The regulatory sciences for stem cell-based medicinal products

doi:10.1007/s11684-014-0323-5

Front. Med.

2014, Vol. 8

Issue (2) : 190-200 https://doi.org/10.1007/s11684-014-0323-5

REVIEW

The regulatory sciences for stem cell-based medicinal products

Bao-Zhu Yuan, Junzhi Wang(

)

National Institutes for Food and Drug Control, Beijing 100050, China

Download: PDF(177 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

Keywords stem cell-based medicinal products (SCMPs) stem cell therapy (SCT) safety effectiveness standards guidelines regulatory science

Corresponding Author(s): Junzhi Wang

Issue Date: 21 May 2014

Cite this article:

Bao-Zhu Yuan,Junzhi Wang. The regulatory sciences for stem cell-based medicinal products[J]. Front. Med., 2014, 8(2): 190-200.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-014-0323-5
https://academic.hep.com.cn/fmd/EN/Y2014/V8/I2/190

Tab.1 The representative stem cell clinical trials at different phases

Tab.2 The representative Chinese stem cell companies/developers and products

Tab.3 The representative clinical trials of MSCs in China registered in www.Clinicaltrials.gov

Fig.1 Promoting stem cell regulatory sciences.

1	ISSCR Guidelines for Clinical Translation of Stem Cells. 2008
2	MP De Miguel, S Fuentes-Julián, A Blázquez-Martínez, CY Pascual, MA Aller, J Arias, F Arnalich-Montiel. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 2012; 12(5): 574−591 https://doi.org/10.2174/156652412800619950 pmid: 22515979
3	FDA. 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). 2008
4	Chinese Ministry of Health and Family Planning & China Food and Drug Control Document. Interim Regulatory Guidance: guidelines for quality control and preclinical studies of the stem cell medicinal products. 2013
5	L Elmgren, X Li, C Wilson, R Ball, J Wang, K Cichutek, M Pfleiderer, A Kato, M Cavaleri, J Southern, T Jivapaisarnpong, P Minor, E Griffiths, Y Sohn, D Wood. A global regulatory science agenda for vaccines. Vaccine 2013; 31(Suppl 2): B163−B175 https://doi.org/10.1016/j.vaccine.2012.10.117 pmid: 23598478
6	clinicaltrials.gov website
7	M Olausson. Bioengineered vascular graft with autologous stem cells: first use in the clinic. Regen Med 2012; 7(6 Suppl): 12−15 https://doi.org/10.2217/rme.12.99 pmid: 23210807
8	IH Schulman, JM Hare. Key developments in stem cell therapy in cardiology. Regen Med 2012; 7(6 Suppl): 17−24 https://doi.org/10.2217/rme.12.80 pmid: 23346572
9	TA Blenkinsop, B Corneo, S Temple, JH Stern. Ophthalmologic stem cell transplantation therapies. Regen Med 2012; 7(6 Suppl): 32−39 https://doi.org/10.2217/rme.12.77 pmid: 23210809
10	VK Prasad, KG Lucas, GI Kleiner, JA Talano, D Jacobsohn, G Broadwater, R Monroy, J Kurtzberg. Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal™) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study. Biol Blood Marrow Transplant 2011; 17(4): 534−541 pmid: 20457269
11	A Bersenev. Regenerative Medicine and Cell Therapy Industry in 2012. RegenMed Digest. 2012.
12	RA Barker. Stem cells and neurodegenerative diseases: where is it all going? Regen Med 2012; 7(6 Suppl): 26−31 https://doi.org/10.2217/rme.12.64 pmid: 23210808
13	asianscientist.com website
14	ARM Annual Report. Cellular Reprogramming and Disease Modeling. 2013. 24−26
15	A Bersenev. Regenerative Medicine and Cell Therapy Industry in 2011. RegenMed Digest. 2011
16	A Bersenev. Alliance for Regenerative Medicine’s 2012 Report. RegenMed Digest. 2012.
17	DS McMahon, H Thorsteinsdóttir, PA Singer, AS Daar. Cultivating regenerative medicine innovation in China. Regen Med 2010; 5(1): 35−44 https://doi.org/10.2217/rme.09.78 pmid: 20055687
18	Ministry of Heath Reports. Surveys of Stem Cell Clinical Studies and Uses in China. 2012
19	Chinese Ministry of Health and Family Planning & China Food and Drug Control Document. Interim Regulatory Guidance: general requirements for conducting clinical studies of the stem cell-based medicinal products. 2013
20	Chinese Ministry of Health and Family Planning & China Food and Drug Control Document. Interim Regulatory Guidance: qualification for institutions conducting studies of the stem cell-based medicinal products. 2013
21	M Dominici, K Le Blanc, I Mueller, I Slaper-Cortenbach, F Marini, D Krause, R Deans, A Keating, Dj Prockop, E Horwitz. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315−317 pmid: 16923606
22	CA Herberts, MS Kwa, HP Hermsen. Risk factors in the development of stem cell therapy. J Transl Med 2011; 9(1): 29 https://doi.org/10.1186/1479-5876-9-29 pmid: 21418664
23	EMA. Guideline on Human Cell-Based Medicinal Products. 2007
24	EMA. Reflection Paper on Stem Cell-Based Medicinal Pproducts. 2011
25	FDA. Guidance for Human Somatic Cell Therapy and Gene Therapy. 1998
26	Chinese Pharmacopoeia Commission. Chinese Pharmacopoeia. 2010 Version. Part III. Beijing: China Medical Science Press. 2010
27	Guidelines for Clinical Studies and Quality Control of Human Somatic Cells (in Chinese). 2003
28	WHO. Recommendations for the Evaluation of Animal Cell Cultures as Substrates for the Manufacture of Biological Medicinal Products and for the Characterization of Cell Banks. 2010
29	FDA. Guidance for Industry−Current Good Tissue Practice (CGTP) and Additional Requirements for Manufactures of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
30	K Tarte, J Gaillard, JJ Lataillade, L Fouillard, M Becker, H Mossafa, A Tchirkov, H Rouard, C Henry, M Splingard, J Dulong, D Monnier, P Gourmelon, NC Gorin, L Sensebé; Société Française de Greffe de Moelle et Thérapie Cellulaire. Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood 2010; 115(8): 1549−1553 https://doi.org/10.1182/blood-2009-05-219907 pmid: 20032501
31	G Lepperdinger, R Brunauer, A Jamnig, G Laschober, M Kassem. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp Gerontol 2008; 43(11): 1018−1023 https://doi.org/10.1016/j.exger.2008.07.004 pmid: 18694815
32	G Lazennec, C Jorgensen. Concise review: adult multipotent stromal cells and cancer: risk or benefit? Stem Cells 2008; 26(6): 1387−1394 https://doi.org/10.1634/stemcells.2007-1006 pmid: 18388305
33	E Närvä, R Autio, N Rahkonen, L Kong, N Harrison, D Kitsberg, L Borghese, J Itskovitz-Eldor, O Rasool, P Dvorak, O Hovatta, T Otonkoski, T Tuuri, W Cui, O Brüstle, D Baker, E Maltby, HD Moore, N Benvenisty, PW Andrews, O Yli-Harja, R Lahesmaa. High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity. Nat Biotechnol 2010; 28(4): 371−377 https://doi.org/10.1038/nbt.1615 pmid: 20351689
34	RS Wong. Mesenchymal stem cells: angels or demons? J Biomed Biotechnol 2011; 2011: 459510 https://doi.org/10.1155/2011/459510 pmid: 21822372
35	EA Rayment, DJ Williams. Concise review: mind the gap: challenges in characterizing and quantifying cell- and tissue-based therapies for clinical translation. Stem Cells 2010; 28(5): 996−1004 pmid: 20333747
36	FDA. Guidance−Potency Tests for Cellular and Gene Therapy. 2011
37	M Werner, T Mayleben, G Van Bokkelen. Autologous cell therapies: the importance of regulatory oversight. Regen Med 2012; 7(6 Suppl): 100−103 https://doi.org/10.2217/rme.12.90 pmid: 23210820
38	M Breitbach, T Bostani, W Roell, Y Xia, O Dewald, JM Nygren, JW Fries, K Tiemann, H Bohlen, J Hescheler, A Welz, W Bloch, SE Jacobsen, BK Fleischmann. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 2007; 110(4): 1362−1369 https://doi.org/10.1182/blood-2006-12-063412 pmid: 17483296
39	G Moll, I Rasmusson-Duprez, L von Bahr, AM Connolly-Andersen, G Elgue, L Funke, OA Hamad, H Lönnies, PU Magnusson, J Sanchez, Y Teramura, K Nilsson-Ekdahl, O Ringdén, O Korsgren, B Nilsson, K Le Blanc. Are therapeutic human mesenchymal stromal cells compatible with human blood? Stem Cells 2012; 30(7): 1565−1574 https://doi.org/10.1002/stem.1111 pmid: 22522999
40	US 21CFR211—Current Good Manufacturing Practice for Finished Pharmaceuticals
41	US 21CFR312—Investigational New Drug Application
42	US 21CFR610—General Biological Products Standards
43	US 21CFR1271—Human Cells, Tissues, and Cellular and Tissue-Based Products
44	US FDA. Draft Guidance—Preclinical Assessment of Investigational Cellular and Gene Therapy Products. 2012
45	US FDA. Draft Guidance—Design of Early-Phase Clinical Trials. 2013
46	B George. Regulations and guidelines governing stem cell based products: clinical considerations. Perspect Clin Res 2011; 2(3): 94−99 https://doi.org/10.4103/2229-3485.83228 pmid: 21897884
47	US Pharmacopeia<1046>Cellular and Tissue-Based Products
48	US Pharmacopeia<1043>Ancillary Materials for Cell, Gene and Tissue-engineered Products
49	MA HamburgIncreasing the Prestige of Regulatory Sciences. FDA Commissioner,s speech. 2011
50	BJ Wagner. Cell standardization: purity and potency. Regen Med 2012; 7(6 Suppl): 89−92 https://doi.org/10.2217/rme.12.69 pmid: 23210818
51	L Buckler. Why the stem cell sector must engage with social media. Regen Med 2012; 7(6 Suppl): 120−123 https://doi.org/10.2217/rme.12.95 pmid: 23210824
52	M Krampera, J Galipeau, Y Shi, K Tarte, L Sensebe; MSC Committee of the International Society for Cellular Therapy (ISCT). Immunological characterization of multipotent mesenchymal stromal cells—The International Society for Cellular Therapy (ISCT) working proposal. Cytotherapy 2013; 15(9): 1054−1061 https://doi.org/10.1016/j.jcyt.2013.02.010 pmid: 23602578

[1]	Zehong Huang, Yingying Su, Tianying Zhang, Ningshao Xia. A review of the safety and efficacy of current COVID-19 vaccines[J]. Front. Med., 2022, 16(1): 39-55.
[2]	Wei Tian, Bo Liu, Da He, Yajun Liu, Xiaoguang Han, Jingwei Zhao, Mingxing Fan, International Society for Computer Assisted Orthopaedic Surgery. Guidelines for navigation-assisted spine surgery[J]. Front. Med., 2020, 14(4): 518-527.
[3]	Guanghua Rong,Wenlin Bai,Zheng Dong,Chunping Wang,Yinying Lu,Zhen Zeng,Jianhui Qu,Min Lou,Hong Wang,Xudong Gao,Xiujuan Chang,Linjing An,Yan Chen,Yongping Yang. Cryotherapy for cirrhosis-based hepatocellular carcinoma: a single center experience from 1595 treated cases[J]. Front. Med., 2015, 9(1): 63-71.
[4]	Jonathan Skupsky, Ke-Qin Hu. Current hepatitis B treatment guidelines and future research directions[J]. Front. Med., 2014, 8(2): 145-157.
[5]	Zhi-Ruo ZHANG PhD, Jian-Qing MI MD, Zhao-Jun WEN MA, Sai-Juan CHEN MD, PhD, Zhu CHEN PhD, Long-Jun GU MD, Jing-Yan TANG MD, PhD, Shu-Hong SHEN MD, PhD, . Using sound Clinical Paths and Diagnosis-related Groups (DRGs)-based payment reform to bring benefits to patient care: A case study of leukemia therapy[J]. Front. Med., 2010, 4(1): 8-15.
[6]	Jin-Nong ZHANG MD, Bo PENG BA, Jamile WOODS MD, Wei PENG MD, PhD, . Review of recent guidelines for the management of severe sepsis and septic shock[J]. Front. Med., 2010, 4(1): 54-58.

Viewed

Full text

Abstract

Cited

Shared

Discussed