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Compounding Pharmacy ConundrumCompounding Pharmacy Conundrum: “We Cannot Live Without Them but We Cannot Live With Them” According to the Present Paradigm FREE TO VIEW

Roy Guharoy, PharmD, MBA, FCCP; John Noviasky, PharmD, BCPS; Ziad Haydar, MD, MBA; Mohamad G. Fakih, MD, MPH; Christian Hartman, PharmD, MBA
Author and Funding Information

From Ascension Health (Drs Guharoy and Haydar), St. Louis, MO; the University of Massachusetts Medical School (Drs Guharoy and Hartman), Worcester, MA; the SUNY-Upstate Medical University Hospital at Community General (Dr Noviasky), Syracuse, NY; the Department of Infection Prevention and Control (Dr Fakih), St. John Hospital and Medical Center, Detroit, MI; the Wayne State University School of Medicine (Dr Fakih), Detroit, MI; and Wolters Kluwer Health (Dr Hartman), Minneapolis, MN.

Correspondence to: Roy Guharoy, PharmD, MBA, FCCP, Ascension Health, 11775 Borman Dr, Ste 340, St. Louis, MO 63146; e-mail: Roy.Guharoy1@umassmed.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(4):896-900. doi:10.1378/chest.13-0212
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Compounding pharmacies serve a critical role in modern health care to meet special patient care needs. Although the US Food and Drug Administration (FDA) has clearly delineated jurisdiction over drug companies and products manufactured under Good Manufacturing Practice (GMP) regulations to ensure quality, potency, and purity, compounding pharmacies are regulated by the State Boards and are not registered by the FDA. In recent years, some compounding pharmacies acted like a manufacturer, preparing large amounts of injectable drugs with interstate activities. Multiple outbreaks have been linked to compounding pharmacies, including a recent outbreak of fungal meningitis related to contaminated methylprednisolone, exposing > 14,000 patients in multiple states. This tragedy underscores the urgency of addressing safety related to compounding pharmacies. There is a call for action at the federal and state levels to set minimum production standards, impose new labeling conditions on compounded drugs, and require large-scale compounders be regulated by the FDA. “Industrial” compounding must come under FDA oversight, require those pharmacies to meet GMP standards, and ensure quality and safe products for patient use. Moreover, compliance with the Institute for Safe Medication Practices 2011 recommendations that any type of sterile compounding must be in compliance with the United States Pharmacopoeia chapter 797 guidelines will reduce the risk of patient harm from microbial contamination. Finally, other critical factors that require close attention include addressing injectable products compounded in hospitals and other outpatient health-care centers. The FDA and State Boards of Pharmacy must be adequately funded to exercise the oversight effectively.

Compounding pharmacies serve a critical role in modern health care and they meet special patient care needs. Pharmacists compounded 80% of prescriptions through the 1950s.1 They prepared tablets, powders, capsules, suppositories, pills, cachets, ointments, pastes, lotions, liniments, tinctures, and wet dressings.1 However, the paradigm changed in the 1960s with the commercial availability of many products, and pharmacy practice gradually transitioned to dispensing of US Food and Drug Administration (FDA)-approved commercial products. The practice of compounding re-emerged in the 1980s and has evolved over the years because of drug shortages, discontinuation of many commercially available products, outsourcing of IV products by hospital pharmacies, and clinician demand for “custom-made” compounded products. Today, pharmacies compound flavored products, dye-free products, products without specific allergens, chemotherapeutic agents, noncommercial formulations, and other customized products. At present, 7,500 pharmacies specialize in compounding in the United States.2 According to the International Association for Compounding Pharmacists, 1% to 3% of all prescriptions are compounded by these pharmacies.3

Compounding pharmacies are currently in the spotlight after an epidemic of meningitis was linked to contaminated epidural methylprednisolone injections produced by one company in Massachusetts.4,5 As of January 14, 2013, the Centers for Disease Control and Prevention (CDC) reported 678 patients developed serious infections related to the outbreak, including 375 cases of meningitis, and 44 patients have died.6 The mold Exserohilum rostratum was implicated in the majority of the cases. Although the outbreak affected 19 states, Michigan accounted for more than one-third of the cases. This tragedy has exposed our vulnerability and has created an opportunity for a thorough examination of the contributing factors that led to practices resulting in patient harm.

Although the FDA has clearly delineated jurisdiction over drug companies, and products are manufactured under Good Manufacturing Practice (GMP) regulations to ensure quality, potency, and purity, compounding pharmacies are regulated by the state boards and are not registered by the FDA.7,8 In the past, pharmacies compounded products based on individual prescriptions to serve individual patients with special needs. As evident in the current tragedy, wherein 14,000 patients were exposed to potentially contaminated methylprednisolone with about 5% of them developing serious infections, some compounding pharmacies are acting like a manufacturer, preparing large amounts of injectable drugs with interstate activities. However, no state regulation requires them to obtain a special license or follow GMP regulations as required by the FDA for drug manufacturers. Instead of FDA governance, the compounding pharmacies are expected to follow “good compounding practices,” a set of standards developed by the United States Pharmacopoeia, a private group that sets standards for drugs in the United States. They are not required to keep records and report quality-related problems, as mandated by the FDA for the drug manufacturers. The FDA can only take action once a problem is identified, which may be too late, as identified in the meningitis epidemic.

State boards of pharmacy provide inconsistent oversight and lack resources and expertise to provide oversight of the compounding pharmacies.1,810 This is borne out by previous experience with contaminated products. In 2002, four patients developed meningitis after receiving epidural injections of preservative-free methylprednisolone acetate prepared by a compounding pharmacy that was contaminated with Exophiala dermatitidis.11 In 2004, a Missouri pharmacy failed to recall approximately 1.4 million doses of respiratory solution contaminated with Burkholderia cepacia distributed nationally.12 An analysis of 10 compounded progesterone suppositories from 10 randomly selected pharmacies found that nine pharmacies did not meet the limits set for approved products. Suppositories supplied by one pharmacy were contaminated with Comamonas acidoverans.13 Thirty-six samples of compounded drugs analyzed by the FDA in 2006 found one-third failed at least one quality test.14 In 2011, nine people died of Serratia marcescens bacteremia among 19 patients receiving contaminated total parenteral solutions at six Alabama hospitals prepared by a compounding pharmacy.15,16 The Institute for Safe Medication Practices in 2011 recommended that any type of sterile compounding must be undertaken with great care and in compliance with the United States Pharmacopoeia (USP) chapter 797 guidelines for compounding sterile products to prevent death and patient harm from microbial contamination.17 They also called upon all state boards of pharmacy to ensure enforcement of all aspects of USP 797 standards by the compounding pharmacies.

There have been attempts to provide more rigorous oversight of the compounding industry. In 1992, the FDA issued a compliance policy guide attempting to regulate large-scale compounding, resulting in a safe-harbor compounding statute being enacted in 1997. It prohibited advertising and promotion of compounded drugs, on the basis that dispensing occurs in response to a prescription for an individual patient. In response, seven compounding pharmacies pursued legal action and were able to prevent implementation 2 days prior to start date. The Supreme Court overturned the law partly in a five to four decision in 2002 based on protection of commercial free speech, leaving the statute in limbo.18 As a result, the FDA developed a less prescriptive guidance that did not mention interstate-shipment provisions or advertising. Key provisions included possible enforcement action against compounding products prior to the receipt of a valid prescription, commercially available, or removed from market for a safety reason.19 However, the provisions were mostly ignored by the specific compounding pharmacy involved in the recent meningitis tragedy.

In response to the past and most recent problems, there is a call for action on the federal as well as state level. Two bills were recently introduced in the Congress to amend section 503A of the Federal Food, Drug, and Cosmetic Act that would require more oversight on the federal level. One bill, HR 6638, called the Supporting Access to Formulated and Effective Compounded Drug Act, would establish a database on the pharmacies for use by the FDA and states.20 It requires the FDA to set minimum production standards, impose new labeling conditions on compounded drugs, and train state regulators. The second bill, HR 6584, called the Verifying Authority and Legality in Drug Compounding Act, would preserve traditional small compounding pharmacy practice and require large-scale compounders be regulated by the FDA.21 The bill clearly delineates the FDA’s authority to oversee compounding pharmacies while preserving state regulatory authority for traditional small compounding companies. In the aftermath of the meningitis tragedy caused by the compounding pharmacy in Massachusetts, Governor Deval Patrick has proposed new state legislation that will establish strict licensing requirements for compounding sterile drugs, let the state assess fines against pharmacies for violation of regulations, protect whistleblowers who work in the compounding pharmacies, and reorganize the pharmacy board to include more members who are independent of the pharmacy.22 The State Board of Pharmacy in Massachusetts has also approved emergency regulations to enhance oversight that allow the state to track volume and distribution to determine whether the pharmacy is acting more like a manufacturing facility and therefore is subject to FDA regulation.23 It is expected that other states will follow suit.

There are other critical factors that require close attention to protect our patients and close any gaps related to medication compounding. Injectable products are routinely compounded in surgery centers, clinics, operating rooms, nursing units at hospitals, nursing homes, and EDs nationwide. The individuals preparing the products may not follow aseptic techniques and may not be evaluated for competency to compound the products. For example, there were two recent outbreaks of Staphylococcus aureus infection at outpatient clinics involving hospitalization of 10 patients and one death, where single-dose preservative-free vials were used for multiple patients.24 The outbreaks underscore the need for a process to ensure competence and strict adherence to aseptic techniques when injectable drugs are used. In addition, custom-made injectable drugs are routinely used in surgery centers and clinics despite lack of scientific evidence of such therapy.8,25,26 Clinicians should be judicious in making clinical decisions.

The shortages of major critical care drugs in recent years have forced thousands of hospitals and clinics to rely upon compounding pharmacies to meet critical needs. The shortages have put our patients in danger of not receiving life-saving medications. The affected drugs are mostly generic injectable products, and the reasons for shortages are multifaceted27 and attributed to problems at supply chain, consolidation of manufacturers from several to few, production, quality, and scarcity of raw chemicals.28 Drug shortages have been identified for oncology, antimicrobials, analgesics, anesthetic agents, cardiovascular medications, vitamins, and others, affecting the practice of all providers.28,29 The list of commonly administered critical care medications have included, but not been limited to, amiodarone, atropine, digoxin, diazepam, diltiazem, epinephrine, furosemide, heparin, lidocaine, morphine, norepinephrine, and propofol.30 Cost burden resulting from use of expensive alternate drugs and additional labor costs are estimated at $415 million annually.31 In a survey of 3,063 anesthesiologists in 2012, 7% had to postpone and 4% had to cancel cases because of shortage of anesthetic.32 In a recent publication, event-free survival distributions among children with Hodgkin lymphoma in the chemotherapy regimen with cyclophosphamide (substituted for mechlorethamine) was 75%, compared with 88% in the mechlorethamine regimen group (used prior to shortage).33 The authors commented that “the drug shortage is an intolerable situation for young people with curable diseases.” The number of new drug shortages escalated from 88 in 2002 to 267 in 2011 and 204 in 2012 (Erin Fox, PharmD, Drug Information Resource Center, University of Utah, personal communication, January 4, 2013). As of January 4, 2012, the website of the American Society of Health System Pharmacists lists 228 ongoing shortages, for which there are no therapeutic alternates for several critical drugs.34 Despite the passage of the FDA safety and Innovation Act in 2012 requiring manufacturers to notify of impending shortages, it seems unlikely that the shortages will disappear soon, because other problems associated with shortages need to be addressed. The compounding pharmacies fill the void by repackaging products or preparing them from raw chemicals. The growing reliance on compounding pharmacies further highlights the urgent need for setting regulations for compounding standards and other requirements as required from the manufacturers.

Hospitals prepare the majority of IV compounding products in the United States. In a survey among 1,403 hospitals by the American Society of Hospital Pharmacists in 2011, 65% reported having a USP 797-compliant clean room. The results differed significantly by hospital size, with > 87.5% of the largest hospitals (≥ 600 beds) and 48.1% of hospitals with < 50 beds having a compliant room.35 The overall compliance rate was 65%. Considering the potential severe adverse impact on patient care, hospitals need to assess their compliance with USP 797 standards. Often, lack of space or adequate financing is cited as a barrier for such implementation. In addition, hospital pharmacies should have adequate resources to prepare the majority of the IV compounded products, if feasible.

It is clear that compounding pharmacies provide a service that is unique, and they are here to stay. However, finding ways that will ensure better and more consistent patient safety is the conundrum. With the public outcry in mind, it seems the current void of compounding pharmacies oversight will be resolved in the near future. However, the passage of law is not sufficient to achieve the goal of patient safety unless the FDA and state boards are adequately funded so that they can exercise the enforcement effectively. The recent outbreak in Massachusetts was caused by the mass production of a contaminated injectable. This tragedy highlights the urgent need for strengthening and clarifying the FDA’s oversight. And, most importantly, compounding pharmacies should be required to ensure compliance to sterility and quality control as outlined by the USP 797. “Industrial” compounding must come under FDA oversight, which will require those pharmacies to meet GMP standards and ensure quality and safe products for patient use. The state boards of pharmacy must safeguard compliance by the traditional compounding pharmacies. Massachusetts Congressman Markey, the sponsor of Congressional bill HR 6584, stated “the tragedy is clearly just the tip of an industry iceberg that has long needed reform and federal oversight and it demands the strongest response from Congress, federal and state authorities to ensure safeguards are in place to protect patients.”36 As witnessed, the coordinated efforts between the clinicians, patients, and regulatory agencies during the crisis were remarkable, and the partnership helped us to protect the lives of many patients. The same spirit needs to establish a streamlined process between federal and state regulators to prevent this tragedy from reoccurring in the future. We should take all the steps necessary to ensure that compounded drugs are sterile and uncontaminated. In addition, we need to close the gaps in supply chain and unsafe practices in hospitals and ambulatory care areas to deliver safer care to our patients.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The content of the manuscript is based on personal opinion of the authors and does not in any way represent the official view of the affiliated organization.

CDC

Centers for Disease Control and Prevention

FDA

US Food and Drug Administration

GMP

Good Manufacturing Practice

USP

United States Pharmacopoeia

Shaughnessy AF. Meningitis outbreak shines light on compounding pharmacies. BMJ. 2012;345:e7432. [CrossRef] [PubMed]
 
Silverman E. FDA and compounders: more oversight needed? Pharmalot. October 5, 2012.http://www.pharmalot.com/2012/10/fda-compounders-more-oversight-needed. Accessed January 1, 2013.
 
International Academy of Compounding Pharmacists responds to meningitis outbreak tied to compounding pharmacyInternational Academy of Compounding Pharmacists responds to meningitis outbreak tied to compounding pharmacy. International Academy of Compounding Pharmacist website.http://www.iacprx.org/associations/13421/files/IACP Responds to Meningitis Outbreak Release October 2012.pdf. Accessed January 1, 2013.
 
Pettit AC, Kropski JA, Castilho JL, et al. The index case for the fungal meningitis outbreak in the United States. N Engl J Med. 2012;367(22):2119-2125. [CrossRef] [PubMed]
 
Kainer MA, Reagan DR, Nguyen DB, et al;; Tennessee Fungal Meningitis Investigation Team Tennessee Fungal Meningitis Investigation Team. Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med. 2012;367(23):2194-2203. [CrossRef] [PubMed]
 
Multistate fungal meningitis outbreak-current case count. Centers for Disease Control and Prevention website.http://www.cdc.gov/hai/outbreaks/meningitis-map.html. Accessed January 17, 2013.
 
Outterson K. Regulating compounding pharmacies after NECC. N Engl J Med. 2012;367(21):1969-1972. [CrossRef] [PubMed]
 
Drazen JM, Curfman GD, Baden LR, Morrissey S. Compounding errors. N Engl J Med. 2012;367(25):2436-2437. [CrossRef] [PubMed]
 
Wilson LE, Blythe D, Sharfstein JM. Fungal meningitis from injection of contaminated steroids: a compounding problem. JAMA. 2012;308(23):2461-2462. [PubMed]
 
Alcorn T. Meningitis outbreak reveals gaps in US drug regulation. Lancet. 2012;380(9853):1543-1544. [CrossRef] [PubMed]
 
Centers for Disease Control and Prevention (CDC)Centers for Disease Control and Prevention (CDC). Exophiala infection from contaminated injectable steroids prepared by a compounding pharmacy—United States, July-November 2002. MMWR Morb Mortal Wkly Rep. 2002;51(49):1109-1112. [PubMed]
 
Missouri Department of Economic DevelopmentMissouri Department of Economic Development. Missouri Board of Pharmacy takes action against Kansas City Company. Missouri Division of Professional Registration website.http://www.pr.mo.gov/boards/pharmacy/press/2003-10-03.pdf. March 10, 2003. Accessed January 1, 2013.
 
Mahaguna V, McDermott JM, Zhang F, Ochoa F. Investigation of product quality between extemporaneously compounded progesterone vaginal suppositories and an approved progesterone vaginal gel. Drug Dev Ind Pharm. 2004;30(10):1069-1078. [CrossRef] [PubMed]
 
U.S. Department of Health and Human ServicesU.S. Department of Health and Human Services. 2006 limited FDA survey of compounded drug products. US Food and Drug Administration website.http://www.fda.gov/drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm204237.htm. March 22, 2010. Accessed January 1, 2013.
 
Food and Drug Administration (FDA) warning letter (no. 2012-NOL-15) to Advanced Specialty Pharmacy dba Meds IV. Inspections, compliance, enforcement, and criminal investigations. US Food and Drug Administration website.http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm296483.htm. March 16, 2012. Accessed January 1, 2013.
 
Update on DHPQ’s response support to recent outbreak investigations. Health Care Infection Control Practices Advisory Committee Meeting. June 2012, Atlanta. Division of Healthcare Quality Promotion (DHQP). National Center for Emerging and Zoonotic Infectious Diseases Control and Prevention. Centers for Disease Control website.http://www.cdc.gov/maso/facm/pdfs/HICPAC/2012061415_HICPAC_MINUTES.pdf. Accessed January 5, 2013.
 
Institute for Safe Medicine Practices (ISMP)Institute for Safe Medicine Practices (ISMP). TPN-related deaths call for FDA guidance and pharmacy board oversight of USP 797. ISMP Safety Alert (Acute care edition). April 7, 2011. Institute for Safe Medicine Practices website.http://www.ismp.org/NEWSLETTERS/ACUTECARE/articles/20110407.asp. Accessed January 1, 2013.
 
Outterson K. Higher First Amendment hurdles for public health regulation. N Engl J Med. 2011;365(7):e13. [CrossRef] [PubMed]
 
U.S. Food and Drug AdministrationU.S. Food and Drug Administration. Importation of active pharmaceutical ingredients requirements CPG 460.200 pharmacy compliance policy guides manual (table M). May 2002.http://www.fda.gov/downloads/AboutFDA/Centersoffices/CDER/ucm118050.pdf. Accessed January 1, 2013.
 
POCAG Act.http://www.govtrack.us/congress/bills/112/hr6638. Accessed January 5, 2013.
 
Goodnough A, Grady D. Massachusetts plans stricter control of compounding pharmacies.New York Times. January 4, 2013.http://www.nytimes.com/2013/01/05/us/massachusetts-plans-stricter-control-of-compounding-pharmacies.html. Accessed January 5, 2013.
 
National Association of Boards of PharmacyNational Association of Boards of Pharmacy. MA Board of pharmacy approves emergency regulations for compounding pharmacies. National Association of Boards of Pharmacy website.http://www.nabp.net/news/ma-board-of-pharmacy-approves-emergency-regulations-for-compounding-pharmacies. November 7, 2012. Accessed January 5, 2013.
 
Centers for Disease Control and Prevention (CDC)Centers for Disease Control and Prevention (CDC). Invasive Staphylococcus aureus infections associated with pain injections and reuse of single-dose vials—Arizona and Delaware, 2012. MMWR Morb Mortal Wkly Rep. 2012;61(27):501-504. [PubMed]
 
Cohen SP, White RL, Kurihara C, et al. Epidural steroids, etanercept, or saline in subacute sciatica: a multicenter, randomized trial. Ann Intern Med. 2012;156(8):551-559. [PubMed]
 
Staal JB, de Bie R, de Vet HC, Hildebrandt J, Nelemans P. Injection therapy for subacute and chronic low-back pain. Cochrane Database Syst Rev. 2008;3(3):CD001824. [PubMed]
 
U.S. Food and Drug AdministrationU.S. Food and Drug Administration. Prescription drug shortages: examining a public health concern and potential solutions. US Food and Drug Administration website.http://www.fda.gov/NewsEvents/Testimony/ucm282956.htm. December 15, 2011. Accessed January 5, 2013.
 
Chabner BA. Drug shortages—a critical challenge for the generic-drug market. N Engl J Med. 2011;365(23):2147-2149. [CrossRef] [PubMed]
 
Rochon PA, Gurwitz JH. Drug shortages and clinicians: no time for complacency. Arch Intern Med. 2012;172(19):1499-1500. [PubMed]
 
Alspach JG. Is the drug shortage affecting patient care in your critical care unit? Crit Care Nurse. 2012;32(1):8-13. [CrossRef]
 
Drug shortages in healthcare—a patient safety and cost of care issue. Premier Healthcare Alliance. Premier Inc. website.http://www.premierinc.com/safety/topics/drug_shortage/index.jsp. August 2011. Accessed January 1, 2013.
 
American Society of AnesthesiologistsAmerican Society of Anesthesiologists. 2012 ASA drug shortage survey results. American Society of Anesthesiologists website.http://www.asahq.org/For-Members/Advocacy/Washington-Alerts/2012-ASA-Drug-Shortage-Survey-results.aspx. April 17, 2012. Accessed January 4, 2013.
 
Metzger ML, Billett A, Link MP. The impact of drug shortages on children with cancer—the example of mechlorethamine. N Engl J Med. 2012;367(26):2461-2463. [CrossRef] [PubMed]
 
Drug shortages: current drugs. American Society of Health-System Pharmacists website.http://www.ashp.org/drugshortages/current. Accessed January 4, 2013.
 
Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: dispensing and administration—2011. Am J Health Syst Pharm. 2012;69(9):768-785. [CrossRef] [PubMed]
 
Schnirring L. Center for Infectious Disease Research and Policy, University of Minnesota. Report: deaths, illness linked to compounding pharmacies not new. Center for Infectious Disease Research and Policy website.http://www.cidrap.umn.edu/cidrap/content/other/news/oct2912fungal.html. October 29, 2012. Accessed January 1, 2013.
 

Figures

Tables

References

Shaughnessy AF. Meningitis outbreak shines light on compounding pharmacies. BMJ. 2012;345:e7432. [CrossRef] [PubMed]
 
Silverman E. FDA and compounders: more oversight needed? Pharmalot. October 5, 2012.http://www.pharmalot.com/2012/10/fda-compounders-more-oversight-needed. Accessed January 1, 2013.
 
International Academy of Compounding Pharmacists responds to meningitis outbreak tied to compounding pharmacyInternational Academy of Compounding Pharmacists responds to meningitis outbreak tied to compounding pharmacy. International Academy of Compounding Pharmacist website.http://www.iacprx.org/associations/13421/files/IACP Responds to Meningitis Outbreak Release October 2012.pdf. Accessed January 1, 2013.
 
Pettit AC, Kropski JA, Castilho JL, et al. The index case for the fungal meningitis outbreak in the United States. N Engl J Med. 2012;367(22):2119-2125. [CrossRef] [PubMed]
 
Kainer MA, Reagan DR, Nguyen DB, et al;; Tennessee Fungal Meningitis Investigation Team Tennessee Fungal Meningitis Investigation Team. Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med. 2012;367(23):2194-2203. [CrossRef] [PubMed]
 
Multistate fungal meningitis outbreak-current case count. Centers for Disease Control and Prevention website.http://www.cdc.gov/hai/outbreaks/meningitis-map.html. Accessed January 17, 2013.
 
Outterson K. Regulating compounding pharmacies after NECC. N Engl J Med. 2012;367(21):1969-1972. [CrossRef] [PubMed]
 
Drazen JM, Curfman GD, Baden LR, Morrissey S. Compounding errors. N Engl J Med. 2012;367(25):2436-2437. [CrossRef] [PubMed]
 
Wilson LE, Blythe D, Sharfstein JM. Fungal meningitis from injection of contaminated steroids: a compounding problem. JAMA. 2012;308(23):2461-2462. [PubMed]
 
Alcorn T. Meningitis outbreak reveals gaps in US drug regulation. Lancet. 2012;380(9853):1543-1544. [CrossRef] [PubMed]
 
Centers for Disease Control and Prevention (CDC)Centers for Disease Control and Prevention (CDC). Exophiala infection from contaminated injectable steroids prepared by a compounding pharmacy—United States, July-November 2002. MMWR Morb Mortal Wkly Rep. 2002;51(49):1109-1112. [PubMed]
 
Missouri Department of Economic DevelopmentMissouri Department of Economic Development. Missouri Board of Pharmacy takes action against Kansas City Company. Missouri Division of Professional Registration website.http://www.pr.mo.gov/boards/pharmacy/press/2003-10-03.pdf. March 10, 2003. Accessed January 1, 2013.
 
Mahaguna V, McDermott JM, Zhang F, Ochoa F. Investigation of product quality between extemporaneously compounded progesterone vaginal suppositories and an approved progesterone vaginal gel. Drug Dev Ind Pharm. 2004;30(10):1069-1078. [CrossRef] [PubMed]
 
U.S. Department of Health and Human ServicesU.S. Department of Health and Human Services. 2006 limited FDA survey of compounded drug products. US Food and Drug Administration website.http://www.fda.gov/drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm204237.htm. March 22, 2010. Accessed January 1, 2013.
 
Food and Drug Administration (FDA) warning letter (no. 2012-NOL-15) to Advanced Specialty Pharmacy dba Meds IV. Inspections, compliance, enforcement, and criminal investigations. US Food and Drug Administration website.http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm296483.htm. March 16, 2012. Accessed January 1, 2013.
 
Update on DHPQ’s response support to recent outbreak investigations. Health Care Infection Control Practices Advisory Committee Meeting. June 2012, Atlanta. Division of Healthcare Quality Promotion (DHQP). National Center for Emerging and Zoonotic Infectious Diseases Control and Prevention. Centers for Disease Control website.http://www.cdc.gov/maso/facm/pdfs/HICPAC/2012061415_HICPAC_MINUTES.pdf. Accessed January 5, 2013.
 
Institute for Safe Medicine Practices (ISMP)Institute for Safe Medicine Practices (ISMP). TPN-related deaths call for FDA guidance and pharmacy board oversight of USP 797. ISMP Safety Alert (Acute care edition). April 7, 2011. Institute for Safe Medicine Practices website.http://www.ismp.org/NEWSLETTERS/ACUTECARE/articles/20110407.asp. Accessed January 1, 2013.
 
Outterson K. Higher First Amendment hurdles for public health regulation. N Engl J Med. 2011;365(7):e13. [CrossRef] [PubMed]
 
U.S. Food and Drug AdministrationU.S. Food and Drug Administration. Importation of active pharmaceutical ingredients requirements CPG 460.200 pharmacy compliance policy guides manual (table M). May 2002.http://www.fda.gov/downloads/AboutFDA/Centersoffices/CDER/ucm118050.pdf. Accessed January 1, 2013.
 
POCAG Act.http://www.govtrack.us/congress/bills/112/hr6638. Accessed January 5, 2013.
 
Goodnough A, Grady D. Massachusetts plans stricter control of compounding pharmacies.New York Times. January 4, 2013.http://www.nytimes.com/2013/01/05/us/massachusetts-plans-stricter-control-of-compounding-pharmacies.html. Accessed January 5, 2013.
 
National Association of Boards of PharmacyNational Association of Boards of Pharmacy. MA Board of pharmacy approves emergency regulations for compounding pharmacies. National Association of Boards of Pharmacy website.http://www.nabp.net/news/ma-board-of-pharmacy-approves-emergency-regulations-for-compounding-pharmacies. November 7, 2012. Accessed January 5, 2013.
 
Centers for Disease Control and Prevention (CDC)Centers for Disease Control and Prevention (CDC). Invasive Staphylococcus aureus infections associated with pain injections and reuse of single-dose vials—Arizona and Delaware, 2012. MMWR Morb Mortal Wkly Rep. 2012;61(27):501-504. [PubMed]
 
Cohen SP, White RL, Kurihara C, et al. Epidural steroids, etanercept, or saline in subacute sciatica: a multicenter, randomized trial. Ann Intern Med. 2012;156(8):551-559. [PubMed]
 
Staal JB, de Bie R, de Vet HC, Hildebrandt J, Nelemans P. Injection therapy for subacute and chronic low-back pain. Cochrane Database Syst Rev. 2008;3(3):CD001824. [PubMed]
 
U.S. Food and Drug AdministrationU.S. Food and Drug Administration. Prescription drug shortages: examining a public health concern and potential solutions. US Food and Drug Administration website.http://www.fda.gov/NewsEvents/Testimony/ucm282956.htm. December 15, 2011. Accessed January 5, 2013.
 
Chabner BA. Drug shortages—a critical challenge for the generic-drug market. N Engl J Med. 2011;365(23):2147-2149. [CrossRef] [PubMed]
 
Rochon PA, Gurwitz JH. Drug shortages and clinicians: no time for complacency. Arch Intern Med. 2012;172(19):1499-1500. [PubMed]
 
Alspach JG. Is the drug shortage affecting patient care in your critical care unit? Crit Care Nurse. 2012;32(1):8-13. [CrossRef]
 
Drug shortages in healthcare—a patient safety and cost of care issue. Premier Healthcare Alliance. Premier Inc. website.http://www.premierinc.com/safety/topics/drug_shortage/index.jsp. August 2011. Accessed January 1, 2013.
 
American Society of AnesthesiologistsAmerican Society of Anesthesiologists. 2012 ASA drug shortage survey results. American Society of Anesthesiologists website.http://www.asahq.org/For-Members/Advocacy/Washington-Alerts/2012-ASA-Drug-Shortage-Survey-results.aspx. April 17, 2012. Accessed January 4, 2013.
 
Metzger ML, Billett A, Link MP. The impact of drug shortages on children with cancer—the example of mechlorethamine. N Engl J Med. 2012;367(26):2461-2463. [CrossRef] [PubMed]
 
Drug shortages: current drugs. American Society of Health-System Pharmacists website.http://www.ashp.org/drugshortages/current. Accessed January 4, 2013.
 
Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: dispensing and administration—2011. Am J Health Syst Pharm. 2012;69(9):768-785. [CrossRef] [PubMed]
 
Schnirring L. Center for Infectious Disease Research and Policy, University of Minnesota. Report: deaths, illness linked to compounding pharmacies not new. Center for Infectious Disease Research and Policy website.http://www.cidrap.umn.edu/cidrap/content/other/news/oct2912fungal.html. October 29, 2012. Accessed January 1, 2013.
 
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    Print ISSN: 0012-3692
    Online ISSN: 1931-3543