Budget Bind

THE FOOD & DRUG Administration has had its share of bad press lately. Most notably, the agency scrambled to track down a deadly contaminant in the blood-thinning drug heparin after FDA investigators mistakenly inspected the wrong Chinese drug manufacturing facility. This situation is the result of an agency that has been underfunded and increasingly overtasked during the past few years.

This trend of underfunding is perpetuated in President George W. Bush's proposed 2009 budget, which falls far short of what many lawmakers, health advocacy groups, and industry trade associations say is needed to ensure the safety of the nation's food and drug supply.

Under the President's spending blueprint, FDA would get nearly $2.4 billion for the next fiscal year, including $1.8 billion in funds directly appropriated by Congress and $626 million in industry user fees. If approved by Congress, the 2009 budget would amount to a $51 million—or 5.7%—increase over the agency's current budget.

FDA says the Bush Administration's proposal includes strategic increases to strengthen food protection, modernize drug safety, and hire additional staff. "This budget enables us to continue development of the staff and programs necessary to safeguard the food we eat and improve the safety and development of drugs, vaccines, devices, and other medical products," FDA Commissioner Andrew C. von Eschenbach says.

But critics contend the budget plan offered by the White House is not nearly enough to remedy FDA's current shortfalls in staffing and other resource needs. "The Administration's slight funding increase proposed for FDA is woefully inadequate," Rep. Bart Stupak (D-Mich.), chairman of the House Energy & Commerce Subcommittee on Oversight & Investigations, remarked at a recent hearing held to examine deficiencies at the agency.

FDA, which regulates $1.5 trillion worth of goods comprising one-quarter of the U.S. economy, has been under fire in recent months for a series of large-scale food recalls, drug safety lapses, and the failure to inspect foreign drug plants. Most recently, a contaminated ingredient used to make heparin entered the U.S. from a facility in China that had never been inspected by FDA because of a mix-up with the company's name.

"For more than a year, the Committee on Energy & Commerce has held hearing after hearing underscoring the breakdowns in FDA's efforts to protect Americans against tainted food, drugs, and other dangerous imports," Stupak said. "A central theme in all of these investigations is that the agency lacks the resources to do its job. It is truly broken."

Three recent independent assessments of the agency, including one conducted by FDA's own science advisory panel, have reached the same conclusion: At current staffing and funding levels, FDA is ill-equipped to protect the American public from unsafe products.

"The amount in the Administration's proposed budget is not only inadequate, it is barely half of what FDA needs just to keep pace with inflation," former FDA deputy commissioner William K. Hubbard says. "FDA's ability to fulfill its mission could be in serious jeopardy if additional increases aren't enacted."

Hubbard is now working with the Alliance for a Stronger FDA, a broad-based advocacy coalition whose 180 members include seven former FDA commissioners, consumer groups and professional organizations, and trade associations representing the biotech, generic drug, and brand-name pharmaceutical industries.

The alliance is urging Congress to provide $2.1 billion for FDA for the fiscal year beginning on Oct. 1-an increase of about $380 million over the 2008 appropriation. "The public health is in jeopardy because of FDA's inability to conduct food and import inspections and to have a modern information technology [IT] system," Hubbard remarks. "We want FDA to be capable of meeting the public's expectations."

FDA's Science Advisory Board has made a similar recommendation, calling for a $375 million increase in direct appropriations to FDA for 2009 to help restore the agency. The panel also says an additional $450 million increase will be needed in 2010 and $460 million in each of the following three years.

"The years of neglect cannot be wiped away instantly," wrote Gail H. Cassell, vice president of scientific affairs at Eli Lilly & Co. and leader of the board's subcommittee on science and technology, in a letter to several Democratic committee chairmen who requested the budget assessment. "FDA needs a very substantial increase in resources if it is to protect us as the public expects and Congress demands."

In December, the advisory panel issued a scathing critique that detailed how funding and staffing have not kept pace with FDA's ever-growing responsibilities. "This imbalance is imposing a significant risk to the integrity of the food, drug, cosmetic, and device regulatory system, and hence the safety of the public," the science board concluded.

The report describes a "plethora of inadequacies" at the agency, including infrequent inspections of manufacturers, a "badly broken" food-import system, and a depleted FDA staff, which is about the same size as it was 15 years ago despite huge growth in the agency's responsibilities. Instead of being proactive, the report says, the agency is often in "fire-fighting" mode.

The assessment, the result of a yearlong review by a panel of experts from academia, industry, and other government agencies, also found that FDA "suffers from serious scientific deficiencies and is not positioned to meet current or emerging regulatory responsibilities." The agency has a "dearth" of scientists who understand emerging technologies, and turnover rates in some scientific positions at FDA are twice that of other government agencies.

In addition, FDA's IT systems are so "obsolete" that reports of product dangers are not quickly compared and analyzed, and inspectors' reports are still handwritten and slow to move through the system, the assessment notes. "Critical data reside in large warehouses sequestered in piles and piles of paper documents" with no backup, including clinical trial data, according to the report.

FDA's von Eschenbach acknowledged many of the criticisms and unveiled initiatives for recruitment, training, and drug safety during a Feb. 29 speech at the National Press Club in Washington, D.C. According to the commissioner, FDA must make significant changes to keep up with fast-moving scientific discoveries and complex global markets that mean more and more U.S. food and medicine are produced abroad, often in developing countries that provide less than adequate product oversight.

"The simple truth as I see it today is that the FDA of the 20th century is not adequate to regulate the food and drugs of the 21st century," von Eschenbach declared. "It is no secret in Washington that as FDA's responsibilities have grown, the resources devoted to them have not kept pace. Strengthening FDA for this new century will require an investment, providing our agency with a budget and authorities that are commensurate with the scale and scope of our mission."

AMONG THE HARSHEST criticisms that have been leveled at the embattled agency is that it has been slow to respond to drug safety problems that emerge after a medicine reaches the market. On that front, von Eschenbach said FDA would launch a new postmarket surveillance program called the "Sentinel Initiative." Partnering with other health organizations, the program will create a national electronic database of information about the safety of medicines as they are used by large diverse populations, potentially enabling FDA to spot signs of trouble faster, he explained.

Although drugmakers support increases in FDA's budget primarily to help speed up the lengthy approval process for new products, consumer advocates maintain that many of the agency's problems can be traced to its reliance on the pharmaceutical industry to partially bankroll its operations.

"The situation at FDA has never been worse than now," Sidney M. Wolfe, director of Public Citizen's Health Research Group, told the House appropriations subcommittee that controls FDA's purse strings at a Feb. 27 hearing. "Congress must act quickly to restore confidence in FDA by removing the considerable influence of the drug industry, which currently funds almost two-thirds of FDA's budget for drug approval."

Under the 1990 Prescription Drug User Fee Act, which Congress reauthorized last year, FDA collects fees from industry to help support the new-drug approval process. FDA says the law enables shorter review times and a more predictable process, while still maintaining high-quality assessments. But Wolfe claimed the system creates an unacceptable conflict of interest.

"FDA's public health mission is too important to be left to funding by the drug industry, with all of the concessions and negotiations that industry extracts for paying the majority of the bill for the FDA drug approval process," Wolfe testified.

Rep. Rosa L. DeLauro (D-Conn.), who presided over the appropriations subcommittee hearing, said it will take more than just an increase in funding to fix the extensive problems at FDA. "The existing culture at FDA that has allowed political and corporate interests to permeate the decision-making process at the expense of irrefutable science is a critical concern that increased funding will not solve," she said.

In recent years, DeLauro noted, FDA scientists have often complained about interference from top-level FDA appointees on behalf of corporate and political interests. "They feel that factors other than good science play a role in important FDA decisions," DeLauro said. "We must push back against the influence of big pharma."

The most recent crisis involving FDA has been over the safety of imported active pharmaceutical ingredients, an issue highlighted by the scandal involving contaminated heparin, which has been linked to 19 deaths and 900 illnesses in the U.S. FDA has said it intended to inspect the Chinese manufacturer of an ingredient in the drug, but instead it checked another plant in the agency's database with a similar name (C&EN, Feb. 25, page 8).

On March 12, DeLauro wrote a letter to the Department of Health & Human Services (HHS) calling on the department to investigate FDA's failure to conduct a preapproval inspection of the proper facility. "While FDA has sought to portray this as an isolated incident, we cannot determine whether that was the case until we understand what transpired," DeLauro wrote in her letter to HHS Inspector General Daniel R. Levinson. "If this was not an isolated situation, we need to determine the scope of the problem at FDA and how to address it."

Since 2002, FDA's budget for inspections of foreign drug facilities has decreased 25%. During this same time, the number of overseas plants manufacturing drugs for shipment to the U.S. has rapidly increased. The Government Accountability Office reports that 80% of all active drug ingredients consumed in the U.S. are now imported, with 40% made in China and India. Earlier this month, FDA received approval from the State Department to establish eight staff positions in China, pending authorization from the Chinese government (C&EN, March 24, page 28).

"Many Americans are surprised that so many drugs and their ingredients come from foreign places, but the truly worrisome surprise is that FDA is struggling to ensure that these medicines won't harm the people who take them," says Rep. Joseph L. Barton of Texas, ranking Republican on the House Energy & Commerce Committee. "Drug manufacturing went global over the past decade, but FDA didn't keep up. It continues with the same limited knowledge, the same strategy, and the same second-class status for the foreign inspection program."

BARTON SAYS he plans to introduce legislation in the near future that would update the Food, Drug & Cosmetic Act to give FDA explicit authority over unsafe food or drugs produced overseas for export to the U.S. "Officials need more resources, but they also need fresh thinking and a new approach," he remarks. "I'm ready to give Commissioner von Eschenbach the support he requires to effectively detect and reject the tainted drugs that are arriving from abroad."

Democrats say more ambitious reforms are needed. Energy & Commerce Committee Chairman John D. Dingell (D-Mich.) is cosponsoring legislation with Stupak that would charge companies a fee to help pay for inspections of imported food and drug shipments. "Tainted imports are slipping into our country undetected, and the resulting problems will continue to grow if we don't take immediate steps to tighten safety measures," Dingell says.

Funds generated by the fee would be used to hire additional personnel to perform inspections at both the U.S. border and abroad, as well as at FDA labs to increase analysis of food and drug imports. The money would also be used to test import samples and research new testing techniques.

In addition, the proposed Food & Drug Import Safety Act (H.R. 3610) would grant FDA new authority to issue mandatory recalls, halt imports of certain products until a foreign facility can demonstrate that steps have been taken to rectify an identified problem, and increase civil monetary penalties for manufacturers or importers that violate federal law. Dingell and Stupak also plan to hold hearings in April to examine the events that led to the distribution of contaminated batches of heparin (see page 8).

"With a record 378 recalls last year on everything from peanut butter to pet food to drugs, it is clear FDA has failed to protect the American people from unsafe products," Stupak says. "The sad reality is that Americans can expect more episodes similar to what we are now seeing with heparin unless FDA implements wholesale changes."