An outbreak of a rare, non-contagious form of fungal meningitis in 2012 has sickened over 700 individuals in 20 states. There has been extensive policy discussion and news coverage about the safety of compounded drugs and the role of federal and state governments in regulating compounded drugs and compounding pharmacies. A number of policy questions about Food and Drug Administration authority and resources were raised in congressional hearings held by the Energy and Commerce Committee of the U.S. House of Representatives, and the Health, Education, Labor, and Pensions Committee of the U.S. Senate. This report provides information and links to selected resources related to compounded drugs and compounding pharmacies. This report includes sections on Federal Law; Congressional Hearings; Proposed Federal Legislation; Other Congressional Documents; Congressional Support Agency Products; FDA Agency Guidance and Regulations, Meetings, and Related Documents; FDA Actions on Drug Compounding; Other Federal Agency Actions and Resources; Selected State Resources; and Articles from Legal, Professional, and Scientific Journals.
In September 2012, the Centers for Disease Control and Prevention (CDC), the Tennessee Department of Health, the Food and Drug Administration (FDA), and other state health departments1 began investigating a rare, non-contagious2 outbreak of fungal meningitis. As of March 4, 2013, 20 states have reported 720 infections (including fungal meningitis and other conditions) and 48 deaths.3 Patients at risk are those who received injections of contaminated, preservative-free methylprednisone acetate produced by the New England Compounding Center (NECC) after May 2012.4 On October 4, 2012, the FDA verified that NECC was the source of the contaminated products.5
There has been extensive news coverage of the outbreak, which raised issues about the safety of compounded drugs and the role of federal and state governments in regulating compounded drugs and compounding pharmacies.6 A number of policy questions about FDA authority and resources were raised in congressional hearings held by the Energy and Commerce Committee of the U.S. House of Representatives and the Health, Education, Labor, and Pensions Committee of the U.S. Senate.7
This report provides selected resources on the federal government's oversight of compounded drugs and compounding pharmacies, with an emphasis on relevant federal law and regulation and the activities of federal agencies related to and following the 2012 fungal meningitis outbreak. Resources from three states that have direct roles in this outbreak through licensing NECC, or reporting and tracking the fungal meningitis outbreak, are included as well. After a brief background section, the selected resources presented in this report appear in the following order:8
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.10 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.11 Compounding is a component of the practice of pharmacy and has historically been regulated at the state level, along with the licensure of pharmacy professionals and the regulation and licensure of pharmacies.12
The FDA is a regulatory agency within the Department of Health and Human Services (HHS). A key FDA responsibility, under the Federal Food, Drug, and Cosmetic Act (FFDCA), is the regulation of the safety and effectiveness of drugs sold in the United States.13 Notwithstanding state regulation of pharmacies and the practice of pharmacy, the "FDA has determined that it should seriously consider enforcement action" over activities of a compounding pharmacy "when the scope and nature of a pharmacy's activities raise the kinds of concerns normally associated with a drug manufacturer and result in significant violations of the new drug, adulteration, or misbranding provisions of the Act [FFDCA]."14 The recent FDA activities related to the fungal meningitis outbreak are not its first related to drug compounding. In the past the FDA has addressed the compounding of specific drugs (e.g., hormone replacement therapies for women, Makena, and colchicine15) and contamination of compounded drugs.16 The next sections detail the existing federal role with regard to compounded drugs and compounding pharmacies.
Congress moved to clarify the FDA's role in the regulation of drug compounding by adding Section 503A (21 U.S.C. 353a) to the FFDCA as part of the FDA Modernization Act of 1997 (FDAMA, P.L. 105-115). Section 503A exempts compounded drugs from FFDCA requirements regarding drug adulteration, misbranding, and new drug approval process, provided that certain conditions are satisfied.17 Specifically, a drug product must be compounded by a licensed pharmacist or physician for an identified individual patient based on a valid prescription that was not solicited.18 The compounded drug must comply with certain U.S. Pharmacopoeia standards or a relevant national formulary monograph, or be made from FDA-approved drug ingredients, and must meet certain manufacturing criteria.19 The drug compounded must not be one that appears on a list of drugs or drug products (published by the Secretary of HHS) 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.20 Finally, the drug compounder may not "compound regularly or in inordinate amounts … any drug products that are essentially copies of a commercially available drug product."21
Section 503A of FFDCA also 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.22 This was challenged by several compounding pharmacies as an impermissible regulation of speech under the First Amendment. The case went to the 5th and 9th Courts of Appeals and eventually to the U.S. Supreme Court, which agreed that the regulation was unconstitutional as it was not a permitted restriction of speech.23 Whether the rest of the provisions of Section 503A are severable from the free speech provision, and are thus binding, is uncertain.24
Section 510 of FFDCA requires the registration of establishments involved in the manufacture, propagation, compounding, or processing of a drug or drugs; however, it specifically excludes pharmacies functioning in conformance with local laws.
The House Energy and Commerce Committee and the Senate Committee on Health, Education, Labor, and Pensions held hearings on the 2012 fungal meningitis outbreak and its relationship to FDA authority to regulate compounded drugs and compounding pharmacies. These hearings and related documents are listed below.
This section includes selected proposed legislation on the federal regulation of compounded drugs and compounding pharmacies. To date, no legislation has been proposed in the 113th Congress. This section does not include bills that would expand payment or financing of certain compounded drugs for specific diseases or conditions.25
This draft elicited comments from a variety of interested parties, some of which are presented below.
This section includes letters and reports from Members of Congress relevant to the 2012 fungal meningitis outbreak, compounded drugs, and compounding pharmacies.
The following CRS materials address legal issues in drug compounding as well as federal regulation relevant to the current issues posed by the 2012 fungal meningitis outbreak.
This testimony by Janet Heinrich, Director, Health Care—Public Health Issues, was delivered to the Committee on Health, Education, Labor, and Pensions of the U.S. Senate (October, 23, 2003).
In this guidance, excerpted below, FDA identifies its authorities over certain types of activities of compounding pharmacies—those akin to manufacturers—while otherwise deferring to the regulatory prerogative of state pharmacy boards.28
Generally, FDA will continue to defer to state authorities regarding less significant violations of the Act related to pharmacy compounding of human drugs. FDA anticipates that, in such cases, cooperative efforts between the states and the Agency will result in coordinated investigations, referrals, and follow-up actions by the states.
However, when the scope and nature of a pharmacy's activities raise the kinds of concerns normally associated with a drug manufacturer and result in significant violations of the new drug, adulteration, or misbranding provisions of the Act, FDA has determined that it should seriously consider enforcement action.
This regulation lists drugs withdrawn or removed from the market for reasons of safety or effectiveness and which may not be compounded under the exemptions of Section 503A(a) of FFDCA.
On December 19, 2012, the FDA held two meetings regarding state and federal roles in pharmacy compounding. FDA first had an intergovernmental meeting with state officials and then hosted a public meeting titled "Framework for Pharmacy Compounding: State and Federal Roles." This public meeting included a summary of the results of the earlier intergovernmental meeting on the different roles of state and federal governments in regulating compounded drugs and compounding pharmacies. The meeting materials, archived webcast, and transcript are available on the FDA website:
The following FDA documents address compounding activities.
The documents below discuss FDA requirements for prescription drug manufacturers, including those relating to adverse event reporting, inspections, sterility, and Current Good Manufacturing Practices (CGMPs). These materials provide background information on the regulation of manufacturing practices considered important in assuring the safety and effectiveness of prescription drugs.
The FDA maintains a webpage with information on pharmacy compounding with a variety of information, including news and updates; information for consumers; information for health care providers; regulatory and policy information; FDA actions; and related topics.
The FDA maintains a website with updates on the 2012 fungal meningitis outbreak.
Selected FDA information bulletins and updates on the 2012 fungal meningitis outbreak are listed below in descending chronological order:
The following is a selection of FDA announcements and actions relevant to different compounded products and the marketing of prescription drugs without required FDA approval. These documents were selected based on their relevance to policy issues in the federal oversight of compounded drugs.
CDC is involved in the 2012 fungal meningitis outbreak due to its responsibility to protect public health, including through disease surveillance. CDC has taken specific actions related to the 2012 fungal meningitis outbreak. The following is a selection of CDC announcements and actions chosen based on their relevance to policy issues in the federal oversight of compounded drugs.
Selected CDC information bulletins and updates, and Morbidity and Mortality Weekly Reports (MMWR), are listed below.
DOJ is involved in drug compounding issues through its responsibility to enforce the federal laws of the United States, including those regulating prescription drugs, compounded drugs, and compounding pharmacies. DOJ has pursued legal action in the past related to pharmacies that compound drugs; the following list represents cases found on the DOJ website.
The Board of Registration in Pharmacy of the Massachusetts Executive Office of Health and Human Services (EOHHS) licenses pharmacy professionals and pharmacies. The EOHHS maintains a website specific to the 2012 fungal meningitis outbreak and the New England Compounding Center (NECC) product recall and investigation.
Colorado took actions against NECC in 2011 and 2012 for the unlawful distribution of prescription drugs. The documents below are related to those actions.
Tennessee was one of the first states to identify the 2012 fungal meningitis outbreak. Its Department of Health maintains a website focusing on the 2012 fungal meningitis outbreak.
This section lists selected articles selected from a search of PubMed/Medline. The search terms focus on public health concerns and included variations of pharmacy compounding, compounded drugs, adverse effects, and fatalities.
The authors acknowledge the contributions to this report by Jennifer Staman, Legislative Attorney, American Law Division; Ada Cornell, Information Research Specialist, Domestic Social Policy Division (DSP); Meredith Peterson, Section Head, Knowledge Services Group/DSP; [author name scrubbed], Deputy Assistant Director, DSP; and [author name scrubbed], Specialist in Health Policy, Health Services and Research/DSP.
Beth Bell, Director, Director, National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS), "Testimony Before the Health, Education, Labor, and Pensions Committee, U.S. Senate: The CDC and Public Health Response to the 2012 Fungal Meningitis and Other Infections Outbreak," pp. 2-6, http://www.help.senate.gov/imo/media/doc/Bell.pdf.
This form of fungal meningitis is non-contagious; the more common form of meningitis is bacterial and is infectious. See http://www.cdc.gov/meningitis/fungal.html.
Centers for Disease Control and Prevention, Multistate Fungal Meningitis Outbreak—Current Case Count, http://www.cdc.gov/hai/outbreaks/meningitis.html.
Centers for Disease Control and Prevention, Multistate Fungal Meningitis Outbreak, http://www.cdc.gov/HAI/outbreaks/currentsituation/.
Beth Bell, Director, National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention, HHS, "Testimony Before the Health, Education, Labor, and Pensions Committee, U.S. Senate: The CDC and Public Health Response to the 2012 Fungal Meningitis and Other Infections Outbreak," p. 6, http://www.help.senate.gov/imo/media/doc/Bell.pdf.
Lena H. Sun and Kimberly Kindy, "FDA inspects specialty compounding pharmacies in targeted action," Washington Post, March 1, 2012, http://articles.washingtonpost.com/2013-03-01/national/37368259_1_pharmacies-drug-evaluation-inspection; Kimberly Kindy, Lena H. Sun, and Alice Crites, "Compounding pharmacies have been linked to deaths, illnesses and safety failures for years," Washington Post, February 7, 2013, http://articles.washingtonpost.com/2013-02-07/national/36970682_1_medications-for-individual-patients-massachusetts-pharmacy-meningitis-outbreak; Andrew Pollack and Sabrina Tavernise, "Oversight Failures Documented in Meningitis Outbreak," New York Times, November 21, 2012, http://www.nytimes.com/2012/11/22/health/documents-show-fdas-failures-in-meningitis-outbreak.html; Denise Grady, "Deaths Stir a Dispute on Powers of FDA," New York Times, November 20, 2012, http://www.nytimes.com/2012/11/20/health/tainted-drug-deaths-spawn-heated-debate-over-fdas-powers.html?ref=health&_r=0; Sabrina Tavernise, "FDA Chief Seeks Expanded Authority to Improve Safety of Drug Compounders," New York Times, November 14, 2012, http://www.nytimes.com/2012/11/15/health/fda-asking-for-more-control-over-drug-compounding.html?ref=health; and Eric Lichtblau and Sabrina Tavernise, "Friends in Congress Have Helped Drug Compounders Avoid Tighter Rules," New York Times, November 13, 2012, http://www.nytimes.com/2012/11/14/health/niche-drugmakers-get-help-on-capitol-hill.html?pagewanted=all&_r=0.
U.S. Congress, House Committee on Energy and Commerce, Subcommittee on Oversight and Investigations, The Fungal Meningitis Outbreak: Could It Have Been Prevented, 112th Cong., 2nd sess., November 14, 2012, http://search.proquest.com/docview/1151991974/13AA2A2331776953950/1?accountid=41647. U.S. Congress, Senate Committee on Health, Education, Labor, and Pensions, Pharmacy Compounding: Implications of the 2012 Meningitis Outbreak, 112th Cong., 2nd sess., November 15, 2012, http://www.help.senate.gov/hearings/hearing/?id=5f5def0d-5056-a032-5297-eab57634d209.
Articles or sources listed in this report are available from the Congressional Research Service. Please contact [author name scrubbed], [phone number scrubbed].
This section relies on CRS Report R40503, FDA's Authority to Regulate Drug Compounding: A Legal Analysis, by Jennifer Staman.
Food and Drug Administration, "Pharmacy Compounding," page last updated March 1, 2013, http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm. ; and see also Western States Medical Center v. Shalala, 238 F.3d 1090, 1092 (9th Cir. 2001).
Western States Medical Center et al. v. Shalala, 69 F. Supp. 2d 1288, 1292 (D. Nev. 1999). See also Statement of Steven K. Galson, Acting Director, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, before the Senate Committee on Health, Education, Labor, and Pensions, hearing on "Federal and State Role in Pharmacy Compounding and Reconstitution: Exploring the Right Mix to Protect Patients," (Oct. 23, 2003).
Comments of Margaret Hamburg, Commissioner of Food and Drugs, FDA, Transcript of Public Meeting "Framework for Pharmacy Compounding: State and Federal Roles," December 19, 2012; and Western States Medical Center et al. v. Shalala, 69 F. Supp. 2d 1288, 1292 (D. Nev. 1999).
For more information about the FDA's responsibilities with regard to prescription drugs, see CRS Report R41983, How FDA Approves Drugs and Regulates Their Safety and Effectiveness, by [author name scrubbed].
See section identified as "Policy" in Food and Drug Administration, Pharmacy Compounding: Compliance Policy Guidance, CPG Sec. 460.200, Washington, DC, May 2002, http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074398.htm.
Makena is a product that is used to reduce the risk of preterm birth and colchicine is a drug used to treat gout.
For more information, see "FDA Actions on Drug Compounding."
See Section 127 of P.L. 105-115 (FFDCA 503A).
21 U.S.C. §353(a)
21 U.S.C. §353a(b)(1).
21 U.S.C. §353a(b)(1).
21 U.S.C. §353a(b)(1)(D).
21 U.S.C. §353a(c).
Western States, 535 U.S.357 (2002).
For more information on legal issues, see CRS Report R40503, FDA's Authority to Regulate Drug Compounding: A Legal Analysis, by Jennifer Staman.
Copies of this draft legislation are available from [author name scrubbed], CRS, [phone number scrubbed].
Please note, agency rules have the force and effect of law; guidance documents are considered to be a general statement of policy.
For a discussion of the legal and regulatory issues in light of legal challenges, see S. A. Coffina, "Coming Soon: Increased Scrutiny of Compounding Pharmacies," Bloomberg/BNA Pharmaceutical Law & Industry Report (November 16, 2012), and CRS Report R40503, FDA's Authority to Regulate Drug Compounding: A Legal Analysis, by Jennifer Staman.
For the full text of articles, please contact [author name scrubbed], CRS, [phone number scrubbed].
This prescription drug is used to reduce the risk of preterm birth.
For the full text of articles, please contact [author name scrubbed], CRS, [phone number scrubbed].