Biologics revolution: The intersection of biotechnology, patent law, and pharmaceutical regulation

Georgetown Law Journal

Volumn 98, Issue 2, 2010, Pages 535-564

  Tam, Joyce Wing Yan ^a  

^a NONE

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EID: 77749254924     PISSN: 00168092     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (251)

1. Ingrid Kaldre, The Future of Generic Biologics: Should the United States "Follow-On" the European Pathway?, DUKE L. & TECH. REV., Nov. 6, 2008, ¶¶ 1-2, http://www.law.duke.edu/journals/dltr/articles/2008dltr0009.html.
2. Huub Schellekens, Follow-On Biologics: Challenges of the "Next Generation," NEPHROLOGY DIALYSIS TRANSPLANTATION, May 2005, at iv31, iv31.
3. Andrew Wasson, Taking Biologics for Granted? Takings, Trade Secrets, and Off-Patent Biological Products, DUKE L. & TECH. REV., Mar. 1, 2005,¶ 1, ¶ 2, http://www.law.duke.edu/ journals/dltr/articles/2005dltr0004.html.
4. Alan J. Morrison, Biosimilars in the United States: A Brief Look at Where We Are and the Road Ahead, 26 BIOTECHNOLOGY L. REP. 463, 464 (2007).
5. See, e.g., Donna M. Gitter, Innovators and Imitators: An Analysis of Proposed Legislation Implementing an Abbreviated Approval Pathway for Follow-On Biologics in the United States, 35 FLA. ST. U. L. REV. 555, 562 (2008).
6. See Gregory N. Mandel, The Generic Biologies Debate: Industry's Unintended Admission That Biotech Patents Fail Enablement, VA. J. L. & TECH., Fall 2008, ¶ 1, ¶ 8.
7. Id. ¶ 9.
8. See, e.g., Press Release, AARP, AARP: Biologics Bill Will Lower Prices of Most Expensive Drugs (Mar. 11, 2009), available at http://www.aarp.org/aarp/presscenter/pressrelease/articles/Biologics-Bill- Introduction.html.
9. See, e.g., Press Release, Biotechnology Indus. Org., New Proposed Biosimilars Pathway Filled With Potholes (Mar. 11, 2009), available at http://www.bio.org/news/pressreleases/newsitem.asp?id=2009-0311-02.
10. See WENDY H. SCHACHT & JOHN R. THOMAS, FOLLOW-ON BIOLOGICS: INTELLECTUAL PROPERTY AND INNOVATION ISSUES, CRS RL 33901, at 7-8 (2009) (describing the debate over the level of data and clinical trials necessary for abbreviated approval of FOBs).
11. Id. at 7; Mandel, supra note 6, ¶ 76.
12. See Mandel, supra note 6, ¶ 70.
13. Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984).
14. JOHN R. THOMAS, PHARMACEUTICAL PATENT LAW 348 (2005).
15. Id. at 350.
16. Kiernan Murphy & Kaitlin Mara, Industry Pushes for Biosimilars Approval Process; Some IGOs Take Notice (Feb. 24, 2009), http://www.ip-watch. org/weblog/2009/02/24/industry-pushes-for-biosimilars-approval-process-some- igos-take-notice/.
17. Gary C. Messplay & Colleen Heisey, Follow-On Biologics: The Evolving Regulatory Landscape, BIOEXECUTIVE INT'L, May 2006, at 42, 44.
18. Linda Hull Felcone, The Long and Winding Road to Biologic Follow-Ons, BIOTECHNOLOGY HEALTHCARE, May 2004, at 20, 29.
19. Mandel, supra note 6, ¶ 19.
20. 21 U.S.C. § 355 (2006).
21. 42 U.S.C. § 262(a)(1) (2006); Gitter, supra note 5, at 563-64.
22. Mandel, supra note 6, ¶ 33.
23. Id. ¶ 38.
24. THOMAS, supra note 14, at 7-9 (describing the approval process from initial testing to approval of the NDA).
25. Michael Dickson & Jean Paul Gagnon, Key Factors in the Rising Cost of New Drug Discovery and Development, 3 NATURE REVS. 417, 418 fig.1 (2004).
26. Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 669-70 (1990).
27. Mandel, supra note 6, ¶ 23.
28. Id.
29. Rebecca S. Eisenberg, The Role of the FDA in Innovation Policy, 13 MICH. TELECOMM. TECH. L. REV. 345, 357-58 (2007) (describing the lobbying efforts by pioneer and generic drug companies leading up to the passage of the Hatch-Waxman Act).
30. Patent Fairness Act of 1999: Hearing on H.R. 1598 Before the H. Subcomm. on Courts and Intellectual Property of the H. Comm. on the Judiciary, 106th Cong. 2-3 (1999) (statement of the Biotechnology Industry Organization), available at http://www.bio.org/ip/positions/tstm070199. asp.
31. Matthew Avery, Continuing Abuse of the Hatch-Waxman Act by Pharmaceutical Patent Holders and the Failure of the 2003 Amendments, 60 HASTINGS L.J. 171, 171-72 (2008).
32. Sarah Eurek, Hatch-Waxman Reform and Accelerated Market Entry of Generic Drugs: Is Faster Necessarily Better?, DUKE L. & TECH. REV., Aug. 13, 2003, ¶ 1, http://www.law.duke.edu/ journals/dltr/articles/2003dltr0018.html.
33. Douglas Robinson, Recent Administrative Reforms of the Hatch-Waxman Act: Lower Prices Now in Exchange for Less Pharmaceutical Innovation Later?, 81 WASH. U. L. Q. 829, 830 (2003).
34. THOMAS, supra note 14, at 308.
35. See JOHN THOMAS, PROPRIETARY RIGHTS IN PHARMACEUTICAL INNOVATION: ISSUES AT THE INTERSECTION OF PATENTS AND MARKETING EXCLUSIVITIES, CRS RL 33288, at 6 (2006).
36. See Eurek, supra note 32, ¶ 2 (noting that generic drug companies must wait for innovators' patents to expire before initiating FDA approval process, creating a significant delay for market entry of the generic product).
37. Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98-417, 98 Stat. 1585 (codified as amended at 21 U.S.C. §§ 271(e), 335 (2006)).
38. See Eurek, supra note 32, ¶ 2.
39. LAURENCE J. KOTLIKOFF, STIMULATING INNOVATION IN THE BIOLOGICS INDUSTRY 10 (2008), available at http://people.bu.edu/kotlikoff/New%20Kotlikoff%20Web%20Page/ Kotlikoff-Innovation-in-Biologics21.pdf. The study was funded by Teva Pharmaceuticals, one of the largest generic pharmaceutical companies in the world.
40. THOMAS, supra note 14, at 285. Under the Act, a patent proprietor may obtain an extension equal to one-half of the period between the Investigational New Drug Application and the New Drug Application plus the entirety of the FDA review period. Id.
41. Id. at 284-85.
42. Id. at 300.
43. Mandel, supra note 6, ¶ 26.
44. David Bickart, Developments in Pharmaceutical and Biotech Patent Law, in PRACTISING LAW INSTITUTE, PHARMACEUTICAL AND BIOTECH PATENT LAW 208, 215 (2008).
45. Id. at 218.
46. THOMAS, supra note 14, at 311.
47. Id.
48. Id.
49. Id. at 312.
50. Id. at 349.
51. 35 U.S.C. § 156(f)(2)(A) (2006). "The term 'drug product' means the active ingredient of a new drug, antibiotic drug, or human biological product (as those terms are used in the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act)." Id. (emphasis added).
52. Gitter, supra note 5, at 575-76. The FDA will not approve section 505(b)(2) applications for biologic products originally approved under PHSA, which includes most biologics. Id. at 580.
53. Id. at 580.
54. Mandel, supra note 6, ¶ 43 (citing S. REP. No. 105-43 (1997)).
55. Id. 144.
56. Gitter, supra note 5, at 576. In approving the section 505(b)(2) application for the FOB, Omnitrope, the FDA warned that the agency's action did not mean that other "more complex and/or less well understood" FOBs could obtain FDA approval using the same pathway. Id. at 580.
57. A. Taylor Corbitt, The Pharmaceutical Frontier: Extending Generic Possibilities to Biologic Therapies in the Biologics Price Competition and Innovation Act of 2007, 18 DEPAUL J. ART TECH. & INTELL. PROP. L. 365, 379-80 (2008).
58. Gitter, supra note 5, at 575-76; Kaldre, supra note 1, ¶ 11.
59. Michael Kleinberg & Kristen Wilkinson Mosdell, Current and Future Considerations for the New Classes of Biologicals, 61 AM. J. OF HEALTH-SYSTEM PHARMACY 695, 695 (2004); Kaldre, supra note 1, ¶¶ 11-13.
60. Scott Gottlieb, Biosimilars: Policy, Clinical, and Regulatory Considerations, 65 AM. J. OF HEALTH-S YSTEM PHARMACY S2, S5 (2008).
61. Morrison, supra note 4, at 465.
62. Gitter, supra note 5, at 602-03.
63. Id. at 592.
64. Id.
65. Id. at 591-92.
66. GENERIC PHARM. ASS'N, BIOPHARMACEUTICALS ("FOLLOW-ON" PROTEIN PRODUCTS): SCIENTIFIC CONSIDERATIONS FOR AN ABBREVIATED APPROVAL PATHWAY 10 (2004), available at http://www.gphaonline.org/sites/default/files/ GPhA%20White%20Paper%20on%20Generic%20Biopharmaceuticals.pdf.
67. Id. at 11-12.
68. Gitter, supra note 5, at 595.
69. Steven Sklar, Corporate Counsel, Leydig, Voit & Mayer, Ltd., Congress Debates The Future of Generic Biologics (Sept. 2007), http://www.leydig.com/ publications/articles-publications-25.
70. Id.
71. Hogan & Hartson LLP, Regulation of "Biosimilars" in the European Union, EU BULLETIN, Jun. 18, 2004, at 2, http://www.hhaw.com/files/Publication/f8bed036-dc7b-42c6-a4a0-b2776a956014/ Presentation/PublicationAttachment/07fe85f-a0d5-4ccc-a96f-afec79554fbd/ 1475-040618-reg-biosimilars-eubulletin.pdf.
72. Biotechnology Indus. Org., BIO Principles on Follow-On Biologics (Mar. 26, 2007), http://bio.org/healthcare/followonbkg/Principles.asp.
73. Id.; see Kaldre, supra note 1, ¶ 11 (discussing the complexity of biologics).
74. Meenu Wadhwa & Robin Thorpe, Unwanted Immunogenicity: Implications for Follow-On Biologicals, 41 DRUG INFO. J. 1, 3 (2007).
75. See Gopi Shakar et al., Scientific and Regulatory Considerations on the Immunogenicity of Biologies, 24 TRENDS IN BIOTECHNOLOGY 274, 274 (2006).
76. Gitter, supra note 5, at 605.
77. Id. at 604.
78. Id. at 604-05.
79. Id. at 605.
80. The Law of Biologic Medicine: Hearing Before the S. Comm. on the Judiciary, 108th Cong. 10 (2004) (statement of Dr. Lester M. Crawford, then-Acting Commissioner, FDA).
81. Erwin A. Blackstone & Joseph P. Fuhr Jr., Generic Biopharmaceutical Drugs: An Economic and Policy Analysis, BIOTECHNOLOGY HEALTHCARE, Feb. 2007, at 43, 45, available at http://www.biotechnologyhealthcare.com/journal/fulltext/4/1/BH0401043. pdf.
82. See Safe and Affordable Biotech Drugs: The Need for a Generic Pathway: Hearing Before the H. Comm. on Oversight and Government Reform, 110th Cong. 80 (2007) (statement by Dr. William Schwieferman, independent consultant) ("[T]he evidence clearly demonstrates that comparability processes soundly support the approval of biogenetics without the need for large and questionable clinical trials...."); GENERIC PHARM. ASS'N, supra note 66, at 7.
83. Rebecca Eisenberg, The Shifting Functional Balance of Patents and Regulation, 19 HEALTH AFF. 119,120 (2001).
84. Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980) (internal citations omitted).
85. The enablement requirement is embodied in 35 U.S.C. § 112 (2006), which reads, "The specification shall contain a written description of the invention, and of the manner and process of making and using it in such full, clear, concise, and exact terms as to enable any person skilled in the art ... to make and use the same...."; see also Mandel, supra note 6, ¶ 22.
86. THOMAS, supra note 14, at 208.
87. Id.
88. Mandel, supra note 6, ¶ 72.
89. See, e.g., Biotechnology Indus. Org., supra note 72.
90. Id.
91. Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750 F.2d 1569,1576 (Fed. Cir. 1984).
92. Mandel, supra note 6,174.
93. Biotechnology Indus. Org., supra note 72.
94. See In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988) (laying out the eight-factor test to determine whether experimentation is unduly burdensome, commonly known as "the Wand factors").
95. See In re Wright, 999 F.2d 1557,1562-63 (Fed. Cir. 1993).
96. Bruce S. Manheim Jr., Patricia Granahan & Kenneth J. Dow, 'Follow-On Biologics': Ensuring Continued Innovation in the Biotechnology Industry, 25 HEALTH AFF. 394, 399 (2006).
97. See Mandel, supra note 6,175.
98. Dale L. Carlson, Katarzyna Przychodzen & Petra Scamborova, Patent Linchpin for the 21st Century? - Best Mode Revisited, 45 IDEA 267, 269 (2005).
99. Manheim, supra note 96, at 398.
100. Id.
101. THOMAS, supra note 14, at 464.
102. Festo v. Shoketsu Kinzoku Kogyo Kabushiki, 344 F.3d 1359, 1366-67, 1374 (Fed. Cir. 2003). This is known as prosecution history estoppel.
103. See Kaldre, supra note 1, ¶ 20.
104. Paul Chamberlain, Biogenerics: Europe Takes Another Step Forward While the FDA Dives for Cover, 9 DRUG DISCOVERY TODAY 817, 818 (2004);
105. see also Council Directive 2004/27, 2004 O.J. (L 136) 34 (EC).
106. See European Meds. Agency [EMEA], Human Medicines, http://www.emea.europa.eu/index/indexh1.htm (last visited Aug. 12, 2009).
107. EMEA, Comm. for Medicinal Prods. for Human Use (CHMP), Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues, at 4, EMEA Doc. CHMP/BWP/49348/2005 (Feb. 22, 2006).
108. EMEA, Questions and Answers on Biosimilar Medicines (Similar Biological Medicinal Products), EMEA Doc. 74562/2006 Rev. 1 (Oct. 22, 2008).
109. R. F. Kingham & E. Lietzan, Current Regulatory and Legal Considerations for Follow-On Biologics, 84 CLINICAL PHARMACOLOGY & THERAPEUTICS 633, 634 (2008).
110. EMEA, supra note 106, at 3-4.
111. Kaldre, supra note 1,121.
112. See EMEA, supra note 107.
113. EMEA, CHMP, Guideline on Similar Biological Medicinal Products, at 4, EMEA Doc. CHMP/437/04 (Oct 30,2005).
114. Messplay & Heisey, supra note 17, at 44.
115. EMEA, CHMP, Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical Issues, at 4-6, EMEA Doc. CHMP/BMWP/42832/2005 (Feb. 22, 2006).
116. Kaldre, supra note 1, ¶¶ 22-23.
117. Andrzej Wiecek & Ashraf Mikhail, European Regulatory Guidelines for Biosimilars, NEPHROLOGY DIALYSIS TRANSPLANTATION, October 2006, at v17, v19.
118. Suzanne M. Sensabaugh, Biological Generics: A Business Case, 4 J. GENERIC MED. 186, 188 (2007), available at http://www.palgrave-journals.com/jgm/journal/v4/n3/pdf74950067a.pdf.
119. Kingham & Lietzan, supra note 108, at 634.
120. See About Health Canada Main Page, http://www.hc-sc.gc.ca/ahc-asc/ index-eng.php (last visited Aug. 12, 2009).
121. HEALTH CAN., DRAFT GUIDANCE FOR SPONSORS: INFORMATION AND SUBMISSION REQUIREMENTS FOR SUBSEQUENT ENTRY BIOLOGICS (SEBs) § 1.1 (Mar. 27, 2009), http://www.hc-sc.gc.ca/dhp-mps/consultation/biolog/2009-03- seb-pbu-notice-avis-eng.php.
122. Id. § 1.4.
123. Id.
124. Id. § 2.3.1.4.
125. Id. § 2.1.3.
126. Id. § 1.2.
127. Id. § 2.3.1.
128. Id. §§ 2.1.4, 2.3.1.4. The reference drug must have been previously authorized for sale in Canada.
129. Id. § 2.3.1.1.
130. Id. § 1.5.
131. Id. §§ 1.5 & 2.1.2.
132. Id. § 2.3.1.1.
133. The consultation period closed on May 26, 2009. Health Can., Notice - Release of a Revised Version of the Draft Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics (SEBs) (Mar. 27, 2009), http://www.hc-sc.gc.ca/dhp-mps/consultation/biolog/2009-03-seb-pbu-notice-avis- eng.php.
134. Health Can., Questions and Answers to Accompany the Release of the Subsequent Entry Biologics Guidance Document, http://www.hc-sc.gc.ca/dhp-mps/ consultation/biolog/2009-03-seb-pbu-qa-qr-eng.php (last visited Aug. 12, 2009).
135. HEALTH CAN., supra note 120, § 1.3.4; Health Can., supra note 133.
136. Posting of Donald Zuhn to Patent Docs, http://www.patentdocs.org/2009/04/ third-followon-biologics-bill-introduced.html (Apr. 1, 2009, 23:52 EST).
137. H.R. 1427, 111th Cong. (2009).
138. S. 726, 111th Cong. (2009).
139. Consumer, Business and Labor Groups Endorse Bipartisan Senate Bill Authorizing Biogenerics, PR NEWSWIRE, Mar. 26, 2009, available at http://www.redorbit.com/news/health/1661113/consumer-business-and-labor- groups-endorse-bipartisan-senate-bill-authorizing/.
140. H.R. 1548, 111th Cong. (2009).
141. Lynne Taylor, New U.S. Biogenetics Bill Offers 14 Years' Market Exclusivity, March 20, 2009, http://www.eatg.org/eatg/Global-HIV-News/EMEA- FDA/New-US-biogenerics-bill-offers-14-years-market-exclusivity.
142. Press Release, Rep. Anna Eshoo, Reps. Eshoo, Inslee, and Barton Introduce Pathway for Biosimilars Act (Mar. 17, 2009), available at http://eshoo.house.gov/index.php?option=com-content&task=view&id= 581&Itemid=79.
143. See Press Release, Rep. Henry A. Waxman, Bipartisan Group of Members Introduces "Promoting Innovation and Access to Life-Saving Medicines Act" (Mar. 11, 2009), available at http://waxman.house. gov/News/DocumentSingle.aspx?DocumentID= 115183.
144. H.R. 1427, 111th Cong. § 3(a)(2) (2009); see also H. Comm. on Energy & Commerce, Detailed Outline of the Promoting Innovations and Access to Life-Saving Medicine Act (March 11, 2009), available at http://energycommerce.house.gov/Press-111/20090311/hr1427-detailedsummary.pdf (last visited Apr. 2, 2009).
145. H.R. 1427 § 3(a)(2).
146. Id.
147. Id.
148. See H. Comm. on Energy & Commerce, supra note 143.
149. Id.
150. H.R. 1427, 111th Cong. § 3(a)(2) (2009); Hogan & Hartson LLP, Waxman Bill Creates Risks, Opportunities, PHARMACEUTICAL AND BIOTECHNOLOGY UPDATE, Mar. 16, 2009, http://www.hhlaw.com/ files/Publication/eff54d95-647b-4157-8520-0539f8301935/Presentation/ PublicationAttachment/a63a8b58-2f97-4997-bdae-140582431d50/PharmaBioUpdate- March2009.pdf.
151. H.R. 1427 § 3(a)(2).
152. H.R. 1548, 111th Cong. § 101(a)(2) (2009).
153. Id. (emphasis added).
154. Id.
155. Id.
156. Id. (emphasis added).
157. Id.
158. Id.
159. THOMAS, supra note 14, at 349.
160. Id. at 348.
161. Eisenberg, supra note 29, at 355.
162. THOMAS, supra note 35, at 20.
163. Id. at 14.
164. THOMAS, supra note 14, at 349.
165. 21 U.S.C. § 355(j)(5)(F)(iv) (2006). This also applies to any salt or ester of a previously FDA-approved active ingredient. § 355(j)(5)(F)(v).
166. THOMAS, supra note 14, at 350.
167. Martin Sipkoff, FDA Approach to Generics May Be a Mixed Blessing, MANAGED CARE, Feb. 2008, at 20, available at http://www.nxtbook.com/nxtbooks/medimedia/managedcare-200802/(last visited Aug. 22, 2009).
168. Bickart, supra note 44, at 291.
169. Id. at 291-92.
170. THOMAS, supra note 14, at 353.
171. Id.
172. THOMAS, supra note 35, at 7.
173. THOMAS, supra note 14, at 354.
174. Id.
175. Id.
176. Id.
177. Emily Waltz, Western Biotechs Ponder Follow-On Possibilities, 26 NATURE BIOTECHNOLOGY 962, 962 (2008).
178. The Generic Biologics Debate Heats Up with Introduction of Rival House Bill, LIFE SCIENCES ALERT (Crowell & Moring LLP, Washington, D.C.), Mar. 24, 2009, http://www.crowell.com/NewsEvents/ Newsletter.aspx?id=1189.
179. THOMAS, supra note 14, at 637.
180. THOMAS, supra note 35, at 15-16.
181. Id. at 16.
182. Id.
183. Id.
184. THOMAS, supra note 14, at 637.
185. HEALTH CAN., DATA PROTECTION UNDER C.08.004.1 OF THE Food and Drug Regulations § 3 (2009).
186. Id. § 3.1.
187. Id. § 3.2.
188. See James N. Czaban & Robert J. Scheffel, Wiley Rein LLP, Waxman Bill Brings Controversial New Concepts and Questions to Biosimilars Debate (Mar. 13, 2009), http://www.wileyrein.com/publications.cfm?sp= articles&id=4587.
189. Hogan & Hartson LLP, supra note 149, at 1-2.
190. Czaban & Scheffel, supra note 187.
191. Id.
192. Id.
193. H.R. 1427, 111th Cong. § 3(a)(2) (2009).
194. Id.
195. Id.
196. H.R. 1548, 111th Cong. § 101(a)(2) (2009).
197. Id.
198. KOTUKOFF, supra note 39, at 6.
199. Laurence Kotlikoff, Op-Ed, Clearing the Way for Low-Cost Biogenerics, BOSTON GLOBE, Oct 26, 2008, available at http://www.boston.com/bostonglobe/editorial-opinion/oped/articles/2008/ 10/26/clearing-the-way-for-low-cost-biogenerics/.
200. THOMAS, supra note 35, at 13.
201. Codified in 35 U.S.C. § 156 (2006).
202. Pathway for Biosimilars Act Protects Patients, Promotes Competition, Preserves Innovation and Creates Quality Jobs, Lilly Says, PR NEWSIRE, Mar. 17, 2009, http://www.bloomberg.com/apps/news?pid= conewsstory&refer=conews&tkr=LLY%3AUS&sid=acyg5iSk5xz4.
203. Sensabaugh, supra note 117, at 189.
204. Id.
205. See, e.g., SCHACHT & THOMAS, supra note 10, at 23.
206. See, e.g., Crowell & Moring LLP, supra note 177.
207. Henry Grabowski, Follow-On Biologics: Data Exclusivity and the Balance Between Innovation and Competition, 7 NATURE REVS. DRUG DISCOVERY 479, 486 (2008), available at http://fds.duke.edu/db?attachment-25-1301-view-503.
208. Id. at 487.
209. Id. at 486.
210. Posting of Donald Zuhn to Patent Docs, http://www.patentdocs.org/2008/11/ white-paper-from-former-house-ways-and-means-economist-finds-7year-data- exclusivity-period-to-be-suf.html (Nov. 20, 2008, 23:49 EST).
211. ALEXANDER BRILL, PROPER DURATION OF DATA EXCLUSIVITY FOR GENERIC BIOLOGICS: A CRITIQUE 4, 11 (2008), http://www.tevadc.com/Brill-Exclusivity-in- Biogenerics.pdf.
212. Tufts Ctr. for the Study of Drug Dev., Average Cost To Develop a New Biotechnology Product Is $1.2 Billion, Nov. 9, 2006, http://csdd.tufts.edu/NewsEvents/NewsArticle.asp?newsid=69.
213. Tufts Ctr. for the Study of Drug Dev., Innovative R & D Strategies Remain Key to Developing New Medicines, Jan. 5, 2005, http://csdd.tufts. edu/NewsEvents/RecentNews.asp?newsid=51.
214. Grabowski, supra note 206, at 482.
215. See ELAINE WHITMORE, DEVELOPMENT OF FDA-REGULATED MEDICAL PRODUCTS: PRESCRIPTION DRUGS, BIOLOGICS, AND MEDICAL DEVICES 47 fig. 4.1, 48 fig. 4.2 (2004).
216. Tufts Ctr. for the Study of Drug Dev., supra note 212.
217. See DRUG AND BIOLOGICAL DEVELOPMENT 18 (Ronald P. Evens ed., 2007) (writing that lost sales awaiting regulatory review costs the company an average of $1.3 million per day).
218. See H.R. 1427, 111th Cong. § 3(a)(2) (2009); H.R. 1548, 111th Cong. § 101(a)(2) (2009).
219. Posting of Kurt R. Karst to FDA Law Blog, http://www.fdalawblog.net/fda- law-blog-hyman-phelps/2009/03/rep-waxman-introduces-followon-biologics-bill- legislation-hews-closely-to-hatchwax-man-exclusivity-pa.html (Mar. 11, 2009, 11:15 EST).
220. Id.
221. H.R. 1548 § 101(a)(2).
222. Id.
223. Sensabaugh, supra note 117, at 189.
224. See, e.g., KOTUKOFF, supra note 39, at 4.
225. Mark J. Belsey et al., Biosimilars: Initial Excitement Gives Way to Reality, 5 NATURE REVS. DRUG DISCOVERY 535, 535 (2006).
226. Cathy Dombrowski, Most Biosimilars Would Need Clinical Trials, ASCO Tells House Panel, PINK SHEET, Jun. 9, 2008, available at http://www.fdalegislativewatch.com/2008/06/most-biosimilar.html.
227. Gitter, supra note 5, at 604.
228. See H. COMM. ON ENERGY AND COMMERCE, Q's AND A's ON THE "PROMOTING INNOVATION AND ACCESS TO LIFE-SAVING MEDICINE ACT" 1 (2009), http://energycommerce.house.gov/Press-111/20090311/ Generic%20Biologics%20Q%20and%20A.pdf.
229. H.R. 1427, 111th Cong. § 3(a)(2) (2009).
230. HEALTH CAN., supra note 120, §§ 1.2, 2.1.3.
231. Id. § 2.3.1.4.
232. Kaldre, supra note 1, ¶ 21.
233. EMEA, supra note 106, at 4.
234. H.R. 1548, 111th Cong. § 101(a)(2) (2009).
235. See H.R. 1427, 111th Cong. § 3(a)(2) (2009) (but incorporating the explicit immunogenicity requirement of the Eshoo bill).
236. See H.R. 1427 § 3(a)(2).
237. See EMEA, supra note 106, at 4.
238. See H.R. 1548 § 101(a)(2).
239. See HEALTH CAN., supra note 120, § 2.3.1.4.
240. See H.R. 1427 § 3(a)(2).
241. Manheim, supra note 96, at 396.
242. See id.
243. See id. at 401.
244. See id.
245. See H.R. 1427, 111th Cong. § 3(a)(2) (2009).
246. See H.R. 1548, 111th Cong. § 101(a)(2) (2009).
247. See H.R. 1427 § 3(a)(2).
248. Thomas Gryta, Generic Biologics Face Hurdles, WALL ST. J., Mar. 4, 2009, available at http://online.wsj.com/ article/SB123614292238326905.html.
249. See SCHACHT & THOMAS, supra note 10, at 14.
250. Id.
251. U.S. CONST, art. I, § 8.