Arguing that the issue of the safety of compounded pharmaceutical products is now at a "critical point," US Food and Drug Administration (FDA) Commissioner Margaret Hamburg plans to tell legislators at a hearing today that her agency needs more resources and authority to better do its job, according to a copy of Hamburg's testimony.
Legislators with the House of Representative's Energy and Commerce Subcommittee on Oversight and Investigations have for several weeks been planning a follow-up hearing to a November 2012 hearing that investigated an outbreak of fungal meningitis that had at the time killed dozens and injured hundreds more.
The outbreak had been linked to methylprednisolone acetate (MPA) compounded at the New England Compounding Center (NECC)-a firm legislators noted had long been known to regulators for quality deficiencies. Subsequent inspections by FDA and Massachusetts officials found sordid conditions at the site, including rampant sterility problems. In several cases, mold was found to be located directly within the production hoods, while "white, filamentous substances" were found in autoclaves used to sterilize bulk drug products.
At the time of the November 2012 hearing, however, legislators expressed less concern with NECC, whose owners refused to testify before the committee, and instead focused their ire on Hamburg, arguing time and again that the agency had not acted forcefully enough to regulate the compounding industry.
Previous: Legislators, FDA Outline Cases in Advance of Major Hearing on Pharmaceutical Compounding
Hamburg: We're Doing all That We Can with What we Have
Since that hearing, FDA has-as it frequently touts-been quite busy, inspecting 31 pharmaceutical compounding facilities, of which 29 were found to be deficient. Hundreds of products related to those firms have since been recalled, including two recalls announced on the eve of the hearing affecting sterile products manufactured by two additional companies.
But, as Hamburg notes in her testimony, this issue is not a new one. Hamburg recounts several episodes involving deficient compounding pharmacies-contaminated steroid injections in California in 2001; contaminated cardioplegia solution in 2005; superpotent colchicine in 2007; bacterial infections from parenteral nutrition products in 2011; and contaminated sterile ophthalmic drug products in 2012.
"These incidents are emblematic of long-standing issues associated with the practice of compounding and the public health concerns that can result from unsafe practices in compounding pharmacies," Hamburg explained.
But if the problems are endemic, the agency's options to confront them are few, she argues. Legal challenges to FDA's authority, an evolving compounding industry, aggressive challenges to FDA inspectors, and a difficult and expensive inspection process have all drained agency resources and made it difficult for regulators to address problems.
Another problem: The industry has become so large in some cases that to shut down even a single compounder would mean shutting off the drug supply for dozens, perhaps hundreds, of hospitals around the country, potentially causing major disruptions in the form of drug shortages. "FDA should have more tailored authorities appropriate" for taking enforcement actions against pharmacies, Hamburg said. At present, its authority is largely predicated on the ability to label a product a "new drug," thereby requiring it to go through a lengthy and costly drug approval process before being allowed to be marketed.
Hamburg also reiterated that judicial decisions around the country have fragmented its authority, creating safe havens of sorts in which its ability to inspect is not necessarily recognized by the courts. "As a result, FDA has limited knowledge of pharmacy compounders and compounding practices and limited ability to oversee their activities," she said.
Hamburg conceded in her testimony, however, that FDA could have been "more aggressive in pursuing enforcement actions against compounding pharmacies within our current limited authority."
"I can assure you that we are being more aggressive now," she added, noting her creation of an agency-wide steering committee meant to address compounding issues, as well as its crackdown on deficient compounding operations.
Calls for a New Framework
Hamburg's prepared testimony also calls for a new framework, one largely similar to the one she outlined in advance of her November 2012 testimony.
See: Hamburg Calls for New Regulatory Authority in Wake of Compounding Scandal
Hamburg also noted that she now believes FDA should have the same inspectional authority over compounders as it does for traditional manufacturers, which notably allows for it to obtain samples of drugs and active pharmaceutical ingredients, inspect records of manufacturing and shipments, and more.
Notably present in her testimony is something Hamburg first alluded to the other week in an FDA Voice blog posting: User fees for compounders.
"FDA looks forward to working with the Congress on potential improvements," Hamburg said. "User-fee-funded regulatory program may be appropriate to support the inspections and other oversight activities outlined in this framework."
"We look forward to working with Congress to explore the appropriate funding mechanisms to support this work, which could include registration or other fees, as Congress has authorized and FDA has successfully implemented in other settings."
GOP Fires Back Pre-Emptively
Republican members of the House, however, were quick to turn their attention toward other matters in a statement released in advance of the hearing. In February 2013, those members had threatened to subpoena documents from FDA, saying that the agency had failed to respond to repeated requests for relevant information.
See: Legislators Threaten to Subpoena FDA over Requested Documents
"We now understand why FDA was so reluctant in cooperating in our investigation and withheld the documents and information for months until we threatened to issue a subpoena," wrote Committee Chairman Fred Upton (R-MI) and Oversight and Investigations Subcommittee Chairman Tim Murphy (R-PA). "We know the actions of NECC and Ameridose led to 53 tragic and unnecessary deaths, and we know the FDA had ample opportunity to intervene before those tainted vials were ever distributed, but they did not do so. We must learn from FDA's mistakes of the past to ensure a similar public health disaster is not repeated. We owe it to the families who lost loved ones and those hundreds of Americans who are still sick and suffering who may never return to leading normal, healthy lives."
The GOP legislators said three points in particular struck them about the documents FDA had provided them:
- "FDA has known for years that NECC and Ameridose were significantly engaged in drug manufacturing activities and operating well outside the bounds of traditional pharmacy compounding."
- "FDA has also received a litany of complaints about NECC and Ameridose, a number of which directly involved the safety and sterility of the companies' products."
- "Information received by FDA about NECC and Ameridose, including complaints about the safety and sterility of their products, was not shared with state regulators."
Their findings likely portend a contentious hearing to come, and a difficult one for Hamburg. What remains to be seen, then, is whether Hamburg's pleas for additional authority and resources will be met with sympathy, hostility, or a tempest of both.
The meeting starts at 10 a.m. EST, and will likely last for several hours. It may be seen live via an online webcast here. Archived committee footage can usually be found here.