Pharmacy compounding of Bioidentical Hormone Replacement Therapy (BHRT): A proposed new approach to justify FDA regulation of these prescription drugs

Food and Drug Law Journal

Volumn 63, Issue 2, 2008, Pages 459-491

  Patsner, Bruce ^a  

^a UNIVERSITY OF HOUSTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CONJUGATED ESTROGEN; CONJUGATED ESTROGEN PLUS MEDROXYPROGESTERONE ACETATE; ESTRADIOL; ESTRATEST; ESTRIOL; ESTRONE; HERBACEOUS AGENT; HORMONE; HORMONE DERIVATIVE; NON PRESCRIPTION DRUG; PROGESTERONE; TRIEST;

ADVERTIZING; BREAST CANCER; CLINICAL PHARMACY; CLINICAL PRACTICE; COURT; DOCTOR PATIENT RELATION; DRUG EFFICACY; DRUG FORMULATION; DRUG INDUSTRY; DRUG INFORMATION; DRUG LEGISLATION; DRUG MANUFACTURE; DRUG MARKETING; DRUG SAFETY; EVIDENCE BASED MEDICINE; FOOD AND DRUG ADMINISTRATION; GOVERNMENT REGULATION; HORMONE SUBSTITUTION; HUMAN; INTERNET; LAW ENFORCEMENT; LAW SUIT; MEDICAL SOCIETY; MENOPAUSAL SYNDROME; PRESCRIPTION; REVIEW; STROKE; UNITED STATES; WOMEN'S HEALTH;

ADVERTISING AS TOPIC; BIOLOGICAL PRODUCTS; CONSUMER PRODUCT SAFETY; DRUG APPROVAL; DRUG COMPOUNDING; DRUG INDUSTRY; HISTORY, 20TH CENTURY; HORMONE REPLACEMENT THERAPY; HUMANS; INTERNET; LEGISLATION, DRUG; MENOPAUSE; ORGANIZATIONS; PHARMACEUTICAL SERVICES; PRESCRIPTIONS, DRUG; TERMINOLOGY AS TOPIC; THERAPEUTIC EQUIVALENCY; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 44849119303     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (211)

1. FDA Webview, statement on Compounding, available at http://www.fdaveb.com (last accessed Jan. 10, 2008).
2. Exact figures on the number of women who have switched from commercial hormone prescription drugs to bioidentical compounds are impossible to find. Websites such as www.womentowomen.com which advertise that "we've helped millions of women" do not provide precise numbers either (last accessed Apr. 17, 2008).
3. Not all marketed hormone therapy prescription drug products have an approved NDA, have undergone adequate testing, or have been removed from the market even after FDA has determined that there is no added benefit from one of the components of a combination product. For example, Estratest manufactured by Solvay Pharmaceuticals is a widely prescribed prescription drug used to treat the same symptoms bioidentical hormones are prescribed for yet has never been approved by FDA.
4. The Endocrine Society, Senate Investigates Bioidentical Hormones. The Endocrine Society As Expert Witness, ENDOCRINE NEWS, June 2007. U.S. Senate Special Committee on Aging, April 19, 2007.
5. Tara Parker-Pope, Popular Menopause Hormones Made from Plants Come Under Scrutiny, WALL STREET JOURNAL, October 25, 2001, at D1.
6. Wyeth, Citizen Petition to FDA < Docket 2005-0411, Re: Citizen Petition seeking FDA actions to counter flagrant violations of the law by pharmacies compounding bio-identical hormone replacement therapy, drugs that endanger public health. Submitted October 5, 2005, available at http://www.fda.gov/ohrms/dockets/dockets/05p0411/05p-0411-cp00001-01-vol1.pdf (last accessed Sep. 19, 2006).
7. Id.
8. Associated Press, FDA Cracks Down on "Bio-Identical" Hormones, available at http:www.msnbc.com/id/22575578 (last accessed Jan. 10, 2008).
9. th Congress (2007) (prepared statement of Steven K. Galson, M.D., Director of the Center for Drug Evaluation and Research at FDA), available at http://www.fda.gov/ola/2007/ hormone041907.html (last accessed Dec. 6, 2007). During this presentation Dr. Galson reiterated FDA's view that compounded drugs are "new drugs" within the meaning of the Food, Drug and Cosmetic Act (FDCA) despite recent judicial rulings directly negating this precise contention. (Hereinafter abbreviated as Galson).
10. rd edition
11. Each of these tenets will be discussed in separate sections.
12. Medical Center Pharmacy v. Gonzales, 451 F. Supp. 2d 854 (W.D. Tex 2006).
13. The issue of whether FDA has any jurisdiction over compounding at all, outside of a very narrowly defined area such as prescription drugs for which pharmacy compounding poses a unique set of technical problems, is the meta-issue behind the current dispute over pharmacy compounding of bioidentical hormone therapy prescription drugs. FDA continues to claim potential jurisdiction over all of pharmacy compounding, choosing only to exercise enforcement discretion. The Pharmacy profession maintains that regulation of compounding belongs to the states. This non-meeting of the ways is evident in reading Dr. Galson's comments to the Senate Committee, see ref. 5, supra.
14. Galson, supra note 7.
15. th Circuit 2001).
16. Thompson v. Western States Med. Ctr. et al., 535 U.S. 357, 360-61 (2002). "Drug compounding is a process by which a pharmacist or doctor combines, mixes, or alters ingredients to create a medication tailored to the needs of an individual patient."
17. th Congress (2003) (statement of Daniel A. Herbert, RPh, President Elect, American Pharmaceutical Association) [hereinafter Herbert testimony].
18. Id.
19. Id.
20. th ed. 2005)
21. Id.
22. Federal Food, Drug and Cosmetic Act, 21 U.S.C. (1938) [hereafter referred to as "the Act"].
23. James A. Sundberg, Extemporaneous Compounding in the Hospital Pharmacy, 1 INTERNATIONAL JOURNAL OF P HARMACEUTICAL COMPOUNDING 314 (1997).
24. David W. Newton, Compounding Paradox: Taught Less and Practiced More, 7 INTERNATIONAL JOURNAL OF PHARMACEUTICAL COMPOUNDING 399 (2003).
25. Id.
26. TH ANNUAL MEETING OF THE NORTH AMERICAN MENOPAUSE SOCIETY (October 11, 2006)[Hereinafter Patsner].
27. Peter Barton Hutt, Drug Regulation in the United States, 2 INT'L J. OF TECH. ASSESSMENT IN HEALTH Care 619 (1986).
28. The exact reason for this is not known. It may have been because the pharmaceutical industry was undergoing a more rapid expansion than the pharmacy industry, or because the pharmacy industry was just beginning to experience some economies of scale. Alternatively, the motivation may have been the belief that this policy would improve public health and be beneficial to the public. Or, Congress' intent may have truly been to not focus on pharmacy compounding at all.
29. Kefauer-Harris amendment
30. Galson, supra note 7 at 3.
31. Id.
32. Id.
33. Pharmacy Compounding: Customizing Prescription Drugs, FDA CONSUMER MAGAZINE, July-August 2000, available at http://www.fda.gov/fdac/features/2000/400_compound.html (last accessed June 15, 2005).
34. This would come back to haunt FDA in Western States Med. Ctr. v. Thompson 535 U.S. 357, 369 (2002)("[T]he Government acknowledges that requiring FDA approval of all drug products compounded by pharmacies would, as a practical matter, eliminate the practice of compounding.").
35. Galson, supra note 7.
36. Id.
37. Food and Drug Administration Compliance Policy Guide 7132.16, Subject: Manufacture, distribution and promotion of adulterated, misbranded, or unapproved new drugs for human use by state-licensed pharmacies. FDA Office of Enforcement, Division of Compliance Policy, March 16, 1992, available at http://www.fda.gov/ora/compliance_ref/cpg/cpgdrg/cpg460-200.html [hereinafter "1992 Compliance Policy Guide].
38. Federal and State Role in Pharmacy Compounding and Reconstitution: Re: October 23, 2003 Hearing Exploring the Right to Mix to Protect Patients (statement of John A. Gans, PharmD, Executive Vice President, American Pharmaceutical Association).
39. Food and Drug Administration Modernization Act of 1997, 21 U.S.C. 301 (1997 (hereinafter abbreviated as FDAMA).
40. Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 301, et. seq. (2004) [hereinafter FDCA or the Act]
41. FDAMA, supra note 37.
42. Id.
43. Id.
44. Id.
45. Id.
46. Western States Medical Center v. Shalala, 69 F. Supp.2d 1288 (D.Nev. 1999).
47. Id.
48. Id.
49. Central Hudson Gas & Elec. Corp. v. Public Service Commission, 447 U.S. 557 (1980).
50. th Circuit 2001).
51. Id.
52. Thompson v. Western States Medical Center, 535 U.S. 357 (2002).
53. Galson, supra note 7 at 3.
54. Galson, supra note 7 at 3.
55. Compliance Team
56. FDA Compliance Policy Guide § 460.200, at Policy 1, available at http://www.fda.gov/ora/compliance_ref/cpg/cpgdrg/cpg460-200.html (hereinafter FDA 2002 Compliance Guide).
57. Id.
58. Id.
59. Id.
60. Id.
61. Id.
62. Galson, supra note 7 at 3.
63. FDA 2002 Compliance Guide, supra note 50.
64. Id.
65. Under the specific language of 21 U.S.C. §§ 360(g)(1) and 374 (a)(2)(A), pharmacies are expressly exempt from FDA registration as manufacturers FDAMA's original provisions essentially exempted the overwhelming majority of compounded prescription drugs from the core new drug approval requirements of the FDCA. The FDCA does contain exemptions to its manufacturing provisions for pharmacies. The statute exempts pharmacies from the registration and inspection requirements for manufacturers provided the pharmacies meet certain requirements, such as complying with state laws and performing compounding activities in their normal course of business, and as such protects a broad range of pharmacy compounding practices from the traditional regulatory requirements of manufacturers..
66. Medical Center Pharmacy v. Gonzales, 451 F. Supp. 2d 854 (W.D. Tex. 2006).
67. Id.
68. Id.
69. Id.
70. Id.
71. Covington & Burling. Food & Drug E-Alert. "Western District of Texas Compounding Decision on Medical Center Pharmacy v. Gonzales. September 27, 2006, available at www.cov.com (last accessed Dec. 23, 2007).
72. Daniel Meron, Legal Developments Relevant to FDA Authority, 62 FOOD & DRUG L.J. 443 (2007). "This case is now on appeal to the Fifth Circuit, and we hope that the Fifth Circuit will place the task of balancing the risks and benefits of compounding back at the FDA - where it belongs."
73. FDAMA § 503(A).
74. Medical Center Pharmacy v. Gonzales, 451 F. Supp. 2d 854 (W.D. Tex. 2006). FDA's argument is that all pharmacy compounded prescription drugs are new drugs. This argument has been rejected by courts.
75. Western States Medical Center v. Shalala, supra note 48.
76. Id. U.S. District Court Judge David A. Ezra unequivocally held that volume "does nothing" to distinguish manufacturing from compounding."
77. Western States Medical Center v. Shalala, supra note 48.
78. Merson, Supra, at 51, 443. "But when volume or other circumstances of compounding suggest that the pharmacy is actually acting like a drug manufacturer, FDA will consider enforcement actions. In short, FDA has strived to preserve the many beneficial instances of traditional compounding, while at the same time making sure that abusive practices, involving bulk compounding, remain the subject of our enforcement." The term "bulk" is not defined, and based on Chief Counsel's arguments seems to be somewhat interchangeable with "high volume." Courts have rejected the use of the volume of compounding to label a pharmacy a "manufacturer" and not a "compounder..."
79. FDA CONCEPT PAPER: DRUG PRODUCTS THAT PRESENT DEMONSTRABLE DIFFICULTIES FOR COMPOUNDING BECAUSE OF REASONS OF SAFETY OR EFFECTIVENESS, available at http://www.fda.gov/cder/fdama/ difconc.htm (last accessed July 25, 2005): a "compounded drug product is a drug product made in response to, or in anticipation of, receipt of a valid prescription order or a notation on a valid prescription order from a licensed practitioner that states the compounded product is necessary for the identified patient. Compounding does not include mixing, reconstituting, or similar acts that are performed in accordance with the directions contained in approved labeling provided by the product's manufacturer and other manufacturer directions consistent with that labeling...the drug product may only be compounded if FDA has not identified it, by regulation, as a drug product that 'presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product.'" (Refs. Sections 503A(b)(3) and 503A(f) of the Act.
80. Herbert Testimony, supra note 15.
81. Id.
82. In fairness to FDA the Agency must weigh the risk/benefits of interfering with any pharmacy activity in the context of limited administrative resources as well as shifting priorities from the Executive Branch.
83. Herbert Testimony, supra note 15
84. Id.
85. Id.
86. Good Compounding Practices Applicable to State Licensed Pharmacies, Subpart A, Park Ridge, IL: NABP, 1993.
87. Food and Drug Administration, Center for Drug Evaluation and Research, FDA Concept Paper: Drug Products That Present Demonstrable Difficulties for Compounding Because of Reasons of Safety or Effectiveness, available at http://www.fda.gov/cder/fdama/difconc.htm (last accessed July 25, 2005).
88. Herbert testimony, supra at 15.
89. Id.
90. Id.
91. Good Compounding Practices Applicable to State Licensed Pharmacies, Supra.
92. Herbert testimony, supra at 15.
93. Id.
94. Id.
95. See Signature Pharmacy™, available at http://www.signaturepharmacy. com (last accessed February 2, 2005). "Signature pharmacy has a consultation form that you can submit over the internet. You will receive a phone call by one of our professionals to talk about the recommendations."
96. Id.
97. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry, Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms - Recommendations for Clinical Evaluation, January 2003 [hereinafter FDA Estrogen Guidance Document].
98. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry, Female Sexual Dysfunction: Clinical Development of Drug Products for Treatment, May 2000. [hereinafter FDA FSD Guidance Document].
99. Testimony of the American Pharmacists Association before the Senate Committee on Health, Education, Labor and Pensions, "On Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients, October 23, 2003, "...our position is that when an FDA-approved, commercially available product can meet a patient's need, it should be employed as the preferred course of action. However, when a patient's particular situation obviates the use of commercial products, the knowledge and skills of a compounding pharmacist can be extremely valuable, even lifesaving." The emphasis is on the words "need" and "obviates." There are different needs, and not all of them necessarily justify use of a compounded prescription drug.
100. FDA FSD Guidance Document, supra note 92. Female Sexual Dysfunction or FSD is a general term which encompasses several different entities, among them Hypoactive Sexual Desire Disorder or HSDD.
101. th Cong. 39 (2003) (prepared statement of Steven K. Galson, M.D., Deputy Director of the Center for Drug Evaluation and Research at FDA).
102. Johann Wolfgang von Goethe, German dramatist, novelist, poet & scientist (1749-1832), available at The Quotations Page, www.quotationspage.com (last accessed Jan. 22, 2008).
103. th ed. 2003).
104. THE NEW OXFORD AMERICAN DICTIONARY (Oxford University Press, 2001).
105. th ed. 2003).
106. Again visit Signature Pharmacy at www.signaturepharmacy.com for their "Natural Hormone Replacement Therapy" section of their website. Or see Natural Alternatives, Estriol USP-Bio-identical Natural Estrogen, available at http://all-new-you.com/1bioidentical_estriol.html (last accessed Nov. 29, 2005).
107. American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, Committee on Gynecologic Practice, Compounded Bioidentical Hormones, No. 322, November 2005. "Bioidentical hormones are plant-derived hormones that are biochemically similar or identical to those produced by the ovary or body." The terms "similar" and "identical" are not equivalent. "Body" may be redundant, as "ovary" is clearly part of the "body"; it would make more sense to specify the part of the body other than the ovary which is being referred to.
108. Id.
109. Id.
110. The most widely prescribed commercial prescription drug product for treatment of menopausal symptoms is Premarin, which is isolated from mare's urine (PREgnant MARe's urine). Premarin is manufactured by Wyeth Pharmaceuticals, the sponsor of the Citizen Petition on compounding pharmacies submitted to FDA, and is a favorite target of bioidentical hormone compounding pharmacy websites which emphasize that their products are more "natural."
111. A perusal of the BHRT product description on compounding pharmacy websites often note that their products have been chemically altered so that they are "identical" to endogenous human estrogens.
112. th Annual Meeting of the North American Menopause Society (October 11, 2006)["Most studies did not support a protective role for estrio, and consequently, research on estriol as a breast-safe estrogen was abandoned 20 years ago ... Women who have a strong preference for use of estriol should be counseled on the entirety of the data."
113. Again visit Signature Pharmacy at www.signaturepharmacy.com for their "Natural Hormone Replacement Therapy" section of their website.["Natural hormone therapy has many potential benefits: May help protect against endometrial and breast cancers"].
114. FDA defines what is "drug", a "medical device" in the Act.
115. There is no uniformly agreed upon definition of "bioidentical" provided by the pharmacy or pharmacy compounding industry.
116. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Cosmetics and Colors Fact Sheet, Hypoallergic Cosmetics, available at http://www.cfsan.fda.gov/~dms/cos-224.html (last accessed Jan. 22, 2008).
117. Chevron U.S.A. v. Natural Resource Defense Council, Inc., 467 U.S. 837 (1984).
118. Galson, supra note 7.
119. Women's Health Initiative, The estrogen-plus-progestin study, available at http://www.nhlbi.nih.gov/whi/estro_pro.htm (last accessed September 18, 2006)[hereinafter WHI study].
120. Galson, supra note 7.
121. David M. Herrington and Timothy D. Howard, From Presumed Benefit to Potential Harm - Hormone Therapy and Heart Disease, 349 N. ENGL. J. MED. 519 (2003).
122. WHI study, supra note 111.
123. Id.
124. Rowan T. Chlebowski, Susan L. Hendrix, Robert D. Langer et al. The Women's Health Initiative Randomized Trial, Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women, 289 JAMA 3243 (2003).
125. Hormone Therapy, Summary of Balancing Risks and Benefits 104(4) SUPP OBSTET. GYNECOL. 128S (2004).
126. See website for Profile Health, available at www.profilehealth. com/about.
127. Esther Hing and Kate M. Brett, Changes in U.S. Prescribing Patterns of Menopausal Hormone Therapy, 2001-2003, 108 OBSTET. GYNECOL. 33 (2006).
128. MSNBC, 'Bioidentical' female hormone use questioned. No evidence they are safer than synthetic versions, medical group says, available at http://www.msnbc.com/id/9874568 (last accessed Oct. 31, 200.5).
129. Also see Susan Ince, Are "Natural" Hormones Safer? MORE, November 2005, at 187;
130. ACOG TODAY, Clinical Issues, November-December 2005: Michele G. Curtis, MD, past vice chair of the Committee on Gynecologic Practice, "One of our concerns is quality control - there has been little clinical testing on most compounded products to determine whether they're safe or effective." Lila E. Nachtigall, MD, Bioidentical versus Nonbioidentical Hormones, Proceedings from the Postgraduate Course presented prior to the 17th Annual Meeting of the North American Menopause Society (October 11, 2006)[Hereinafter Nachtigall].
131. Perhaps the most aesthetically displeasing is the in-flight magazine featuring a picture of a muscle-bound elderly male physician with body like Arnold Schwarzenegger's and a head like Dick Cheney's. The advertisement promotes "natural" hormone therapy for men.
132. Daniel A. Farber. THE FIRST AMENDMENT 158 (Foundation Press 2003). "The Central Hudson test can be broken into two parts. The threshold inquiry is whether the regulated speech is misleading or concerns an illegal activity. If so, it receives no constitutional protection. The government can regulate truthful advertising about lawful transactions, however, only if it passes a three-prong inquiry: a) Is the governmental interest a "substantial" one? b) Does the regulation "directly" advance the governmental interest? c) Is the regulation tailored to the governmental interest?
133. Testimony of the American Pharmacists Association before the Senate Committee on Health, Education, Labor and Pensions, "On Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients, October 23, 2003, supra, note 93, at 7: "The profession's definition of compounding does not encompass the preparation of massive amounts of a drug product with the contemplation of distribution to a mass market of unknown users in unknown venues." In fact, the widescale magazine and Internet direct to consumer advertising of BHRT to consumers is exactly that, and either places the pharmacy before the patient and physician in the "triad" relationship, or for those compounding pharmacies which conduct their own lab tests, interpret the results and then "advise" the patient, effectively eliminate the physician part of the triad, regardless of the amount of lip service paid to the physician, and negate the individualization requirement.
134. Howard M. Hoffman Esq., The Critical Role and Legality of Pharmacy Compounding in the Modern Marketplace, FDLI UPDATE, September/October 2004, at 30. One would be hard pressed to find a better example of the law of unintended consequences than this statement. If the statement is true, it must also be true that when there is a suitable drug (suitable being a medical, not a personal determination, for a prescription drug) that is commercially available then a compounded drug is inappropriate and should not be prescribed at all.
135. Wyeth. Citizen Petition to FDA, Docket 2005-0411, RE: Citizen Petition seeking FDA actions to counter flagrant violations of the law by pharmacies compounding bio-identical hormone replacement therapy, drugs that endanger public health. Submitted October 6, 2005, available at http://www.fda.gov/ohrms/ dockets/05po411/05p-0411-cp00001-01-vol1.pdf (last accessed Sep. 19, 2006)[hereinafter Wyeth Citizen Petition].
136. FDA Estrogen Guidance Document, supra note 91.
137. Id.
138. Id.
139. Id.
140. American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, Committee on Gynecologic Practice, Compounded Bioidentical Hormones, No. 322, November 2005.
141. Wyeth Citizen Petition, supra note 125.
142. Public Citizen, Hormone Replacement Therapy Drugs Mixed by Pharmacies Are Unsafe, Public Citizen Reveals on WorstPills.org Web Site, available at http://www.citizen.org/pressroom/print_release.cfm?ID=2550 (last accessed August 2, 2006).
143. American Pharmacists Association, Response to Citizen Petition Filed on Behalf of Wyeth, Docket No. 2005P-0411, May 3, 2006.
144. International Academy of Compounding Pharmacists (IACP), Comments to Citizen Petition Filed on Behalf of Wyeth, Docket No. 2005P-0411, July 11, 2006.
145. FDA Webview, statement on Compounding, available at http://www.fdaveb.com (last accessed Jan. 10, 2008).
146. Michael Specter, Miracle in a Bottle. THE NEW YORKER, February 2, 2004, at 64. ("Dietary supplements are unregulated, some are unsafe - and Americans can't get enough of them").
147. Charles A. Morris and Jerry Avorn, Internet Marketing of Herbal Products, 290 JAMA 1505 (2003).
148. Wyeth Citizen Petition, supra note 125
149. Id.
150. Galson, supra note 7.
151. Wyeth Citizen Petition, supra, note 125.
152. American Pharmacists Association, Response to Citizen Petition Filed on Behalf of Wyeth, Docket No. 2005P-0411, May 3, 2006, supra note 135.
153. Wyeth Citizen Petition, supra note 125.
154. Medical Center Pharmacy v. Gonzales, 451 F. Supp. 2d 854 (W.D. Tex. 2006), supra, note 61.
155. Herbert Testimony, supra note 15.
156. A quick perusal of any one of dozens of compounding pharmacy internet sites for compounded BHRT reveals a demonstrable attempt to represent these products as a legitimate replacement for commercial hormone therapy drug products. The information is not designed to emphasize the need for a "custom" medication for a medical condition (e.g., vasomotor symptoms) that is not being adequately treated with a commercial product, but rather to globally characterize one set of products as less natural, less safe, less effective than another absent any proof. There is a strange blend of both classic drug claims re: disease or prevention of disease, as well as dietary supplement claims for general health benefits (e.g. ,looking or feeling younger).
157. See section III definitions of compounding and manufacturing.
158. Wyeth Citizen Petition, supra note 125.
159. Id.
160. Id.
161. Nachtigall, supra note 120. Dr. Nachtigall's update of the 2004 data confirmed this.
162. Heidi D. Nelson, Commonly Used Types of Postmenopausal Estrogen for Treatment of Hot Flashes. A Scientific Review, 291 JAMA 1610 (2004).
163. Lisa A Boothby, Paul L. Doering and Simon Kipersztok, Bioidentical hormone therapy: a review, 11 MENOPAUSE 356 (2004).
164. Id.
165. Nachtigall, supra, note 120. See also Tara Parker-Pope, Popular Menopause Hormones Made From Plants Come Under Scrutiny, WALL STREET JOURNAL, October 25, 2001, at D1. The comments from medical professionals whose business is to promote bioidentical hormone therapy sometimes have to read to be believed. An excellent example is this one from Steven F. Hotze, founder of the Hotze Wellness Center in Houston and owner of a compounding pharmacy that is leading the legal fight against FDA: "Nobody ever did a double-blind study to see if we need water on grass - we just know that. We know they work because our patients get well. That is a scientific experiment of one, and it works over and over again." One could of course make the same argument for the role of manure on grass.
166. Id.
167. Food and Drug Administration, Center for Drug Evaluation and Research, Report: Limited FDA Survey of Compounded Drug Products, January 2003, available at http://www.fda.gov/cder/pharmcomp/survey.htm (last accessed Sep. 19, 2006). Most compounded prescription drug products do not undergo rigorous clinical testing for safety or efficacy, and there are serious concerns regarding the purity, potency and quality of compounded drug products. From June 2001 to December 2001 FDA analyzed 29 product samples from 12 compounding pharmacies making a variety of different medications. Of the 29 tested, 10 (34 percent) failed one or more standard quality tests performed. Nine of the ten failing products failed assay or potency tests.
168. Nachtigall, supra note 120.
169. Id.
170. Signature Pharmacy™, Signature Hormone Pharmacy Specializes in Women's Health, available at http:www.signaturepharmacy.com (last accessed Feb. 2, 2005).
171. Id.
172. Patsner, supra note 24.
173. Village Compounding Pharmacy, Specialty Pharmacist Makes Custom Formulas with High-Tech Equipment and Even Higher Standards, available at http://www.villagecompounding.com (last accessed Feb. 2, 2005).
174. Nachtigall, supra note 120. "Due to its weaker potency, estriol can never be given in doses equivalent to estradiol, but it still carries risks associated with estrogen. These include endometrial hyperplasia and stimulation of MCF breast cancer cell lines."
175. Xcel, The Technology of Compounding, available at http://www.xcelhealthcare.com/techcompound.htm (last accessed Apr. 5, 2005).
176. Id.
177. Nachtigall, supra note 120
178. Galson, supra note 7.
179. A nice overview of this issue is provided by Prescription Access Litigation, Current Lawsuits, available at http://www.prescriptionaccess.org/ lawsuitssettlements/current_lawsuits?id=0012.
180. th Annual Meeting of the North American Menopause Society (October 11, 2006)[Hereinafter Richardson].
181. Galson, supra note 7.
182. See the information page of the manufacturer, available at http://www.premarin.com (last accessed Apr. 18, 2008). A nice summary of the chemical characteristics of Premarin® is also contained in Wikipedia, available at http://en.wikipedia.org/wiki/Premarin (last accessed Apr. 17, 2008).
183. Medical Center Pharmacy v. Gonzales, 451 F. Supp. 2d 854 (W.D. Tex. 2006
184. Daniel Meron, Legal Developments Relevant to FDA Authority, 62 FOOD & DRUG L.J. 443 (2007). "This case is now on appeal to the Fifth Circuit, and we hope that the Fifth Circuit will place the task of balancing the risks and benefits of compounding back at the FDA - where it belongs."
185. Though a strong term, junk medicine is merely an extension of the concept of junk science which has appeared repetitively in the legal literature since the Daubert v. Merrell Dow Pharmaceuticals 509 U.S. 579 (1993) decision, used to describe a situation where a scientific theory with little or no evidentiary basis is used to justify either a widespread clinical practice or determination by a trier of fact.
186. FDA Estrogen Guidance Document, supra note 91.
187. Id. The determination of menopausal status is based on measurement of serum FSH (follicle-stimulating hormone) and LH (leuteinizing hormone), not serum estrogen or progesterone levels
188. Id.
189. Id.
190. Id.
191. Id. See also clinical guidelines on hormone replacement therapy published by the American College of Obstetricians and Gynecologists (ACOG).
192. th Annual Meeting of the North American Menopause Society (October 11, 2006) ("Salivary assays used to measure estradiol and progesterone are generally not recommended for clinical use because of variable concentrations...individual cycles show substantial variability from day to day and are, therefore, of limited value.")
193. Richardson, supra note 170.
194. Id.
195. FDA Estrogen Guidance Document, supra note 91.
196. Chevron U.S.A. v. Natural Resource Defense Council, Inc., 467 U.S. 837 (1984).
197. American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, Committee on Gynecologic Practice, Compounded Bioidentical Hormones, No. 322, November 2005. The Committee goes on to write "The problem with salivary testing and monitoring of free hormone levels is twofold: 1) there is no biologically meaningful relationship between sex steroidal hormone concentrations and free serum hormone concentrations and 2) there is large within-patient variability in salivary hormone concentrations. Salivary hormone levels vary depending on diet, time of day of testing, the specific hormone being tested, and other variables." Although one could argue that there might be a hidden agenda by the physicians on ACOG's Gynecologic Practice Committee, the Committee is made up of a diverse group of academics and government representative from NIH and FDA who critically review all of the available medical literature on a given topic, including less accepted practices, in drafting the Opinion.
198. FDA Estrogen Guidance Document, supra note 91.
199. American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, Committee on Gynecologic Practice, Compounded Bioidentical Hormones, No. 322, November 2005, supra, note 185.
200. Id.
201. Testimony of the American Pharmacists Association before the Senate Committee on Health, Education, Labor and Pensions, "On Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients, October 23, 2003, "...our position is that when an FDA-approved, commercially available product can meet a patient's need, it should be employed as the preferred course of action." supra note 90.
202. Chevron, supra at 184.
203. The Endocrine Society Position Statement on Bioidentical Hormones, October 2006, available at http://www.endo-society.org/publicpolicy/ insider/2006/Postition_Statement_onBHArt1.cfm (last accessed January 23, 2008).
204. Herbert Testimony, supra note 15.
205. This comment appears on multiple compounding pharmacy internet website.
206. Wolf Utian MD, letter to ACOG from North American Menopause Society, Gyn Practice Committee Notes, Pharmaceutical Compounding Outline, Committee on Gynecologic Practice, November 15, 2004.
207. Gonzales v. Raich, 545 U.S. 1 (2005). In this case the Supreme Court held that the dispensing of new, unapproved drugs (in this case Cannabis) had to await federal approval, even when both their physicians and an individual state (in this case California) approved of its use.
208. Herbert Testimony, supra note 13.
209. Oliver Wendell Holmes, THE PROFESSOR AT THE BREAKFAST TABLE, 1839.
210. Steven H. McNamara, Dietary Supplemenst of Botanicals and Other Substances: A New Era of Regulation, 50 FOOD AND DRUG L. J., 341 (1995).
211. Abigail Alliance for Better Access to Developmental Drugs and Washington Legal Foundation v. von Eschenbach, 445 F.3d 470 (D.C. Cir. 2006).