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Compounding Problems and Compounding Confusion: Federal Regulation of Compounded Drug Products and the FDAMA Circuit Split

Published online by Cambridge University Press:  06 January 2021

Jesse M. Boodoo
Jesse M. Boodoo*
Affiliation:
Boston University School of Law; Brown University
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Extract

Drug compounding is the long-standing pharmacy practice of mixing, combining, or altering ingredients to create drugs tailored to individual patient needs. Compounding is as old as the practice of pharmacy and close to the heart of the modern profession. Indeed, the mortar and pestle – an iconic emblem of compounding – have long been the prevailing symbol of pharmacy. Prior to the emergence of commercially available drug products, the practice of compounding was the practice of pharmacy – to create medicines, early pharmacists inevitably needed to extract and compound natural vegetable, animal, and mineral substances. In one impressive example of successful early compounding, God commanded Moses to “compoundeth” a holy anointing oil of myrrh, cinnamon, cassia, olive oil, and sweet calamus. Not generally one to shrink from a challenge, Moses followed God’s recipe and used his compounded oil to anoint the vessels of the Tabernacle and High Priest.

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Article
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American Journal of Law & Medicine , Volume 36 , Issue 1 , March 2010 , pp. 221 - 248
Copyright
Copyright © American Society of Law, Medicine and Ethics and Boston University 2010

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References

1 See Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients: Hearing Before the S. Comm. on Health, Educ., Labor and Pensions, 108th Cong. 54 (2003) (statement of Daniel A. Herbert, President-elect, American Pharmaceutical Association) [hereinafter Herbert Testimony].

2 Exodus 30:22-33 (King James).

3 Id. at 30:26.

4 Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, § 127, 111 Stat. 2296, 2328 (1997) (codified at 21 U.S.C. § 353a) (2006).

5 Thompson v. W. States Med. Ctr., 535 U.S. 357, 377 (2002).

6 Compare W. States Med. Ctr. v. Shalala, 238 F.3d 1090 (9th Cir. 2001) (finding unconstitutional provisions not severable from compounding provisions and therefore declaring the FDAMA's compounding provisions unconstitutional in their entirety) with Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383 (5th Cir. 2008) (finding unconstitutional provisions severable from the compounding provisions).

7 W. States Med. Ctr., 238 F.3d at 1096-97.

8 Med. Ctr. Pharmacy, 536 F.3d at 401.

9 See David L. Cowen & William H. Helfand, Pharmacy: An Illustrated History 186 (1990).

10 James, A. Sundberg, Extemporaneous Compounding in the Hospital Pharmacy, 1 Int’l J. Pharm. Compounding 314, 314 (1997)Google Scholar.

11 See Susanne, A. Quallich, Compounded Medications: Made to Order?, 23 Urologic Nursing 361, 361 (2003)Google Scholar.

12 See id.; Timothy, B. McPherson et al., Prevalence of Compounding in Independent Community Pharmacy Practice, 46 J. Am. Pharm. Assoc. 568, 569 (2006)Google Scholar (citations omitted). Today's pharmacy students continue to receive somewhat limited instruction in compounding. Among pharmacy college curricula, “very little if any attention is given to the principles of sterile production related to compounding.” Kamal Sabra, Letter, Standards for Pharmacy Compounding, 60 Am. J. Health-Syst. Pharm. 1593, 1593 (2003). Many states, however, require by law that pharmacists have sufficient training and education to perform at least some minimal compounding services. See W. States Med. Ctr. v. Shalala, 69 F. Supp. 2d 1288, 1291 (D. Nev. 1999).

13 See Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix To Protect Patients: Hearing Before the S. Comm. on Health, Educ., Labor and Pensions, 108th Cong. 38-39 (2003) (statement of Steven Galson, Deputy Director, Center of Drug Evaluation and Research, Food and Drug Administration) [hereinafter Galson Testimony]; Susan Ince, Mixed Up Medicine, Prevention, Mar. 2009, at 122, 126. Today, the allure of all-natural medicines continues to drive public interest in compounded drugs, particularly in the area of hormone replacement therapy. See Bruce, Patsner, Pharmacy Compounding of Bioidentical Hormone Replacement Therapy (BHRT): A Proposed New Approach to Justify FDA Regulation of These Prescription Drugs, 63 Food & Drug L.J. 459, 475-77 (2008)Google Scholar.

14 Marlene Cimons, A Return to the Mortar and Pestle, L.A. Times, Oct. 2, 2000, at 1.

15 Ince, supra note 13, at 124.

16 J.H. Perrin, Comments on Drugs Difficult To Compound and the Quality of Chemicals To Be Used in Compounding, 25 Drug Dev. & Indus. Pharm. 553, 557 (1999).

17 See Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients: Hearing Before the Senate Comm. on Health, Educ., Labor and Pensions, 108th Cong. 33 (2003) (statement of Janet Heinrich, Director, Health Care – Public Health Issues, GAO) [hereinafter Heinrich Testimony].

18 Ince, supra note 13, at 124; Galson Testimony, supra note 13, at 39.

19 Galson Testimony, supra note 13, at 39.

20 See Eric Schwam, Severe Accidental Overdose of 4-Aminopyridine Due to a Compounding Pharmacy Error, J. Emergency Med. (forthcoming 2010) (manuscript at 2, available online from J. Emergency Med.). For well over a century, compounding pharmacists have generally relied on instructions found in the United States Pharmacopeia, a widely-recognized compendium of drug standards. See Med. Ctr. Pharmacy, 536 F.3d at 388 (noting the incorporation of Pharmacopeia standards into the Federal Food, Drug, and Cosmetic Act).

21 Herbert Testimony, supra note 1, at 55.

22 See Schwam, supra note 20, at 2.

23 See Herbert Testimony, supra note 1, at 56.

24 Andrew Pollack, Sugary Mix Is Just What the Flu Doctor Ordered, N.Y. Times, Oct. 4, 2009, at A4.

25 See Galson Testimony, supra note 13, at 39.

26 See Herbert Testimony, supra note 1 at 56.

27 See id. at 55. “Almost all chemotherapy involves drugs and drug combinations that are compounded, or at least reconstituted, by pharmacists.” Id.

28 See Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients: Hearing on Oversight Before the Senate Comm. on Health, Education, Labor, & Pensions, 108th Cong. 47 (2003) (statement of Sarah Sellers, PharmD, Executive Director, The Center for Pharmaceutical Safety) [hereinafter Sellers Testimony]; Ince, supra note 13, at 127.

29 Herbert Testimony, supra note 1, at 55.

30 Id.

31 Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients: Hearing on Oversight Before the Senate Comm. on Health, Educ., Labor, and Pensions, 108th Cong. 85-86 (2003) (statement of the American Pharmacists Association) [hereinafter APA Testimony].

32 See Herbert Testimony, supra note 1, at 55.

33 See Ince, supra note 13, at 127.

34 APA Testimony, supra note 31, at 85.

35 See, e.g., W. Va. Code St. R. § 15-1-19.4 (2009).

36 Galson Testimony, supra note 13, at 39.

37 Thompson v. W. States Med. Ctr., 535 U.S. 357, 358 (2002).

38 Sellers Testimony, supra note 28, at 48.

39 Heinrich Testimony, supra note 17, at 33. Because pharmacies are not required to report compounding-related adverse events to the FDA, and are rarely required to report such events to State Boards of Pharmacy, the precise number of drug compounding errors is unknown. Id.

40 See Sellers Testimony, supra note 28, at 48-50 (characterizing the primary risks of compounding as subpotency, superpotency, and contamination).

41 V. Subramaniam & G. Sokol et al., Survey of Drug Products Compounded by a Group of Community Pharmacies: Findings from a Food and Drug Administration Study (2002), available at http://www.fda.gov/OHRMS/DOCKETS/dockets/05p0116/05p-0116-cp00001-10-Exhibit-09-vol1.pdf. The United States Pharmacopeia “is a non–governmental, official public standards–setting authority for prescription and over–the–counter medicines and other healthcare products manufactured or sold in the United States.” U.S. Pharmacopeia, About U.S.P., http://www.usp.org/aboutUSP/ (last visited Feb. 2, 2010); see also supra note 20.

42 Subramaniam & Sokol, supra note 41.

43 United States v. Courtney, 362 F.3d 497, 498-99 (8th Cir. 2004); see also Florence R. Parker, FDA Administrative Enforcement Manual 175 (2005).

44 Parker, supra note 43, at 175.

45 Erin Hallissy & Sabin Russell, Who's Mixing Your Drugs?, S.F. CHRON., June 23, 2002, at A1.

46 Parker, supra note 43, at 175.

47 U.S. Dep't of Health & Human Servs., Food & Drug Admin., Center for Drug Evaluation and Research, Limited FDA Survey of Compounded Drug Products (2006), available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm204237.htm.

48 Schwam, supra note 20, at 1-3. 4-Aminopyridine is an orphan drug not yet approved by the FDA. Id. at 1. Nevertheless, the drug is widely discussed on multiple sclerosis websites and available with a doctor's prescription from a compounding pharmacist. Id.

49 Id. at 2.

50 See Ince, supra note 13, at 125; Ctrs. for Disease Control & Prevention, Deaths from Intravenous Colchicine Resulting from a Compounding Pharmacy Error - Oregon and Washington, 56(40) MMWR 1050, 1050-52 (2007).

51 See Centers for Disease Control and Prevention, supra note 50, at 1051-52.

52 See Ince, supra note 13, at 125; Centers for Disease Control and Prevention, supra note 50, at 1051-52.

53 Sellers Testimony, supra note 28, at 49.

54 Id.

55 Id. at 46-47.

56 Lawrence A. Trissel et al., Effect of Two Work Practice Changes on the Microbial Contamination Rates of Pharmacy-Compounded Sterile Preparations, 64 Am. J. Health- Syst. Pharm. 837, 838 (2007); see also Am. Soc’y Health-System Pharmacists, ASHP Guidelines on Quality Assurance for Pharmacy-Prepared Sterile Products, 57 Am. J. Health- Syst. Pharm. 1150 (2000) (setting forth the currently prevailing quality assurance guidelines for compounded products).

57 Trissel, supra note 56, at 838.

58 Hallissy & Russell, supra note 45.

59 Id.

60 Id.

61 Id.

62 Erin Hallissy, No One at Pharmacy Admits Responsibility, S.F. Chron., June 23, 2002, at A21.

63 See Charlotte Muller, The Overmedicated Society: Forces in the Marketplace for Medical Care, SCIENCE, May 5, 1972.

64 Galson Testimony, supra note 13, at 39.

65 Id.

66 ApothéCure, Inc., http://www.apothecure.com/biocean.php (last visited Jan. 4, 2010).

67 See Thompson v. W. States Med. Ctr., 535 U.S. 357, 383-84 (2002) (Breyer, J., dissenting).

68 The level of compounding promotion and advertisement is impressive. Professor Bruce Patsner writes of compounded natural hormone replacements: “[I]t is often impossible to use public transportation without being confronted by advertising and promotion for these products and being bombarded by their alleged salutary effects.” Patsner, supra note 13, at 476.

69 W. States Med. Ctr., 535 U.S. at 387 (Breyer, J., dissenting).

70 A representative FDA Warning Letter to such a pharmacy reads in part:

The Agency remains seriously concerned … about the public health risks associated with the large-scale production of massive quantities of inhalation solutions without these products being required to meet all the laws and regulations applicable to a drug manufacturer. This concern exists especially in light of your firm's need to conduct a class 1 recall of 5 lots of various Albuterol inhalation solutions due to contamination with Serratia liquefaciens in December 2001 … . Your firm purports to be a compounding pharmacy … . You repeatedly manufacture the same inhalation products in such large quantities that the use of commercial scale equipment is required. You do not have prescription orders on hand for individually identified patients for all requests for compounded drug products that you receive.

FDA Warning Letter to Med-Mart Pulmonary Services, Sept. 30, 2002, available at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2002/ucm145144.htm.

71 Sellers Testimony, supra note 28, at 47; see also Perrin, supra note 16, at 556 (“Compounders have long ignored patents, orphan drugs statuses, and so on … . The copying of commercial products [under the guise of compounding] is not allowed in any other industrialized nation and must be stopped in the United States.”).

72 Joseph, L. Fink III, Compounding Versus Manufacturing in Pharmacy Practice: A Regulatory Challenge, 8 J. PHARM. PRAC. 103, 104 (1995)Google Scholar.

73 United States v. Baxter Healthcare Corp., 712 F. Supp. 1352, 1354 (N.D. Ill. 1989).

74 United States v. Baxter Healthcare Corp., 901 F.2d 1401, 1415 (7th Cir. 1990).

75 Id. at 1411-12.

76 Larry D. Sasich, Comments on a Draft of the Safe Drug Compounding Act of 2007, Public Citizen, Mar. 5, 2007, available at http://www.citizen.org/publications/release.cfm?ID=7519.

77 Sellers Testimony, supra note 28, at 47.

78 See Perrin, supra note 16, at 556. Such compounders have been especially effective in the “all-natural” area. See Ince, supra note 13, at 126.

79 Baxter Healthcare Corp., 901 F.2d at 1409; see also Tamira Mullarkey, Pharmacy Compounding of High-Risk Level Products and Patient Safety, 66 Am. J. Health-Syst. Pharm. S4, S8 (2009) (observing that the risk-amplification problem associated with compound-manufacturing is likely exacerbated by “ineffective oversight of pharmacy compounding” on both a state and federal level).

80 See infra Part V.

81 See id.

82 See Heinrich Testimony, supra note 17, at 31.

83 Sellers Testimony, supra note 28, at 51.

84 See Heinrich Testimony, supra note 17, at 33.

85 See id. at 32. The Vermont Board of Pharmacy, for example, did not conduct any routine pharmacy inspections between 1995 and 2003 due to a shortage of inspectors. Id. at 35.

86 See id.

87 21 U.S.C. §§ 301-450 (2006).

88 Jeffrey N. Wasserstein & Kurt R. Karst, Fifth Circuit Medical Center Pharmacy v. Mukasey Decision Creates Circuit Split Over FDCA § 503A Pharmacy Compounding “Safe Harbor,” FDA Law Blog, http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2008/07/fifth-circuit-m.html (last visited Jan. 3, 2010).

89 Federal Food, Drug, and Cosmetic Act of 1938, Pub. L. No. 75-717, 52 Stat. 1040 (1938).

90 21 U.S.C. § 321(g)(1) (2006).

91 21 U.S.C. § 355(a) (2006).

92 21 U.S.C. § 321(p) (2006). The 1962 amendments expanded the category of “new drugs” from those drugs not generally recognized as safe to those drugs not generally recognized as safe and effective. Pub. L. No. 87-781, 76 Stat. 781 (1962); see also Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609, 612-14 (1973). Since this change, “courts have interpreted expansively the Act's provisions to require pre-market approval of virtually all prescription drugs.” Galson Testimony, supra note 13, at 41.

93 21 U.S.C. § 355(b) (2006); 21 C.F.R. § 314.50 (2009).

94 The Act requires the Commissioner to disapprove any application when there is a lack of ‘substantial evidence’ that the applicant's drug is effective … . Evidence may be accepted only if it consists of ‘adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved … .’ Weinberger, 412 U.S. at 630.

95 Joseph, A. DiMasi et al., The Price of Innovation: New Estimates of Drug Development Costs, 22 J. Health Econ. 151, 180 (2003)Google Scholar.

96 James Robert Nielsen, Handbook of Federal Drug Law 14 (1992).

97 21 U.S.C. § 355(b) (2006); 21 C.F.R. § 314.50 (2009).

98 21 U.S.C. § 352 (2006).

99 21 U.S.C. § 351 (2006).

100 Galson Testimony, supra note 13, at 41.

101 See id.; Sundberg, supra note 10, at 314.

102 See Thompson v. W. States Med. Ctr., 535 U.S. 357, 362 (2002).

103 “Ironically, the proposed change in FDA's role in regulating compounding pharmacies came at a time when the business model for compounding pharmacies had not taken on the trajectory some current pharmacies have because the Internet was not widely used in the public domain for marketing purposes.” Patsner, supra note 13, at 464.

104 See id.; Jesse, C. Vivian, The FDA Mandate: Never Give Up, Never, 11 U.S. Pharmacist 84, 84 (2006)Google Scholar; Fink, supra note 72, at 104.

105 See, e.g., Fink, supra note 72, at 104.

106 U.S. Food and Drug Admin., Compliance Policy Guide 7132.16, Manufacture, Distribution and Promotion of Adulterated, Misbranded, or Unapproved New Drugs for Human Use by State-Licensed Pharmacies, Mar. 16, 1992 [hereinafter “1992 CPG”] (reprinted in Petition for Writ of Certiorari at 76a, Thompson v. Western States Medical Center, 535 U.S. 357 (2002) (No. 01-344)).

107 Id. at 71a-72a.

108 Id.

109 Id. at 76a-77a.

110 Id.

111 See Galson Testimony, supra note 13, at 41; Fink, supra note 72, at 111.

112 See Roger A. Fairfax, “Phederalism“: The Regulation of Pharmacy Compounding and Two Years in the Regulatory Turf War Between Pharmacy and the Food and Drug Administration 17-19 (1998) (unpublished manuscript, on file with the Legal Electronic Document Archive), available at http://leda.law.harvard.edu/leda/data/211/rfairfax.html.

113 See id. at 20-24. Then-FDA commissioner David Kessler called the proposed elimination of FDA regulation of compounding “one of the most glaring examples of a provision that undermines FDA's authority to protect the public from unsafe and ineffective products” and warned of a rising “shadow industry of unapproved generic drugs.” Michael F. Conlan, Compounding Protection Bill Could Lead to Patient Deaths, Kessler Charges, 140 Drug Topics 22, May 20, 1996.

114 Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, § 127, 111 Stat. 2296, 2328 (1997) (codified at 21 U.S.C. § 353a) (2006).

115 21 U.S.C. § 353a(a) (2006).

116 Id. §§ (b)(1)(A)-(B).

117 Id. § (b)(1)(C).

118 Id. § (b)(1)(D).

119 Id. § (b)(3)(A).

120 21 U.S.C. § 353a(b)(3)(B) (2006).

121 Id. §§ 353a(a); 353a(c).

122 Thompson v. W. States Med. Ctr., 535 U.S. 357, 365 (2002). Interestingly, one of the plaintiffs was ApothéCure, the Texas internet pharmacy that sold over 3,000 doses of superpotent colchicine leading to three deaths in Washington and Oregon. See supra Part III. See also ApothéCure, Inc., http://www.apothecure.com/ (last visited Jan. 3, 2010) (“We are one of the most respected and well-known compounding pharmacies in the nation … . With Creative Custom Compounding as our goal, we have developed numerous unique and effective compounded products … . You will discover the latest and most advanced treatments and protocols, along with a multitude of new and innovative products.”). Once the case reached the Supreme Court, the International Academy of Compounding Pharmacists, National Community Pharmacists Association, and American Pharmaceutical Association filed amicus briefs in support of the plaintiff-respondents.

123 W. States Med. Ctr., 535 U.S. at 365; see also 21 U.S.C. §§ 353a(a); 353a(c).

124 W. States Med. Ctr., 535 U.S. at 365-66.

125 W. States Med. Ctr. v. Shalala, 238 F.3d 1090, 1097 (9th Cir. 2001).

126 Id. at 1096.

127 Id. at 1097.

128 Id.

129 Id.

130 21 U.S.C. § 391 (2006).

131 W. States Med. Ctr. v. Shalala, 238 F.3d 1090, 1097-98 (9th Cir. 2001)

132 Thompson v. W. States Med. Ctr., 535 U.S. 357, 365-66 (2002).

133 Id. at 366.

134 Id.

135 Id. at 377.

136 447 U.S. 557, 566 (1980). Specifically, Central Hudson presents a four-prong test which asks: (1) whether the speech at issue concerns lawful activity and is not misleading; (2) whether the asserted governmental interest is substantial; (3) whether the restriction directly advances the asserted governmental interest; and (4) whether the restriction is not more extensive than is necessary to serve that interest. Each prong of the test must be answered in the affirmative for the restriction to be upheld. Id.

137 W. States Med. Ctr., 535 U.S. at 368-73.

138 Id. at 371.

139 Id. at 372.

140 Id. at 373.

141 Id. at 378-79 (Breyer, J., dissenting).

142 Id. at 379 (Breyer, J., dissenting). In response to this point by the dissent, the majority observed that the Government had never actually asserted this interest in its briefs. Id. at 373. The majority further faulted this interest for resting on “the questionable assumption that doctors would prescribe unnecessary medications” and the “fear that people would make bad decisions if given truthful information about compounded drugs.” Id. at 374.

143 Thompson v. W. States Med. Ctr., 535 U.S. 357, 382 (2002) (Breyer, J., dissenting).

144 See id. at 360-61, 376-77.

145 Id. at 382-83 (Breyer, J., dissenting).

146 Id. at 382 (Breyer, J., dissenting).

147 Id. at 385 (Breyer, J., dissenting).

148 See Patsner, supra note 13, at 466.

149 U.S. Food and Drug Admin., Compliance Policy Guide § 460.200, available at http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074398.htm [hereinafter Updated CPG].

150 Id.

151 Id.

152 1992 CPG, supra note 106, at 72a.

153 Updated CPG, supra note 149 (“Some ‘pharmacies’ that have sought to find shelter under and expand the scope of the exemptions applicable to traditional retail pharmacies have claimed that their manufacturing and distribution practices are only the regular course of the practice of pharmacy”).

154 Id.

155 Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383, 392 (2008).

156 Id.

157 Med. Ctr. Pharmacy v. Gonzalez, 451 F. Supp. 2d 854, 868 (W.D. Tex. 2006).

158 Id. at 862-63.

159 Id.

160 Id. at 863.

161 Id.

162 Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383, 408-09 (5th Cir. 2008).

163 Id. at 401.

164 Id. at 402 n.42.

165 Id. at 403.

166 Id. at 403-04.

167 Id. at 394.

168 Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383, 400 (5th Cir. 2008).

169 Id.

170 Id. at 394 (emphasis in original).

171 Regan v. Time, Inc., 468 U.S. 641, 653 (1984).

172 Alaska Airlines, Inc. v. Brock, 480 U.S. 678, 684 (1987).

173 Id. at 685.

174 Id. at 684.

175 21 U.S.C. § 391 (2006).

176 Brock, 480 U.S. at 686.

177 W. States Med. Ctr. v. Shalala, 238 F.3d 1090, 1097-98 (9th Cir. 2001).

178 Id. at 1098.

179 Michael, D. Shumsky, Severability, Inseverability, and the Rule of Law, 41 Harv. J. on Legis. 227, 240 (2004)Google Scholar.

180 Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383, 402 (5th Cir. 2008).

181 W. States Med. Ctr., 238 F.3d at 1097.

182 S. Rep. No. 105-43, at 67 (1997)

183 H.R. Conf. Rep. 105-399, at 94 (1997) (Conf. Rep.).

184 W. States Med. Ctr., 238 F.3d at 1096-97.

185 See Lorillard Tobacco Co. v. Reilly, 533 U.S. 525, 557 (2001) (“[W]e have acknowledged the theory that product advertising stimulates demand for products … .”); Cent. Hudson Gas & Elec. Corp. v. Public Serv. Comm'n, 447 U.S. 557, 569 (1980) (“There is an immediate connection between advertising and demand … .”).

186 New York v. United States, 505 U.S. 144, 186 (1992); see also United States v. Booker, 543 U.S. 220, 258-65 (2005) (striking down and severing the mandatory provisions of the Federal Sentencing Guidelines and observing that “[t]he system remaining after excision, while lacking the mandatory features that Congress enacted, retains other features that help to further” Congress’ “initial and basic sentencing intent” of promoting certainty, fairness, and flexibility in sentencing).

187 Thompson v. W. States Med. Ctr., 535 U.S. 357, 372-73 (2002) (emphasis added).

188 Id. at 372-73.

189 See Fairfax, supra note 112, at 28; Supplemental Brief of Appellees at 8-21, Med. Ctr. Pharm. v. Mukasey, 536 F.3d 383 (5th Cir. 2008) (No. 06-51583).

190 Med. Ctr. Pharmacy, 536 F.3d at 399.

191 See Fairfax, supra note 112, at 30-32.

192 United States v. Bader, No. 07-cr-00338-MSK, 2009 WL 2219258, at *13 (D. Colo. July 23, 2009) (“[T]o the extent the operation of FDAMA is germane to this action, it operates as an affirmative defense on which [defendant pharmacist] will bear the burden of proof by a preponderance of the evidence.“).

193 See Updated CPG, supra note 149; Brief for Appellants at 28-29, Medical Center Pharmacy v. Gonzalez, No. 06-51583 (5th Cir. Mar. 30, 2007); Pharmacy Compounding/Compounding of Bio-identical Hormone Replacement Therapies: Hearing Before the Senate Special Committee on Aging, 110th Cong. (2007) (statement of Steven K. Galson, Director, Center of Drug Evaluation and Research, Food and Drug Administration), available at http://www.fda.gov/NewsEvents/Testimony/ucm154031.htm.

194 See Galson Testimony, supra note 13, at 44.

195 See FDA Warning Letter to Med-Mart Pulmonary Services, supra note 70; Wedgewood Village Pharmacy, Inc. v. United States, 421 F.3d 263, 274-75 (3d Cir. 2005).

196 See supra Part VI.B.

197 Id.

198 Because the issue goes to the FDA's construction of a statute that it administers, the necessary lens for the argument is Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc. 467 U.S. 837 (1984). Under Chevron, the first question is “whether Congress has directly spoken to the precise question at issue.” Id. at 842. If Congress has done so, its “unambiguously expressed intent” must be respected. Id. at 842-43. If Congress has not done so, a reviewing court must respect the FDA's construction of the statute as long as it is “not arbitrary, capricious, or manifestly contrary to the statute.” Id. at 843-44.

199 S. Rep. No. 105-43, at 67 (1997) (“The committee has found that clarification is necessary to address current concerns and uncertainty about the Food and Drug Administration's regulatory authority over pharmacy compounding.”).

200 See supra note 88 & accompanying text; see also supra Part V.

201 Thompson v. W. States Med. Ctr., 535 U.S. 357, 369 (2002) (citing Brief for Petitioners).

202 Representative John M. Coffee remarked during debate on the FDCA: “Pharmacists are licensed to compound and dispense drugs. Electricians, plumbers, and steam engineers pursue their respective trades under license. But there is no such control to prevent incompetent drug manufacturers from marketing any kind of lethal potion.” Extension of Remarks of Rep. John M. Coffee, 83 CONG. REC. 2279, 2279 (June 1, 1938) (quoting Henry A. Wallace, Secretary of Agriculture).

203 See Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383, 398 (5th Cir. 2008).

204 Brief of Appellees at 8-9, Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383 (5th Cir. 2008) (No. 06-51583), (quoting Memorandum by FDA Counsel in Response to FDA's Proposal to Regulate Positron Emission Tomography) (emphasis omitted).

205 See supra note 198.

206 United States v. Boston Farm Ctr., Inc., 590 F.2d 149, 151 (5th Cir. 1979) (quoting 21 U.S.C. § 336 (2006)); see also 21 U.S.C. § 336 (2006); Med. Ctr. Pharmacy, 536 F.3d at 399.

207 Compounding, Repackaging, or Manufacturing?, Drug and Device Law Blog, July 31, 2009, http://druganddevicelaw.blogspot.com/2009/07/compounding-repackaging-or.html.