By Rachel A. Hardy, MA, RAC

On 27 Nov 2013, the Food and Drug Administration gained new tools to regulate drug compounding when President Barack Obama signed the Drug Quality and Security Act (DQSA). In this legislation, Congress addressed longstanding questions of the FDA’s jurisdiction over compounding pharmacies, which are licensed by the states (US House of Representatives 2013a).

Tragic events prompted Congress to act. An outbreak of fungal meningitis in late 2012, which took a toll of more than 60 deaths and at least 750 sickened in 20 states, was traced back to an injected steroid produced by the New England Compounding Center (NECC), a compounding pharmacy that was licensed by the Massachusetts Board of Registration in Pharmacy (US CDC 2013).

Now we can scrutinize the guidance documents that FDA issued since late 2013 and ask: How does FDA plan to address the type of safety issues that led to the NECC tragedy? More specifically, will all facilities that produce sterile injectable drugs to be shipped across state lines be held to the standard of current Good Manufacturing Practice (cGMP)? I searched the following documents for evidence of FDA’s current thinking: two draft guidances—Registration for Human Drug Compounding Outsourcing Facilities, and Current Good Manufacturing Practice: Interim guidance for Human Drug Compounding Outsourcing Facilities, and a final guidance—Pharmacy Compounding of Human Drug Products (FDA 2013, 2014a, 2014b). The comment period for the cGMP guidance is open until 2 Sept 2014.

Facilities that engage in drug compounding can choose to register with the FDA—or not, according to the DQSA law (US House of Representatives 2013a). Registration is voluntary, so compounders that register—called compounding outsourcing facilities—would be held to the cGMP standard, while non-registered compounders—called pharmacies—would not be. According to the FDA draft guidance: “Outsourcing facilities will be inspected by FDA and must comply with other provisions of the FD&C Act, such as current good manufacturing practice (cGMP) requirements” (FDA 2013).

Compounding outsourcing facilities are defined in the new law: “a facility at one geographic location or address that … is engaged in the compounding of sterile drugs; has elected to register as an outsourcing facility; and complies with all of the requirements of this section” (US House of Representatives 2013a).

CGMP is defined in the FDA regulations:

“methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packing, or holding of a drug [ensures] … that such drug meets the requirements of the act as to safety, and has the identity and strength and meets the quality and purity characteristics that it purports or is represented to possess. …. The failure to comply …. shall render such drug to be adulterated” (21 CFR 210.1).

The 2012 fungal meningitis outbreak was traced to a failure of cGMP involving supposedly sterile drugs. When the FDA had sealed vials of methylprednisolone acetate from NECC tested after the outbreak, it found a fungal contaminant. This made the drug “adulterated” by definition (21 CFR 210.1). Moreover, the FDA inspection report concluded that the drug was adulterated because NECC failed to follow cGMP. For instance, the NECC found bacteria and mold when sampling its own “clean rooms” (FDA 2012; Hardy 2013).

The July 2014 draft guidance on cGMP for outsourcing facilities focused “on those aspects of 21 CFR part 211 that relate to sterility assurance of sterile drug products and the safety of compounded drug products more generally” (FDA 2014a). Among the topics it outlined were control systems and procedures for preventing contamination, environmental monitoring in aseptic processing areas, and controls over the drug components. Each of these aspects was inadequately controlled at NECC, which lead to the fungal meningitis outbreak (FDA 2012; Hardy 2013).

Whether facilities choose to register with FDA, I argue, has implications for the quality and safety of the United States’ drug supply. Applying cGMP principles helps to ensure the quality and safety of drugs and medical devices. Those that register with FDA—compounding outsourcing facilities—are held to the cGMP standard (FDA 2013). Those that do not register—pharmacies—will continue to be regulated by the states and are mostlyexempt from cGMP (FDA 2014b). In Massachusetts, a 2014 law grants new powers to its state pharmacy board, including to require licenses for producing sterile drugs (Oldfield 2014). However, each state has its own standards and inspection schemes, some thorough, some grossly inadequate (US House of Representatives 2013b). It is hard to conclude anything about the effect of increased regulation of compounders with FDA, so long as registration is voluntary.


Rachel A. Hardy, MA, RAC, is a data management technician in oncology at Duke University and a member of NCRAF. She has six years of experience applying cGCP, including in clinical operations, in a clinic, and in medical writing. She can be reached at [email protected]


US House of Representatives. HR 3204. Drug Quality and Security Act. An act to amend the Federal Food, Drug, and Cosmetic Act with respect to human drug compounding and drug supply chain security, and for other purposes. Title I: Drug Compounding. Signed into law 27 Nov 2013.  Accessed 18 Jul 2014.


Multistate Fungal Meningitis Outbreak Investigation. US Centers for Disease Control and Prevention website. Updated 23 Oct 2013.  Accessed 18 July 2014.


US Food and Drug Administration. Draft Guidance for Industry:  Registration for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act. December 2013. Accessed 18 July 2014.


US Food and Drug Administration. Draft Guidance for Industry: Current Good Manufacturing Practice: Interim guidance for Human Drug Compounding Outsourcing Facilities. July 2014. Accessed 18 July 2014.


US Food and Drug Administration. Guidance for Industry: Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act. July 2014. Accessed 18 July 2014.

US Food and Drug Administration. Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs, General. 21 CFR §210.1. Revised 1 April 2012. Accessed 18 July 2014.


US Food and Drug Administration. Inspectional Observations Form FDA 483. To Barry J. Cadden, owner, New England Compounding Pharmacy, Inc. Dated 2 Oct. 2012. Redacted revised 26 October 2012. Accessed 18 July 2014.


Hardy R. “Public safety concerns support FDA call for compounding pharmacy regulation.” September 2013. Regulatory Focus. Regulatory Affairs Professionals Society.  Accessed 18 July 2014


Oldfield E. Massachusetts Institutes Stricter Compounding Law. Posted 14 July 2014. Pharmacy Times. From


US House of Representatives. State of Disarray: How States’ Inability to Oversee Compounding Pharmacies Put Public Health At Risk. Published 15 April 2013. Accessed 10 July 2014.


Copyright 2014 by Rachel A. Hardy