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Archive for the ‘Food Issues’ Category

A Salmon on Every Plate/The Hard Road of Innovation

Thursday, March 14th, 2013


Chicken was once an expensive delicacy. In 1928, America’s quest for a better diet and a better standard of living was summarized by the campaign promise of “a chicken in every pot.” Today, chicken is a ubiquitous, low-cost source of protein, which we largely take for granted. Despite depletion of ocean-based stocks, fish hold similar potential.

To begin this transformation, FDA must approve a scientifically-based innovative product—a faster growing genetically-engineered (GE) Atlantic salmon. When FDA Matters wrote about this subject 18 months ago, I believed the agency was near to approval of this first-ever food product from a GE animal. It is still not resolved and there are implications for all innovations that require FDA approval.

Final comments on the “environmental assessment” of GE salmon are due to FDA in April. Hopefully, this is the final procedural step before a decision. Approval could come mid-year or may take months or may not happen at all. The agency is still dealing with the political fall-out of questionable safety claims from environmental groups…and politicians and companies trying to protect the market for Pacific salmon.

The health benefits of fish are well-known. They are also a valuable source of dietary protein. However, our oceans are over-fished and aquaculture is now the source of almost 50% of the fish consumed worldwide. Expanding the availability of fish products meets a growing demand and is an important component of improved nutrition for Americans.

The proposal before FDA is for a genetically-engineered salmon that is biologically and chemically identical to the Atlantic salmon that is served in restaurants and at our own tables. The only difference is the inclusion of a Chinook salmon gene that provides the potential to grow Atlantic salmon to market size in about half the time.

Opponents have labeled the product as “Franken-fish.” It’s a catchy slogan that tries to devalue over a decade of scientific research and undercut many years of FDA review. Ultimately, the appeal is to emotion—that something dramatically new and different must automatically be dangerous. At some point, scientific review and product safeguards should be sufficient for FDA to make a decision that is based on facts and not fears.

Decisions about new and different products are hard for FDA, as I wrote in a column entitled: “FDA and Things that Might Go Bump in the Night.”  Among other things, I reminded readers that in the late 1970’s and early 1980’s, biotechnology was subject to the same types of concerns and evaluation as FDA is currently giving nanotechnology, GE food and synthetic biology. While there are risks to saying “yes” to innovation, there are also potentially large consequences to saying “no.” Imagine today’s world without biotechnology.

Approval of genetically-engineered animals will always require serious consideration of safety, environmental and ethical issues.  In this case, no one questions the legitimate demands for plentiful, high quality supplies of salmon. Further, the sponsor has agreed upon multiple redundant safeguards. For example, the GE salmon will be sterile females and grown in inland fisheries without access to either wild or farmed salmon stocks.

And yet, the years have piled up, waiting for FDA to be ready to say “yes” or “no” to GE salmon. This isn’t intended as a complaint about FDA…it’s really more of a reminder for the rest of us that a pro-innovation culture at FDA requires hard work from stakeholders.

Scientifically-based, well developed applications are a must. Those of us who support innovation must also make common cause. This is both policy-driven (e.g. by supporting development of regulatory science) and procedural (e.g. not complaining too loudly when FDA takes a somewhat longer deliberative path than we might like).

Further, brave thoughtful decisions by FDA are easier if they are met by public and stakeholder support. GE salmon may be a food, but FDA’s decision affects the environment in which drug, vaccine, and device innovation are also being judged.

Thus, the current fight is not just about “a salmon on every plate.” It is also about whether FDA has the resources and support to sort through the many “alternative futures” represented by the products submitted for its approval.


More information about salmon, aquaculture, regulation of genetically-engineered foods and the current controversy can be found at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/VeterinaryMedicineAdvisoryCommittee/ucm222635.htm and http://www.aquabounty.com/PressRoom/#l7

A final note: I almost never write about or even mention individual products because FDA Matters’ aim is to analyze and comment on policy, regulation, and FDA trends.

This column is an exception because I believe that FDA’s consideration of GE salmon is an important part of understanding the agency’s role in innovation and how such decisions can become far more difficult that they should be. I have no clients or financial interests in development of GE food products.  On the other hand, a salmon dinner is a favorite.

Adulterated Foods/Counterfeit Drugs: Punishment Should Fit the Crime

Thursday, November 29th, 2012

We should all be grateful for the considerable protection we receive from FDA against unsafe food, drugs, devices and other products. This is FDA Matters’ belated but heartfelt Thanksgiving message. Thank you, FDA.

What FDA cannot do alone—and for which we as a society need to step in—is to change the laissez-faire attitude, laws and enforcement affecting intentional contamination and counterfeiting of FDA-regulated products. When Americans die from intentionally tainted milk, counterfeit products or negligently compounded drugs, we need to recognize this as murder. Let’s step treating it as if it were white-collar crime.

Penalties for adulteration of food and brewed products date back as far as the Code of Hammurabi, nearly 4,000 years ago. While unintentional contamination is always a source of potential, even fatal, problems, this is distinct from the widespread and long history of intentional and fraudulent sales of foods as healthful and pure. While not as prominently featured, there is a parallel history of unsafe drugs, devices, cosmetics and other products–now regulated by the FDA and which form a fundamental part of the agency’s history and ongoing mission.  

In recent years, China has gained some notoriety for its particularly strong stance against individuals who intentionally and willfully violated its food and drug laws for their own personal profit. In 2009, two men were executed in China for tainting milk powder with melamine, an industrial chemical. The adulterated milk killed at least six children and reportedly sickened more than 300,000. Those executed were the dairy farmer and milk salesman who were at the center of the scheme. Two years before that, China executed Zheng Xiaoyu, the head of China’s FDA for accepting bribes to allow untested drugs to be approved for marketing.

Leaving aside that many capital crimes in China would not be so here, the offenses involved in the two Chinese examples would certainly appear to merit long jail sentences in the U.S. However, that just doesn’t seem to be the case in the United States—at least looking at the history of food and drug problems in the US over the last 10 years. The massive growth in counterfeit drugs and devices (by definition, intentional crimes of mislabeling and adulteration) only reconfirms the appearance that we are not acting strongly enough to punish people and companies who are intentionally putting Americans at risk.

Why the difference in attitudes? I believe the Chinese would argue that the farmer and the salesman were as responsible as if they had held a gun to the head of six children and murdered them. In the US, the consequence of murdering children in this fashion would likely be execution or life imprisonment. What’s missing in the U.S. (or so it seems) is the understanding that killing people with intentionally tainted food and drugs IS killing them with the same malice as using a gun.

What is different (and of concern) is the concept of a heinous crime. The worst possible interpretation is these were commercially-motivated executions, designed to show the world that the Chinese are tough and their products getting safer. Even still, six murders were involved in the milk tainting case and one purpose of punishment is deterrence. Whatever we may think about the effectiveness of capital punishment, one hopes that those considering crimes involving fake foods and drugs will think twice (and twice again?) before proceeding in China.

We haven’t sent the same strong message to would-be malefactors in the U.S. and those exporting to the U.S.

Given this, we should be thankful to FDA for every day we don’t encounter willfully adulterated foods and intentionally fake and dangerous drugs and devices. And we should be rethinking whether our own standards are in dire need of upgrading. These are not situations in which probation and forgiveness are the right approaches.


PS: To anticipate and deflect some outraged feedback, this column is specifically about gross negligence where the person knew–or should have known– in advance that someone would be likely to die. Such events occur more often than any of us want to acknowledge.

2012 Mid-Year Report on FDA: Opportunities, Threats and Accomplishments

Monday, July 9th, 2012


So much is going on at FDA right now, that it is difficult to pick just one topic for this week’s FDA Matters. Instead, we are going to take a quick tour of some “hot spots” at FDA and how they might affect the agency over the remainder of the year and beyond.

Please read on…there is something for everyone in the topics covered.

The “Lost” FSMA Regulations. At the very end of 2010, Congress passed the Food Safety Modernization Act (FSMA). The law was intended to fundamentally re-set the term under which FDA acts to assure a safe food supply. It focuses on preventing problems, rather than fixing or limiting them afterward. FSMA provides the agency with new authorities and additional resources consistent with FDA’s role of overseeing a global food supply.

The first provisions of FSMA went into effect in January 2012 and additional requirements become effective this month. To guide implementation of these requirements, FDA has produced four draft regulations. None have been published; all are stuck in the review process at OMB.

The mystery of the “lost” FSMA regulations prompted two reporters to call me this past week and ask: is OMB holding back these (and other) regulations until after the election, presumably for political reasons. I couldn’t see an electoral connection, plus the first of the proposed regulations was submitted to OMB in December 2011, a very long time before the election.

The “lost” FSMA draft regulations are worrisome by themselves, but especially with so much else going on at FDA that may require OMB review.  

FDA’s Drug Safety Monitoring Program Hits Target, Will Expand. We don’t read often enough about the successes that come from cooperation and hard-work at FDA. In the 2007 user fee reauthorization legislation, Congress directed FDA to construct a nationwide electronic post-market safety monitoring system that would allow FDA to examine tens of millions of patient records to discover or refute possible safety concerns about FDA-approved products.

In a recent edition of FDA Voice, the FDA’s own blog site, the agency reported that the monitoring system, called “Sentinel,” now has access to the de-identified medical and/or insurance records of about 126 million Americans, collected through 17 data sources (e.g. VA, Kaiser). Sentinel is definitely still a “work in progress” on a number of levels, but it will be of increasing value as medical products become even more complex and even more integral to medical care.  

Funding Ups and Downs. Despite Congressional reauthorization of the prescription drug and medical device user fee programs, the budget authority (BA) (taxpayer-funded) portion of FDA’s budget is still the bulk of the dollars. The Senate has included a small increase in BA funding for FDA for FY 13; the House has proposed a small decrease.

Of compelling concern is the strong potential that FDA (along with all federal discretionary funding programs) will be hit with a 7% to 10% “sequestration”—an across-the-board cut–on January 2, 2013. This would reduce the agency’s budget  by between $175 million and $250 million in FY 13. This is FDA’s “contribution” to saving the federal budget more than $1 trillion over the next 10 years. 

If sequestration occurs, FDA will try to avoid lay-offs by shifting more employees from taxpayer funding to user fees. In that case, increases in user fee income will be backfilling the BA cuts, rather than contributing to real agency growth. Yet, FDA will be obligated to undertake the user fee-driven activities and meet the law’s performance measures as if the new user fee money was paying for additional staff.

User Fee Reauthorization Will Drive, Not Disrupt, the Agency Agenda. Five years ago, the user fee reauthorization (PDUFA 4) didn’t become law until late September, a few days before fiscal year 2008. The combination of immediate deadlines, delays in collecting user fees, and insufficient trained personnel set off a series of problems that took three years to fully overcome.

This time, Congress finished the reauthorization in late June and FDA has been planning the law’s smooth implementation for months. Instead of panic, CDER in particular, seems to be feeling good about the path forward and the many changes called for in PDUFA 5. 

Dr. Janet Woodcock, head of CDER, has listed her priorities as, among other things: timely transition to new user fee requirements (including start-up of new generic drug and biosimilars user fees); dealing with drug shortages, moving forward on data standards and new IT support systems, and advancing regulatory science.

Results are still what matters and there are always critics….but a sense of optimism at CDER is always welcome.


FDA, Me and Maybe the Mafia—A True Story

Monday, May 14th, 2012


In honor of FDA Matters’ third anniversary, I am sharing a personal story. It reflects FDA’s history as a struggle of competing interests—where sometimes reasonable people disagree, often vehemently, while at other times it is obvious that indifference or greed are the driving forces.

Both are a fact of everyday life at FDA and in the FDA-regulated world. Here is my own little story and I still can’t say for sure whether it involved reasonable people or dark forces.

My first recollection of the artificial sweetener, saccharin (distributed under the brand name “Sweet‘N Low”) was a 1977 visit to the House health subcommittee’s staff office. It was overflowing with boxes that contained letters begging Congress to prevent FDA from removing saccharine from the marketplace.

Later that year, Congress passed the Saccharin Study and Labeling Act. This prevented FDA from acting for 2 years and required a warning label on the packaging that said “This product contains saccharin, which has been determined to cause cancer in laboratory animals.”  The law was extended seven times until the issue disappeared in the 1990’s. The labeling requirement was repealed in 2000.*

After I became a Senate staffer in 1979, I was responsible for shepherding through the 1981 and 1983 extension and probably the 1985 extension, which occurred just before I left the Hill.

These were simple bills—short, totally clear in their meaning, and noncontroversial. The only issue (and not a very large one) was that one committee member refused to consent to its unanimous adoption—which slowed the bill at committee and when it got to the Senate floor. I can’t remember any Senator expressing actual concerns about these bills. 

Sometime around 1983, I started receiving regular visits and calls from Joseph Asaro, Vice President of Governmental Affairs for Cumberland Packing, makers of Sweet ‘N Low and a business located near the Brooklyn docks. I remember him as pleasant, but terribly anxious that nothing stand in the way of extending the moratorium every two years.

It never seemed to sink in to him that passage of the extension was routine business of the most ordinary sort. The more I reassured him (so he wouldn’t call as often), the more solicitous he became. Then one afternoon, I received a call from my family—who lived on Long Island, maybe 20 miles from Cumberland Packing’s headquarters. That morning, a delivery truck had arrived with multiple cartons of Cumberland products, including several 1000-packet boxes of Sweet’N Low, and the message: let us know when you run out.**

Although it was probably meant as a generous gift (and didn’t violate any Senate rules), I was quite upset. I had mentioned to Mr. Asaro that I had grown up on Long Island, but never my family’s names or where they lived (and 30 years ago, pre-Internet, identifying people’s connections was a difficult task without such information.)

In my imagination (or maybe in actuality), I felt that I was being reminded that he knew where my family lived….and I needed to pay more attention to the legislation. Despite all efforts on my part to banish such thoughts, I admit I considered the possibility that Cumberland was involved in some way in organized crime and I had been threatened.

In 2006, an unauthorized history of Cumberland Packing was published and I found that my concern was well-founded, although perhaps not true. According to the book, a 1994 Washington Post article stated that Joseph Asaro had been “identified as an associate of the Bonanno crime family in a prosecution memo….” Subsequently, a New York Times article reported that federal prosecutors and Mr. Asaro’s attorneys denied there was any connection.***  

Threats, even implicit ones, are inherently scary—even if the goal was to make me do something that I was planning to do anyway and for which there was strong Congressional and public policy support. Even at the time, I didn’t really think my family was in “harm’s way.” Still, it made me anxious and self-conscious about what was otherwise a routine task.

Other than being an interesting tale, I hope it is a small reminder to every reader that there are employees of the FDA—sometimes inspectors, but more often in the Office of Criminal Investigations and their colleagues at the FBI and Customs—who do put themselves in “harm’s way” in order to protect us. These threats are invisible to most of us, but are no less real because we don’t see them.

We should salute and remember those who take these risks on our behalf, so that we can enjoy the benefits of a safe food and drug supply.


* Subsequent studies never strengthened the connection to cancer in humans. In 1985, FDA supported extension of the moratorium and in 1991 withdrew the proposal to ban saccharine from food. It was delisted as a possible carcinogen in 1997 and the warning label requirement was repealed in 2000. http://www.icarus-japan.com/pdf/Saccharin_English.pdf

** Thanks to my mother and sister for their memories of that day, still quite vivid nearly 30 years later.

*** Sweet and Low: A Family Story by Rich Cohen. Published by Farrar, Straus and Giroux, 2006. The material on the possible linkage with organized crime is a footnote on page 144.

The FDA Matters “Guide to the User Fee Reauthorization Process”

Monday, March 19th, 2012

The prescription drug (PDUFA) and medical device (MDUFA) user fee programs, which run for 5 years, must be renewed by September 30 of this year (last day of the current fiscal year).  House committee staff has just released a 205-page first draft of reauthorization legislation. The Senate has starting releasing drafts on specific issues and has a March 29 hearing scheduled.

Because the PDUFA and MDUFA provisions are pre-negotiated by FDA with industry and patient groups, they are likely to change little. Congress’ focus will be on the backlog of FDA-related legislative proposals that have accumulated while awaiting a “must pass” FDA legislative vehicle. This is FDA Matters’ guide to the process and likely amendments.

To understand the unfolding process for user fee reauthorization in 2012, it is useful to think in terms of four levels of legislative proposals that Congress will consider.

Level One: Renewal of Existing Legislation and Uncontroversial New User Fees. In addition to PDUFA and MDUFA, there are two other programs on the same 5-year reauthorization cycle. The Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) are certain to be reauthorized and may be made permanent.

In this same level are two proposed new user fee programs: the Generic Drug User Fee Act (GDUFA) and the Biosimilars User Fee Act (BSUFA).  These have gone through an abbreviated version of the PDUFA and MDUFA negotiation process, meaning that the FDA proposals reflect input from industry, patient groups and other stakeholders.

Level Two:  Areas of Strong Consensus to Act; Specific Provisions Not Yet Agreed Upon. Despite Congress’ deep partisan differences, there are several areas in which both political parties appear to be in general agreement about adding programs or strengthening authorities at FDA. 

In this level are proposals dealing with drug shortages, incentives for antibiotic drug development, import safety, a core set of medical device process reforms, and some adjustment in the FDA “accelerated approval” pathway for drug and biological products. There is also consensus for dealing with drug supply chain integrity (e.g. anti-counterfeiting), which may be advanced as a separate bill this spring or be folded into the reauthorization legislation.

For the most part, the consensus to act in these areas does not yet include specific legislative language that has bi-partisan support in both the House and Senate. So negotiations are certain, may even be testy at times…but final agreements are near-certain.

Level Three: Areas of Disagreement Where Compromises Are Possible. Ultimately, committee leadership will have to deal with FDA amendments where there are sharp disagreements or a lack of consensus that action is needed.

The two most prominent such issues are the extent of medical device reform and the amount of change needed or appropriate for the drug approval process. In both areas, there is a more limited, core set of proposals that are in level 2.

As with all such areas of disagreement, compromises may ultimately develop. Unlike the issues in level two, these proposals start with disagreements that may lead to negotiations, but with no assurance of inclusion in final legislation.

Beyond those mentioned, the list of issues and amendments that might be offered (and controversial) is limitless, but it is possible that we will see Congress again debating drug re-importation, re-opening the 2010 biosimilars legislation or even considering amendments to Hatch-Waxman. There may also be food safety amendments.

Level Four: Proposals to Dramatically Re-shape FDA and Likely to Be Rejected. A small number of Members of Congress think FDA’s role should be significantly smaller. They see radical surgery on the agency mission as the necessary response to the restraints they feel the agency imposes on industry and on patient access to new therapies.

The possibility exists for amendments that might substantially reduce the agency’s jurisdiction over medical devices or significantly roll back the 1962 Kefauver Amendments that require drugs to demonstrate efficacy (not just safety) before entering the market. There is no reason to think there is a majority in either the Senate or the House for such radical reform or substantial reduction in FDA’s mission. Nonetheless, such proposals may be offered.

Conclusion.  In enacting a timely reauthorization of the user fee programs, Congress will need to consider a range of legislative proposals. As these are offered and discussed, this FDA Matters analysis provides a guide to understanding Congressional activities.


This blog column is a much-shortened version of an article I wrote that appears in the March 2012 issue of Scrip Regulatory Affairs, entitled “Reauthorizing US FDA User Fees: A Slow-Moving Train Wreck?” Readers interested in a copy of the longer article should contact me at sgrossman@fdamatters.com.

Quality and Safety “Just Don’t Get No Respect”

Monday, February 27th, 2012

In every successful company, the glittery careers and the recognizable names belong to people who develop new products that meet consumer and patient needs. Innovation in new products (and careful husbanding of intellectual property and market share) is what brings in the revenue and determines corporate success.

By comparison, there is little recognition and often sparse resources for the people devoted to making sure those products (new and old) are safe and of high-quality. The best product ever developed is worthless, and possibly harmful, if standards are not maintained and manufacture and supply carefully monitored. The stakes are so much higher for FDA-regulated products.

FDA Matters has previously analyzed how “safe” has many meanings. My focus in this column is the safety of processing, manufacturing and distribution of FDA-regulated products. Is the milk we drink safe from adulteration (either intentional or unintentional)? Are medical devices manufactured with sufficient precision?

Does every batch of a biological product deliver consistently safe results? Are sterile conditions maintained when drugs are manufactured? The list of questions is endless because there are a limitless number of ways in which products can be unsafe.   

When FDA Matters has covered quality and safety issues in the past, we have almost always mentioned our suspicion that CEO’s and others in the corporate suites are not concerned enough.  It is reflected in the recalls, the extended plant closings, the drug shortages caused by suppliers unable to produce quality products, and the number of inspection reports (483’s) that contain substantive and non-trivial problems.

We assume that CEO’s want to produce safe and high-quality products. After all, it is bad for business to do otherwise. Yet, we suspect too many corporate executives are overly focused on new product development, marketing and sales and worry too little about the quality and safety of what they already produce.

Close accountability and adequate resources are the necessary ingredients of quality and safety. Too often, the opposite appears to be the case in corporations: inattention, underfunding, delegation to distant subordinates and overreliance on vendor guarantees.

FDA won’t back down from its vigilance. Commissioner Hamburg’s reorganization of the agency was, in part, to consolidate authority over quality and safety and put it in the hands of an immediate subordinate. Dr. Hamburg did what I hope every corporation would do—insist on closer accountability to the CEO with regard to production of safe, high-quality products. This becomes more urgent as the scope of this responsibility becomes global, more complex and harder to manage.

The foundation of the Food, Drug and Cosmetic Act was enacted so long ago and generally has been so successful, it is easy to forget that FDA was created and built for the specific purpose of protecting consumers and the public health from dangerous products. It is the FDA that cleaned up the market in tonics and patent medicines, ensured there were serious consequences for companies that adulterated food and drug products, and created a basic public trust in the foods, medicines, devices and cosmetics that we use daily.

Quality and safety of FDA-regulated products is also on the mind of Congress. A little more than a year ago, it passed the Food Safety Modernization Act, a thorough overhaul of our nation’s approach to assuring Americans have a safe food supply in a global environment.

This year, as part of the reauthorization of user fee legislation, Congress is probably going to adopt additional provisions addressing the safety of drug imports, the need to eliminate drug shortages, and the necessity of supply chain integrity. Also in that legislation will be the Generic Drug User Fee Act, which funds a significant expansion of FDA’s efforts to inspect generic drug facilities.

Industry, Congress and FDA need to continue their focus on innovation and new products. This is the path that will bring better lives to Americans and allow our nation to better compete in the global economy.

While doing so, they must also pay sufficient attention and provide adequate resources to the fundamental, but less glamorous, job of assuring the processing, manufacturing and distribution of safe, high-quality FDA-regulated products. We must insist on this standard in the American marketplace.


FDA Matters Mailbag: Hatch-Waxman, Biosimilars, User Fees and More

Sunday, February 19th, 2012


Over the last month, FDA Matters has covered a wide-range of FDA-related topics: the agency, industry, and Congress, as well as medical innovation, user fee reauthorization legislation, food safety and post-market surveillance. The response has been great: FDA Matters has many new readers and I received a number of interesting questions.


Today’s column touches on biosimilars, Hatch-Waxman, user fees and FDA management. Keep the questions coming!


Is FDA becoming too large for food, drugs and medical devices to be in the same agency?


Last summer, the Commissioner re-organized her office to better manage the growing responsibilities and complexity of the agency’s work. She divided the agency’s work into four parts:

  • food and veterinary medicine
  • medical products
  • global outreach and inspection, and
  • administrative matters overseen by a chief operating officer 

The key is that each of these individuals has line authority to manage their part of the agency, rather than being a staff advisor to the Commissioner.  


With specific regard to foods, there are proposals to move the Center for Food Safety and Applied Nutrition (CFSAN) out of FDA. I believe the Center is best served by being part of the public health focus of FDA.


How do Europe and the US compare in their approaches to biosimilars?


Both the European Medicines Agency (EMA) and FDA are acting cautiously, but in different ways. Europe has focused on a limited number of reference products, building their knowledge and experience one therapeutic category at a time.


In contrast, FDA has already met with sponsors to discuss 11 reference products, presumably covering a number of therapeutic categories. Given FDA’s broader approach, proceeding case-by-case with strong scientific requirements is the best way for FDA to acquire knowledge and experience.


A different comparison was also posed to me: an eager EMA versus a reluctant FDA.  In less than two years, FDA has produced multiple policy speeches and articles, three guidances, held multiple sponsor meetings and allowed several sponsors to begin work. I assure you: FDA is fully committed to biosimilars!


As an aside, anyone familiar with the lack of FDA guidance on product-related social media can tell you how FDA behaves when it is reluctant to act. It looks quite different.


If the user fee reauthorization legislation has the potential to be a vehicle for any FDA-related provision, might Congress re-open Hatch-Waxman?


I shudder at the possibility, but can’t rule it out. I asked a knowledgeable friend what he would propose if given the chance to amend Hatch-Waxman. His reply: get FDA out of the patent enforcement business, yet assure generics the equivalent of the 180-day exclusivity if they win in court.


Since this would benefit generics, a trade-off for innovators could be longer exclusivity for new molecular entity (NME) compounds that lack intellectual property (IP) protection. It might be the same 10 years they receive in the EU or the 12 years for biologics. Similarly, a stronger incentive than 5 to 7 years is needed to generate interest in 505 (b)(2) drug applications in the absence of IP protection. 


I’m not suggesting this, but thought it interesting enough to give his ideas some visibility.


Companies are telling me: it’s hard to justify investing in the US biosimilars market because of the resources it will require. Why is FDA Matters so optimistic?


I hear some of this, too. Certainly, the first generation of biosimilar applicants (and there seem to be plenty of them) are going to pay more–and live with more uncertainty for a longer period of time– than those that start 5 years from now when costs have dropped.


However, those who are successful are going to be rewarded, as I explored more fully in How Biosimilars Will Transform the Marketplace. Put simply:


  • If the first biosimilar approvals from FDA are for solid products with good data and fair pricing, then hospital purchasing groups, pharmaceutical benefit managers and formulary committees are going to move significant market share away from the reference products.

  • In multi-product categories, the market shift may be even greater because there will be therapeutic substitution, not just substitution of the biosimilar for the reference drug.

 I look forward to more reader questions!



FDA and Industry Relations: A Mix of Frustration and Respect

Monday, February 6th, 2012

There is no one answer to the question: what is the state of FDA-industry relations? FDA Matters hears some say: FDA does what industry asks it to do, the agency is a puppet. Others say that FDA is obstinately blocking industries’ path to new, better and innovative products. Yet others say FDA is misguided at points, but well-intentioned and most often right.

The state of FDA-industry relations turns out to be particularly important in 2012. As part of the user fee reauthorization legislation, Congress will be faced with non-user fee amendments affecting every aspect of FDA’s mission, programs and decisions. Industry will be advocating for some; trying to block others, based in part on its relationship with FDA.   

Looking at the situation superficially:

  • FDA and the biopharmaceutical industry would appear to be on good terms. Negotiating the language and terms of the Prescription Drug User Fee Act (PDUFA) reauthorization went relatively smoothly and the agreement addresses a number of industry concerns
  • FDA and the medical device industry would appear to be on shaky terms, at best. The negotiations on the reauthorization of the Medical Devices User Fee Act (MDUFA) have been extended and contentious. Only in the last few days has there been an agreement in principle on a proposal for MDUFA reauthorization.    
  • FDA and the food industry would appear to be on excellent terms. The Food Safety Modernization Act (FSMA) passed in late December 2010. Consumers and most of industry supported the legislation and there has been cooperation by industry on implementation.

In each case, things are more complicated beneath the surface.

Drugs and biologics. Industry is broadly supporting FDA’s proposal for reauthorization of PDUFA, having helped negotiate a number of provisions that will improve the drug development, review and approval model used by the agency. When it comes to the additional amendments to be considered by Congress, the unanimity is already breaking down.  

For example, during 2011, The Biotechnology Industry Association (BIO) released a series of proposals for improving FDA. FDA Matters praised BIO for putting forth a bold agenda, while seeing its centerpiece proposal, a new “progressive approval” pathway, as only a starting point for discussion. In a tacit acknowledgement of FDA opposition (not publicly expressed by FDA) and industry dissension, BIO has recently started advocating instead for changes in the existing FDA accelerated approval process.

Medical devices. The difficult relationship between FDA and the medical device industry is long-standing. Both sides have been able to talk, often quite productively, but ultimately the device industry returns to its default position that the FDA needs to be held accountable for its inconsistent guidance and lack of timeliness in its reviews.

The just-released MDUFA reauthorization agreement in principle (in the form of FDA meeting notes) looks like it can bridge the gap that has divided FDA and the medical device industry…or at least that’s my interpretation of industry and FDA press statements.  However, Congress may yet amend the proposal if industry proves divided  in its support.  As to non-user fee amendments in the medical device area, it is to be assumed (given the history) that they will tend toward contentious, with FDA on the defensive.

Food.  Public discussion of the user fee reauthorization legislation has focused on drug and medical device issues, but nothing prevents food from becoming part of the mix. Any issues or amendments left over from the FSMA debate are fair game, as would anything that went into the final legislation despite objection from FDA or some interest group.  

One of the most prominent “leftover” issues is the extent of fees collected from the food industry to support FDA activities (merely calling them “user fees” is enough to generate a heated discussion). While the issue may come up regardless, there is a strong chance that the President’s budget request will contain legislative proposals for new food fees, starting in FY 13.

Conclusion. As the user fee reauthorization legislation moves forward, it may be too much to ask for fair debate, FDA-industry harmony, and quick resolution of outstanding issues. Time is of the essence—the real deadline is closer to July 1 than September 30

It would also be wonderful if all parties (including Congress and industry) would stick with the issues and refrain from bashing FDA. 


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.


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