Compounded Drugs
Judith M. Glassgold
Specialist in Health Policy
May 23, 2013
Congressional Research Service
7-5700
www.crs.gov
R43082
CRS Report for Congress
Pr
epared for Members and Committees of Congress
Compounded Drugs
Summary
Compounding has been traditionally defined as a process where a pharmacist or a physician
combines, mixes, or alters ingredients to create a medication tailored to the needs of an individual
patient. Traditionally compounded drugs (CDs) are made in response to an individual prescription
from a licensed health provider in the context of a pharmacist’s and health care professional’s
relationship with a specific patient.
Some have suggested that certain activities not traditionally associated with compounding be
considered compounding. Such activities include the large-scale production of drugs to ease
certain drug shortages, to meet outsourcing needs of hospitals, and to supply physician-
administered drugs. Nontraditional compounding may include (1) the production and shipping of
large volumes of drugs across state lines; (2) production of drugs that are copies of FDA-
approved commercially available drugs; (3) provision of CD without a prescription for an
individual patient to receive a compounded version and outside of a professional relationship; and
(4) production of products to third parties, such as hospitals, clinics, physician offices, and home
health providers. These activities could be considered more akin to manufacturing than traditional
compounding, which is considered part of the traditional practice of pharmacy.
Adverse events involving contaminated compounded drugs have drawn attention to the growing
use of nontraditionally compounded drugs in health care delivery. Shortages of sterile generic
drugs and hospital outsourcing are cited as causes of increased numbers of CDs produced by
nontraditional compounders. Efforts to assess the risks and benefits of CDs on public health and
safety are complicated by the lack of publicly available information, including the absence of a
federal adverse event reporting requirement and the lack of information about the number of
drugs compounded, the types of drugs compounded, and the number of businesses in this market.
Policymakers have raised questions regarding how best to improve the safety of CDs while
maintaining patient access to needed medications. Drug compounding has historically been the
focus of state governments through their regulation of pharmacies. Recently, questions have
arisen regarding the extent to which the federal government can regulate the practice of
compounding through the Federal Food, Drug, and Cosmetic Act (FFDCA). Policy discussions
include proposals to modify federal oversight of high-risk activities and products, to improve
federal and state coordination, and to increase use of existing federal authorities.
This report provides background information on CDs and nontraditional compounding
pharmacies relevant to policy discussions. This includes an overview of the 2012 fungal
meningitis outbreak; recent recalls of compounded drugs; definitions of traditional compounding
and nontraditional compounding; information on the CDs produced and by whom; information on
the demand for nontraditional compounding, including the role of shortages of sterile injectable
drugs, hospital outsourcing, and patient and provider demand; and information on adverse events
involving compounded drugs.
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Compounded Drugs
Contents
Introduction ...................................................................................................................................... 1
Background ...................................................................................................................................... 2
Health Concerns Involving CDs ................................................................................................ 3
Background ......................................................................................................................... 3
Adverse Event Reporting .................................................................................................... 5
Traditional Compounding .......................................................................................................... 8
Nontraditional Compounding .................................................................................................. 10
Existing Regulatory Oversight ....................................................................................................... 11
Federal Authorities .................................................................................................................. 11
State Authorities ...................................................................................................................... 12
Industry Self-Regulation ......................................................................................................... 13
Growth of Nontraditional Compounding ....................................................................................... 13
Hospital Compounding and Outsourcing ................................................................................ 15
The Role of Drug Shortages in CD Demand ........................................................................... 16
Shortages of Generic Injectable Drugs .............................................................................. 16
Shortages of CDs ............................................................................................................... 17
Other Sources of Demand for Compounded Products ............................................................ 18
Pharmacist Business Development ................................................................................... 19
Provider Demand............................................................................................................... 19
Issues for Consideration................................................................................................................. 20
Adverse Event Reporting and Labeling ................................................................................... 21
The Federal Role in Oversight................................................................................................. 22
Tables
Table 1. Hospital Beliefs About The Effect of Shortages of Compounded Sterile Products
on Patient Care and Health Care Delivery .................................................................................. 18
Table A-1. -Adverse Events ........................................................................................................... 25
Appendixes
Appendix A. Congressional Hearings on CDs 2012-2013 ............................................................ 24
Appendix B. Selected Adverse Events Involving Compounded Drugs and Solutions .................. 25
Contacts
Author Contact Information........................................................................................................... 30
Acknowledgments ......................................................................................................................... 30
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Compounded Drugs
Introduction
In September 2012, the Centers for Disease Control and Prevention (CDC), the Food and Drug
Administration (FDA), the Tennessee Department of Health, and other state health departments1
began investigating a rare, noncontagious outbreak of fungal meningitis.2 As of May 2013, 20
states had reported 741 infections (including fungal meningitis and other conditions),3 and 55
deaths traced to injections of contaminated, preservative-free methylprednisone acetate produced
by the New England Compounding Center (NECC). NECC, which self-identified as a
compounding pharmacy—not a manufacturer—and was licensed by the state of Massachusetts,
produced large volumes of drugs that were shipped across state lines to health care providers.4
Unlike traditional pharmacy practices, NECC produced drugs without individual prescriptions
and made copies of existing commercially manufactured drugs.5
These serious adverse events6 drew attention to compounded drugs (CDs).7 Six congressional
hearings were held in 2012-2013 to understand the factors that led to these adverse events and
ways to prevent future such incidents; these hearings are listed in Appendix A.8 In these hearings
Members of Congress and stakeholders raised questions regarding how best to improve the safety
of CDs while maintaining patient access to needed drugs.
Issues raised at these hearings include the following: (1) what are CDs; (2) how are CDs made
and by whom; (3) what is the role of CDs in health care delivery; (4) what are the federal and
1 For more information on the events relating to tracking the fungal meningitis outbreak, see 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.
2 This form of fungal meningitis is noncontagious; the more common form of meningitis is bacterial and is infectious.
See http://www.cdc.gov/meningitis/fungal.html.
3 Centers for Disease Control and Prevention, Multistate Fungal Meningitis Outbreak Investigation—Current Case
Count, accessed May 6, 2012, http://www.cdc.gov/hai/outbreaks/meningitis.html.
4 Centers for Disease Control and Prevention, Multistate Fungal Meningitis Outbreak Investigation, accessed May 6,
2012, http://www.cdc.gov/HAI/outbreaks/currentsituation/; see also, http://www.cdc.gov/hai/outbreaks/meningitis-
map.html.
5 Statement of Margaret Hamburg before the Senate Committee on Health, Education, Labor, and Pensions “Pharmacy
Compounding: Implications of the 2012 Meningitis Outbreak,” November 15, 2012,
http://www.fda.gov/NewsEvents/Testimony/ucm327667.htm; A. Goodnough, “Sterility Found Lacking at Drug Site in
Outbreak,” New York Times, October 23, 2012, http://www.nytimes.com/2012/10/24/health/sterility-found-lacking-at-
drug-site-in-meningitis-outbreak.html?ref=health.
6 The Food and Drug Administration (FDA) defines a serious adverse event as any undesirable experience associated
with the use of a medical product in a patient. For more information, see FDA “What is a Serious Adverse Event?”
http://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm.
7 See FDA, “Pharmacy Compounding”
http://www.fda.gov/drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm.
8 In 2003 another hearing was held: “Examining State and Federal Oversight to Ensure the Safety and Quality of Drug
Compounding.” hearing of the Senate Committee on Health, Education, Labor, and Pensions, 108th Congress, 1st
Session, October 22, 2003.
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state roles in oversight of CDs; (5) how safe are CDs; and (6) what steps could be taken to
prevent adverse events from CDs.9
This report provides background information about these issues that may be used to inform the
policy discussion as Congress considers legislation. This report focuses on (1) available
background information on CDs and compounding pharmacies; (2) changes in the role of CDs in
healthcare delivery; (3) factors leading to an increase of compounding; (4) safety of CDs,
including a table of selected publicly available adverse events; and (5) a brief summary of policy
issues raised to date. This report includes material on CDs for human patients and does not
include a discussion of veterinary drug compounding or the compounding of dietary supplements.
Issues of public health and safety of CDs are tied to the regulation and oversight of CDs. This
report includes brief information on federal, state, and professional efforts to increase the safety
of CDs. Information on the federal regulation of CDs is addressed in other CRS reports: CRS
Report R40503, FDA’s Authority to Regulate Drug Compounding: A Legal Analysis, by Jennifer
Staman, and CRS Report R43038, Federal Authority to Regulate the Compounding of Human
Drugs, by Andrew Nolan. Information on the regulation of commercially manufactured drugs can
be found in CRS Report R41983, How FDA Approves Drugs and Regulates Their Safety and
Effectiveness, by Susan Thaul.
Background
Compounding has been traditionally defined as a process where a pharmacist or a physician
combines, mixes, or alters ingredients to create a medication tailored to the needs of an individual
patient. Traditionally compounded drugs (CDs) are made in response to an individual prescription
from a licensed health provider in the context of a pharmacist’s and health care provider’s
professional relationship with a specific patient. CDs provide alternatives to standard
commercially manufactured drugs when such drugs do not meet the unique medical needs of a
patient (e.g., due to a need for an allergen-free drug, weight-based dosing, or alternate modes of
delivery), or are unavailable due to discontinuation, unavailability, or shortages. Shortages of
sterile generic drugs and hospital outsourcing are cited as causes of the increased reliance of
health care providers on CDs.10
Some have suggested that certain activities not traditionally associated with compounding be
considered compounding. Such activities include the large-scale production of drugs to ease
certain drug shortages, to meet outsourcing needs of hospitals, and to supply physician-
administered drugs. Nontraditional compounding may include (1) the production and shipping of
large volumes of drugs across state lines; (2) production of drugs that are copies of FDA-
approved commercially available drugs; (3) production of drugs outside of a personal relationship
with a patient and without a prescription for an individual patient to receive a compounded
version; and, (4) providing products to third parties, such as hospitals, clinics, physician offices,
and home health providers. These activities may be considered more akin to manufacturing than
9 See information in Appendix A.
10 Office of the Inspector General, Memorandum Report: High-Risk Compounded Sterile Preparations and
Outsourcing by Hospitals that Use Them, Department of Health and Human Services, OEI-01-13-00150, Washington,
DC, April 1, 2013; K. Fiore, “Drug Shortages Spark Use of Compounders,” (October 18, 2012),
http://www.medpagetoday.com/MeetingCoverage/ASA/35406.
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traditional compounding, which is considered part of the traditional practice of pharmacy. In this
report, references to these types of activities will be called “nontraditional compounding.”
Health Concerns Involving CDs
Background
Adverse events stemming from CDs in 2012 are the starting point for the current policy debate
about existing regulatory oversight of CDs. The 2012 fungal meningitis outbreak was triggered
by contaminated sterile CDs, injectable methylprednisolone, and was the worst recorded adverse
event involving CDs,11 with news reports indicating that up to 14,000 individuals were exposed to
this product.12 Contaminated sterile drugs pose the most serious threats to human health, and can
cause death.13 Details on this event are listed in the following text box.14
Fall 2012 Fungal Meningitis Events
•
September 26, 2012, NECC recal s three lots of methylprednisolone acetate, an injectable steroid.
•
October 4, 2012, the FDA verified that NECC, a compounding center in Massachusetts, was the source of the
contaminated compounded injectable methylprednisolone.15
•
October 6, 2012, NECC recalled all compounded products from its Framingham, MA, facility.16 The FDA urges
health care providers to follow up with patients who received injectable and ophthalmic products.
•
October 31, 2012, Ameridose, a company associated with NECC, recal ed al unexpired products in circulation.
Source: CDC “Related Drug Recal s” http://www.cdc.gov/hai/outbreaks/currentsituation/archive.html, accessed May 6, 2012.
The safety of CDs has been a concern of Congress for over two decades due to the expansion of
nontraditional compounding.17 Potential safety risks for CDs include problems with potency (i.e.,
11 M.R. Cohen, “Meningitis cases spotlight broken system,” Philly.com, October 17, 2012,
http://www.philly.com/philly/health/Meningitis-cases-spotlight-broken-system.html.
12 J. Aleccia, “Fungal Meningitis Outbreak Tied to Steroid Shots, Isn’t the First, Reports Show,” October 18, 2012,
http://vitals.nbcnews.com/_news/2012/10/18/14517177-fungal-meningitis-outbreak-tied-to-steroid-shots-isnt-the-first-
reports-show?lite.
13 Ibid., p. 5.
14 An expanded overview of events related to the 2012 fungal meningitis outbreak can be found in CRS Report
R42837, Selected Resources on Federal Oversight of Compounding Pharmacies, by Judith M. Glassgold, Susan Thaul,
and Janet Kinzer.
15 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.
16 See CDC “Related Drug Recalls” http://www.cdc.gov/hai/outbreaks/currentsituation/archive.html, accessed May 6,
2012.
17 For information on congressional concerns regarding drug compounding that led to Section 503A, see U.S. Congress,
Senate Committee on Labor and Human Resources, Food and Drug Modernization and Accountability Act of 1997, S.
830, 105th Cong., 1st sess., July 1, 1997, S.Rept. 105-43, pp. 67-69. For information on recent concerns with some
references to the history of federal oversight, see “Pharmaceutical Compounding: Proposed Legislative Solution,”
hearing of the Committee of Health, Education, Labor, and Pensions, U.S. Senate, May 9, 2013; “A Continuing
Investigation into the Fungal Meningitis Outbreak and Whether It Could Have Been Prevented?”, hearing of the
Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, U.S. House of Representatives,
April 26, 2013; “Pharmacy Compounding: Implications of the 2012 Meningitis Outbreak,” hearing of the Committee of
(continued...)
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the dosage is inaccurate, either too strong or too weak), purity (e.g., the drug contains other
chemicals that could be harmful), and contamination (the drug is contaminated with a bacteria,
fungus, or virus).18
The FDA conducted surveys in 2001 and 2006 to assess identity, strength, quality, and purity
issues for CDs.19 In a nonrandom survey of compounded drugs available over the internet, about
one-third (33%) failed analytic testing, mostly regarding potency or uniformity of dosage. In
these surveys, the rates of analytic testing failures for compounded drugs were higher than those
for commercially available drugs, where only 2% of drugs failed analytic testing.20 There is no
specific federal or state requirement that an individual CD be tested for potency, purity, and
sterility prior to being sold or administered.21 The compounder of a product may voluntarily
perform such tests along with other quality control processes.22
Safety issues with CDs also have been found by state pharmacy boards.23 Certain states have
started testing a certain percentage of compounded drugs for nondisciplinary purposes. For
example, the State of Missouri Board of Pharmacy initiated a testing program in 2003 for
compounded drugs and each year tests a certain number of finished products.24 Over the course of
the testing program, 15%-25% of the CDs were found to have problems with drug potency,
ranging from a sub-potent drug with 0%—no active ingredient present—to a super-potent drug
with almost 400% of the prescribed dosage. An inaccurate dose may present a risk of harm to the
patient through a risk of toxicity (super-potent) or the risk of ineffective treatment (sub-potency)
(see, for example, Table A-1, years 2010, 2007).25
(...continued)
Health, Education, Labor, and Pensions, U.S. Senate, November 15, 2012; “The Fungal Meningitis Outbreak: Could It
Have Been Prevented?”, hearing of the Subcommittee on Oversight and Investigations, Committee on Energy and
Commerce, U.S. House of Representatives, November 14, 2012, “Examining State and Federal Oversight to Ensure the
Safety and Quality of Drug Compounding.”
18 See US Pharmacopeial Convention-NF, General Chapter <797> Pharmaceutical Compounding – Sterile Preparations
and USP-NF <795> Non-Sterile Compounding.
19 See FDA, “Results” of “Report: Limited FDA Survey of Compounded Drug Products,”
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm204237.htm;
“Stabilityhttp://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm204237.
htm.
20 Ibid., and FDA, “Results of Report: Limited FDA Survey of Compounded Drug Products,”
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm155725.htm.
21 See National Council of State Legislators, “State Regulation of Compounding Pharmacies,”
http://www.ncsl.org/issues-research/health/regulating-compounding-pharmacies.aspx; Statement and response to
questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health, Education, Labor and Pensions,
“Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013.
22 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington, DC, p.3.
23 A report from Rep. Markey’s office details safety issues brought to state boards and transmitted to that office, see
http://markey.house.gov/sites/markey.house.gov/files/documents/Compounding%20Pharmacies%20-
%20Compounding%20Risk%20FINAL_0.pdf.
24 See Missouri Board of Pharmacy annual reports 2006-2011, http://pr.mo.gov/pharmacists-annual-reports.asp.
25 T. Mullarkey, “Pharmacy Compounding of High-Risk Products and Patient Safety,” American Journal of Health-
System Pharmacists, vol. 66 (Suppl5), (September 1, 2009), p. S9.
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The lack of resources to carry out testing of CDs appears to be a problem in several states.26 For
example, a newspaper reported that Texas passed a law to provide for inspections of
compounding pharmacies, but did not authorize funds for such purposes until 2007; once funded,
testing dropped by two-thirds in 2012 compared to 2010 due to state budget cuts.27
Adverse Event Reporting
There is no federal requirement for producers of CDs to report adverse events, so the actual
number of individuals harmed by CDs is unknown.28 Policymakers have had concerns with CDs29
that date back almost two decades;30 these include reports of contamination of products that
should be sterile, sub- or super-potent dosages, and impurities.31
Table A-1 provides a selected compilation of publicly available reports of adverse events
involving CDs and other compounded medical products with details about the date, the number of
states affected, the number of people affected, mortality (if any), drug involved, condition treated,
and other characteristics, such as whether the product was shipped across state lines or was an
off-label use.32 The vast majority of these adverse events involve sterile compounded products.33
Sterile compounded products include injectable drugs, IV-delivered drugs and solutions,
26 See discussion of limited state resources in the public meeting: “Framework for Pharmacy Compounding: State and
Federal Roles,” December 19, 2012, starting on p. 22,
http://www.fda.gov/downloads/NewsEvents/MeetingsConferencesWorkshops/UCM335791.pdf.
27 E. Dexheimer, "As Pharmacies Face Scrutiny, State Oversight Drops," Austin Statesman, November 3, 2012,
accessed May 20, 2013. See also, National Association of Boards of Pharmacy, “Texas Board Surveys Pharmacies
About Compounding Practices, Will Seek Legislative Support for Additional Inspectors,”
http://www.nabp.net/news/texas-board-surveys-pharmacies-about-compounding-practices-will-seek-legislative-
support-for-additional-inspectors, accessed May 20, 2013.
28 Statement and response to questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health,
Education, Labor and Pensions, “Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013.
29 U.S. General Accounting Office, Prescription Drugs: State and Federal Oversight of Drug Compounding by
Pharmacies, 04-195T, September 23, 2003, http://www.gao.gov/products/GAO-04-195T.
30 Information on these concerns can be found on FDA webpages of adverse events, warning letters, manufacturer
recall notices, and in professional journals. See section: “Articles from Legal, Professional, and Scientific Journals” in
CRS Report R42837, Selected Resources on Federal Oversight of Compounding Pharmacies, by Judith M. Glassgold,
Susan Thaul, and Janet Kinzer; and FDA, “Results” of “Report: Limited FDA Survey of Compounded Drug Products,”
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm155725.htm.
31 For a selected group of resources see CRS Report R42837, Selected Resources on Federal Oversight of
Compounding Pharmacies, by Judith M. Glassgold, Susan Thaul, and Janet Kinzer; also, FDA “Pharmacy
Compounding,”
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm; and
FDA, “Introduction: 2006 Limited FDA Survey of Compounded Drug Products,”
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm204237.htm.
32 Off-label use of a prescription drug or device refers to the ability of licensed health care providers to prescribe or use
the drug for indications, conditions, patients, dosages or routes of administration not yet evaluated and approved by the
FDA as part of a new drug approval application.
33 Sterile compounding differs from nonsterile compounding. When compounding exclusively with sterile ingredients,
sterility must be maintained in all phases of production; when compounding with nonsterile ingredients, sterility must
be achieved for the finished product. These processes require special equipment, facilities, and personnel training. See
T. Mullarkey, “Pharmacy Compounding of High-Risk Products and Patient Safety,” American Journal of Health-
System Pharmacists, vol. 66 (Suppl5), (September 1, 2009), p. s5; see USP-NF, “General Chapter <797>
Pharmaceutical Compounding – Sterile Preparations,” http://www.usp.org/store/products-services/usp-compounding.
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inhalation drugs, and parenteral nutrition that are administered directly into the body and must be
sterile to assure patient safety.34
There is no specific federal requirement for the reporting of adverse events with CDs, so that this
information is by nature selective and cannot be used to draw inferences about the overall risks of
CDs. Reports of incidents with CDs that do not rise to adverse events are excluded from the
table.35 Table A-1 also includes other characteristics of CDs, including where it was evident that
CDs were shipped across state lines, an element of nontraditional compounding and high-volume
facilities, whether CD were prescribed for off-label uses, and whether a drug shortage was in
effect. For example, a shortage of generic preservative-free methylprednisolone was reported by
some sources prior to the 2012 fungal meningitis outbreak, which was caused by compounded
versions of that drug.36
The 2012 fungal meningitis outbreak led to greater scrutiny by federal and state authorities of
sterile CDs.37 In 2013, FDA and state authorities inspected certain facilities that produce sterile
CDs and found a variety of safety concerns.38 Later, some, but not all, of these compounders
issued product recalls due to sterility concerns.39 Recalls of sterile CDs in 2013 are listed in the
following text box.40
2013 Manufacturer Recalls of Sterile CDs
•
On May 17, 2013, the FDA announced that Pentec Health, Inc. initiated a recal of nutritional prescriptions for
renal patients due to a lack of sterility assurance. No adverse events had been reported as of the date of recall.41
•
On May 6, 2013, the FDA alerted health care providers of concerns regarding sterility assurance for sterile drugs
produced and distributed by the Compounding Shop. The FDA reports that the Compounding Shop is in the
34 E. S. Kastango, American Society of Health-System Pharmacists, “The ASHP Discussion Guide for Compounding
Sterile Preparations,” http://www.ashp.org/s_ashp/docs/files/HACC_797guide.pdf.
35 Some reports included concerns with products, but no adverse events. See for instance, M.P. Goldman, “Sodium
Tetradecyl Sulfate for Sclerotherapy Treatment of Veins: Is Compounded Pharmacy Solution Safe?” American Society
for Dermatologic Surgery, vol. 30, pp. 1454-1456; K. Hundley, “Lincare Pharmacy Runs Afoul of Missouri
Regulators,” St. Petersburg Times, April 18, 2003; S. Sellars and W.H. Utian, “Pharmacy Compounding Primer for
Physicians: Prescriber Beware, ” Drugs, vol. 72, no. 16, pp. 2043-2050.
36 In early 2012, Hospira was listed on the FDA shortages website as discontinuing methylprednisolone:
http://www.fda.gov/drugs/drugsafety/drugshortages/ucm050794.htm. Another site reports a shortage of
methylprednisolone in May 2012, http://eraycollins.blogspot.com/2012/05/shortage-of-injectable.html; and K. Kindy,
L.H. Sun, and A. 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.
37 See Testimony of Margaret Hamburg at a hearing of the Subcommittee on Oversight and Investigations, Committee
on Energy and Commerce, U.S. House of Representatives, “A Continuing Investigation into the Fungal Meningitis
Outbreak and Whether It Could Have Been Prevented?”, April 26, 2013.
38 FDA, 2013 Inspections,
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicR
eadingRoom/ucm340853.htm, accessed May 6, 2012, and http://www.fda.gov/Safety/Recalls/default.htm, accessed
May 6, 2012.
39 Ibid.
40 This list of recalled CD is current as of May 18, 2013.
41 See FDA
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm352939.htm.
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process of recalling products.42
•
On April 22, 2013, Nora Apothecary and Alternative Medicine recalled all lots of sterile compounded products
produced on or before April 19, 2013, due to the lack of sterility assurance and concerns associated with quality
control processes. No adverse events had been reported as of the date of recal .43
•
On April 21, 2013, Balanced Solutions Compounding Pharmacy (Balanced Solutions), a division of Axium
Healthcare Pharmacy, Inc., of Lake Mary, FL, recalled all lots of its sterile nonexpired drug products due to a lack
of sterility assurances associated with the quality control processes. No adverse incidents had been reported as
of the date of recall.44
•
On April 15, 2013, NuVision Pharmacy recalled all lots of all compounded lyophilized products due to sterility
assurance concerns. No adverse events had been reported as of the date of recal .45 On May 18, 2013, the FDA
expanded its alert to health care providers to al sterile drug products made and distributed by NuVision.46
•
On April 15, 2013, ApothéCure, Inc. recalled all lots of all sterile products compounded, repackaged, and
distributed by Apothécure, Inc. due to sterility assurance concerns. No adverse events had been reported as of
the date of recall.47
•
On April 05, 2013, Green Valley Drugs recalled all lots of all sterile products compounded, repackaged, and
distributed by the firm due to quality control concerns. No adverse events had been reported as of the date of
recall.48
•
On March 25, 2013, state regulators halted production of sterile products made by Pallimed, a compounding
pharmacy, and requested a recal of al sterile products.49 Pallimed issued such a recall March 26, 2013. No
adverse events had been reported as of the date of recall.50
•
On March 20, 2013, Clinical Specialties Compounding Pharmacy recalled all sterile products repackaged and
distributed due to the company’s lack of confidence in product sterility.51 This followed a recall on March 18,
2013, of Avastin compounded for ophthalmic use. No adverse events had been reported as of the date of
recall.52
•
On March 17, 2013, Med Prep recal ed al lots of its compounded drugs due to mold contamination.53 This
fol owed the recal of a single product line on March 16, 2013. No adverse events had been reported as of the
date of recall.54
42 See FDA
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm351326.htm.
43 See http://www.fda.gov/Safety/Recalls/ucm349040.htm.
44 See http://www.fda.gov/Safety/Recalls/ucm348723.htm.
45 See FDA Recalls: http://www.fda.gov/Safety/Recalls/ucm348095.htm.
46 See FDA
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm352949.htm?sou
rce=govdelivery.
47 See FDA Recalls: http://www.fda.gov/Safety/Recalls/ucm348094.htm.
48 See FDA Recalls: http://www.fda.gov/Safety/Recalls/ucm347559.htm.
49 C. Conaboy and K. Lazar, "State Halts Drug Production at Woburn Pharmacy," Boston Globe, March 24, 2013,
http://bostonglobe.com/lifestyle/health-wellness/2013/03/25/woburn-compounding-pharmacy-issues-recall-sterile-
products/j7QDTvv5WIHO1FU8W6mNGP/story.html.
50 See http://www.fda.gov/Drugs/DrugSafety/DrugRecalls/.
51 See FDA “Recall – Firm Press Release”, http://www.fda.gov/Safety/Recalls/ucm344786.htm?source=govdelivery.
52 See FDA Recalls http://www.fda.gov/Safety/Recalls/ucm344377.htm.
53 FDA, “Medprep Consulting Inc. Announces Voluntary Nationwide Recall of All Lots of All Compounded Products
Due to Potential Mold Contamination,” March 17, 2013, http://www.fda.gov/Safety/Recalls/ucm344787.htm.
54 See FDA Recall: http://www.fda.gov/Safety/Recalls/ucm344189.htm.
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Traditional Compounding
Traditional compounding is a process where a pharmacist or a physician “combines, mixes, or
alters ingredients to create a medication tailored to the needs of an individual patient”55 in
response to a prescription from a health care provider. CDs can include different formulations of
drugs (e.g., liquid instead of tablet), doses, and certain ingredients (e.g., allergen-free, dye-free).56
This report will use the phrase “traditional compounding” to reference the historical use of the
term compounding.
CDs can provide patients drugs tailored to their individual health needs. The benefits of
traditional compounding include (1) providing individualized drugs when commercially produced
drugs do not meet the health requirements of an individual patient; and (2) maintaining access to
certain prescription drugs that are not commercially available due to shortages, unavailability, or
discontinuation, among other factors.57
The number of CDs made cannot be determined due to the lack of publicly available
information.58 Currently no federal reporting requirement exists for producers of CDs with
respect to their compounding activities.59 The most recent attempt to assess the number of CDs
was through a survey commissioned by the FDA in 2001. This report estimated that 650
pharmacies filled about 13 million prescriptions for compounded prescription drugs per year.60
Some stakeholders estimate that anywhere from 1% to 5% of all prescriptions filled annually are
for CDs,61 but the basis of this information cannot be verified.62
There is also no publicly available information on the types of CDs made, for instance, the
percentage of CDs that include dosage, formulation, or ingredient alterations, or that are produced
in response to shortages of commercially manufactured drugs. The lack of information on the
current scope of compounding presents challenges for public health authorities and policy
makers.
55 “Thompson v. Western States,” 535 U.S. 357 at 360-361.
56 Ibid.
57 Ibid., p. 361. Cost may be a factor in certain circumstances, see D. J. DeNoon, reviewed by L.J. Martin, “FDA:
Pharmacies Can Still Make Preterm Birth Drug,” http://www.webmd.com/baby/news/20110330/fda-generic-makena-
ok; and “FDA Statement on Makena”
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm279098.htm.
58 Statement and response to questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health,
Education, Labor and Pensions, “Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013.
59 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.
60 Testimony of Steven Galson, FDA, at a hearing of the Senate Committee on Health, Education, Labor, and Pensions,
108th Congress, 1st Session, October 22, 2003, “Examining State and Federal Oversight to Ensure the Safety and
Quality of Drug Compounding.”
61 Since close to 4 billion prescriptions are filled annually in the United States, this percentage would yield a range of
40-200 million CDs annually.
62 P. M. Barrett, “America's Shadow Pharmacies,” Bloomberg Businessweek, November 14, 2012; and Denise Grady,
Sabrina Tavernise, and Andrew Pollack, “In a Drug Linked to a Deadly Meningitis Outbreak, a Question of Oversight,”
New York Times, October 4, 2012, http://www.nytimes.com/2012/10/05/health/news-analysis-a-question-of-oversight-
on-compounding-pharmacies.html. Another estimate of 30-50 million annually is from the FDA, see Testimony of
Steven Galson, FDA, at a hearing of the Senate Committee on Health, Education, Labor, and Pensions, 108th Congress,
1st Session, October 22, 2003, “Examining State and Federal Oversight to Ensure the Safety and Quality of Drug
Compounding.”
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Pharmacists, or technicians supervised by a licensed pharmacist, and physicians can produce
CDs.63 Compounding is part of the standard practice of pharmacy and is within the scope of state
licensure of pharmacists and pharmacies.64 The number of pharmacists engaged in compounding
on a regular basis is difficult to evaluate due to a lack of publicly available information.65 The
most recent attempt to survey pharmacists, commissioned by the FDA, found that the majority of
compounded prescriptions are filled by a small number of pharmacies, and for some, CDs are the
majority of their business.66 Others provide different estimates. Janet Woodcock, Director of the
FDA Center for Drug Evaluation and Research (CDER), stated in a recent interview that 28,000
pharmacies compound drugs nationwide.67 The American Pharmacists Association (APhA), a
trade association of pharmacists, reports that there are 7,500 pharmacies in the United States that
specialize in compounding.68 The International Academy of Compounding Pharmacies, a trade
association representing the compounding profession, has 2,700 members.69 As of January 2013,
there were 163 pharmacies in the United States accredited by the Pharmacy Compounding
Accreditation Board, which offers a voluntary accreditation process for compounding
pharmacies.70
Existing sources of publicly available information on specific CD products include those listed by
compounding pharmacies on their websites,71 products described by professional associations,72
products mentioned in scientific journals, and on CDC and FDA websites due to warning and
other notices.73 These CDs include, among others, drugs for pain management (including
63 States license health care professionals. The scope of permitted activities of pharmacy professionals is largely
determined by state law. For an example of a job description for a compounding professional, see
http://www.wedgewoodpharmacy.com/jobs/pharmacy-technician-general-compounding.html, accessed April 1, 2013.
64 National Council of State Legislators, “State Regulation of Compounding Pharmacies,” http://www.ncsl.org/issues-
research/health/regulating-compounding-pharmacies.aspx. Telephone conversation between the author and Joe
Cabaleiro, Executive Director, Pharmacy Compounding Accreditation Board, January 4, 2013; and, see American
Pharmacists Association, “Frequently Asked Questions about Pharmaceutical Compounding,”
http://www.pharmacist.com/frequently-asked-questions-about-pharmaceutical-compounding, accessed May 20, 2013.
65 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington DC.
66 Steven Galson, FDA, at a hearing of the Senate Committee on Health, Education, Labor, and Pensions, 108th
Congress, 1st Session, October 22, 2003, “Examining State and Federal Oversight to Ensure the Safety and Quality of
Drug Compounding.” The FDA provided limited information on this study, so its reliability cannot be assessed.
67 See J. Woodcock interview with an industry newsletter, Pharmalot:
http://www.lawofcompoundingmedications.com/2013/04/during-pharmalot-interview-fda.html.
68 See http://www.pharmacist.com/compounding-just-the-facts.
69 See the International Academy of Compounding Pharmacies website, http://www.iacprx.org.
70 Telephone conversation between the author and Joe Cabaleiro, Executive Director, Pharmacy Compounding
Accreditation Board, January 4, 2013.
71 Products provided by compounding pharmacies can be found on websites generated by standard searches of the web
with keywords such as “compounding pharmacies.” Further, the website of the Pharmacy Compounding Accreditation
Board, a private nonprofit organization that accredits compounding pharmacies has a list of accredited compounding
pharmacies, http://www.pcab.org/. A list of products provided by compounded pharmacies can be found on the
websites of accredited members, see for instance, CarePro Compounding.
http://www.careprohs.com/pharmacies/compounding/ or A & O pharmacy,
http://www.aopharmacy.com/compounding.html.
72 Statement of K. Thompson, American Society of Health-System Pharmacists, hearing of Committee on Health,
Education, Labor, and Pensions, U.S. Senate, November 12, 2012,
http://www.help.senate.gov/imo/media/doc/Thompson7.pdf.
73 FDA Actions,
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/#compliance See list
(continued...)
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alternate delivery, combined medications, dosage variations), hormone replacement therapies for
women (including bioidentical hormones) and men (e.g., testosterone), men’s and women’s
health, sports medicine, weight-loss, dental care, veterinary care, pediatric patients, and hospice
care.74 Some compounded products include items advertised as treatments for Autism/ADHD,75
“adrenal fatigue,”76 or fat-elimination;77 the FDA and others have raised questions regarding these
claims.78
Nontraditional Compounding
As noted earlier, some enterprises have engaged in certain activities not traditionally associated
with compounding, but have asserted that these activities should be considered compounding.79
Such activities include the large-scale production of drugs to ease certain drug shortages, to meet
outsourcing needs of hospitals, and to supply physician-administered drugs.80 Nontraditional
compounders make a variety of products, including sterile injectables, parenteral nutrition, and
drugs on the FDA shortage list.81 Sterile injectable CDs include epidurals (for childbirth and pain
management), nerve-blocking agents, drugs for pain management, and antibiotics.82 Individuals
might receive these products in a hospital, doctor’s office, or other medical facility as a
medication, an IV solution, or nutrition.
(...continued)
of resources in CRS Report R42837, Selected Resources on Federal Oversight of Compounding Pharmacies, by Judith
M. Glassgold, Susan Thaul, and Janet Kinzer for examples of medical and scientific journals and FDA resources.
74 For more information, see the following compounding pharmacies’ websites: http://www.pccarx.com/join-pcca/;
http://www.moorespharmacy.com/testimonials.htm; and http://www.hotzehwc.com/en-US/Treatment-
Programs/FAQ.aspx.
75 For example, see the following compounding pharmacy website: http://www.myvillagegreen.com/compounding-
pharmacy/.
76 For example, see the following compounding pharmacy http://www.hotzehwc.com/en-US/Treatment-
Programs/Adrenal-Fatigue.aspx.
77 In some instances the FDA has issued warning letters to compounding pharmacies regarding the claims of these
products. For example, see FDA, "FDA Issues Warning Letters for Drugs Promoted in Fat Elimination Procedure,"
press release, April 7, 2010, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2010/ucm207453.htm.
78 “FDA Warns Marketers of Unapproved ‘Chelation’ Drugs,
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm229358.htm; FDA Warning Letter CIN-10-94106-12,
Libido Edge Labs, LLC, 06/10/2010; R. Sood et al., “Counseling Postmenopausal Women About BioIdentical
Hormones: Discussion Point 10: Adrenal Fatigue Does Not Mean Adrenal Insufficiency,” Journal of the Board of
Family Medicine, vol. 24, no. 2, (2011), pp. 202-210;
79 See for instance, objections by compounding pharmacies to FDA regulation, including Medical Ctr. Pharm., 536
F.3d and Franck’s Lab, 816 F. Supp. 2d.
80 The term “nontraditional” compounding is found in a number of sources: 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); Office of the Inspector General, Memorandum Report: High-Risk
Compounded Sterile Preparations and Outsourcing by Hospitals that Use Them, Department of Health and Human
Services, OEI-01-13-00150, Washington, DC, April 1, 2013. Another term used for this activity is “compounding
manufacturing” (Source: Draft legislation by the Senate Committee on Health, Education, and Labor circulated in the
113th Congress).
81 Parenteral nutrition is IV administered nutrition, which bypasses the digestive tract.
82 See PharMedium, “Compounding Services,” http://www.pharmedium.com/compounding/index.html, accessed May
20, 2013.
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Some nontraditional compounders have large numbers of customers. For example, PharMedium,
a large-scale compounder, reported 2,300 hospital customers for a variety of compounded
products.83 NECC, the compounder involved in the fungal meningitis outbreak of 2012, was
listed on a FDA website as having over 20,000 customers, including physicians, clinics, and
hospitals.84
Existing Regulatory Oversight
Drug compounding has historically been the focus of state governments through their regulation
of pharmacies. Recently questions have arisen regarding the extent to which the federal
government can regulate the practice of compounding through the Federal Food, Drug, and
Cosmetic Act (FFDCA). This section discusses federal and state authorities, as well as industry
self-regulation.
Federal Authorities85
Federal authority over compounding largely stems from the Federal Food Drug and Cosmetics
Act (FFDCA), enacted in 1938, and its subsequent amendments, including the Food and Drug
Administration Modernization Act (FDAMA) of 1997, which added compounding-specific
provisions to the FFDCA in Section 503A. Litigation over Section 503A’s advertising provisions
has created doubt, however, over the legal effect of FDAMA’s compounding provisions.86
The precise limit to federal authority with respect to drug compounding remains uncertain, as the
federal authority to regulate traditional drug compounding has been discussed by very few courts,
and each court that has approached the issue did so from a unique factual setting that colored the
eventual outcome of the case.87 Courts appear to agree that the federal government can regulate
compounding activity that is akin to manufacturing (i.e., nontraditional compounding), and courts
have afforded deference to the FDA’s interpretation of when a compounder is acting like a
manufacturer, which appears to be within the FDA’s discretion.88 However, there is not a bright-
line distinction between behaviors that are “akin to manufacturing” and those of a traditional
compounding pharmacy. As a result, uncertainty remains regarding the possible limits to the
FDA’s current authority to regulate traditional compounding practices.
Even assuming that FDA has the authority to regulate traditional compounding, as a matter of
policy, the FDA has generally declined to test the current limits of its authority to regulate
83 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington DC, p. 7.
84 See FDA http://www.fda.gov/downloads/Drugs/DrugSafety/FungalMeningitis/UCM325466.pdf, accessed May 20,
2013.
85 Unless otherwise noted this section is based on CRS Report R43038, Federal Authority to Regulate the
Compounding of Human Drugs, by Andrew Nolan. For more information, see CRS Report R43038, and CRS Report
R40503, FDA’s Authority to Regulate Drug Compounding: A Legal Analysis, by Jennifer Staman.
86 Ibid., see the above reports for a discussion of Section 503A.
87 See generally Franck’s Lab, 816 F. Supp. 2d at 1235-1239 (discussing the cases that have examined the scope of the
FDA’s authority with respect to compounding).
88 See, e.g., Wedgewood Village Pharmacy, 421 F.3d at 272-73.
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compounding, preferring instead to defer to state governments with respect to the regulation of
“traditional compounding.”89
State Authorities
Traditional compounding is a component of the practice of pharmacy and has typically been
regulated by the states as “part of their regulation of pharmacies”90 and the licensing of
pharmacists as health care professionals.91 There is great variety in existing state legislation
addressing CDs.92 Certain states have passed new laws, or are considering revisions of laws and
regulations for compounding pharmacies, in part due to recent events.93 The National Association
of Boards of Pharmacies (NABP) has listed summaries of approved and proposed state changes to
permitted compounding practices.94
State boards of pharmacy evaluate pharmacists and pharmacies on compounding practices and
facilities.95 Compounding from bulk ingredients is generally an approved part of pharmacy
practice,96 with some states requiring all licensed pharmacies to offer compounding services.97
Some states follow NABP model language and permit a pharmacist to compound drugs to
patients only upon receipt of a valid prescription from a doctor or other medical practitioner
licensed to prescribe medication.98 Some states require a special license for compounding sterile
medications, which requires special facilities and adherence to sterile methods.99 Other states
license a separate class of pharmacy facility that produces drugs for pharmacies or other
providers, such as central fill pharmacies.100 Finally, some states permit pharmacies to make exact
copies of commercial products in response to discontinued products or drug shortages.101
89 See CPG §460.200 (May 29, 2002); see also CPG §608.400 (July 14, 2003).
90 W. States Med. Ctr., 535 U.S. at 361.
91 R.R. Abood, Pharmacy Practice and the Law, 6th ed. Sudbury, MA: Jones and Bartlett (2011).
92 This report is not meant to be a comprehensive survey of state law regulations on pharmacy compounding. For more
information on the topic, the National Conference of State Legislators provides summaries of existing state laws and
new initiatives. See “State Regulation of Compounding Pharmacies,” updated April 13, 2013,
http://www.ncsl.org/issues-research/health/regulating-compounding-pharmacies.aspx.
93 Ibid.
94 See National Association of Boards of Pharmacies, http://www.nabp.net/news/tagged/compounding.
95 Ibid.
96 See, e.g., Fla. Admin. Code Ann. 64B16-27.700(1)(c).
97 See, e.g., 49 Pa. Code § 27.18(p)(2); W. Va. Code St. Rules, tit. 15, § 19.4.
98 See, e.g., Okla. Admin. Code §§ 535:15-10-3, 535:15-10-9(d); Colorado State Board of Pharmacy Rule 3.02.10.
99 See for instance, California Business and Professional Code Section 4127 regarding standards for compounding
injectable sterile products, http://www.leginfo.ca.gov/cgi-bin/displaycode?section=bpc&group=04001-
05000&file=4127-4127.8, accessed May 21, 2013.
100 See New Jersey 13:39-4.18(a) et seq. Procedures for Centralized Prescription Handling,
http://www.njconsumeraffairs.gov/adoption/pharmado_100509.htm.
101 See H.2. “The Pharmacy Act and Drug Control Act with Related Statutes”, Commonwealth of Virginia, (July 1,
2012), http://www.dhp.virginia.gov/Pharmacy/pharmacy_laws_regs.htm.
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Industry Self-Regulation
Professional programs in pharmacy are accredited and pharmacists generally receive formal
education and professional training with respect to the practice of compounding drugs.102
Pharmacists can participate in a voluntary accreditation process for compounding established by
professional pharmacy organizations, and the U.S. Pharmacopeial Convention (USP).103 As of
December 2012, 163 facilities nationwide have this accreditation.104
Professional standards and guidelines for CDs are established by the USP in published standards:
Chapter 797 “Pharmaceutical Compounding—Sterile Preparations” for sterile products and
Chapter 795 “Pharmaceutical Compounding—NonSterile Preparations.” USP Standard 797
includes standards for facilities, procedures, and staff in order to produce safe sterile drugs, such
as sterilizing equipment, a sterile clean room, special ventilation, and decontamination
processes.105
Not all pharmacies or compounders adhere to these USP standards, and these standards, unless
required by state law, are voluntary.106 To date, 20 states have laws that require full adherence to
USP Standard 797.107
USP standards are designed for pharmacy compounding and may not be suitable for large-scale
production of CDs.108 Commercial production of drugs is addressed by the current good
manufacturing practices (cGMP) required by Section 501 of the FFDCA for commercial
manufacturers; cGMP requires certain manufacturing practices as well as adverse event
reporting.109
Growth of Nontraditional Compounding
Some believe that the numbers and types of CDs and other products (IV and parenteral nutrition)
are increasing,110 coinciding with increasing demand for certain compounded products111 due to a
102 W. States Med. Ctr., 535 U.S. at 361 (noting that as a “traditional component of the practice of pharmacy,
compounding is taught as a part of the standard curriculum at most pharmacy schools.”)
103 The U.S. Pharmacopeial Convention (USP) is a scientific nonprofit organization that sets standards for the identity,
strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured and distributed
worldwide. USP’s drug standards are referenced in FFDCA. The Pharmacy Compounding Accreditation Board
(PBAB) sets standards for compounding, http://www.pcab.org/.
104 See National Conference of State Legislatures, “State Regulation of Compounding Pharmacies, Updated April 16,
2013.
105 See USP-NF, “General Chapter <797> Pharmaceutical Compounding – Sterile Preparations,” (Date), Appendix A.
106 Ibid., p. 9.
107 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington DC, p. 8.
108 Ibid.
109 See also FDA “Facts About Current Good Manufacturing Practices”
http://www.fda.gov/drugs/developmentapprovalprocess/manufacturing/ucm169105.htm
110 J. Lee, “Investors Buying Compounders,” ModernHealthcare.com, January 19, 2013,
http://www.modernhealthcare.com/article/20130119/MAGAZINE/301199973; F. Gebhart, “Flush with victory,
compounding pharmacists see demand soar,” Drug Topics, vol. 144, no. 2 (January 17, 2000), pp. 28-31; and testimony
by Steven Galson, FDA, before the Senate Committee on Health, Education, Labor, and Pensions, October 23, 2003,
(continued...)
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variety of reasons, including (1) an increase in hospital outsourcing of CDs; (2) drug shortages,
unavailability, and discontinuation of FDA-approved drugs;112 (3) interest in individualized
products by physicians and consumers; and (4) an increased interest by pharmacists in new
markets.113
As noted earlier, the exact number of business facilities engaged in nontraditional compounding
is unclear.114 In 2013, the FDA inspected nontraditional compounding facilities that were engaged
in sterile compounding and lists 36 facilities that it inspected located around the country.115 Some
of these facilities, such as Central Admixture Pharmacy Services and PharMEDium Services,
have multiple locations. Press and other sources indicate growth of centralized compounding
facilities that provide outsourcing and related activities to pharmacies and hospitals.116 Some of
these compounding facilities include compounding pharmacies, central fill pharmacies,117 and
outsourcing pharmacies.118 Some states, but not all, permit certain types of consolidated services,
such as “shared services” or “central fill IV pharmacies,”119 which make products for distribution
among a variety of providers. For example, Med Prep Consulting, Inc. lists itself as a state-
licensed central fill pharmacy and provides products to other pharmacies.120
(...continued)
http://www.fda.gov/NewsEvents/Testimony/ucm115010.htm.
111 J. Lee, “Investors Buying Compounders,” ModernHealthcare.com, January 19, 2013,
http://www.modernhealthcare.com/article/20130119/MAGAZINE/301199973.
112 E.S. Kastango, Outsourced Medications: How Can You Know They Are Safe? Clinical IQ, 2013,
http://pharmacyonesource.com/images/simplifi797/Outsourcing-Meds.pdf.
113 T. Mullarkey, “Considerations in Pharmacy Compounding and the Treatment of Spasticity, Introduction,” American
Journal of Health-System Pharmacies, vol. 66 (Suppl5), s2-3; V. Yancey et al., “Perceptions of Pharmaceutical Care
Among Pharmacists Offering Compounding Services,” Journal of the American Pharmaceutical Association, vol. 48,
pp. 508-514 (2008); R. Jones, “Custom Cures,” Wayne State Alumni Magazine, spring 2010, pp. 10-11,
http://mydigimag.rrd.com/publication/index.php?i=37104&m=&l=&14&pre=&ver=swf&p=10; and Professional
Compounding Centers of America, “Compounding and Pharmacists,” http://www.pccarx.com/pharmacists/.
114 Statement and response to questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health,
Education, Labor and Pensions, “Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013.
115 See FDA website “2013 Pharmacy Inspections,”
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicR
eadingRoom/ucm340853.htm.
116 K. Kindy, L.H. Sun, and A. 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; C. Lomax,
“IV Outsourcing: Doing More with Less,” White Paper, Pharmacy Purchasing and Products,
http://www.pppmag.com/white_papers/.
117 A central fill pharmacy is defined as a pharmacy which is permitted by the state in which it is located to prepare
prescriptions on behalf of a retail pharmacy (pursuant to a valid prescription) to be distributed by the retail pharmacy to
the patient if the two pharmacies have a contractual agreement. See for instance, 21 CFR 1300.01 “Definitions.”
118 “Outsourcing pharmacy” refers to the transmitting of a prescription order from a primary pharmacy to a secondary
“outsourcing” pharmacy that prepares the prescription. See for instance: Maryland Office of the Secretary of State,
http://www.dsd.state.md.us/comar/SubtitleSearch.aspx?search=10.34.04.
119 See New Jersey 13:39-4.18(a) et seq. Procedures for Centralized Prescription Handling,
http://www.njconsumeraffairs.gov/adoption/pharmado_100509.htm.
120 FDA, “Medprep Consulting Inc. Announces Voluntary Nationwide Recall of All Lots of All Compounded Products
Due To Potential Mold Contamination,” March 17, 2013, http://www.fda.gov/Safety/Recalls/ucm344787.htm.
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Hospital Compounding and Outsourcing
Hospitals commonly compound drugs, IV solutions, and IV nutrition. For example, children’s
hospitals compound a variety of products such as pediatric dosages or products that are not
commercially available.121 One source reports that increases in use of drugs dosed by weight,122
rather than in commercially available dosing, and the expansion of treatment of disorders that
require personalized dosing have led to a growth of hospital-based compounding.123
Trends in health care include increasing hospital consolidation and integration of hospitals,124
leading to consolidated purchasing and centralized production, including the production of
CDs.125 For example, the Cleveland Clinic Health System, a network of 10 hospitals and 15
pharmacies, reported that in 2012, approximately 870,000 doses were compounded at its central
facility.126 Cleveland Clinic reported that 56% of its products were compounded for the needs of
specific patients;127 44% were made in anticipation of patient needs in a large hospital, such as the
preparation of syringes used in the operating room, epidurals, narcotic infusions, doses not
commercially available, and medications that were unavailable due to drug shortages.128 Smaller
facilities in rural areas may increase the outsourcing of CDs due to need for specialty intravenous
products without the facilities to produce such products.129 Reductions in staff or insufficient staff
or facilities to continue compounding; streamlining workflow; and cost savings may also be
factors related to outsourcing by facilities.130
121 Telephone conversation between author and Joe Cabaleiro, Executive Director, Pharmacy Compounding
Accreditation Board, January 4, 2013. Recent amendments to the FFDCA require more extensive tests and labeling for
prescription drugs for children. For more information about prescription drugs for children see CRS Report RL33986,
FDA’s Authority to Ensure That Drugs Prescribed to Children Are Safe and Effective, by Susan Thaul, and CRS
Report R42680, The Food and Drug Administration Safety and Innovation Act (FDASIA, P.L. 112-144), coordinated by
Susan Thaul.
122 Such drugs include epidurals for pain management during childbirth or chronic pain conditions, and chemotherapy.
123 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington DC, p. 5.
124 Ibid., p. 4; K. Douglass and E.S. Kastango, “Consolidation of Pharmacy Compounding Services: An Alternative to
Outsourcing,” International Journal of Pharmaceutical Compounding, vol. 5, no. 2 (March/April 2001), pp. 140-144,
http://www.clinicaliq.com/content/consolidation.pdf.
125 Ibid. See also Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital
Association, “Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington,
DC.
126 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington, DC, p. 4.
127 Products for an individual patient include: anti-infectives, pain management therapies, chemotherapy drugs,
replacement fluids and electrolytes, and ophthalmic preparations. See Pharmacy Compounding Summit: Summary of a
Stakeholder Meeting, Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital
Association, February 6, 2013, Washington DC, p. 4.
128 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington, DC, p. 4.
129Ibid., p. 5, see text related to Prattville Baptist Hospital.
130 See, C. Lomax, “IV Outsourcing: Doing More with Less,” White Paper, Pharmacy Purchasing and Products,
http://www.pppmag.com/white_papers/; Pew Charitable Trust, American Society of Health-System Pharmacists, and
American Hospital Association, “Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6,
2013, Washington, DC, p. 5.
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As noted earlier, there is limited information on the numbers of outsourced compounded
products, as the records of compounding entities are not publicly reported. However, a 2013
report of the Office of the Inspector General (OIG) of the Department of Health and Human
Services (HHS) on outsourcing of sterile products by hospitals found that 25% used “high-risk”
sterile products, those made from nonsterile ingredients, while 92% of hospitals used
compounded sterile products that were not “high-risk”.131 The reasons hospitals provided for
outsourcing sterile compounded products include drug shortages and their lack of capacity to
produce products that remained stable over time and thus had a long shelf-life. Stability and
extended shelf-life permit hospitals to store products for use as patient needs emerge. Shortages
were cited as a reason for outsourcing by 62% of hospitals, as were stability (69%) and extended
shelf-life (62%).132
The Role of Drug Shortages in CD Demand
Shortages of Generic Injectable Drugs
Shortages of commercially available drugs, especially shortages of generic sterile products, play a
central role in the increased demand for CDs.133 The drug shortages may be temporary or
permanent and are due to a variety of factors including voluntary discontinuation of products,
supply chain problems, and production issues, including safety problems at commercial
manufacturers.134 Certain compounders advertise their ability to fill certain back-ordered drugs or
those in short supply on their websites.135 Shortages of commercially manufactured drugs are
predicted to continue, leading to continued demand for certain compounded products.136
131 Office of the Inspector General, Memorandum Report: High-Risk Compounded Sterile Preparations and
Outsourcing by Hospitals that Use Them, Department of Health and Human Services, OEI-01-13-00150, Washington,
DC, April 1, 2013, p. 4.
132 Ibid., p. 6.
133 E.S. Kastango, 2013; and C.Y. Johnson, "Compounding Pharmacies Fill Important Medical Niche," Boston Globe,
November 3, 2012, http://www.bostonglobe.com/metro/2012/11/02/compounding-pharmacies-filled-niche-for-major-
hospitals/47MsPtBMEkT67TQmfNXF8O/story.html; K. Fiore, “Drug Shortages Spark Use of Compounders,”
(October 18, 2012), http://www.medpagetoday.com/MeetingCoverage/ASA/35406; and T. Meyer, “Overseeing
Outsourced Compounding During Shortages,” Pharmacy Purchasing and Products, June 2012,
http://www.pppmag.com/article/1141/June_2012/Overseeing_Outsourced_Compounding_during_Shortages/#.T9k83K
BsIlQ.blogger; K. Thomas, “Lapses at Big Drug Factories Add to Shortages and Danger,” New York Times, October
17, 2012, http://www.nytimes.com/2012/10/18/business/drug-makers-stalled-in-a-cycle-of-quality-lapses-and-
shortages.html?pagewanted=all.
134 K. Thomas, “Lapses at Big Drug Factories Add to Shortages and Danger,” New York Times, October 17, 2012,
http://www.nytimes.com/2012/10/18/business/drug-makers-stalled-in-a-cycle-of-quality-lapses-and-
shortages.html?pagewanted=all.
135 See Wedgewood Pharmacy, “Drug Shortages and Alerts,” http://www.wedgewoodrx.com/healthcare-
professionals/current-drug-shortages-and-alerts.html, and http://www.wedgewoodpharmacy.com/news/press-
room/wedgewood-pharmacy-compounds-gentamicin-as-sulfate-40mg-ml-injection-solution-during-manufacturer-
.html, accessed April 1, 2013; Preckshot Professional Pharmacy
http://www.preckshotpharmacy.com/rss2html.php?XMLFILE=http://www.pharmdjd.com/u/rss/meds_s.xml&TEMPL
ATE=unavailable_medications.html,accessed April 5, 2013; Universal Arts Pharmacy http://www.uaprx.com/,
accessed April 5, 2013.
136 J. Lee, “Investors Buying Compounders,” ModernHealthcare.com, January 19, 2013,
http://www.modernhealthcare.com/article/20130119/MAGAZINE/301199973; K. Fiore, “Drug Shortages Spark Use of
Compounders,” October 18, 2012, http://www.medpagetoday.com/MeetingCoverage/ASA/35406; and T. Meyer,
“Overseeing Outsourced Compounding During Shortages,” Pharmacy Purchasing and Products, June 2012,
(continued...)
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Physicians, hospitals, and other health care providers may turn to compounders to meet a time-
sensitive need when specific drugs may be temporarily unavailable.137 A 2013 report by the
Office of the Inspector General (OIG) of the Department of Health and Human Services (HHS)
surveyed hospitals participating in Medicare and found that many hospitals turn to compounding
pharmacies to provide drugs to maintain supply due to shortages of commercially manufactured
FDA-approved drugs. According to the OIG report, 68% of hospitals indicated that they sought a
CD due to a drug shortage.138
The FDA and other safety advocates are concerned because reportedly 73% of drug shortages are
for sterile injectable generic drugs, which are some of the most difficult drugs to compound
safely.139 Several generic commercial manufacturers have struggled with manufacturing problems
that have led to interruptions in supply of sterile generic drugs.140 For example, as of May 15,
2013, a major generic manufacturer in this business sector, Hospira, has recalled eight different
sterile injectable drugs for 2012 and 2013.141 An alternative to sterile injectable CDs and generics
are brand-name sterile injectables. These are less likely to be in short supply or suffer from
quality problems;142 however, brand-name sterile drugs usually cost more than generic or
compounded products.143
Shortages of CDs
Recalls of products from compounding pharmacies may also exacerbate drug shortages.144
Ameridose and NECC ended production of certain sterile drugs in 2012-2013 due to problems
(...continued)
http://www.pppmag.com/article/1141/June_2012/Overseeing_Outsourced_Compounding_during_Shortages/#.T9k83K
BsIlQ.blogger. Sections 1001-1008 of the Food Drug Safety and Administration Act (P.L. 112-144) included
provisions to ease shortages, see FDA website
http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendm
entstotheFDCAct/FDASIA/ucm313121.htm.
137 K. Thomas, “Drug Shortages Persist in U.S., Harming Care,” New York Times, November 16, 2012,
http://www.nytimes.com/2012/11/17/business/drug-shortages-are-becoming-persistent-in-
us.html?pagewanted=all&_r=0&pagewanted=print; K. Fiore, “Drug Shortages Spark Use of Compounders,” October
18, 2012, http://www.medpagetoday.com/MeetingCoverage/ASA/35406; and T. Meyer, “Overseeing Outsourced
Compounding during Shortages,” Pharmacy Purchasing and Products, June 2012,
http://www.pppmag.com/article/1141/June_2012/Overseeing_Outsourced_Compounding_during_Shortages/#.T9k83K
BsIlQ.blogger.
138 Office of the Inspector General, Memorandum Report: High-Risk Compounded Sterile Preparations and
Outsourcing by Hospitals that Use Them, Department of Health and Human Services, OEI-01-13-00150, Washington,
DC, April 1, 2013.
139 See 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.
140 See FDA Recalls: K. Thomas, “Lapses at Big Drug Factories Add to Shortages and Danger,” New York Times,
October 17, 2012, http://www.nytimes.com/2012/10/18/business/drug-makers-stalled-in-a-cycle-of-quality-lapses-and-
shortages.html?pagewanted=all.
141 See FDA Recalls: http://www.fda.gov/Drugs/DrugSafety/DrugRecalls/.
142 J. Woodcock and M. Wosinska, “Economic and Technological Drivers of Generic Sterile Injectable Drug
Shortages,” Clinical Pharmacology and Therapeutics,” vol. 93, no. 2, (February 2013), pp.170-176.
143 Ibid.
144 E. Palmer, "Compounder Recall May Make Drug Shortages More Severe," FiercePharmaManufacturing, October
31, 2012, http://www.fiercepharmamanufacturing.com/story/compounder-recall-may-make-drug-shortages-more-
severe/2012-10-31.
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with sterility, and these drugs were already in short supply.145 In 2013, compounders recalled
certain products produced at these facilities;146 some of these products were drugs listed on the
FDA shortages website. For example, drugs recalled by Med Prep in March 2013 include drugs
on the FDA Current Drug Shortage Index.147
CD shortages heighten problems of patient access to commercially manufactured generic drugs
when there are shortages. Table 1 details the perceptions of hospitals about the effect of
disruptions in supply of sterile products from compounding pharmacies. Almost 50% of
respondents perceived that health care delivery would be seriously impacted, while only 11.5%
perceived that the effect on patient health would be life-threatening.
Table 1. Hospital Beliefs About The Effect of Shortages of Compounded Sterile
Products on Patient Care and Health Care Delivery
Perceived Level of Risk to Patients/Disruption of Care
Percentage of Hospitals
Life Threatening/Major Disruptions
11.5
Not Life Threatening/Great Impact
48.1
Little Impact/Inconvenience
16.6
No Impact at Al
23.8
Source: Adapted by CRS from Office of Inspector General, Department of Health and Human Services,
Memorandum Report; “High Risk Compounded Sterile Preparations and Outsourcing by Hospitals that Use
Them” OEI-01-13-00150, p. 14.
Other Sources of Demand for Compounded Products
A growth of interest in customized products, including allergen-free drugs, single administration
of multiple drugs, and individualized formulations of drugs (such as liquids instead of tablets)
may play a role in heightened demand for CDs.148 The sources of this demand include physician
and patient demand as well as changing pharmacist business models. There appears to be an
increase in marketing of CDs for treatment of common disorders, such as menopausal symptoms
(e.g., “bio-identical” hormones), men’s health, and weight loss, which may lead to an increase in
demand for these CDs.149 150
145 K. Thomas, “Lapses at Big Drug Factories Add to Shortages and Danger,” New York Times, October 17, 2012,
http://www.nytimes.com/2012/10/18/business/drug-makers-stalled-in-a-cycle-of-quality-lapses-and-
shortages.html?pagewanted=all.
146 See FDA Drug Recalls, http://www.fda.gov/Drugs/DrugSafety/DrugRecalls/.
147 Compare FDA, “Drug Shortage Index,” March 11, 2013,
http://www.fda.gov/drugs/drugsafety/drugshortages/ucm050792.htm, with list of drugs recalled by Med Prep, March
17, 2013, http://www.fda.gov/Safety/Recalls/ucm344229.htm.
148 E. Palmer, "Compounder Recall May Make Drug Shortages More Severe," FiercePharmaManufacturing, October
31, 2012, http://www.fiercepharmamanufacturing.com/story/compounder-recall-may-make-drug-shortages-more-
severe/2012-10-31; Y. Johnson, "Compounding Pharmacies Fill Important Medical Niche," Boston Globe, November
3, 2012, http://www.bostonglobe.com/metro/2012/11/02/compounding-pharmacies-filled-niche-for-major-
hospitals/47MsPtBMEkT67TQmfNXF8O/story.html.
149 K. Cubert, “Compounding Pharmacies in the US: Doctor’s orders: Drug Shortages and Demand from the Aging
Population Will Benefit Stores,” IBIS World Industry Report OD5706, May 2012, pp. 10-11; see also, FDA “How
(continued...)
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Pharmacist Business Development
Compounding may provide pharmacists alternatives to expand business growth. Pharmacy
publications have emphasized how compounding pharmacists improve their own professional
satisfaction through providing more individualized services and increased engagement with
patients.151 This reflects an evolution to business models that expand pharmacist roles in areas of
patient care beyond distributing commercially manufactured products.152
A 2012 article in Business Week describes drug compounding as a growing business sector, and
describes how focusing on compounding can provide a new market niche for community
pharmacies.153 Some of these pharmacies may be exploring new business models due to increased
competition with chain pharmacies and retailers to fill prescriptions for commercially
manufactured drugs. This account appears consistent with material on certain compounding
pharmacies’ websites that describes business development from community pharmacies into a
market niche in compounded products (both prescription drugs and dietary supplements).154
Provider Demand
Demand may be generated in part by off-label prescribing by physicians for a variety of reasons,
including drug prices and shortages. As Table A-1 indicates, some of the incidents of
contamination and adverse events are for CDs prescribed for off-label uses. Off-label prescribing
allows physicians flexibility to prescribe medications they feel are necessary for patient health.155
Off-label use of a CD may present additional, but unknown risks. For example, two common off-
label uses of sterile CD are a compounded version of a chemotherapy drug, Avastin, for use to
treat macular degeneration, and preservative-free methylprednisolone for back pain.156 There have
(...continued)
Widespread is the Marketing of Compounded “BHRT” drugs?”;
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm183088.htm; and
a compounding pharmacy site, Precision Compounding Pharmacy:
http://www.precisioncompoundingpharmacy.com/?q=bhrt.
150 The FDA has issued warnings about the evidence of the usefulness or uniqueness of CDs for these indications.
FDA, see “Bio-Identicals: Sorting Myths from Facts,”
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm049311.htm.
151 V. Yancey et al., “Perceptions of Pharmaceutical Care Among Pharmacists Offering Compounding Services,”
Journal of the American Pharmacists Association, vol. 48, no. 4 (Jul/Aug 2008), pp. 508-514; and R. Jones, “Custom
Cures,” Wayne State Alumni Magazine, spring 2010, pp. 10-11,
http://mydigimag.rrd.com/publication/index.php?i=37104&m=&l=&14&pre=&ver=swf&p=10.
152 See for instance. Chain Drug Review, “2012 Retail Forecast: Chain Drug Eyes Broader Role,”
http://www.chaindrugreview.com/inside-this-issue/news/01-02-2012/2012-retail-forecast-chain-drug-eyes-broader-
role; Council on Credentialing in Pharmacy, “Scope of Contemporary Pharmacy Practice: Roles, Responsibilities, and
Functions of Pharmacists and Pharmacy Technicians, Journal of the American Pharmacy Association, vol. 50, no. 2
(March-April, 2010), e35-e69.
153 P.M. Barrett, “America’s shadow pharmacies,” Business Week, http://www.businessweek.com/articles/2012-11-
14/americas-shadow-pharmacies.
154 For instance, see Kelley Ross https://www.krrph.com/about-us/history.aspx, accessed March 31, 2013.
155 Ibid., and R. Dresser & J. Frader, “Off-label prescribing: A Call for Heightened Professional and Governmental
Oversight,” Journal of Law and Medical Ethics, vol. 37, no. 3, pp. 476-486.
156 R. Lowes, “Compounding Pharmacy Crackdown Continues with Avastin Recall,”
http://www.medscape.com/viewarticle/781039 accessed May 20, 2013; J. B. Staal et al., "Injection therapy for subacute
and chronic low back pain: An updated Cochrane Review," Spine, vol. 34, no. 1 (January 2009), pp. 49-59. Evidence
(continued...)
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been recent adverse events with compounded Avastin, the main appeal of which is its lower price
compared to FDA-approved drugs to treat macular degeneration (see Table A-1, 2011).157
Preservative-free methylprednisolone is used to treat back pain (see Table A-1, years 2012, 2002,
2001). Compounded versions of this drug by NECC were the cause of the 2012 fungal meningitis
outbreak.158
The processes for creating sterile CDs require special equipment, facilities, and personnel
training.159 When compounding exclusively with sterile ingredients, sterility must be maintained
in all phases of production; when compounding with nonsterile ingredients, sterility must be
achieved for the finished product requiring a sterilization process or related procedure that does
not affect product stability. Regulators and industry agree that the highest risk to patient safety is
from those sterile products made from nonsterile ingredients.160
Issues for Consideration
Consumers, pharmacists, pharmacy compounders, hospitals, Congress, and state and federal
regulators all have a stake in access to, and safety of, needed drugs. Increasing demand for CDs
by patients and providers, drug shortages, consolidation of hospital services, and other factors
have led to changes in health delivery. The potential risks to public health of product failures have
increased as nontraditional compounding has expanded.161 Given the expansion of sterile
compounding, balancing patient access to CDs with patient safety has become more complex.162
Thus, some stakeholders believe that changes in business trends, such as drug shortages and
outsourcing of compounding, must be taken into consideration in considering changes in
professional standards and federal and state oversight and regulation of CD.163
(...continued)
differs on whether these off-label treatments are effective.
157 Ibid.
158 See CDC, Multistate Fungal Meningitis Outbreak Investigation - Current Situation,
http://www.cdc.gov/HAI/outbreaks/currentsituation/.
159 See T. Mullarkey, “Pharmacy Compounding of High-Risk Products and Patient Safety,” American Journal of
Health-System Pharmacists, vol. 66 (Suppl5), (September 1, 2009), p. s5; see USP-NF, “General Chapter <797>
Pharmaceutical Compounding – Sterile Preparations,” http://www.usp.org/store/products-services/usp-compounding.
160 Office of the Inspector General, Memorandum Report: High-Risk Compounded Sterile Preparations and
Outsourcing by Hospitals that Use Them, Department of Health and Human Services, OEI-01-13-00150, Washington,
DC, April 1, 2013; “FDA Concept Paper: Drug Products That Present Demonstrable Difficulties for Compounding
Because of Reasons of Safety and Effectiveness,” updated 04/20/2009,
http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendm
entstotheFDCAct/FDAMA/ucm100205.htm; 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, pp. 10; and see USP-NF, “General Chapter <797> Pharmaceutical Compounding – Sterile Preparations,”
http://www.usp.org/store/products-services/usp-compounding.
161 Statement and response to questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health,
Education, Labor and Pensions, “Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013,
http://www.help.senate.gov/hearings/hearing/?id=f9b68c5e-5056-a032-52b6-4e632afd726a.
162 For more information, see hearing of the Senate Committee on Health, Education, Labor and Pensions,
“Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013,
http://www.help.senate.gov/hearings/hearing/?id=f9b68c5e-5056-a032-52b6-4e632afd726a.
163 See statements and response to questions of Panel 2 at “Pharmaceutical Compounding: Proposed Legislative
Solution,” a hearing of the Senate Committee on Health, Education, Labor and Pensions, May 9, 2013,
(continued...)
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Three issues have emerged in the congressional hearings about CDs: (1) adverse event reporting,
(2) labeling, and (3) modifying federal oversight of nontraditional compounding. These issues
will be discussed in the following section.
Adverse Event Reporting and Labeling
There is a lack of publically available information on the number and types of adverse events
involving compounded drugs, as there is no requirement that compounders report adverse events
to federal authorities,164 and state requirements vary.165 Adverse event reporting is not required by
federal regulators for producers of CDs as it is for prescription drugs, nonprescription drugs, and
dietary supplements.166 Without knowing the total number of compounded products made, as well
as the total number of adverse events, it is difficult to ascertain the overall safety of CDs or to
understand the benefits and risks of using CDs.
The publicly available information on CDs is published by public health authorities, FDA
inspections of facilities listed on websites, records of state licensing boards, and reports in
professional journals documenting adverse events. Adverse events can be voluntarily reported to
the FDA MedWatch database, but without mandatory reporting, the completeness of the
information cannot be ascertained.167
Labeling specifying that a drug or another product is compounded is not a universal
requirement.168 Due to the complexity of the supply chain and the growth of nontraditional
compounding, patients and providers may not realize that a drug has been compounded. Unlike
traditional compounding where a patient is given a prescription by a physician for a CD,
nontraditional CDs are not necessarily identified as compounded.169 Given the potential benefits
(...continued)
http://www.help.senate.gov/hearings/hearing/?id=f9b68c5e-5056-a032-52b6-4e632afd726a.
164 Adverse events are reported to poison control centers, FDA, CDC, or state public health authorities. Adverse event
reporting is required for commercially manufactured drugs (21 U.S.C. §355-1), nonprescription drugs (21 U.S.C.
§379aa), and dietary supplements (21 U.S.C. §379aa-1); for more information see, CRS Report R41983, How FDA
Approves Drugs and Regulates Their Safety and Effectiveness, by Susan Thaul and CRS Report R43062, Regulation of
Dietary Supplements, by Amalia K. Corby-Edwards. Also see Guidance for Industry
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM299138.pdf; FDA
Adverse Event Reporting System
http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/surveillance/adversedrugeffects/default.htm.
165 A few, but not all, states require some form of reporting of adverse incidents from CDs, see National Council of
State Legislators, “State Regulation of Compounding Pharmacies,” http://www.ncsl.org/issues-
research/health/regulating-compounding-pharmacies.aspx; see for instance, Massachusetts
http://www.mass.gov/eohhs/docs/dph/quality/boards/necc/121101-pharmacy-board-draft-emergency-regs.pdf, and
Texas http://law.onecle.com/texas/occupations/562.153.00.html.
166 Statement and response to questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health,
Education, Labor and Pensions, “Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013.
167 See http://www.fda.gov/Safety/MedWatch/default.htm.
168 Statement and response to questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health,
Education, Labor and Pensions, “Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013. H.R.
6584 and H.R. 6638 introduced in the 112th Congress and draft legislation by the Senate Committee on Health,
Education, Labor, and Pensions circulated in the 113th Congress include provisions that provide for patient information
on whether a drug is compounded in labeling.
169 Statement and response to questions, Janet Woodcock, FDA at a hearing of the Senate Committee on Health,
Education, Labor and Pensions, “Pharmaceutical Compounding: Proposed Legislative Solution,” May 9, 2013.
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and risks of CDs, an argument could be made for providing patients this information as part of
informed consent for medical treatment.170 Informed consent for treatment is an ethical and a
legal requirement to ensure that a patient fully understands the potential risks and benefits of a
medical procedure.171 CDs and other compounded solutions pose potential risks and benefits that
may be different from commercially manufactured products. Informed consent is based on a
patient’s knowledge and understanding of a medical procedure; as most patients assume that
drugs are commercially manufactured, this additional information could be seen as necessary to
ensure patient consent.172
The Federal Role in Oversight
Policymakers have raised questions regarding how best to improve the safety of CDs while
maintaining patient access to needed medications, including the need for new legislation and
increased accountability.173 In testimony to Congress, FDA administrators have expressed
reservations about nontraditional compounding activities that are akin to manufacturing (i.e.,
nontraditional compounding) and their potential risks to public safety.174 The FDA recommends
increased federal oversight of sterile compounding and certain other high-risk activities.175
Attempts to clarify federal authority over nontraditional compounding is represented in certain
elements of draft bipartisan legislation of the Senate Committee on Health, Education, Labor and
Pensions (HELP)176 and in legislation introduced in the 112th Congress.177 For example, a
170 See for instance “Pharmacy Compounding: Facts and Information,” specifically “When Are Compounded Drugs
Necessary,” and “Disclosure” http://www.ppsinc.org/phcom/03risk.htm; and M. R. Cohen, “New legislation would
help users identify source of a compounded drug,” Philly.com, http://www.philly.com/philly/blogs/healthcare/New-
legislation-would-help-users-identify-source-of-a-compounded-drug.html#D0rsmdaRGFqMCMWT.99.
171 T. L. Beauchamp and J. F. Childress, Principles of Biomedical Ethics, 9th ed. (New York: Oxford University,
2009).
172 See for instance “Pharmacy Compounding: Facts and Information,” specifically “When Are Compounded Drugs
Necessary,” and “Disclosure” http://www.ppsinc.org/phcom/03risk.htm; and M. R. Cohen, “New Legislation Would
Help Users Identify Source of a Compounded Drug,” Philly.com, http://www.philly.com/philly/blogs/healthcare/New-
legislation-would-help-users-identify-source-of-a-compounded-drug.html#D0rsmdaRGFqMCMWT.99.
173 See transcripts of: “A Continuing Investigation into the Fungal Meningitis Outbreak and Whether It Could Have
Been Prevented?”, hearing of the Subcommittee on Oversight and Investigations, Committee on Energy and
Commerce, U.S. House of Representatives, April 26, 2013; “Pharmacy Compounding: Implications of the 2012
Meningitis Outbreak,” hearing of the Committee of Health, Education, Labor, and Pensions, U.S. Senate, November
15, 2012; “The Fungal Meningitis Outbreak: Could It Have Been Prevented?” hearing of the Subcommittee on
Oversight and Investigations, Committee on Energy and Commerce, U.S. House of Representatives, November 14,
2012; “Examining State and Federal Oversight to Ensure the Safety and Quality of Drug Compounding.” hearing of the
Senate Committee on Health, Education, Labor, and Pensions, 108th Congress, 1st Session, October 22, 2003.
174 For instance, see Testimony of Margaret Hamburg, Commissioner of Food and Drugs, before the Committee of
Health, Education, Labor, and Pensions, U.S. Senate, November 15, 2012,
http://www.fda.gov/NewsEvents/Testimony/ucm327667.htm; Statement of Margaret Hamburg before the
Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, U.S. House of Representatives,
November 14, 2012, http://www.fda.gov/NewsEvents/Testimony/ucm327664.htm; and, Steven Galson, FDA, at a
hearing of the Senate Committee on Health, Education, Labor, and Pensions, 108th Congress, 1st Session, October 22,
2003, “Examining State and Federal Oversight to Ensure the Safety and Quality of Drug Compounding.”
175 Ibid.
176See Draft legislation posted at: http://www.help.senate.gov/newsroom/press/release/?id=0aa068ee-4f2a-4e31-9fd6-
39f4d7472a5a&groups=Ranking,Chair.
177 See H.R. 6584 introduced by Representative Markey and H.R. 6638 introduced by Representative DeLauro.
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provision in the draft HELP legislation would create new authorities for FDA oversight of
“compounding manufacturers” (i.e., nontraditional compounders).178
Some Members of Congress argue that new FDA authorities should await better implementation
of existing authorities.179 For example, a House Committee on Energy and Commerce report
questions whether a lack of enforcement by FDA and state authorities of certain vendors is an
issue.180 The report cites safety violations at NECC in prior years, which do not appear to have
been resolved despite FDA involvement.181
Some in the compounding pharmacy industry believe that the current safety issues are isolated to
certain vendors and that compounding, in general, is not unsafe.182 Some compounding
associations have reservations about the FDA having new authorities; others support increased
FDA oversight.183 Many acknowledge that compounded health care products have become more
complex and health delivery more complicated. In a recent report, the Association of Health-
System Pharmacists (AHSP) and American Hospital Association (AHA) noted that there was
general support from stakeholders in these associations for (1) FDA oversight of certain
nontraditional compounding pharmacies (e.g., providing a CD without a prescription and shipped
over state lines); (2) improved communication between state and federal regulators; (3) a list of
“do-not-compound” CDs; and (4) improved access to USP compounding monographs that
provide guidance to compounders on making certain CDs.184
178 See Senate HELP draft legislation 2013, http://www.help.senate.gov/imo/media/KER13169.pdf.
179 U.S. Congress, House Committee on Energy and Commerce, Subcommittee on Oversight and Investigations,
Majority Memorandum RE: Hearing on "The Fungal Meningitis Outbreak: Could It Have Been Prevented?",
November 12, 2012, and “A Continuing Investigation into the Fungal Meningitis Outbreak and Whether It Could Have
Been Prevented?”, hearing of the Subcommittee on Oversight and Investigations, Committee on Energy and
Commerce, U.S. House of Representatives, April 26, 2013.
180 U.S. Congress, House Committee on Energy and Commerce, Subcommittee on Oversight and Investigations,
Majority Memorandum RE: Hearing on "The Fungal Meningitis Outbreak: Could It Have Been Prevented?", prepared
by Subcommittee on Oversight and Investigations Staff, 112th Cong., 2nd sess., November 12, 2012, pp. 25,
http://energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/Hearings/OI/20121114/HMTG-
112-HHRG-IF02-20121114-SD001.pdf.
181 Ibid., pp. 6-23.
182 Testimony from David Miller, International Academy of Compounding Pharmacists, Committee on Health,
Education, Labor, and Pensions, “Pharmacy Compounding Implications of the 2012 Meningitis Outbreak,” November
15, 2012, http://www.help.senate.gov/imo/media/doc/Miller8.pdf.
183 See Panel II statements and response to questions, “Pharmaceutical Compounding: Proposed Legislative Solution,”
a hearing of the Committee on Health, Education, Labor, and Pensions, May 9, 2013; Press Release, PharMedium,
March 26, 2013, http://www.lawofcompoundingmedications.com/2013/03/pharmedium-supports-new-fda-
category.html, accessed May 3, 2013.
184 Pew Charitable Trust, American Society of Health-System Pharmacists, and American Hospital Association,
“Pharmacy Compounding Summit: Summary of a Stakeholder Meeting,” February 6, 2013, Washington DC, p. 14.
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Compounded Drugs
Appendix A. Congressional Hearings on CDs 2012-
2013
•
“Examining Drug Compounding,” hearing of the Subcommittee on Health of the Committee on Energy and
Commerce, U.S. House of Representatives, May 23, 2013.
•
Executive Session, S. 959 Pharmaceutical Compounding Quality and Accountability Act, hearing of the
Committee of Health, Education, Labor, and Pensions, U.S. Senate, May 22, 2013. Reported out of Committee, S.
959 as amended.185
•
“Pharmaceutical Compounding: Proposed Legislative Solution,” hearing of the Committee of Health, Education,
Labor, and Pensions, U.S. Senate, May 9, 2013.
•
“A Continuing Investigation into the Fungal Meningitis Outbreak and Whether It Could Have Been Prevented?”,
hearing of the Subcommittee on Oversight and Investigations, Committee on Energy and Commerce, U.S. House
of Representatives, April 26, 2013.
•
“Pharmacy Compounding: Implications of the 2012 Meningitis Outbreak,” hearing of the Committee of Health,
Education, Labor, and Pensions, U.S. Senate, November 15, 2012.
•
“The Fungal Meningitis Outbreak: Could It Have Been Prevented?”, hearing of the Subcommittee on Oversight
and Investigations, Committee on Energy and Commerce, U.S. House of Representatives, November 14, 2012.
Source: House Committee on Energy and Commerce: http://energycommerce.house.gov/hearings; Senate Committee on
Health, Education, Labor and Pensions: http://www.help.senate.gov/hearings/.
185 For latest version of bill text, see
http://www.help.senate.gov/imo/media/052213_S._959_Compounding_KER13207.pdf.
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Appendix B. Selected Adverse Events Involving Compounded Drugs and
Solutions
Table A-1. -Adverse Events
2001-present
Condition/
# States Reported Reported
Disease
Other
Date Affected
Cases
Deaths
Adverse Events
Drug Issue
Treated
Product
Characteristics
2012
20
741
55
Fungal meningitis and other infectionsa
Fungal contamination
Lumbar and
Preservative-free
Off-label use,
other back
methylprednisolone
shipped across
pain
injections
state lines, drug
shortage
2012 -
6
33
NA
Fungal eye infection, 23 cases of partial Fungal contamination
Eye surgery
Eye injections,
Shipped across
2011
to severe vision lossb
Brilliant B retinal dye
state lines
and triamcinolone
2011
2
21
NA
Bacterial eye infection, one case of
Bacterial contamination
Macular
Eye injections:
Off-label use,
meningitis and encephalitis; four cases
degeneratio
Intravitreal use of
shipped across
of loss of eyesight, three cases eye
n
bevacizumab (Avastin) state lines
removalc
injections
2011 1
5
NA
Blindnessd
Lack of purity—presence Macular
Eye injections:
Off-label use
of another medication
degeneratio
intravitreal use of
n
bevacizumab (Avastin)
injections
2011
1
19
9
Bacterial bloodstream infectione
Bacterial contamination
Nutrition
Parenteral nutrition
Drug Shortage
solution
2010 1
1
1
Fatal
overdosef
Super-potent dosage
IV solution
Sodium chloride
- -
2007 2
3
3
Fatal
overdoseg
Super-potent dosage
Back pain
Colchicine
Off-label use
2007
2
8
NA
Bacterial bloodstream infectionh
Bacterial contamination
Pain control IV-solution, fentanyl
Shipped across
state lines
CRS-25
Condition/
# States Reported Reported
Disease
Other
Date Affected
Cases
Deaths
Adverse Events
Drug Issue
Treated Product Characteristics
2007 1
1
1
Drug
toxicityi
Drug Stability/Age
Chronic
Antibiotic administered
Off-label use
airway
by nebulizer
infection
2006-
6
80
NA
Bacterial bloodstream infectionj
Bacterial contamination
IV flush,
IV solution
Shipped across
2004
reduction
heparin/saline
state lines
of blood
clots
2006 1
1
1
Fatal overdosek Super-potent
dosage
Cancer
Chemotherapy
- -
(pediatric)
infusion
2006 1
1
1
Fatal overdosel
Super-potent dosage
Nutrition
Parenteral nutrition
- -
(pediatric)
2005
Unavailable 2
NA
Bacterial bloodstream infectionm
Bacterial contamination
IV flush
Preservative-free
- -
heparinized saline
2005
1
5
3
Systemic inflammatory response
Contamination Cardiac
Health infusion,
Shipped across
syndromen
conditions
cardioplegia
state lines
2005
2
6
NA
Bacterial eye infection, partial or
Bacterial contamination
Assessment
Trypan blue—eye
Shipped across
complete loss of vision, 2 eye
of eye
stain
state lines
removalso
conditions
2005
5
18
NA
Bacterial bloodstream infectionp Bacterial
contamination
IV solution
Magnesium sulfate
Shipped across
state lines
2004
1
2
NA
Bacterial bloodstream infection
Bacterial contamination
IV flush
Heparin/vancomycin,
Shipped across
(pediatric)q
syringes
hemophilia
state lines
2004
5
64
NA
Bacterial bloodstream infectionr
Bacterial contamination
IV flush
Heparin/saline Shipped
across
syringes
state lines
2004
1
16
NA
Hepatitis C infections Contaminated
with
Diagnosis of
Radio-isotope use in
- -
Hepatitis C virus
cardiac
cardiac stress tests
conditions
2002 1
5
1
Fungal
meningitist
Fungal contamination
Back pain
Preservative-free
Off-label use,
methylprednisolone
drug shortage
acetate injections
CRS-26
Condition/
# States Reported Reported
Disease
Other
Date Affected
Cases
Deaths
Adverse Events
Drug Issue
Treated Product Characteristics
2001
1
11
3
Bacterial meningitis, epidural abscess,
Fungal contamination
Back pain,
Preservative-free
Off-label use,
injected joints and spineu
joint pain
betamethasone
drug shortage
injection
2001 1
4
NA
Bacterial meningitis, other infectionsv Bacterial
contamination Gastric
IV Ranitidine
- -
(pediatric)
reflux
Source: This list has two sources (1) a CRS literature search of medical and scientific databases such as Medline and PubMed with search terms included “drug
compounding,” and “adverse effects,” “quality control,” “risk assessment,” “drug contamination,” “disease outbreaks,” “complications,” “administration and dosage,”
“fatal outcome,” and “medication errors.” These selected adverse events resulted in reported patient illness and/or death. This is list is not comprehensive as not all
adverse effects of compounded medications may be reported to federal and state authorities or result in published articles; (2) Pew Charitable Trust compilation of
adverse events associated with compounded medications (2001-present), Appendix B of Summary of Stakeholder Meeting, Pharmacy Sterile Compounding Summit.
Available at http://www.ashp.org/compounding%20summit, accessed April 18, 2012. The CRS and Pew Trust lists overlap except for two adverse events that are included
only in this report; these two events are italicized.
Notes: “NA” means not applicable. “Unknown” means not included in source document. Off-label use of a prescription drug or device refers to the ability of licensed
health care providers to prescribe or use the drug for indications, conditions, patients, dosages or routes of administration not yet evaluated and approved by the FDA as
part of a new drug approval application. Drug Shortage designation is based on either a specific discussion of those issues in the article or a third-party source, such as
the FDA, the American Health-System Pharmacists or professional article. Specific sources for the reports of adverse events are listed below:
a. CDC, “Multistate fungal meningitis outbreak investigation,” http://www.cdc.gov/HAI/outbreaks/meningitis.html and see
http://www.fda.gov/Drugs/DrugSafety/ucm270296.htm. See footnote 36 for discussion of drug shortage.
b. S. Huang, et al., “Notes from the field: Multistate outbreak of post procedural fungal endophthalmitis associated with a single compounding pharmacy,” Morbidity and
Mortality Weekly Report (MMWR), vol. 61, no. 17 (March-April 2012), pp. 310-311. See also, FDA
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm296383.htm.
c. R. A. Goldberg et al., “An Outbreak of Streptococcus Endophthalmitis After Intravitreal Injection of Bevacizumab,” American Journal of Ophthalmology, (February,
2012), pp. 204-208; A. B. Frost and M. A. Kainer, “Safe Preparation and Administration of Intravitreal Bevacizumab Injections,” New England Journal of Medicine, vol.
365, no. 23 (December 2011), 2238.
d. Department of Veterans Affairs, Office of Inspector General, “Healthcare Inspection Oversight Review of Ophthalmology, Adverse Drug Events, VA Greater Los
Angeles Healthcare System, Los Angeles, California.” Report No. 12-01515-151, (April 12, 2012), http://www.va.gov/oig/pubs/VAOIG-12-01515-151.pdf.
e. FDA: Safety: Meds IV Pharmacy, IV Compounded Products Recall; and N. Gupta et al., “Investigation of an outbreak of Serratia marcescens Bloodstream infections in
patients receiving total parenteral nutrition – Alabama, 2011”, Authors affiliated with CDC and Alabama Dept. of Health, Paper presented at conference IDSA,
October, 2011, https://idsa.confex.com/idsa/2011/webprogram/Paper31248.html; and C. A. Thompson, “Bacteremia outbreak tied to improper filtration by
compounding pharmacy,” American Journal of Health System Pharmacy, vol. 68, no. 22, (2011), pp. 2110-11, http://www.ashp.org/menu/News/PharmacyNews/.
f.
B. Vitello, “Lutheran General to pay $8.25 million in baby’s death,” Daily Herald, April 5, 2012. http://www.dailyherald.com/article/20120405/news/704059806/.
CRS-27
g. N. J. McKeown et al., “Deaths from intravenous colchicine resulting from a compounding pharmacy error – Oregon and Washington,” Morbidity and Mortality Weekly
Report, vol. 56, no. 40, (October 12, 2007), pp. 1050-1052, http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5640a3.htm.
h. L.A. Maragakis et al., “Sphingomonas paucimobilis Bloodstream infections associated with contaminated intravenous fentanyl,” Emerging Infectious Disease, vol. 15, no. 1
(2009), pp. 12-18, and FDA, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/UCM338614.pdf.
i.
M. S. McCoy, “Compounded Colistimethate as Possible Cause of Fatal Acute Respiratory Distress Syndrome” New England Journal of Medicine, vol. 357, no. 22
(November 29, 2007), pp. 2310-2311.
j.
L.A. Maragakis et al., “Sphingomonas paucimobilis Bloodstream infections associated with contaminated intravenous fentanyl,” Emerging Infectious Disease, vol. 15, no. 1
(2009), pp. 12-18, and FDA, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/UCM338614.pdf.
k. Institute for Safe Medication Practices. Medication Safety Alert. “Failed check system for chemotherapy leads to pharmacist’s no contest plea for involuntary
manslaughter,” April 23, 2009. http://www.ismp.org/newsletters/acutecare/articles/20090423.asp. Accessed January 9, 2013.
l.
M. Grissinger, “A Fatal Zinc Overdose in a Neonate. Confusion of Micrograms with Milligrams,” Pharmacy and Therapeutics, vol. 36, no. 7, (July 2011), pp. 393-394,
409.
m. J. F. Perz et al. “Pseudomonas putida Septicemia in a Special Care Nursery Due to Contaminated Flush Solutions Prepared in a Hospital Pharmacy,” Journal of Clinical
Microbiology, vol. 43, no. 10, (October 2005), pp. 5316-5318.
n. Maryland State Board of Pharmacy. “Order for Summary Suspension.” In the matter of Central Admixture Pharmacy Services, Inc.
http://www.dhmh.maryland.gov/pharmacy/docs/FormalOrders/C/C.A.P.S%2011-15-05.pdf.
o. R. Sunenshine et al., “An Outbreak of Postoperative Gram-Negative Bacterial Endophthalmitis Associated with Contaminated Trypan Blue Ophthalmic Solution,”
Clinical Infectious Diseases, vol. 48, no. 11, (April 2009), pp. 1580-1583.
p. R. H. Sunenshine et al., “A Multi-state Outbreak of Serratia marcescens Bloodstream Infection Associated with Contaminated Intravenous Magnesium Sulfate from a
Compounding Pharmacy.” Clinical Infectious Disease, vol. 45, (2007), pp. 527-533.
q. M. R. Held et al., “Life-threatening sepsis caused by Burkholderia cepacia from contaminated intravenous flush solutions prepared by a compounding pharmacy in
another state,” Pediatrics, vol. 118, no. 1(July 1, 2006), pp. e212 -e215.
r. U.S. Centers for Disease Control and Prevention, “Pseudomonas Bloodstream Infections Associated with a Heparin/Saline Flush—Missouri, New York, Texas, and
Michigan, 2004–2005,” Morbidity and Mortality Weekly Report, vol. 54, no. 11 (March 2005), pp. 269-272; and U.S. Centers for Disease Control and Prevention,
“Update: Delayed Onset Pseudomonas fluorescens Bloodstream Infections After Exposure to Contaminated Heparin Flush—Michigan and South Dakota, 2005–
2006,” Morbidity and Mortality Weekly Report, vol. 55, no. 35 (September 2006), pp. 961-963.
s. Patel, P.R. et al., “Hepatitis C Virus Infections From a Contaminated Radiopharmaceutical Used in Myocardial Perfusion Studies,” Journal of the American Medical
Association, (October 6, 2006), vol. 296, pp. 2005-2011.
t.
CDC, “Exophilia Infection from Contaminated Injectable Steroids Prepared by a Compounding Pharmacy –United States,” July-November 2002. MMWR, 51(49)
(December 13, 2002), pp.1109-1112.
u. R. Civen et al., “Outbreak of Serratia marcescens infections following injection of betamethasone compounded at a community pharmacy,” Clinical Infectious Disease,
vol. 43, no. 7 (August 22, 2006), pp. 831-837.
CRS-28
v. D. Selenic et al., “Enterobacter cloacae bloodstream infections in pediatric patients traced to a hospital pharmacy,” American Journal of Health System Pharmacies,
vol.14, no. 60 (July 14, 2003), pp.1440-1446.
CRS-29
Compounded Drugs
Author Contact Information
Judith M. Glassgold
Specialist in Health Policy
jglassgold@crs.loc.gov, 7-9455
Acknowledgments
The author acknowledges the assistance of Amalia Corby-Edwards, Analyst in Public Health and
Epidemiology, DSP; Ada Cornell, Information Research Specialist, DSP; Janet Kinzer, Information
Research Specialist, DSP; Andrew Nolan, Legislative Attorney, ALD; Michaela Platzer, Specialist in
Industrial Organization and Business, RSI; Amanda Sarata, Specialist in Health Policy, DSP; and Susan
Thaul, Specialist in Drug Safety and Effectiveness, DSP in the writing of this report.
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