The drugs stop here: A public health framework to address the drug shortage crisis

Food and Drug Law Journal

Volumn 67, Issue 1, 2012, Pages

  Hoffman, Sharona ^a,b,c,d  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

^b WELLESLEY COLLEGE   (United States)

^c HARVARD LAW SCHOOL   (United States)

^d UNIVERSITY OF HOUSTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIKACIN; COCAINE; DOXORUBICIN; MAGNESIUM SULFATE; PACLITAXEL;

ATTENTION DEFICIT DISORDER; DRUG COST; DRUG INDUSTRY; DRUG MANUFACTURE; DRUG MARKETING; ECONOMIC ASPECT; FOOD AND DRUG ADMINISTRATION; HEALTH CARE; HEALTH CARE COST; HOSPITAL; HUMAN; LAW; MEDICARE; PATIENT CARE; POLICY; REIMBURSEMENT; REVIEW; TAX; TREATMENT OUTCOME;

DRUG INDUSTRY; HUMANS; PHARMACEUTICAL PREPARATIONS; PUBLIC HEALTH; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84864151770     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (196)

1. Transcript of Food and Drug Administration Center for Drug Evaluation and Research Drug Shortage Workshop, September 26, 2011 [hereinafter FDA Workshop].
2. Gardiner Harris, F.D.A. Is Finding Attention Drugs in Short Supply, N. Y. TIMES, Jan. 1, 2012, at A1.
3. Roni Caryn Rabin, Drug Scarcity's Dire Cost, and Some Ways to Cope, N. Y. TIMES, Dec. 13, 2011, at D1.
4. FDA Workshop, supra note 1, at 20.
5. CDER MANUAL OF POLICIES AND PROCEDURES MAPP 6003.1 at 2 (2006), available at http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ ManualofPoliciesProcedures/UCM079936.pdf;
6. Prescription Drug Shortages: Examining a Public Health Concern and Potential Solutions, Statement of Sandra Kweder, M.D. Before the Committee on Health, Education, Labor and Pensions, United States Senate, December 15, 2011, at http://www.fda.gov/NewsEvents/Testimony/ucm282956.htm [hereinafter Kweder Statement]. Dr. Kweder is the Deputy Director of the FDA's Office of New Drugs Center for Drug Evaluation and Research.
7. Kevin Haninger et al., Economic Analysis of the Causes of Drug Shortages 3 (Oct. 2011), available at http://aspe.hhs.gov/sp/reports/2011/drugshortages/ ib.pdf;
8. Joseph M. Hill & Cynthia Reilly, Can the United States Ensure an Adequate Supply of Critical Medications? 1 FDLI's FOOD & DRUG POL'Y FORUM 1, 1 (August 24, 2011), available at http://www.fdli.org/pubs/policyforum/ (noting that "the number of shortages has nearly tripled since 2006" and that the number of shortages in 2011 was expected to be larger than the 2010 figure).
9. U.S. Food and Drug Administration, A Review of FDA's Approach to Medical Product Shortages 3 (October 31, 2011) [hereinafter FDA Review], available at http://www.fda.gov/downloads/aboutfda/reportsmanualsforms/reports/ucm277755.pdf.
10. Id.; Jocelyn Kaiser, Shortages of Cancer Drugs Put Patients, Trials at Risk, 332 SCIENCE 523, 523 (2011) (noting that shortages "have tripled since 2006").
11. See U.S. Food and Drug Administration, Biologic Product Shortages, at http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/Shortages/default. htm.
12. Biologies, unlike drugs are "derived from living sources (such as humans, animals, and microorganisms" and include "blood, vaccines, allergenics, tissues, and cellular and gene therapies." U.S. Food and Drug Administration, About CBER, at http://www.fda.gov/AboutFDA/CentersOffices/ OfficeofMedicalProductsandTobacco/CBER/ucm123340.htm.
13. FDA Workshop, supra note 1, at 41;
14. C. Lee Ventola, The Drug Shortage Crisis in the United States: Causes, Impact, and Management Strategies, 36 P & T 740, 741 (2011) (indicating that the U.S. has suffered from shortages of medical supplies).
15. Id. (explaining why the University of Utah's statistics are different from the FDA's).
16. Erin R. Fox et al., ASHP Guidelines on Managing Drug Product Shortages in Hospitals and Health Systems, 66 AM. J. HEALTH-SYST. PHARM. 1399, 1400 (2009).
17. Fox et al., supra note 12 at 1405; U.S. Food and Drug Administration, FDA and Manufacturers Work to Prevent Drug Shortages, at http://www.fda.gov/Drugs/ DrugSafety/DrugShortages/ucm257746.htm.
18. Ventola, supra note 10, at 740.
19. Id.; FDA Workshop, supra note 1, at 42.
20. FDA Review, supra note 7, at 4.
21. Id.
22. Haninger et al., supra note 6, at 1; Mandy L. Gatesman & Thomas J. Smith, The Shortage of Essential Chemotherapy Drugs in the United States, 365 N. ENGL. J. MED. 1653, 1653 (2011);
23. Steven Reinberg, Cancer Drug Shortages Getting Worse, FDA Says, HEALTHDAY (August 24, 2011), available at http://yourlife.usatoday.com/health/story/2011- 08-28/Cancer-drug-shortages-getting-worse-FDA-says/50148996/1.
24. Ventola, supra note 10, at 740 (listing heart drugs, pain medications, intravenous electrolytes, leucovorin, propofol, morphine, hydromorphone, furosemide, amino acids, and technetium-99m); Valerie Jensen & Bob A. Rappaport, The Reality of Drug Shortages - The Case of the Injectable Agent Propofol, 363 N. ENGL. J. MED. 806,806 (2010) (discussing the critical shortage of propofol, "a fast-onset, short-acting sedative-hypnotic agent used for the induction and maintenance of anesthesia or sedation.");
25. Hill & Reilly, supra note 6, at 1 (listing "anti-cancer drugs, anesthetics, and nutritional therapies"); Harris, supra note 2, at A1 (discussing the shortage of generic drugs to treat attention deficit hyperactivity disorder); Bruce A. Chabner, Drug Shortages - A Critical Challenge for the Generic-Drug Market, 365 N. ENGL. J. MED. 2147, 2147-48 (2011) ("The list of generic drugs in short supply across all medical specialties is astounding and includes antibiotics, anesthetic agents, antihypertensive medications, and common electrolyte solutions and vitamins.").
26. Rola Kaakeh et al., Impact of Drug Shortages on U.S. Health Systems, 68 AM. J. HEALTH-SYST. PHARM. 1811, 1814 (2011). The survey was completed by 353 directors of pharmacy. Id. at 1811.
27. Id. at 1815.
28. Id.
29. Coleen Cherici et al., Navigating Drug Shortages in American Healthcare: A Premier Healthcare Alliance Analysis 3 (March 2011), available at http://www.premierinc.com/about/news/11-mar/drug-shortage-white-paper-3-28-11. pdf (surveying pharmacy experts from hospitals as well as "infusion, oncology and surgery centers; outpatient and retail pharmacies; and long-term care facilities").
30. Id.
31. Ventola, supra note 10, at 741; Erin R. Fox, Drug Shortage Update Current Status & Significant Trends, at http://www.fda.gov/downloads/Drugs/ NewsEvents/UCM274565.pdf.
32. U.S. Food and Drug Administration, Current Drug Shortages, at http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm.
33. Fox et al., supra note 12, at 1400; FDA Review, supra note 7, at 4 (indicating that "active pharmaceutical ingredient shortages" accounted for 10% of reported shortages).
34. Fox et al., supra note 12, at 1400.
35. Id.
36. Fox et al., supra note 12, at 1400; FDA Review, supra note 7, at 4 (indicating that "problems at the manufacturing facility" accounted for 43% of reported shortages);
37. Robert Steinbrook, Drug Shortages and Public Health, 361 N. ENGL. J. MED. 1525, 1525 (2009) (discussing the "viral contamination of a Genzyme Manufacturing plant in Massachusetts" that caused shortages of drugs for Gaucher's disease and Fabry's disease).
38. FDA Review, supra note 7, at 4.
39. Fox et al., supra note 12, at 1402; Ventola, supra note 10, at 742.
40. Ventola, supra note 10, at 742.
41. FDA Review, supra note 7, at 4; see also, Kweder Statement, supra note 5 (stating that "[i]n 2010, the top five generic sterile injectable manufacturers accounted for 80 percent of the sterile injectables sold in the U.S. market by volume.").
42. Fox et al., note 24, at 1401.
43. Id.; Valerie Jensen et al., FDA's Role in Responding to Drug Shortages, 59 AM. J. HEALTH-SYST. PHARM. 1423, 1424 (2002).
44. See infra Part U.C.
45. Fox et al., supra note 12, at 1401.
46. Ventola, supra note 10, at 742.
47. Id.
48. Id.
49. Id.; FDA Review, supra note 7, at 4; Hill & Reilly, supra note 6, at 2.
50. FDA Review, supra note 7, at 4.
51. Hill & Reilly, supra note 6, at 4; Ventola, supra note 10, at 742.
52. Gatesman & Smith, supra note 18, at 1653-54.
53. Id.
54. Ventola, supra note 10, at 742.
55. Jensen & Rappaport, supra note 19, at 806.
56. Haninger et al., supra note 6, at 1.
57. Jensen & Rappaport, supra note 19, at 806.
58. Chabner, supra note 19, at 2149.
59. Gatesman & Smith, supra note 18, at 1655.
60. Haninger et al., supra note 6, at 3-4.
61. Id. See supra note 13 and accompanying text for definition of medically necessary products.
62. Haninger et al., supra note 6, at 4.
63. Id.
64. U.S. Department of Health & Human Services, Statement by Sherry Glied Ph.D. Assistant Secretary for Planning and Evaluation U. S. Department of Health and Human Services (HHS) on Prescription Drug Shortages: Examining a Public Health Concern and Potential Solutions before Committee on Health, Education, Labor and Pensions United States Senate (December 15, 2011), at http://www.hhs.gov/asl/testify/2011/12/t20111215c.html [hereinafter Glied Statement].
65. Haningeret al., supra note 6, at 4.
66. Hill & Reilly, supra note 6, at 4.
67. Harris, supra note 2, at A17.
68. U.S. Food and Drug Administration, Unapproved Drugs Initiative, at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ EnforcementActivitiesbyFDA/SelectedEnforcementAclionsonUnapprovedDrugs/ ucm118990.htm; Ventola, supra note 10, at 749.
69. Ventola, supra note 10, at 749; Cherici et al., supra note 23, at 2.
70. Gatesman & Smith, supra note 18, at 1654.
71. Id.; Mireille Jacobson et al., How Medicare's Payment Cuts for Cancer Chemotherapy Drugs Changed Patterns of Treatment, 29 HEALTH AFF. 1391,1392 (2010);
72. Centers for Medicare and Medicaid Services, 2012 ASP Drug Pricing Files, at https://www.cms.gov/McrPartBDrugAvgSalesPrice/01a17-2012ASPFiles.asp (stating that payment amounts "are 106 percent of the Average Sales Price (ASP) calculated from data submitted by drug manufacturers" with "quarter to quarter price changes").
73. Gatesman & Smith, supra note 18, at 1654.
74. Haninger et al., supra note 6, at 7-8.
75. Id. at 8.
76. Ventola, supra note 10, at 750.
77. Id. at 750-51; Susan Jenks, Efforts Underway to Curb Drug Shortages, 103 J. NAT'L CANCER INSTIT. 914, 914 (2011) ("In recent weeks, shortages in cytarabine injections raised the specter ... of denying leukemia patients a chemotherapy drug carrying their best hope for survival").
78. FDA Workshop, supra note 1.
79. Id. at 110.
80. Id. at 115. Parenteral nutrition is given intravenously using customized, sterile formulas and a central IV line when a patient cannot eat and digest normally. Id. at 88-89. See also, Ventola, supra note 10, at 751 (describing the same incident).
81. FDA Workshop, supra note 1, at 110.
82. Id. at 142, 248.
83. Maryn McKenna, Hospital Pharmacists Scrambling Amid Vast Drug Shortages, 57 ANNALS OF EMERGENCY MED. 13A, 13A-14A (2011) (describing medical errors including "a 20-fold overdose of dexmedetomidine because the staff were not familiar with dosing for the alternative drug").
84. Gatesman & Smith, supra note 18, at 1653.
85. Id.
86. Id. at 83-101.
87. Id. at 103. Fortunately, the patient's pharmacy was able to obtain additional supplies of IV magnesium sulfate, which she was still receiving at the time of her testimony. However, the patient remained concerned about how she would fare in the future. Id. at 105.
88. Ventola, supra note 10, at 751.
89. Id.; Jenks, supra note 62, at 914.
90. Kaakeh et al., supra note 20, at 1812.
91. Id. at 1814.
92. Id.
93. FDA Workshop, supra note 1, at 329.
94. Fox et al., supra note 12, at 1401.
95. Ventola, supra note 10, at 750.
96. Gatesman & Smith, supra note 18, at 1653. See also, FDA Workshop, supra note 1, at 265 (describing a markup of 4,500 percent in which a blood pressure medication that is normally priced at $25.90 was offered for $1200).
97. Cherici et al., supra note 23, at 7.
98. FDA Workshop, supra note 1, at 264.
99. Id. at 752; Kaiser, supra note 8, at 523 ("Shortages can also complicate clinical trials").
100. FDA Workshop, supra note 1, at 123; Kweder statement, supra note 5.
101. Sharona Hoffman & Andy Podgurski, Improving Health Care Outcomes through Personalized Comparisons of Treatment Effectiveness Based on Electronic Health Records, 39 J. L. MED. & ETHICS 425, 425 (2011).
102. American Recovery and Reinvestment Act of 2009, tit. VIII, Pub. L. No. 111-5, 123 Stat. 115, 177-78 (2009).
103. Patient Protection and Affordable Care Act of 2010, Pub. L. No. 111-148, §6301, 124 Stat. 119 (2010), codified at 42 U.S.C. § 1320e (2006).
104. 42 U.S.C. §1320e(a)(2)(A)(2006).
105. Ventola, supra note 10, at 752 (discussing strained professional relationships).
106. FDA Workshop, supra note 1, at 248.
107. See U.S. Food and Drug Administration, The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective, at http://www.fda.gov/drugs/ resourcesforyou/consumers/ucm143534.htm.
108. See supra notes 58-60 and accompanying text.
109. See supra note 53-55 and accompanying text.
110. Ventola, supra note 10, at 752; Jensen & Rappaport, supra note 19, at 807.
111. See supra note 39 and accompanying text.
112. See supra note 49 and accompanying text.
113. U.S. Food and Drug Administration, supra note 91.
114. See supra note 30 and accompanying text; FDA Workshop, supra note 1, at 82-87 (providing an account of a patient who suffered excruciating side effects from a substitute chemotherapy agent).
115. LAWRENCE O. GOSTIN, PUBLIC HEALTH LAW: POWER, DUTY, RESTRAINT 35 (2000)
116. U.S. CONST. art. I, §8, cl. 1, 3.
117. GOSTIN, supra note 99, at 35-38.
118. Id. at 38-40.
119. Id. at 35, 40-41.
120. 21 U.S.C.§§ 301-399 (2006).
121. Sharona Hoffman, Responders' Responsibility: Liability and Immunity in Public Health Emergencies, 96 GEO. L. J. 1941-46 (2008).
122. H.R.J. Res. 193, 104th Cong., §, 110 Stat. 3877 (1996) (establishing a mutual aid agreement that has been enacted by all states that is triggered by a governor's declaration of emergency and request for assistance).
123. Pub. L. No. 107-188, § 143(a), 116 Stat. 594, 627-29 (2002) (codified at 42 U.S.C. § 1320b-5 (2006) (authorizing the Secretary of Health and Human Services to waive or modify certain legal requirements that apply to health care providers furnishing goods and services in an emergency area).
124. 42 U.S.C.A. § 247d-6d (2006) (addressing immunity from liability relating to the administration and use of covered emergency countermeasures).
125. Pub. L. No. 108-276,118 Stat. 835 (2004) (codified at 42 U.S.C.A §247d-6a (2006 & West Supp. 2011) (providing that during a declared emergency, the Secretary of Health and Human Services may authorize the emergency use of a product that is not yet "approved, licensed, or cleared for commercial distribution").
126. See Hoffman, supra note 106, at 1922, 1941-42, and 1945-46.
127. FDA Review, supra note 7, at 4. See also, Kweder Statement, supra note 5 (asserting that by December 15th, the FDA had prevented 195 shortages in 2011).
128. FDA Review, supra note 7, at 4. See also, Jensen et al., supra note 32, at 1424-25.
129. FDA Review, supra note 7, at 4. See also, Jensen et al., supra note 32, at 1424-25.
130. Kweder Statement, supra note 5.
131. Id.
132. Jensen et al., supra note 32, at 1425; Jensen & Rappaport, supra note 19, at 807 (noting that in response to a propofol shortage, the FDA "temporarily allowed the importation into the United States of the unapproved drug Fresenius Propoven 1%, a propofol product approved in other countries").
133. Exec. Order No. 13,588, 76 Fed. Reg. 68295 (Nov. 3, 2011).
134. Id. at §.2.
135. Id. at § 3.
136. Id. at § 4.
137. Id.
138. See supra Parts I and III.
139. Jensen et al., supra note 32, at 1424.
140. 21 U.S.C. §356c (2006).
141. th Cong. (2011) at http://www.govtrack.us/congress/billtext.xpd?bill=h112-2245; http://www.govtrack.us/congress/billtext.xpd?bill=s112-296.
142. 21 U.S.C. §356c (2006).
143. H.R. 2245 at §506C(b)(1)-(5); S. 296 at §2(a)(2)-(5). The bills also establish exceptions to the standard notification requirements.
144. H.R. 2245 at §506C(b)(7); S. 296 at §2(a)(6).
145. H.R. 2245 at §506C(c); S. 296 at §§2(d) and (3).
146. H.R. 2245 at §506C(b)(6); S. 296 at §2(b).
147. http://www.govtrack.us/congress/bill.xpd?bill=s112-296; http://www.govtrack.us/congress/bill.xpd?bill=h112-2245.
148. Ventola, supra note 10, at 755; Stephen Barlas, Severe Drug Shortages Impose Heavy Costs on Hospital Pharmacies: Senate Bill Might Help ... or Not, 36 P&T 242, 242 (2011).
149. Barlas, supra note 131, at 302.
150. See supra note 129 and accompanying text.
151. See supra note 25 and accompanying text (stating that 55% of shortages are of unknown origin).
152. H.R. 2245 at §506C(c)(4)(b).
153. See supra Part U.C.
154. But see Ventola, supra note 10, at 753 (stating that in the face of shortages, the "FDA has been fairly successful in influencing manufacturers to increase production" and that "[s]ome companies have even produced drugs at a loss, because they recognized a critical need for them).
155. 21 U.S.C. §355(i). See generally, Gerald J. Mossinghoff, Overview of the Hatch-Waxman Act and Its Impact on the Drug Development Process, 54 FOOD & DRUG L. J. 187 (1999).
156. 21 U.S.C. §355(j)(2)
157. Chabner, supra note 19, at 2148.
158. Id. See also, American Society of Health-System Pharmacists et al., Drug Shortages Summit November 5, 2010 Summary Report 4 (2011) at http://www.ashp.org/drugshortages/summitreport (suggesting that the FDA "[r]equire manufacturing redundancies (e.g., multiple manufacturing sites for a sole product or multiple [active pharmaceutical ingredients] API sources, when available) as part of ... [its] approval process").
159. Chabner, supra note 19, at 2148.
160. Id. at 2148-49.
161. See supra notes 95 and 134 and accompanying text.
162. See supra Part II (discussing causes of shortages).
163. American Society of Health-System Pharmacists et al., supra note 140, at 7; Lars Noah, Triage in the Nation's Medicine Cabinet: The Puzzling Scarcity of Vaccines and Other Drugs, 54 S. C. L. REV. 741, 765-66 (2003).
164. Centers for Disease Control and Prevention Office of Public Health Preparedness and Response, Strategic National Stockpile (SNS), at http://www.cdc.gov/phpr/stockpile/stockpile.htm [hereinafter CDC OPHPR].
165. Id.
166. American Society of Health-System Pharmacists et al., supra note 140, at 7.
167. Noah, supra note 144, at 766; CDC OPHPR, supra note 145.
168. CDC OPHPR, supra note 145 (stating that "[t]he SNS Program ensures that the medical materiel stock is rotated and kept within potency shelf-life limits. This involves quarterly quality assurance/quality control checks (QA/QC's) on all 12-hour Push Packages, annual 100% inventory of all 12-hour Push Package items, and inspections of environmental conditions, security, and overall package maintenance"); Ventola, supra note 10, at 756 (arguing against stockpiling by individual health care facilities).
169. Bronwyn Mixter, Sen. Hatch Developing Bill to Address 'Growing Crisis' of Medicine Shortages, 19 HEALTH CARE POL'Y REP. 1880, 1880 (2011); Gatesman & Smith, supra note 18, at 1655; Chabner, supra note 19, at 2149.
170. See supra notes 58-60 and accompanying text.
171. Gatesman & Smith, supra note 18, at 1654; Renee Twombly, Medicare Cost Containment Strategy Targets Several Oncology Drugs, 96 J. NAT'L CANCER INST. 1268, 1268 (2004).
172. Gatesman & Smith, supra note 18, at 1655.
173. Id. (noting that "Kaiser Permanente, Veterans Affairs, and most academic centers" already pay their physicians salaries).
174. Id.
175. See supra notes 2, 53-55 and accompanying text; Hill & Reilly, supra note 6, at 4.
176. Department of Justice, Final Plan for Retrospective Review of Existing Regulations Pursuant to Executive Order 13563, at 14 (August 22, 2011), available at http://www.justice.gov/open/doj-rr-final-plan.pdf.
177. Id.
178. See supra note 95 and accompanying text.
179. Hill & Reilly, supra note 6, at 4; Mixter, supra note 150 at 1880.
180. Pub. L. No. 102-571, 106 Stat. 4491 (1992) (codified primarily at 21 U.S.C.A. §§ 379g, 379h); U.S. Food and Drug Administration, The Prescription Drug User Fee Act, at http://www.fda.gov/ForIndustry/UserFees/ PrescriptionDrugUserFee/default.htm.
181. 21 U.S.C. § 379h(g) (2006), U.S. Food and Drug Administration, supra note 161.
182. Meeting notice, 76 Fed. Reg. 76738 (2011) (announcing "a public meeting to discuss proposed recommendations for enactment of a Generic Drug User Fee Act (GDUFA)").
183. Kweder Statement, supra note 5.
184. Id.
185. Hill & Reilly, supra note 6, at 4.
186. 21 U.S.C. § 379h(a)(1)(F).
187. Noah, supra note 144, at 767-70 (suggesting implementation of a model based on the workers' compensation system or a "regulatory compliance defense.").
188. Hoffman, supra note 105, at 1941-46.
189. Id. at 1959-67.
190. See supra Part II.
191. Haninger et al., supra note 6, at 15; Glied Statement, supra note 51.
192. Glied Statement, supra note 51 (noting that "failure-to-supply clauses, however, provide no reimbursement if there are no alternative sources for the drug, do not reimburse for resources expended looking for other sources, and are of limited duration.").
193. Alven Weil, Failure-to-Supply Pharmacy Program Saves Hospitals More than $3.5 Million by Attacking Drug Shortage Problems, at http://www. premierinc.com/about/news/10-dec/fts120910.jsp.
194. See supra notes 48-52 and accompanying text.
195. FDA Workshop, supra note 1, at 99.
196. Id. at 101.