Top officials with the US Food and Drug Administration (FDA) will against find themselves in the firing line of congressional legislators in the coming week as the House Energy and Commerce Committee says it's not finished probing the agency's response to a recent outbreak of fungal meningitis.
Pharmaceutical compounding pharmacies enjoy a relatively unusual regulatory exemption in the US whereby they can compound products without having first sought regulatory approval so long as they create the products specifically for a single patient with a valid prescription. Historically, these compounding pharmacies have largely been overseen by state-not federal-regulatory officials, and most commonly state boards of pharmacy.
The industry, once small, has expanded rapidly in recent years as the Internet has allowed pharmacies to take orders from all across the US, and drug shortages have placed an increased reliance on compounders to make up for the quality failures of federally regulated pharmaceutical manufacturers.
But that expansion has come with problems, both for the compounding industry and FDA, which has seen its authority to regulate the compounding facilities eroded by a series of court cases over the last two decades.
Industry's problems, however, seem more troubling.
In the waning months of 2012, FDA began to receive troubling reports of patients with a rare form of fungal meningitis, which were ultimately traced back to a compounding facility in Massachusetts known as the New England Compounding Center (NECC). 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.
A Congressional Hearing
The outbreak of fungal meningitis killed dozens of patients and left ill hundreds, prompting legislators-some furious-to call FDA Commissioner Margaret Hamburg before the House Energy and Commerce Committee and the Senate Health, Education, Labor and Pensions (HELP) Committee to justify her agency's actions.
The hearings were perhaps notable for their open hostility, with some legislators openly lashing out at Hamburg for the agency's perceived failings.
In a memorable exchange, Rep. Tim Murphy (R-PA) launched into a scathing rebuke of Hamburg, accusing her of a failure of leadership. "What you have to do is easy, ma'am. Leadership is easy if you're willing to accept it, and you are not."
"Go look in the eyes of the victims and try to comfort them with that," he added, referring to Hamburg's answer over definitional complexity.
Could FDA Have Done More?
One frequent source of contention at the hearings was the history of FDA and NECC. Legislators said their investigation had found that FDA investigated NECC several times over the course of the prior decade, and had then found nearly identical problems as the ones that led to the meningitis outbreak.
"I was stunned and angered to learn that an inspection of the NECC by the FDA and the Mass Board over 10 years ago identified contamination in the very same drug at issue in the current outbreak," said committee chairman Fred Upton (R-MI). "The reason for that inspection? Patients had been hospitalized with meningitis-like symptoms."
"This is simply inexcusable," he added. "After observing multiple violations of the Food, Drug, and Cosmetic Act leading up to FDA's 2006 Warning Letter, why did the agency fail to conduct a single follow-up inspection?"
Those same legislators also pressed Hamburg for additional details about these inspections, saying they felt their requests had not been adequately responded to by FDA. In February 2013, House legislators issued something of an ultimatum: Either hand over all relevant documents, or we'll subpoena them instead.
A New Hearing
It's unclear whether FDA complied with that demand, but now Rep. Murphy and other legislators are planning to revisit the compounding issue, saying that Hamburg has once again been called to testify in a hearing entitled, "A Continuing Investigation Into the Fungal Meningitis Outbreak and Whether It Could Have Been Prevented."
"The evidence so far demonstrates the NECC should have been shut down long before fifty people tragically lost their lives from contaminated injections," said Murphy, who is chairman of the subcommittee on Oversight and Investigations. "With many more still sick, we will continue investigating the breakdown at the FDA so a public health disaster like this one never happens again. The FDA owes the American public the peace of mind that it will do all it can to protect the integrity of the nation's drug supply chain, and the goal of our investigation is to ensure that happens."
FDA is likely to have new details to report to Murphy since their last exchange. At the time, Hamburg had issued a new framework that called for the agency to be given new authority to regulate compounders. That call seems to have fallen on deaf ears.
Since then, Hamburg has floated the idea of user fees to help FDA afford to regulate compounders-a recent favorite of Democrats and Republicans alike, who have implemented new fees on the biosimilar and generic pharmaceutical industries in the last 12 months.
But most significant of all for Hamburg may be her ability to report that FDA is cracking down on compounders at the fastest rate in recent memory. The agency has already released over a dozen deficient inspection reports (Form 483s) to compounders, the majority of which cite major sterility concerns. Those inspections have also prompted several recalls.
A Matter of Resources?
Still, Hamburg may have trouble answering some of the same questions presented at the last hearing, including why the agency didn't do more, and sooner. In an interview with the industry blog Pharmalot in April 2013, FDA's Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), and Howard Sklamberg, head of CDER's Office of Compliance, seemed to say that at least some of their hesitancy to go after compounders in recent years was an issue of resources.
"This is no way to regulate an industry," explained Woodcock. "Sure, we could have gone out and done more inspections like this and battled each one in court. But there are 28,000 compounding pharmacies of any type and we don't know who's who, because they don't send us anything or tell us. So how would we regulate that industry when we go there and have to get a warrant from a judge to walk in the door? You could say we could battle in court and get in the firm, but what about the other 27,999? We have to have a scheme - these firms we regulate or we don't."
In response to a later question, Woodcock expanded on that point again: "We could get totally tied up in lawsuits and we would have to stop inspecting the drug industry. And that would be great, for some people. Any time we have to go to court, we have to get warrants; we have to do all these things. It isn't to say we weren't doing it before. It was done for cause. During those 10 years, we were getting court rulings partly because we were active in that space. So nothing would prevent us from having ongoing reactive programs"
Sklamberg, too, elaborated on this point, saying that there are, "realistically, with the government, limited resources."
"We made this a top if not the top priority for the drug inspection program over the last few months," he continued. "The agency can always choose to target a specific thing as opposed to something else. And when we go through this process and have the resistance and have people having us get warrants and challenge our legal authority, it's a bigger resource expenditure and bigger opportunity cost for the agency."
That could be a hard argument to sell to legislators, especially given the number of patients killed or injured.