to be " substantial") are listed in the Annex).
98. HEALTH CANADA, GUIDANCE DOCUMENT FOR CELL, TISSUE AND ORGAN ESTABLISHMENTS: SAFETY OF HUMAN CELLS, TISSUES AND ORGANS FOR TRANSPLANTATION, 15 (2009).
99. AUSTRALIAN GOV'T, DEPART. OF HEALTH AND AGEING THERAPEUTIC GOODS ADMIN., Regulatory Framework for Biologicals, TGA (Jun. 8, 2011), http://www.tga.gov.au/ industry/biologicals-framework.htm.
100. 21 U.S.C. § 331(a),(b).
101. Id., at § 331(k).
102. Regenerative Sciences and FDA - FAQs, supra note 46.
103. Plaintiff's Motion for Summary Judgment at 23-25, United States of America v. Regenerative Sciences, LLC, et al (2011) (No. 1:10-CV-01327-RMC) (filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.) available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.com/pdf/ I%2019%20Plaintiff's%20Motion%20for%20Summary%20Judgment%20010711.pdf.
104. E.g. RSI Welcomes Opportunity to Fight, supra note 44;
105. Regenerative Sciences and FDA - FAQs, supra note 46.
106. 42 U.S.C. § 264(a).
107. Order of Dismissal, supra note 6,;
108. see also Plaintiff's Motion to Dismiss Defendants' Counterclaims, United States of America v. Regenerative Sciences, LLC, et al, (2011) (No. 1:10-CV-01327-RMC) (Filed Jan. 7, 2011) (U.S. Dist. Ct. D.C.), available at HYMAN, PHELPS & MCNAMARA PC http://www.hpm.com/pdf/ I%2020%20Plaintiff's%20Motion%20to%20Dismiss%20Defs'%20Counterclaims%20010711. pdf.
109. FDA, PROPOSED APPROACH TO REGULATION, supra note 61, at 12; Halme & Kessler, supra note 58, at 1732.
110. García Gómez et al., supra note 13, at 1462; Shane M. Ward, Global Harmonization of Regulatory Requirements for Premarket Approval of Autologous Cell Therapies, 55 FOOD & DRUG L.J. 225-43, 231 (2000).
111. 21 C.F.R. § 1271.15(b)
112. Halme & Kessler, supra note 58, at 1732.
113. 21 C.F.R. § 1271.90(a)(1) (exempting autologous cells and tissues from donor eligibility and screening requirements).
114. Plaintiff's Opposition to Defendants' Motion to Dismiss Pursuant to Rules 12(b)(1) and 12(b)(6) of the Federal Rules of Civil Procedure, Regenerative Sciences, Inc. v. United States Food and Drug Administration, et al., (May 11, 2009) (No. 109CV00411) 2009 WL 2956106 (U.S. Dist. Ct, D. Colo.) [hereinafter Plaintiff's Opposition].
115. 21 C.F.R. § 1271.3(d) [emphasis added].
116. Plaintiff's Opposition, supra note 96;
117. Mary Ann Chirba & Stephanie M. Garfield, FDA Oversight of Autologous Stem Cell Therapies: Legitimate Regulation of Drugs and Devices or Groundless Interference with the Practice of Medicine?, VII J. HEALTH & BIOMED. L. 233, 253-54 (2011).
118. Plaintiff's Opposition, supra note 96.
119. E.g. FDA, APPLICATION OF CURRENT STATUTORY AUTHORITIES, supra note 57;
120. U.S. FOOD AND DRUG ADMIN., GUIDANCE ON APPLICATIONS FOR PRODUCTS COMPRISED OF LIVING AUTOLOGOUS CELLS MANIPULATED EX VIVO AND INTENDED FOR STRUCTURAL REPAIR OR RECONSTRUCTION; AVAILABILITY, 61(103) Fed. Reg. 26523-24 (1996) [hereinafter FDA, GUIDANCE ON APPLICATIONS).
121. See Chirba & Garfield, supra note 98, at 266 (note 208).
122. But see id. at 267, arguing that the change should be seen as substantive rather than procedural. Although it is true that the change did substantively affect the regulatory categorization of autologous cell therapies, again it must be appreciated that FDA had already made it clear, prior to the public consultations on the HCT/P framework, that autologous products would be included in its scope.
123. RSI Welcomes Opportunity to Fight, supra note 44;
124. Regenerative Sciences and FDA - FAQs, supra note 46.
125. RSI Welcomes Opportunity to Fight, supra note 44.
126. Id.; Regenerative Sciences and FDA - FAQs, supra note 46.
127. See Goodridge v. Pfizer Canada Inc., 2010 O.N.S.C. 1095, 101 O.R. (3d) 202 (Can.);
128. HEALTH CANADA, HEALTH PRODUCTS AND FOOD BRANCH, RESPONSE TO RECOMMENDATIONS TO HEALTH CANADA OF THE CORONER'S JURY INTO THE DEATH OF ASHLEY MARIE ATKINSON, (2003), available at http://www.hc-sc.gc.ca/ahc-asc/pubs/hpfb- dgpsa/death-deces-atkinson-eng.php.
129. See MEDS. AND HEALTHCARE PRODS. REG. AGENCY, Drug Safety Update: Off-Label or Unlicensed Use of Medicines: Prescribers' Responsibilities, MHRA (Apr. 2009), http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/ CON087990.
130. United States v. Evers, 453 F. Supp. 1141 (M.D. Ala. 1978);
131. U.S. DEP'T OF HEALTH & HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., 'Off-Label' and Investigational Use of Marketed Drugs, Biologics, and Medical Devices - Information Sheet, (Oct. 18, 2010), available at http://www.fda.gov/ RegulatoryInformation/Guidances/ucm126486.htm.
132. U.S. DEP'T OF HEALTH & HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., GUIDANCE FOR INDUSTRY: GOOD REPRINT PRACTICES FOR THE DISTRIBUTION OF MEDICAL JOURNAL ARTICLES AND MEDICAL OR SCIENTIFIC REFERENCE PUBLICATIONS ON UNAPPROVED NEW USES OF APPROVED DRUGS AND APPROVED OR CLEARED MEDICAL DEVICES, (Jan. 2009), available at http://www.fda.gov/RegulatoryInformation/Guidances/ucm125126.htm;
133. John E. Osborn, Can I Tell You the Truth? A Comparative Perspective on Regulating Off-Label Scientific and Medical Information, 10 YALE J. HEALTH POL'Y L. & ETHICS 299, 308-12 (2010).
134. E.g. Rebecca Dresser & Joel Frader, Off-Label Prescribing: A Call for Heightened Professional and Government Oversight, 37(3) J. L. MED. & ETHICS 476 (Fall 2009);
135. Randall S. Stafford, Regulating Off-Label Drug Use - Rethinking the Role of FDA, 358 NEW ENG. J. OF MED. 1427 (2008).
136. Dresser & Frader, supra note 111, at 478; Jacob Rogers, Freedom of Speech and FDA's Regulation of Off-Label Drug Uses, 76 GEO. WASH. L. REV. 1429.
137. FDA, HCT/P FINAL RULE, supra note 78, at 5452.
138. United States of America v. Loran Medical Systems, Inc., et al., 25 F. Supp. 2d 1082 (C.D. Cal. 1997).
139. Elie Dolgin, Survey Details Stem Cell Clinics ahead of Regulatory Approval, 16 NATURE MEDICINE 495, 495 (2010);
140. David Cyranoski, Texas Prepares to Fight for Stem Cells, 477 NATURE 377, 377 (2011) [hereinafter Cyranoski, Texas Prepares to Fight];
141. see also Cultured Autologous Stem Cell Therapy: Medical Procedure Or Drug?, STEMCELLDIGEST.NET (Aug. 22, 2010), http://www.stemcelldigest.net/ stemcell/2010/08/cultured-autologous-stem-cell-therapy-medical-procedure-or- drug.html (naming two other companies that use cultured autologous mesenchymal stem cells in patients).
142. Editorial, Regulators Must Step Up Stem Cell Oversight, 16 NATURE MEDICINE 492 (2010) [hereinafter Regulators Must Step Up].
143. See Maureen L. Condic & Mahendra Rao, Regulatory Issues for Personalized Pluripotent Cells, 26 STEM CELLS 2753 (2008);
144. Amy Zarzeczny et al., iPS Cells: Mapping the Policy Issues, 139 CELL 1032 (2009) [hereinafter Zarzeczny et al., iPS];
145. Melissa K. Carpenter & Larry A. Couture, Regulatory Considerations for the Development of Autologous Induced Pluripotent Stem Cell Therapies, 5 REGENERATIVE MEDICINE 569 (2010).
146. Cyranoski, FDA Challenges, supra note 9, at 909 (quoting Christopher Centeno).
147. Id. (quoting Douglas Sipp).
148. E.g CAT, Use of Unregulated Stem-Cell, supra note 2; Qiu, supra note 2; Lindvall & Hyun, supra note 2.
149. Doug Sipp, The Rocky Road to Regulation, NATURE REPORTS STEM CELLS (Sep. 23, 2009), http://www.nature.com/stemcells/2009/0909/090923/full/stemcells.2009. 125.html [hereinafter Sipp, Rocky Road];
150. Regulators Must Step Up, supra note 117.
151. Regulators Must Step Up, supra note 117.
152. One legal academic article discussing the case was published shortly before this article went to press: Chirba & Garfield, supra note 98.
153. E.g. Delia Wilder, Potential Arthritis Treatment Advance Blocked by FDA, LIFEEXTENSION (January 2011), http://www.lef.org/magazine/mag2011/jan2011- Potential-Arthritis-Treatment-Advance-Blocked-by-FDA-01.htm;
154. FDA Stops Stem Cells in USA, POLITICOL NEWS (Aug. 7, 2010), http://www.politicolnews.com/fda-stops-stem-cells-in-usa/ (last updated Mar. 18, 2011);
155. Heidi Stevenson, FDA Bans Stem Cell Therapy That Saved UK Boy's Life & Man's Leg, GAIA HEALTH (Aug. 14, 2010), http://www.gaia-health.com/ articles251/000288-uk-boys-life-and-mans-leg-saved-by-stem-cell-therapy-that- fda-bans.shtml.
156. Regenerative Sciences and FDA - FAQs, supra note 46;
157. Jeff Morris & L. Stephen Coles, Will FDA Kill Adult Stem Cell Medicine?, h+ MAGAZINE (May 1, 2009), http://hplusmagazine.com/2009/05/01/will- fda-kill-adult-stem-cell-medicine/;
158. Barbara Hanson, Autologous Stem Cells-Hope for the Future, GAIA HEALTH (Jun. 12, 2009), http://www.gaia-health.com/articles51/000055-Stem-Cell- Advocacy.shtml.
159. Amy Zarzeczny et al., Stem cell Clinics in the News, 28 NATURE BIOTECHNOLOGY 1243, 1245 (2010).
160. Patient Voices, ICMS: INTERNATIONAL CELLULAR MEDICINE SOCIETY, http://cellmedicinesociety.org/patients/patient-voices (last visited Jun. 25, 2011);
161. FDA Stops Stem Cells in USA, supra note 125.
162. Douglas Sipp, Stem Cell Stratagems in Alternative Medicine, 6(3) REGENERATIVE MED. 407, 411 (2011).
163. E.g. American Doctors Form Group to Oppose FDA's Stance on Adult Stem Cells, ADULT STEM CELL THERAPY BLOG (Mar. 27, 2009), http://stem-cell-therapy. blogspot.com/2009/03/american-doctors-form-group-to-oppose.html [hereinafter American Doctors Form Group to Oppose FDA];
164. FDA Stops Stem Cells in USA, supra note 125;
165. FDA Blunders Stem Cell Research, POLITICOL NEWS (Aug. 9, 2010), http://www.politicolnews.com/fda-blunders-stem-cell-research/ (stating that there is "proof" that Regenexx "works and is harmless with no side effects");
166. Patient Voices, supra note 128 (The well-established use of adult stem cell transplants in cancer treatment is sometimes cited as evidence that treatments like Regenexx, without acknowledging the differences between them - most notably that Regenexx, unlike those established treatments, is more than minimally manipulated); Hanson, supra note 126;
167. A. Rahman Ford, Why Libertarians should Care about Autologous Stem Cells, BUREAUCRASH (Mar. 14, 2011), http://bureaucrash.com/2011/03/14/why- libertarians-should-care-about-autologous-stem-cells/. Centeno also points to the many published studies reporting use of MSCs for many different conditions: see Morris & Coles, supra note 126.
168. RSI Welcomes Opportunity to Fight, supra note 44;
169. see also Jack Minor, Under Obamacare FDA Considers Person's Body a Drug, GREELEY GAZETTE (Sep. 30, 2010), http://www.greeleygazette.com/press/?p=5826 (citing Centeno as saying "FDA's issue has never been about the safety of the procedure.").
170. E.g. Ryan Abbott, Feds Challenge Stem-Cell Treatment, COURTHOUSE NEWS SERVICE (Aug. 10, 2010), http://www.courthousenews.com/2010/08/10/29439.htm; Wilder, supra note 125.
171. E.g. Patient Voices, supra note 128; Hanson, supra note 126.
172. Adult Stem Cells Now!, REGENEXX™ (Mar. 31, 2009, 12:40 PM), http://www.regenexx.com/2009/03/adult-stem-cells-now.
173. Regenerative Sciences and FDA - FAQs, supra note 46.
174. Wilder, supra note 125; Patient Voices, supra note 128; Hanson, supra note 126.
175. Hanson, supra note 126; FDA Stops Stem Cells in USA, supra note 125;
176. FDA Blunders Stem Cell Research, supra note 130;
177. FDA Tries to Shut Down Regenerative Sciences, FIGHT AGING (Aug. 9, 2010) http://www.fightaging.org/archives/2010/08/fda-tries-to-shut-down-regenerative- sciences.php; Ford, supra note 121.
178. E.g. Patient Voices, supra note 128;
179. FDA Stops Stem Cells in USA, supra note 125;
180. FDA Blunders Stem Cell Research, supra note 130.
181. Hanson, supra note 126.
182. E.g. RSI Welcomes Opportunity to Fight, supra note 44; Morris & Coles, supra note 126 (quoting Christopher Centeno);
183. see also FDA Stops Stem Cells in USA, supra note 125;
184. FDA Blunders Stem Cell Research, supra note 130.
185. Morris & Coles, supra note 126.
186. Wilder, supra note 125; FDA Stops Stem Cells in USA, supra note 125; Stevenson, supra note 125.
187. 21 C.F.R. pt. 312, subpt. I; U.S. DEP'T OF HEALTH AND HUMAN SERVICES, U.S. FOOD AND DRUG 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. pt. 312, subpt. E, which provides for expedited ("fast-track") review for drugs for life-threatening and severely debilitating illnesses.
188. E.g. Ford, supra note 130.
189. RSI Welcomes Opportunity to Fight, supra note 44.
190. Abbott, supra note 132 (quoting Christopher Centeno).
191. Minor, supra note 131 (quoting Centeno).
192. E.g. Patient Voices, supra note 128; Ford, supra note 130.
193. Regenerative Sciences and FDA - FAQs, supra note 46.
194. Minor, supra note 131 (quoting Centeno as stating that if FDA is successful, a doctor would not be able to recommend fish oil to a patient with high cholesterol because it is not an approved drug).
195. Christopher J. Centeno, Our Patients' Autologous Stem Cells are Drugs: FDA Moving Down a Dangerous Slippery Slope, AGE MANAGEMENT MEDICINE GROUP (Apr. 2010), http://www.agemed.org/AMMGejournal/April2010/ RegenerativeMedicineApril2010.aspx [hereinafter Centeno, FDA Slippery Slope].
196. Minor, supra note 131; Bob Unruh, It's Begun: Obamacare Shutters Pain Treatment, WORLDNETDAILY (Aug. 16, 2010, 9:13 PM), http://www.wnd.com/?pageId= 191177.
197. Minor, supra note 131; see also Unruh, supra note 152, (Centeno is quoted as saying that FDA's position is part of a "massive federalist move" and that "Obamacare" requires "a lot of infringement" of state authority over the practice of medicine).
198. Ford, supra note 130.
199. RSI Welcomes Opportunity to Fight, supra note 44.
200. For example, see the comments posted in response to Ed Silverman, FDA Seeks Injunction Against Stem Cell Company, PHARMALOT (Aug. 6, 2010, 4:12 PM), http://www.pharmalot.com/2010/08/fda-seeks-injunction-against-stem-cell-company/ ;
201. Patient Voices, supra note 128; Hanson, supra note 126; Wilder, supra note 125. (One article goes so far as to compare FDA regulation of autologous therapies with slavery, apparently on the basis that it would involve the "commodification" of human beings: Ford, supra note 130).
202. E.g. Minor, supra note 131; Patient Voices, supra note 128;
203. RSI Welcomes Opportunity to Fight, supra note 44.
204. Barbara von Tigerstrom, Product Regulation and the Clinical Translation of Stem Cell Research, 5 STEM CELL REVS. & REPS. 135, 137 (2009).
205. Shaker Kits and Stem Cells in a Grocery Bag, REGENEXX™ (Mar. 26, 2011, 6:34 AM), http://www.regenexx.com/2011/03/shaker-kits-and-stem-cells-in-a- grocery-bag/.
206. Fitness to Practice Panel re: Dr. Robert Theodore Henri Kees Trossel, (GEN. MED. COUNCIL, U.K.) (Sep. 29, 2010), available at http://www.gmc-uk.org/ static/documents/content/Trossel.pdf.
207. Id., at 35.
208. Administrative Complaint at paras, 19-20, Department of Health v. Zannos G. Grekos (D.O.H. Case No. 2010-14317) (Mar. 14, 2011), available at http://www.circare.org/pd/grekos-20110314.pdf;
209. see Liz Freeman, Bonita Doctor Seeks State Hearing on Stem Cell Therapy, Bone Marrow Practice, NAPLES NEWS (Mar. 20, 2011, 6:30 PM), http://www. naplesnews.com/news/2011/may/20/Zannos-Grekos-stem-cell-Regenocyte-Therapeutic- lee/;
210. Doug Sipp, Regenocyte's Grekos' License Restricted over Patient Death, STEM CELL TREATMENT MONITOR (Apr. 30, 2011, 2:26 AM), http://sctmonitor. blogspot.com/2011/04/regenocytes-grekos-loses-medical.html.
211. However, it was reported recently that the Texas Medical Board is considering the adoption of a policy on stem cell treatments: see Cyranoski, Texas Prepares to Fight, supra note 116, 378.
212. E.g. Alessandro Blasimme, Panel Presentation at Bringing Regenerative Medicine to the Clinic: Trials and Tribulations in Europe and Beyond, Regenerative Medicine in Europe (REMEDiE) Closing Conference, Stem Cells in Translation: Self-Governance and Public Accountability in the Quest for Regenerative Medicine, (Apr. 19, 2011) (a copy of the presentation is on file with the author).
213. RSI Welcomes Opportunity to Fight, supra note 44.
214. Regenerative Sciences and FDA - FAQs, supra note 46;
215. INT'L CELLULAR MED. SOCIETY, LAB PRACTICES GUIDELINES: VERSION 1.0, (Apr. 15, 2009), available at http://www.cellmedicinesociety.org/attachments/055- ICMS%20Lab%20Practices%20Guidelines.pdf.
216. ICMS Board of Directors, ICMS: INTERNATIONAL CELLULAR MEDICINE SOCIETY, http://www.cellmedicinesociety.org/home/boards-and-councils/board-of- directors〉 (last visited Jun. 25, 2011).
217. Slematix™ Obtains Exclusive License to Regenexx™, supra note 28.
218. LAB PRACTICES GUIDELINES: VERSION 1.0, supra note 166.
219. ICMS Institutional Review Board (IRB), ICMS: INTERNATIONAL CELLULAR MEDICINE SOCIETY, http://www.cellmedicinesociety.org/home/boards-and-councils/ irb (last visited Jun. 25, 2011).
220. ICMS Frequently Asked Questions, ICMS: INTERNATIONAL CELLULAR MEDICINE SOCIETY, http://www.cellmedicinesociety.org/home/faqs (last visited Jun. 25, 2011).
221. Sipp, Rocky Road, supra note 122.
222. Adult Stem Cells Now!, supra note 134;
223. American Doctors Form Group to Oppose FDA, supra note 130.
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239. ISSCR GUIDELINES, supra note 189;
240. Insoo Hyun et al., New ISSCR Guidelines Underscore Major Principles for Responsible Translational Stem Cell Research, 3 CELL STEM CELL 607 (2008).
241. For example, one report is based on 28 patients with hip injuries followed for 6 months and 12 followed for 12 months: see Regenerative Sciences, Regenexx, supra note 7 at 21.
242. The Clinic also provides other types of treatment: see the Clinic's website at CENTENO-SCHULTZ CLINIC, http://www.centenoschultz.com/ (last visited Jun. 25, 2011). Information on the Regenexx website indicates that physical therapy or other "conservative care" will often be recommended: FAQ's, supra note 8.
243. Regenerative Sciences, Regenexx, supra note 7, at 13-14, 21.
244. See the recent review by Irene Tracey, Gelling the Pain You Expect: Mechanisms of Placebo, Nocebo and Reappraisal Effects in Humans, 16 NATURE MED. 1277 (2010) (Notably, "More expensive placebo treatments produce significantly more placebo analgesia than less expensive ones" id., at 1282).
245. See Jonathan Kimmelman, Francoise Baylis & Kathleen Cranley Glass, Stem Cell Trials: Lessons from Gene Transfer Research, HASTINGS CENTER REPORTS 23, 25-26;
246. Insoo Hyun, Allowing Innovative Stem Cell-Based Therapies Outside of Clinical Trials: Ethical and Policy Challenges, 38(2) J. L. MED. & ETHICS 277, 281(2010).
247. Centeno, FDA Slippery Slope, supra note 151.
248. Regenerative Sciences and FDA - FAQs, supra note 46.
249. Karinne Ludlow, Diana M. Bowman & Dwayne D. Kirk, Hitting the Mark or Falling Short with Nanotechnology Regulation?, 27(11) TRENDS IN BIOTECHNOLOGY 615, 615 (2009).
250. Karen Martell, Alan Trounson & Elona Baum, Stem Cell Therapies in Clinical Trials: Workshop on Best Practices and the Need for Harmonization, 7(4) CELL STEM CELL 451, 451 (2010);
251. Sebastian C. Sethe, The Implications of "Advanced Therapies" Regulation, 13 REJUVENATION RESEARCH 327, 327 (2010).
252. U.S. DEP'T OF HEALTH & HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., STRATEGIC PRIORITIES 2011-2015: RESPONDING TO PUBLIC HEALTH CHALLENGES IN THE 21ST CENTURY, at 2 (2011), available at http://www.fda.gov/downloads/AboutFDA/ ReportsManualsForms/Reports/UCM252092.pdf.
253. Fink et al., supra note 58, at 1662.
254. Id.; Jeffrey L. Fox, FDA Scrutinizes Human Stem Cell Therapies, 26(6) NATURE BIOTECHNOLOGY 598, 599 (2008);
255. Robert A. Preti, Bringing Safe and Effective Cell Therapies to the Bedside, 23(7) NATURE BIOTECHNOLOGY 801, 802 (2005).
256. Preti, supra note 207, at 802.
257. Fink et al., supra note 58, at 1663; Fox, supra note 207, at 599; COMMITTEE FOR ADVANCED THERAPIES AND CAT SCIENTIFIC SECRETARIAT, Challenges with Advanced Therapy Medicinal Products and How to Meet Them, 9 NATURE REVS. DRUG DEV. 195, 197 (2010).
258. E.g. U.S. DEP'T OF HEALTH AND HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., CENTER FOR BIOLOGICS EVALUATION AND RESEARCH, GUIDANCE FOR INDUSTRY: POTENCY TESTS FOR CELLULAR AND GENE THERAPY PRODUCTS, (Jan. 2011), available at http://www.fda.gov/downloads/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/ UCM243392.pdf [hereinafter FDA, GUIDANCE ON POTENCY TESTS];
259. U.S. DEP'T OF HEALTH AND HUMAN SERVICES, U.S. FOOD AND DRUG ADMIN., CENTER FOR BIOLOGICS EVALUATION AND RESEARCH, GUIDANCE FOR FDA REVIEWERS AND SPONSORS: CONTENT AND REVIEW OF CHEMISTRY, MANUFACTURING, AND CONTROL (CMC) INFORMATION FOR HUMAN SOMATIC CELL THERAPY INVESTIGATIONAL NEW DRUG APPLICATIONS (INDs) (Apr., 2008), available at http://www.fda.gov/downloads/ BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/ Xenotransplantation/ucm092705.pdf;
260. FDA, GUIDANCE FOR HUMAN SOMATIC CELL THERAPY, supra note 58.
261. Fink et al., supra note 58, at 1663.
262. E.g. FDA, APPLICATION OF CURRENT STATUTORY AUTHORITIES, supra note 57;
263. FDA, GUIDANCE ON APPLICATIONS, supra note 100.
264. 21 C.F.R. § 1271.90(a)(1).
265. Chris Mason & Peter Dunnill, Assessing the Value of Autologous and Allogeneic Cells for Regenerative Medicine, 4(6) REGENERATIVE MED. 835 (2009).
266. Centeno, FDA Slippery Slope, supra note 151.
267. Ward, supra note 92, at 232.
268. Carpenter & Couture, supra note 118, at 577; Angela Osborne, Overcoming Manufacturing and Financial Challenges of Personalised Cell Therapies, 4(22) PHARMACEUTICAL TECH. EUROPE 30 (2010).
269. E.g. FDA, GUIDANCE FOR HUMAN SOMATIC CELL THERAPY, supra note 58, at 11.Ward, supra note 92, at 232-33, 237;
270. R. Botta & G. Migliaccio, Cell-Based Treatments: Advanced Therapies and Transplants, 43 TRANSPLANTATION PROCEEDINGS 338, 339 (2011).
271. Mason & Dunnill, supra note 214, at 845; Carpenter & Couture, supra note 118, at 570.
272. Condic & Rao, supra note 118, at 2755-56.
273. Mason & Dunnill, supra note 214, at 844.
274. Amy Zarzeczy et al., iPS, supra note 118, at 1036.
275. Stevenson, supra note 125 ("each individual case in which a person's stem cells are used is considered a different drug. That means... that a full drug approval process must be undergone each time stem cells are taken and grown for use on that same person.").
276. FDA, GUIDANCE ON POTENCY TESTS, supra note 210, at 3.
277. August 22, 1997 Approval Letter by U.S. FOOD AND DRUG ADMIN. to Tim Surgenor for Carticel, (Aug. 22, 1997), available at http://www.fda.gov/ BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm171702. htm;
278. April 29, 2010 Approval Letter from U.S. FOOD AND DRUG ADMIN. to Dendreon Corporation for Provenge, (Apr. 29, 2010): http://www.fda.gov/ BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210215. htm;
279. June 21, 2011 Approval Letter by U.S. FOOD AND DRUG ADMIN, to Jeanne M. Novak for Laviv, (June 21, 2011), available at http://www.fda.gov/ BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm260486. htm.
280. EUROPEAN MEDICINES AGENCY: EVALUATION OF MEDICINES FOR HUMAN USE, ASSESSMENT REPORT FOR CHONDROCELECT, (No. EMEA/H/C/00878) (2009), available as http://www.ema.europa.eu/docs/en-GB/document-library/EPAR---Public-assessment- report/human/000878/WC500026035.pdf.
281. Mesoblast Receives TGA Regulatory Approval to Commercially Manufacture Adult Stem Cell Products, MESOBLAST (Jul. 21, 2010), http://www.mesoblast.com/ download/178/.
282. Carpenter & Couture, supra note 118, at 577.
283. 21 C.F.R. pt. 312, subpt. I; FDA, EXPANDED ACCESS TO INVESTIGATIONAL DRUGS, supra note 143.
284. Id., at § 1271.60(d).
285. 21 U.S.C. § 353a.
286. Id., at § 353a(b)(1)(A).
287. Regulation (EC) 1394/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products and Amending Directive 2001/83/EC and Regulation (EC) 726/2004, 2007 O.J. (L324), art. 28.
288. Id., at art. 28(2).
289. ISSCR GUIDELINES, supra note 194, at 4-5.
290. Hyun, supra note 199, at 282-83 (also discussing off-label use as another way in which innovative treatment can occur outside clinical trials); von Tigerstrom, supra note 158, at 136-37.
291. Centeno, FDA Slippery Slope, supra note 151.
292. E.g. ISSCR GUIDELINES, supra note 194, at 5.
293. Chad A. Landmon & Tara R. Rahemba, Human Tissue and Stem Cell Therapies: Revolutionary New Therapies that Face Increasing FDA Scrutiny, 2010(6) UPDATE 16, 19 (2010).
294. Mason & Dunnill, supra note 214, at 848.
295. Alex John London, Jonathan Kimmelman & Marina Elena Emborg, Beyond Access p. Protection in Trials of Innovative Therapies, 328 SCIENCE 829 (2010).
296. See e.g. Martell, Trounson & Baum, supra note 204, at 451; Sethe, supra note 204, at 328; Preti, supra note 207, at 803.