FDA and Its Regulated Industries: A Cornerstone of America's Economic Future

On March 7, the Alliance for a Stronger FDA released a white paper on the far-reaching and positive economic impact of a strong FDA and the industries it oversees.  The report is intended to provide interested parties, including Congress and Executive Branch policymakers, with information on FDA’s role in economic growth. A number of groups--consumers, patient advocates and industry--provided comments to the Alliance on the impact of FDA on the American economy.

“Most policymakers have heard that FDA-regulated industries account for nearly 25% of U.S consumer spending,” said Nancy Bradish Myers, President of the Alliance for a Stronger FDA and President of Catalyst Healthcare Consulting. “However, many have not thought about the major negative economic impact if FDA, the primary regulator of those industries–which employ millions and are net exporters of U.S. products—is not adequately funded by federal dollars.” 

She added: “FDA is a regulatory agency that can help the economy expand. It is one of the reasons that industry, patients and consumers support a strong, appropriately funded FDA that has the resources to assure that our foods are safe and our biopharmaceutical, medical devices and vaccines are safe and effective.”

The Alliance for a Stronger FDA white paper, entitled “The U.S. Food and Drug Administration: A Cornerstone of America’s Economic Future” provides useful information about medical products, the American food supply, and FDA’s role in fighting bio- and agro-terrorism. It also describes some of the advantages of maintaining U.S. leadership role in the global economy and the potential costs to the domestic economy and U.S. exports if FDA falls behind.  

“Food contributes nearly $1.2 trillion to our economy, or 8% of the U.S. gross domestic product. Ensuring the safety of our food supply is as essential as providing for our national defense,” said Caroline Smith DeWaal, an Alliance Board Member and Director of Food Safety at the Center for Science in the Public Interest. “Protecting our food supply is a major part of FDA’s mission, and both the food industry and consumers benefit from a strong FDA and a growing economy.”

“No agency with a critical role like FDA’s should be asked to do more, with less,” said Margaret Anderson, Vice President of the Alliance and Executive Director of FasterCures.  “If we are to advance medical progress and improve patients’ lives--which will significantly bolster the US economy--we need to start making the FDA a national priority.”  

The Alliance’s 180 members--comprised of consumer, patient, professional and research groups, companies, trade associations, and individuals--represent millions of Americans who support increased appropriated funding for FDA.  More information about the Alliance can be found at www.StrengthenFDA.org.

The full report – The U.S. Food and Drug Administration: A Cornerstone of America’s Economic Future -- can be downloaded from the Alliance’s web site.

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WHAT OTHERS ARE SAYING ABOUT THE IMPACT

OF FDA ON THE AMERICAN ECONOMY

AdvaMed (Advanced Medical Technology Association)

“Everyday, America’s medical technology companies are developing life-saving, life-enhancing advancements in patient care. This progress doesn’t occur in a vacuum. It’s critical to patients, continued innovation and future economic growth that our regulatory processes support the next great leap forward in medical progress. That’s why we support a well-resourced FDA with well-trained reviewers who have appropriate scientific expertise.” Stephen J. Ubl, President and CEO

Alliance for Aging Research

“Over the next 30 years, there will be no greater challenge to the U.S. than dealing with the human and economic consequences of the graying of America.  To improve lives and bend the cost curve of billions of health care dollars, we will need investment and innovation from the medical products industries.  An effective working partnership with the FDA is essential.” Dan Perry, President & CEO

AstraZeneca

“AstraZeneca favors a well-funded and scientifically world-class FDA that has the resources it needs to bring safe, effective and innovative medicines to patients in the United States. Developing and making new medicines available not only helps improve peoples’ health, it helps grow the American economy.” Rich Fante, President, U.S. & CEO North America

Biotechnology Industry Organization (BIO)

“The promise of the life sciences – economic expansion, jobs, and new therapies for unmet medical needs – requires an adequately funded FDA and a strong, reliable regulatory environment.” James C. Greenwood, President & CEO

Center for Science in the Public Interest

“Food contributes nearly $1.2 trillion to our economy, or 8% of the U.S. gross domestic product. Ensuring the safety of our food supply is as essential as providing for our national defense. It is a major part of FDA’s mission. Both the food industry and consumers benefit from a strong FDA and a growing economy.” Caroline Smith DeWaal, Director of Food Safety

FasterCures/The Center for Accelerating Medical Solutions

“No agency with a critical role like FDA’s should be asked to do more, with less. If we are to advance medical progress and improve patients’ lives--which will significantly bolster the US economy--we need to start making the FDA a national priority.” Margaret Anderson, Executive Director

Friends of Cancer Research

“Innovation – in the form of new drugs, vaccines, and medical devices – has vastly improved the health of people around the world and has thus far been a pillar supporting the US economy.  Without further financial investment in the science at FDA, future innovation is put at severe risk.”   Dr. Ellen Sigal, Chair and Founder

Medtronic

"The growth of Medtronic and the medical device industry is truly an American success story. To write the next chapter, we need a business environment that fosters innovation, drives job creation and supports principled collaboration between industry, government and medical professionals.  A strong, fully-funded FDA is vital to creating a more predictable and consistent regulatory system, making it possible for patients to get faster access to novel medical technology." Bill Hawkins, Chairman and CEO

National Research Center for Women and Families

“As public health experts and advocates, we know that Americans depend on a strong FDA to ensure the safety and effectiveness of medical products made by companies that also produce jobs and grow our economy.” Diana Zuckerman, PhD,  President

National Organization for Rare Disorders

"There are innumerable diseases and conditions for which patients are awaiting new therapies. These can only come from viable and vibrant biopharmaceutical and medical devices industries whose investments grow America and move us closer to helping patients with unmet medical needs.” Peter Saltonstall, President

Pharmaceutical Research and Manufacturing Association (PhRMA)

"America’s biopharmaceutical research companies are among the most innovative, research-driven enterprises in the world. Combined, they employ around 650,000 high-skill, high-wage men and women; and, every direct job supports nearly 3.7 additional American jobs. Our industry invests tens of billions annually in research and development. But, without a strong, science-driven, appropriately funded FDA, patients wouldn’t realize any of the benefits of the life-saving and life-enhancing therapies that our companies produce." John J. Castellani, President and CEO.  

FDA Is Fighting on Two Fronts

FDA is still a 20th century agency. It lacks the databases, technologies and tools to do its work. It does not have the depth of manpower to be experts in all the increasingly complex sciences associated with medical products and foods. It lacks the confidence to consistently make decisions based on risk-benefit analysis, rather than leaning toward the highly restrictive Precautionary Principle.

FDA Matters can’t see any downside to the FDA gaining the technology, the manpower and the confidence to transform itself into the 21st century FDA that our nation needs. Yet, Commissioner Hamburg has to fight on two fronts to preserve her ability to make the necessary changes.

The new Congress has a different set of priorities than the previous two. Deficit cutting and government accountability are on everyone’s mind.

Under a House-passed bill that would fund the federal government in Fiscal Year (FY) 11, the FDA would be allotted $241 million below the level at which it was funded in FY 10. Were this to become law, the agency would need to cut new programs, abandon initiatives and probably lay off staff. To reach agreement with the House, the Senate will also have to cut the federal budget, although perhaps not the funds for FDA.

A 21st century FDA requires capacity to meet new challenges. This won’t occur if the FDA’s budget is being cut.

At the same time, Congress is increasing its oversight/investigative activities. Oversight of FDA needs to occur, but it comes at a price. Investigative hearings are a potent reminder to FDA that cautious, risk-adverse decisions are the ones Congress won’t question. Thus, FDA is reinforced in being a 20th Century agency, rather than encouraged to modernize and think more broadly about problem-solving in the 21st century.

Also, there is an ongoing shift from public funding of FDA to industry funding. User fees pay for very specific tasks. Over-reliance on them reduces the flexibility that FDA leadership needs to handle public health challenges, especially modernizing and strengthening the agency.

Prevailing with Congress won’t be easy and must be considered Commissioner Hamburg’s top priority. At the same time, she must deal with growing unhappiness among FDA-regulated medical product companies.

Based on some recent FDA decisions (e.g. on three weight-loss therapies), many in industry believe FDA is erecting an insurmountable wall of trial design and safety requirements, all intended to slow or deny approval for large-population drugs. Yet, the blockbuster drug (rather than personalized medicine) will remain the industry’s primary business model for at least the next 10 years. Further, Americans still need safe and effective drugs that can treat hundreds of thousands of patients.

Similarly, there have been a number of skirmishes about review standards for medical devices. FDA has moved slowly, listened hard and made compromises. However, with some justification, industry still fears that proposed new standards and procedures will be expensive and delay approval of safe and effective medical devices in the US. FDA also finds itself being compared to the European system, where medical devices are approved far more quickly.

Current industry unhappiness might not be such a challenge for the Commissioner, except for its likely impact on user fee negotiations, agency funding, Congressional oversight and the national debate over how to stem the flow of American jobs and capital to Europe and Asia.  

Ultimately, the FDA’s “fight” with Congress and “fight” with industry come down to one issue: the creation of a 21st century FDA.

It won’t happen if Congress doesn’t fund modernization, tears FDA apart with investigations or relies too heavily on user fees. It also won’t happen if industry—which is the natural advocate for a more modern FDA—can’t work with the FDA to synchronize public health and safety concerns…with efficient and effective ways to review and approve new therapies.

 Steven

FDA and Congress: FY 11 Deficit Reduction Could Cut Deep   February 13th, 2011

Based on budget-cutting actions in the House of Representatives, the FDA is now vulnerable to substantial cuts in its current-year programs. This column analyzes the House situation for FY 11, based on analysis I have done for the Alliance for a Stronger FDA, which is the leading voice for increased appropriations for FDA. Read the rest of this entry

Will the New Congress Be Good for FDA-Regulated Industries?     December 19th, 2010

FDA Matters is hearing that FDA-regulated industries will benefit from the 2010 election. It is assumed that a Republican-led House and more Republicans in the Senate will benefit drug, device and food companies. After all, aren’t Republicans more business-friendly and more concerned about perceived regulatory excess?

Those saying and thinking these things may be in for a rude awakening. Everybody—FDA, industry, patients and consumers—is going to have a rough time over the next two years. Industry will be heard more often, but not always have the winning position. Read the rest of this entry

FDA and Election 2010: Oversight and Investigations     November 13th, 2010

The return of a Republican majority in the House of Representatives means an increase in Congressional oversight and investigations. This mirrors 2006, when the Democrats took back Congress and immediately started investigating the Bush administration. Once again, the agency will find itself buffeted by political forces that are as concerned about “scoring points” as they are about improving government. FDA Matters thinks this will have a large impact on FDA, as well as the agency’s stakeholders.  Read the rest of this entry

The State of the FDA—January 2011

FDA's touches the lives of every American at least 6 to 10 times each day. The agency oversees 80% of the nation's food supply, all of human/animal medical products and cosmetics, and almost all radiation-emitting devices. Altogether, the agency is responsible for about 20% of all consumer dollars spent in the United States.

With the President set to deliver his State of the Union address to Congress in 10 days, it seemed a good time for FDA Matters to provide its view of the "State of the FDA." At the beginning of 2011, the agency is doing well, but has a lot of catching-up to do and faces a number of threats.

Strengths: FDA's most important strength is the dedication of the agency's staff and the leadership of Commissioner Hamburg's team. They have made great strides in advancing the public health mission of the FDA, aided by increasing appropriations and the momentum of a new presidency. The renewed emphasis on public health has become a core strength of the FDA.

The agency's commitment to science is another strength. Not every decision can be answered with science (e.g. policy on social media), but a substantial number can. The FDA is successfully building its scientific capabilities, although it is a work in progress. Similarly, the agency's new initiatives to establish an international presence represent a strong response to the challenges of globalization.

Weaknesses: While FDA has been doing better, it is still an organization with workplace issues. Within the agency, barriers still exist to sharing knowledge across offices and divisions. To the broader world, the whole agency seems insular. In particular, the FDA makes inadequate use of expertise that lies outside the agency, particularly in academia.

FDA's information technology (IT) systems are grossly inadequate for an agency with such large, far-flung responsibilities. Some major, badly needed databases aren't going to be available anytime soon, preventing the agency from making the best, most well-supported decisions.It also dooms staff to perform tedious work that could be done in seconds with better tools.

Opportunities: Within FDA, there is the potential for a 21st century regulatory and public health agency that could be the world's benchmark for decades. While such standing is a goal in itself, it is also true that the world-wide use of FDA standards opens up export markets and can contribute to our nation's economic growth.

To realize this opportunity, FDA needs to do a better job in explaining regulatory science to Congress, the media and the public. The tools and standards FDA uses every day are still largely anchored in the last century. Public investment in improving regulatory science is what will bring the agency into the new century.

Another opportunity for the agency is to break the secrecy of how decisions are made. Observers often wonder about the agency's rationale. Industry needs the benefit of understanding the agency's actions. Dr. Hamburg and other senior FDA leaders have taken an important step by publishing more articles in mainstream journals. The handling of internal dissent in FDA's ranks was accomplished deftly in last summer's Avandia decision. In doing so, honestly and forthrightly, FDA increased it credibility and was better able to defend its ultimate decision.

A very different type of opportunity is presented by FDA's ongoing consolidation of personnel at just two locations, White Oak and College Park. This provides the opportunity for a more cohesive workforce, as well as a more efficient one.

Threats: FDA's largest threat relates to its funding and the possibility of being dragged back by budget cutting. Several years of increases have greatly helped the agency, but it is not enough to offset decades of budgetary neglect or carry the agency forward without more money. The gap can widen quickly because FDA's responsibilities keep increasing: more complex science, globalization and two major new laws to implement, food safety and bio-similars.

Another looming threat comes from the ongoing negotiations for re-authorization of pharmaceutical and medical device user fees. FDA needs the funding, but not the likely hit on its public credibility. When Congress considers renewal legislation in 2012, the agency is likely to be caught in the crossfire between those who think FDA is too industry-friendly and those who think the agency impedes FDA-regulated industries in bringing new, sometimes life-saving products to market.

Compounding this threat, user fee re-authorization will probably be the only FDA legislation that must pass Congress over the next two years. Dozens of legislator are going to try to get their FDA-related concerns addressed in the legislation. No one knows how much damage the final legislation might do to FDA.

Steven

Will the New Congress Be Good for FDA-Regulated Industries?

THIS IS THE LAST OF MY 2010 COLUMNS ON FDA AND THE NEW INCOMING CONGRESS. LINKS ARE AT THE BOTTOM OF THIS PAGE.

FDA Matters is hearing that FDA-regulated industries will benefit from the 2010 election. It is assumed that a Republican-led House and more Republicans in the Senate will benefit drug, device and food companies. After all, aren't Republicans more business-friendly and more concerned about perceived regulatory excess?

Those saying and thinking these things may be in for a rude awakening. Even worse, they may find themselves nostalgic for the "good old days" (whenever those were). Everybody—FDA, industry, patients and consumers—is going to have a rough time over the next two years. Industry will be heard more often, but not always have the winning position.

To start with, the Republican House of Representatives is going to be asking lots of questions about policies and programming initiated by the Executive Branch during the last two years, including FDA.  Because of their backgrounds as heads of big-city public health department, Commissioner Hamburg and Principal Deputy Sharfstein are more prepared then most political appointees.

However, they have never experienced the volume or magnitude of these inquiries. Neither FDA nor any stakeholder benefits if FDA is busy answering Congressional letters or preparing for oversight hearings on the Hill…..instead of reviewing products, setting standards and conducting inspections.

Even in the Senate, oversight and investigations are going to make a big comeback. This is a byproduct of budget politics: if there is no money to spend and big divisions over authorizing legislation, then Members turn to investigations to fill the time and command national attention.

Beyond FDA, regulated industries are going to come under increased scrutiny. The incoming chairman of the House Oversight and Government Reform has already announced plans to investigate the over-use of expensive medical devices and probe the way food recalls are handled. Imported food, drugs and raw ingredients from China may be given oversight scrutiny. Current investigations are going to continue on quality manufacturing in drugs, biotech products and OTC drugs.

Senator Grassley, as Ranking Minority on the Senate Finance Committee, has held investigations of tax-exempt hospitals, non-profit advocacy groups, FDA and FDA-regulated industries. Senator Hatch, who will be Grassley's successor in the post, has already indicated his intention to continue many of Grassley's issues and to have a tough investigations staff.

The Alliance for a Stronger FDA has already established that consumer and patient groups, health professional societies, associations and industries have a common interest in a strong FDA through increased appropriations. In the face of the current budget-cutting fervor, it remains to be seen whether industry will be able to convince legislators that FDA needs more resources from general revenue.

Separate, but related: a year from now, the drug, biotech and medical device industries will be trying to limit the amount of new user fees they will be required to pay when user fees legislation is re-authorized in 2012. It is hard to see how business' complaining about excessive fees will prevail against Congress' need to increase FDA funding from sources other than general revenue.

From these examples, it is possible to see a larger theme. Republicans generally believe that industry, without too much government intervention, should be relied upon for job creation in the US. Most of the party rhetoric is focused on achieving these through reducing the federal budget, trimming federal regulations and regulatory agencies, and making sure that "the people" who voted for them in the last election feel they are being heard.

The FDA context is different. Most FDA-regulated companies want simplification of the regulatory requirements and more certainty in their implementation, but are not interested in eliminating FDA's regulatory structure or limiting its ability to assure public health and safety. Thus, industry would not benefit from efforts to starve, roll-back, harass or marginalize the agency. The worst-case for the next two years is that Congress might try all four and not listen to industry concerns about negative outcomes.

Steven

"Must-Pass Legislation" Key to FDA's Future
December 12th, 2010

FDA Matters believes that the 2010 election will profoundly affect the FDA's mission, priorities, funding, standards and work flow. Eighteen months from now, FDA's leadership team will probably be the same, but the agency won't be. At the moment, there is only one "must-pass" item on Congress' FDA agenda: the next round of user fee renewals that will come before Congress in the Spring of 2012. Read the rest of this entry

Two Strategies for FDA Legislation in 2011
December 5th, 2010

The current Congress has two primary FDA-related accomplishments: have been less visible: an abbreviated approval pathway for bio-similar drugs; and a food safety bill that may be enacted before Congress adjourns. FDA Matters believes that any FDA-related legislation will falter in 2011 if it does not follow the strategy behind one or the other of these efforts. Read the rest of this entry

FDA and Election 2010: Oversight and Investigations
November 13th, 2010
 

President Obama's election and the distraction of health reform have distracted us from the disruption that divided government imposes on FDA. With the new Republican majority, the agency will find itself buffeted by political forces that are as concerned about "scoring points" as they are about improving government. FDA Matters thinks this will have a large impact on FDA, as well as the agency's stakeholders. Read the rest of this entry

FDA and Election 2010: Deficit Reduction and Appropriations
November 6th, 2010
 

So-called "wave elections"–where one party overwhelms the other–are particularly hard to judge. The ground rules are going to change dramatically– in ways that no one can fully anticipate. At first, each side refuses to compromise. Then, something happens that sets the pattern for whether people will work together and on what issues. This may take months to resolve or may occur before the new Congress arrives. As things change, FDA Matters thinks there are some key issues for FDA-watchers to monitor. Read the rest of this entry

“Must-Pass Legislation” Key to FDA’s Future

This is the fifth straight column looking at FDA and Congress. This reflects FDA Matters' belief that the 2010 election will profoundly affect the agency's mission, priorities, funding, standards and work flow. Eighteen months from now, FDA's leadership team will probably be the same, but the agency won't be.

Identifying and understanding the likely changes to FDA requires examining the meaning of "must-pass legislation" and its escalating importance as a quarrelsome Congress turns into a divided Congress. At the moment, there is only one "must-pass" item on Congress' FDA agenda: the next round of user fee renewals that will come before Congress in the Spring of 2012. 

"Must-pass" legislation is a bill or resolution that Congress is compelled to pass in order to maintain the functions or functioning of government. The best examples are appropriations bills, Congressional budget resolutions, and legislation to increase the limits on the national debt. Sometimes, "must pass" is defined by the agenda of a political party or the President, as was the case with health care reform.

Looking at this Congress' two FDA-related legislative accomplishments, "must pass" played a role in both. Representative Anna Eshoo (D-CA) had the votes to advance her version of bio-similars in place of the version supported by House Energy and Commerce Committee Chair Henry Waxman (D-CA). Occasionally Committee Chairs don't have the votes to prevail; they re-gain leverage by not scheduling a mark-up. This was not an option for Waxman because Eshoo's bio-similars bill was offered as an amendment to the "must pass" health care reform bill.

Because of the breadth of mostly bi-partisan support for food safety legislation, it was possible for it to advance as regular legislation in both the House and Senate. However, procedural barriers have now stalled the Senate-passed version in the House and it might not become law. The House responded by adding food safety legislation to the FY 11 Continuing Resolution (CR) that will fund the government when the current one runs out at midnight on December 18. This tactic may not ultimately work, but the CR is definitely "must pass legislation."

With some exceptions, it is hard to anticipate what pieces of legislation become "must-pass." In theory, FDA might go an entire Congress without enactment of any major legislation. This can't be the case for the incoming Congress because authority to collect both prescription drug and medical device user fees expires on September 30, 2012. In the months prior to that date, Congress will face a choice: pass re-authorizing legislation or deprive the agency of $700 million in revenue each year. Thus, "user fee legislation" = "must-pass legislation."

User fees need to be renewed every five years. The last round of user fee re-authorizations resulted in the Food and Drug Administration Amendment Act (FDAAA). It is complicated and emerged after extremely tough negotiations. The final legislation was 155 pages long and had 11 separate Titles. It is at: http://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW-110publ85.pdf.

Commissioner Hamburg, Members of Congress, and most FDA stakeholders have wish lists of ways they would change FDA and the laws it implements. None of these--at least not any major ones--are likely to pass in 2011 without broad bi-partisan support.

But 2012 will be another story. In the process of adopting the "must pass" user fee reauthorizations, we can anticipate Congress considering dozens of provisions and programs that don't relate to user fees. Lawmakers and stakeholders will all have a chance to put their mark on the FDA in 2012.

Steven

Two Strategies for FDA Legislation in 2011          December 5th, 2010
The current Congress has two primary FDA-related accomplishments: an abbreviated approval pathway for bio-similar drugs; and a food safety bill that may be enacted before Congress adjourns. FDA Matters believes that any FDA-related legislation will falter in 2011 if it does not follow the strategy behind one or the other of these efforts. Read the rest of this entryy

FDA Funding and the Appropriations Drama       November 28th, 2010 
 The process for passing appropriations bills should be similar from one year to the next. After all, it is a one-directional, regimented process. Yet, I have been through 30 or so appropriations cycles and each one seems to have its own unique story to tell. This year's efforts would make a riveting "made for television" movie "based on a true story." FDA Matters doesn't know how it will end, especially for FDA. Read the rest of this entry

FDA and Election 2010: Oversight and Investigations   November 13th, 2010 
President Obama's election and the health reform debate have distracted us from the disruption that "divided government" imposes on FDA. With the new Republican majority, the agency will find itself buffeted by political forces that are as concerned about "scoring points" as they are about improving government. FDA Matters thinks this will have a large impact on FDA, as well as the agency's stakeholders. Read the rest of this entr 

FDA and Election 2010: Deficit Reduction and Appropriations     November 6th, 2010 
 So-called "wave elections"–where one party overwhelms the other–are particularly hard to judge. The ground rules are going to change dramatically– in ways that no one can fully anticipate. At first, each side refuses to compromise. Then, something happens that sets the pattern for whether people will work together and on what issues. This may take months to resolve or may occur before the new Congress arrives. As things change, FDA Matters thinks there are some key issues for FDA-watchers to monitor. Read the rest of this entry  

Two Strategies for FDA Legislation in 2011

The current Congress will be remembered for its 15-month battle to enact health reform legislation. The FDA-related accomplishments have been less visible: an abbreviated approval pathway for bio-similar drugs included in the health reform law; and a food safety bill that may be enacted before Congress adjourns later this month.

In both cases, unanimity was never possible, but working majorities formed and prevailed. FDA Matters believes that any FDA-related legislation will falter in 2011 if it does not follow the strategy behind one or the other of these efforts. 

Bio-similars. The Democrats (Senator Kennedy and Representative Eshoo) leading the bi-partisan effort—and most of the Democratic rank and file who supported the legislation--come from high-tech, life sciences states and districts. Republicans joined the Democrats because of similar home-town support from life sciences companies and interest in promoting a pro-innovation, pro-economic development agenda.

The combination of Democrats with biotech interests and Republicans became a powerful force. It is also an approach that can be duplicated next year with a reasonable chance of success.

Indeed, another such effort is already underway regarding the medical device review process at FDA. Two weeks ago, 8 members of the Minnesota Congressional delegation sent Commissioner Hamburg a letter stating:

We support the FDA's work to improve the process for the approval of safe and effective Class II medical devices but we must work to ensure that we continue to foster life-saving innovation and growth….and a larger goal of saving and improving patients' lives….Changes that may jeopardize that goal should not be made unless there is clear evidence that the changes are necessary to address a public health problem.

The letter was signed by the state's 2 Democratic Senators, 3 of its Republican House members and 3 of its Democratic House members. Elsewhere, the letter mentions that Minnesota has over 500 medical device companies that employ almost 35,000 residents at average pay-levels almost 50% higher than the state average.

Food Safety. As with bio-similars, there was a widespread consensus that food safety reform legislation was needed. The similarities between the two efforts end there.

Hill staff and key constituency groups held extensive discussions about needed changes. After lots of disagreements and some very tough negotiating, most Democrats and Republicans found enough common ground to move forward in the House.

The Senate also evolved a compromise version—somewhat different from the House, but with a similar breadth of support. Action stalled in the Senate because of cost issues and concerns about small food producers. But the core of support never disappeared.

When those concerns were addressed in the Senate, the other extraneous issues and disagreements fell away. Even the House appeared to have signaled that they would accept the Senate bill, rather than face further negotiation that might delay action until next Congress. Such deference has become increasingly uncommon in Congress.

I don't want to minimize the difficulties in establishing and conducting negotiations on food safety. It may still fail. What made agreement possible was the willingness of constituency groups to work together, despite strongly held views that were often opposed. This approach can also work next year for other issues, as a broad-base of constituency groups lead Congress to a bi-partisan agreement on legislation.

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The current Congress has not been known for its bi-partisanship. Some commentators think bi-partisanship may disappear altogether in the new Congress. Nonetheless, FDA is an area where getting the parties together is possible.

If consumer and patient groups, industry and associations and the Administration or Congress want to get anything done in 2011, they would do well to consider how the bio-similars and food safety strategies might apply to their cause.

Steven

The Minnesota delegation's letter to Commissioner Hamburg about changes in the process of approving medical device. http://www.hpm.com/pdf/MNLegConcerns.pdf

Some relevant past columns:

All FDA Stakeholders Affected by Medical Device Reforms        October 31st, 2010
There are so many visible, contentious FDA issues right now….that reform of the medical device approval process has received only a fraction of the attention it deserves. Other centers at FDA and non-device stakeholders need to be watching more closely. FDA Matters is. Read the rest of this entry

FDA: An Honest Broker on the Slow Path to Bio-similars      October 24th, 2010
FDA Matters enthusiasm for bio-similars is a matter of public record. The market will build slowly, but 10 years from now the new law will be seen as ushering in a new age of biopharmaceutical product development. Read the rest of this entry

Fall Scorecard for Follow-on Biologics        September 11th, 2009
The creation of a regulatory pathway for follow-on biologics (FOB) has become a favorite topic of FDA Matters. The substance of the legislation is important and the politics are fascinating. It should get even better this fall. Read the rest of this entry

FDA and Election 2010: Oversight and Investigations

The return of a Republican majority in the House of Representatives means an increase in Congressional oversight and investigations. This mirrors 2006, when the Democrats took back Congress and immediately started investigating the Bush administration.

President Obama's election and the distraction of the health reform debate have helped us forget the impact of divided government on FDA. Once again, the agency will find itself buffeted by political forces that are as concerned about "scoring points" as they are about improving government. FDA Matters thinks this will have a large impact on FDA, as well as the agency's stakeholders.

In the House of Representatives, there are three committees that exercise "oversight and investigations" jurisdiction (O&I) over the FDA. The primary ones are the Energy and Commerce Committee and the Oversight and Government Reform Committee. The Appropriations Committee also conducts O&I.

The Energy and Commerce Committee intends to investigate the scope of work and expenditures under FDA's contract with McKinsey & Company, an international management consulting firm that has been asked to improve the productivity of the generic drug review office. Once the Energy and Commerce has reorganized itself for the new Congress and priorities are set, there are sure to be more areas under investigation.

The Oversight and Government Reform Committee is off to a faster start because outgoing chair Representative Edolphus Towns (D-NY) and incoming chair Representative Darrell Issa (R-CA) were already working together on manufacturing problems in the drug industry. This has now become an investigation of whether understaffing in FDA's Puerto Rico office led to inadequate oversight of industry.

FDA is under scrutiny all the time. Congress' watchdog arm, the General Accounting Office (GAO), regularly reports on areas where they believe FDA should do better. Likewise, the HHS Inspector General keeps a watchful eye on the agency. In a more helpful, but often no less critical mode, the Institute of Medicine also oversees many aspects of FDA programs.

What may make 2011 different?

Dr. Hamburg and Dr. Sharfstein can expect to spend countless more days preparing for and testifying at oversight hearings. Their involvement is the tip of the iceberg, with staff at every level being pulled from other work to respond to Congress. Some key staff that were able to focus on big picture issues this year...are likely to be in "damage control" mode most of next year.

FDA's competence will be questioned publicly, then magnified by the media. FDA has a lot of problems. Oversight can contribute to improvements. However, any loss of public confidence in FDA is a serious barrier to the agency doing its job better.

This may also lead to questions about whether the agency should receive more monies….when, in fact, many of the problems (not all of them) cannot be fixed without more resources. For example, unless you believe there are FDA staff sitting idle, how does understaffing in FDA's Puerto Rico office get resolved without a larger appropriation?

Oversight of food safety may lead to more effective use of resources, but cannot obviate the need for more inspectors. Oversight of medical products may lead to more conservative decisions by the agency, further slowing new therapies for patients.

As oversight of FDA ramps up, so too will oversight of industry. FDA Matters has exhorted CEO's to see quality controls, good manufacturing and improved sales and marketing practices to be integral to whether its products represent a public good. O&I is likely to be unflinching in its exposure of those who have not taken this to heart.

In the end, FDA will survive. Hopefully, it will be a better agency, while preserving its needed funding growth. Meantime, it is inevitable that FDA and industry will feel some pain.

Steven

My apologies to readers who may have received more than one mailing last week. The end of daylight savings time caused repeat distribution of several columns. Hopefully, it is now fixed.

 FDA and Election 2010: Deficit Reduction and Appropriations      November 7th, 2010

So--called "wave elections"–where one party overwhelms the other–are particularly hard to judge. The ground rules are going to change dramatically– in ways that no one can fully anticipate. At first, each side refuses to compromise. Then, something happens that sets the pattern for whether people will work together and on what issues. This may take months to resolve or may occur before the new Congress arrives. As things change, FDA Matters thinks there are some key issues for FDA-watchers to monitor. Read the rest of this entry

Quality Control Woes: What's a CEO to Do?    June 2nd, 2010
Medical products companies are struggling to assure FDA and the American people that their products are "safe as manufactured and distributed." We don't know whether quality control has become lax, FDA is discovering more problems or industry has just had a run of bad luck. We do know that quality control relies on a lot of people maintaining tough standards…and that manufacturing is rarely a priority of a drug and device company CEO. FDA Matters asks: "what's a CEO to do?" Read the rest of this entry

Black, White, Shades of Gray      November 13th, 2009
Civil and criminal investigations are becoming a more prominent feature in the world of FDA-regulated industries. People who never gave any thought to this….suddenly find themselves needing to understand how investigations work. Being FDA-regulated means "always worrying that you will have to say you're sorry." But it matters whether you are apologizing to FDA or trying to apologize to investigators. Read the rest of this entry

All FDA Stakeholders Affected by Medical Device Reforms

There are so many visible, contentious FDA issues right now….that reform of the medical device approval process has received only a fraction of the attention it deserves. Other centers at FDA and non-device stakeholders need to be watching more closely. FDA Matters is.

The key area being examined is how FDA regulates Class II (medium risk) devices. Generally, they require a 510(k) Premarket Notification to be marketed. Under this process, a sponsor must show that a device is "substantially equivalent" to a device already marketed. The 510(k) is significantly less rigorous and time consuming than a full Product Marketing Application (PMA), the medical device equivalent of a drug NDA or a biologics BLA. A related area under review is the broad interpretation that "substantially equivalent" has been given.

Given the realities of the medical device industry, such an abbreviated process is necessary. In pharmaceuticals, product life cycles are typically 8 to 10 years or more after approval. In contrast, devices are being improved constantly. Products, as approved, might be on the market only 18 months to 2 years before the devicemaker is ready with improvements.

Thirteen months ago, FDA released an internal review of the agency's (mis)handling of the 510(k) device approval of a product from a company named ReGen. The report provided an inventory of issues to be re-evaluated and immediate impetus for FDA to improve the medical device approval process.

At the time, I expressed hope that FDA could formulate changes by itself, rather than give Congress a reason to consider amendments to the medical device statute. FDA also saw it this way and asked the IOM to formulate recommendations while the agency proceeded internally to develop its own proposals.

FDA released its recommendation in August, with public comments due in October. Industry agreed with some of the proposals, but was unhappy about the breadth of FDA's initiative and some specific recommendations. Some consumer groups thought the FDA proposals did not go far enough.

As a result of industry concerns, a bipartisan group of Members of the House Energy and Commerce Committee have written to Commissioner Hamburg asking FDA to slow down its implementation of changes. The group was careful not to endorse or criticize FDA's actions. The Members requested more transparency and reminded FDA of the importance to patients and the economy of medical device innovation. Similar caution and concerns are being expressed to FDA from the Senate side.

Why should other parts of FDA and non-device stakeholders care about these developments? First, FDA showed a rare capacity for self-criticism in the ReGen report. These types of inquiries will occur elsewhere at FDA when system failures occur.

Second, FDA has decided that it has the insight and statutory authority to substantially overhaul a major approval pathway. It has been doing so without close Congressional scrutiny. If food safety reform legislation isn't enacted this year, FDA may need to proceed in a similar manner. Other efforts may eventually be undertaken with drugs, biologics and other medical products.

Third, Congress may be taking a more bipartisan approach to FDA. A system of checks and balances may be evolving between Congress and FDA, where the agency is given room to develop policies under the arms-length scrutiny of Congress.

Fourth, the current effort is reminiscent of Representative Eshoo's successful efforts to add biosimilars legislation to health care reform. The key was that Democrats from states with biopharmaceutical companies were willing to join with Republicans in supporting changes in FDA's laws and actions. The current effort makes clear that medical device companies are capable of bringing together a similar coalition.

I recommend keeping an eye out for further developments in medical device reform. The lessons learned may well affect your own interests.

Steven

When Abbreviated May Not Mean Faster or Easier    July 25th, 2010

FDA is working on an approval pathway for bio-similars, re-examining the way medical devices are reviewed, trying to upgrade the quality and speed of generic drug reviews and will soon be evaluating its process for granting accelerated approvals to drugs. These seemingly unconnected activities all have in common that they are supposed to be abbreviated processes to get new products to patients more quickly without risking safety or quality problems. Read the rest of this entry »

"No Surprise" That Medical Devices Are Under Scrutiny    October 1st, 2009

Five weeks ago, I wrote a column entitled, "Re-Evaluating the Medical Device Approval Process." It was not widely-read. I assumed it was because everyone already knew that a review was underway at FDA with more activity coming. Apparently, I was wrong. Read the rest of this entry »

Re-evaluating the Medical Device Approval Process    August 27th, 2009

Earlier this year, a GAO report concluded that many high risk medical devices have not been adequately reviewed. In June, the House Health Subcommittee held the first of what may be a series of hearings on medical devices. The media appears increasingly interested in medical devices and is raising more questions.

All these events are a prelude to FDA and Congress undertaking a major re-evaluation of the product approval process for medical devices. It would be a relief if FDA could diagnose and treat its own medical device problems, leaving the Congress and the media to watch. Read the rest of this entry »

FDA: An Honest Broker on the Slow Path to Biosimilars

FDA Matters' enthusiasm for biosimilars is a matter of public record. The market will build slowly, but 10 years from now the new law will be seen as ushering in a new age of biopharmaceutical product development. FDA will present the next glimpse of the future on November 2 and 3, 2010, when it holds hearings on implementing the new approval pathway.

The key to the future will be the FDA's strong commitment to expanding prescriber and patient choice among biological products. FDA will be satisfied (and successful) if the new law stimulates biosimilars, bio-betters, and innovative new biological products, along with a dramatic increase in knowledge about the nature and characterization of biologic products.

Misunderstandings abound about the new law and how it is likely to reshape the biopharmaceutical landscape. Experts keep saying that innovator (reference) products have been granted 12 years of market exclusivity. Reading the sentences carefully, data exclusivity prevents biosimilar products from being approved through the new abbreviated biosimilars pathway for 12 years. It does not prevent approval of a biosimilar through a traditional biological license application (BLA).

There is also the perception that the biosimilars market will be limited to billion-dollar products and a few companies that have the capital to enter the marketplace. Despite this view, there are at least five or six companies ready to advance biosimilar and bio-better products over the next few years. More will come.

Over time, innovation will bring costs down and significantly lower barriers to market entry. Competition will bring prices down to competitive levels. Discounts may not be as low as those in the generic drug market, but significant savings will result from 20% to 30% discounts on drugs costing $50,000 per year and more.

We are told many things about the agency: it is going to lower standards, be extremely cautious, fail to develop adequate guidance for industry or proceed with no ground rules, etc. Passage of Hatch-Waxman 26 years ago elicited similar concerns. A quarter century later, that law has resulted in 70% of US prescriptions being filled with generic drugs.

The path to a more vigorous biopharmaceuticals market will not be easy. The law is not well-written and the patent provisions seem an additional barrier. FDA will be very cautious about the new approval pathway, but it may look favorably on biosimilars submitted as BLA's. Although I don't agree, it has been suggested that even a single serious safety problem for an approved biosimilar will kill the market. Also, at least one reimbursement expert has told me that a biosimilars market may never emerge because doctors lack financial incentives to use these products.

The Federal Register notice for next week's FDA hearings lists a careful series of questions upon which the agency wants comment. At the hearings, expect little, if any, feedback from FDA. They won't ask many questions either. At the risk of leaving everyone guessing, the agency will keep its own counsel, determined to be an honest broker among competing interests.

Guidances and regulations take years to develop and publish. FDA will proceed carefully and consistent with its public responsibilities. The impact will not be measured by how many products come through the new abbreviated pathway (perhaps not many) or how many products are deemed "interchangeable" (maybe none).

FDA's ultimate success will be the broad expansion of biopharmaceutical products. This will happen eventually, but patience will be required.

Steven

Background on the FDA hearing on biosimilars:

http://edocket.access.gpo.gov/2010/pdf/2010-24853.pdf

Information if you want to attend the hearing or watch the webcast:

http://www.fda.gov/Drugs/NewsEvents/ucm221688.htm

Data Exclusivity and Bio-Similars: Both More and Less Than It Seems

May 2nd, 2010

FDA Matters has been very upbeat about the prospects for the bio-similar marketplace. With this in mind, this column explores why there is a persistent belief that the bio-pharmaceutical industry got something better than data exclusivity. I also explore whether data exclusivity will really provide valuable protection for original reference biologic products. Read the rest of this entry »

Follow-on Biologics: 1-2-3-GO

March 21st, 2010

The long fight is over for follow-on biologic (FOBs). The world of biopharmaceuticals will never be the same, but not in the ways that many players expect. Here is FDA Matters' guide to understanding the next phase. Read the rest of this entry »

The Follow-on Biologics Market

Since the debate began several years ago, the policy and politics of follow-on biologics (FOB) have been driven by assumptions and projections of the anticipated market. FDA Matters believes there has been a lot of fuzzy thinking about what type of companies will be players and how they will position themselves. The Federal Trade Commission report, released last week, is just the latest illustration. Read the rest of this entry »

Success is Uncertain for FDA’s Regulatory Science Initiative

FDA Matters was an early advocate for regulatory science. It has been exciting to see the concept grow from the Commissioner's first public speech to the President's request for $25 million in FY 2011. And now, FDA has released a White Paper describing the Regulatory Science Initiative (RSI).

It is an excellent report and I applaud those who worked hard to create it. Still, I have misgivings about the way the White Paper characterizes regulatory science, leading to concerns about whether RSI will develop the necessary political and public support to be a long-term, permanent part of FDA.

According to the report:

"Regulatory science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality and performance of FDA-regulated products." (emphasis added).

I would suggest that:

"Regulatory science is the tools, techniques and knowledge needed by food, medical product and other FDA regulators to carry out their public responsibilities."

FDA's definition makes regulatory science about what FDA develops (new tools, standards, etc.) and about regulated products. Instead, it should be about how regulatory science makes it possible for FDA to carry out its public health mission in an increasingly complex scientific and global environment. It needs to be clear that consumers, patients and regulated industries benefit when regulators have sophisticated, state-of-the-art capabilities and use them transparently, so that no stakeholder has to guess about the agency's approach. These are public purposes for which it is possible to gather broad support.

Most agency funds are spent to carry out applied regulatory science. A smaller, but not insignificant part of the agency budget is already being spent to create and improve regulatory science. For example, much of the budget of the Center for Food Safety and Nutrition that is not spent on inspections and enforcement is focused on better tools and knowledge to create a safer food supply. Most of the work of the National Center for Toxicological Research is devoted to improving regulatory science through the creation of science-based standards.

Regulatory science is not new and is much larger than an agency initiative. Rather, it is a re-conceptualization of who the agency is and what it does. Without this larger and more visionary framework, I fear that RSI is going to be underfunded by Congress and pushed aside when dollars are tight.

What reason is there to think so? The Critical Path Initiative (CPI) was launched with significant fanfare. The original report was one of the most lucid statements I have ever read from a government agency. The projects that Critical Path supported appear to have been well-conceived and responsive to broad, serious regulatory science needs within FDA.

Yet, the Critical Path completely failed to capture Congress' imagination. It received very modest financial support from Congress, even in the last few years when the FDA's budget expanded significantly.

RSI risks the same failure if Congress and other policymakers can neither explain "regulatory science" nor understand why it is fundamental to FDA's mission success. As judged by CPI funding and the limited enthusiasm that it generated, Congress saw it as a nice add-on, but not a necessity.

If RSI can't do better than this, it will not grow and prosper once the initial excitement fades. This would be a great shame because improving regulatory science is essential to making FDA into a 21st century regulatory agency.

That's why it matters what FDA says now about the RSI. Undoubtedly, the agency wants regulatory science to be seen as a better, more holistic way to understand and improve the agency. At the moment, it still looks more like a collection of worthwhile agency improvements that have been bundled into a new initiative.

Steven

The FDA White Paper, Advancing Regulatory Science for Public Health, can be found here, along with the Commissioner's speech on the topic at the National Press Club: http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/default.htm

One of several earlier FDA Matters' columns on regulatory science:

CARS: The Vehicle for FDA's Future October 25th, 2009

Since Labor Day, Commissioner Hamburg has spoken a number of times about the importance of regulatory science. She is right. FDA must have the scientific tools and methodologies to be a 21st century regulatory agency. FDA needs to define regulatory science, develop programs to support it, and package them in a way that will quickly bring recognition and funding. Read the rest of this entry »

FDA: A Hit and A Miss

FDA Matters has watched FDA handle the Avandia decision differently from any prior controversy. I like the new approach. In the same week, FDA provided a status report on its long-overdue social media and Internet communications policy. Because the agency's efforts have been glacial, the prospect of useful guidance is dim. I think this is a serious problem.

FDA's Handling of the Avandia Situation. A HIT

FDA Matters was heartened by the agency's deft handling of the Avandia situation. Previous columns have explored how hard it is to achieve cultural change at FDA and why it requires the Commissioner and the agency's senior leadership to be role models.

With the Avandia decision, the agency has demonstrated progress toward two related changes: improved transparency and allowing internal dissent to become part of the public dialog.

Transparency is not part of the FDA's DNA. Despite this, the agency has responded to the President's government-wide transparency initiative with a serious effort. In doing so, it has struggled--mostly against itself--in making its processes and decisions more readily available within and outside FDA.

The Avandia advisory committee meeting and the FDA website were remarkably transparent about the controversy and the details. To clarify the ultimate decision, Drs. Woodcock, Sharfstein and Hamburg authored a 1500-word explanation, which appeared in the New England Journal of Medicine.

Embracing dissent has always been hard for FDA. Its customary position of "speaking with one voice" is not an accurate reflection of what happens when well-trained, analytically-oriented people gather to make a decision. With Avandia, Commissioner Hamburg has conspicuously incorporated dissent into the process.

Cultural change at FDA is difficult and always takes time. The Avandia decision is a significant step forward, demonstrating that agency leadership is committed to changes and understands that it must serve as role models.

FDA's Handling of Policy Development for New Media: A MISS

As a rule, businesses do not like additional regulation. There are two exceptions: where it levels the playing field with competition and when it creates certainty on how companies should conduct their activities. These are the exact reasons why FDA-regulated medical products companies have repeatedly asked FDA to issue policy guidance on Internet activities.

As best I can tell, FDA's first hearing, "FDA and the Internet: Advertising and Promotion of Medical Products" occurred on October 16 and 17, 1996. http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm175775.htm. That's 14 years ago!

While FDA has studiously ignored the opportunity to provide policy guidance and regulation, the Internet has become a primary means of written and visual communication. Search engines control an ever expanding numbers of online interactions. Social media has flourished.

Apart from agency action against some companies for activities that many consider ethical and reasonable and a two-day hearing in November 2009…not much progress seems to have occurred toward providing more direction to industry. At a Food and Drug Law Institute meeting last week, the agency suggested a draft guidance--the first of many--may be issued later this year. Even assuming this occurs on schedule, it will take at least a year to finalize.

I suggested last year that FDA was mistaken to see Internet policy development as overwhelming. Rather, it is a number of smaller issues that can be addressed separately without a broad Internet policy. An additional advantage of this approach: it recognizes that any Internet policy guidance will be outdated before FDA can ever issue it.

After 14 years, this calls for the intervention of agency leadership, not continued delays.

Steven

Gardner Harris of the New York Times also observed the changes at FDA that have occurred as part of the Avandia decision. His column is at: http://www.nytimes.com/2010/09/25/health/policy/25avandia.html?_r=1&emc=eta1.

For those interested in more coverage of FDA and social media, I recommend Mark Senak's Eye on FDA column at www.eyeoffda.com.

Is the New FDA Different than the Old FDA?

June 13th, 2010

Two weeks ago, FDA Matters explored Dr. Hamburg's legacy, focusing on advocacy for resources, prioritizing regulatory science and upgrading enforcement. These will be accomplished before she leaves office. But is she making similar progress in creating "a new FDA, including changes in agency culture?" Read the rest of this entry »

Dissent and Efficiency: Difficult Trade-offs for FDA
May 9th, 2010

FDA has a reputation for being tough on dissent, whether it comes from employees or regulated companies. Whatever the truth has been in the past, FDA is trying to develop an institutional cultural that welcomes and accepts dissent from employees, industry and other stakeholders. It is difficult, even messy, to do this. Read the rest of this entry »

Internet Communications: FDA Needs to Divide the Issues to Conquer the Problem
December 2nd, 2009

Creating an Internet communications policy for regulated medical product companies is so daunting that FDA has largely ignored the responsibility. New policy will not be announced anytime soon. FDA needs a different approach. This is not a matter of a large, complicated problem with many facets. Rather, it is a number of smaller problems that can be addressed separately. Read the rest of this entry »

ACRA: Little Attention to an Important Appointment

For more than a year, FDA Matters has talked about the position of Associate FDA Commissioner for Regulatory Affairs (ACRA), who is the agency's chief officer for inspections, enforcement and compliance. Of FDA's appropriated (non-user fee) budget, the ACRA oversees one-third of the agency's monies and more than 40% of the staff. It is FDA Matters that dubbed the ACRA the "uncrowned prince" of FDA.

Because of the importance of ACRA and the level of resources it receives, we have been awaiting a new appointee to this long-vacant position. This has now occurred, but the announcement was so unassuming as to raise concerns.

Dara Corrigan, JD, will be the new ACRA and run the Office of Regulatory Affairs (ORA). She is a veteran of the HHS Inspector General's office and has also held policy positions at HHS. We wish her well. We also hope that she and the Commissioner can return this position to the visibility it needs.

Congressional and media attention are increasingly focused on FDA's capacity to perform effective inspections and rigorously enforce the law. The agency's good name and public credibility are tied to success in these areas.

Since the Commissioner has so many roles, she needs someone to be the highly-visible, public face of tough enforcement at FDA. Two decades ago, when I worked at HHS, the Inspector General was a former professor who had become the supervisor of the organized crime units in the FBI's Chicago Office. He was a good, smart man and a friend…but you knew immediately that you didn't want to be a target of one of his investigations.

FDA needs Ms. Corrigan to perform this function on behalf of ORA and FDA.

Well run, conscientious companies have little to fear. If you run a solid plant operation, import ingredients with care, use multiple system controls, and renew your commitment to pedigree and chain of custody, you are unlikely to be affected by a stronger ORA. If you have an inspections or enforcement problem: cooperate with FDA and correct it quickly.

On the other hand, if you are cutting corners, heedless of consumer and patient risk, or stonewalling the agency, you deserve what you get from FDA.

Commissioner Hamburg is working to make the agency more scientifically knowledgeable, more innovation-oriented and a more reliable partner in its interactions with industry and other stakeholders. She doesn't have the leeway to accomplish these goals if she doesn't continue to strengthen inspections and enforcement.

It makes sense to take ORA out of the FDA shadows and make it a more visible force. The initial announcement did not live up to this.

Steven

Commissioner Hamburg's Most Important Personnel Decision
February 21st, 2010

With due respect to the many fine individuals that Commissioner Hamburg has recruited, FDA Matters thinks the most important appointment needs to be made soon: choosing the right person to be Associate Commissioner for Regulatory Affairs. Read the rest of this entry »

The Uncrowned Prince of FDA
September 15th, 2009

Which FDA line manager has the most appropriated resources to work with in FY 09? Is it Janet Woodcock, head of the drug center or Stephen Sundlof, [then]head of the food center? The correct answer: neither. Read the rest of this entry »

FDA’s “Summer of Safety Concerns”

One of industry's great fears is that FDA will become obsessed by theoretical or miniscule safety concerns and ignore the difficult realities of providing consumers with a varied and plentiful food supply and providing patients with effective medical therapies.

It is even possible to think this has occurred. It has been a long summer of media and Congressional attention to safety: whether drug manufacturing, medical products already on the market or Salmonella contaminated eggs. A closer look suggests to FDA Matters that theoretical safety risks and inappropriate FDA concerns about safety are not the issue.

As laid out in more detail in "Safe": Many Meanings Complicate FDA Policymaking, there is a strong tendency to think of FDA's safety mission as if it were one type of activity. There are at least six different meanings of "safe" that are relevant to FDA.

For example, we want our food to be "inherently safe," "safe from intentional and negligent contamination" and "safe from unintentional contamination." Much of FDA's attention to food safety this summer has been about unintentional contamination (seafood in the Gulf and eggs with Salmonella).

The agency needs more resources for food inspections and, in the case of eggs, it should benefit from implementation of new standards that were already being phased in. New food safety legislation should also help, but only if Congress appropriates the funds for it to work properly. Whatever substantive or political barriers exist to passage of this legislation, there does not appear to be widespread disagreement about FDA's role or the standards it applies in assuring food safety.

We want medical products (drugs, biologics and devices) to be "safe as tested pre-approval,""safe as used post-approval" and "safe as manufactured and distributed." None of this summer's medical product safety issues appear to be about nuances of safety or shifts in FDA's approach to balancing risk and benefits in these three areas of safety concern.

Concern over potential cardiovascular risks from the diabetes drug Avandia existed before its approval. I do not see this as an issue of FDA standards or focus—but rather conflict over the proper interpretation of studies and data. Policymakers and industry should be wary of drawing any larger meaning from this about FDA's policies on safety.

Much of the rest of the summer's medical product safety issues were about "safe as manufactured and distributed." There seems to be consensus—even among those with problems-- that real lapses occurred and were violations of reasonable safety policies. As described in prior columns, this requires CEO's to take manufacturing and distribution seriously, rather than for FDA to re-think its existing safety policies.

While this may have been FDA's "summer of safety concerns," there doesn't seem to have been any change in how the agency balances competing demands involving safety. As the FY 11 appropriations process comes to a conclusion this Fall, there is good reason to put more funding into safety analysis and enforcement. Drawing any larger conclusions is, at best, premature and probably unwarranted.

Steven

Since before Memorial Day, FDA Matters has blogged extensively about FDA and safety issues, although this was not planned. Here is a sampling of columns:

"Safe": Many Meanings Complicate FDA Policymaking May 23rd, 2010

FDA Matters is in favor of safe foods and safe medical products. Who isn't? If you are a consumer, maybe that's all that matters. However, being in favor of safe foods and safe medical products is not enough if you are FDA, the media, Congressional authorizers and appropriators, OMB, and industry. It sounds good, but what does it really mean? In the FDA context, "safe" means many things, some of which are barely related to each other.
Read the rest of this entry »

Not Too Soon to Consider the Hamburg Legacy May 27th, 2010

May 18 marked one year since Dr. Margaret Hamburg was sworn in as Commissioner of the US Food and Drug Administration. The challenges are great, the torrent of issues is never-ending and most days you can smile but you can't win. Nonetheless, I think it has been a very good first year for her and for Principal Deputy Commissioner, Dr. Joshua Sharfstein. It may seem premature to be discussing "the Hamburg legacy." But you know that she is thinking about it (all commissioners do), so why can't FDA Matters talk about it? Read the rest of this entry »

Quality Control Woes: What's a CEO to Do? June 2nd, 2010

Medical products companies are struggling to assure FDA and the American people that their products are "safe as manufactured and distributed." We don't know whether quality control has become lax, FDA is discovering more problems or industry has just had a run of bad luck.

We do know that quality control relies on a lot of people maintaining tough standards…and that manufacturing is rarely a priority of a drug and device company CEO. Earlier this year, in the wake of Toyota's problems, FDA Matters asked: "what's a CEO to do?" Read the rest of this entry »

FDA to Industry: Contractors R U June 17th, 2010

It seems a rather uncontroversial proposition: FDA-regulated companies are responsible for their vendors, including every contracted piece of work that is done on the company's behalf. If problems develop, it makes no difference whether a company did it…or a contractor did it for them. Two seemingly unrelated items this week suggest that FDA is becoming concerned about whether FDA-regulated companies are overseeing their vendors. Read the rest of this entry »

Hot Town, Summer in the City—2010 July 11th, 2010

For the news media, the only FDA story this coming week will be the two-day advisory committee meeting reviewing the diabetes drug, Avandia. Missing from public dialogue is the extraordinary (perhaps unprecedented) number of large, consequential projects that FDA will be working on this summer. Every part of FDA is involved in some initiative that could become a "game-changer" for the agency. Read the rest of this entry »

Benefit, Risk and the Coming Age of REMS August 8th, 2010

FDA supposedly swings back and forth between emphasizing "expedited approvals of promising therapies" and "extended pre-approval examination of every safety issue." Current thinking is that FDA is now leaning more toward the safety end of this spectrum.

FDA Matters thinks a lot of this is perceptual. Approval decisions reflect FDA's honest and relatively clear judgment on medical need, quality of the clinical data, and the risks and benefits of a specific product. Mostly, I can understand FDA's decisions, even when I don't agree. Still, there is a lot of tension within FDA and with various stakeholders about approvals versus safety risk. Read the rest of this entry »

For Those Who Don’t Work With Patients: A Reality Check

Guest Column: Summer, Camp, Kids, Cancer

By Margaret Anderson, Executive Director, FasterCures

While we focus on improving the efficiencies of the system that discovers treatments and cures for disease, there are untold numbers of people taking a medical treatment journey right now. For the kids partaking in the 28th year of Camp Fantastic in Virginia this week, they get to focus more on the fun, and less on the challenges of coping with a cancer diagnosis and with treatment. Camp Fantastic is a program of a nonprofit called Special Love that gives cancer families support.

I learned of this amazing place from Kathy Russell, who has been involved since its beginning and who also runs the Children's Inn at NIH. The NIH Children's Inn helps families with kids in treatment at the NIH Clinical Center to get a bit of normalcy in their lives by providing a warm atmosphere for them to stay in versus an isolating hotel room. The overriding philosophy is that families make a key difference in the lives of their sick children. The work they do represents the full spectrum of NIH investment – from bench to bedside.

By the end of my chat with Kathy, after I dabbed my eyes, I was ready to pack my bags and tell everyone I knew to come with me to help prepare Camp Fantastic and allow kids there to take a break from cancer and be just kids. This year there will be nearly 100 kids at Camp Fantastic between ages 7-17. Usually one-half of them are in active treatment and there are upwards of 60 medical professionals (in addition to countless other folks) who volunteer their time before and during the camp. They literally set up a mini-hospital on-site because it's in a remote location and far from a hospital with specialized pediatric oncology services. She told me of how kids get their bloodwork done in the am, and a van takes the samples into NIH to do labs and then turns back around with results and medication.

Every year, at least one child is usually transported from the camp in an ambulance or a helicopter to a hospital for further treatment, requiring diligent attention to medical details as well as a carefully thought through psychosocial plan of action to share that news with the other campers. Families are communicated with each day, and as you'd imagine many are nervous and excited about their kids being there. Some children participate while in their final stages of life.

Their families make the ultimate sacrifice by being selfless enough to share their children with others, so that their kids can live out their final hopes and dreams – the same dreams we all have. To do the things we dream of doing, especially those seemingly simple things associated with summertime.

Stories like this remind me of the passion and dedication of the medical research community, of the care providing community, and of the volunteer community. It's a reality check for me, and for those of us who work on policy-related issues. These kids and their families point out the obvious – that time is of the essence in all we are doing to get to faster cures.

It can be hard to make the FasterCures message personal at times as we deal with mostly macro-level issues, but hearing about Camp Fantastic reminded me why we do what we do. Because it's summer vacation time, and every kid (and for that matter, every grown-up) deserves a shot at creating their own lazy crazy hazy days of summer memories.

www.fastercures.org

With thanks to Margaret and Faster Cures for allowing me to reprint this from their blog.

Steven

One of my earlier columns for FDA Matters:

Patients Come First

November 11th, 2009

Most seriously-ill patients wake each morning wondering how they will surmount the day's challenges. They are concerned about the health of all Americans, but can't help being focused upon their own medical situation. Most of the people I know in the medical products industry wake each morning with the hope that their day's efforts can contribute to improving the health of all Americans, as well as provide specific benefits to seriously-ill patients.

The world-views of patients and industry are not dissimilar. They can share a dream (and an action plan)…if it is built on an unwavering commitment to patients coming first. Read the rest of this entry »

Late Friday Afternoon: FDA, Politics, and Scientific Integrity

When my Smartphone delivered an e-mail at 5:12 p.m. on Friday: "FDA approv…," I knew that FDA had just announced something controversial. All public relations people (including those at FDA) have been taught that late Friday is the time to release stories you don't want to receive much attention.

Indeed, it was the 5-day emergency contraceptive pill, Ella, that was approved. So far, FDA seems to have achieved its goal of less coverage. But I was left wondering if the announcement required that treatment and why it led one advocate to describe the decision as "further evidence that the FDA is committed to restoring scientific integrity in its decisions."

Abortion is, of course, one of the so-called "third rails" in American politics. For politicians, this means: if you touch it, you will get burned politically. It has never been easy for FDA either. For many years, they were caught in the middle of Congressional and societal fights over the abortifacient, RU-486.

As I have written before (link below), FDA has been a master of little-noticed decisions that create or re-position a disease category. With the new approval, they seem on relatively safe ground in deciding it is an emergency contraceptive. Apparently, there is a nuance as to whether the drug's mechanism of actions solely delays ovulation or also makes the womb less receptive to implantation. There may be a theological difference, but I don't see any practical difference.

Ella's approval doesn't seem to have been a hard decision and I can't imagine FDA found it particularly difficult. By announcing the decision late on Friday afternoon, they probably made it seem more consequential and controversial than if they had sent out a more complete press release at a time more conducive to news coverage.

That brings me back to whether this approval is really about "restoring scientific integrity" in FDA decisions. The comparison is being made to the controversy over Plan B, an emergency contraceptive with a much shorter window of efficacy than Ella.

The main issues for FDA regarding Plan B were: should the drug be available over-the-counter (OTC) without the input of a prescribing physician and whether it should be available OTC for women under 18. In my opinion, these were not primarily scientific issues, but social and societal ones. It is completely unlike the current approval of Ella, which will be dispensed only by prescription and doesn't raise the same societal issues or maybe doesn't raise any at all.

I am not defending the Bush administration's handling of Plan B. They could not have done a worse job and they deserve the criticisms they received. But the administration was probably right that the issues were not primarily scientific ones and required input from politically-accountable levels of the government and elected officials—people who have responsibility for public policy that impacts social and societal interests. The Bush Administration should have been more honest about that, rather than pushing the decision down to FDA officials.

Apart from a couple of decisions like Plan B, which are rare, controversial and were badly mishandled, I don't see that the agency made scientific decisions during those years that lacked integrity. There are always controversies about application of "safe" and "effective" standards….and accusations that science is being ignored. Ella is science-based decisionmaking and business as usual for FDA, not some restoration of agency integrity.

Steven

The FDA press release and the WP and NYT coverage:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm222428.htm

http://www.washingtonpost.com/wp-dyn/content/article/2010/08/13/AR2010081305098.html

http://www.nytimes.com/2010/08/14/health/policy/14pill.html?scp=1&sq=ella%20contraceptive&st=cse

An earlier column that is relevant. It includes a brief comment on FDA and pregnancy.

FDA: Invisible Arbiter of What Constitutes Disease

November 19th, 2009

According to Wikipedia, "disease" refers to any condition that causes pain, dysfunction, distress and social problems. What constitutes disease is more varied and changeable than this definition might suggest.

The nature of disease and its constant changes are pertinent to FDA, which often makes decisions on behalf of society that reshape our understanding of disease. Read the rest of this entry »

Benefit, Risk and the Coming Age of REMS

FDA supposedly swings back and forth between emphasizing "expedited approvals of promising therapies" and "extended pre-approval examination of every safety issue." Current thinking is that FDA is now leaning more toward the safety end of this spectrum.

FDA Matters thinks a lot of this is perceptual. Approval decisions reflect FDA's honest and relatively clear judgment on medical need, quality of the clinical data, and the risks and benefits of a specific product. Mostly, I can understand FDA's decisions, even when I don't agree. Still, there is a lot of tension within FDA and with various stakeholders about approvals versus safety risk.

In 2007, Congress thought it was doing FDA a favor by providing new tools to speed approvals while better controlling safety risks. The agency is now required, prior to approval of each drug and biologic, to consider the possible value of a Risk Evaluation and Mitigation Strategy (REMS) plan.

REMS replaced a succession of more limited FDA programs designed to decrease the risk that medical products result in adverse outcomes. Risk reduction might involve more detailed patient materials to be dispensed with a prescription, mandated patient counseling, restricted distribution channels (e.g. only specialty pharmacies) and so on.

Congress also thought it was doing industry a favor. The expectation was that REMS plans would provide a way for FDA to approve more drugs when there were important patient benefits, but also significant safety risks. Control the risks….and the benefits of a medical product will more often outweigh those risks. At least at the beginning, REMS plans helped FDA approve some drugs that had languished at the agency.

As I recollect, industry was, at best, lukewarm toward REMS and found it hard to see what favor Congress was bestowing on them. They feared that approvals would come with REMS plans that were so onerous that patient access to new therapies would be threatened (along with the company's hoped-for market). Many patient organizations agreed that REMS might inappropriately restrict patient access.

In an ideal world, physicians would prescribe omnisciently, always giving patients the right drug at the right dose to maximize the treatment benefit with little risk of bad outcomes. In turn, patients would diligently absorb and follow all drug information and instructions they receive, thus benefiting from the therapy with a negligible risk. And patients would always know what side effect or symptom meant they should return to the doctor. They would also know how the instructions attached to one drug related to instructions on another drug.

Instead, our current system is far from ideal. REMS remains the immediate best hope of reducing adverse outcomes and therapeutic failures. FDA recognizes this and has devoted substantial effort to making REMS work. For example, FDA is testing whether REMS by drug class and indication (e.g. opioids for long-term pain) can maximize patient benefit, level the playing field for competing products, and reduce the agency's workload.

Even more importantly, the FDA recently held two days of hearings to receive feedback from patients, industry, physicians, pharmacists and health plans. All have a stake in REMS plans that are effective without being onerous or confusing.

Based on my experience, it will take five years of debate, reaction, and conflicting demands for FDA to work out some fundamental and predictable rules for REMS plans. Gauging by the calendar and substantive progress, FDA is about halfway there.

Everyone in the medical products industries needs to keep an eye on the evolution of REMS. Its long-term success is critical to FDA's careful weighing of "expedited approvals of promising therapies" and "extended pre-approval examination of every safety issue."

Steven

Some earlier related columns:

When Abbreviated May Not Mean Faster or Easier
July 25th, 2010

FDA is working on an approval pathway for bio-similars, re-examining the way medical devices are reviewed, trying to upgrade the quality and speed of generic drug reviews and will soon be evaluating its process for granting accelerated approvals to drugs.

These seemingly unconnected activities all have in common that they are supposed to be abbreviated processes to get new products to patients more quickly without risking safety or quality problems. FDA Matters thinks FDA should articulate its philosophy about how these short-cuts should work and what standards apply in all instances. Read the rest of this entry »

"Safe": Many Meanings Complicate FDA Policymaking
May 23rd, 2010

FDA Matters is in favor of safe foods and safe medical products. Who isn't? If you are a consumer, maybe that's all that matters.

However, being in favor of safe foods and safe medical products is not enough if you are FDA, the media, Congressional authorizers and appropriators, OMB, and industry. It sounds good, but what does it really mean? In the FDA context, "safe" means many things, some of which are barely related to each other.
Read the rest of this entry »

Has FDA Slipped Back into Anti-industry Mode?
January 13th, 2010

An industry CEO wrote me to observe: FDA is returning to the anti-industry paradigm of the past.  His concern is understandable. Yet, I respectfully disagreed with him. It is natural to fear change. It is easy to confuse activism with ideology.

FDA Matters believes there are two perspectives from which to judge the situation of FDA versus industry. Read the rest of this entry »

When Abbreviated May Not Mean Faster or Easier

FDA is working on an approval pathway for bio-similars, re-examining the way medical devices are reviewed, trying to upgrade the quality and speed of generic drug reviews and will soon be evaluating its process for granting accelerated approvals to drugs.

These seemingly unconnected activities all have in common that they are supposed to be abbreviated processes to get new products to patients more quickly without risking safety or quality problems. FDA Matters thinks FDA should articulate its philosophy about how these short-cuts should work and what standards apply in all instances.

There is a constant tension between going faster and going slower in making any approval decision. No matter what it does, the agency will be criticized by somebody who thinks they should have waited longer or acted more quickly. The four abbreviated processes seem to bring particular problems because they challenge regulators to balance safety vs. risk and faster vs. slower. In addition, they tend to heighten the distance between companies that are winners and losers.

There is constant tumult around generic drugs. Is proving bio-equivalence really enough to prove two drugs will work the same and thus speed market availability of the generic? Given the relative ease of a generic approval, why does the Office of Generic Drugs have a large and ever-growing backlog?

Likewise, there are always questions about the medical device review process. In particular, the 510(k) approval process is never without skeptics. Many would like all complex devices to meet standards similar to drug approvals. Others point to the quicker pace of innovation and the more incremental nature of new devices as reasons to reserve more elaborate reviews for the most complex and groundbreaking devices.

FDA is currently deciding how to implement the newly created bio-similar pathway. Many (this author included) have suggested that many products for which this abbreviated process was designed will find it advantageous to use the traditional approval route. Surely, this is not why new approval paths are created.

Accelerated approval allows drugs for significant unmet medical needs, primarily life-threatening diseases, to gain market access while further clinical testing is underway. It is not often used (nor should it), but in special cases it allows patients and their physicians to make their own judgments about the risk of the drug relative to the potential benefit. This process is likely to be reviewed now that a drug with accelerated approval proved unsuccessful in further testing.

FDA should always be looking to create greater predictability in its actions. Abbreviated processes hold the potential to benefit patients, increase access, lower costs, and promote innovation. The actual mix of FDA actions more often obscures this, leaving abbreviated pathways to look like an industry battleground rather than a reasoned way to maximize public good.

I envision FDA guidelines on abbreviated pathways that will tell agency employees, patients and industry about appropriate expectations, conditions for use of pathways, levels of proof, and avenues for appeals or to provide greater clarification.

Without this larger FDA view, we will have more of the same: abbreviated approval processes that are often not faster or easier….nor in the public interst.

Steven

For those readers still thinking about this month's Avandia advisory committee, which featured a sharply divided FDA, this recent column may be useful:

Dissent and Efficiency: Difficult Trade-offs for FDA
May 9th, 2010

FDA has a reputation for being tough on dissent, whether it comes from employees or regulated companies. It is often alleged that FDA employees with contrary views are re-assigned, marginalized or ousted. Within the regulated industries, there is a widespread belief that arguing with FDA has adverse consequences for a company.

Whatever the truth has been in the past, FDA is trying to develop an institutional cultural that welcomes and accepts dissent from employees, industry and other stakeholders. It is difficult, even messy, to do this. Yet, FDA's reputation and authority rests on showing that it listened to all competing views–without unreasonably slowing the decisionmaking process. Read the rest of this entry »

PhRMA’s Choice: A Man for All Reasons?

The Pharmaceutical Research and Manufacturers of America (PhRMA) has announced John Castellani as its new CEO and President. For the past 9 years, he has been the head of the Business Roundtable, a very successful association of corporate CEO's.

History tells us that the choice of a new PhRMA President will reflect the Board's view of the state of the industry and its most pressing needs. The new appointment continues that tradition.

At the outset, let me say that Mr. Castellani appears to be eminently qualified. He has roots in corporate America and has spent years steering a powerful association. He knows how to manage CEO's. Early news coverage has characterized him as a manager, straight-shooter and non-partisan (although he mostly contributes to Republican campaigns).

However, there is more to his appointment. In a column earlier this year (link below), FDA Matters examined the past five Presidents of PhRMA, going back to the 1970's. It is hard to imagine that the same association could be led by individuals with such different backgrounds. Yet, on examination, each appointment was appropriate for the industry's needs at the time they were appointed.

Whether the PhRMA search committees have acted intuitively or consciously, their choices have been spot-on to what the industry needed.

In the earlier column, I stated: When his [Tauzin's] successor is chosen, it will tell us a lot about how the pharmaceutical industry sees itself….and what the big pharmaceutical companies think is their next major challenge. I think there are two such challenges faced by the bio-pharmaceutical industry:

• Strengthen solidarity with non-pharma industries, and
  
• Preserve its status as a major domestic industry, despite the growth and pull of globalization.
  

CEO's from other US industries are far more concerned about rising health care costs than the well-being of pharma companies. There have been moments when it seemed possible that broad industry groups might support positions affecting pharmaceutical companies that they would never support for their own companies.

For example, PhRMA would have great difficulty winning fights on re-importation and drug price negotiations if the rest of corporate America took the opposite position. To reduce or eliminate this possibility, who better to choose than the man who has represented the larger corporate community for the last 9 years?

With regard to the second challenge, PhRMA has successfully leveraged its status as a major domestic industry with a positive contribution to the American economy. This has helped soften the politically dangerous perception that American taxpayers, insurers and patients are cross-subsidizing the cost of medicines in other countries.

To sustain that leverage in the face of globalization, PhRMA needs to demonstrate that the US is still the home of the bio-pharmaceutical industry and that the growth of the industry is matched (or exceeded) by the economic benefit to the US. Who better to choose than a nationally-recognized advocate for policies to create domestic job growth and investment?

Some readers may say that these are not reasons enough to drive the choice of Castellani. Or they might argue that these are side-benefits rather than the primary point. I acknowledge that he is a "man for all reasons" and an obvious choice now that it has been announced.

I am intentionally looking at a larger perspective on the appointment, trying to see how it relates to the most important determinants of the long-term success or failure of PhRMA. My conclusion:

If John Castellani can maintain solidarity with corporate America, grow the perceived role of the pharmaceutical industry in the US economy, and manage the staff's communications and lobbying efforts….then everything should turn out fine for PhRMA.

Let me know what you think?

Steven

The press release announcing the appointment is at: http://www.phrma.org/news/news/john_j_castellani_lead_phrma_new_president_ceo.

An interesting profile: http://www.whorunsgov.com/Profiles/John_Castellani.

An interesting analysis: http://www.muckety.com/John-J-Castellani/96246.muckety

My earlier column:

Transition at PhRMA
February 14th, 2010

Former Representative Billy Tauzin tendered his resignation this week, ending a 5 ½ year tenure as President of the Pharmaceutical Research and Manufacturing Association (PhRMA). When his successor is chosen, it will tell us a lot about how the pharmaceutical industry sees itself….and what the big pharmaceutical companies think is their next major challenge. Here is FDA Matters' analysis. Read the rest of this entry »

Hot Town, Summer in the City—2010

For the news media, the only FDA story this coming week will be the two-day advisory committee meeting reviewing the diabetes drug, Avandia. Based on an earlier article (link below), FDA Matters will be looking at how Dr. Hamburg's FDA handles the discordant voices coming from within the agency.

Missing from public dialogue is the extraordinary (perhaps unprecedented) number of large, consequential projects that FDA will be working on this summer. Every part of FDA is involved in some initiative that could become a "game-changer" for the agency.

FDA shares at least two summer issues with Congress: comprehensive food safety reform and drug safety reorganization. Food safety legislation has passed the House. A different version is awaiting Senate floor action. Since final legislation is not guaranteed, FDA is working hard to develop an approach that is not dependent on statutory changes.

Although drug safety is not an active legislative item, several senior Members of Congress have been persistently calling for re-organization and other changes in how drug safety is evaluated and tracked. The Avandia advisory committee meeting has providing focus for these critics, but their positions do not depend on the outcome.

FDA's efforts to stay in control of drug safety are reflected in at least three initiatives that FDA is working on this summer: creating workable risk management plans (REMS) to accompany drug approvals; safety issues that are becoming part of the negotiations on renewal of drug user fees; and continuing efforts to update Sentinel and related tools for tracking adverse events and safety signals in large populations.

FDA continues its efforts to clarify its policies on safety and effectiveness of medical devices. Pre-approval issues include possible changes in the 510(k) pathway. Post-approval efforts include better device tracking.

Follow-on biologics (now re-named bio-similars) are also keeping FDA busy. This is the first new drug approval pathway in 25 years and FDA has already declared itself ready to accept product applications. At the same time, the agency has acknowledged that there are multiple policy issues to be resolved before agency guidance will be available. What FDA decides now (both on applications and policy) will reshape the world of bio-pharmaceuticals.

Some other top-level agency initiatives with potentially large consequences:

• FDA is grappling with its role in comparative effectiveness research.
  
• The FDA's Transparency Task Force has just reported its findings and recommendations.
  
• Upgrading inspections and enforcement are an immediate and ongoing priority for the agency.
  
• FDA is building a new relationship with NIH through a series of initiatives that will fail without serious attention.
  

Around the agency, here are a few more that could bring significant changes:

• FDA, NIH, patients and industry are trying to upgrade research on rare diseases and increase approvals of orphan drugs.
  
• FDA has promised guidance later this year on medical product communications on the Internet and in social media.
  
• FDA is wrestling with antibiotic use in food animals and kicking up some controversy.
  
• Implementation of the year-old tobacco legislation is ratcheting up after various provisions became effective in June.
  

Even upcoming product reviews may have interesting consequences. Over the next few months, FDA will be looking at three new drugs to treat obesity. This is a difficult product category with a history of safety problems. Yet, millions of Americans are likely to use these products if they are approved.

Despite the number of potential "game-changers" I have identified…no one knows better than Drs. Hamburg and Sharfstein how incomplete my list is. Fortunately, FDA has a great staff. I suspect most of them will be overloaded this summer.

Steven

FDA commissioners need to stay focused on their legacy, while dealing with the mountain of important issues discussed in today's column:

Not Too Soon to Consider the Hamburg Legacy
May 27th, 2010

May 18 marked one year since Dr. Margaret Hamburg was sworn in as Commissioner of the US Food and Drug Administration. The challenges are great, the torrent of issues is never-ending and most days you can smile but you can't win. It may seem premature to be discussing "the Hamburg legacy." But you know that she is thinking about it (all commissioners do), so why can't FDA Matters talk about it? Read the rest of this entry »

My earlier column that relates to the Avandia advisory committee meeting:

Dissent and Efficiency: Difficult Trade-offs for FDA
May 9th, 2010

FDA has a reputation for being tough on dissent, whether it comes from employees or regulated companies. Whatever the truth has been in the past, FDA is trying to develop an institutional cultural that welcomes and accepts dissent from employees, industry and other stakeholders. It is difficult, even messy, to do this. Yet, FDA's reputation and authority rests on showing that it listened to all competing views–without unreasonably slowing the decisionmaking process. Read the rest of this entry »

FDA to Industry: Contractors R U

It seems a rather uncontroversial proposition: FDA-regulated companies are responsible for their vendors, including every contracted piece of work that is done on the company's behalf. If problems develop, it makes no difference whether a company did it…or a contractor did it for them. Two seemingly unrelated items this week suggest that FDA is becoming concerned about whether FDA-regulated companies are overseeing their vendors.

This is not just about contract manufacturing. FDA's concerns extend to company/contractor relationships in marketing, distribution, communications, clinical trials, pre-clinical development, etc. FDA Matters expects food and device companies to be under similar pressure to improve their oversight of vendors, since the concerns about contractor reliability should be similar.

Beyond the well-publicized quality control problems at some major companies, FDA may foresee industry-vendor relationships as a more general concern. Perhaps FDA sees controls on the burgeoning responsibilities of contractors (out-sourcing) as a natural extension of the agency's regulatory responsibilities. FDA may also be signaling to industry that it will do them no good to whine: our contractors let us down and, therefore, the company shouldn't be held accountable.

New rules for outsourcing drug manufacturing. The Wall Street Journal reported on a conference in Ohio at which FDA officials said they will propose strict regulations for companies that outsource drug manufacturing. The goal is to hold sponsor companies more accountable for their vendors, whether in the US or abroad. In the past three years, violations of good manufacturing practices (GMPs) have increased threefold for contractors, while remaining stable for sponsors.

Despite what some might consider an unwelcome extension of regulatory controls, the items discussed by FDA are fairly benign. It even seems a little odd that FDA does not already require them. Specifically, the FDA will propose rules that include:

• FDA warnings about manufacturing violations will go to both the contractor and the sponsor, not just the contractor,
  
• sponsors will be required to conduct on-site audits at contract manufacturing facilities to ensure the quality of production and the safety and purity of ingredients, rather than allowing sponsors to rely on off-site review of records and reports compiled by the contractor.
  

New standards for evaluating clinical trial protocols. Dickinson's FDA Webview covered an FDA presentation at the Drug Information Association meetings in DC about changes in the agency's oversight of clinical trial design and implementation. Company protocols will need to be accompanied by information about how the study incorporates "quality by design" (i.e. companies must plan quality into the project rather than assume it happens as a byproduct of earnest effort).

Henceforth, the agency will consider the "operational merit" of a proposed protocol in additional to the traditional review of "scientific merit." On a practical level, this means that FDA will want to know why the study will have 60 sites instead of 30, why sites were chosen, how investigators were selected, who's monitoring sites and how investigators will be trained.

FDA presented this in the context of clinical trial results that can be relied upon…..but it relates directly to an activity primarily done by company contractors, whether a contract research organization (CRO) or academic researchers.

However much the latter example (clinical trials) appears to differ from the former example (drug manufacturing), the principles are essentially the same. FDA is telling companies: you are responsible for your vendors and we want evidence that you are watching them much more closely than you have in the past.

No company can be stronger than its weakest vendors. FDA-regulated companies should start now to evaluate their contractors, then extend and strengthen their everyday oversight.

Steven

Wall Street Journal article: "FDA to Propose Tougher Rules for Outsourcing Drug Manufacturing," appeared on June 15, 2010. http://online.wsj.com/article/SB10001424052748704324304575307421660792654.html#articleTabs%3Darticle

Dickinson's FDA Webview, www.fdaweb.com, "Clinical Studies Will Need More Design Details: FDA," June 14, 2010 (by subscription or individual articles may be purchased) http://www.fdaweb.com/login.php?sa=v&aid=D5115187&cate=&stid=%241%24Wl1.n52.%24zGTEH.bvqbwrCcWcM%2FA3k .

Quality Control Woes: What's a CEO to Do?

June 2nd, 2010

Medical products companies are struggling to assure FDA and the American people that their products are "safe as manufactured and distributed." We don't know whether quality control has become lax, FDA is discovering more problems or industry has just had a run of bad luck. We do know that quality control relies on a lot of people maintaining tough standards…and that manufacturing is rarely a priority of a drug and device company CEO. Earlier this year, in the wake of Toyota's problems, FDA Matters asked: "what's a CEO to do?" Read the rest of this entry »