Global harmonization of regulatory requirements for premarket approval of autologous cell therapies

Food and Drug Law Journal

Volumn 55, Issue 2, 2000, Pages 225-243

  Ward, Shane M ^a  

^a Intracel Corp   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL PRODUCT;

ADOPTIVE IMMUNOTHERAPY; DRUG APPROVAL; DRUG LEGISLATION; DRUG MARKETING; DRUG SCREENING; GOVERNMENT; HUMAN; HUMAN CELL; INTERNATIONAL STANDARD UNIT; MARKETING; MEDICAL INFORMATION; PRACTICE GUIDELINE; PUBLIC HEALTH; REVIEW; UNITED STATES;

CELL TRANSPLANTATION; DRUG APPROVAL; EUROPEAN UNION; HUMANS; INTERNATIONAL COOPERATION; JAPAN; MODELS, THEORETICAL; TRANSPLANTATION, AUTOLOGOUS; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 0033938613     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (138)

1. Pub. L. No. 57-244, 32 Stat. 728 (1902).
2. Ch. 288, 37 Stat. 309 (1912) (codified at 42 U.S.C. §§ 201 et seq. (1997)).
3. Pub. L. No. 75-717, 51 Stat. 1040 (1938) (codified as amended 21 U.S.C §§ 301 et seq. (1994)).
4. See Stephen R. Scott, United States: Introduction, in GLOBAL BIOTECHNOLOGY PRODUCT REGISTRATION: E.U., U.S., AND JAPAN 271, 272 (Mark-Michael Struck et al. eds., 1997).
5. FDA has stated that "human organ transplants could possibly be regulated as drugs, devices, or biological products, [but] [i]t is . . . by no means clear that such an interpretation would be consistent with the legislative intent underlying the definitions or that it would withstand judicial challenge." PETER BARTON HUTT & RICHARD A. MERRILL, FOOD AND DRUG LAW: CASES AND MATERIALS 696 (2d ed. 1991) (quoting Hearing Before the Subcomm. on Sci. and Tech., 98th Cong. (1983) (statement by FDA concerning its legal authority to regulate human organ transplants and to prohibit their sale)).
6. See Edward L. Korwek, Human Biological Drug Regulation, in 2 FUNDAMENTALS OF LAW AND REGULATIONS, VOLUME II: AN IN-DEPTH LOOK AT THERAPEUTIC PRODUCTS 323, 351 (David G. Adams et al. eds., 1997) (citing United States v. Evers, 453 F. Supp. 1141 (D. Ala, 1978), aff'd, 643 F.2d 1043 (5th Cir. 1981) as a case applying the 'practice of medicine' exception to new drug regulations).
7. See id. at 345.
8. Id. at 352.
9. See Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair or Reconstruction, 61 Fed. Reg. 26, 523 (May 28, 1996).
10. See id. at 26, 527.
11. FDA, GUIDANCE FOR HUMAN SOMATIC CELL THERAPY AND GENE THERAPY 3 (Mar. 1998).
12. CBER, TISSUE ACTION PLAN (Mar. 15, 1998).
13. FDA, PROPOSED APPROACH TO REGULATION OF CELLULAR AND TISSUE-BASED PRODUCTS 9 (Feb. 28, 1997). The availability of this document was announced at 62 Fed. Reg. 9721 (1997).
14. Establishment Registration and Listing of Manufacturers of Human Cellular and Tissue-Based Products, 63 Fed. Reg. 26, 744 (1998).
15. Id. at 26, 746.
16. See id. at 26, 746-7.
17. See Annex to Regulation 2309/93, as amended 1993 O.J. (L 214/1) and 1998 O.J. (L 88/7).
18. Commission Communication on the Community Marketing Authorization Procedures for Medicinal Products, 1998 O.J. (C 229) 5.
19. See EMEA, CONCEPT PAPER ON THE DEVELOPMENT OF A COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS, POINTS TO CONSIDER ON HUMAN SOMATIC CELLULAR THERAPY (Feb. 25, 1999).
20. CPMP, Points to Consider on Human Somatic Cellular Therapy, CPMPBWP/41450/98 Draft (Dec. 16, 1999).
21. See id. at 2.
22. See infra Section III.B.2.
23. See infra note 106 and accompanying text.
24. See TOSHIE TSUCHIYA & AKITADA NAKAMURA, RESEARCH AND REGULATORY SITUATIONS OF TISSUE ENGINEERING IN JAPAN, at 5 (available from Division of Medical Devices, National Institute of Hygienic Sciences, Tokyo, Japan).
25. See WILLIAM J.C. CURRIE, NEW DRUG APPROVAL IN JAPAN 55 (1995).
26. See TSUCHIYA & NAKAMURA, supra note 24, at 5 (For "autogeneic cell products . . . each product is different and the present approval system is not applicable. Therefore, we need a new system for those.").
27. See Hirome Okabe, Japan, in GLOBAL BIOTECHNOLOGY PRODUCT REGISTRATION: E.U., U.S., AND JAPAN 146, 162-163 (1997).
28. See id.
29. See TSUCHIYA & NAKAMURA, supra note 24, at 5.
30. See New Materials Japan, Genzyme Starts Clinical Trials of Autologous Cartilage in Japan, Sept. 1, 1999, available in LEXIS Japan Country Files, IAC-ACC-NO: 55603979.
31. See TSUCHIYA & NAKAMURA, supra note 24, at 5.
32. See Sharon Smith Holston, An Overview of International Cooperation, 52 FOOD & DRUG L.J. 197, 197-199 (1997).
33. See Linda R. Horton, Phillip Chao, Walla Dempsey & Eric Flamm, International Harmonization of the Regulation of Drugs and Biologics, in FUNDAMENTALS OF LAW AND REGULATION, VOLUME II: AN IN-DEPTH LOOK AT THERAPEUTIC PRODUCTS 437, 451 (David G. Adams et al. eds., 1997).
34. Id.
35. See id. at 452-3.
36. Id.
37. Id. at 453.
38. See id.
39. See id. at 453-4
40. See id. at 454-5.
41. See generally Smith Holston, supra note 32.
42. GUIDANCE FOR HUMAN SOMATIC CELL THERAPY AND GENE THERAPY, supra note 11.
43. See id.
44. See FDA Talk Paper, FDA Grants Accelerated Approval to Help Repair Damaged Knee Cartilage, Aug. 25, 1997, at 1.
45. See Scott D. Gillogly, Michael Voight & Tab Blackburn, Treatment of Articular Cartilage Defects of the Knee With Autologous Chondrocyte Implantation, 28 J. ORTHOP. SPORTS PHYS. THER. 241 (Oct. 1998).
46. See Hans Smola et al., Alternative Delivery of Keratinocytesusing a Polyurethane Membrane and the Implications for its Use in the Treatment of Full-Thickness Burn Injury, 24 BURNS 7 (Feb. 1998).
47. See Scott P. Bruder et al., Mesenchymal Stem Cells in Osteobiology and Applied Bone Regeneration, CLIN. ORTHOP. S247 (Oct. 1998).
48. See Phillip K. Li, Effective Treatment of High-Grade Lymphoproliferative Disorder After Renal Transplantation Using Autologous Lymphocyte Activated Killer Cell Therapy, 32 AM. J. KIDNEY DIS. 813 (Nov. 1998).
49. See Richard K. Burt & Anne E. Traynor, Hematopoietic Stem Cell Therapy of Autoimmune Diseases, 5 CURR. OPIN. HEMATOL. 472 (Nov. 1998).
50. See Jan B. Vermorken et al., Active Specific Immunotherapy for Stage II and Stage III Human Colon Cancer: A Randomized Trial, 353 LANCET 345 (Jan. 1999).
51. PROPOSED APPROACH TO REGULATION OF CELLULAR AND TISSUE-BASED PRODUCTS, supra note 13, at 9.
52. See id. at 12.
53. See GUIDANCE FOR HUMAN SOMATIC CELL THERAPY AND GENE THERAPY, supra note 11, at 7-11; PROPOSED APPROACH TO REGULATION OF CELLULAR AND TISSUE-BASED PRODUCTS, supra note 13, at 15.
54. See GUIDANCE FOR HUMAN SOMATIC CELL THERAPY AND GENE THERAPY, supra note 11, at 7-11; PROPOSED APPROACH TO REGULATION OF CELLULAR AND TISSUE-BASED PRODUCTS, supra note 13, at 15.
55. See ICH, Guidance on Specifications: Test Procedures and Acceptance Criteria for Biotechnological/ Biological Products, 64 Fed. Reg. 44,928, 44,933 (1999).
56. See Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair or Reconstruction, supra note 9.
57. CPMP, Points to Consider on Human Somatic Cellular Therapy, supra note 20, at 9.
58. See Martha A. Wells, Overview of FDA Regulation of Human Cellular and Tissue-Based Products, 52 FOOD & DRUG L.J. 401 (1997).
59. CBER, POINTS TO CONSIDER IN HUMAN SOMATIC CELL THERAPY AND GENE THERAPY (1991).
60. Application of Current Statutory Authorities to Human Somatic Cell Therapy Products and Gene Therapy Products, 58 Fed. Reg. 53,248 (1993).
61. Id. at 53,251.
62. See Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair or Reconstruction, supra note 9.
63. See Knee Cartilage Repair - Accelerated Approval of Autologous Cell Therapy, WORLD HEALTH ORGANIZATION PHARMACEUTICALS NEWSLETTER (World Health Org., Geneva, Switzerland), Nov. and Dec. 1997, at 1.
64. Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair or Reconstruction, supra note 9, at 6.
65. Id. at 6-7.
66. Id. at 9.
67. Id.
68. FDA, GUIDANCE FOR THE SUBMISSION OF CHEMISTRY, MANUFACTURING AND CONTROLS INFOFMATION AND ESTABLISHMENT DESCRIPTION FOR AUTOLOGOUS SOMATIC CELL THERAPY PRODUCTS (Jan. 1997).
69. WILLIAM J. CLINTON & ALBERT GORE, REINVENTING THE REGULATION OF HUMAN TISSUE, NATIONAL PERFORMANCE REVIEW (Feb. 1997).
70. PROPOSED APPROACH TO REGULATION OF CELLULAR AND TISSUE-BASED PRODUCTS, supra note 13, at 9.
71. See FDA Unveils New Plan to Regulate Human Tissues, 349 LANCET 784 (Mar. 15, 1997).
72. Id. at 14 (emphasis in the original).
73. Id. at 17.
74. See id. at 18-19.
75. TISSUE ACTION PLAN, supra note 12.
76. Id. at 2.
77. See id. at 4.
78. GUIDANCE FOR HUMAN SOMATIC CELL THERAPY AND GENE THERAPY, supra note 11.
79. Establishment Registration and Listing of Manufacturers of Human Cellular and Tissue-Based Products, supra note 14.
80. See id. at 26,754.
81. See International Conference on Harmonization; Guidance on Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, 64 Fed. Reg. 44,928 (1999).
82. Id. at 44,930.
83. See Fernand Sauer, A New and Fast Drug Approval System in Europe, 31 DRUG INFO. J. 1, 2 (1997).
84. See EMEA, FOURTH GENERAL REPORT (1998).
85. Id.
86. In a concept paper, the EMEA noted that "rapid development in the cell biology and biotechnology fields has opened new possibilities to use somatic cells for therapeutic purposes. . . [and] fee present guideline issued by the CPMP relating to somatic gene therapy. . . does not fully cover all aspects of somatic cell therapy." EUROPEAN AGENCY FOR EVALUATION OF MEDICINAL PRODUCTS, Concept Paper on the Development of a Committee for Proprietary Medicinal Products, Points to Consider on Human Somatic Cell Therapy (Feb. 25, 1999).
87. Council Directive 89/341/EEC 1989 O.J. (L 142) 11, as corrected by 1989 O.J. (L 176) 55; Council Directive 89/342/EEC 1989 O.J. (L 142) 14; Council Directive 89/343/EEC 1989 O.J. (L 142) 14; Council Directive 89/381/EEC 1989 O.J. (L 181) 44.
88. Council Directive 65/65/EEC 1965 O.J. (L 22); Council Directive 75/318/EEC 1975 O.J. (L 147) 1; Second Council Directive 75/319/EEC 1975 O.J. (L 147) 13; Commission Directive 91/507/EEC 1991 O.J. (L 270) 32.
89. Mark-Michael Struck, European Union, in GLOBAL BIOTECHNOLOGY PRODUCT REGISTRATION: E.U., U.S., AND JAPAN 5 (1997).
90. See Introduction, EMEA NEWSLETTER (EMEA London, UK), Nov. 3997, at 2.
91. See FOURTH GENERAL REPORT, supra note 84, at 73-7. Significant research has failed to produce any evidence that an ACT has been approved through the EMEA as of March 2000.
92. See, e.g., CPMP, Points to Consider on Human Somatic Cellular Therapy, supra note 20.
93. Supra note 86.
94. Id.
95. See generally CPMP, Points to Consider on Human Somatic Cellular Therapy, supra note 20.
96. Id. at 2.
97. Id. at 9.
98. Id.
99. See id. at 8.
100. Id.
101. Genzyme Tissue Repair's Carticel (autologous cultured chondrocytes) and Epicel (epidermal autograft) and AVAX's M-Vax (autologous melanoma vaccine) currently are or will be available commercially soon in one or more EU member states. See Avax's Melanoma Vaccine Nears Launch, SCRIP, Sept. 29, 1999 at 23; Genzyme Tissue Repair, Carticel A utologous Cultured Condrocytes (last visited Aug. 10, 1999) ; Genzyme Tissue Repair, Epicel Epidermal Autograft (last visited Aug. 10, 1999) .
102. Genzyme Tissue Repair's Carticel (autologous cultured chondrocytes) and Epicel (epidermal autograft) and AVAX's M-Vax (autologous melanoma vaccine) currently are or will be available commercially soon in one or more EU member states. See Avax's Melanoma Vaccine Nears Launch, SCRIP, Sept. 29, 1999 at 23; Genzyme Tissue Repair, Carticel A utologous Cultured Condrocytes (last visited Aug. 10, 1999) ; Genzyme Tissue Repair, Epicel Epidermal Autograft (last visited Aug. 10, 1999) .
103. Genzyme Tissue Repair's Carticel (autologous cultured chondrocytes) and Epicel (epidermal autograft) and AVAX's M-Vax (autologous melanoma vaccine) currently are or will be available commercially soon in one or more EU member states. See Avax's Melanoma Vaccine Nears Launch, SCRIP, Sept. 29, 1999 at 23; Genzyme Tissue Repair, Carticel A utologous Cultured Condrocytes (last visited Aug. 10, 1999) ; Genzyme Tissue Repair, Epicel Epidermal Autograft (last visited Aug. 10, 1999) .
104. See Phillipe Hervé, The Emergence of Cell Therapy in France. Public Health, Regulations and Other Controversial Issues, 39 HEMATOL. CELL THER. 189 (1997).
105. See id.
106. The Genzyme Tissue Repair website states that Carticel is "marketed in the United States and Europe." See Carticel Autologous Cultured Condrocytes, supra note 101. When the Genzyme Tissue Repair customer service telephone number was called on June 30, 1999, however, a company representative stated that the product was available commercially in the United Kingdom, France, Germany, and Italy, as well as a number of other European countries without regulatory approval.
107. See FDA Talk Paper, FDA Grants Accelerated Approval to Help Repair Damaged Knee Cartilage, (Aug. 25, 1997), at 1.
108. The Netherlands and Germany are two of the least demanding European countries in terms of regulatory requirements.
109. Avax's Melanoma Vaccine Nears Launch, supra note 101.
110. Masanobu Yamada, The Approval System for Biological Products in Japan, 31 DRUG INFO. J. 1385, 1389 (1997).
111. See CURRIE, supra note 25, at 2.
112. Okabe, supra note 27, at 163.
113. See id.
114. Although AVAX has stated that its melanoma vaccine will be commercialized there soon. See AVAX Melanoma Vaccine M-Vax Nearing Commercialization in the Netherlands, Germany and Japan, Company Press Release, (Sept. 14, 1999).
115. TSUCHIYA & NAKAMURA supra note 24, at 5.
116. See id.
117. Id. at 7.
118. See LINDA R. HORTON, INTERNATIONAL HARMONIZATION FOR DRUGS AND BIOLOGICS, presented at BIOEAST, WASHINGTON D.C., at 4 (Jan. 18, 1996).
119. See id.
120. Pub. L. No. 105-115, 111 Stat. 2296 (1997), amending 21 U.S.C. §§ 301 et seq. (1994).
121. See David G. Adams & Nathan A. Beaver, Key Provisions of the Food and Drug Administration Modernization Act of 1997 Relating to Drugs and Biologics, in FUNDAMENTALS OF LAW AND REGULATION SUPPLEMENT: AN IN-DEPTH LOOK AT THE 1997 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT 29, 49 (Richard M. Cooper ed., 1999).
122. 21 U.S.C. § 383.
123. FDA, CDER 1998 REPORT TO THE NATION, inside cover (1998).
124. See Smith Holston, supra note 32, at 197-199.
125. See id. at 199.
126. Paul M. Booth, FDA Implementation of Standards Developed by the International Conference on Harmonisation, 52 FOOD & DRUG L.J. 203, 203 (1997).
127. See Guidance on Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, supra note 81.
128. See Smith Holston, supra note 32, at 199.
129. See Booth, supra note 124, at 203.
130. See ICH, ICH Past and Future (visited Mar. 26, 2000) .
131. See Booth, supra note 124, at 204-205.
132. The Rapporteur is selected from the Topic Leaders within the six-member EWG. See ICH, The ICH Harmonisation Process (last visited Mar. 26, 2000) .
133. It should be noted that "FDA employs a notice-and-comment process in adopting ICH guidelines mere as guidance, in accordance with the agency's good guidance practices policy." Horton et al., supra note 33, at 44
134. See Booth, supra note 124, at 205; Horton et al., supra note 33, at 446.
135. Establishment Registration and Listing of Manufacturers of Human Cellular and Tissue-Based Products, supra note 14, at 26,744.
136. Pub. L. No. 105-115, 111 Stat. at 2324 (modifying FDCA § 503(g)(4)(B)(iii)).
137. See Guidance on Applications for Products Comprised of Living Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair or Reconstruction, supra note 9.
138. There are no available estimates of the number of ACTs currently in development. On December 10 and 11, 1998, however, FDA and the NCI held a conference on the topic of tumor vaccines. This demonstration of an extremely large amount of interest in a small subset of ACTs suggests that there are many products in testing now. See FDA-NCI WORKSHOP ON TUMOR VACCINES, PROGRAM BOOK (Dec. 10-11, 1998).