Full opinion text
MEMORANDUM OPINION LAMBERTH, District Judge. This matter comes before the court on the parties’ cross-motions for summary judgment. Upon consideration of the memoran-da filed in support of and in opposition to the respective motions, the relevant legal authorities, and the entire record, and finding that there is no genuine issue of material fact, plaintiffs motion for summary judgment will be granted and defendants’ cross-motion will be denied. I. FACTUAL BACKGROUND Plaintiff Washington Legal Foundation (‘WLF”) is a nonprofit public interest law and policy center that defends “the rights of individuals and businesses to go about their affairs without undue influence from government regulators.” See Complaint ¶5. In this action, WLF seeks to enjoin the Food and Drug Administration, (“FDA”) and the Department of Health and Human Services (“HHS”) from enforcing policies restricting certain forms of manufacturer promotion of off-label uses for FDA-approved drugs and devices. The policies at issue — expressed through Guidance Documents — concern manufacturer distribution of reprints of medical textbooks and peer-reviewed journal articles (“enduring materials”), and manufacturer involvement in continuing medical education seminars and symposia (“CME”). See Final Guidance on Industry-Supported Scientific and Educational Activities, 62 Fed.Reg. 64074 (1997); Advertising and Promotion; Guidances, 61 Fed.Reg. 62800 (1996). Plaintiff seeks a declaratory judgment that the FDA policies expressed in the Guidance Documents violate the rights of its members under the First Amendment of the Constitution. It further requests that the court enter preliminary and permanent injunctions against defendants, preventing them from enforcing, relying upon, or otherwise giving effect to the Guidance Documents. A. Statutory & Regulatory Framework The FDA derives its authority to regulate various aspects of the medical and pharmaceutical industries from a complex statutory and regulatory scheme, a major portion of which is embodied in the Food, Drug and Cosmetic Act, 21 U.S.C. § 301, et seq. In order for a prescription drug or class III medical device to be distributed by a manufacturer in interstate commerce, the manufacturer is required to demonstrate, through a rigorous series of pre-elinical and clinical trials, that the drug or medical device is both safe and effective for each of its intended uses. 21 U.S.C. § 355(a), (b), Q'). FDA makes its final approval decisions under the “substantial evidence” standard. See 21 U.S.C. § 355(d). As part of the approval process, the FDA also reviews the proposed “labeling” for the drug, which includes, inter alia, all proposed claims about the drug’s risks and benefits, as well as adequate directions for use. See, e.g., 21 U.S.C. § 352(f). Labeling is a term of art that encompasses all written, printed or graphic material “(1) upon any [drug or device] or any of its containers or wrappers, or (2) accompanying such [drug or device].” 21 U.S.C. § 321(k) & (m). The most self-evident form of labeling is the package insert that accompanies the drag, but the term has also been construed to include nearly every form of drag company promotional activity, including booklets, pamphlets, mailing pieces, bulletins, and all literature that supplements, explains, or is otherwise textually related to the product. See 21 C.F.R. § 202.1(1)(2) (1997); Kordel v. United States, 335 U.S. 345, 350, 69 S.Ct. 106, 93 L.Ed. 52 (1948); United States v. Vitamin Indus., Inc., 130 F.Supp. 755, 765-66 (D.Neb.1955). The FDA will only approve the new drag application if the labeling conforms with the uses that the FDA has approved. Congress has closely examined whether alternative uses for approved drugs — treatments not on the approved label — should be subjected to the same FDA review procedures as the initial claim. In 1962, Congress amended the definition of a “new drag,” 21 U.S.C. § 321(p), to make clear that drags must be demonstrated safe and effective for “use under the conditions prescribed,” meaning that all uses for a drag must obtain FDA approval. See also 108 Cong.Rec. S17366 (daily ed. Aug. 23,1962) (statement of Senator Eastland). Therefore, if a manufacturer wishes to market or promote a product for an unlabeled use, it must resubmit the drag for another series of clinical trials similar to those from the initial approval. Until this subsequent approval has been granted, the unapproved use is considered to be off-label. Off-label uses include treating a condition not indicated on the label, or treating the indicated condition but varying the dosing regimen or the patient population. Manufacturer promotion of off-label uses constitutes mis-branding. See 21 U.S.C. § 352. Central to this litigation is that what a manufacturer may lawfully claim that a drag does under the statutory and regulatory scheme, and what a physician may prescribe a drug for, do not match. Once a drag has been approved by the FDA for marketing for any use, the actual prescription choices regarding those drags are left to the discretion of the physician. See, e.g., 59 Fed.Reg. 59820, 59821 (1994) (noting that the agency has restated this policy on numerous occasions). A physician may prescribe an approved drag for any medical condition, irrespective of whether FDA has determined that the drag is safe and effective with respect to that illness. That physicians may presently prescribe off-label is not in dispute. See Defendants’ Response to Plaintiff’s Statement of Material Facts ¶ 9 (noting that off-label prescribing is appropriate in the context of the physician-patient relationship); see also Deposition of William K. Hubbard, Associate Commissioner for Policy Coordination at 59-61 (March 21, 1996) (“Hubbard Deposition”). The FDA contends that it accepts the practice of off-label use by physicians as part of its enforcement discretion, see Defendants’ Response to Plaintiff’s Statement of Material Facts ¶ 2; Defendants’ Reply to Plaintiff’s Memorandum in Opposition at 6 (“Defendants’ Reply Memorandum”), though it appears to be an open question as to whether the FDA could currently regulate this aspect of the practice of medicine if it wished to do so. B. The Pros & Cons of Off-Label Use Whether characterized as either “the standard of care” or “treacherous,” off-label uSe of FDA-approved drugs by physicians is an established aspect of the modern practice of medicine. See, e.g., Off-Label Drugs, Reimbursement Policies Constrain Physicians in Their Choice of Cancer Therapies, GAO/ PEMD-91-14 at 5 (Sept.1991) (“GAO Report”) (noting that the use of off-label treatments is widespread). The precise extent upon which physicians rely upon off-label uses is disputed by the parties. A study cited by FDA concludes that off-label prescribing for the 64 .most frequently prescribed drug products is low — constituting only 4.7% of all prescriptions for patented drugs, and 2.0% for off-patent drugs. See Off-Label Use Associated With the Prescribing of the Most Frequently Used Drug Products in the United States, 1995 (unpublished draft, May 24, 1996) at 4. However, when one looks to specific areas of medicine, the picture as to off-label use changes dramatically. The General Accounting Office Report looking at anti-cancer drugs found that 25% of anticancer drugs were prescribed off-label and 56% of cancer patients were given at least one drug off-label. See GAO Report at 4. These uses are especially prevalent when the cancer has reached an, advanced stage. Off-label prescribing is also common in pediatrics, where drug manufacturers are justifiably reluctant to subject children to experimental clinical trials. See Hubbard Deposition at 77. Even the FDA acknowledges that in some specific and narrow areas of medical practice, practitioners consider off-label use to constitute the standard of good medical care. See Defendants’ Response to Plaintiff’s Statement of Material Facts ¶4; Deposition of Byron L. Tart, Director, Promotion and Advertising Policy Staff (March 15, 1996) at 153 (“Tart Deposition”) (stating that public health may benefit from off-label uses in some circumstances). As off-label uses are presently an accepted aspect of a physician’s prescribing regimen, the open dissemination of scientific and medical information regarding these treatments is of great import. The FDA acknowledges that physicians need reliable and up-to-date information concerning off-label uses. “[M]ore generically, we certainly believe it’s very appropriate for physicians to get information about off-label uses from the many sources that they get them. And, of course, they get them from CME; they get them from on-line databases; they get them through textbooks; they get them through discussions with colleagues; they get them through going to a medical center and grand rounds.... FDA does not desire or intend to interfere with that process.” Hubbard Deposition at 62-63; Defendants’ Memorandum of Points and Authorities in Opposition to Plaintiff’s Motion for Summary Judgment at 21 (“Defendants’ Opposition Memorandum”). The need for reliable information is particularly acute in the off-label treatment area because the primary source of information usually available to physicians — the FDA approved label — is absent.- See Defendants’ Response to Plaintiff’s Statement of Material Facts ¶ 12 (noting that labeling is unavailable for off-label uses); Declaration of Robert Temple, M.D. ¶ 8 (“Temple Declaration”) (noting that some information concerning new uses will not be reflected in the approved labeling and that “[pjhysicians are completely free to consider this information and to rely on it in making treatment decisions”). It is not the case however, that off-label prescription practices are wholly unproblematic. ' Off-label uses have, in some circumstances, proven to be harmful. For example, in the 1980’s, physicians began to prescribe, off-label, two ánti-arrythmic drugs, encainide and flecainide, to treat minor disturbances in patients who had recently had heart attacks. Patients who took these drugs had a two- and-one-half fold increase in mortality, and estimates of the total number of deaths attributable to this off-label ‘treatment’ range from 3,000 to 10,000 patients per year. See Temple Declaration at ¶21 (also noting the absence of promotion by sponsors). Even in cases, in which the off-label use is not “toxic,” prescribing a drug that is merely not effective may be no less harmful, because the ineffective prescription regimen will have been substituted for an effective one. See id. ¶ 22 (addressing another example concerning the off-label use of “calcium channel blockers” which subsequently proved to be ineffective, which meant that patients were being deprived of the more effective on-label treatment). In light of the problems that have arisen out of off-label prescription practices, the FDA, consistent with its mission to protect the public health, claims that it must develop solutions. The agency notes that “the ordinary citizen here has little ability to protect himself or herself from the potential harm associated with unproven uses of drugs and devices. For this reason, FDA has been charged with preventing such harm.” Defendants’ Opposition Memorandum at 20. (citing U.S. v. Dotterweich, 320 U.S. 277, 280, 64 S.Ct. 134, 88 L.Ed. 48 (1943)). C. The Guidance Documents and the Food and Drug Modernization Act 1. Continuing Medical Education (CME) Guidance In the late 1980’s, drug and device companies greatly increased the resources devoted to sponsoring CME seminars. Concerns about the promotional practices of drug manufacturers caught the attention of Congress, which conducted hearings in 1990 to investigate the matter. Among the issues addressed in those hearings was manufacturers’ promotion of unapproved claims for approved products. See Advertising, Marketing and Promotional Practices of the Pharmaceutical Industry, 1990: Hearing Before the Senate Committee on Labor and Human Resources, 101st Cong. 2, 5, 8-13 (1990) (“Pharmaceutical Hearings”). In response, FDA developed a Draft Concept Paper that endeavored to identify instances in which the industry could support scientific and educational programs that addressed off-label uses without violating the Food and Drug Act, which proscribes the misbranding of drugs. However, this concept paper, in defendants’ words, “generated even more confusion.” Defendants’ Opposition Memorandum at 14. After meeting with representatives of the drug and device industry and CME providers, FDA published a Draft Policy Statement on Industry Supported Scientific and Educational Activities, 57 Fed.Reg. 56412 (1992) which again attempted to describe elements that would be significant in determining when a manufacturer-supported program inappropriately promoted off-label uses. The focus of FDA’s inquiry was whether the discussion of off-label use was independent of the promotional influence of the sponsoring manufacturer. After receiving and reviewing all comments with regard to the Draft Policy Statement (including a citizen’s petition submitted by plaintiff Washington Legal Foundation), the FDA revised its guidance and published the final guidance on December 3, 1997. See 62 Fed.Reg. 64074 (1997). In the final guidance, the FDA recognized the importance of supporting the full exchange of views in scientific and educational discussions, “including discussions of unapproved uses.” Id. at 64095. The guidance was designed to distinguish between those situations in which CME is “independent from, the substantive influence of the supporting company,” and therefore not subject to regulation, as opposed to when the manufacturer is in a position to influence the presentation of information, “or otherwise transform an ostensively independent program into a promotional vehicle.” Id. The FDA developed twelve factors to consider in evaluating programs and activities to determine “independence” which include: who controls the content and selects presenters and the moderator; whether there is meaningful disclosure as to the company’s funding and whether unapproved uses will be discussed; the focus of the program, such as whether the central theme is on one product; the relationship between supporting companies and the CME provider; audience selection; opportunities for meaningful discussion and questioning; dissemination of information; ancillary promotional activities; and any complaints raised by the provider, presenters or attendees regarding attempts by the supporting company to influence content. Id. at 64097-99. Additionally, while not required, a written agreement between the provider and the supporting company “can provide valuable evidence as to whether an activity is independent and non-promotional.” Id. at 64099. This written agreement is intended to demonstrate that the sponsoring company has no involvement in the CME seminars such that it might influence the content, and that the provider is solely responsible for designing and conducting the activity. 2. Enduring Materials Guidance Documents The second set of Guidance Documents concern the distribution of enduring materials — textbook excerpts and article reprints from medical and scientific journals. See 61 Fed.Reg. 52800 (1996). These Guidances restrict manufacturer distribution of enduring materials when the publications address off-label uses for the company’s previously approved products. Similar to the CME Guidance, the FDA noted the need to “strike the proper balance between the need for an exchange of reliable scientific data and information within the health care community, and the statutory requirements that prohibit companies from promoting products for unapproved uses.” Id. As to sponsor/manufacturer distribution of reprints of professional journal articles, the Guidance requires that the principal subject of the article should be the use(s) or indieation(s) that has been approved by the FDA, and the article should report the initial study by the FDA on that approved use; that the reprint should be from a bona-fide peer-reviewed journal; that any effectiveness rates, data, analyses, uses, regimens and the like that are different from the approved labeling shall be prominently stated on the face of the reprint; and that the information shall disclose all material facts and shall not be false or misleading. Id. at 52801. It is largely the first requirement with which plaintiff takes issue. As to reference texts (medical textbooks and compendia), the work may not have been written, edited, excerpted or published specifically at the request of a drug, device or biologic firm, unless the text was prepared in a manner that results in a balanced presentation; the content may not have been reviewed, edited or significantly influenced by the manufacturer; the text should not be available primarily through the manufacturer — it should be generally available in other outlets such as bookstores; and, the reference text should not focus on any particular drug and device, “nor should it have a significant focus on unapproved uses of the drug(s), deviee(s) or biologieal(s).” Id. Notably, these restrictions on the dissemination of enduring materials apply only when the drug manufacturer or sponsor seeks to initiate distribution of the materials. Dissemination of article reprints and reference texts that would otherwise violate the Guid-ances are permissible when that distribution is responsive to a physician’s inquiry. See Tart Deposition at 53-54. The court will return to this point in greater detail in evaluating the merits of the case. 3. The Food and Drug Modernization Act of 1997 On November 21, 1997, President Clinton signed into law the Food and Drug Modernization Act of 1997, PubL. No. 105-115, 111 Stat. 2296 (to be codified at 21 U.S.C. § 360aaa, et seq.). These Amendments differ from the Guidances in that they will permit manufacturer distribution of written information concerning the safety, effectiveness or benefit of an unapproved use of a previously approved drug under specified conditions. The most notable condition is that the manufacturer must submit an application to have the new use approved by the FDA, or certify that such an application will be submitted within six months after the date of the initial dissemination. See § 551(b). The statute also directly addresses physician-initiated inquiries, as it states, “Nothing in section 551 shall be construed as prohibiting a manufacturer from disseminating information in response to an unsolicited request from a health care practitioner.” See § 557(a). The legislation does not address CME seminars. The 1997 Modernization Act will become effective no later than one year from the date of enactment, or upon the Secretary’s issuance of final regulations. See id. § 557(d). Consequently, the October 1996 Guidance Documents will be superseded by statute at that time. II. ANALYSIS A Summary Judgment Fed.R.Civ.P. 56(c) provides that, “summary judgment shall be rendered forthwith if the pleadings, depositions, answers to interrogatories, and admissions on file, together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law.” The rule provides that “the mere existence of some alleged factual dispute between parties will not defeat an otherwise properly supported motion for summary judgment; the requirement is that there be no genuine issue of material fact.” Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 247-248, 106 S.Ct. 2505, 91 L.Ed.2d 202 (1986); Celotex Corp. v. Catrett, 477 U.S. 317, 323, 106 S.Ct. 2548, 91 L.Ed.2d 265 (1986). B. Classification of Manufacturer Sponsorship of CME Seminars and Distribution of Enduring Materials Under Current First Amendment Jurisprudence The threshold question that this court is called upon to answer is how to classify the “speech” at issue. Plaintiff argues that it is scientific and academic speech, which is entitled to the highest level of First Amendment protection. Defendants challenge this assertion by first making a somewhat difficult to discern argument that the Guidance Documents regulate conduct. A closer examination demonstrates that what the FDA is actually contending is that because the federal government has the broad power to regulate the pharmaceutical industry, the Guidances are incidental encroachments upon speech and entirely compatible with the First Amendment. In the alternative, FDA claims that the Guidance Documents at most regulate commercial speech, which is subject to a more relaxed inquiry than core First Amendment speech. 1. Speech or Conduct? FDA’s first contention — that the Guidance Documents are a restraint upon conduct and not upon speech — may be addressed quickly. There is little question that the relevant “conduct” is the off-label prescription of drugs by physicians. The distribution of enduring materials and sponsorship of CME seminars addressing and encouraging that conduct is speech. Mailing enduring materials and/or discussing off-label uses is not inherently “treacherous”; it is only treacherous (if at all) to the extent that physicians choose to pay attention to the message communicated and alter their prescription practices accordingly. As plaintiff’s counsel aptly noted at oral argument, the activities at issue in this ease are only “conduct” to the extent that moving one’s lips is “conduct,” or to the extent that affixing a stamp and distributing information through the mails is “conduct.” FDA clearly recognizes the difference between speech and conduct in noting that “[throughout its papers WLF repeatedly mistakes actual off-label use by physicians with the promotion of off-label use by manufacturers ... FDA’s concerns are directed only to the latter.” Defendants’ Reply Memorandum at 6 (emphasis added). See also id. at 20 (“the Guidance Documents apply only to those situations in which manufacturers ‘cross the line’ between education and promotion”). This court is hard pressed to believe that the agency is seriously contending that “promotion” of an activity is conduct and not speech, or that “promotion” is entitled to no First Amendment protection. There may certainly be a “line” between education and promotion as regards a drug manufacturer’s marketing activities, but that is the line between pure speech and commercial speech, not between speech and conduct. Clearly, defendants do not truly subscribe to this point of view, as they note that “[i]t is the promotional connection with the company that is key”, followed by a cite to Bolger v. Youngs Drug Products Corp., 463 U.S. 60, 67, 103 S.Ct. 2875, 77 L.Ed.2d 469 (1983), which, of course, concluded that the promotional activity at issue was to be analyzed as commercial speech. See Defendants’ Opposition Memorandum at 21. 2. Do the Guidance Documents Address Fully Regulable Speech Not Covered by the First Amendment Because the Food and Drug Industry is Extensively Regulated? The FDA next asserts that the speech regulated by the Guidance Documents falls outside of the ambit of the First Amendment because of the federal government’s extensive power to regulate the pharmaceutical industry through the Pure Food and Drug Act, 21 U.S.C. § 331 et seq. See 62 Fed.Reg. at 64077-78; Defendants’ Opposition Memorandum at 19-22. The agency claims that “FDA is well within its statutory authority to take such actions as are necessary to ensure that drugs and devices comply with the approval requirements of the [Food and Drug] Act.” Defendants’ Reply Memorandum at 8. (“Defendants’ Reply Memorandum”). In support of this argument, the FDA first looks to Ohralik v. Ohio State Bar Ass’n, 436 U.S. 447, 456 (1978), which notes that “[njumerous examples could be cited of communications that are regulated without offending the First Amendment” such as information about securities, corporate proxy statements, the exchange of price and production information among competitors in antitrust regulation, and employer’s threats of retaliation for the labor activities of employees. (citations omitted). FDA also notes Oh-ralik’s pronouncement that “the State does not lose Its power to regulate commercial activity deemed harmful to the public whenever speech is a component of that activity.” Id. See also Dun & Bradstreet, Inc. v. Greenmoss Builders, Inc., 472 U.S. 749, 759 n. 5, 105 S.Ct. 2939, 86 L.Ed.2d 593 (1985) (noting that certain types of communications may be regulated without offending the First Amendment). The FDA also directs the court’s attention to Securities & Exchange Commission v. Wall Street Publishing Institute, Inc., 851 F.2d 365, 373 (D.C.Cir.1988), in which this circuit concluded that regulation of the exchange of information in the securities industry was subject only to limited First Amendment scrutiny. In so holding, the Court of Appeals stated that “the government may have the power to regulate Stock Market Magazine, not because the articles are ‘commercial speech,’ but rather because of the federal government’s broad powers to regulate the securities industry.” Id. at 372. The Court of Appeals went on to note that “[s]peech relating to the purchase and sales of securities, in our view, forms a distinct category of communications in which the government’s power to regulate is at least as broad as with respect to the general rubric of commercial speech.” Id. The court finds that the cases relied upon by FDA do not support its position here. First, the argument that a certain subset of speech may be considered completely outside of the First Amendment framework because the speech occurs in an area of extensive government regulation is a proposition whose continuing validity is at best questionable in light of the Supreme Court’s most recent commercial speech cases. Ohralik, of course, predated the seminal commercial speech case of Central Hudson Gas and Electric Corp. v. Public Service Comm’n of New York, 447 U.S. 557, 100 S.Ct. 2343, 65 L.Ed.2d 341 (1980), by three years. Since the Central Hudson decision, the Supreme Court has consistently applied a speech analysis whether under the pure speech or commercial speech framework to cases involving statutes and/or regulations in areas subject to extensive state or federal regulation. See, e.g., Rubin v. Coors Brewing Co., 514 U.S. 476, 115 S.Ct. 1585, 131 L.Ed.2d 532 (1995) (alcohol labeling); Turner Broadcasting System, Inc. v. FCC, 512 U.S. 622, 114 S.Ct. 2445, 129 L.Ed.2d 497 (1994) (telecommunications); Pacific Gas and Electric Co. v. Public Utilities Comm’n of California, 475 U.S. 1, 106 S.Ct. 903, 89 L.Ed.2d 1 (1986) (utilities); Friedman v. Rogers, 440 U.S. 1, 99 S.Ct. 887, 59 L.Ed.2d 100. (1979) (optometry). Significantly, even in the attorney conduct area— the area directly at issue in Ohralik — the court has recently used the commercial speech framework to uphold a restriction on speech. In Florida Bar v. Went for It, Inc., 515 U.S. 618, 635, 115 S.Ct. 2371, 132 L.Ed.2d 541 (1995), the Court noted, “[particularly because the standards and conduct of state-licenced lawyers have traditionally been subject to extensive regulation by the States, it is all the more appropriate that we limit our scrutiny of state regulation to a level commensurate with the ‘subordinate position’ of commercial speech in the scale of First Amendment values.” (citing Board of Trustees of the State University of New York v. Fox, 492 U.S. 469, 477, 109 S.Ct. 3028, 106 L.Ed.2d 388 (1989), quoting Ohralik, 436 U.S. at 456). This statement indicates, if not demands, that areas subject to extensive regulation are to be scrutinized as commercial speech, and not beyond First Amendment scrutiny, as defendants argue. Any lingering doubt as to whether the government may impose restrictions upon speech without offending the First Amendment merely because it has the authority to regulate the underlying activity was resolved in 44 Liquormart, Inc. v. Rhode Island, 517 U.S. 484, 116 S.Ct. 1495, 134 L.Ed.2d 711 (1996). In that case, the Supreme Court expressly rejected the concept embodied in Posadas de Puerto Rico Assoc. v. Tourism Co. of Puerto Rico., 478 U.S. 328, 106 S.Ct. 2968, 92 L.Ed.2d 266 (1986), that because the government had the power to extensively regulate in a certain area (casino gambling) it also had the authority to regulate speech without raising First Amendment concerns. The court held: The text of the First Amendment makes clear that the Constitution presumes that attempts to regulate speech are more dangerous than attempts to regulate conduct. That presumption accords with the essential role that the free flow of information plays in a democratic society. As a result, the First Amendment directs that the government may not suppress speech as easily as it may suppress conduct. 44 Liquormart, 517 U.S. at 512, 116 S.Ct. 1495. In rejecting the “greater includes the lesser” concept of Posadas (or, in reversing the application of the descriptive terms, see id.) the Court expressly stated, “speech restrictions cannot be treated as simply another means that the government may use to achieve its ends.” Id. One need only juxtapose this statement with the FDA’s claim that merely because it does not regulate off-label use, it need not surrender all enforcement authority to grasp the weakness of the agency’s position. FDA’s argument that it may freely limit manufacturer dissemination of enduring materials and sponsorship of CME seminars as one among several regulatory options because of the government’s broad power to regulate the food and drug industry does not comport with current First Amendment jurisprudence, and therefore must be rejected. Furthermore, other courts that have assessed the constitutionality of various FDA labeling, advertising and promotion regulations and/or disclosure requirements have proceeded directly to a commercial speech analysis without even considering this “area of extensive regulation” argument advanced by the defendants here. Cases concerning “health claim” labeling restrictions are most instructive, as the agency has advanced a similar “separate area of extensive regulation” rationale in defense of its requirements. See & Food Labeling; General Requirements for Health Claims for Food, 58 Fed.Reg. 2478, 2525 (1993). In Nutritional Health Alliance v. Shalala, 953 F.Supp. 526 (S.D.N.Y.1997) plaintiffs challenged the constitutionality of a series of regulations dictating that any claim relating a particular nutrient to prevention of a particular disease or health condition had to be supported by “significant scientific agreement” among qualified experts before the manufacturer’could label the product with that claim. See 21 C.F.R. § 101.14. The court concluded that this regulation should be analyzed as commercial speech under the Central Hudson test. See id. at 529. Other health claim regulation challenges have been resolved using the commercial speech framework. See Pearson v. Shalala, 1998 WL 440621, Civ. A. No. 95-1865(GK) (D.D.C. Jan. 12, 1998) (using the commercial speech framework to uphold FDA regulations); National Council for Improved Health v. Shalala, 893 F.Supp. 1512, 1516-17 (D.Utah 1995) (noting that a facial challenge to the labeling regulations implicated the First Amendment, and employing the Central Hudson framework to determine if the regulations infringed free speech), vacated on other grounds, 122 F.3d 878 (10th Cir.1997). Also, in United States v. General Nutrition, Inc., 638 F.Supp. 556, 562 (W.D.N.Y.1986), the court concluded that labeling is “clearly commercial speech.” In a similar vein, in Federal Trade Comm’n v. Brown & Williamson Tobacco Corp., 778 F.2d 35 (D.C.Cir.1985) the D.C. Circuit was presented with a First Amendment challenge to the Federal Trade Commission’s requirement that all claims as to milligram tar ratings had to be substantiated through the FTC or an FTC-approved methodology. The validity of the injunction against the tobacco company was analyzed under the Central Hudson test. See id., at 43. Similarly, in Association of Nat’l Advertisers, Inc. v. Lungren, 44 F.3d 726, 728-29 (9th Cir.1994), a California statute making it unlawful for a manufacturer to claim that products were “ozone friendly,” “biodegradable,” “photodegradable,” “recyclable,” or “recycled” unless that product met the statutory definition of those terms was held to implicate commercial speech. In light of the fact that analytically similar cases challenging regulations on labeling and promotion have not adopted the FDA’s stance that the First Amendment is not violated because the “Guidance Documents are merely an outcome of the overall statutory scheme,” Defendants’ Reply Memorandum at 10, and in light of prevailing First Amendment speech doctrine, in particular 44 Li-quormart, this court finds that the Guidance Documents are subject to First Amendment scrutiny. 3. Pure Speech or Commercial Speech? Having concluded that the Guidance Documents are restrictions upon speech, and that the speech must be analyzed under a First Amendment framework, the next inquiry is as to whether manufacturer distribution of enduring materials and sponsorship of CME seminars discussing off-label uses are pure speech or commercial speech. As a preliminary matter, the court notes that the aforementioned health claim labeling cases consistently utilized the commercial speech framework. The resolution of this question is not an easy one, as the communications present one of those “complex mixtures of commercial and non-commercial elements.” Bolger, 463 U.S. at 81, 103 S.Ct. 2875 (Stevens, J. concurring). Typical “commercial speech” is authored and/or uttered directly by the commercial entity that wishes to financially benefit from the message. A purveyor of goods or services makes claim about his products to order to induce a purchase. In this instance, by contrast, the speech that the manufacturers wish to “communicate” is the speech of others — the work product of scientists, physicians and other academics. It is beyond dispute that when considered outside of the context of manufacturer promotion of their drug products, CME seminars, peer-reviewed medical journal articles and commercially-available medical textbooks merit the highest degree of constitutional protection. Scientific and academic speech reside at the core of the First Amendment. See, e.g., Keyishian v. Board of Regents, 385 U.S. 589, 603, 87 S.Ct. 675, 17 L.Ed.2d 629 (1967); Board of Trustees of Leland Stanford Junior University v. Sullivan, 773 F.Supp. 472, 474 (D.D.C.1991) (“It is equally settled, however, though less commonly the subject of litigation, that the First Amendment protects scientific expression and debate just as it protects political and artistic expression.”). Plaintiff claims that because this speech merits full protection when uttered by a scientist or academic, the level of constitutional scrutiny should not change merely because a corporation wishes to enhance the distribution of that message. Cf. First National Bank of Boston v. Bellotti, 435 U.S. 765, 784, 98 S.Ct. 1407, 55 L.Ed.2d 707 (1978) (holding that the expression of views on matters of public importance does not lose First Amendment protection merely because a corporation seeks to utter the speech); New York Times v. Sullivan, 376 U.S. 254, 266, 84 S.Ct. 710, 11 L.Ed.2d 686 (1964) (noting that statements do not lose constitutional protection because they are presented in the form of a paid advertisement). Furthermore, plaintiff notes that even though a manufacturer may “have an economic motivation” for dissemination of the speech, that is insufficient, without more, to transform the enduring materials and CME seminars into commercial speech. Bolger, 463 U .S. at 67, 103 S.Ct. 2875. Finally, because the manufacturer is disseminating information that will be of professional use to a physician whether or not the physician ultimately prescribes (and the patient thereby purchases) the drug at issue, the speech arguably does much “more than just propose a commercial transaction.” Virginia State Board of Pharmacy v. Virginia Citizens Consumer Council, 425 U.S. 748, 762, 96 S.Ct. 1817, 48 L.Ed.2d 346 (1976); see also id. at 759, 96 S.Ct. 1817 (concluding that commercial speech was squarely before the court because the pharmacist did not wish to report a newsworthy fact). Plaintiff argues that “there is no evidence that the speech at issue proposes a commercial transaction.” Plaintiffs Opposition Memorandum at 13. The court must disagree with this statement. The mechanism by which a commercial transaction may be “proposed” can vary widely. In the consumer goods area, of course, the proposal usually involves a manufacturer making a claim about its product that encourages the purchase of the product. However, there are certainly instances in which a manufacturer promotes and induces the purchase of its product by directing attention to favorable information generated by wholly independent organizations. For example, auto manufacturers often encourage purchase of vehicles by noting that a certain model has been rated # 1 in a customer satisfaction survey, or that a trade magazine has pronounced the vehicle “Car of the Year.” No one would seriously dispute that an auto dealer was proposing a commercial transaction if he mailed reprints of the customer satisfaction surveys or the magazine articles to past customers who were likely to be looking for a new car in the near future. Similarly, restaurants frequently encourage patronage through promoting favorable magazine reviews — and even go so far as to prepare reprints of these reviews to display in the windows of the establishment. These reprints would likely not merit the same degree of First Amendment protection as a political campaign poster hanging in the same window. The peculiarities of the prescription drug industry make dissemination of scientific research results an especially important and prevalent marketing tool. Though patients are the end-point purchasers of prescription drugs, their choices are constrained by physicians because a patient can only obtain the manufacturer’s products with a physician’s authorization — a prescription. To the extent that physicians are the gatekeepers to sales, the marketing efforts must be directed at them. That fact, combined with the reality that a typical patient is unlikely to strongly challenge a physician’s recommendation concerning a prescription, or have the education and background to make informed choices among equally effective treatments, means that the treating physician is going to be target of much of the pharmaceutical industry’s attention. And, despite the FDA’s occasional statements in its briefs to the contrary, physicians are a highly educated, professionally-trained and sophisticated audience. In making prescribing decisions, doctors want (and need) to know first and foremost if the drug is the most safe and effective means to treat the conditions suffered by the patients. One critical source of that information is the research product of other physicians, scientists and academics. Manufacturers, keenly aware of this, want to get scientific information demonstrating the efficacy of their products in the hands of physicians. See, e.g., Pharmaceutical Hearings at 9 (documenting that the money spent on physician symposia increased from $2.72 million in 1974 to $85.92 million in 1988). Defendants have provided this court with substantial evidence that making physicians aware of research concerning their drugs has a positive effect on the number of prescriptions written, which is equal to a positive effect on sales. See Jerry Avorn et al., “Scientific Versus Commercial Sources of Influence on the Prescribing Behavior of Physicians,” 73 Am. JMed. 4r-8 (1982) (study concluding that a drug company sponsorship of CME events was found to lead to an increáse in the purchase of the funding company’s products); Marjorie A. Bowman and David L. Pearle, “Changes in Drug Prescribing Patterns Related to Commercial Company Funding of Continuing Medical Education,” 4 Journal of Continuing Education in the Health Professions 13, 13-20 (1988). Consequently, there can be little question that the reason that drug manufacturers wish to disseminate enduring materials and sponsor CME seminars is because they believe that such activity will increase the sales volume of their drugs. So, a compelling question is raised: does speech that would be fully protected as scientific and/or educational speech become transformed into commercial speech, with its reduced level of protection, by the mere fact that a commercial entity seeks to distribute it in order to increase its sales of the product addressed in the speech? Whether or not a given communication constitutes commercial speech is predicated upon “the ‘eommonsense’ distinction between speech proposing a commercial transaction ... and other varieties of speech.” Bolger, 463 U.S. at 64, 103 S.Ct. 2875 (quoting Ohralik, 436 U.S. at 455-56, 98 S.Ct. 1912); see also City of Cincinnati v. Discovery Network, Inc., 507 U.S. 410, 423, 113 S.Ct. 1505, 123 L.Ed.2d 99 (1993); Board of Trustees of the State University of New York v. Fox, 492 U.S. 469, 473-74, 109 S.Ct. 3028, 106 L.Ed.2d 388 (1989). Bolger directs a reviewing court to look to three factors in determining whether a form of communication merits full or reduced First Amendment protection. These factors are: (1) whether the speech is eoncededly an advertisement; (2) whether the speech refers to a specific product; and (3) whether the speaker has an economic motivation for disseminating the speech. Bolger, 463 U.S. at 66, 103 S.Ct. 2875. If all three factors are present, the speech “may properly be characterized as commercial speech.” Wall Street Publishing, 851 F.2d at 372 (citing Bolger, 463 U.S. at 66-67, 103 S.Ct. 2875). See also Association of National Advertisers, 44 F.3d at 728; U.S. Healthcare v. Blue Cross of Greater Philadelphia, 898 F.2d 914 (3d Cir.1990). The application of these factors directs the conclusion that manufacturer sponsorship of CME seminars at which the sponsor’s products are discussed and the distribution of enduring materials focusing on the manufacturer’s product are properly classified as commercial speech. Despite plaintiffs protestations to the contrary, the activities at issue do “propose a commercial transaction” as they suggest that a physician should prescribe — and a consumer therefore will purchase — the subject drug. Virginia State Board of Pharmacy, 425 U.S. at 762, 96 S.Ct. 1817. As to the first prong of Bolger, the court finds that these activities are advertisements as that term is commonly understood. An advertisement “call[s] public attention to, especially by emphasizing desirable qualities so as to arouse a desire to buy or patronize.” Webster’s Ninth New Collegiate Dictionary (1990). Through distributing enduring materials and sponsoring CME seminars, drug manufacturers call a physician’s attention to the subject drug product, show that the drug effectively treats a certain condition (emphasize a desirable quality) in the hopes that the physician will prescribe (buy or patronize) the drug. The fact that an effective means for accomplishing that goal is through providing the academic research results generated by others does not mean that the activity is not an “advertisement.” As to the second prong, the textbook excerpts, article reprints, and symposia presumptively refer to a specific product — the drug that is the subject of the off-label use. Were pharmaceutical manufacturers attempting to provide free yearly subscriptions to the Journal of American Medicine, or seeking to support CME regardless of whether their products would ultimately be addressed, a different conclusion might be compelled, as the speech would be closer to a public service. But, as long as the manufacturer seeks to disseminate information centered upon its product, this prong of the test is satisfied. Finally, the pharmaceutical companies clearly have an economic motivation for providing the information; as explained in some detail previously, the promotional efforts at issue have a positive effect on a physician’s prescription practices and therefore on sales. See Avom at 4-8; Bowman & Pearle at 13-20. The facts from Bolger provide considerable support for the conclusion that manufacturer dissemination of enduring materials and sponsorship of CME seminars is properly classified as commercial speech. Among the informational pamphlets that Young’s Drug Products wished to mail included one entitled “Plain Talk About Venereal Disease,” which discussed condom use without any specific reference to the varieties manufactured by the company. Bolger, 463 U.S. at 67 n. 13, 103 S.Ct. 2875. The court still concluded that the pamphlet constituted commercial speech. In the instant case, one could similarly argue that the reprints and seminars are merely informational, and the faet that more prescriptions are written as a result of the manufacturer’s efforts is no different than if more prescriptions were written as a result one physician referring a peer to an article. However, because this information is in fact supplied by the manufacturer, and because the primary purpose for supplying the information is to encourage the purchase of the featured product, the court must conclude that the speech is “entitled to the qualified but nonetheless substantial protection accorded to commercial speech.” Id. at 68, 103 S.Ct. 2875. Furthermore, this conclusion makes sense when one considers the rationale underlying the Supreme Court’s determination that less exacting review is to be afforded commercial speech. The general purpose of the commercial speech doctrine is to “protect consumers from misleading, deceptive or aggressive sales practices.” 44 Liquormart, 517 U.S. at 501, 116 S.Ct. 1495; Discovery Network, 507 U.S. at 426, 113 S.Ct. 1505 (noting that it is the state’s interest in preventing commercial harms that allows the government to subject commercial speech to greater «restrictions). At first glance, it is hard to fathom how dissemination of enduring materials or sponsorship of CME seminars could constitute a deceptive or aggressive sales practice. After all, the physician may obtain the same information from sources other than the manufacturer, and the information is clearly not subject to reduced First Amendment scrutiny in their hands. However, to understand the potential for harm one must look both at the promotional activity in the aggregate and to the substantial resources available to manufacturers. For any given off-label prescription drug treatment, there may be a wide variety of scientific research data available, some of which concludes that the off-label treatment is effective, some of which concludes that the treatment is not. On other hand, manufacturers will likely only seek to disseminate information that presents their product in a favorable light. That fact, combined with the considerable financial resources available to pharmaceutical companies, means that findings concluding that a drug effectively treats a condition is more likely, to reach a physician than studies reaching the opposite conclusion. Therefore, physicians could be led to believe that a certain drug is safe and effective because , a manufacturer has found, and aggressively promoted, “the one” article that supports use of their drug, even if there exists considerable evidence to the contrary. The potential to mislead, and the harm that could result, convinces this court that it is permissible to “depart from the rigorous review that the First Amendment generally demands.” 44 Liquormart, 517 U.S. at 501, 116 S.Ct. 1495. For the aforementioned reasons, this court finds that the speech addressed by the Guidance Documents is properly classified as commercial speech. C. The Commercial Speech Test Applied Having concluded that manufacturer distribution of enduring materials and suggesting content or speakers for CME seminars in which the focus is on the sponsor’s product is properly classified as commercial speech, this court will now analyze the constitutionality of the Guidance Documents under Central Hudson’s four-prong test. 1. The Speech Is Neither Unlawful Nor Inherently Misleading “[T]he First Amendment does not protect commercial speech about unlawful activities.” 44 Liquormart, 517 U.S. at 497 n. 7, 116 S.Ct. 1495 (citing Pittsburgh Press Co. v. Pittsburgh Comm’n on Human Relations, 413 U.S. 376, 93 S.Ct. 2553, 37 L.Ed.2d 669 (1973)). “False, deceptive, or misleading advertising remains subject to restraint.” In re R.M.J., 455 U.S. 191, 200, 102 S.Ct. 929, 71 L.Ed.2d 64 (1982); see also Virginia State Board of Pharmacy, 425 U.S. at 771-72, 96 S.Ct. 1817 (“[u]ntruthful speech, commercial or otherwise, has never been protected for its own sake.”) (citations omitted). The speech here addresses using FDA-approved drugs to treat conditions and in treatment regimens other than those set forth in the label approved by the FDA. As explained above, FDA does not purport to regulate the practice of medicine, and the agency has long recognized that, in general, physicians may use an approved drug or device for an unapproved use. See 59 Fed.Reg. 59280, 59281 (1994) (“once a [drug] product has been approved for marketing, a physician may prescribe it for uses in treatment regimens or patient populations that are not included in the approved labeling”); see also Proposed New Drug, Antibiotic, and Biologic Drug Product Regulations, 48 Fed.Reg. 26720, 26733 (1983). It is obvious that the off-label prescription of previously approved drugs by physicians is presently lawful activity. In claiming that the speech at issue involves “illegal activities,” the FDA does not seriously press any argument that off-label prescriptions are illegal. Rather, the agency directs attention to the statutory basis for the Guidance Documents and asserts that the speech cannot survive the first prong of the Central Hudson test because a drug or device is considered to be misbranded as a matter of law if it is promoted by the manufacturer for an off-label use. See 21 U.S.C. § 352. Therefore, when a manufacturer disseminates information about a drug product that diverges from the treatments included on the label, that manufacturer may be engaged in misbranding, which is illegal. See, e.g., 62 Fed.Reg. at 64079. However, the tautological nature of this argument exposes its shortcomings. The proper inquiry is not whether the speech violates a law or a regulation, but rather whether the conduct that the speech promotes violates the law. The Supreme Court formulates the restriction this way: “[T]he First Amendment does not protect commercial speech about unlawful activities.” 44 Liquormart, 517 U.S. at 497 n. 7, 116 S.Ct. 1495 (emphasis added). Were the FDA’s characterization of what constitutes “lawful activity” accurate, First Amendment protections for commercial speech could be all but eviscerated by the government: First Amendment challenges to speech restrictions would be defeated by noting that Congress had made the speech illegal, and therefore unlawful activity is at issue. The flaw in the FDA’s reasoning is perhaps best demonstrated by example. In Rubin v. Coors Brewing Co., 514 U.S. 476, 115 S.Ct. 1585, 131 L.Ed.2d 532 (1995) the challenged statute prohibited the display of alcohol content on beer labels. Under the FDA’s definition of “illegal activity,” the statute would have been a satisfactory restriction on commercial speech because printing alcohol content on beer labels would render the product “misbranded.” It is clear that when the Supreme Court declares that the First Amendment does not protect illegal activity, it is referring to the conduct that the speech is promoting (e.g., prostitution, counterfeiting, narcotic use, and the like), and not the speech subject to the restriction. Therefore, only at such time as off-label prescriptions are proscribed by law could the FDA legitimately claim that speech at issue addresses “illegal activities.” Whether the speech subject to the restrictions in the Guidance Documents is truthful and non-misleading presents a somewhat closer question. Notably, speech that is merely “potentially misleading” does not render it able to be proscribed under the commercial speech test without further analysis. “If the ‘protections afforded commercial speech are to retain their force, we cannot allow rote invocation of the words ‘potentially misleading’ to supplant [the government’s burden].’ ” Ibanez v. Florida Department of Business and Professional Regulation, 512 U.S. 136, 146, 114 S.Ct. 2084, 129 L.Ed.2d 118 (1994) (internal citation omitted). In order to end the Central Hudson analysis on the first prong, the speech must be “inherently misleading,” which is defined in Central Hudson as “more likely to deceive the public than to inform it.” Central Hudson, 447 U.S. at 563, 100 S.Ct. 2343 (citations omitted); see also In re R.M.J., 455 U.S. at 202, 102 S.Ct. 929. Whether speech is “inherently misleading” depends upon, inter alia, the “possibilities for deception,” see Friedman, 440 U.S. at 13, 99 S.Ct. 887; whether “experience has proved that in fact that such advertising is subject to abuse,” In re R.M.J., 455 U.S. at 203, 102 S.Ct. 929; and, “the ability of the intended audience to evaluate the claims made.” Id. (quoted in Association of National Advertisers, 44 F.3d at 731.) In its Summary of Comments proceeding the Final Guidance on CME activities, the FDA affirmatively declared that the scientific and educational activities at issue in this case were not inherently misleading. See 62 Fed.Reg. at 64079 (instead remarking that they were “clearly potentially misleading”). However, in its memorandum in support of its motion for summary judgment, the agency takes a markedly different stance, claiming that the speech is “inherently misleading,” and that ‘the Act prescribes a specific system for determining the “truth’ of claims about drugs and devices.” Defendants’ Memorandum of Points and Authorities at 32. The FDA was correct the first time. In asserting that any and all scientific claims about the safety, effectiveness, contraindications, side effects, and the like regarding prescription drugs are presumptively untruthful or misleading until the FDA has had the opportunity to evaluate them, FDA exaggerates its overall place in the universe. It is certainly the case that by statute, no drug may be introduced or delivered into interstate commerce without FDA approval, and that the claims that a manufacturer may make about a drug through labeling, advertising and other forms of promotion are subject to FDA regulatory authority. However, the conclusions reached by a laboratory scientist or university academic and presented in a peer-reviewed journal or textbook, or the findings presented by a physician at a CME seminar are not “untruthful” or “inherently misleading” merely because the FDA has not yet had the opportunity to evaluate the claim. As two commentators astutely stated, “the FDA is not a peer review mechanism for the scientific community.” See Lars Noah & Barbara A Noah, Liberating Commercial Speech: Product Labeling Controls and the First Amendment, 47 Fla.L.Rev. 63, 96 (1995). The agency puts it another way: “[t]he fact that [a use] is not an approved indication should not be viewed [by HCFA] as some sort of determination by FDA that the use is inappropriate or — is ineffective.” See Hubbard Deposition at 141. And, at least one other court concurs. “Although the Government argues that health claims that have not been FDA approved are inherently misleading, not all potential health claims are misleading; at least some can be presented in a non-misleading fashion.” Nutritional Health Alliance, 953 F.Supp. at 529. Interestingly, and quite significantly, the FDA has a categorically different view on whether article reprints or CME seminars addressing off-label treatments are “inherently misleading” when anyone other than the drug manufacturer is responsible for their dissemination. See Hubbard Deposition at 46 (“only when a drug company gets involved [and the use is promotional] ... do we have a concern”); Tart Deposition at 155 (“the doctor should have as much information as he feels necessary to use that drug or device on his patient, and that physician is obligated to get that information”). For example, in the Reprint Guidance, it cannot go unnoted that the FDA has no objection to • manufacturer distribution pursuant to a request by a physician, or distribution from any source other than the drug manufacturer. “Defendants’ witnesses have made clear that physicians are free to receive information about off label-uses from numerous other sources.... ” Defendants’ Reply Memorandum at 20; see also Defendants’ Response to Plaintiffs Statement of Material Facts ¶ 19. Obviously, the exact same journal article or textbook reprint cannot be inherently conducive to deception and coercion when it is sent unsolicited, yet of significant clinical value when mailed pursuant to a request. Additionally, the FDA makes no effort to regulate discussion of off-label uses at a CME seminar when there is no pharmaceutical company involvement, but a seminar in which a company-does not suggest the content or the speakers could be just as convincing as to the possible benefits of an off-label use, if not more so, because an attendee is less likely to view such a presentation with a jaded eye. Whether or not the manufacturer plays a role in the dissemination, scientific and academic speech concerning off-label use is either “treacherous anecdotal evidence,” or it is not. It is clear that it is not. Were the materials at issue here either actually or inherently misleading, one would have to conclude that the FDA would be derelict to not proscribe dissemination under all circumstances. FDA notes that another court in this district has apparently considered whether all claims subject to an FDA regulatory scheme are, by definition, “inherently misleading” by virtue of the fact that the FDA has not evaluated those claims. In Pearson v. Shalala, 1998 WL 440621, Civ.A. No. 95-1865(GK) (D.D.C. Jan. 12,1998), the court addressed a constitutional challenge to FDA regulations requiring agency authorization before a manufacturer could label dietary supplements with health claims. In upholding the regulations, the court concluded that “[f]or a health claim label not to be inherently misleading the FDA must find it to be supported by significant scientific agreement.” Id. at *17. However, that statement must be considered in the context in which it was made. The health claims that the manufacturer wanted to include on the label had already been proven by the FDA to be untruthful. See id. at *18-20. The court carefully reviewed each of the four claims, why they were in fact false, and then noted that “[g]iven that each of these claims failed to meet the ‘significant scientific agreement’ standard, the FDA found each to be inherently misleading.” Id. at 20. This court agrees that a regulatory agency clearly may proscribe speech that the agency has proven to be actually misleading and untruthful under the Central Hudson framework. Nothing in this opinion limits the FDA’s ability to strictly enforce any rule, regulation or guidance that sanctions the dissemination of information that is actually false or misleads. Second, and more significantly, the Pearson court went on to note that, “in the unlikely event that Plaintiffs were able to propose health claims that were not misleading, even though they could not meet the