FDA Commissioner Margaret A. Hamburg, MD, today told a congressional panel investigating the deadly fungal meningitis outbreak tied to the New England Compounding Center (NECC), in Framingham, Mass., that current law “is not well suited” to regulate large compounding pharmacies.

“Sterile products produced in advance of or without a prescription and shipped interstate should be subject to the highest levels of controls, established by FDA and appropriate to the activity, similar to cGMP [current Good Manufacturing Practices] standards applicable to conventional drug manufacturing,” Dr. Hamburg told the House Energy and Commerce Subcommittee on Oversight and Investigations.

“We have been hampered in our ability to protect the American people because of ambiguities regarding FDA’s enforcement authority, legal challenges and adverse court decisions” surrounding what she termed nontraditional compounders—companies that produce large quantities of sterile products “in advance of or without receiving a prescription, where the drug is distributed out of [the] state in which it was produced.”

The House hearing was the latest in a series of congressional inquiries following last year’s deadly outbreak of meningitis associated with contaminated compounded methylprednisolone acetate produced by NECC. To date, more than 50 people have died and about 730 have been stricken in 20 states.

Energy and Commerce Committee Chairman Rep. Fred Upton (R-MI) questioned whether the FDA had done its job effectively. “What did the FDA know about NECC and Ameridose [a company tied to NECC] and what did FDA do about it?” Mr. Upton asked, in reference to numerous warnings that the agency had received about NECC and the lack of follow-up to its own inspections and warning letters. “It sickens me that this could have been prevented.”

“Ten years of warning signs, alarm bells and flashing red lights were deliberately ignored,” added subcommittee chairman Rep. Tim Murphy (R-PA).
Dr. Hamburg testified that the FDA’s oversight authority of compounding pharmacies has been “hampered by gaps and ambiguities in the law” created by conflicting court decisions. For example, although provisions of the Food and Drug Administration Modernization Act of 1997 exempts compounded drugs from many aspects of FDA oversight, various courts have issued conflicting rulings about the matter.

“As a result, FDA has limited knowledge of pharmacy compounders and compounding practices and limited ability to oversee their activities. I wish we had been more aggressive, and I can assure you that we are being more aggressive now,” she said.

Rep. Henry Waxman (D-CA), the committee’s ranking minority member, noted that although the FDA had missed important opportunities to act in regard to NECC, “it’s Congress’ job to fix the law; we must do more than blame the agency.”

Increased Investigations
From February to April 2013, the FDA sent inspectors to 31 compounding facilities in 18 states. There they uncovered dozens of unsafe practices, including unidentified black particles floating in vials of supposedly sterile medicine; rust and mold in clean rooms where sterile injectable medications were produced; technicians handling supposedly sterile products with their bare hands; and a lack of appropriate air filtration systems. The FDA has posted copies of Form 483 for each facility documenting unsafe conditions it uncovered.

In her written testimony, Dr. Hamburg proposed legislation based on a “risk-based framework” that would differentiate between “traditional compounding” in which medication is prepared for a specific patient from a prescription or order from a licensed practitioner and “nontraditional compounding” in which products are prepared in advance of or without receiving a prescription and distributed out of state. Traditional compounding activities would continue to be overseen by state pharmacy boards, she said, whereas nontraditional compounding would come under “clear and appropriate federal standards and oversight,” including the ability to collect and test samples and examine records. “We look forward to working with Congress in striking the right balance,” Dr. Hamburg said.

This proposed framework is an outgrowth of the so-called “three-prong test” that the FDA has been privately discussing with lawmakers based on whether the product is sterile, is shipped interstate and compounded before a prescription is received, according to the International Academy of Compounding Pharmacists (IACP), a trade association. In a March 20, 2013 letter to senators, the IACP called the establishment of a new regulatory category “premature” and warned that the three-prong test could infringe on state oversight of compounding pharmacies. “Since FDA is already empowered by Congress to govern the manufacture of drugs, FDA has the existing authority to apply drug manufacturing regulations as they see fit within the law,” the IACP wrote.

Not every large compounding company agrees with the IACP. In a March 26 statement, PharMEDium Services LLC, a large outsource producer of customized sterile compounds for hospital IV and epidural therapies, said that “support the passage of federal legislation to establish a new FDA category for sterile compounders governed by applicable current Good Manufacturing Practices.”

In an April 15 statement posted on its website, PharMEDium reiterated its faith in FDA taking on a stronger—and better defined—role in the oversight of compounding. “The production of compounded sterile preparations in anticipation of a prescription is a difficult practice for states to oversee, especially when these preparations are shipped across state lines,” the company noted. “Accordingly, PharMEDium believes Congress must move swiftly to clarify FDA’s legal authority over the compounding pharmacy industry, distinguish it from the appropriate role of state boards of pharmacy, strengthen governing standards, and facilitate effective inspections and enforcement.”

PharMEDium's position on the regulation of compounding is particularly relevant, given the fact that FDA inspectors observed various problems at the company’s compounding facilities during inspections this year. In February 2013, PharMEDium said it was “committed to maintaining the highest levels of quality and safety in sterile preparations,” and that it has been “fully responsive” to all FDA concerns (see Pharmacy Practice NewsMarch 2013).

Other groups, including the American Society of Health-System Pharmacists (ASHP), also support strengthening the FDA’s oversight of large-scale compounding pharmacies that produce large amounts of products and then sell them to entities other than the end user. In a Jan. 18, 2013 letter to the FDA, Christopher J. Topoleski, ASHP’s federal regulatory affairs director, said the society “believes that compounding service providers that operate at the scale and scope of manufacturers should be required to register with the FDA, share details about their operations with the Agency, and submit to routine inspections.”

Such oversight is not needed for hospital-based compounding services, Mr. Topoleski added, because those facilities prepare medications for patients within a hospital or hospital system, which also are accredited and have significant internal safeguards formularies, infection control and risk management committees.

On Feb. 6, 2013, ASHP, the Pew Charitable Trusts and the American Hospital Association convened a Pharmacy Compounding Summit, which brought together stakeholders from health-system organizations, government, compounding companies and others. Consensus recommendations included the need to clarify the roles of federal and state authorities over sterile compounding practices; strengthen federal oversight of compounding activities not currently overseen by states that represent higher risk due to product volume, category of product, whether product is patient-specific and breadth of distribution; better define and standardize licensing categories for patient care sites, companies and others involved in compounding; and explore creation of new standards that combine US Pharmacopeia Chapter <797> and current cGMPs to facilitate oversight of large-scale compounding facilities.