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The Legal and Regulatory Status of Biosimilars

How Product Naming and State Substitution Laws May Impact the United States Healthcare System

Published online by Cambridge University Press:  06 January 2021

Jordan Paradise
Jordan Paradise*
Affiliation:
Schering-Plough Professor of Law, Seton Hall University School of Law
*
Email: [email protected]. J.D., Chicago-Kent College of Law; B.S., University of Michigan at Ann Arbor.
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Abstract

Alongside the constitutional controversy ultimately addressed by the Supreme Court, the colossal Patient Protection and Affordable Care Act (ACA) ushered in a new paradigm for regulation of biologics by the Food and Drug Administration (FDA). Nestled within the expansive ACA, the Biologics Price Competition and Innovation Act (BPCIA) set forth an abbreviated pathway to market for “biosimilar” and “interchangeable” biological products. While the current BPCIA implementation debate focuses chiefly on the scope of scientific and technical assessments by the FDA and the effect on the emergent biosimilar industry, two issues will prove essential for determinations of access to and costs of the resulting products: how the biosimilar and interchangeable biosimilar biologics are to be named, and whether pharmacist substitution is appropriate for products the FDA deems interchangeable. This article examines the current debate surrounding the use of nonproprietary names for biosimilar biologics, as well as state efforts to reconcile automatic substitution laws for the eventual products. In particular, the article addresses the implications for patients and the United States health care system, highlighting the potential negative effect on anticipated cost-savings, hindrances for effective tracking and reporting of adverse events, and a general lack of consistency in state laws.

Type
Articles
Information
American Journal of Law & Medicine , Volume 41 , Issue 1 , March 2015 , pp. 49 - 84
Copyright
Copyright © American Society of Law, Medicine and Ethics and Boston University 2015

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References

1 Nat'l Fed'n of Indep. Bus. v. Sebelius, 132 S. Ct. 2566 (2012).

2 Patient Protection and Affordable Care Act, Pub. L. No. 111-148, 124 Stat. 119 (2010) (codified as amended in scattered sections of 26 and 42 U.S.C.).

3 Biologics Price Competition and Innovation Act of 2009, Pub. L. No. 111-148, tit. VII, §§ 7001-7003, 124 Stat. 804 (codified as amended at 21 U.S.C. §§ 355, 355c and 42 U.S.C. § 262).

4 Federal Food, Drug, and Cosmetic Act, 21 U.S.C. §§ 301-399f (2012 & Supp. I 2013).

5 U.S. Gov't Accountability Office, GAO-12-371R, Drug Pricing: Research on Savings from Generic Drug Use 10 (2012), available at http://gao.gov/assets/590/588064.pdf. However, other sources are more conservative. In 2010, an opinion editorial in the New York Times reported that the generic drug industry estimates that it has saved the United States health care system approximately $734 billion over the same period of time. Anthony D. So & Samuel L. Katz, Op. Ed., Biologics Boondoggle, N.Y. Times, Mar. 8, 2010, at A23.

6 Fed. Trade Comm'n, Emerging Health Care Issues: Follow-on Biologic Drug Competition 12 (2009).

7 Blue Cross Blue Shield of Mich., Brand-Name vs. Generic Drug Costs (2013), https://www.bcbsm.com/pdf/ps_generic.pdf.

8 So & Katz, supra note 5, at 823.

9 For example, Cerezyme, a treatment for Gaucher disease, costs $200,000 a year. Id. Erbitux, a treatment for head and neck cancer, costs $110,000 a year. Cuatrecasas, Pedro, Drug Discovery in Jeopardy, 116 J. Clinical Investigation 2837, 2840 (2006)CrossRefGoogle ScholarPubMed.

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11 Id. (citing Randi Hernandez, Strategic Channel Approaches for the Distribution of Specialty Pharmaceuticals, Specialty Pharmacy Times (Dec. 20, 2012), http://www.specialtypharmacytimes.com/news/Strategic-Channel-Approaches-for-the-Distribution-of-Specialty-Pharmaceuticals).

12 Id. (citing Biologicals Boom, Generics & Biosimilars Initiative (Feb. 15, 2013), http://www.gabionline.net/Biosimilars/Research/Biologicals-boom).

13 Cathy Dombrowski, Biosimilar Market Success May Come Down to Brand Pricing Strategies, The Pink Sheet, Feb. 17, 2014, at 11.

14 Hatch-Waxman Act, Pub. L. No. 98-417, 98 Stat. 1585 (1984) (codified in scattered sections of 15, 21, and 35 U.S.C.).

15 The FDA approved the first biosimilar product in March 2015 following extensive advisory committee hearings. Press Release, FDA, FDA Approves First Biosimilar Product Zarxio (Mar. 6, 2015), available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm.

16 For a complete description of the NDA process, see 21 U.S.C. § 355(b)(1) (2012 & Supp. I 2013).

17 Hatch-Waxman Act, Pub. L. No. 98-417, tit. I, § 101, 98 Stat. 1585 (1984) (codified as amended at 21 U.S.C. § 355 (2012 & Supp. I 2013)).

18 21 C.F.R. §§ 201.10(g)(1), 202.1(b)(1) (2014). See also Dep't Health & Human Servs. [HHS], FDA, Guidance for Industry: Product Name Placement, Size, and Prominence in Advertising and Promotional Labeling (2013), available at http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070076.pdf.

19 See Blue Cross Blue Shield of Mich., supra note 7.

20 21 U.S.C. § 355(c)(3)(F)(iii).

21 35 U.S.C. § 155A (2012).

22 See 21 U.S.C. § 355(j)(2)(A)(vii)(IV), (5)(B)(iii)-(iv).

23 35 U.S.C. § 271(e)(1).

24 21 C.F.R. § 320.1(e) (2014).

25 21 U.S.C. § 355(j)(2)(A)(i)–(iii). For the full requirements of the ANDA, see id. § 355(j).

26 Id. § 355(b)(1). The new drug approval process requires three core phases of clinical trials following a successful investigational new drug application. For a discussion of these requirements, see, for example, Paradise, Jordan, Reassessing Safety for Nanotechnology Combination Products: What Do Biosimilars Add to Regulatory Challenges for the FDA?, 56 St. Louis U. L.J. 465, 479-483 (2012)Google Scholar.

27 Bioavailability is defined as “the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.” 21 C.F.R. § 320.1(a).

28 Overview of Pharmacokinetics, Merck Manual, http://www.merckmanuals.com/professional/clinical_pharmacology/pharmacokinetics/overview_of_pharmacokinetics.html (last updated May 2014).

29 Overview of Pharmacodynamics, Merck Manual, http://www.merckmanuals.com/professional/clinical_pharmacology/pharmacodynamics/overview_of_pharmacodynamics.html (last updated Sept. 2013).

30 21 U.S.C. § 355(j)(5)(A)–(E). This challenge is achieved through a “paragraph IV” certification to the FDA and subsequent litigation, where the generic sponsor asserts that the brand drug patent is not legally valid or is otherwise unenforceable. Upon such a determination of invalidity or unenforceability by a court of law, the generic drug may enter the market and receives 180-day generic exclusivity for successfully challenging the patent. Id. § 355(j)(5)(C).

31 HHS, FDA, Approved Drug Products with Therapeutic Equivalence Evaluations (34th ed. 2014) [hereinafter The Orange Book].

32 Id. at vii.

33 Id. at vi.

34 Id. at x.

35 Id. at xiii.

36 Id. at xi.

37 Constitution of the World Health Organization, July 22, 1946, 1948 U.N.T.S. 185, 188.

38 Publications, World Health Org., www.who.int/medicines/services/inn/publication/en/ (last visited Feb. 9, 2015).

39 World Health Org. [WHO], Guidelines on the Use of International Nonproprietary Names (INNs) for Pharmaceutical Substances, at 1, WHO Doc. WHO/PHARMS/NOM 1570 (1997).

40 Id.

41 See id. at 2.

42 Id. at 1.

43 Guidance on INN, WHO, www.who.int/medicines/services/inn/innquidance/en/ (last visited Feb. 9, 2015).

44 See About Us: USAN Council, Am. Med. Ass'n, www.ama-assn.org/ama/pub/physician-resources/medical-science/united-states-adopted-names-council/about-us.page? (last visited Feb. 9, 2015).

45 Rules for Coining Names, Am. Med. Ass'n, www.ama-assn.org/ama/pub/physician-resources/medical-science/united-states-adopted-names-council/naming-guidelines.page? (last visited Feb. 9, 2015).

46 Nat'l Library of Med., Generic Name Stems, Drug Info. Portal, druginfo.nlm.nih.gov/drugportal/jsp/drugportal/DrugNameGenericStems.jsp (last visited Feb. 10, 2015).

47 21 U.S.C. § 355(j)(2)(A)(v) (2012 & Supp. I 2013). Exceptions include “changes required because of differences” approved by the FDA or “because the new drug and the listed drug are produced or distributed by different manufacturers.” Id.

48 See Think INN, Prescribe INN, Dispense INN: Good Professional Practice, 50 Prescrire Int'l 184, 188 (2000).Google Scholar

49 21 U.S.C. § 353(b)(1).

50 HHS, Office of the Assistant Sec'y for Planning & Evaluation, ASPE Issue Brief: Expanding the Use of Generic Drugs 3-4 (2010), available at aspe.hhs.gov/sp/reports/2010/genericdrugs/ib.pdf (citing Al Sheppard, IMS Health, Generic Medicines: Essential Contributors to the Long-Term Health of Society, available at www.imshealth.com/imshealth/Global/Content/Document/Market_Measurement_TL/Generic_Medicines_GA.pdf).

51 See MedWatch: The FDA Safety Information and Adverse Event Reporting Program, FDA, www.fda.gov/Safety/MedWatch/ (last visited Feb. 10, 2015).

52 See id.

53 21 U.S.C. § 321(k) (2012).

54 Id. § 321(m).

55 Consideration of misbranding is to include “the extent to which the labeling or advertising fails to reveal facts material in the light of such representations or material with respect to consequences which may result from the use of the article to which the labeling or advertising relates under the conditions of use prescribed in the labeling or advertising thereof or under such conditions of use as are customary or usual.” Id. § 321(n).

56 Misbranding is tied directly to the label, where the FDA has both general authority under title 21, sections 331 to 337 of the United States Code, and specific authority for new drug misbranding violations under title 21, sections 352 and 355 of the United States Code. 21 U.S.C. §§ 331-337; id. §§ 352, 355.

57 Id. § 352(f).

58 21 C.F.R. § 201.66(c) (2014).

59 21 U.S.C. § 353(b).

60 21 C.F.R. § 201.57(c).

61 21 C.F.R. § 201.10.

62 Pharmacovigilance, WHO, www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/ (last visited Feb. 10, 2015).

63 21 C.F.R. § 314.80(c)(1)(iii).

64 Id. § 314.80(c).

65 Id. § 314.80(a).

66 Id.

67 Id.

68 Id.

69 In addition to filing these reports to the FDA, drug manufacturers must also file field alert reports with local field offices within three days. Field alert reports relay manufacturing problems typically involving imminent health risks. The field report is linked to the principles of good manufacturing practices rather than labeling issues. These reports often involve product quality issues. For example, the detection of bacterial contamination within a product sample would require a field alert report. Id. § 314.81(b)(1).

70 Id. §314.80(c)(1)(i).

71 See id. § 314.80(d)(1).

72 Id. § 314.80(c)(1)(ii).

73 Id.

74 Id. § 314.80(c)(2)(i).

75 Id.

76 Id. § 314.80(c)(2)(ii)(c).

77 Id. § 314.81(b)(2).

78 Id.

79 Id. § 314.80(f)(1).

80 See HHS, FDA, Form FDA 3500A (2015).

81 See id. at 1.

82 21 C.F.R. § 314.80(i).

83 Id. § 314.80(j).

84 See HHS, supra note 80, at 3.

85 See MedWatcher, https://medwatcher.org/register (last visited Feb. 10, 2015).

86 FDA Adverse Event Reporting System (FAERS), FDA, www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ (last updated Sept. 8, 2014).

87 See id.; Postmarket Drug and Biologic Safety Evaluations, FDA, www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/ucm204091.htm (last updated Jan. 2, 2015).

88 See FDA Adverse Event Reporting System (FAERS), supra note 86; Managing Drug Safety Issues, FDA, www.fda.gov/ForConsumers/ConsumerUpdates/ucm107846.htm (last updated Oct. 14, 2014).

89 Food and Drug Administration Amendments Act of 2007, Pub. L. No. 110-85, 121 Stat. 823 (codified as amended in scattered sections of 21 U.S.C.).

90 See 21 U.S.C. §§ 355(o)–(p), 355-1 (2012 & Supp. I 2013).

91 Id. § 355-1(a).

92 Id. § 355-1.

93 Id. § 352(y)–(z); see also id. § 333(f)(4).

94 Id. § 355(k).

95 Id. § 355(j)(2)(A)(v).

96 See Abbreviated New Drug Application Regulations, 57 Fed. Reg. 17950, 17961 (Apr. 28, 1992).

97 21 C.F.R. § 314.70 (2014). The “0” refers to the immediacy, or zero-day lead time.

98 Id. § 314.70(c)(6).

99 Wyeth v. Levine, 555 U.S. 555 (2009).

100 PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011).

101 Mutual Pharmaceutical Co. v. Bartlett, 133 S. Ct. 2466 (2013).

102 Wyeth, 555 U.S. at 581.

103 Bartlett, 133 S. Ct. at 2480 (design defect); PLIVA, 131 S. Ct. at 2581-82 (failure to warn).

104 Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products, 78 Fed. Reg. 67,985 (proposed Nov. 2013).

105 Id. at 67,988.

106 Press Release, FDA, FDA Takes Action to Speed Safety Information Updates on Generic Drugs (Nov. 8, 2013), available at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm374171.htm.

107 Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products, 78 Fed. Reg. at 67,989.

108 Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products: Correction and Extension of Comment Period, 78 Fed. Reg. 78,796 (Dec. 27, 2013).

109 Duke, Jon D. & Kesselheim, Aaron S., The Food and Drug Administration's Role in Promoting Consistent Labels for Generic Drugs, 174 JAMA Internal Med. 1213, 1213 (2014)CrossRefGoogle ScholarPubMed. While the authors note that this is a valid concern, they also point out that this is no different than the current situation except that the changes are driven by brand manufacturer changes rather than generic manufacturer changes. Id.

110 Letter to Margaret A. Hamburg, Comm'r, FDA (Jan. 22, 2014), available at energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/letters/20140122FDA.pdf.

111 Id.

112 Id.

113 A biological product is defined as a “virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.” Public Health Service Act § 351(i), 42 U.S.C. § 262(i) (2012).

114 What Are “Biologics” Questions and Answers, FDA, www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm133077.htm (last updated Apr. 14, 2009).

115 Paradise, Jordan, The Devil Is in the Details: Health-Care Reform, Biosimilars, and Implementation Challenges for the Food and Drug Administration, 51 Jurimetrics 279, 281 (2011)Google Scholar.

116 Id.

117 In comparison to biologics, drugs are statutorily defined as “(A) articles recognized in the official United States Pharmacopoeia, …; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component ….” 21 U.S.C. § 321(g)(1) (2012). A new drug is defined as “(1) Any drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling ….” Id. § 321(p)(1).

118 New drugs may also be approved to market through what is called the “505(b)(2)” process. See id. § 355(b)(2). Over the counter (OTC) drugs adhering to an OTC Monograph can enter the market without review, as they are “generally recognized … as safe and effective ….” See id. § 321(p).

119 See 42 U.S.C. § 262 (2012).

120 See 21 U.S.C. § 355(b)(1).

121 Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, 111 Stat. 2296 (codified as amended in scattered sections of 21 U.S.C.).

122 CDER oversees biological products including monoclonal antibodies for in vivo use, proteins for therapeutic use, immunomodulators, growth factors and enzymes, and nonvaccine immunotherapies. See Transfer of Therapeutic Products to the Center for Drug Evaluation and Research, FDA, www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm133463.htm (last updated Feb. 22, 2010).

123 CBER oversees biological products, including allergenics, cellular products, tissue products, gene therapy products, vaccines, and blood and blood products. See About CBER, FDA, www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm123340.htm (last updated Jan. 21, 2010).

124 21 U.S.C. § 355(j); see also 42 U.S.C. § 262.

125 Biologics Price Competition and Innovation Act of 2009, Pub. L. No. 111-148, tit. VII, §§ 7001-7003, 124 Stat. 804 (codified as amended at 21 U.S.C. §§ 355, 355c and 42 U.S.C. § 262).

126 H.R. 1038, 110th Cong. (2007).

127 H.R. 1956, 110th Cong. (2007).

128 H.R. 5629, 110th Cong. (2008).

129 S. 1695, 110th Cong. (2007).

130 42 U.S.C. § 262(k) (2012).

131 Frank, Richard G., Regulation of Follow-on Biologics, 357 New Eng. J. Med. 841, 841 (2007)CrossRefGoogle ScholarPubMed.

132 Id.

133 42 U.S.C. § 262(i)(2).

134 Id. § 262(k)(2)(A)(i).

135 See 21 U.S.C. 355(j)(2)(A)(v) (2012 & Supp. I 2013); supra Part III.C (discussing ANDA requirements).

136 42 U.S.C. § 262(k)(2)(A)(ii).

137 Id. § 262(i)(3).

138 Id. § 262(k)(4)(B).

139 See Implementation of the Biologics Price Competition and Innovation Act of 2009, FDA, www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ucm215089.htm (last updated Mar. 10, 2011).

140 See Biologics Price Competition and Innovation Act of 2009; Meetings on User Fee Program for Biosimilar and Interchangeable Biological Product Applications; Request for Notification of Stakeholder Intention to Participate, 75 Fed. Reg. 76,472 (Dec. 8, 2010); Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request for Comments; 75 Fed. Reg. 61,497 (Oct. 5, 2010). Details of these public hearings, including written public comments and PowerPoint testimony files, are available at www.regulations.gov. Docket numbers are FDA-2010-N-0602-0001 (“Biologics Price Competition and Innovation Act of 2009; Meetings: User Fee Program for Biosimilar and Interchangeable Biological Product Applications; Request for Notification of Stakeholder Intention to Participate”) and FDA-2010-N-0477-0001 (“Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing”).

141 See FDA, Guidance for Industry: Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009 (2012)[hereinafter Biosimilars Questions and Answers], available at www.fda.gov/downloads/Drugs/Guidances/UCM273001.pdf; FDA, Guidance for Industry: Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product (2012) [hereinafter Quality Considerations], available at www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291134.pdf; FDA, Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (2012) [hereinafter Scientific Considerations], available at www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf.

142 See FDA, Guidance for Industry: Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product (2014) [hereinafter Clinical Pharmacology].

143 Biosimilars Questions and Answers, supra note 141, at 11-12.

144 Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations, FDA, available at www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm411418.htm (last updated Jan. 27, 2015) [hereinafter Purple Book].

145 Mari Serebrov, Purple Will Be the New Orange for Biosimilar Makers, BioWorld, http://www.bioworld.com/content/purple-will-be-new-orange-biosimilar-makers-0 (last visited Feb. 11, 2015).

146 Generic Biosimilar Applications to FDA Increasing, HealthCare Roundtable e-News (Sept. 3. 2014), www.healthcareroundtable.org/public/463.cfm#biosimilar.

147 Senior, Melanie, Biosimilar Battle Rages on, Amgen Fights Both Sides, 31 Nature Biotech. 269, 269 (2013)CrossRefGoogle ScholarPubMed.

148 42 U.S.C. § 262(l) (2012).

149 Press Release, Sandoz, FDA Accepts Sandoz Application for Biosimilar Filgrastim (July 24, 2014), available at sandoz.com/media_center/press_releases_news/global_news/2014_07_24_FDA_accepts_Sandoz_application_for_biosimilar_filgrastim.shtml.

150 See Anna Edney, Novartis Biosimilar of Amgen's Neupogen Wins United States Panel Backing, Bloomberg Bus. (Jan. 7, 2015), www.bloomberg.com/news/articles/2015-01-07/novartis-biosimilarof-amgen-s-neupogen-wins-u-s-panel-backing.

151 See Press Release, Sandoz, supra note 149.

152 Id.

153 Natalie Grover & Samantha Kareen Nair, FDA Panel Unanimously Backs Novartis' Copy of Amgen's Neupogen, Reuters (Jan. 7, 2015), www.reuters.com/article/2015/01/07/us-novartis-amgenfda-idUSKBN0KG29220150107.

154 See FDA, FDA Briefing Document: Oncologic Drugs Advisory Committee Meeting 60 (2015), available at www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM428780.pdf [hereinafter FDA Briefing Document].

155 Press Release, FDA, supra note 15.

156 Id.

157 FDA, Guidance Agenda: New and Revised Draft Guidances CDER Is Planning to Publish During Calendar Year 2015 (Feb. 27, 2015), available at www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm417290.pdf.

158 See Small Molecule Versus Biological Drugs, Generics and Biosimilars Initiative (June 29, 2012), www.gabionline.net/Biosimilars/Research/Small-molecule-versus-biological-drugs.

159 See id.

160 Scientific Considerations, supra note 141, at 7-8.

161 Id. at 12.

162 Id. at 21.

163 See Clinical Pharmacology, supra note 142.

164 See id. at 14.

165 FDA Briefing Document, supra note 154, at 60.

166 See WHO, International Nonproprietary Names (INN) for Biological and Biotechnological Substances: A Review, at 115, INN Working Doc. 05.179 (2008), available at www.who.int/medicines/areas/quality_safety/quality_assurance/INNBiologicalBiotechnologicalSubstancesReviewTRS948Annex5.pdf.

167 WHO, International Nonproprietary Names (INN) for Biological and Biotechnological Substances: A Review, at iv, INN Working Doc. 05.179 (2013), available at www.who.int/medicines/services/inn/BioRev2013.pdf.

168 International Nonproprietary Names (INN) Working Group Meeting on Nomenclature for Monoclonal Antibodies (mAb), Oct. 6-7, 2008, Meeting Report, INN Working Doc. 08.242, available at www.who.int/medicines/services/inn/ApprovedFinalWHOINNWGroupMeetingNMAreport.pdf.

169 WHO, International Nomenclature and Gene Therapy Products, 19 WHO Drug Info. 101, 103 (2005)Google Scholar, available at whqlibdoc.who.int/druginfo/19_2_2005.pdf.

170 WHO, supra note 167. The document divides substances into eleven categories: blood products, fusion proteins, gene therapy products, glycosylated compounds, non-glycosylated compounds, immunoglobins, monoclonal antibodies, skin substitutes, transgenic products, vaccines, and cell-therapy products. Several categories of biologics are not assigned an INN: blood products, skin substitutes, vaccines, and immunoglobins. Id. at 6-12.

171 See WHO, International Nonproprietary Names Modified, INN Working Doc. 05.167/3, available at www.who.int/medicines/services/inn/INNMreview%20paperWkDoc167_Feb06_3_.pdf.

172 Ronald A. Rader, Nomenclature of New Biosimilars Will Be Highly Controversial, 9 BioProcess Int'l, June 2011, at 26, 28.

173 Lisa Emrich, Medications for MS, HealthCentral.com (Dec. 1, 2010), www.healthcentral.com/multiple-sclerosis/c/19065/125649/beta/.

174 Edward C. Lawrence, Biosimilars Delay Causing Billions in Wasteful, Unnecessary Drug Spending, RxObserver Blog (June 30, 2014), www.rxobserver.com/?p=2302.

175 Directive 2004/27, of the European Parliament and of the Council of 31 March 2004 Amending Directive 2001/83/EC on the Community Code Relating to Medicinal Products for Human Use, art. 1, 2004 O.J. (L 136) 34, 39.

176 Biosimilars Approved in Europe, Generics & Biosimilars Initiative (Aug. 7, 2011), http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe.

177 Id.

178 See Neupogen: Indications, RxList, www.rxlist.com/neupogen-drug/indications-dosage.htm (last visited Feb. 12, 2015).

179 See Product-Specific Biosimilar Guidelines, Eur. Meds. Agency, www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000408.jsp&mid=WC0b01ac058002958c (last visited Feb. 12, 2015).

180 Gitter, Donna M., Informed by the European Union Experience: What the United States Can Anticipate and Learn from the European Union’s Regulatory Approach to Biosimilars, 41 Seton Hall L. Rev. 559, 586 (2011)Google ScholarPubMed.

181 55th Consultation on International Nonproprietary Names for Pharmaceutical Substances, Geneva, Switz., Oct. 16-18, 2012, Executive Summary, at 3, INN Working Doc. 13.329 (Feb. 2013), available at www.who.int/medicines/services/inn/55th_Executive_Summary.pdf?ua=1.

182 Id.

183 See WHO, Biological Qualifier: An INN Proposal, INN Working Doc. 14.342 (July 2014), available at www.who.int/medicines/services/inn/bq_innproposal201407.pdf.

184 Id. at 4.

185 Id.

186 Id.

187 See, e.g., Ronald A. Rader, INN/WHO Has Issued a Proposal for a Biological Qualifier (BQ) to Be Appended to INNs, BIOPHARMA, www.biopharma.com/biopharmacopeia//bq.html (last visited Feb. 12, 2015). Rader proposes that BQs should be assigned to manufacturing facilities with “no needless bureaucratic complications.” Id.

188 See WHO, supra note 183, at 3.

189 Gitter, supra note 180, at 587 (citing WHO Informal Consultation on International Nonproprietary Names (INN), Geneva, Switz., Sept. 4-5, 2006, Policy for Biosimilar Products, INN Working Doc. 07.211, available at www.who.int/medicines/services/inn/BiosimilarsINN_Report.pdf).

190 Id. at 587.

191 See id.

192 Cathy Dombrowski, Biosimilar Naming Fight: Could Brand Names for All Resolve the Problem?, The Pink Sheet, Feb. 10, 2014, at 13.

193 M. Nielsen Hobbs, GPhA and Actavis Divorcing: Biosimilars Behind the Rift, The Pink Sheet, Mar. 3, 2014, at 16.

194 About: The Association, Generic Pharmaceutical ass'n, www.gphaonline.org/about/thegpha-association (last visited Feb. 12, 2015).

195 Hobbs, supra note 193.

196 James G. Dickinson, Must Biosimilar Names Be Distinct? No, Experts Argue, Med. Marketing & Media (Feb. 5, 2014), www.mmm-online.com/must-biosimilar-names-be-distinct-no-experts-argue/article/332772/.

197 Senior, supra note 147.

198 Andrew Pollack, Biotech Firms, Billions at Risk, Lobby States to Limit Generics, N.Y. Times (Jan. 28, 2013), www.nytimes.com/2013/01/29/business/battle-in-states-on-generic-copies-of-biotech-drugs.html?_r=2&.&.

199 Richard Dolinar, It's All About the Name: What Is the Imperative of Adopting Unique Names for Biologic and Biosimilar Therapeutics?, Food & Drug L. Pol'y Forum, Nov. 28, 2012, at 1, 12.

200 BIO et al., Policy Position on Naming of Biotechnology-Derived Therapeutic Proteins 2 (2006), available at http://www.who.int/medicines/services/inn/WHO_INN-Research-basedIndustriesJointPosition.pdf.

201 Letter to the Editor: BIO Responds to Biosimilar Naming Article, Pharma & MedTech Bus. Intelligence (July 11, 2013), https://www.pharmamedtechbi.com/publications/rpm-report/first-take/2013/4/bio-responds-to-biosimilar-naming-article.

202 Brenda Sandburg, Waiting for Biosimilars: From Manufacturing to Litigation, Stakeholders Prepare for United States Market, The Pink Sheet, June 16, 2014, at 19, 21.

203 Novartis, Biosimilars: Naming Requirements (2006), www.novartis.com/downloads/corporate-responsibility/resources/positions/biosimilars-naming-requirements.pdf.

204 Naming of Biosimilars, Generic Pharmaceutical Ass'n, www.gphaonline.org/gpha-media/gpha-resources/1naming-biosimilars (last visited Feb. 12, 2015).

205 Letter from Am. Pharmacists Ass'n et al. to Div. of Dockets Mgmt. (May 25, 2012), available at www.ncpanet.org/pdf/leg/may12/joint_biosimilar_letter.pdf.

206 Id. at 2.

207 Id.

208 Id.

209 Dombrowski, supra note 192.

210 Sandburg, supra note 202, at 20.

211 Id.

212 Id. at 21.

213 Citizen Petition from Jay P. Seigel, Chief Biotechnology Officer, Johnson & Johnson, to Div. of Dockets Mgmt., FDA 11-12 (Jan. 7, 2014), available at www.janssen.com/JnJ%20Petition%20Biosimilars%20Naming%20FINAL.pdf.

214 Sandburg, supra note 202, at 20.

215 Fed. Trade Comm'n, Follow-on Biologics Workshop (Feb. 4, 2014) (transcript available at www.ftc.gov/system/files/documents/public_events/171301/140204biologicstranscript.pdf).

216 Comments, Fed. Trade Comm'n, www.ftc.gov/policy/public-comments/initiative-531 (last visited Feb. 13, 2015).

217 Dombrowski, supra note 192.

218 Id. at 14.

219 Id.

220 Sandburg, supra note 202, at 20; Letter from Am. Pharmacists Ass'n et al., supra note 205, at 2.

221 Sandburg, supra note 202, at 20.

222 Dombrowski, supra note 192 (citing Derrick Gingery, FDA Wants Biosimilar Naming Guidance Released Before Approving an Application, The Pink Sheet, Feb. 5, 2014).

223 See Press Release, FDA, supra note 15.

224 Erin Durkin, Biosimilar Advisory Meeting May Offer Final Platform for Naming Debate, FDA Week, Dec. 26, 2014, at 1, 4, available at insidehealthpolicy.com/biosimilar-advisory-meeting-may-offer-final-platform-naming-debate.

225 Id.

226 See HHS, supra note 50, at 7-9.

227 See id. at app. A.

228 Vivian, Jesse C., Generic-Substitution Laws, 33 U.S. Pharmacist 30, 32-33 (2008)Google Scholar.

229 See HHS, supra note 50, at app. A.

230 See id.

231 See id.

232 Vivian, supra note 228.

233 Id.

234 Id.

235 42 U.S.C. § 262(i)(3) (2012).

236 See infra Part V.A.

237 See, e.g., Biosimilars Overview, Patients for Biologics Safety & Access, www.biosimsafety.org/biosimilars-overview/ (last visited Feb. 14, 2015).

238 See Senior, supra note 147.

239 Hobbs, supra note 193, at 17.

240 Sandburg, supra note 202, at 20.

241 Id. Note that Actavis recently split from GPhA as a result of a partnership with Amgen in the biosimilars realm. See discussion supra Part V.A.

242 Sandburg, supra note 202, at 20-21.

243 Dombrowski, supra note 192.

244 Sandburg, supra note 202, at 20.

245 Richard Cauchi, State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars, Nat'l Conference of State Legislatures (Feb. 4, 2015), www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-ofbiosimilars.aspx. The eight states are Delaware, Florida, Indiana, Massachusetts, North Dakota, Oregon, Utah, and Virginia. Id.

246 Id. The fifteen states that have considered legislation are Arkansas, Arizona, California, Colorado, Georgia, Illinois, Maryland, Michigan, Mississippi, Nevada, New Jersey, Pennsylvania, Texas, Vermont, and Washington. Id.

247 Id.

248 Greg Avery, Biosimilars Bill Approved by Colorado Legislature, Denver Bus. J. (Mar. 10, 2015), www.bizjournals.com/denver/blog/boosters_bits/2015/03/biosimilars-bill-approved-by-colorado-legislature.html.

249 See supra Figure 1.

250 Id.

251 Fla. Stat. Ann. § 465.0252(2)(c) (West 2014).

252 Ind. Code Ann. § 16-42-25-5(a) (West 2007 & Supp. 2014).

253 Fla. Stat. Ann. § 465.0252(2)(c); see also Pollack, supra note 198.

254 See supra Figure 1.

255 Sandburg, supra note 202, at 20.

256 N.D. Cent. Code § 19-02.1-14.3-2(d) (2009 & Supp. 2013).

257 Ind. Code Ann. § 16-42-25-5(a).

258 Mass. Gen. Laws ch. 112, § 12EE(d) (2012 & Supp. 2014).

259 Fla. Stat. Ann. § 465.0252(2)(c) (West 2014); Va. Code Ann. § 54.1-3408.04(D) (2013).

260 Utah Code Ann. § 58-17b-605.5(2)(d) (LexisNexis 2012 & Supp. 2014).

261 See supra Figure 1.

262 Current as of Feb. 15, 2015.

263 Del. Code. Ann. tit. 24, § 2549A (2011 & Supp. 2014).

264 Fla. Stat. Ann. § 465.0252 (West 2014).

265 Ind. Code Ann. § 16-42-25-1 to -8 (West 2007 & Supp. 2014).

266 Mass. Gen. Laws ch. 112, § 12EE (2012 & Supp. 2014).

267 N.D. Cent. Code § 19-02.1-14.3-1 to -3 (2009 & Supp. 2013).

268 Or. Rev. Stat. Ann. § 689.522 (West 2008 & Supp. 2014).

269 Utah Code Ann. § 58-17b-605.5 (LexisNexis 2012 & Supp. 2014).

270 Va. Code Ann. § 54.1-3408.04 (2013).

271 Mass. Gen. Laws ch. 112, § 12EE(f) (2012 & Supp. 2014).

272 Dombrowski, supra note 192, at 12.

273 See supra Figure 1.

274 See, e.g., Del. Code. Ann. tit. 24, § 2549A(a)(1) (2011 & Supp. 2014); Va. Code Ann. § 54.1-3408.04(A) (2013).

275 See. e.g., Utah Code Ann. § 58-17b-605.5(6)(a) (LexisNexis 2012 & Supp. 2014).

276 Ind. Code Ann. § 16-42-25-4(2)(A) (West 2007 & Supp. 2014).

277 Utah Code Ann. § 58-17b-605.5(6)(a). The law also reads that substitution can be prohibited by the notation “dispense as written.” Id.

278 See supra Figure 1.

279 See id.

280 Robert Weissman & Hannah Brennan, Public Citizen, Competition Inhibitors: How Biologics Makers Are Leveraging Political Power to Maintain Monopolies and Keep Prices Sky-High 26-28 (2014), available at www.citizen.org/documents/report-biologics-industry-leverages-political-power-to-maintain-monopolies-and-inflate-prices.pdf.

281 Dan Stanton, Cali Gov Vetoes Biosimilar Bill, Thwarting Amgen and Genentech, BioPharma Rep. (Oct. 16, 2013), www.biopharma-reporter.com/Markets-Regulations/Cali-Gov-vetoes-biosimilar-bill-thwarting-Amgen-and-Genentech.

282 Adrianne Appel, Massachusetts Governor Signs Biosimilars Bill with Patient Notification, 12 Pharm. Law & Industry Rep. (BNA) No. 26, at 916 (June 24, 2014).

283 Weissman & Brennan, supra note 280, at 27.

284 See Sandburg, supra note 202, at 20.

285 Alaric DeArment, Reports: FDA Says Carve-out Bills ‘Undermine Trust' in Biosimilars, Drug Store News (Aug. 29, 2013), www.drugstorenews.com/article/reports-fda-says-carve-out-bills-undermine-trust-biosimilars.

286 See Dombrowski, supra note 192, at 13.

287 Brenda Sandburg, Biosimilar Substitution Legislation Emphasizes Electronic Health Records, The Pink Sheet, Dec. 15, 2014, at 11, 11.

288 Randi Hernandez, Industry Players Reach Compromise on Biosimilar Substitution, BioPharm Int'l (Dec. 12, 2014), www.biopharminternational.com/industry-players-reach-compromise-biosimilar-substitution.

289 Id.

290 Sandburg, supra note 288, at 11.

291 Id.

292 Current as of February 15, 2015.

293 See, e.g., Grabowski, Henry et al., Biosimilar Competition: Lessons from Europe, 13 Nature Revs. Drug Discovery 99 (2014)CrossRefGoogle ScholarPubMed; Grabowski, Henry et al., Does Generic Entry Always Increase Consumer Welfare?, 76 Food & Drug L.J. 373 (2012)Google Scholar; Grabowski, Henry, Follow-on Biologics: Data Exclusivity and the Balance Between Innovation and Competition, 7 Nature Revs. Drug Discovery 479 (2008)CrossRefGoogle ScholarPubMed; Grabowski, Henry et al., Implementation of the Biosimilar Pathway: Economic and Policy Issues, 41 Seton Hall L. Rev. 511 (2011)Google ScholarPubMed; Grabowski, Henry et al., Recent Trends in Brand-Name and Generic Drug Competition, 17 J. Med. Econ. 207 (2014)CrossRefGoogle ScholarPubMed.

294 Biosimilars Naming Debate Intensifies, Generics & Biosimilars Initiative (Nov. 22, 2013), gabionline.net/Biosimilars/General/Biosimilars-naming-debate-intensifies.

295 See id.

296 See discussion supra Part III.B.

297 See discussion supra Part III.C.

298 Biosimilars Questions and Answers, supra note 141, at 11-12.

299 See Kurt R. Karst, The Biosimilars State Legislation Scorecard, FDA Law Blog (Sept. 4, 2013), www.fdalawblog.net/fda_law_blog_hyman_phelps/2013/09/biosimilars-state-legislation-scorecard.html.