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User Fee Reauthorization: FDA Is In Trouble If 2007 Repeats Itself

Monday, January 30th, 2012

Starting this week, the House will hold hearings on reauthorizing the drug and medical device user fee programs that fund one-fourth of the agency. While user fees have become largely non-controversial, this “must-pass” legislation is Congress’ opportunity to consider dozens of other FDA issues, some controversial and many time-consuming.

During the last user fee reauthorization in 2007, multiple non-user fee issues delayed enactment of a new law until September 27, just a few days before the start of the new fiscal year. In FDA Matters’ view, FDA is in serious trouble in 2012 if it once again takes until September to complete the user fee reauthorization legislation.  

There are two user fee programs up for reauthorization this year: the Prescription Drug User Fee Act (PDUFA) and the Medical Device User Fee Act (MDUFA). In addition, two new user fee programs have been proposed by FDA. One covers generic drugs and the other biosimilars and interchangeable biologics.

If only these four user fees were at stake (two renewals, two new), Congress could conceivably be finished by July 1, 2012. This would be optimum for giving FDA enough time to invoice and collect the user fees for the coming fiscal year (FY 13). It would also give FDA time to start making new hires and to work on any additional requirements in the new law. A lot of things could be in place by the start of the fiscal year on October 1, 2012.

However, almost no FDA legislation has passed since the last reauthorization five years ago. Pent-up demand for FDA amendments is enormous and delays are to be expected. July 1 does not look like a realistic target to complete legislation.

What happened in 2007 is beyond instructive, it is frightening. As a general precaution, FDA left many staff positions vacant during 2007, just in case the user fee monies were not renewed. As required by law, FDA compiled lists of employees it could not pay if user fee monies were not available on October 1, 2007. The agency narrowly avoided actually having to send out RIF (lay-off) notices to individual employees. While the RIF process was a formality, this created a great deal of distraction within the agency. 

Simultaneously, the timing for invoicing companies and collecting fees was disrupted and fee revenue was not collected, as it usually is, by October 1. While FDA was dealing with this (which required delays in hiring), it faced the harsh reality that many provisions of the new law became effective immediately and had to be addressed with existing staff.

Memories seem to vary about the impact in 2007. I remember significant problems; others have told me the disruption was not consequential. In fact, there is direct evidence of the impact.

Below is a slide from a December 2011 presentation given by Dr. John Jenkins, head of the Office of New Drugs (OND) in the Center for Drug Evaluation and Research (CDER). His intent was not to focus on 2007 or to draw comparisons, but the point seems quite clear.

The chart shows the number of pending drug applications on which FDA was behind schedule (as judged by the timeframes established in the user fee law). The green bars represent the most important applications, those involving new molecular entities (NMEs). The light blue bars represent other drug and biologics applications, while the violet bars represent applications for additional efficacy indications.

A backlog started to form in the second half of 2007. It increased significantly and lasted for more than 24 months. There may well have been other factors at work, but it seems more than a coincidence that the problems started at the same time as the disruption caused by the new law.

If 2012 becomes a repeat of 2007, then FDA will find itself under withering criticism later this year for not reviewing innovative drug applications in a timely fashion. Medical device are likely to be similarly impacted. FDA will be unhappy, companies with pending applications will be outraged, and patients will be short-changed as potential new therapies are delayed.

Congress needs to commit to speed up the process, minimize amendments, and make new provisions effective six months or a year after enactment. What is possible by July 1 is a House-Senate agreement on a very limited piece of non-controversial legislation that addresses user fees and perhaps one or two other items.

It is a disservice to FDA and the public health for Congress to do otherwise.


The State of the FDA—January 2012

Tuesday, January 24th, 2012

FDA is the only federal agency that touches the lives of every American several times every day. Its remarkably broad mandate includes all medical products and 80% of the nation’s food supply, plus countless other products. Despite this, when the President delivers his State of the Union (SOTU) address to Congress this week, it is unlikely that FDA will rate a mention.

FDA Matters will instead provide its second annual “State of the FDA.” As reflected in last week’s column, FDA did well in 2011, but one year’s progress does not change the continued precarious state of the FDA. Here is our analysis:

Strengths: FDA’s most important strength is the dedication of the agency’s staff  and the leadership of Commissioner Hamburg’s team. In the current environment, their efforts are invisible to the public they serve and largely unappreciated. If safe foods and safe and effective medications are important to you, say “thank you” to the FDA staff that make it possible.

The agency’s independence is another key strength of the FDA. At the moment, many FDA observers don’t see it that way, viewing the HHS Secretary’s decision to overrule FDA on Plan B as evidence that the agency is weak and dependent. However, Plan B is a ‘one-of-a –kind” controversy, presenting uniquely difficult and combustible issues that aren’t present in 99.9 percent of FDA’s decisions. If you look at the totality of FDA actions, the agency is remarkably independent from HHS and the White House. Rather than a weakness, this is one of the agency’s strengths.

Weaknesses: Despite a number of recent, laudable efforts at improvement, the FDA is still disorganized and largely ineffective in communicating its messages to the public, media, stakeholders and Congress. Notably, an analysis published in the journal, Medical Care, last week concluded that: although some [FDA] communication efforts had a strong and immediate effect, many had little or no impact on drug use or health behaviors and several had unintended consequences.

FDA’s information technology (IT) systems continue to be grossly inadequate for an agency with such large, far-flung and complex responsibilities. Some progress has been made with analytic data bases, such as the Sentinel program to track post-market safety, and with data bases that improve the flow of information within the agency and between field and headquarters. The October 2011 appointment of a new chief information officer with industry experience is a hopeful sign.

Opportunities: The promise of science has never been brighter. And Dr. Hamburg, to her credit, has made it a priority to improve the agency’s scientific bench strength—better credentials, better training and better tools.

This provides FDA and the medical products industries with the opportunity to forge a new “social contract” with regard to scientific standards and product approvals. FDA must commit to becoming less formalistic and bureaucratic in its dealings with companies. It must demonstrate (not just accept) that advancing medical innovation is an integral part of the FDA’s role in promoting public health. In turn, industry needs to accept that “science, fairly evaluated within predictable guidelines,” is an appropriate expectation as opposed to a system based on short-cuts to market and ill-defined, “leap of faith” assumptions about safety and efficacy. In addition, industry bashing of FDA needs to end. It is counterproductive to everyone’s interests.

Equally promising is the opportunity to significantly upgrade the safety of the American food supply. Even with the devotion of FDA staff to this cause, we are lucky that the reported levels of foodborne disease and product adulteration are not higher. The year-old Food Safety Modernization Act (FSMA) is, by general agreement, a blueprint for moving to a new level, one where a safer food supply reflects smart decisions.

Threats: The largest threat to FDA is inadequate funding. As science has become more complex, industry more global and information more integral to every human interaction, FDA oversees a rapidly expanding portfolio of products and responsibilities. Even without the threat of budget cuts facing all federal agencies, it would be hard to grow the FDA budget enough to stay ahead.

A related threat is the potential for massive expansion of FDA’s unfunded mandates during Congressional reauthorization of the drug and medical device user fee programs. FDA is almost certain to be given new (and needed) authority for drug import inspections and drug shortages. In addition, Congress will consider and most likely pass a dozen or more other new programs or significant changes in FDA regulation. FDA will almost certainly have to implement these new requirements without additional appropriations. 


For those who may be interested, here is a link to “The State of the FDA—January 2011” http://www.fdamatters.com/?p=1240.

Medical Innovation, Food Safety, and Imports: Did FDA Have A Good Year in 2011?

Monday, January 16th, 2012

 Before turning to 2012, FDA Matters wanted to take one more look at FDA’s performance in 2011. So much happens at FDA that it’s easy to lose perspective. And no matter what the agency does, somebody will be unhappy. So, should Commissioner Hamburg feel good about the last 12 months?


FDA Matters thinks it comes down to how well FDA handled the three most important challenges it faced:

  • improving the medical product review process, including stimulating innovation;
  • implementing the Food Safety Modernization Act; and
  • advancing the agency’s ability to assure the safety of imports.

Before exploring these particulars, FDA Matters feels FDA staff and Dr. Hamburg should be applauded just for surviving the daily grinding pressure of the agency’s workload. As I have noted previously, FDA’s greatest strength is its people.

Medical Product Review Processes. Was it a good year? The approval process for drugs, biologics and medical devices elicited widespread criticism that FDA was too slow, too risk-averse, underweighted patient benefit, and was demanding certainty where none was possible. The unhappiness was constant and palpable from medical device stakeholders; more muted, but still quite strong among bio-pharmaceutical stakeholders.


As the year went on, this critique of the agency increasingly coalesced under the rubric of innovation. Specifically, FDA was accused of creating processes and making decisions that stifle American innovation and cost American jobs.

FDA formulated its response in several ways:

Optimistically, I believe these actions are the start of a turning point for the agency. The largest barrier is not agency leadership’s willingness to promote innovation…rather it is that combining public health and innovation requires a new identity for the agency, something that can't happen overnight.


Food Safety. Was it a good year? At the very end of 2010, Congress passed the Food Safety Modernization Act (FSMA), which creates a sophisticated risk-based food safety system that stretches from the farm to our tables. The new law created or enhanced FDA authority in the following areas: prevention, inspection and compliance, response to problems, imports, and enhanced partnerships with other food safety agencies.


Implementing the new law is a complex multi-faceted task that has been made even more difficult by inadequate funding. Further, many of the new law’s mandates became effective quickly, leaving little opportunity for manpower and IT resources to be mustered to the tasks.


The agency just released its one-year progress report and there seems to be general consensus that the agency has done a tough job well. Year two (2012) will be at least as challenging, but we are definitely one-year closer to a safer food supply.

Imports. Was it a good year? The third major challenge to FDA in 2011 was continuous rapid globalization of the world markets for food, drugs, and medical devices. Almost every country in the world produces raw materials, ingredients or finished goods that become part of imported products regulated by the FDA.  


In July 2011, the FDA issued a special report, Pathway to Global Product Safety and Quality, which describes the enormous impact of globalization on FDA-regulated products. FDA is responding through:

  • closer partnerships with its foreign counterparts and public-and private-sector third parties,
  • development of global data information systems,
  • continued expansion of its capabilities in intelligence gathering, and
  • allocation of agency resources based on the risk of a food safety problem.

During 2011, the agency further expanded its network of overseas offices and reorganized its headquarters oversight. The latter was accomplished by appointing Deborah Autor as the new Deputy Commissioner for Global Regulatory Operations and Policy.   

Conclusions. In upcoming columns, we will be detailing the challenges facing FDA in 2012. Meantime, we urge Dr. Hamburg and all of FDA to take a moment to think back with pride to 2011. You had a good year.


Post-Market Safety: Can Sentinel Do Some of the Heavy Lifting?

Wednesday, January 4th, 2012


In the FDA-regulated world, success is often defined as approval of a new product or indication based on two, well-controlled clinical trials. However, the scrutiny doesn’t end there. FDA’s mission includes determining whether already-approved drugs perform safely and effectively when used by large numbers of patients in routine medical practice. 


To understand what happens under these “real world conditions,” FDA has expanded its post-market  efforts, including development of a monitoring system (called Sentinel) that will be able to track drug usage and medical history information on tens of millions of patients. Although such information will be useful, it can only provide post-hoc inferences, not proof of causation. Even with this limitation, FDA Matters thinks developing the system is worthwhile and may provide multiple benefits. 


There are multiple tools for assessing post-approval safety and efficacy that fit loosely under the rubric of pharmacovigilance. When approving medical products, FDA mostly relies on data that comes from pre-specified hypotheses that are tested through randomized, placebo-controlled, double-blind clinical trials. In contrast, the data that comes from pharmacovigilance is inherently less rigorous; indeed it constitutes a form of “data dredging” that FDA abhors. The heart of the problem is that:  

Real world data sets = uncontrolled variables + inconsistent data collection + questionable data accuracy.

When FDA and manufacturers collect adverse events reports, they know there will be underreporting of incidents, as well as limited ability to judge whether problems are drug-related. When FDA looks at the Medicare database, they know that information submitted as part of medical claims is unreliable and subject to systemic bias (e.g. medical coding is designed to support reimbursement, not public health analysis).

The Sentinel database should be superior because it incorporates medical records and patient registry information, along with claims data. Still it provides inferences, not proof.

Active surveillance—continuously monitoring millions of health records—is only worthwhile if these limitations are acknowledged. It can never provide certainty about whether drugs are safe and effective. It can tell you what is worth further examination…but can never tell you the cause of any problem that is identified.

As the FDA mantra goes: association is not causation. No matter how many health records and claims data are reviewed, this is still true.

Clinical trials have limitations, also. Trials don’t tell us how a drug will be used by prescribers. They can never provide complete information about patient outcomes for those individuals with several medical conditions (i.e. multi-morbidity) or who take many medications simultaneously (i.e. poly-pharmacy).

By inference (although not with certainty), pharmacovigilance and active surveillance could bring us closer to addressing potential problems that can’t be resolved by clinical trials. For example, many years ago, I worked on a drug to treat pre-term labor. As I recollect, there were two instances of respiratory problems in a trial of several hundred women. No one could say for sure whether this effect was caused by the drug or occurred at random. A study large enough to find out was infeasible.

Based on the potential respiratory problem, FDA rejected the drug despite the benefits it might have provided to women experiencing pre-term labor. If this same situation were to come up today…maybe FDA would decide differently, knowing it could collect patient outcomes information through pharmacovigilance, particularly active surveillance.

Ideally, FDA would know everything it needs to know about a drug at the time of its approval. Information derived from review of real world data sets can never be as good. But properly understood and carefully analyzed, the inferences derived from pharmacovigilance can add to our understanding about safety, efficacy, drug interactions and side effects.


Instead of just using that capacity to identify post-approval problems, FDA needs to incorporate pharmacovigilance into its thinking about when to approve drugs and with what conditions. FDA’s capacity to do pharmacovigilance and active surveillance should lead to a greater willingness by FDA to approve drugs, particularly those with otherwise solid benefit-risk equations, but burdened by questions that cannot be resolved prospectively or through clinical trials (even in phase 4).


Patients would benefit if FDA made this one of the Sentinel priorities.




This column first appeared on June 21, 2011. It is one of my favorites from last year.

FDA and Congress: Prospects for 2012

Monday, December 19th, 2011

Barely more than a year ago, the US experienced a “wave” election—sweeping a Republic majority into the House of Representatives and reducing the Democratic majority in the Senate. As a result, FDA faced a Congress in 2011 that contained fewer friends and less support than previously.

The consequences, thus far, have been small. Congress became so absorbed with deficit reduction that it accomplished little else this year and spent almost no time on FDA issues. Circumstances will change this in 2012 and, fortunately, we have strong clues about Congressional attitudes and priorities.

At the end of 2010, FDA Matters devoted six blog columns to examining the impact of the election on FDA and its regulated industries. As predicted, Congress was more interested in deficit reduction in 2011 than any other topic. This shows no sign of abating.

For FDA, this means constant pressure from Congress on funding, particularly from sequestration and other threats of across-the-board cuts in federal spending. FDA’s best position is always to have its needs evaluated on an individual agency basis—rather than being part of a larger funding action.

Congress chose not to address FDA’s FY 11 appropriation in the post-election session. Instead, it addressed this in April of 2011 on fairly favorable terms to the agency.

Similarly, FY 12 appropriations demonstrated that Congress was still receptive to partially meeting FDA’s growing resource needs, but it became clearer that future funding increases will be even harder to get. Arguments for FDA being an exception to deficit reduction will be made often next year by agency supporters within Congress and by outside advocates.

In general, very little legislation passed Congress in 2011 and virtually none without bi-partisan support. FDA Matters pointed out that achieving such consensus was possible on FDA issues when Democrats from technology-oriented regions joined with Republicans on positions that could enjoy industry/patient or industry/consumer support. This approach did not produce any legislation in 2011.

However, technology-oriented Democrats are likely to join Republicans in shaping the user fee reauthorization legislation, which Congress “must-pass” in 2012. It seems certain that the bi-partisan pathways will produce most of the legislation, including new authority for drug import inspections, incentives for development of antibiotics and provisions to address drug shortages.

I expected a substantial ramp-up of Congressional oversight and investigations of FDA and regulated industries, which never materialized. There were a few hearings, but never the vehemence or persistence that would have represented a major change from the previous Congress.  I still believe there will be an uptick in these activities, but most likely it will be deferred until late 2012 or 2013, after Congress adopts the user fee reauthorization legislation.

A final column last year asked the provocative question: will the new Congress be good for FDA-regulated industries? Republicans generally want federal regulations and regulatory agencies trimmed back significantly. In contrast, FDA-regulated industries generally want more flexible regulatory requirements and greater certainty in their implementation, but are not interested in eliminating FDA’s regulatory responsibilities or limiting its ability to assure public health and safety.

So far, this Congress has not come to a firm conclusion about FDA. It has not embraced FDA as an essential government service—like national defense and air-traffic controllers—but neither has it marked FDA as a particular target to starve, roll-back, harass or marginalize.

The deciding factor may be how FDA responds to Congress’ insistence that FDA be a positive force in the advancement of American innovation and a contributor to US competitiveness. This is precipitating an identity crisis at FDA, which the agency is working hard to resolve.

If FDA succeeds in integrating innovation into its mission, priorities and processes, then Congress will be able to see FDA (and the support it enjoys) as being essentially different than other regulatory agencies that do not have widespread public support.  This is the optimum position for FDA in its relationship with Congress.


Beyond Plan B: Scientific Integrity and a Possible Third Class of Drugs

Monday, December 12th, 2011

Patient access to the emergency hormonal contraceptive “Plan B One-Step” has been one of the most combustible issues ever faced by FDA. It received more attention last week when FDA approved expanded access for adolescents under 17 and HHS Secretary Katherine Sebelius promptly overruled the agency because she found inadequate scientific support for the decision. (For my readers outside the US, here is a New York Times article that provides background).

FDA Matters wonders: has FDA’s scientific decisionmaking authority been thwarted in some lasting way, as some have claimed? Is it time to reconsider proposals for a new category of drugs for which pharmacists are the gatekeeper?

Under the Federal Food, Drug and Cosmetic Act and other laws, the Secretary of HHS has the legal authority to make virtually all decisions within the Department’s jurisdiction. Most of this authority has been delegated to subordinates, including the FDA Commissioner, although the delegation can be withdrawn at any time. No one remembers an instance in which the Secretary explicitly overruled FDA.

Was there a lapse in communications between FDA and HHS? Normally, the Secretary and the Commissioner (or their staffs) discuss controversial decisions before they are made and a compromise reached. Had this occurred, FDA would have announced that compromise as the agency’s decision and taken the heat for ignoring its advisors and staff.  

The alternative explanation, which I hope is true, is that there was an understanding that FDA’s voice should be heard and its integrity preserved, while the Secretary would take the heat for the decision by overruling the agency. This would be consistent with an approach that Commissioner Hamburg has championed: that government should be more honest and transparent about disagreements, as long as everyone understands that someone with decisionmaking authority will actually make a decision.

Either way, it is important to recognize that Plan B has proven to be a “one-of-a-kind” controversy, presenting uniquely difficult issues that aren’t present in 99.9% of FDA’s decisions. I see no reason for commentators to be writing, as one did:  “FDA’s medical and scientific integrity has been forever blighted by these frankly political decisions.”

Secretary Sebelius is not going to make a habit of questioning the scientific support for FDA’s decisions. Nor have we any reason to fear the death of FDA’s integrity or to conclude that it can no longer be a scientifically-driven regulatory agency.

Leaving aside the merits of either FDA or HHS’s position, the Plan B controversy provides an impetus to consider whether there should be a third class of drugs that are neither prescription-only (Rx) nor over-the-counter (OTC). The day after the HHS decision, John Jenkins, director of FDA’s Office of New Drugs, suggested just such a connection between Plan B and a potential third class of drugs known as “behind the counter” drugs (BTC).   

BTC, which has been discussed for decades, relies upon pharmacists to dispense these drugs without a prescription and independent of a physician-office visit. Pharmacists are the most widely distributed of all health care professionals, as well as the most readily accessible. BTC would empower them to provide additional education, monitor appropriate use and discourage misuse for a wide variety of drugs. 

Currently, OTC products containing pseudoephedrine are handled as BTC because of their potential use in making methamphetamine. According to Dr. Jenkins, statins are potential candidates for BTC status, as might other drug classes where petitions for Rx to OTC switches have been denied but there is still potential for safe patient self-treatment without a physician office visit.

In sum, accessibility to the emergency contraceptive Plan B continues to be a disruptive and controversial issue for FDA. However, this is a unique issue and there should be no continuing damage to FDA because the agency was overruled by HHS. A third class of drugs could evolve out of this that might be beneficial to patients across a number of diseases and drug classes, including hormonal contraceptives.



FDA Bashing: The Wrong Way to Improve FDA

Monday, December 5th, 2011

FDA is imperfect in many ways: it can be hard to predict, maddeningly slow to decide, and inflexible in the face of complex situations. Yet, FDA does remarkably well at carrying out its difficult public health mission. Plus, the agency is constantly striving for improvement.

These points seem lost on agency critics bent on bashing the agency. To believe many of them, FDA is bureaucratically and culturally driven to be ineffective…. and heedless of the impact of its actions on industry innovation and patients in medical need. FDA Matters says: nonsense!

FDA bashing is not a victimless crime. It is a slur on the agency’s good name and many accomplishments. It impedes rational efforts to improve FDA process and performance. It is a barrier to fruitful dialog between FDA and its stakeholders. It drains agency resources and threatens its funding.

FDA bashing is also an incendiary, fostering an environment of “simple, neat and wrong solutions” aimed at fixing the agency.*

FDA bashers make it seem like the world would be a better place if the agency didn’t exist or if its powers were dramatically circumscribed. It’s hard to make FDA a more effective public health and regulatory agency in the midst of such misguided rhetoric. FDA was created–and further empowered over the last 100 years—precisely because regulatory oversight is necessary to assure a safe food supply and safe and effective medical products.

When FDA makes predictable, science-based decisions, patients and consumers benefit from quality products…and industry has the level playing field needed to assure fair competition. This works well most of the time. I’ve heard it said: the world only notices FDA when something goes wrong. That’s largely true.

Believing in FDA and its mission does not require silence or uncritical booster-ism. Let’s all agree that FDA needs to do a lot better before it can be considered the model  for a modern food and drug regulatory agency.

There is a bright dividing line between FDA bashing and working to improve the agency. FDA Matters has praised the Biotechnology Industry Association (BIO) for its positive agenda, even while expressing reservations about BIO’s specific proposals for independent agency status for FDA and a new progressive approval pathway. There have been many positives (and much progress) in the negotiations over medical device user fee reauthorization, even as industry and the agency have bickered privately and in public about the direction of the program.

FDA Matters has been disappointed by many others–industry, patients, Congress, media, and think-tanks–who have emphasized agency bashing at their meetings and in their public communications. Often, the bashing starts with the wrong premise (the agency is largely broken) and concludes with the wrong prescription (break down the agency’s culture and processes and rebuild anew). Not only are these wrong, but they crowd out practical and constructive dialog about agency improvement.

FDA has (in my view) gone out of its way to welcome comments and respond thoughtfully. There is so much more to do….but the agency is not hiding from criticism or arguing reforms are unnecessary.

Other stakeholders seem to be responding in kind. I am involved with at least two efforts to build FDA reform agendas and would welcome the opportunity to participate in others.

FDA Matters believes the right way to improve FDA is through constructive recommendations and thorough discussion. FDA and our nation deserve better than vitriol about how FDA is destroying jobs and is “the enemy.”


* After H.L. Mencken’s admonition that “for every complex problem, there is a solution that is simple, neat and wrong.”

FDA’s Fuzzy Funding Future

Monday, November 28th, 2011

While not all of FDA’s problems are caused by a lack of resources, few of its problems can be solved without better funding. Money matters. “Safer foods” requires funding to implement the Food Safety Modernization Act. “Faster and safer drug and device approvals” are only possible with funds to pay additional reviewers and build improved regulatory systems.

FDA has an enormous job and its responsibilities grow every year. Funding increases over the last five years have not offset decades of underfunding and under-investment in the agency. FDA Matters believes the next 12 months will determine FDA’s funding future.

The Outlook for Appropriations. FDA’s FY 12 funding is now set. The agency will have $50 million more to spend this fiscal year, for a total of $2.5 billion. While this increase is not large, FDA did quite well in the face of a possible $285 million cut. The agency was one of the few federal programs to receive more dollars than in FY 11.

 It’s too early to project next year’s appropriation. The President’s FY 13 request will be released in early February 2012. Because the Budget Control Act (BCA) of 2011 requires aggregate domestic discretionary spending to be lower than FY 12, competition for funding will become even more intense. Congress will need to be persuaded that FDA funding is a priority and needs to be an exception to funding constraints.

Also as a result of BCA, there is a very real threat to FY 13 FDA funding, as part of mandatory across-the-board cuts (“sequestration”) scheduled to take place on January 1, 2013. Unless Congress passes substantial deficit reduction legislation next year in lieu of sequestration, FDA must prepare for a possible cut in the range of $150 million to $250 million.   

Prospects for User Fees. In addition to appropriations, the Prescription Drug User Fee Act (PDUFA) provides FDA with supplemental funding from industry to support review of applications for new drugs and biologics. A similar program (MDUFMA) supports review of medical devices. There are also several smaller fee programs, as well as user fees that support the FDA’s tobacco center.  This chart shows the amount and growth of revenue derived from industry fees:  

All numbers approximate

FY 2009

FY 2010

FY 2011


$    512 million

$    573 million

$   667 million


$      47 million

$      57 million

$     57 million



$    235 million

$   450 million


All Fee Revenue (inc. smaller programs)

$    637 million

$    922 million

$ 1.224  billion

PDUFA and MDUFMA are expected to be renewed in FY 12 with higher revenue targets. With so much pressure on appropriations, Congress will be tempted to see user fees as the answer to FDA’s growing funding needs. However, user fees are only available for specific purposes and do not support FDA’s full mission.

Further, Congress has no qualms about increasing the amount of user fees, then bemoaning the agency’s increasing reliance on industry funding.  This is not a situation where “all money is green.” Increases in appropriated funding are still critical to a well-functioning FDA.

Delays in Enacting User Fee Legislation and the Possible Impact of Unfunded Mandates. FDA’s future funding is further obscured by the nature of the process of renewing the user fee programs. For example, delays in adopting legislation could result in funding shortages in early FY 13, making it harder for FDA to fulfill its obligations. In turn, this will contribute to Congressional concerns about whether FDA is spending monies efficiently and effectively.

Further, Congress “must pass” renewal of user fee programs in 2012, creating a situation where multiple FDA-related amendments are certain to be considered. Such amendments, if they become law, are likely to expand the agency’s responsibilities without adding additional funds for implementation.


Here are November 2011 columns you may have missed:

Animal Research: An Update on One of FDA’s Core Values     November 22nd, 2011

Bold Discussions: Possible New Approval Pathways for Breakthrough Drugs November 14th, 2011

By Whose Standards: FDA’s Identity Crisis and the Level Playing Field  November 7th, 2011

Animal Research: An Update on One of FDA’s Core Values

Tuesday, November 22nd, 2011

The value of animal research in the life sciences is considered an NIH issue. FDA Matters believes that FDA and its stakeholders should be equally involved.

Animal research is the vital first step in the development of new medical products. Before any safety or efficacy testing is permitted in humans, FDA must be satisfied with animal testing data submitted by the product sponsor. Pick any medical breakthrough and you will find animals were tested prior to humans.

For understandable reasons, we tend to focus on the human part of new products. Which patients will be helped and by how much? By the time a company files a New Drug Application (NDA) or the equivalent in biologics and devices, the headline is the human data. While the animal data is always relevant, it has largely served its purpose as the gateway for human trials.

We talk about the people part without recognizing that the pipeline of innovative drugs and devices would collapse if a broad range of research on animals (e.g. non-human primates, pigs, sheep, dogs, rats, mice, zebrafish, fruit flies, worms) was heavily restricted. Over 96% of the animals used in biomedical research are rodents, birds, fish and invertebrates. As background, there is an excellent summary on the need for animal research available from the advocacy organization, Americans for Medical Progress.

Everybody should be for protecting the welfare of animals. Any means to lessen our dependence on research animals should be welcome. Animals should always be treated ethically and pain reduced or eliminated. The fewest number of animals should be used to reach a conclusion that can be relied upon. Laboratories should be accredited and subject to inspection. Problems should be addressed within a facility under the watchful eye of government, accrediting and licensing agencies and in accordance with the Animal Welfare Act.

Since I last wrote on this topic two years ago, the nature of the animal rights movement in the United States has shifted. Successful prosecutions under the 2006 Animal Enterprise Terrorism Act (AETA) have purged some of the more violent elements of the movement and discouraged others from engaging in destructive acts. However, a small number of activists still use tactics of harassment, intimidation, and vandalism against some research scientists and veterinarians involved in working with laboratory animals.

Many of the research advocacy groups say a greater threat to medical progress is proposed state and federal legislation, often authored by animal rights lobbyists, that has little to do with animal welfare but rather seeks to restrict or raise the cost of animal-based research. An example is The Great Ape Protection and Cost Savings Act legislation, which continues to draw strong support in Congress. As of April 29, 2012, the House version (HR 1513) has 165 sponsors and the Senate version (S 810) has 14 sponsors.  

These bills would virtually eliminate chimpanzee research, which includes work in vaccines, hepatitis, HIV/AIDS, malaria and some types of cancers. Although we use only a comparatively small number of chimpanzees in animal research, I am told that the work often provides essential information that cannot be obtained in any other way.

While the legislation is purportedly about animal welfare, these bills are really designed to limit the biomedical research that we all support and which, we hope, results in FDA-approved medical products.

For me, the choice is easy. I want a product or procedure tested in animals before it is given to me or my loved ones. I believe in protecting animals, but human rights come first.

The importance of animal research needs to be a core value for FDA. Those who benefit from animal research (including patients and industry) need to provide the manpower and financial resources to counter the animal rights movement in America and its threat to medical progress for humans.


Bold Discussions: Possible New Approval Pathways for Breakthrough Drugs

Monday, November 14th, 2011

For discussion purposes, let’s assume that there is a broad consensus that patients would benefit if new drugs and devices could get to the US market sooner. Current market barriers can be fearsome: long timeframes, high cost and regulatory uncertainty.  How can we fix this problem? What costs and risks are involved in getting products to patients faster?

These are old questions, renewed this year by the Biotechnology Industry Organization’s (BIO) proposal to create a “progressive approval” process. This is controversial, but also worthy of widespread discussion. FDA Matters finds itself interested and open-minded about ways to permit earlier market-access if patients will benefit and the safety risk minimized.

Currently, FDA has several mechanisms for helping drugs move faster through the approval process, but only one might be said to be an alternative pathway. FDA describes it as follows:

ACCELERATED APPROVAL:  [I]n 1992 FDA instituted the Accelerated Approval regulation, allowing earlier approval of drugs to treat serious diseases, and that fill an unmet medical need based on a surrogate endpoint….For example…FDA might now approve a drug based on evidence that the drug shrinks tumors because tumor shrinkage is considered reasonably likely to predict a real clinical benefit [e.g. prolonged survival].

Since creation of the program, FDA has granted an average of about four accelerated approvals to drugs each year, sometimes for more than one clinical indication. More than half of these indications have been shown subsequently to have clinical benefit and FDA has converted the approval from accelerated to regular. Others accelerated approval drugs are still being studied and a few have been withdrawn.  

FDA has itself shown interest in moving beyond accelerated approval. Early this fall, FDA released a report, Driving Biomedical Innovation: Initiatives to Improve Products for Patients. In a section entitled “Expedited Drug Development Pathway,” the agency observes:

Sometimes during the development of a new drug to treat a serious or life-threatening disease that has few therapeutic options, the new treatment performs much better than standard-of-care in the early trials. While there is general agreement that such a drug should be developed quickly, there is not a common understanding of how to appropriately speed up development while simultaneously gathering adequate evidence about the performance of the product.

FDA envisions a series of meeting with stakeholders to develop this concept and answer a number of difficult questions about the nature of a new pathway and how it could be implemented.

Consistent with this, BIO had already been talking about transforming the FDA approval process by permitting a “progressive approval” and market access for innovative products that:

  • treat an unmet medical need,
  • significantly advance the standard of care, or
  • are highly targeted therapies for distinct sub-populations.

The November 11, 2011 BioCentury reported that Senator Kay Hagan (D-NC) will be circulating draft legislation to create two new FDA approval pathways, presumably beginning the process of providing details for BIO’s concept. Here are the new approaches:

  • Progressive approval would require data "reasonably likely" to predict clinical benefit, the standard currently used for accelerated approval. Unlike accelerated approval, drugs could receive progressive approval without data from a surrogate endpoint.
  • Exceptional approval could be granted when the data necessary to satisfy the standard for approval "cannot ethically, feasibly or practicably be generated."

Much more needs to be said about how these would be implemented. In particular, it is not uncommon for a drug to produce solid safety data and/or startlingly good efficacy data in phase 2 (preliminary human trials), then fail in phase 3 (clinical trials to support approval).

Even after we see the bill text, the BIO/Hagan effort must still be seen as a conversation starter. But it is a discussion well worth having.


Of possible interest to readers:

While the accelerated approval approach has been successful, it also raises a host of methodological questions. One of the best critiques is Professor Tom Fleming’s Surrogate Endpoints And FDA’s Accelerated Approval Process (Health Affairs, 2005).


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