Informal guidance and the FDA

Food and Drug Law Journal

Volumn 66, Issue 4, 2011, Pages

  Lewis, Kevin Michael ^a  

^a HARVARD LAW SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMBIGUITY; COURT; FOOD AND DRUG ADMINISTRATION; GOVERNMENT; HEALTH CARE POLICY; HISTORY OF MEDICINE; LAW; MEDICATION ERROR; PRACTICE GUIDELINE; REVIEW; SOCIAL PARTICIPATION; UNITED STATES;

GUIDELINES AS TOPIC; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; LEGISLATION, DRUG; LEGISLATION, FOOD; MEDICAL DEVICE LEGISLATION; POLICY MAKING; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84873161946     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (391)

1. E.g., Chevron, U.S.A., Inc. v. Nat'l Res. Def. Council, 467 U.S. 837, 843-44 (1984)
2. (quoting Morton v. Ruiz, 415 U.S. 199, 231 (1974));
3. James Hunnicutt, Another Reason to Reform the Federal Regulatory System: Agencies' Treating Nonlegislative Rules as Binding Law, 41 B.C. L. REV. 153, 155-56 (1999);
4. Cass R. Sunstein, Chevron Step Zero, 92 VA. L. REV. 187, 188-198 (2006);
5. Antonin Scalia, Judicial Deference to Administrative Interpretations of Law, 1989 DUKE L.J. 511, 516-17.
6. But see generally Mark Seidenfeld, Chevron's Foundation, 86 NOTRE DAME L. REV. 273 (2011) (rejecting the notion of "congressional intent to delegate interpretive primacy to agencies").
7. Policies promulgated through rulemaking are known as "regulations, " "legislative rules," or just "rules." See Hunnicutt, supra note 2, at 153. Rulemaking is in turn split into two categories: informal and formal rulemaking. Id. at 159 (citing 5 U.S.C. §§ 553, 556-57 (1994)). Because the overwhelming majority of regulations are promulgated through informal rulemaking, id., the reader may safely assume that every instance of the word "rulemaking" in this article refers to informal rulemaking.
8. See generally M. Elizabeth Magill, Agency Choice of Policymaking Form, 71 U. CHI. L. REV. 1383, 1386 (2004); see also 5 U.S.C. §§ 553-57 (2011).
9. The rulemaking process imposes other procedural requirements as well. For an excellent summary, see, e.g., Connor N. Raso, Strategic or Sincere? Analyzing Agency Use of Guidance Documents, 119 YALE L.J. 782, 788 (2010);
10. Anne Joseph O'Connell, Political Cycles of Rulemaking: An Empirical Portrait of the Modern Administrative State, 94 VA. L. REV. 889, 900-02 (2008). Rules promulgated by agencies are "legally binding, generally applicable, and nonretroactive." Raso, supra at 788.
11. Magill, supra note 4, at 1386.
12. Id. Guidance documents are also often referred to as "nonlegislative rules," "interpretative rules," "statements of policy," or "guidelines," as well as "innumerable" other synonyms. Hunnicutt, supra note 2, at 153, 177. For an excellent and extensive definition of guidance, see Raso, supra note 5, at 785 n.1.
13. Magill, supra note 4, at 1386; see also Raso, supra note 5, at 785 n.1.
14. Hunnicutt, supra note 2, at 157-76 (citing 5 U.S.C. § 553(b)(A) (1994)).
15. Nina A. Mendelson, Regulatory Beneficiaries and Informal Agency Policymaking, 92 CORNELL L. REV. 397, 406-07 (2007).
16. Id. at 407. Some scholars have decried this aspect of informal guidance. See, e.g., Robert A. Anthony, Interpretive Rules, Policy Statements, Guidances, Manuals, and the Like - Should Federal Agencies Use Them to Bind the Public?, 41 DUKE L.J. 1311, 1315 (1992) ("While these nonlegislative rules by definition cannot legally bind, agencies often inappropriately issue them with the intent or effect of imposing a practical binding norm upon the regulated or benefited public.");
17. JAMES T. O'REILLY, FOOD AND DRUG ADMINISTRATION § 4:24 4-87 (3d ed. 2007) (quoting Byerly, FDA Administrative Procedures: The Myth and the Reality in FOOD, DRUG, AND COSMETIC INDUSTRY 43 (V. Kleinfeld ed. 1972));
18. see generally Hunnicutt, supra note 2. Others have viewed the rule-like effects of guidance more charitably. Lars Noah, FDA's New Policy on Guidelines: Having Your Cake and Eating it Too, 47 CATH. U. L. REV. 113, 120-142 (1997);
19. Todd D. Rakoff, The Choice Between Formal and Informal Modes of Administrative Regulation, 52 ADMIN L. REV. 159 (2000).
20. Mendelson, supra note 10, at 397. See also Erica Seiguer and John J. Smith, Perception and Process at the Food and Drug Administration: Obligations and Tradeoffs in Rules and Guidances, 60 FOOD & DRUG L.J. 17, 29-30 (2005) ("[I]n practice[,] . . . industry treats guidances no differently than rules . . . Most business people don't know the difference between a reg[ulation passed through rulemaking] and a guidance, so by and large the business field does not care. All they want is clarity [and consistency].").
21. Stephen M. Johnson, Good Guidance, Good Grief!, 72 MO. L. REV. 695, 695 (2007). Guidance in its current form is such a new phenomenon that, as late as 2000, neither the leading Administrative Law treatise nor eminent administrative law casebooks listed "guidance" in their indexes. Rakoff, supra note 11, at 160. Indeed, when FDA issued its "Good Guidance Practices," which will be described infra Section I.H.2, "FDA had to devote the first part of its statement simply to defining what it was talking about." Id. at 159-60.
22. Cf. O'Connell, supra note 5, at 917 (discussing different types of policymaking, including nonlegislative rulemaking, i.e. guidance).
23. Magill, supra note 4, at 1399.
24. Id. at 1398-99.
25. Rakoff, supra note 11, at 163.
26. Id. at 168; John C. Carey, Is Rulemaking Old Medicine at the FDA?, 3-6 (1997), in FOOD AND DRUG LAW: AN ELECTRONIC BOOK OF STUDENT PAPERS (Peter Barton Hutt, ed., 2011), available at http://www.law.harvard.edu/faculty/hutt/book- index.html.
27. See generally, e.g., Rakoff, supra note 11; Seiguer and Smith, supra note 12.
28. Rakoff, supra note 11, at 159-60.
29. For a historical overview of FDA and its predecessors, see Peter Barton Hutt, Symposium on the History of Fifty Years of Food Regulation Under the Federal Food, Drug, and Cosmetic Act: A Historical Introduction, 45 FOOD DRUG COSM. L. J. 17, 18 (1990).
30. Noah, supra note 11, at 115.
31. United States Department of Agriculture, Bureau of Chemistry, FIDs 1-25, Introduction (1905). Individual FIDs will hereinafter be cited as "FID # (year of issuance)."
32. FID 28 (1905).
33. FID 46 (1906).
34. FID 51 (1907).
35. FID 147 (1912).
36. FID 44 (1906).
37. FID 44 (1906).
38. Researching FDA with Published Primary Sources, http://www.fda.gov/ AboutFDA/WhatWeDo/History/ResearchTools/ ResearchingFDAwithPublishedPrimarysources/default.htm (last visited Jun. 30, 2011) [hereinafter Primary Sources].
39. 21 U.S.C. § 301 et seq. (1938).
40. Peter Barton Hutt, Philosophy of Regulation Under the Federal Food, Drug, and Cosmetic Act, 50 FOOD & DRUG L.J. 101, 102 (1995 (Historical Article, originally published in 1973)).
41. Carey, supra note 18, at 3.
42. Noah, supra note 11, at 114.
43. Id. at 115-16 (1997); William Van Brunt, Advisory Opinions, 32 FOOD DRUG COSM. L. J. 304, 305 (1977).
44. VINCENT A. KLEINFELD AND CHARLES WESLEY DUNN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1938-1949 561 (1949) [hereinafter 1938-49].
45. Noah, supra note 11, at 114.
46. A collection of every TC issued by FDA may be found in 1938-1949, supra note 37, at 561-753. TCs will hereinafter be cited as "TC-# (date of issuance)."
47. Primary Sources, supra note 31.
48. TC-32 (Feb. 9, 1940).
49. TC-114 (Feb. 29, 1940).
50. TC-229 (Apr. 11, 1940).
51. TC-86 (Feb. 21, 1940).
52. 5 U.S.C. 500 et seq. (1946).
53. See Robert L. Rabin, Federal Regulation in Historical Perspective, 38 STAN. L. REV. 1189, 1264-66 (1986)
54. (citing Report of the Special Committee on Administrative Law, 63 A.B.A. REP. 331, 346-51 (1938)).
55. Hunnicutt, supra note 2, at 153-54.
56. 5 U.S.C. §§ 551-59, 701-06 (1946).
57. George B. Shepherd, Fierce Compromise: The Administrative Procedure Act Emerges from New Deal Politics, 90 NW. U. L. REV. 1557, 1559 (1996).
58. Wolf Heydebrand, Government Litigation and National Policymaking: From Roosevelt to Reagan, 24 LAW & SOC'Y REV. 477, 488-89 (1990).
59. 1938-49, supra note 37, 561.
60. E.g., Rakoff, supra note 11, at 164-65.
61. 1938-49, supra note 37, 561.
62. Compare Appendix A, Figure 2, infra, with Appendix A, Figure 3, infra. I should note, however, that the average annual number of TCs is skewed heavily by the massive number of TCs issued in 1940. Furthermore, I have not performed a quantitative analysis to determine whether this divergence is statistically significant, so my conclusion is necessarily impressionistic. Finally, correlation is not causation; a more rigorous examination, controlling for more variables, would be necessary to confirm that the enactment of the APA in fact resulted in fewer guidance documents. Given the massive overhaul of administrative procedure that the APA effected, however, this inference is extremely plausible.
63. See, e.g., 21 C.F.R. § 3.1 (historical version, 1947) (citing § 3, 60 Stat. 237 (1946)). Had FDA been required to utilize notice-and-comment procedures, the regulations would also have cited the rulemaking requirements of the APA, codified in § 4 of 60 Stat. 237. See also Eve H. Bachrach, Federal Regulation of Soap Products, in THE COSMETIC INDUSTRY: SCIENTIFIC AND REGULATORY FOUNDATIONS, 61, 64 (Norman F. Estrin, ed. 1984);
64. VINCENT A. KLEINFELD AND CHARLES WESLEY DUNN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1953-1957 xiii (1957) (distinguishing between Statements of General Policy or Interpretation and regulations promulgated with "the force and effect of law") [hereinafter 1953-57]; 5 U.S.C. § 553(b)(A) (2011) ("interpretative rules" and "general statements of policy" exempt from the required rulemaking procedures established by the APA);
65. 22 Fed. Reg. 7393 (1957) (stating that FDA Statement issued in conformity with APA's public information procedures but not its rulemaking requirements).
66. 1938-49, supra note 37, xvii.
67. e.g., "The Federal Security Agency no longer regards all salt substitutes as new drugs;" Statement of General Policy or Interpretation 3.20 (Feb. 14, 1951), in VINCENT A. KLEINFELD AND CHARLES WESLEY DUNN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1951-1952 385 (1953) [hereinafter 1951-52]; "Labeling of Antibiotic Drugs for Veterinary Use;" Statement of General Policy or Interpretation 3.25 (Aug. 15, 1951), in 1951-52, supra, 388; "The use of antibiotic drugs as food preservatives constitutes a public health hazard . . . [and] may be deemed an adulteration." Statement of General Policy or Interpretation 3.29 (Feb. 18, 1953), in 1953-57, supra note 58, 310.
68. See, e.g., VINCENT A. KLEINFELD AND ALAN H. KAPLAN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1958-60 223, n.* (1961) [hereinafter 1958-60].
69. 1953-57, supra note 58, 808.
70. Id.; 1958-60, supra note 61, 223.
71. 1953-57, supra note 58, 808.
72. Though all cases experienced fairly immediate per vagina bleeding post self-induced treatment, none terminated her pregnancy; instead, the caustic agents burned the vaginal fornix severely; in fact, the vast majority of cases delivered liveborn, normal fetuses after attempted abortion." BB Obeng, The Lay Use of Potassium Permanganate as an Abortifacient., 22 BR. J. CLIN. PRACT. 465 (1968), abstract available at http://www.ncbi.nlm.nih.gov/pubmed/5696512.
73. Formal Statement of General Policy or Interpretation 3.7 (Aug. 23, 1960), in 1958-60, supra note 61, 225-26. This Statement was amended on February 3, 1962. VINCENT A. KLEINFELD AND ALAN H. KAPLAN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1961-64 262-63 (1965) [hereinafter 1961-64].
74. Informal Statement of General Policy or Interpretation 3.202 (Nov. 30, 1957), in 1953-57, supra note 58, 809.
75. Compare Informal Statement of General Policy or Interpretation 3.208 (Nov. 28, 1959), in 1958-60, supra note 61, 237-43 with Formal Statement of General Policy or Interpretation 3.5 (Sept. 5, 1958), in 1958-60, supra note 61, 224.
76. Compare VINCENT A. KLEINFELD AND ALAN H. KAPLAN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1965-68 483-512 (1973) [hereinafter 1965-68]
77. with VINCENT A. KLEINFELD, ALAN H. KAPLAN, & STEPHEN A. WEITZMAN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1969-1974 (1976).
78. Carey, supra note 18, at 2-4.
79. Compliance Policy Guides 〉 Introduction, http://www.fda.gov/ICECI/ ComplianceManuals/CompliancePolicyGuidanceManual/ucm116791.htm (last visited Jul. 7, 2011) [hereinafter CPG Introduction].
80. CPG § 270.100 Final Container Labels - Allergenic Extracts Containing Glycerin; Reporting Changes (originally issued Jul. 1976), available as revised at http://www.fda.gov/ICECI/Compliance-Manuals/ CompliancePolicyGuidanceManual/ucm122803.htm.
81. CPG § 220.100 - IS Shipment Biologicals for Medical Emergency (originally issued Dec. 1977), available as revised at http://www.fda.gov/ICECI/ ComplianceManuals/CompliancePolicyGuidance-Manual/ucm073860.htm.
82. CPG § 555.600 Filth from Insects, Rodents, and Other Pests in Foods (originally issued Jan. 1973), available as revised at http://www.fda.gov/ICECI/ ComplianceManuals/CompliancePolicyGuidanceManual/ucm074559.htm.
83. 40 Fed. Reg. 40682, 40694 (1975).
84. Manual of Compliance Policy Guides, http://www.fda.gov/ICECI/ ComplianceManuals/CompliancePolicyGuidanceManual/default.htm. [hereinafter Manual of CPGs]
85. 40 Fed. Reg. 40682, 40694 (1975).
86. O'REILLY, supra note 11, § 4:25 4-93.
87. See infra Section I.H.3.
88. See generally Peter Barton Hutt, FDA Court Actions & Recent Legal Developments, 39 ASS'N OF FOOD & DRUG OFFICIALS Q. BULL. 11 (1975);
89. Peter Barton Hutt, Public Information and Public Participation in the Food and Drug Administration, 36 ASS'N OF FOOD & DRUG OFFICIALS Q. BULL. 212 (1972) [hereinafter Hutt, Public Info].
90. 40 Fed. Reg. 40682, 40695 (1975).
91. 40 Fed. Reg. 40682, 40682-83 (1975).
92. Noah, supra note 11, at 114 (citing 42 Fed. Reg. 4680, 4708-10 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (1997)).
93. 42 Fed. Reg. 4680, 4708-10 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (2011)).
94. Subject, of course, to the possibility that FDA might later modify its policy.
95. 42 Fed. Reg. 4680, 4709 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (2011)) ("An advisory opinion may be used in administrative or court proceedings to illustrate acceptable and unacceptable procedures or standards, but not as a legal requirement . . . A person may rely upon a guideline with assurance that it is acceptable to the Food and Drug Administration, or may follow different procedures or standards. Where a person chooses to use different procedures or standards, he may, but is in no instance required to, discuss the matter in advance with the Food and Drug Administration to prevent the expenditure of money and effort on activity that may later be determined to be unacceptable."). See also Noah, supra note 11, at 116-18 ("The regulation does nothing more than bind FDA in the sense that it agrees to issue reliable advice about how it interprets the requirements imposed by the statute and regulations. Formal advisory opinions and guidelines would not, for instance, give third parties the right to object to Agency decisions accepting submissions by a regulated firm that are allegedly inconsistent with those opinions or guidelines.").
96. 42 Fed. Reg. 4680, 4709 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (2011)).
97. 40 Fed. Reg. 40682, 40694 (1975).
98. 21 C.F.R. § 10.90(b) (historical version, 1978).
99. 42 Fed. Reg. 4680, 4708 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (2011)).
100. 42 Fed. Reg. 4680, 4709 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (2011)).
101. See Noah, supra note 11, at 114, 116-18.
102. 42 Fed. Reg. 4680, 4694 (1977).
103. 42 Fed. Reg. 4680, 4708-09 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (2011)). However, not ail commentators view the guidance request process as particularly beneficial for industry. "It is axiomatic that the person requesting the agency's advice must be prepared to live with any answer received, even an unfavorable one, and that some particularly uncertain areas are best left unexplored." O'REILLY, supra note 11, § 4:25 4-95
104. (citing Kleinfeld, Approach to FDA: Tactics and Strategy, in FEDERAL REGULATION OF THE DRUG INDUSTRY (V. Kleinfeld ed. 1972)). Some attorneys' views on the process are therefore well summed up by the following pithy quote: "When to write the Agency: Practically never." Id.
105. 42 Fed. Reg. 4680, 4709-10 (1977) (codified as amended at 21 C.F.R. §§ 10.85, 10.90 (2011)) ("A guideline may be amended or revoked upon approval of the amended guideline or revocation of the guideline by the relevant bureau director and publication by the Commissioner in the Federal Register of a notice of such amendment or revocation. The notice shall state (i) the title of the guideline, (ii) the subject matter it covers, and (iii) the office or individual responsible for maintaining the guideline."). See also Noah, supra note 11, at 114.
106. Noah, supra note 11, at 114.
107. 467 U.S. 837 (1984).
108. To determine whether the statutory text unambiguously addresses the question at issue, courts utilize the "traditional tools of statutory construction." Id. at 843 n.9.
109. Id. at 842-43.
110. Sunstein, supra note 2, at 188. But see Christensen v. Harris County, 529 U.S. 576, 596 (2000) (Breyer, J., dissenting) (arguing that Chevron was an outgrowth of prior caselaw, rather than a massive change to it).
111. Jeffrey A. Pojanowski, Reason and Reasonableness in Review of Agency Decisions, 104 NW. U. L. REV. 799, 804 (2010)
112. (citing Peter H. Schuck & E. Donald Elliott, To the Chevron Station: An Empirical Study of Administrative Law, 1990 DUKE L.J. 984, 1029-43));
113. Elizabeth Garrett, Legislating Chevron, 101 MICH. L. REV. 2637, 2645 n.35 (2003).
114. But see Connor N. Raso & William N. Eskridge, Jr., Chevron as a Canon, Not a Precedent: An Empirical Study of What Motivates Justices in Agency Deference Cases, 110 COLUM. L. REV. 1727, 1739-40 (2010) (summarizing empirical studies suggesting ambiguity regarding whether Chevron actually increased judicial deference to agency interpretations).
115. James T. O'Reilly, Losing Deference in FDA's Second Century: Judicial Review, Politics, and a Diminished Legacy of Expertise, 93 CORNELL L. REV. 939, 941-42 (2008) (internal citations omitted).
116. Jonathan R. Siegel, Guardians of the Background Principles, 2009 MICH. ST. L. REV. 123, 130.
117. Pojanowski, supra note 103, at 804 (citing Schuck & Elliott, supra note 103, at 1029-43). But see Raso & Eskridge, supra note 103, at 1739-40.
118. O'Reilly, supra note 104, at 941-42.
119. 476 U.S. 974 (1986).
120. Id. at 976-78 (quoting 46 Fed. Reg. 7448 (1981)) ("On some occasions, FDA has instead set 'action levels' through a less formal process. In setting an action level, FDA essentially assures food producers that it ordinarily will not enforce the general adulteration provisions of the Act against them if the quantity of the harmful added substance in their food is less than the quantity specified by the action level.").
121. National Pharmaceutical Alliance v. Henney, 47 F.Supp.2d 37 (D.D.C. 1999);
122. Berlex Laboratories, Inc. v. FDA, 942 F.Supp. 19 (D.D.C. 1996).
123. See generally Patricia G. Chapman, Has the Chevron Doctrine Ran Out of Gas? Senza Ripieni Use of Chevron Deference or the Rule of Lenity, 19 MISS. C. L. REV. 115, 137 (1998).
124. Alliance for Bio-Integrity v. Shalala, 116 F.Supp.2d 166, 176-179 (D.D.C. 2000).
125. Id. at 172-73.
126. Sunstein, supra note 2, at 208-10. "Without pausing to explore the [question of whether Chevron deference is warranted for interpretations formulated without formal procedures,] the Court [in Young] deferred to the agency and upheld its interpretation." Id. at 208. Young therefore seemed to suggest that the Chevron doctrine operates as follows: "Whenever an agency makes an authoritative interpretation of a statute that it administers, that interpretation falls under the Chevron framework, unless the agency's self-interest is so conspicuously at stake that it is implausible to infer a congressional delegation of law-interpreting power. On this approach, it is necessary only to know whether purported interpreters authoritatively speak for the agency itself. If they do, the Chevron framework applies." Id. at 210. As explained in greater detail infra Section I.I., however, this interpretation of Chevron was not borne out in subsequent cases. See also United States v. Mead Corp., 533 U.S. 218, 239-261 (2001) (Scalia, J., dissenting) ("Whereas previously a reasonable agency application of an ambiguous statutory provision had to be sustained so long as it represented the agency's authoritative interpretation, henceforth such an application can be set aside unless 'it appears that Congress delegated authority to the agency generally to make rules carrying the force of law,' as by giving an agency 'power to engage in adjudication or notice-and-comment rulemaking, or ... some other [procedure] indicating] comparable congressional intent,' and 'the agency interpretation claiming deference was promulgated in the exercise of that authority.'" (citations omitted)).
127. John P.C. Duncan, The Course of Federal Preemption of State Banking Law, 18 ANN. REV. BANKING L. 221, 266 (1999).
128. See supra note 11.
129. See generally Carey, supra note 18, For an excellent yet succinct historical summary of the ossification of notice-and-comment rulemaking, see Rakoff, supra note 11, at 164-65. But see O'Connell, supra note 5, at 932-36 (arguing "that the procedural costs to rulemaking (from the agency's perspective) are not so high as to prohibit considerable rulemaking activity by agencies").
130. Rakoff, supra note 11, at 168.
131. Id. See generally Seiguer and Smith, supra note 12.
132. 57 Fed. Reg. 47314, 47314 (1992).
133. Id. at 47315.
134. 818 F.2d 943 (D.C. Cir. 1987); 57 Fed. Reg. 47314, 47315 (1992).
135. Noah, supra note 11, at 137 (citing CNI, 818 F.2d at 948-49).
136. 57 Fed. Reg. 47314, 47315 (1992).
137. See generally Noah, supra note 11.
138. 62 Fed. Reg. 8961, 8962-63 (1997).
139. Id. (codified as amended at 21 C.F.R. § 10.115 (2011)).
140. 21 C.F.R. § 10.115 (2011).
141. 62 Fed. Reg. 8961, 8961 (1997).
142. Rakoff, supra note 11, at 168.
143. 61 Fed. Reg. 9181, 9181 (1996).
144. Pub. L. No. 105-115, §405, 111 Stat. 2296, 2368-69 (codified at 21 U.S.C. § 371(h) (1997)). See also Paul R. Noe & John D. Graham, Due Process and Management for Guidance Documents: Good Governance Long Overdue, 25 YALE J. ON REG. 103, 107 (2008).
145. 21 C.F.R. § 10.115 (historical version, 2001); 21 C.F.R. § 10.115 (2011).
146. Id. § 10.115(i)(iii).
147. Id. §§ 10.115(i)(i), (i)(iv).
148. 21 C.F.R. § 10.115(c)(1) (2011).
149. Id. § 10.115(c)(2).
150. See 5 U.S.C. § 553 (2011); Hunnicutt, supra note 2, at 180; Michael Jon Andersen, Sound Guidance: FDA Rulemaking for Off-Label Pharmaceutical Drug Marketing, 60 CASE W. RES. L. REV. 531, 536-37 (2010).
151. See also 65 Fed. Reg. 56468, 56473 (2000) (differentiating informal guidance from notice-and-comment rulemaking).
152. 21 C.F.R. § 10.115(g)(1)-(3) (2011).
153. Mendelson, supra note 10, at 425-26. See also United States v. Nova Scotia Food Prods. Corp., 568 F.2d 240, 252-253 (1977). Some have viewed this aspect of the GGPs quite negatively. Seiguer and Smith, supra note 12, at 30 (noting that some industry representatives believe that "even though FDA accepts comments from the public, . . . it is very unusual for FDA to actually change its position or incorporate any of the feedback into the guidance").
154. 21 C.F.R. § 10.115(g)(1)(iv)(A) (2011).
155. See Nova Scotia, 568 F.2d at 252-253 (holding a regulation invalid for failing to respond to significant comments, inter alia).
156. 21 C.F.R. § 10.115(g)(4) (2011).
157. Compare id. § 10.115(g)(4)(i) with id. § 10.115(g)(1).
158. Compare id. § 10.115(g)(4)(i) with id. § 10.115(g)(1). See also Andersen, supra note 140, at 537.
159. 21 C.F.R. §§ 10.115(g)(5), (f)(4) (2011).
160. Id. § 10.115(f)(2).
161. Id. § 10.115(f)(3).
162. Id. § 10.115(j).
163. Id. § 10.115(d)(1).
164. Id. § 10.115(d)(3). But see Hunnicutt, supra note 2, at 182-83 (criticizing this provision's lack of clarity).
165. Supra notes 134-135.
166. 21 C.F.R. § 10.115(e) (2011).
167. Id. §§ 10.115(l),(o).
168. Noah, supra note 11, at 114; 57 Fed. Reg. 47314, 47314 (1992);
169. 61 Fed. Reg. 9181, 9181 (1996).
170. 21 C.F.R. § 10.115 (historical version, 2001).
171. Compare 21 C.F.R. § 10.90(b) (historical version, 1978) with 21 C.F.R. § 10.90(b) (2011).
172. Compare 42 Fed. Reg. 4680, 4708-09 (1977) with 21 C.F.R. § 10.85 (historical version, 2001) ("An advisory opinion represents the formal position of FDA on a matter and except as provided in paragraph (f) of this section, obligates the agency to follow it until it is amended or revoked. The Commissioner may not recommend legal action against a person or product with respect to an action taken in conformity with an advisory opinion which has not been amended or revoked.").
173. 21 C.F.R. § 10.85(d) (2011).
174. "FDA issues virtually no advisory opinions of the type described in [21 C.F.R. § 10.85(a)] . . . Most documents that have the same status as an advisory opinion . . . fall within the preambles to proposed or final regulations, the compliance policy guides, and the other items identified in that subsection. Considering the number of Federal Register preambles, that is undoubtedly by far the greatest, and most important, source of statements that have the status of an advisory opinion." Letter, supra note 85.
175. Barbara J. Evans & Eric M. Meslin, Encouraging Translational Research Through Harmonization of FDA and Common Rule Informed Consent Requirements for Research with Banked Specimens, 27 J. LEGAL MED. 119, 157 n.118 (2006).
176. 57 Fed. Reg. 47314, 47317 (1992) ("An advisory opinion represents the best advice of FDA on a matter at the time of its issuance. However, an advisory opinion does not bind the agency, and it does not create or confer any rights, privileges, or benefits for or on any person." (emphasis added)). FDA mentioned the proposed provision several years later, but did not give much useful information for resolving the paradox at issue: "In the Federal Register of October 15, 1992 . . . FDA proposed to amend §§10.85 and 10.90, which address advisory opinions and guidelines, to delete the provisions that obligate the agency to follow advisory opinions and guidelines until they are amended or revoked (except in unusual situations involving immediate and significant danger to health). As set forth in the proposed rule, those provisions appear to be inconsistent with the general principle that Federal agencies may not be estopped from enforcing the law. Although FDA has not yet issued a final rule, the agency plans to make final decisions on the 1992 proposal under that rulemaking."
177. 61 Fed. Reg. 9181, 9183 n.1 (1996) (internal citations omitted). In a subsequent volume of the Federal Register, FDA perfunctorily responded to a comment requesting an explanation of how the GGPs affected the status of advisory opinions: "We issue advisory opinions under § 10.85. We anticipate modifying § 10.85 and explaining the effect of § 10.115 on previously issued advisory opinions in a separate rulemaking effort. As such, the comment is outside the scope of this rulemaking."
178. 65 Fed. Reg. 56468, 56474 (2000). This rulemaking never took place, and the proposed amendment was never unearthed. See infra note 178.
179. 57 Fed. Reg. 47314, 47314 (1992).
180. Compare 21 C.F.R. § 10.85 (historical version, 2001) with 21 C.F.R. § 10.85 (2011).
181. Telephone Interview with Peter Barton Hutt, Senior Counsel, Covington & Burling LLP, Former Chief Counsel for the Food and Drug Administration (July 8, 2011) (on file with author) [hereinafter Telephone Interview]. For an example of this confusion in the academic literature, compare Rebecca M. Bratspies, Glowing in the Dark: How America's First Transgenic Animal Escaped Regulation, 6 MINN. J.L. SCI. & TECH. 457, 476 n.78 (2005) (arguing that a particular document was an advisory opinion that bound the FDA)
182. with Lars Noah, Managing Biotechnology's [R]evolution: Has Guarded Enthusiasm Become Benign Neglect?, 11 VA. J.L. & TECH 4, 63 n.233 (2006) (arguing the opposite);
183. see also Drew L. Kershen, Health and Food Safely: The Benefits of BT-Corn, 61 FOOD & DRUG L.J. 197, 212 n.98 (2006) (assuming FDA's proposal regarding advisory opinions had been finalized);
184. Margaret Gilhooley, The Administrative Conference and the Progress of Food and Drug Reform, 30 ARIZ. ST. L.J. 129, 144 (1998) (same); O'REILLY, supra note 11 § 4:24 4-88-92 (placing CPGs in the "FDA guidance documents" section rather than the "advisory opinions" section, despite their status as advisory opinions under 21 C.F.R. § 10.85). See also Hunnicutt, supra note 2, at 184-85 (arguing that the GGPs insufficiently specify which types of nonlegislative rules constitute non-binding "guidance documents").
185. O'REILLY, supra note 11 § 4:25 4-93 ("Formal FDA pronouncements on specific sets of facts are advisory opinions . . . [they are] rarer and more weighty than a guideline, more specific, and more binding."); Telephone Interview, supra note 167. Also, compare 21 C.F.R. § 10.115(b) (2011) with id. § 10.85(d).
186. Indeed, 21 C.F.R. § 10.85(a)(2)(iv) suggests that advisory opinions should only be issued on "policy issue[s] of broad applicability," even though advisory opinions purport to be less broad than guidance documents. 21 C.F.R. § 10.85(a)(2)(iv) (2011) (emphasis added). See also Telephone Interview, supra note 167.
187. See also, e.g., 67 Fed. Reg. 77498, 77499 (2002) ("An advisory opinion represents the formal position of FDA on a matter of general applicability" (emphasis added)).
188. "A statement of policy or interpretation made in the following documents, unless subsequently repudiated by the agency or overruled by a court, will constitute an advisory opinion: . . . (3) Compliance policy guides issued by FDA beginning in 1968 and codified in the Compliance Policy Guides manual." 21 C.F.R. § 10.85(d) (2011) (emphasis added).
189. Id. § 10.85(e) (2011).
190. See, e.g., CPG § 500.500 Guidance Levels for 3-MCPD(3-chloro-1,2- propanediol) in Acid-Hydrolyzed Protein and Asian-Style Sauces (Mar. 14, 2008), available at http://www.fda.gov/ICECI/ComplianceManuals/ CompliancePolicyGuidanceManual/ucm074419.htm ("This Compliance Policy Guide represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public." (emphasis added));
191. CPG § 280.100 - Stability Requirements - Licensed In Vitro Diagnostic Products (Aug. 14, 2000), available at http://www.fda.gov/ICECI/ ComplianceManuals/CompliancePolicyGuidanceManual/ucm073881.htm (same);
192. CPG § 490.100 Process Validation Requirements for Drug Products and Active Pharmaceutical Ingredients Subject to Pre-Market Approval (revised Mar. 12, 2004), available at http://www.fda.gov/ICECI/ComplianceManuals/ CompliancePolicyGuidanceManual/ucm074411.htm (same);
193. CPG § 110.100 Certification for Exports (revised Apr. 14, 2000), available at http://www.fda.gov/ICECI/ComplianceManuals/ CompliancePolicyGuidanceManual/ucm073830.htm (describing the document as both a "CPG" and a "guidance document"). Many similar documents may be found at Manual of CPGs, supra note 78.
194. See Guidance Documents, http://www.fda.gov/Food/ GuidanceComplianceRegulatoryInformation/GuidanceDocuments/default.htm (last visited Jul. 18, 2011) [hereinafter Guidance Documents].
195. 21 C.F.R. § 10.115(e) (2011).
196. See CPG § 100.550 Status and Responsibilities of Contract Sterilizers Engaged in the Sterilization of Drugs and Devices (revised Oct. 3, 2006), available at http://www.fda.gov/ICECI/Compliance-Manuals/ CompliancePolicyGuidanceManual/ucm073824.htm (providing new or different regulatory expectations to all contract sterilizers of all drugs and devices). Note that although CPGs count as binding advisory opinions under 21 C.F.R. § 10.85, this CPG is preceded by a disclaimer that it "does not operate to bind FDA." Id. Also note that these revisions establishing new regulatory expectations occurred several years after October 19, 2000, the effective date for the GGPs, and are therefore subject to its restrictions against using policymaking tools other than guidance documents to informally communicate regulatory expectations.
197. See, e.g., 65 Fed. Reg. 56468, 56468 (2000).
198. See also CPG § 100.700 GWQAP Pre-Award Evaluation - Inadequate Information to Evaluate Prospective Supplier (revised Apr. 25, 2005), available at http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ ucm073826.htm;
199. CPG § 110.300 Registration of Food Facilities Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (issued Dec. 2003), available at http://www.fda.gov/ICECI/ComplianceManuals/ CompliancePolicyGuidanceManual/ucm122876.htm;
200. CPG § 110.310 Prior Notice of Imported Food Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002: Compliance Policy Guide, Guidance for FDA and CBP Staff (May 2009), available at http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/ GuidanceDocuments/FoodDefenseandEmergencyResponse/ucm153055.htm.
201. 65 Fed. Reg. 56468, 56474 (2000).
202. § 10.85 has not changed since FDA announced that the agency anticipated modifying it. Compare 21 C.F.R. § 10.85 (historical version, 2001) with 21 C.F.R. § 10.85 (2011). Furthermore, an examination of all Federal Register documents that cite 21 C.F.R. § 10.85 obtained using the "KeyCite Citing References" function on Westlaw on July 9, 2011 revealed no sign that FDA has any current intention of undertaking this rulemaking process.
203. See 21 C.F.R. § 10.85(f) (2011).
204. "An agency must follow its own regulations until they are validly amended or rescinded." PETER L. STRAUSS, TODD D. RAKOFF & CYNTHIA R. FARINA, GELLHORN AND BYSE'S ADMINISTRATIVE LAW: CASES AND COMMENTS 913-914 (Revised 10th ed. 2003)
205. (citing Accardi v. Shaughnessy, 347 U.S. 260 (1954);
206. United States v. Nixon, 418 U.S. 683 (1974);
207. INS v. Yang, 519 U.S. 26 (1996)).
208. Cf. FDA v. Brown & Williamson Tobacco Corp. 529 U.S. 120, 133 (2000) ("It is a 'fundamental canon of statutory construction that the words of a statute must be read in their context and with a view to their place in the overall statutory scheme.' A court must therefore interpret the statute 'as a symmetrical and coherent regulatory scheme,' and 'fit, if possible, all parts into an harmonious whole.'" (internal citations omitted)). There is no reason to believe this canon would not also be applicable to the construction of regulations.
209. 5 U.S.C. §706(2)(A)(2011).
210. E.g., Bowles v. Seminole Rock & Sand Co., 325 U.S. 410, 413-14 (1945).
211. If a guidance document "effectively amend[s]" or "contradict[s] the meaning of" a rule promulgated through notice-and-comment rulemaking, courts are likely to deem it a legislative rule that itself must pass through notice-and-comment rulemaking to have effect. Raso, supra note 5, at 788-90 (citing Am. Mining Cong. v. MSHA, 995 F.2d 1106 (D.C. Cir. 1993);
212. Hemp Indus. Ass'n v. DEA, 333 F.3d 1082, 1087-91 (9th Cir. 2003);
213. Alaska Prof'l Hunters Ass'n v. FAA, 177 F.3d 1030, 1034 (D.C. Cir. 1999)).
214. See 21 C.F.R. § 10.115(c)(1) (2011).
215. 21 U.S.C. § 371(h)(1)(B) (2011) ("guidance documents shall not be binding on the Secretary").
216. 65 Fed. Reg. 7321, 7328 (2000) ("In 21 CFR part 10, remove the words 'guideline' and 'guidelines' wherever they appear and add in their place the words 'guidance document' and 'guidance documents,' respectively, in the following places: . . . Section 10.85(d)(5)"). 21 C.F.R. § 10.85(d) is the subsection that lists various documents that count as advisory opinions, such as TCs and CPGs.
217. See 21 C.F.R. §§ 10.85(g), 10.115(k) (2011).
218. Id. § 10.85(f).
219. Id. § 10.115(d)(3). But see Hunnicutt, supra note 2, at 182-83 (criticizing the provision's lack of clarity).
220. See generally O'Reilly, supra note 104; David C. Vladeck, FDAand Deference Lost: A Self-Inflicted Wound or the Product of a Wounded Agency? A Response to Professor O'Reilly, 93 CORNELL L. REV. 981 (2008).
221. See generally, e.g., Sunstein, supra note 2.
222. 529 U.S. 576 (2000).
223. Id. at 587 (emphasis added).
224. Sunstein, supra note 2, at 212 (quoting Christensen, 529 U.S. at 587).
225. 323 U.S. 134, 140 (1944). Many believed Skidmore to be "an anachronism" that failed to survive Chevron. Christensen, 529 U.S. at 589 (Scalia, J., concurring in part and concurring in the judgment).
226. Skidmore, 323 U.S. at 140.
227. E.g., Johnson, supra note 13, at 741.
228. Lisa Schultz Bressman, How Mead Has Muddled Judicial Review of Agency Action, 58 VAND. L. REV. 1443, 1446-47 (2005);
229. but see Nat'l Cable & Telecomms. Ass'n v. Brand X Internet Servs., 125 S.Ct. 2688, 2691 (2005) (holding that prior judicial interpretation of ambiguous statutory provision does not preclude Chevron deference to subsequent agency interpretation).
230. Sunstein, supra note 2, at 212.
231. See O'Reilly, supra note 104, at 941-42.
232. Sunstein, supra note 2, at 212.
233. 533 U.S. 218 (2001).
234. Id. at 221-239.
235. Id. at 226-27.
236. Sunstein, supra note 2, at 214 (quoting Mead, 533 U.S. at 229-31).
237. Id. at 214-15.
238. "Any suggestion that rulings intended to have the force of law are being churned out at a rate of 10,000 a year at an agency's 46 scattered offices is simply self-refuting." Mead, 533 U.S. at 233. See also Sunstein, supra note 2, at 215.
239. Sunstein, supra note 2, at 216.
240. 535 U.S. 212 (2002).
241. Sunstein, supra note 2, at 217 (citing Barnhart, 535 U.S. at 221). Although the interpretation at issue in Barnhart had, subsequent to its issuance, been promulgated as a regulation through the notice-and-comment rulemaking process, the Court "consider[ed] the agency's interpretation as if it had never been issued through notice-and-comment rulemaking" and nonetheless concluded that Chevron deference was warranted. Bressman, supra note 199, at 1456 (citing Barnhart, 535 U.S. at 219-221).
242. Barnhart, 535 U.S. at 222.
243. Sunstein, supra note 2, at 217 (citing Barnhart, 535 U.S. at 222).
244. Id. at 218. See also Id. at 216 (describing Chevron Step Zero as a "complex, . . . rule-free inquiry").
245. Eric R. Womack, Into the Third Era of Administrative Law: An Empirical Study of the Supreme Court's Retreat from Chevron Principles in United States v. Mead, 107 DICK. L. REV. 289, 327-28, 341 (2002);
246. Peter A. Appel, Wilderness and the Courts, 29 STAN. ENVTL. L.J. 62, 114 (2010);
247. Amy J. Wildermuth, Solving the Puzzle of Mead and Christensen: What Would Justice Stevens Do?, 74 FORDHAM L. REV. 1877, 1899 (2006).
248. But see Kristin E. Hickman & Matthew D. Krueger, In Search of the Modern Skidmore Standard, 107 COLUM. L. REV. 1235 (2007) (suggesting that Skidmore respect, while less deferential than Chevron deference, is still a relatively deferential standard).
249. O'Connell, supra note 5, at 932-33. However, some argue that "Mead has had no impact whatever on FDA with respect to the choice between informal guidance and notice-and-comment rulemaking" because the advantages of guidance, particularly "the ease with which guidance can be issued," still outweigh the potential loss of judicial deference. Letter, supra note 85.
250. Bressman, supra note 199, at 1446-47; Mead, 533 U.S. 218, 246-250 (2001) (Scalia, J., dissenting).
251. See generally, e.g., Sunstein, supra note 2 ("the extraordinary complexity introduced by the emerging law of Step Zero serves no useful purpose"); Bressman, supra note 199; Mead, 533 U.S. at 239-261 (Scalia, J., dissenting).
252. Seidenfeld, supra note 2, at 279-80.
253. Wilderness Soc'y v. United States Fish & Wildlife Serv., 316 F.3d 913, 921 (9th Cir. 2003) (Graber, J.), rev'd en banc, 353 F.3d 1051 (9th Cir. 2003).
254. Bressman, supra note 199, at 1461.
255. Id. at 1459.
256. See generally id. at 1458-64.
257. See generally id. at 1464-69.
258. See generally id. at 1469-74.
259. Although somewhat outside the scope of this article, it is not even clear that regulations promulgated through notice-and-comment rulemaking that carry the force of law are automatically entitled to Chevron deference after Mead. Id. at 1448 (citing Nat'l Cable & Telecomms. Ass'n v. Brand X Internet Servs., 125 S.Ct. 2688, 2712 (Breyer, J., concurring)).
260. See Kellogg v. Wyeth, 612 F.Supp.2d 421, 433 n.6 (D.Vt. 2008).
261. Raso, supra note 5, at 794-95 (citing Bowles v. Seminole Rock & Sand Co., 325 U.S. 410, 414 (1945)).
262. See, e.g. CPG § 110.310 Prior Notice of Imported Food Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (May 2009), available at http://www.fda.gov/Food/ GuidanceComplianceRegulatoryInformation/GuidanceDocuments/ FoodDefenseandEmergencyResponse/ucm15305s.htm (interpreting 21 CFR §§ 1.276-1.285);
263. Guidance for Industry: Bottled Water: Arsenic; Small Entity Compliance Guide (Apr. 2009), available at http://www.fda.gov/Food/ GuidanceComplianceRegulatoryInformation/GuidanceDocuments/ ChemicalContaminantsandPesticides/ucm151384.htm (interpreting various FDA regulations). See generally Guidance Documents, supra note 173.
264. See Wyeth v. Levine, 129 S.Ct. 1187, 1201-02 (2009) (policy expressed in legislative rule did not merit deference due to major change in longstanding position without warning or opportunity to comment);
265. Riegel v. Medtronic, Inc., 552 U.S. 312, 326-27 (2008) (finding statutory language unambiguous and thus discussing Mead only hypothetically).
266. 21 C.F.R. § 10.85(d)(1) (2011). But see Section I.H.3. supra.
267. Wyeth, 129 S.Ct. at 1201-02 (2009).
268. Farina v. Nokia, Inc., 625 F.3d 97, 127 n.27 (3d Cir. 2010) (describing Wyeth's rationale).
269. See infra note 237.
270. Several cases concerned policies expressed in legal briefs, informal adjudications, or letters to individual parties on case-specific matters, none of which can be classified as guidance documents for a general audience. Mylan Labs., Inc. v. Thompson, 389 F.3d 1272, 1278-84 (D.C. Cir. 2004);
271. Apotex, Inc. v. FDA, 226 Fed.Appx. 4 at *1 (D.C. Cir. 2007);
272. Sottera, Inc. v. FDA, 627 F.3d 891, 903-04 (D.C. 2010);
273. Horn v. Thoratec Corp., 376 F.3d 163, 177-79 (3d Cir. 2004);
274. Doe v. Rumsfeld, 297 F.Supp.2d 119, 131-32 (D.D.C. 2003);
275. Collagenex Pharm., Inc. v. Thompson, 2005 WL 256561 (D.D.C. 2005);
276. Allergan, Inc. v. Crawford, 398 F.Supp.2d 13 (D.D.C. 2005). Although letters to individual parties may be technically categorized as guidance documents, they rarely set wide-ranging, general policies due to their individualized, case-specific nature. I have also excluded from this discussion any circuit or district court cases that were subsequently reversed or vacated.
277. 575 F.3d 329, 340-42 (3d Cir. 2009).
278. Id. at 340 (emphasizing that only federal law, such as statutes and regulations, and not mere federal policy, may preempt state law) (quoting Fellner v. Tri-Union Seafoods, LLC, 539 F.3d 237, 243 (3d Cit 2008)). The opinion at no point mentions Chevron or Skidmore, which further indicates the court's decision was more likely based on the presumption against preemption than on any specific doctrine of deference to agency interpretations. For other cases refusing to grant deference to informal FDA statements claiming preemption of state law, see also, e.g., Fellner, 539 F.3d 237;
279. In re Zyprexa Prods. Liab. Litig., 489 F.Supp.2d 230, 272-74 (E.D.N.Y. 2007);
280. Perry v. Novartis Pharm. Corp., 456 F.Supp.2d 678, 682-84 (E.D.Pa. 2006) ("Thus, to the degree that FDA seeks to address ambiguities in the FDCA or in its own regulations, we will give that opinion great weight. Where, however, the agency attempts to 'supply, on Congress's behalf, the clear legislative statement of intent required to overcome the presumption against preemption,' no deference is warranted." (internal citations omitted));
281. Tucker v. SmithKline Beecham Corp., 596 F.Supp.2d 1225, 1230-33 (S.D.Ind. 2008). For cases generally illustrating the presumption against federal preemption of state law,
282. see generally Rice v. Santa Fe Elevator Corp., 331 U.S. 218 (1947);
283. Cipollone v. Liggett Group, Inc., 505 U.S. 504 (1992). As a doctrinal matter, it is uncertain how the presumption against preemption interacts with the Chevron doctrine.
284. Compare Massachusetts v. DOT, 93 F.3d 890 (D.C. Cir. 1996)
285. with Brannan v. United Student Aid Funds, Inc., 94 F.3d 1260 (9th Cir. 1996).
286. 421 F.3d 263, 272-73 (3d Cir. 2005).
287. Id. (quoting Barnhart v. Walton, 535 U.S. 212, 222 (2002)).
288. Bartlett v. Mut. Pharm. Co., 659 F.Supp.2d 279, 302-04 (2009) (refusing to grant Chevron deference to footnote in proposed FDA regulation that "was not incorporated into the final version of the rule and therefore was not subjected to the notice-and-comment procedure");
289. Barnhill v. Teva Pharm. USA, Inc., Slip Copy, 2007 WL 6947996 at *46 (S.D.Ala. 2007) ("An agency's advisory opinion is entitled to deference only to the extent it has the power to persuade.");
290. Weiss v. Fujisawa Pharm. Co., 464 F.Supp.2d 666, 673-76 (E.D.Ky. 2006) ("Even though it represents FDA's formal position on a matter and obligates the agency to follow it until amended or revoked, an advisory opinion is also entitled only to limited deference because it is not subject to notice and comment procedures." (internal citations omitted));
291. Von Koenig v. Snapple Beverage Corp., 713 F.Supp.2d 1066, 1076 (E.D.Cal. 2010);
292. In re Vioxx Prods. Liab. Litig., 501 F.Supp.2d 776, 786-87 (E.D. La. 2007).
293. Weiss, 464 F.Supp.2d at 673-76 ("FDA's position has not been consistent and is therefore entitled only to Skidmore deference."); Kellogg v. Wyeth, 612 F.Supp.2d 421, 432-35 (D.Vt. 2008); Vioxx, 501 F.Supp.2d at 786-87.
294. But see Thomas L. Casey, III, Towards Function and Fair Notice: Two Models for Effecting Executive Policy Through Changing Agency Interpretations of Ambiguous Statutes and Rules, 2008 MICH. ST. L. REV. 725, 735 n.64 (arguing that "the 'consistency' of an agency's interpretation has generally not been a deciding factor in lower court cases applying Skidmore subsequent to Mead") (citing Hickman & Krueger, supra note 215, at 1286).
295. Perry, 456 F.Supp.2d at 682-84.
296. In Sandoz, Inc. v. Leaviti, 427 F.Supp.2d 29 (D.D.C. 2006), the court cited Mead for the proposition that an agency could not contradict or ease the plain terms of the statute it administers. Id. at 37 n.9. This, however, seems more like a Chevron Step One issue than a Step Zero issue that would necessitate resort to the Mead doctrine.
297. Chevron, U.S.A., Inc. v. National Resources Defense Council, Inc., 467 U.S. 837, 842-43 (1984) ("First, always, is the question whether Congress has directly spoken to the precise question at issue. If the intent of Congress is clear, that is the end of the matter; for the court, as well as the agency, must give effect to the unambiguously expressed intent of Congress.").
298. See supra note 237. For further discussion regarding how FDA's changed policy in preemption has led to lost deference, see O'Reilly, supra note 104, at 967-72.
299. See Bressman, supra note 199, at 1445-46. But see Hickman & Krueger, supra note 215 (suggesting that most appellate courts use a "sliding scale" approach that balances a variety of factors).
300. See, e.g., David M. Dudzinski, Reflections on Historical, Scientific, and Legal Issues Relevant to Designing Approval Pathways for Generic Versions of Recombinant Protein-Based Therapeutics and Monoclonal Antibodies, 60 FOOD & DRUG L.J. 143, 212-13 (2005).
301. Bressman, supra note 199, at 1459-60.
302. See generally O'Reilly, supra note 104.
303. "There is no denying the complexity of the statutory regime under which FDA operates, FDA's expertise or the careful craft of the scheme it devised to reconcile the various statutory provisions." Mylan Labs., Inc. v. Thompson, 389 F.3d 1272, 1280 (D.C. Cir. 2004).
304. Accord Collagenex Pharm., Inc. v. Thompson, 2005 WL 256561 at *8 (D.D.C. 2005);
305. Allergan, Inc. v. Crawford, 398 F.Supp.2d 13, 21-22 (D.D.C. 2005).
306. Wedgewood Village Pharmacy, Inc. v. United States, 421 F.3d 263, 272-73 (3d Cir. 2005).
307. Bressman, supra note 199, at 1463.
308. 533 U.S. 218, 232 (2001).
309. Cf. Bressman, supra note 199, at 1462-63 (citing Wilderness Soc'y v. United States Fish & Wildlife Serv., 353 F.3d 1051 (9th Cir. 2003));
310. Schneider v. Feinberg, 345 F.3d 135, 143 (2d Cir. 2003)).
311. Sunstein, supra note 2, at 216.
312. Bressman, supra note 199, at 1458-60.
313. 529 U.S. 576, 587 (2000).
314. Sunstein, supra note 2, at 214-15 ("[T]he Court in Mead squarely rejected a possible reading of Christensen: that agency interpretations lacking the force of law, or not preceded by formal procedures, would always be evaluated under Skidmore.").
315. 533 U.S. 218, 233 (2001).
316. See Appendix A, Figure 5, infra. Accord Seiguer and Smith, supra note 12, 26 (Exhibit 5) (demonstrating that FDA issues a total of approximately 100 guidance documents a year). Letters to individual firms from lower-level FDA employees may not be entitled to a high level of deference on this ground, however.
317. 535 U.S. 212, 222 (2002); Sunstein, supra note 2, at 231-32.
318. See United States v. Mead Corp., 533 U.S. 218, 226-27 (2001).
319. Letter, supra note 85 ("It is my observation . . . that Mead has had no impact whatever on FDA with respect to the choice between informal guidance and notice-and-comment rulemaking. FDA has overwhelmingly chosen informal guidance for extremely practical reasons - namely, the ease with which guidance can be issued."). Accord Appendix A, Figure 5, infra.
320. Seiguer and Smith, supra note 12, at 25-26.
321. See Appendix A, Figure 5, infra.
322. See, e.g., Guidance for Industry: Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans (Apr. 2003), available at http://www.fda.gov/BiologicsBloodVaccines/ GuidanceComplianceRegulatoryInformation/Guidances/Xenotransplantation/ucm0143S4. htm;
323. Guidance for Industry: ANDAs: Pharmaceutical Solid Polymorphism: Chemistry, Manufacturing, and Controls Information (Jul. 2007), available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/ucm072866.pdf;
324. Guidance for Industry: Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Small Entity Compliance Guide (Dec. 2010), available at http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/ GuidanceDocuments/SmallBusinessesSmallEntityComplianceGuides/ucm238182.htm.
325. Vladeck, supra note 191, at 983, 989-90, 998-99.
326. E.g., Raso, supra note 5, at 804-05; Jessica Mantel, Procedural Safeguards for Agency Guidance: A Source of Legitimacy for the Administrative State, 61 ADMIN. L. REV. 343, 351 (2009); Seiguer and Smith, supra note 12, at 24. This proposition is also borne out by empirical analysis. O'Connell, supra note 5, at 936 (data "suggests that notice-and-comment rulemaking has significant costs that agencies want to avoid").
327. Seiguer and Smith, supra note 12, at 24.
328. John F. Manning, Textualism as a Nondelegation Doctrine, 97 COLUM. L. REV. 673, 699 (1997)
329. (quoting Mistretta v. United States, 488 U.S. 361, 415 (1989) (Scalia, J., dissenting)). See also Hutt, supra note 33, at 102.
330. Mendelson, supra note 10, at 410.
331. Id. It should be noted, however, that the agency would not necessarily need to use informal guidance documents to interpret ambiguous provisions in its regulations; courts permit agencies to use a variety of tools to fill in gaps in their regulations. E.g., Auer v. Robbins, 519 U.S. 452, 461-62 (1997) ("Because the salary-basis test is a creature of the Secretary's own regulations, his interpretation of it is, under our jurisprudence, controlling unless 'plainly erroneous or inconsistent with the regulation.' . . . Petitioners complain that the Secretary's interpretation comes to us in the form of a legal brief but that does not, in the circumstances of this case, make it unworthy of deference." (emphasis added; internal citations omitted)).
332. It is of course difficult to reliably estimate how many infractions would occur in the absence of guidance. However, anecdotal evidence collected from interviews conducted with industry representatives indicates that guidance does indeed prevent regulatory violations. Seiguer and Smith, supra note 12, at 27-31. See also, c.f., FID 44 (Dec. 1, 1906) ("[I]t is evident that an overwhelming majority of the manufacturers, jobbers, and dealers of this country are determined to do their utmost to conform to the provisions of the act . . . It is hoped, therefore, that the publication of the opinions and decisions of the Department will lead to the avoidance of litigation which might arise."); Peter A. Joy, Making Ethics Opinions Meaningful: Toward More Effective Regulation of Lawyers' Conduct, 15 GEO. J. LEGAL Ethics 313, 367-68 (2002) ("agency officials presumably believe that the costs [of guidance] are offset by better voluntary compliance and a reduced need for enforcement"); Mendelson, supra note 10, at 412-13; Hunnicutt, supra note 2, at 172 (citing Anthony, supra note 11, at 1328-30) ("[P]eople tend to acquiesce to that which the government informs them constitutes the law.").
333. Seiguer and Smith, supra note 12, at 29-30.
334. Raso, supra note 5, at 803-04 (citing 21 U.S.C. § 360e).
335. Id. at 803.
336. Courts have often declined to deem policies expressed in guidance document final agency actions ripe for review. Mendelson, supra note 10, at 411-12; Raso, supra note 5, at 795.
337. Mendelson, supra note 10, at 408.
338. Johnson, supra note 13, at 701.
339. 40 Fed. Reg. 40682, 40695 (1975).
340. Bressman, supra note 199, at 1483 (quoting Lisa Schultz Bressman, Beyond Accountability: Arbitrariness and Legitimacy in the Administrative State, 78 N.Y.U. L. REV. 461, 545-46 (2003)).
341. Seiguer and Smith, supra note 12, at 23.
342. Andersen, supra note 140, at 545. Mr. Andersen notes, however, that because "FDA uses the more extensive notice-and-comment[-style] procedure for its guidance documents," as mandated by the GGPs, "that might impose a greater burden on the subsequent administration" to revoke prior guidance. Id. at 545 (citing Jack M. Beermann, Presidential Power in Transitions, 83 B.U. L. REV. 947, 994 (2003)).
343. 40 Fed. Reg. 40682, 40695 (1975) ("The Commissioner recognizes that such guidelines, which do not have the legal status of regulations, are increasingly important in providing assistance both to the regulated industry and to agency employees who are charged with consistent and fair administration of the law. In many instances, such guidelines would be available on an informal basis before comparable regulations could be promulgated.").
344. 40 Fed. Reg. 40682, 40695 (1975).
345. Seiguer and Smith, supra note 12, at 23-24.
346. Mendelson, supra note 10, at 409; see also Johnson, supra note 13, at 702.
347. See generally Seiguer and Smith, supra note 12.
348. Id. at 24, 27.
349. Id. at 24.
350. O'Reilly, supra note 104, at 941-48.
351. See generally id.
352. See generally id. (alleging that FDA has made ill-considered policy reversals to benefit Republican interests during President George W. Bush's administration); Vladeck, supra note 191 (blaming FDA's lost credibility on a confluence of needlessly politicized decisions, crippling resource constraints, and a crisis in leadership).
353. H.R. REP. No. 106-1009, at 1 (2000). See generally, e.g., Hunnicutt, supra note 2; Andersen, supra note 140.
354. Seiguer and Smith, supra note 12, at 29-30.
355. See generally Raso, supra note 5.
356. Seiguer and Smith, supra note 12, at 29-31.
357. Id. at 31.
358. See Mendelson, supra note 10, at 409 (citing Peter L. Strauss, Publication Rules in the Rulemaking Spectrum: Assuring Proper Respectfor an Essential Element, 53 ADMIN. L. REV. 803, 842-43 (2001)) ("Agencies rely on [guidance documents] to ensure that lower-level employees complete forms correctly and make consistent (and thus more predictable) decisions.").
359. Seiguer and Smith, supra note 12, at 30.
360. Hunnicutt, supra note 2, at 180.
361. Seiguer and Smith, supra note 12, at 30-31. For instance, "[t]he recent development process for the guidance on pharmacogenomics data submission was cited as a good example of creating more transparency." Id.
362. Seiguer and Smith, supra note 12, at 30. However, not all industry representatives share this view. Id.
363. Raso, supra note 5, at 795; Johnson, supra note 13, at 712-13.
364. Johnson, supra note 13, at 712; Mendelson, supra note 10, at 412-13.
365. Seiguer and Smith, supra note 12, at 27-31.
366. Vladeck, supra note 191, at 983-84, 989-90, 998-99.
367. Johnson, supra note 13, at 703.
368. "[C]ertain characteristics of regulatory beneficiaries may lead them to be less involved in policy development. First, learning about the existence of guidances before they are finalized can be difficult and expensive unless the agency chooses to give public notice or else initiates contact. Regulatory beneficiary groups may have fewer resources to devote to this sort of information gathering. Second, if regulatory beneficiary groups are diffuse or poorly organized, they may face significant obstacles to organizing in a way that fully represents their interests . . . The intended beneficiaries of these statutes represent extraordinarily large and diffuse groups, including not only those who currently benefit from these laws but also many who cannot yet self-identify (such as . . . fetuses, in the case of toxics and food safety regulation) . . . Third, regulatory beneficiaries may lack the political clout that might otherwise motivate an agency to seek their approval . . . Finally, regulated entities may have more to lose and more to spend than regulatory beneficiaries, giving them both a greater incentive and a greater ability to participate in the process." Mendelson, supra note 10, at 430-31.
369. Id. at 420-24.
370. Id. at 421-22 (citing Heckler v. Chaney, 470 U.S. 821, 831-32 (1985)).
371. 3 cfu/g. See Compliance Policy Guide § 527.300, Dairy Products - Microbial Contaminants and Alkaline Phosphatase Activity (Dec. 2010), available at http://www.fda.gov/downloadsf/ICECI/ComplianceManuals/ CompliancePolicyGuidanceManual/UCM238465.pdf. While the general public's presumed inability to understand and meaningfully comment upon very complex FDA policies certainly does not justify totally excluding the public from the deliberative process, c.f. Hutt, supra note 82, at 220, the benefits of administrative ease likely outweigh the cost of decreased public participation in such cases.
372. 62 Fed. Reg. 8961, 8962-63 (1997).
373. Telephone Interview, supra note 167.
374. Pub. L. No. 105-115, §405, 111 Stat. 2296, 2368-69 (codified at 21 U.S.C. § 371(h) (1997)).
375. Many scholars agree that Congress has the authority to modify the Chevron framework. Cf., e.g., Thomas W. Merrill, Judicial Deference to Executive Precedent, 101 YALE L.J. 969, 1031 (1992).
376. Sunstein, supra note 2, at 228-29. See generally Louis Kaplow, Rules Versus Standards: An Economic Analysis, 42 DUKE L.J. 557 (1992).
377. See, e.g., United States v. Mead Corp., 533 U.S. 218, 241 (2001) (Scalia, J., dissenting).
378. See, e.g., Johnson, supra note 13, 740-41.
379. Bressman, supra note 199, at 1492.
380. 5 U.S.C. § 706(2)(A) (2011). As the Supreme Court has held, "[a]gency inconsistency is not a basis for declining to analyze the agency's interpretation under the Chevron framework. Unexplained inconsistency is, at most, a reason for holding an interpretation to be an arbitrary and capricious change from agency practice under the Administrative Procedure Act." Nat'l Cable & Telecomms. Ass'n v. Brand X Internet Servs., 545 U.S. 967, 981 (2005)
381. (citing Motor Vehicle Mfrs. Ass'n of United States, Inc. v. State Farm Mut. Auto. Ins. Co., 463 U.S. 29, 46-57 (1983)).
382. "The fact that the agency has from time to time changed its interpretation of the term 'source' does not, as respondents argue, lead us to conclude that no deference should be accorded the agency's interpretation of the statute. An initial agency interpretation is not instantly carved in stone. On the contrary, the agency, to engage in informed rulemaking, must consider varying interpretations and the wisdom of its policy on a continuing basis." 467 U.S. 837, 863-64 (1984).
383. See Viadeck, supra note 191, at 983, 989-90, 998-99.
384. See generally Raso, supra note 5.
385. Sunstein, supra note 2, at 227-28 (citations omitted).
386. Id. at 228 (citations omitted).
387. Figures for years 1914-1927 are approximate but the total of 212 is accurate.
388. 1938-49, supra note 37, 561-753.
389. 1938-49, supra note 37, 755-62; VINCENT A. KLEINFELD AND CHARLES WESLEY DUNN, FEDERAL FOOD, DRUG, AND COSMETIC ACT 1949-1950 283-90 (1951); 1951-52, supra note 60, 385-89; 1953-57, supra note 58, 309-22.
390. 1953-57, supra note 58, 807-10; 1958-60, supra note 61, 223-248; 1961-64, supra note 66, 261-72; 1965-68, supra note 69, 483-512.
391. These statistics have been collected from the comprehensive list of FDA guidance documents available at 75 Fed. Reg. 48180, 48180-48233 (2010). (Key: CBER = Center for Biologics Evaluation and Research; CDER = Center for Drug Evaluation and Research; CDRH = Center for Devices and Radiological Health; CFSCAN = Center for Food Safety and Applied Nutrition; CYM = Center for Veterinary Medicine; Comm. = Office of the Commissioner.) Figures include both draft and final guidance, including guidance that is no longer effective. These figures are approximate because the list is both over- and under-inclusive. The figures only represent documents labeled by FDA as "guidance" simpliciter; they do not include CPGS, TCs, informal letters to individual parties, or preambles to federal regulations. The figures also do not include revisions to existing guidance or guidance documents listed without an issuance date on the comprehensive list. Some figures may therefore be deflated. On the other hand, because some centers include some guidance documents under more than one category, some figures may be inflated. The statistics nonetheless paint a reasonably accurate picture of FDA's ever-increasing use of guidance.