Under its traditional definition, drug compounding is a process in which a pharmacist combines, mixes, or alters various drug ingredients to create a medication for an individual patient in response to a practitioner's prescription. It is generally used to prepare medications that are not typically commercially available, such as a drug in a lower dosage for a child, or a drug without a dye or a preservative in response to a patient allergy. Compounding is considered a conventional component of the practice of pharmacy and has historically been regulated at the state level. The Federal Food, Drug, and Cosmetic Act (FFDCA), as amended, establishes certain minimum standards for the manufacturing, marketing, and distribution of drugs, and authorizes the FDA to ensure that drugs and other products marketed in the United States are safe and effective for their intended uses. The act prohibits any person from introducing a "new drug" into interstate commerce unless it is approved by the FDA. A "new drug" is defined by the act as "[a]ny drug (except a new animal drug or an animal feed bearing or containing a new animal drug) the composition of which is such that such drug is not generally recognized … as safe and effective for use under the condition prescribed, recommended, or suggested in the labeling thereof." In order to be determined to be safe and effective, new drugs are subject to a lengthy approval process, which is supervised by the FDA. The FFDCA also contains requirements preventing drugs from being adulterated or misbranded. Until 1997 with the enactment of the FDA Modernization Act of 1997 (FDAMA, discussed below), Congress had not explicitly addressed whether compounded drugs had to meet these requirements of the FFDCA. For approximately the first 50 years of the FFDCA, pharmacists compounded drugs without getting FDA approval for these drugs, and regulation of drug compounding was left to the states. The reason for this, in large part, is because it is widely recognized that compounded drugs could not meet the FFDCA's drug approval requirements because compounded drugs are traditionally made in small amounts for an individual patient (e.g., safety and efficacy trials are impracticable, and compounding pharmacies cannot afford testing for the new drug approval process to meet the needs of individual patients). Thus, the question of whether the FDA could regulate compounded drugs was generally not disputed until around the early 1990s when the FDA became concerned that some pharmacists were engaged in large-scale bulk compounding that was, in the FDA's view, more akin to drug manufacturing and an attempt to avoid the FFDCA's new drug requirements. In response to these perceived abuses, the FDA issued a Compliance Policy Guide in 1992 addressing its position regarding its authority to regulate compounding. The FDA declared "that while retail pharmacies ... are exempted from certain requirements of the [FFDCA], they are not the subject of any general exemption from the new drug, adulteration, or misbranding provisions" of the FFDCA. While the FDA also indicated that its guidance was not intended to affect a pharmacist's traditional role of compounding drugs extemporaneously in reasonable quantities and pursuant to a valid prescription, the FDA warned that it "may, in the exercise of its enforcement discretion, initiate federal enforcement actions … when the scope and nature of a pharmacy's activity raises the kind of concerns normally associated with a manufacturer." The 1992 Compliance Policy Guide set forth certain factors the FDA would consider in determining whether to exercise enforcement discretion against a compounding pharmacy whose activities raise concerns similar to those of drug manufacturers, including soliciting business to compound specific drug products, using commercial scale manufacturing or testing equipment to compound drug products, and compounding (on a regular basis or in excessive amounts) drug products that are commercially available in the market place and that are essentially generic copies of commercially available, FDA-approved drug products. In order to "clarify the status of pharmacy compounding under Federal law," Congress added Section 503A (21 U.S.C. §353a) to the FFDCA as part of the FDA Modernization Act of 1997 (FDAMA), which specifically addressed the FDA's role in the regulation of drug compounding. Section 503A of the FFDCA, as added by FDAMA, exempts compounded drugs from FFDCA requirements regarding drug adulteration, misbranding, and new drug approval, provided that certain conditions are satisfied. Among these requirements, a drug product must be compounded by a licensed pharmacist or physician for an indentified individual patient based on a valid prescription. The compounded drug must comply with standards of an applicable U.S. Pharmacopoeia, or made from FDA-approved drug ingredients, meet certain manufacturing criteria, and the drug compounded must not be one that appears on a list of drugs (published by the Secretary) of drug products that have been withdrawn or removed from the market because the product, or components of the product have been found to be unsafe or not effective. Further, the drug provider compounding the drug may not "compound regularly or in inordinate amounts … any drug products that are essentially copies of a commercially available drug product." Section 503A of the FFDCA also provided that the exemptions from the FFDCA's new drug and other requirements only applied to drug products compounded based on a valid prescription that was not solicited. Further, the section states that a drug may be compounded and subject to the exemptions only if the pharmacy, licensed pharmacist, or licensed physician does not advertise or promote the compounding of any particular drug. In November of 1998, just days after the provision became effective, several compounding pharmacies challenged the restrictions on solicitation and advertising as being an impermissible regulation of speech under the First Amendment. In Western States , a group of licensed pharmacies brought an action against the Secretary of Health and Human Services (HHS) and the Commissioner of the FDA, claiming that FDAMA's restrictions on solicitation and advertising violated the pharmacies' rights to free speech under the First Amendment. The district court evaluated whether the provisions were an impermissible government regulation of commercial speech under the factors articulated in Central Hudson Gas and & Electric v. Pub. Service Comm'n of New York , and granted the pharmacies summary judgment on the basis that the provision was indeed a violation of the First Amendment. In evaluating whether the other provisions of Section 503A remained intact, the district court found that there is "no question" that the other sections could be severed from the remaining sections. The court explained that the modification of the statute did not prevent it from operating as law, based on the numerous other requirements that must be met in the production and distribution of compounded drugs. The Ninth Circuit Court of Appeals affirmed the district court's holding that the speech provisions of section 503A were unconstitutional, but also reversed in part, holding that the compounding provisions were not severable from the rest of the section. In discussing the severability issue, the court explained that the solicitation and advertising provisions were an essential component in balancing the preservation of compounded drugs alongside the desire to prevent pharmacists and others from engaging in drug manufacturing. The court pointed to legislative history that, in its opinion, demonstrated an intent to strike this balance. The court further indicated that the legislative record demonstrated that Congress meant to exempt compounding pharmacists from FFDCA requirements only in return for a prohibition on the promotion of specific compounded drugs. The court also dismissed the applicability of the existing severability clause in the FFDCA as not indicative of a presumption that Congress intended for unoffending provisions of FDAMA to remain valid. The court explained that because Congress approved the severability clause before FDAMA's passage, there was no indication of whether the clause was to only apply to the original FFDCA, or to the FFDCA as amended by FDAMA. In its brief requesting Supreme Court review on the First Amendment issue, the government indicated its acquiescence with the court of appeals' conclusion that, if the solicitation and advertising provisions in Sections 503A(a) and (c) are unconstitutional, they are not severable from the other provisions of Section 503A. Accordingly, the government did not seek review of that holding. The Supreme Court later affirmed the lower court rulings that the speech restrictions were unconstitutional, but because neither party petitioned for certiorari on the severability issue, the Court articulated that it "had no occasion" to review that portion of the court of appeals' decision. Western States did not address the FDA's authority to regulate drug compounding in the absence of the FDAMA provision. Because (at least in part) of the confusion about the extent of the FDA's authority to regulate compounding remaining after this decision, the FDA issued a Compliance Policy Guide in 2002, largely similar to the compliance guide issued in 1992. The FDA stated that because the Supreme Court did not rule on the severability issue, the Court "therefore left in place" the Ninth Circuit holding that the other provisions of Section 503A were not severable, and the section was therefore invalid. Accordingly, the FDA determined that it needed to issue guidance to the compounding industry regarding the factors the agency would consider in exercising enforcement discretion with regard to pharmacy compounding. The FDA indicated that it did not intend the Compliance Policy Guide to regulate traditional compounding practices (i.e., pharmacists who extemporaneously compound reasonable quantities of drugs upon receipt of a valid prescription for an identified patient). In addition, the FDA noted that it would continue to defer to the state authorities regarding "less significant violations" of the FFDCA. However, the FDA explained its concern with pharmacies that were not compounding in the regular course of business, but were manufacturing large quantities of drug products without a prescription for them.