Last updated 10th July 2024: Online ordering is currently unavailable due to technical issues. We apologise for any delays responding to customers while we resolve this. For further updates please visit our website https://www.cambridge.org/news-and-insights/technical-incident
We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
Published online by Cambridge University Press: 06 January 2021
Regenerative medicine (“RM”) is a 21st century technology whose regulation has badly needed a 21st century cure. It is not clear that the 21st Century Cures Act (“Cures Act”) is that cure, but it has not been a poison. For some months prior to the passage of the Cures Act it seemed that it might be a catalyst for really endangering the field by allowing a flood of untested therapies to continue to enter the market. That, fortunately, did not happen. Thus far, the Cures Act has been a useful tonic; its effect on RM has been largely symbolic. But it has allowed the Food and Drug Administration (“FDA”) to redirect resources, and it demanded the quick adoption of guidance. That has allowed the Agency to finalize a regulatory framework that has been sorely needed. The evidentiary flexibility within the Cures Act is extremely important for the development of technologies that do not fit easily into the traditional approval rubric.
1 21st Century Cures Act of 2016, Pub. L. No. 114-225, 130 Stat. 1033, 1039 (2016).
2 See, e.g., Margaret Foster Riley, Twenty-First Century Technology with Twentieth Century Baggage: FDA Regulation of Regenerative Medicine, in FDA in the Twenty-First Century 455, 455-67 (Holly Lynch & Glenn Cohen eds., 2015).
3 Cossu, Guilio et al., Lancet Commission: Stem Cells and Regenerative Medicine, 391 Lancet 883, 989 (2017)Google ScholarPubMed.
4 Id. at 883.
5 Id.
6 See, e.g., George Q. Daley et al., Realistic Prospects for Stem Cell Therapeutics, 2003(1) Am. Soc'y Hematology 398 (2003).
7 See, e.g., Mike Pence, The Empty Promise of Embryonic Stem Cell Research, Hill (Mar. 23, 2009, 4:01 PM), http://thehill.com/blogs/congress-blog/politics/25777-the-empty-promise-of-embryonic-stem-cell-research-rep-mike-pence [https://perma.cc/44S5-MNEF]. While the Cures Act RMAT provisions do not distinguish between stem cell types, the National Institutes of Health funding provisions specifically focus on adult stem cell funding. See 21st Century Cures Act § 1001(b)(4)(D).
8 Robert S. Schwartz, Perspective: The Politics and Promise of Stem Cell Research, 355 New Eng.
J. Med. 1189 (2006).
9 See, e.g., Andrew Joseph, On the Cusp of Payoffs for Patients, Stem Cell Therapy Faces Threat from Unregulated Clinics, Stat (June 16, 2017), https://www.statnews.com/2017/06/16/stem-cell-therapy-patients-threat/ [https://perma.cc/9YUQ-SRK9]; Press Release, U.S. Food & Drug Admin., Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA's New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine (Aug. 28, 2017), https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm573443.htm [https://perma.cc/LN6C-2DMC] (“[D]ishonest actors exploit the sincere reports of the significant clinical potential of properly developed products as a way of deceiving patients and preying on the optimism of patients facing bad illnesses.”).
10 See, e.g., Sipp, Douglas et al., Marketing of Unproven Stem Cell-Based Interventions: A Call to Action, 9 Sci. Translational Med. 1, 1 (2017)CrossRefGoogle ScholarPubMed (noting providers aggressively promoted the use of stem cells for a wide range of indications); Sharon Begley, Three Patients Blinded by Stem Cell Procedure, Physicians Say, Stat (Mar. 15, 2017), https://www.statnews.com/2017/03/15/stem-cell-patients-blind-macular-degeneration/ [https://perma.cc/ZAL5-YJMB] (describing a process where stems cells were mixed with platelet-dense plasma from the patient's blood, and treated with an enzyme, and injected into patient's eyes).
11 60 Minutes: 21st Century Snake Oil (CBS television broadcast Sept. 24, 2010), https://www.youtube.com/watch?v=zupt6RoQgbM.
12 Begley, supra note 10 (noting that clinics that provide unauthorized stem cell treatments generally argue that procedures using stem cells taken from a patient's own body are treatments and not drugs subject to regulation).
13 Id.
14 Riley, supra note 2, at 460.
15 United States v. Regenerative Scis. LLC, 741 F.3d 1314 (D.C. Cir. 2014).
16 The FDA did issue a warning letter to American CryoStem Corporation in January 2018, alleging it was marketing an unapproved drug and noting significant deviations in CGMPs. See Warning Letter from U.S. Food & Drug Admin. to John S. Arnone, Chairman/Chief Exec. Officer, Am. CryoStem Corp. (Jan. 3, 2018), https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm591225.htm [https://perma.cc/V8J4-7FHL].
17 Cossu, supra note 3, at 13 (emphasizing that the cell and gene therapy industry has sharply grown recently with increased governmental and private investment and support).
18 Riley, supra note 2, at 459.
19 Public Health Service Act § 361, 42 U.S.C. § 264.
20 The final rule became effective in 2005 with the “Current Good Tissue Practice for Human Cell, Tissues, and Cellular- and Tissue-Based Product Establishments,” (the CGTP Rule). Current Good Tissue Practice for Human Cell, Tissue, and Cellular and Tissue-Based Product Establishments; Inspection and Enforcement; Final Rule, 69 Fed. Reg. 68,612, 68,680 (Nov. 24, 2004) (codified at 21 C.F.R. pt. 1271). HCT/Ps are defined as articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. These include cellular therapies and combination products consisting of cells/tissue with a device and/or drug. They do not include vascularized organs for transplant, whole blood or blood products, secreted or extracted human products (except semen).
21 See Merrill, Richard A., Human Tissues and Reproductive Cloning: New Technologies Challenge FDA, 3 House J. Health L. & Pol'y 1, 47-49 (2002)Google ScholarPubMed (explaining that the FDA found conventional tissue transplants presented low level of regulatory challenges, but found some tissue-based products raise safety or clinical performance issues, and, therefore, full premarketing safety and effectiveness review would be appropriate, as in the case of a new drug or Class III medical device).
22 21 C.F.R. § 1271.150 (2011). These cover cell and tissue recovery, donor screening and testing, processing and process controls, supplies and reagents, equipment and facilities, environmental controls, storage conditions, product receipt, pre-distribution shipment and distribution, labeling, and deviation requirements.
23 Public Health Service Act § 351.
24 See Riley, supra note 2, at 460 (noting that the FDA stated that minimally manipulated tissues, which are used for their homologous function in the person from whom they were obtained, do not require premarket approval).
25 See generally 21 C.F.R. § 1271.10 (2011).
26 Id. § 1271.20. The full criteria stated in 21 C.F.R. § 1271.10(a) are: (1) The HCT/P is minimally manipulated; (2) The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer's objective intent; (3) The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and (4) Either: (i) The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or (ii) The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and: (a) Is for autologous use; (b) Is for allogeneic use in a first degree or second-degree blood relative; or (c) is for reproductive use. Id. § 1271.10(a).
27 See U.S. Food & Drug Admin., SOPP 8004: Tissue Reference Group (Version 3) (2013), https://www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/proceduressopps/ucm349568.pdf (stating that a manufacturer may request recommendation or decision regarding the classification of an HCT/P and applicability of 21 C.F.R. § 1271.10(a) to the Tissue Reference Group).
28 See, e.g., Am. Ass'n Tissue Banks, Report of Meeting with FDA Commissioner Hamburg (Mar. 12, 2013), https://www.aatb.org/?q=printpdf/1582 (expressing that final decisions of the Tissue Reference Group failed to provide adequate details to the tissue bank regarding how a ruling was reached on a product). For recommendations of the Tissue Reference Group on specific products, see Tissue Reference Group, FDA, http://www.fda.gov/biologicsbloodvaccines/tissuetissueproducts/regulationoftissues/ucm152857.htm [https://perma.cc/69WE-H3PX] (last updated Dec. 15, 2017).
29 21 C.F.R. § 1271.3(f).
30 The U.S. Department of Health and Human Services defines adipose tissue as “a connective tissue composed of clusters of cells (adipocytes) surrounded by a reticular fiber network and interspersed small blood vessels, divided into lobes and lobules by connective tissue septa.” U.S. Dep't. Health & Human Servs., Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use, Guidance for Industry and Food and Drug Administration Staff 8 (Nov. 2017) [hereinafter Regulatory Considerations].
31 U.S. Food & Drug Admin., Proposed Approach to Regulation of Cellular and Tissue-Based Products 17 (Feb. 28, 1997), http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/UCM062601.pdf [hereinafter Proposed Approach to Regulation] (“As additional information is generated about procedures in the ‘more-than-minimal-manipulation’ category, the agency intends to consider them to be in the ‘minimal-manipulation’ category when clinical data and experience show that the procedure does not alter the biological characteristics of the cells or non-structural tissue, or the relevant structure-related characteristics of structural tissue.”).
32 See, e.g., Michael Hiltzik, The FDA Closes a Huge Loophole Used by Bogus Stem-Cell Clinics, but Delay Serious Enforcement for 3 Years, L.A. Times (Nov. 17, 2017), http://www.latimes.com/business/hiltzik/la-fi-hiltzik-fda-stem-cell-20171117-story.html (reporting some stem cell clinics attempted to circumvent the regulation by claiming that their use of liposuctioned fat to produce stem cells for the purpose of reinjecting in a patient to treat diseases must be considered as minimal manipulation of patient's own tissues).
33 21 C.F.R. § 1271.3(c).
34 Adipose Tissue, Encyc. Britannica, https://www.britannica.com/science/adipose-tissue [https://perma.cc/PKQ7-ML67] (last updated Feb. 20, 2018).
35 Regulatory Considerations, supra note 30.
36 See U.S. Dep't Health & Human Servs., Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products: Draft Guidance for Industry and Food and Drug Administration Staff (2014) [hereinafter Minimal Manipulation Draft Guidance].
37 See U.S. Dep't Health & Human Servs., Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue: Regulatory Considerations: Draft Guidance for Industry (2014) [hereinafter Adipose Tissue Draft Guidance].
38 See U.S. Dep't Health & Human Servs., Homologous Use of Human Cells, Tissues, and Cellular and Tissue-Based Products: Draft Guidance for Industry and FDA Staff (2015) [hereinafter Homologous Use Draft Guidance].
39 See id.; Adipose Tissue Draft Guidance, supra note 37; Minimal Manipulation Draft Guidance, supra note 36.
40 Adipose Tissue Draft Guidance, supra note 37, at 3.
41 Id.
42 See U.S. Dep't Health & Human Servs., Same Surgical Procedure Exception Under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception: Draft Guidance for Industry (2014). The draft guidance made it clear that this was more restrictive than minimal manipulation, and included “rinsing, cleansing, sizing, or shaping.” Id. at 3.
43 Kelly Servick, Under 21st Century Cures Legislation, Stem Cell Advocates Expect Regulatory Shortcuts, Sci. (Dec. 12, 2016), http://www.sciencemag.org/news/2016/12/under-21st-century-cures-legislation-stem-cell-advocates-expect-regulatory-shortcuts-0 [https://perma.cc/HP63-ZLWQ].
44 Discussion Document., 114th Cong. (Jan. 2015), https://archives-energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/114/Analysis/Cures/20150127-Cures-Discussion-Document.pdf.
45 Id. at § 2041(a).
46 Discussion Draft, 114th Cong. (Apr. 2015), https://archives-energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/114/20150429DiscussionDraft.pdf.
47 Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act, S. 2689, 114th Cong. (2016).
48 Press Release, Mike Coffman, U.S. Representative, Coffman Introduces REGROW Act (Mar. 17, 2016), https://coffman.house.gov/news/documentsingle.aspx?DocumentID=1257 [https://perma.cc/R4CB-S937].
49 See generally Azuma, Kentaro, Regulatory Landscape of Regenerative Medicine in Japan, 1 Current Stem Cell Rep. 118 (2015)CrossRefGoogle Scholar (detailing Japan's new regulatory framework, aimed at safe and successful RM).
50 Christopher Milne & Josephine Awatin, Growing the Regenerative Medicine Industry in Asia-Pacific with Help from Regulatory Science, Pharma Focus Asia (2016), https://www.pharmafocusasia.com/strategy/regenerative-medicine-industry [https://perma.cc/WD29-XU3V].
51 Press Release, Mike Coffman, supra note 48.
52 S. 2689 § 315B(a).
53 Id. § 315B(b)(6)-(7).
54 Id. § 315B(b)(6).
55 Id. (“The Secretary may permit continued use of such product until the Secretary completes the review of the application and makes a determination.”).
56 Opposition to the full Regrow Act accelerated pathway included the Alliance for Regenerative Medicine and the International Society for Stem Cell Research. See Letter from Edward Lanphier, Chair, All. for Regenerative Med., to Mark Kirk, U.S. Senator (Mar. 31, 2016), https://alliancerm.org/sites/default/files/ARMSenatorKirk_REGROWActletter_March2016_.pdf; Press Release, Int'l Soc'y for Stem Cell Research, ISSCR Opposes the REGROW Act (Sept. 15, 2016), http://www.isscr.org/professional-resources/news-publicationsss/isscr-news-articles/article-listing/2016/09/15/isscr-opposes-the-regrow-act [https://perma.cc/X4QD-Y5V5].
57 Turner, Leigh & Knoepfler, Paul, Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry, 19 Cell Stem Cell 154, 156 (2016)CrossRefGoogle ScholarPubMed.
58 See Press Release, Int'l Soc'y for Stem Cell Research, supra note 56.
59 See id.; Letter from Edward Lanphier to Mark Kirk, supra note 56; Andrew Joseph & Sheila Kaplan, After Criticism from Scientists, Congress Eases Its Pursuit of Faster Stem Cell Therapies, Stat (Nov. 30, 2016), https://www.statnews.com/2016/11/30/stem-cells-cures-act/ [https://perma.cc/DNA2-KLQL].
60 See Sheila Kaplan, Republicans Aim to Pass Cures Act by End of Year, but Democrats Want Changes, Sci. Am. (Nov. 29, 2016), https://www.scientificamerican.com/article/republicans-aim-to-pass-cures-act-by-end-of-year-but-democrats-want-changes/ [https://perma.cc/L465-ZCS9]; Sheila Kaplan, Winners and Losers of the 21st Century Cures Act, Stat (Dec. 5 2016), https://www.statnews.com/2016/12/05/21st-century-cures-act-winners-losers/ [https://perma.cc/DZ4HB9WL].
61 See Kaplan, Republicans Aim to Pass Cures Act, supra note 60.
62 21st Century Cures Act, Pub. L. No. 114-255, § 3033, 130 Stat. 1033, 1101-1103 (2016) (codified as amended at 21 U.S.C. § 356). The legislative language uses the term “Regenerative Advanced Therapies.” The resulting acronym “RAT” proved unpalatable for the affected industry and FDA guidance studiously refers instead to “RMATs.” See James E. Valentine & Frank J. Sasinowski, Regenerative Medicine Advanced Therapy: FDA's Newest Expedited Program Evolves to Keep Pace with Recommendations, FDA L. Blog (Sept. 27, 2017), http://www.fdalawblog.net/2017/09/regenerative-medicine-advanced-therapy-fdas-newest-expedited-program-evolves-to-keep-pace-with-recom/ [https://perma.cc/C98J-S9QF]; Regenerative Medicine Advanced Therapy Designation, FDA, https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm537670.htm [https://perma.cc/J96T-EFZH] (last updated Feb. 2, 2018).
63 As will be discussed, it is still likely a lower standard than that required for other breakthrough therapy drugs. See infra Part IV.
64 21 U.S.C. § 356.
65 Id.
66 See id. § 356g.
67 See generally 21st Century Cures Act, FDA, https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/21stCenturyCuresAct/default.htm [https://perma.cc/9JXY-LDSP] (last updated Sept. 14, 2017).
68 See Kesselheim, Aaron S. & Avorn, Jerry, New “21st Century Cures” Legislation: Speed and Ease vs Science, 317 JAMA 581, 581-82 (2017)CrossRefGoogle ScholarPubMed.
69 See, e.g., 21 U.S.C. §§ 289, 355, 520.
70 Id.
71 See id. §§ 355, 360.
72 See id. § 355.
73 Subtitle D includes §§ 3031-3038 which deal specifically with RM. Id. §§ 355, 360.
74 Id. § 360. RTT laws have garnered significant bipartisan support, often because the negative consequences are hard to understand. See Caplan, Arthur L. & Bateman-House, Alison, Should Patients in Need be Given Access to Experimental Drugs?, 16 Expert Opinion on Pharmacotherapy 1275, 1277-78 (2015)CrossRefGoogle ScholarPubMed; Zettler, Patricia J. & Greely, Henry T., The Strange Allure of State ‘Right-to-Try’ Laws, 174 JAMA Internal Med. 1885, 1885-86 (2014)CrossRefGoogle ScholarPubMed.
75 See supra Part III.A.
76 21 U.S.C. § 356.
77 Id. § 356(g)(8).
78 It was not clear how gene therapies, which have always been treated by the FDA as part of the same broader rubric (the FDA's oversight committee is the Office of Cellular, Tissue, and Gene Therapies), would fit within this definition. Gene therapies, particularly the recently developed T-cell immunotherapies, are among the most promising recent developments. They do not seem to have been considered as part of this formulation, but under its language, they could be. The FDA signaled that it would do so in Commissioner Scott Gottlieb's August 2017 statement. See Press Release, U.S. Food & Drug Admin., supra note 9. The FDA confirmed that gene therapies are eligible for RMAT designation in a November 2017 draft guidance. See U.S Food & Drug Admin., Draft Guidance for Industry: Expedited Programs for Regenerative Medicine Therapies for Serious Conditions (Nov. 2017), https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-bio-gen/documents/document/ucm585414.pdf [hereinafter FDA Draft Guidance: Expedited Programs for Regenerative Medicine].
79 21 U.S.C. § 356.
80 Id.
81 See, e.g., U.S. Food & Drug Admin., Evaluation of Devices Used with Regenerative Medicine Advanced Therapies: Draft Guidance for Industry (2017), https://www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/cellularandgenetherapy/ucm585417.pdf [hereinafter FDA Draft Guidance: Evaluation of Devices].
82 See 21 U.S.C. § 356.
83 Id.
84 Id. § 356(c)(1)(A).
85 Id. § 356(h)(9).
86 Id. § 356(h)(5).
87 See FDA Draft Guidance: Evaluation of Devices, supra note 81, at 2.
88 Id.
89 FDA Draft Guidance: Evaluation of Devices, supra note 81.
90 Alexey Bersenev, What Does the Cures Act Mean for Regulation of Cell Therapy in US?, Cell Trials (Dec. 18, 2016), http://celltrials.info/2016/12/18/cures-act/ [https://perma.cc/F8BU-YFDQ].
91 FDA Draft Guidance: Evaluation of Devices, supra note 81, at 4.
92 21 U.S.C. § 351.
93 See generally FDA Draft Guidance: Evaluation of Devices, supra note 81, at 2-4.
94 Kesselheim & Avorn, supra note 68, at 1 (“In fact, most of these data elements are already used by the FDA.”).
95 Mesoblast Gets FDA RMAT; List of 10 Total Designations So Far, Niche: Knoepfler Lab Stem Cell Blog (Dec. 26, 2017), https://ipscell.com/2017/12/mesoblast-gets-fda-rmat-list-of-10-total-designations-so-far/ [https://perma.cc/SZ3D-ANA7].
96 Michael Mezher, CBER Director Focuses on Flexibility to Advance Regenerative Medicines, RAPS (May 8, 2017), http://raps.org/Regulatory-Focus/News/2017/05/08/27503/CBER-Director-Focuses-on-Flexibility-to-Advance-Regenerative-Medicines/ [https://perma.cc/B52H-CSPB].
97 Mesoblast Gets FDA RMAT, supra note 95.
98 21 U.S.C. § 356(g).
99 Id.
100 Id. § 356.
101 See id. pt. 312(e); U.S Food & Drug Admin., Guidance for Industry: Expedited Programs for Serious Conditions – Drugs and Biologics (May 2014), https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf [hereinafter Expedited Programs for Serious Conditions].
102 FDA Draft Guidance: Expedited Programs for Regenerative Medicine, supra note 78, at 4-6, 8.
103 Id. at 3.
104 Id. at 5.
105 Id. at 6.
106 Id.
107 Id.
108 Id.
109 21 U.S.C. § 356(g).
110 Id. § 356(c).
111 Id. § 356(g).
112 FDA Draft Guidance: Expedited Programs for Regenerative Medicine, supra note 78, at 2-3.
113 Id. at 9.
114 Id. at 10.
115 Id. at 10-11.
116 Kesselheim, Aaron S., Trends in Utilization of FDA Expedited Drug Development and Approval Programs, 1987-2014: Cohort Study, 351 BMJ (h4633) 1, 4 (2015)Google ScholarPubMed.
117 Mezher, supra note 96.
118 See Bailey, Alexander M., An FDA Perspective on Preclinical Development of Cell-Based Regenerative Medicine Products, 32 Nature Biotechnology 721, 721-23 (2014)CrossRefGoogle ScholarPubMed (discussing the necessity of preclinical studies for regenerative medicine due to the complexity and novelty of the field).
119 See Linda F. Hogle, Intersections of Technological and Regulatory Zones in Regenerative Medicine, in Global Perspectives on Stem Cell Technologies 51, 52 (Aditya Bharadwaj ed., 2018); see also Rosemann, Achim & Chaisinthop, Nattaka, The Pluralization of the International: Resistance and Alter-Standardization in Regenerative Stem Cell Medicine, 46 Soc. Stud. Sci. 112, 125 (2016)CrossRefGoogle ScholarPubMed (stating that international clinical trial standards do not promote blinding).
120 Hogle, supra note 119, at 59.
121 See John L. Semple et al., In Vitro, in Vivo, in Silico: Computational Systems in Tissue Engineering and Regenerative Medicine, 11 Tissue Engineering 341, 341-56 (2005) (describing the rapid growth of the field of computational science and the new methods still being developed).
122 See Hammer, Gaël P., Avoiding Bias in Observational Studies, 106 Med. 664, 664-68 (2009)Google ScholarPubMed (discussing the inherent biases present in observational studies and how to avoid these biases).
123 Brodland, G. Wayne, How Computational Models Can Help Unlock Biological Systems, 47 Seminars Cell & Dev. Biology 62, 65 (2015)Google ScholarPubMed.
124 21st Century Cures Act, 21 U.S.C. § 356(g) (also found in Pub. L. No. 114-225, § 3033(g)(6) (2016)).
125 See discussion supra Part I.A.1.
126 Regulatory Considerations, supra note 30, at 3.
127 21 U.S.C. § 356(g) (also found in Pub. L. No. 114-225, § 3033(g)(6) (2016)).
128 Regulatory Considerations supra note 30, at 1. The guidance finalizes several previously issued draft guidances, including the 2014 guidance on minimal manipulation; the 2015 guidance on homologous use, and the 2014 guidance on human cells, tissues, and cellular and tissue-based products from adipose tissue.
129 See id. at 1-24 (detailing the criteria for homologous use and minimal manipulation as defined in 21 C.F.R. 1271.10(a)(1)-(2)).
130 Id. at 6-24.
131 Proposed Approach to Regulation supra note 31.
132 21 C.F.R. § 1271.3(f).
133 Minimal Manipulation and Homologous Use Guidance, supra note 126, at 6.
134 Id. at 6.
135 Id.
136 Id. at 7. The guidance lists bone, skin, amniotic membrane and umbilical cord, blood vessel, adipose tissue, articular cartilage, non-articular cartilage, and tendons or ligaments as structural tissue. Id. at 8. The FDA already has considerable experience with some of these tissues. See, e.g., id. at 1.
137 21 C.F.R. § 1271.3(f)(1).
138 Regulatory Consideration, supra note 30, at 9.
139 Examples of cells or non-structural tissues include reproductive cells or tissues, hematopoietic stem/progenitor cells, lymph nodes and thymus, parathyroid glands, peripheral nerve and pancreatic tissue. Id. at 13-14.
140 21 C.F.R. § 1271.3(f)(2).
141 Regulatory Consideration, supra note 30, at 14.
142 Id. at 9.
143 Id. at 10.
144 Id. at 11.
145 21 C.F.R. §§ 1271.3(c), 1271.10(a)(2).
146 Id. § 1271.10(a)(2); Regulatory Consideration, supra note 30, at 16.
147 Id. § 1271.10(a)(2); Regulatory Consideration, supra note 30, at 20.
148 Regulatory Consideration, supra note 30, at 4, 16.
149 Id. at 16.
150 Id. at 17.
151 Id. at 19.
152 Id. at 20
153 Id. at 19. This clarification is somewhat different from the previous Adipose draft guidance. Compare id. at 19, with Adipose Tissue Draft Guidance, supra note 37, at 5 (stating that injection of recovered adipose tissue into breast for purposes of augmentation is not considered non-homologous because “[t]he basic function of breast tissue is to produce milk,” which “is not a basic function of adipose tissue”).
154 Regulatory Consideration, supra note 30, at 2, 21.
155 Zachary Brennan, FDA Unveils New Regenerative Medicine Framework, RAPS (Nov. 16, 2017), http://raps.org/Regulatory-Focus/News/2017/11/16/28900/FDA-Unveils-New-Regenerative-Medicine-Framework/ [https://perma.cc/2TMA-9S57].
156 See Warning Letter from U.S. Food & Drug Admin. to Am. CryoStem Corp., supra note 16, at 1-2.
157 Id.
158 See Press Release, U.S. Food & Drug Admin., supra note 9.
