House Votes on Health Reform: What’s Next?

By the incredibly close margin of 220 to 215, the US House of Representatives adopted health reform legislation on Saturday evening, November 7, 2009. In the end, abortion restrictions were added…and liberals were forced to accept these and provide the margin of victory.

The content of the House bill is of little significance. However, its passage is an historic event, creating a near-certainty that President Obama will be signing final legislation in the next 3 months.

Everyone's attention will now return to the other side of Capitol Hill. Senate Majority Leader Harry Reid has only one task: find the combination of health reform provisions that can command 60 votes in the Senate. He knows the answer is not in the House bill.

To get to 60 votes, Reid will need to agree to giving states the option of joining a government-run insurance plan or accept a mechanism where a government-run insurance program is triggered only if insurance reform doesn't reduce premiums. Not unlike the House, President Obama will be needed to persuade Senate liberals that this is a better outcome than no legislation at all.

Holding 60 votes may be as challenging as getting 60 votes. News stories have mentioned the possibility that Senators might offer 2000 amendments, regardless of what package Senator Reid offers. Leaving aside the weeks of Senate floor time this would require, every vote would hold the potential to break apart the 60 vote majority that Senator Reid would have labored to put together.

Sharp limits on amendments will be required. Perhaps, the 60-vote majority will have to agree to a text beforehand and then oppose all amendments. The same problem would recur in House-Senate conference...so there will probably be no conference. Instead, four to 10 weeks from now, President Obama will be back on the House side, persuading liberal members that the Senate bill is the best possible. He will be urging them to vote to accept that bill when it comes back to the House for consideration.

So, the House bill means nothing, but its passage will push forward a political process that Democratic leadership cannot allow to fail. They will have no choice but to twist arms until the votes and the process makes success possible.

Where is FDA legislation in all of this? Some version of follow-on biologics will be in the final legislation. The House bill won't matter. The specifics will be those agreed to in the Senate over the next few weeks.

Where is FDA in all of this? Advocates need to strongly and continually reinforce the relevance of the agency in a political world that will be dominated by implementation of health reform. The arguments may seem obvious: safe and effective drugs, biologics and devices are an essential part of preserving and improving human life. This will be true in a reformed system as much as it is today. The difficulty is knowing whether any Members of Congress will be listening.

Steven

Animal Research: One of FDA’s Core Values

Earlier this year, ABC's Nightline did a story about alleged abuses at the nation's largest primate research center. Fueled by this, the Great Ape Protection Act (HR 1326) now has 95 co-sponsors, compared to 29 sponsors on a similar bill in the last Congress.

The bill would virtually eliminate research using chimpanzees, even where there is no other animal model that could serve to predict safety in humans. This is a threat to animal research and, ultimately, to ourselves. The loss of chimpanzees would be a serious blow to research and would encourage animal rights activists to push for even more restrictions.

The value of animal research in the life sciences is considered an NIH issue. The research advocacy groups opposing the legislation are all part of the network that supports NIH

FDA Matters believes that the FDA and its stakeholders should be equally concerned.

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

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

We talk about the people part without recognizing that the pipeline of innovative drugs and devices would narrow without chimpanzee research. It would collapse completely if a broader range of research on animals (e.g. monkeys, pigs, sheep, dogs, rats) was heavily restricted.

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

While purportedly about the welfare of animals, the House bill is really designed to grant rights to animals, starting with chimpanzees. There are elaborate arguments about whether animals should have rights or just have their welfare protected. For me, the choice is easy. I want a product or procedure tested in animals before it is given to me or my loved ones. I believe in protecting animals, but human rights come first.

Chimpanzees are crucial to animal research. If the House bill were to become law, important animal research might be halted in vaccines, hepatitis A, B and C, HIV/AIDS, malaria and some types of cancer. I am told that in these diseases areas, research on chimpanzees often provides essential information that cannot be obtained in any other way.

The importance of animal research needs to be a core value for FDA. The stakeholder community needs to "seize the day" and make clear where its stands. Those who benefit from animal research (including patients) need to provide the manpower and financial resources to counter the animal rights movement in America and its threat to medical progress for humans.

Steven

The ABC Nightline story is at: http://i.abcnews.com/Nightline/story?id=6997869&page=1.

A good review of appropriate animal research activities and processes is at: http://www.arvo.org/EWEB/dynamicpage.aspx?site=arvo2&webcode=AnimalsResearch

There are many good organizations that work to counter the People for the Ethical Treatment of Animals (PETA) and other animal rights organizations. One of the most effective is Americans for Medical Progress (AMP), an organization that educates media and the public about the importance of animal testing in advancing human health. Among other projects, they are organizing scientists to be more pro-active and articulate about the importance of testing on animals. AMP can always use more support for their work, www.amprogress.org.

The Beatings Will Continue…

….until the biopharmaceutical and medical device industries clean up their act.

It has been an expensive year for pharmaceutical companies. Billions of dollars have been paid to federal and state governments and whistleblowers in settlement of allegations and lawsuits. The complaints include off-label marketing and overcharging Medicaid, but there are many others.

While I am sure there are some "innocent" companies that are the targets of allegations, there are far too many expensive settlements and verdicts for industry to claim that they are victims of overzealous prosecutors and "get rich" whistleblowers. Earlier, FDA Matters called on the biopharmaceutical and medical device industries to recognize that "sales are not more important than laws." ("Off-Label Promotion and Whistleblowing" at www.fdamatters.com/?p=479)

I worry that companies figure they are ahead financially as long as profits exceed penalties. Not for long! The civil and criminal complaints are going to increase and settlements and verdicts are going to get larger. Legislation will get even more restrictive….and a wave of bad publicity will haunt the medical products industries and may forever destroy the public appreciation of the human benefits these companies provide.

US attorneys, state attorneys general, and inspectors general will keep probing until there is nothing left to investigate in the biopharmaceutical and medical device area. This won't happen anytime soon.

Over 180 pharmaceutical fraud cases involving more than 500 drug products are being investigated by the Department of Justice under the False Claims Act. Reportedly, most involve allegations of false and misleading statements made with intent to defraud or mislead. An additional back-log of 1000 whistleblower cases is waiting for DOJ to decide whether to participate. (From comments made by Jennifer Bragg, a partner in the law firm, Skadden, Arps, as reported in Dickenson's FDA Webview).

CEO's need to see corporate accountability as their personal responsibility. The handwriting is on the wall, based on the recent successful criminal prosecution of a small biotech CEO. Sometime soon, a US attorney is going to decide that monetary settlements should not be allowed to wipe out criminal charges. As a result, some senior executives in multi-billion dollar pharma companies may go to jail.

CEO's can no longer afford to trust themselves or their corporate management in judging whether they have followed the law. They need to verify. This requires tougher questions, independent audits of sales and marketing efforts, and alerting physicians to report to the company any meeting where a company representative made false or misleading claims. These companies should be hiring and empowering former prosecutors and investigators to review both policy and performance.

I believe in the transformative power of the biopharmaceutical and medical device industries to lengthen lives, deliver cures, control symptoms, and relieve pain. My advice to CEO's is clichéd but true. When the subpoenas arrive: "Do not ask for whom the bell tolls, it tolls for thee." Is anyone listening in the corporate suites?

Steven

The article cited in Dickenson's FDA Webview is available at:

'Whistleblower' Cases Dominate FD&C Act Prosecutions [639 Words] [ Price : $14.95]

With more than 180 pharmaceutical fraud cases now under investigation by the Department of Justice, FD&C Act prosecutions are now largely driven by "whistleblower" lawsuits, according to Eugene Thirolf, director of DoJ's Office of Consumer Litigation. 10/14/2009

CARS: The Vehicle for FDA’s Future

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.

This is a large task for Commissioner Hamburg to take on while running FDA and overseeing products that account for one-quarter of consumer spending. Yet, the agency will never improve if she doesn't find the time. Given increasing globalization, ever more complex science, and new Congressional mandates, the agency may even lose ground without important advances in regulatory sciences.

FDA is already involved in creating scientific tools and methodologies to support good decisions. The Critical Path Initiative (CPI) has been an important first step in creating a list of worthwhile projects to advance regulatory science. Many have been funded.

The National Center for Toxicological Research, a backwater of sorts at FDA, has been quietly supporting the scientific needs of the rest of FDA by developing new scientific tools, methodologies, and knowledge. Subtract field activities from the budget of the Center for Food Safety and Nutrition (CFSAN) and a large part of the Center's remaining budget is devoted to advancing regulatory science (e.g. creating faster assays to test for bacterial contamination).

The Center for Drug Evaluation and Research (CDER) also plays a role. Developing biomarkers is part of advancing regulatory science, as are new tools for surveillance and bioinformatics. The value is realized when these become part of tomorrow's regulatory decisions.

CPI was once considered the way to pull all of these activities together to advance regulatory science at FDA. It has not developed the vision or support necessary to accomplish this. Efforts to develop public-private funding for CPI activities have also been a distraction. We now know that Congress needs to fund these activities so the regulators lead regulatory science, not the regulated.

Several months ago, FDA Matters proposed the creation of the Center for the Advancement of Regulatory Sciences (CARS) at FDA. The Center was to be a defining enterprise—consolidating existing activities within FDA, providing a separate basis for advocacy and funding, and making clear that advances in regulatory science serve the future needs of the FDA Centers. I believe the CARS concept can be a starting point for discussing how advancement of regulatory science can become integrated into FDA's mission.

By talking about advancing regulatory science, Commissioner Hamburg is onto something important. We need to support her and help her develop broad acceptance of regulatory science among the policymakers who authorize programs and appropriate monies for FDA.

Steven

A definition of "regulatory science" and additional discussion are contained in my earlier columns:

Save the Critical Path—Part 1, June 17th, 2009

The American public and the global marketplace wish to have access to innovation—whether in medical products or foods. Simultaneously, there are strong countervailing concerns about product safety. Both occur within an environment in which FDA's knowledge and tools are inadequate and failing.

The Critical Path program and related initiatives in CFSAN and other centers are designed to meet this challenge. Unfortunately, there has never been a sustained agency-wide commitment to these efforts. Further, most of Congress has not embraced the Critical Path, either conceptually or with substantial funding. Read the rest of this entry »

Save the Critical Path—Part 2, June 28th, 2009

Transforming FDA into a first-class, 21st-century regulatory agency will not be easy. It requires planning, commitment and a broad vision. Science-based decisionmaking is a central part of the transformation, but it doesn't just happen by itself. Regulatory science needs to provide the tools, standards and knowledge for FDA to handle an ever-more complex world of science and commerce. Read the rest of this entry »

The Science Board’s IT Report: Too Technical to Read, Too Important to Ignore

Some of FDA's most difficult tasks are: defining the agency's role in nanotechnology, creating a pathway for follow-on biologics, implementing a risk-based food safety system, and establishing the right policy for "new media" communications.

All rolled together, they are not as complicated or important as transforming information technology (IT) at FDA.

The anecdotes are legion:

• adverse events reports come in electronically, are printed and re-keyed into a database;
  
• hardware and software vendors bring people out of retirement to service FDA's out-dated systems (so-called legacy systems);
  
• a report e-mailed to Capitol Hill for the next day arrives after the meeting.
  

I can only vouch for the last one, but the others are believable.

In August, the external FDA Science Board reviewed a report on information technology submitted by its subcommittee. FDA has put substantial resources and made valuable commitments to creating new systems. The biggest gains have been in infrastructure. Progress is being made in hardware, software, integration, capacity, security, infrastructure, and planning.

Clearly, the subcommittee liked what it saw. Their review also highlighted continued challenges in creating a 21^st century IT system capable of supporting all of FDA's mission-critical activities.

The report made some news in trade publications for a few days, then was quickly gone from public view. The issues are too technical to interest most people. Even with a glossary, I confess to not understanding at least half of the report.

Maybe the lack of visibility is alright if FDA and its contractors can absorb the many suggestions and recommendations in the report. FDA Matters recommends that an external review be undertaken every 3 or 4 months to be sure the effort remains on track.

While one can quibble about specific Congressional directives that depend on information technology systems, the main direction has been appropriate. FDA needs to fix the machines, create the databases, and integrate functions

This initiative is so important that non-IT people need to keep informed. Simply put, the agency's ability to conduct its work, increase effectiveness, and become more sophisticated is more contingent on the IT overhaul then the personnel that are being hired into the various centers to conduct the actual work of the agency.

In 5 years, nobody at FDA will be able to do their job if the IT overhaul isn't a success.

Steven

The FDA Science Board subcommittee report was completed in August and can be found on the FDA website at:

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ScienceBoardtotheFoodandDrugAdministration/UCM176824.pdf

In an earlier column, I addressed another facet of the agency's IT challenge:

Turning Data into Knowledge   June 2nd, 2009

Through statute and directive, FDA has been asked to collect, analyze, interpret and utilize massive amounts of data. This includes biological, clinical, adverse event, production and distribution data, medical and food product tracking, and the Sentinel system for early discovery of potential drug safety problems. The systems are not in place to do any of this, at least not at the required level of sophistication. Even if they were, sifting valuable information from background noise is extraordinarily hard. As a result, FDA needs to manage Congressional and public expectations as to "what is possible and when." Read the rest of this entry »

Why Do Some People Dislike FDA?

Yesterday, I received separate posts from three organizations that are anti-industry, one of which dislikes FDA and one of which hates FDA. They are not alone in these feelings. There are many groups and individuals who believe that industry and physician professional societies run FDA. I don't accept their premise or the "facts" from which they launch attacks.

On the same day, I got an update from Americans for Medical Progress (AMP), an organization that educates media and the public about the importance of animal testing in advancing human health. FDA could not do its job without animal studies, both their own and those submitted by sponsors. AMP is among the "good guys" and can always use more support for their work, www.amprogress.org.

I would like to say that all the advocates, such as AMP, are realists and advance the common good by advocating for NIH and FDA….and that all the extreme critics and haters are irrational and inflammatory. It isn't that simple.

The FDA I know is a regulatory agency staffed by smart people trying to do their best. Given its mission, FDA is inherently imperfect and always vulnerable to criticism. The agency has been chronically understaffed and hasn't been able to give every decision the attention it might deserve.

I am on my tenth FDA commissioner. Bad decisions were made during each of their tenures and they all experienced bad days when nothing seemed to work the way it should. Meantime, hundreds of drugs and devices have been approved without subsequent mishap. Our food supply is vulnerable because of globalization, yet it is the safest in the world.

Those who dislike or hate FDA focus almost exclusively on those bad decisions and on the agency's most difficult days. In their minds, that is the FDA. They don't see the rest of the days where things went well: public health improved, patients received new FDA-approved therapies and more than 300 million Americans ate food without an outbreak of foodborne disease.

Because they ignore the good days and focus only on the bad, the haters feel justified in concluding that the agency is corrupt and deserving of vilification. I disagree vehemently with this premise.

I see some of the same problems they do, but recognize the problems are only a small part of FDA's mission and accomplishments. Given this wider perspective, it is misguided to impugn FDA and its staff. Bad days occur, but not because of impure motives or because agency officials blindly listened to the industry's views.

Those who dislike and even hate FDA serve a purpose. Scrutiny makes everyone think and work a little harder to make good decisions. Companies with safe manufacturing plants can still get in trouble with FDA if they haven't documented their safety-related activities. So, too, FDA needs to be able to show it has listened carefully and decided wisely. It can't just assert its decisions are good ones. Better documented and more predictable decisions are needed.

All of this can be taken too far….so that over-cautious decisions become a source of delay or failure in meeting the needs of patient and consumers. The haters would certainly like it that way. The extreme critics serve some useful purposes in a narrow sense, but they are wrong about the big picture of FDA's mission, intent and accomplishments. It is critical that we act civilly in the face of this hatred. That said, we must act to counter their arguments and make sure that the extreme version of FDA-bashing has no reputable standing in Congressional, media and public discourse.

Steven

More predictable decisionmaking at FDA was discussed in an earlier column.

In Praise of Predictability September 3rd, 2009

FDA has always found it challenging to make its actions predictable. This problem will worsen for a number of months while Dr. Hamburg redefines the agency's mission, policies, actions and working assumptions. Once this has been accomplished, the agency will become dramatically more predictable to stakeholders, including Congress. Read the rest of this entry »

Health Reform and FOB’s: From Debate to Done in Thirty Days

On Tuesday morning, October 13, the Senate Finance Committee is scheduled to vote on its version of health reform legislation. This is ground zero in a contest of political will and national priorities that began over 65 years ago. This is big…a tidal wave of change coming to the US health care system.

The Finance Committee bill, once passed, will be melded with the version passed in the Senate Health, Education, Labor and Pension (HELP) Committee. Although it's a small detail in the massive health reform bill, the future of follow-on biologics (FOB's) depends on what comes next.

Since early July, FDA Matters has expressed its political admiration for Representative Anna Eshoo's bi-partisan success in garnering more than 140 cosponsors for her bill. I have never seen a committee chairman face the overwhelming odds this presented to Representative Henry Waxman.

Yet, I reminded my readers that Chairman Waxman has a long-history of "not having the votes" and winning anyway. I repeated this observation in August and again in September. This was confirmed, indirectly, by Waxman in a speech he gave about two weeks ago when he told his audience that he hadn't given up on his version of FOB legislation. He asked them to keep working to get his bill passed.

There are at least four opportunities for the very similar House and Senate FOB provisions to be altered to favor Chairman Waxman's position:

• when the two Senate committees merge their health reform bills,
  
• when the three House committees merge their bills,
  
• when the bill goes to the Senate floor and can be amended, and
  
• during the House-Senate conference to reconcile differences between versions passed by each body.
  

Three of these opportunities will take place behind closed doors where anything can happen. You don't need to "have the votes" to prevail….only to be in the room when the decisions are made. Chairman Waxman will be in Speaker Nancy Pelosi's office when the deal is cut on the House side. His ally, Senator Charles Schumer, will be in Majority Leader Reid's office when the Senate bill is agreed upon. Both Waxman and Schumer will be on the House-Senate conference committee.

I no longer think it will happen this way. This multi-step process is a recipe for legislation to be bogged down until next year when health reform and FOB's will die an agonizing election-year death.

To avoid those delays, the Senate bill will be the Finance Committee bill with:

• some provisions from the HELP committee version,
  
• some provisions necessary for Reid to get to 60 votes in the Senate to avoid a filibuster, and
  
• a few provisions that are high priorities for the House (other than a public plan).

The President will then endorse the Senate bill. Assuming Reid has negotiated carefully and counted correctly, the agreed-upon bill will be moved quickly to the Senate floor. The 60 Senators will have agreed not to offer amendments on the Senate floor (allowing one amendment will allow hundreds).

As soon as the Senate-passed bill reaches the House, the Speaker will schedule an "up or down" vote. The President will help her keep the Democratic majority together. There will be no House-Senate conference.

The pending "behind closed doors" Senate negotiations may be the only time further changes will be made. Afterward, Members of Congress will be able to blame Reid and Pelosi that they weren't allowed to offer amendments favored by whatever constituents and health care stakeholders they were trying to help.

The bio-pharma and generic industries probably have no more than two to three weeks to persuade the Senate negotiators to take their side on data exclusivity and other FOB issues. There may be no second chance.

We are going to go from "debate to done" in thirty days.

Steven

My prior columns on follow-on biologics are at:

Fall Scorecard for Follow-on Biologics,
September 11, 2009

Health Reform and Follow-on Biologics September 6th, 2009

The Best Little Chess Game in Town August 3rd, 2009

Follow-on Biologics and the Dance of Legislation July 5th, 2009

The Follow-on Biologics Market June 23rd, 2009

To Whom Much is Given, Much is Expected

There is good news to report now that House-Senate conferees have finalized work on FDA's FY 10 budget. FDA received $306 million (15%) more to spend this fiscal year. Every center will have more resources to work with (see table at the bottom of this article).

This is the third good year for FDA, after years of bad ones. The agency is still severely underfunded, but progress is finally being made. Now the hard work begins: spending the new money wisely and showing that it has been used to accomplish important public health missions.

Because FDA has been shortchanged for so long, it is almost unfair to expect results in anything less than 3 to 5 years. However, Congress will only be patient for so long. FDA and Dr. Hamburg don't have much time to produce serious improvements.

Even acknowledging that a vastly larger appropriation is still needed, it is understandable why Congress won't wait very long before expecting results:

• In the past two fiscal years (since FY 08), the budget for food programs has increased by more than 50%. Much of the extra money is allocated for field activities (inspections and enforcement).
  
• Budgets for CDER, CBER and CDRH have all grown by more than 30% in the last two fiscal years.
  
• The overall agency appropriation has increased by $776 million over the last three fiscal years (since FY 07). The represents a 50% increase in funding.
  

Dr. Hamburg and Dr. Sharfstein are responsible for moving the agency forward. Congress and the American people will hold them accountable.

They can't do it alone. FDA staff is smart, committed and largely effective. Yet, territorial behavior is fairly common and creates multiple problems. The Commissioner must create a vision of the agency that gives FDA employees a reason to work for the entire agency, not just for their own division or unit.

"To whom much is given, much is expected" applies to all of FDA. It will take a team effort to meet the lofty, but legitimate, expectations that have been created.

------------------

In prior columns, I have focused on other aspects of the appropriation process. Here is an update:

• FDA's Office of Regulatory Affairs (ORA) receives more appropriated funding (about 1/3 of the total) than any other part of FDA. For FY 10, appropriated funding directed to ORA increased by 20% to $847 million. This situation led me to dub the head of ORA as The Uncrowned Prince of FDA, at http://www.fdamatters.com/?p=499.
  

• Unfunded mandates are a continuing concern for FDA, threatening the funding progress that has been made over the few years. Pending legislation (e.g. food safety reform) has not advanced since I last wrote on this topic. On a smaller scale, the FY 10 conference report adds $7 million to cover some new program requirements, in effect acknowledging that these would otherwise be unfunded mandates. My column, Unfunded Mandates Threaten FDA, is at: http://www.fdamatters.com/?p=375.
  

Steven

The House-Senate conference report can be found on pages 210 to 216 at: http://appropriations.house.gov/pdf/Ag_Conf_Rpt_FY2010.pdf.

FY 10 Appropriations for the Food and Drug Administration

Compared to Earlier Years (based on Conference Agreement)

Budget Authority Appropriations (does not include user fees)

(Prepared by the Alliance for a Stronger FDA)

Function Note: budget authority only, by center	FY 08 Actual (December 2007)	FY 09 Final (March 2009)	FY 10 President's Budget Request	FY 10 House-Senate Conf. Final
Food	$   510 million	$   649 million	$   783 million	$ 783 million
Human Drugs	$   353 million	$   413 million	$    458 million	$ 465 million*
Biologics	$   155 million	$   183 million	$    206 million	$ 206 million
Animal Drugs/Feed	$     97 million	$   116 million	$    135 million	$ 135 million
Devices & Radiological Health	$   238 million	$   280 million	$    315 million	$ 315 million
Natl. Ctr. For Toxicological Research	$    44 million	$    52 million	$     59 million	$ 59 million
HQ, Office of Commissioner and Other	$    97 million	$   121 million	$    144 million	$ 144 million
Rent & Facilities Cost	$  220 million	$   223 million	$    237 million	$ 237 million
SUBTOTAL, Salaries and Expenses	$1.714 billion	$2.039 billion	$ 2.338 billion	$ 2.345 billion
Building and Facilities Repair	$ 8 million	$ 16 million	$ 12 million	$ 12 million
TOTAL, ALL Budget Authority Appropriations (no user fees)	$1.722 billion	$2.055 billion	$ 2.350 billion	$ 2.357 billion

* The $7 million increase is intended to pay for some of the additional costs that CDER will bear as a result of Conference report language that contains increased financial commitments to the Critical Path program, generic drug reviews and other CDER programs.

“No Surprise” That Medical Devices Are Under Scrutiny

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.

A lot of people, including Wall Street, seemed surprised when FDA kicked its medical device re-evaluation effort into high gear over the last 10 days. I am not sure why they were surprised. The FDA re-evaluation was a certainty and has significant consequences for businesses and investors.

The medical device process and 510(k) approvals have been in question for a number of years. It has been a long time since there has been a thorough re-evaluation.  GAO is perpetually raising concerns about medical devices and a number of key Congressional leaders are interested. Also, the 510(k) approval process is necessary and defensible, but not easy to understand. It will continue to be a target for media, investigators, and crusaders until the process is re-evaluated and any needed changes made.

In April, Principle Deputy Commissioner Sharfstein acted affirmatively in response to the GAO's early 2009 report on medical devices. Last week, FDA set out its plans for a credible, effective re-evaluation of medical devices. This latest phase of the re-evaluation process featured three major items from FDA:

• Commissioning an IOM study of the medical device classification process, focused on the 510(k) process (which allows new devices to be approved by showing "substantial equivalence" to previously approved products);
  
• Release of FDA's analysis and recommendations based on review of the decision to grant 510(k) approval to a device manufactured by ReGen Biologics; and
  
• Creation of internal working groups to recommend and implement changes without waiting for the IOM report.
  

As FDA made clear during its press conference, the ReGen case is not the reason for FDA's review of the medical device approval process. Rather, approval of the ReGen device has proved to be instructive because so much went wrong. Among other things, there were violations of internal FDA protocols, inconsistent interpretations of the law, widespread confusion within FDA, poor communications with the sponsor company, and questionable involvement of Members of Congress

FDA has turned this experience into an inventory of ways to improve its performance in reviewing medical devices. FDA's analysis of the ReGen approval is well-done and worth reading.

My earlier column had two purposes: to alert readers that medical device re-evaluation is a large, pending activity within FDA; and to argue for FDA to take strong steps so that the re-evaluation process would not be driven by Congressional hearings and legislation.

FDA has now taken those strong steps. I hope that Congress will respect this effort and not intervene.

If the medical device approval process is under re-evaluation….then scientific and medical review staff at FDA (and their supervisors) are going to be careful in their actions. Protocols will be followed, every step will be fully documented, all interested staff will be involved, and near-final decisions will be reviewed more carefully.

This will slow the FDA approval of medical devices until needed changes have been made and confidence in the process restored. Does this actually surprise anyone?

Steven

My original column is at: http://www.fdamatters.com/?p=448. This includes my explanation of the issues and why re-evaluation of the medical device approval process was certain to occur. I conclude that the end-result will be "more than a few tweaks and less than an overhaul" of the medical device approval process.

The FDA press release announcing the IOM study of the 510(k) process: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm183497.htm

The ReGen report and the FDA news conference transcript: http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm183745.htm

FDA Should Stay Out of Health Care Reform

When the new NIH director, Dr. Frances Collins, was interviewed by the New England Journal of Medicine, he stated that one of his priorities is to: "put science to work for health care reform." I hope that Dr. Hamburg isn't having similar thoughts about involving FDA in health care reform.

Health care reform is our nation's #1 health priority. It does not lack for attention, participation and debate. Hundreds of billions of dollars will be driven by the outcome. However, our country will not be better off if every health-related agency diverts its attention and finite budgets to the cause.

I have been watching NIH for more than 30 years. All NIH directors have had the same goal: keep NIH and its biomedical research mission out of politics. Some directors have done this by pretending politics doesn't exist. Others have protected the agency by being consummate politicians. Both strategies have been successful at different times and in the hands of different directors.

I do not remember any NIH director openly welcoming politics into the agency.

The NEJM interviewer asked Dr. Collins' whether NIH will become politicized if it takes an active role in health care reform. He responded:

That is always a risk. I am exploring this. I don't know the answer precisely. I do think the idea that NIH's responsibility for trying to influence public health ends at the point of running a clinical trial and publishing the results may be a little narrow for the climate that we are in. While we are a research organization, and that's always going to be our focus, maybe there is more opportunity now….."

"Putting science to work for health care reform" will politicize NIH. This will not be good for biomedical research...or for America's patients who are waiting for treatments and cures. I hope Dr. Collins' comes to this realization quickly and does not let NIH get distracted.

This same point applies equally to FDA. The agency's plate is full with mission-appropriate responsibilities, including implementation of its new authority over tobacco. More work is coming through food safety reform, follow-on biologics and other administrative and legislative initiatives.

The new FDA leadership has made a strong point that science, not politics, should be the basis of FDA decisionmaking. To this, we can all say: bravo! Involving the agency in health care reform guarantees that politics will creep into the agency's activities and conclusions.

Getting involved in health care reform may be trendy….but it will be destructive, if not disastrous, for FDA. The agency needs to stay on mission and out of health care reform.

Steven

Dr. Collins' NEJM interview can be found at: http://healthcarereform.nejm.org/?p=1808&query=TOC.

Drug Reimportation: A Matter of Faith

Legislation to permit drug reimportation has resurfaced and the Senate may vote on it within the next 4 to 6 weeks. It may be considered as an amendment to the health reform legislation or come up as a free-standing bill. At stake is whether Americans can have access to drugs being sold in overseas markets at heavily discounted prices.

Advocates point to the unfairness of Americans paying more for the same drugs, which are often manufactured in the same overseas plants and use the same suppliers as pharmaceuticals being shipped into the US. If reimportation is permitted, they envision large savings for government programs, health plans and individual patients. They also believe that safety can be assured by limiting reimportation to countries with US-level regulatory and safety controls, such as Canada.

Opponents focus on the strict controls placed on drugs being manufactured for the American market and imported by US-regulated drug companies and wholesalers. While the world is awash in billions of dollars of counterfeit drugs, comparatively little enters the US under the current system. If counterfeits become more common, there is likely to be a significant increase in costly, sometimes deadly, therapeutic failures. This would jeopardize public health and wipe out much of the predicted savings.

Ideological positions have hardened on drug reimportation. There is far more shouting, far fewer efforts to reason and educate. How do we, as patients and consumers in a complex society, decide on the best path for Americans?

Years ago, a drug trade association ran a campaign with the seemingly-paradoxical theme: the only pill we don't test is the one you take yourself. The goal, as I recollect, was better public understanding of how testing and quality controls permeate every stage of drug development and manufacturing.

Because the actual pill can't be tested, the campaign made me realize that there is a critical leap of faith that the drug product you take is identical to the one that was originally shown to be safe and effective. This is not just a matter of chemical sameness, but also dissolution rates, absorption rates, purity, side effect profile, consistent safety and effectiveness across populations, etc.

I have the highest degree of confidence that a branded product is the same as the one that was originally tested and approved. I have nearly the same confidence in generics and regularly use them, although I have had at least one bad experience.

Beyond that, I become very concerned about drugs reimported from overseas. Among the potential problems: ingredient substitution, inconsistent manufacturing, lack of quality controls, inadequate inspections, lack of corporate accountability, and the absence of a strict chain of custody that prevents counterfeits.

This risk is compounded because consumers, pharmacists and doctors might never know whether a therapeutic failure was a result of an individual's biology or because of an inferior copy or counterfeiting. At least with brand and generic drugs, the pharmacy puts the drug's name and manufacturer on the label of the bottle and we can reasonably assume the accuracy of the information.

I have no faith that reimported drugs will, on a consistent basis, be identical to the original products in quality, safety and efficacy.

In most circumstances, potentially inferior goods sell at a steep discount to cover the consumer's risk of product failure. In health care, this is not considered acceptable. The promised price discounts from reimported drugs don't justify the risk to my health from a therapeutic failure.

Steven

Dr. Collins Meet Dr. Hamburg

FDA and NIH should be working together more closely and productively. For this to occur, Dr. Hamburg and Dr. Collins need to bless a higher level of cross-agency commitment. The critical next step is a publicly announced meeting of the two to develop and advance a common agenda.

In an earlier column, I concluded that FDA and NIH are natural allies, with closely-related purposes as public health agencies. They share a similar worldview that medical and scientific knowledge should be derived from random clinical trials.

Subsequently, I wrote a column about the cultural and organizational barriers to a closer working relationship between NIH and FDA. I urged Commissioner Hamburg to meet with Dr. Collins to start breaking down those barriers.

Dr. Collins was interviewed in last week's New England Journal of Medicine and stated his five priorities:

• integrating new technologies to make basic research more productive;
  
• translating basic research into clinical applications;
  
• science in support of health care reform, notably comparative effectiveness;
  
• global health; and
  
• reinvigorating the NIH-oriented research community through support for more young researchers, more innovation-oriented grant review panels, and a stable and predictable funding trajectory for biomedical research.
  

These are appropriate priorities for NIH, but not reassuring to me as an FDA advocate.

Dr. Collins knows that most NIH-driven medical advances can't go "from bench to bedside" except through FDA. Yet, he only mentions FDA once in the interview—to observe that the FDA has put the only clinical trial involving stem cells on hold. Although cooperation on this trial is a good thing, NIH and FDA need a broader, deeper and longer-lasting set of activities and goals.

Undoubtedly, NIH and FDA representatives are discussing how their new bosses can work together within the new Administration. This is necessary and useful, but not sufficient to dramatically improve the relationship between the agencies.

I am clamoring for something that is more public than emissaries feeling each other out.

The two agencies working together are powerfully synergistic….and boundless in the benefits they could bring to the American people by joining forces. The involvement of NIH Institute Directors and FDA Center Directors is essential to building a better, more productive relationship. But it will never happen if it requires them to overcome cultural and tribal impediments that keep resource-maximizing organizations from fully sharing responsibilities, decisions and monies.

Unless Drs. Collins and Hamburg personally create the expectation of cooperation at the highest levels, there will be little movement at the center/institute level. Only Dr. Hamburg and Dr. Collins can set the proper tone, provide guidance and break down the barriers. I previously asked Dr. Hamburg to meet with Dr. Collins.

Now, I urge Dr. Collins to meet with Dr. Hamburg. Please.

Steven

Dr. Collins' NEJM interview can be found at: http://healthcarereform.nejm.org/?p=1808&query=TOC

My two earlier columns on this topic:

FDA and NIH: Natural Allies
June 12th, 2009 http://www.fdamatters.com/?p=299.

Dr. Hamburg Meet Dr. Collins
July 12th, 2009 http://www.fdamatters.com/?p=366.

It’s Time to Change CDER Funding

I did some crunching of FDA budget numbers for my column earlier this week on the Office of Regulatory Affairs (ORA). A by-product of my efforts was an analysis of how the Center for Drug Evaluation and Research (CDER) is funded.

As most readers know, bio-pharma companies pay user fees, based on activities (such as submitting a New Drug Application) and on the number of their manufacturing facilities. The amounts are set by law. As part of the arrangement, FDA agrees to certain performance goals, which are also specified in law.

We often hear how dependent CDER is on user fees. The actual numbers are startling and deserve to be well-aired.

In FY 09, CDER received $413 million dollars, of which $111 million goes to ORA for inspections and enforcement. The remaining $302 million is the appropriated amount available for CDER to fulfill its responsibilities. User fees add another $357 million.

Of CDER's $660 million, 45% comes from appropriations and 55% comes from user fees. The split is similar for employees. Nearly 1300 employees are paid from appropriated monies; 1500 employees are paid from user fee funds.

I do not believe that user fees are corrupting, as some have alleged. The oft-heard insinuation that user fees put FDA "in the pocket of industry" is nonsense.

Nonetheless, the appearance is terrible. Everyone in the FDA stakeholder community agrees—patient groups, companies, consumer groups and associations. No one favors more drug user fees…and most would like to roll back or eliminate them in favor of all-public funding. Is this possible?

The current drug user fee program (PDUFA IV) was signed into law on September 27, 2007 and covers five fiscal years. Although Congress won't act to renew the program before 2012, the FDA will be starting its public hearing process in the first quarter of 2010. This is the first step in creating FDA's legislative proposal for PDUFA V.

This seems like a perfect opportunity to build momentum for a rollback of user fees, leading to a much smaller PDUFA V. Except that it will never happen that way.

FDA won't recommend, and industry won't agree to, a smaller user fee program….unless they are assured that the same amount of funds will be replaced by appropriations. Additional appropriated funds above that level would be even better, since CDER has a lot of needs.

That brings the potential for a smaller user fee program back to Congress. It won't be simple. The user fee programs are authorized by the House Energy and Commerce Committee and the Senate HELP Committee. They will determine the size and scope of PDUFA V.

However, the House and Senate Appropriations committees control the amounts of user fees to be collected and made available to the FDA. If there is to be a larger, offsetting appropriation to replace some user fees, these committees will have the find the money.

A smaller PDUFA V could only happen if House E&C Chair Henry Waxman and House Appropriations subcommittee Chair Rosa DeLauro agree. Likewise, Senate HELP Chair Tom Harkin would have to reach agreement with Senate Appropriations subcommittee chair Herb Kohl to implement a smaller user fee program. The Senate may be easier, since Senator Harkin is the #2 Democrat on Senator Kohl's subcommittee.

One person can cut through all of this and lead the way to a smaller user fee program. When President Obama submits his FY 2011 budget to Congress next February, he could include additional appropriated funds to reduce CDER's reliance on user fees. A good start would be to get the proportion of user fees below 50% of CDER funding.

I wouldn't bet on this happening…..but I can dream, can't I?

Steven

The Uncrowned Prince of FDA

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, head of the food center? The correct answer: neither.

The person with the most resources is Michael Chappell, Acting Associate Commissioner for Regulatory Affairs. In FY 09, he had primary responsibility for about $700 million, 1/3 of the agency's appropriation. He also had management responsibility for 3700 individuals, more than 40% of the agency's appropriated workforce. He is the uncrowned prince of FDA.

Few people know his name or much about the operational entity known as the Office of Regulatory Affairs (ORA). The Office's funding is tucked into each center's appropriation under the unremarkable line item: field. ORA does not even rate a link on the FDA home page. A description of ORA is two levels down:

The FDA's Office of Regulatory Affairs is the lead office for all FDA Field activities as well as providing FDA leadership on imports, inspections, and enforcement policy.  ORA supports the five FDA Product Centers by inspecting regulated products and manufacturers, conducting sample analysis on regulated products, and reviewing imported products offered for entry into the United States.  ORA also develops FDA-wide policy on compliance and enforcement and executes FDA's Import Strategy and Food Protection Plans.  http://www.fda.gov/AboutFDA/CentersOffices/ORA/default.htm

The relative invisibility of ORA appears to be intentional. For example, when the agency issues a press release about an enforcement action, the relevant center director gets the first quote; ORA is always quoted much further down.

Is ORA's continued low profile a good thing? I don't think so.

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 someone like him.

Well run, conscientious companies have little to fear. If you run a solid plant operation, import ingredients with care, use lots of 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 to consumer and patient risk, or stonewalling the agency, you deserve what you get from ORA, strengthened and visible or not.

Commissioner Hamburg intends to make the agency more scientifically knowledgeable, more innovation-oriented and a more reliable partner in its interactions with industry and other stakeholders. A year from now, she will have little leeway to accomplish these goals if she hasn't taken the necessary steps to increase inspections and strengthen enforcement.

In doing so, it makes sense to take ORA out of the FDA shadows and make it a more visible force.

Steven

Post-script: While controlling a surprisingly large amount of the resources, ORA does not operate alone. Each center works with ORA to jointly develop work plans that direct inspection and enforcement priorities for the next fiscal year. My understanding is that this process is a serious endeavor that consumes an appropriately large amount of staff time and effort.

Fall Scorecard for Follow-on Biologics

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.

The House Energy and Commerce Committee and the Senate HELP Committee have both put FOB provisions into their health care reform bills. If the two FOB bills were to be considered in a House-Senate conference on health reform, it would not be hard for conferees to agree on a final version. Yet, for reasons given below, FOB legislation may not become law this year and the current House and Senate provisions may be changed before (or during) conference.

House status. House Energy and Commerce Committee Chairman Henry Waxman has proposed generics-friendly legislation (HR 1427). Fellow Democrat and committee member, Representative Anna Eshoo, has proposed a competing, bio-tech friendly bill (HR 1548). The two have been in a stand-off since introducing their bills in March of this year. With help from Representative Barton, the ranking minority member of the full committee, Eshoo's bill has amassed 142 bi-partisan co-sponsors, about 1/3 of the membership of the full House and far more than the Waxman bill.

An Eshoo amendment was successful during the July health reform mark-up, so FOB is now part of the House health reform package. Her amendment was similar to her original bill, with some changes to make it closer to the Senate compromise bill.

Although the Eshoo amendment has the upper hand, Chairman Waxman still has options. It is possible that FOB's will not emerge from the melding of the three different House committee versions of health reform. House leadership may help him keep FOB out of the final legislation when it is considered by the House. Perhaps there will be changes in the Senate bill, allowing more room for compromises in the House-Senate conference committee.

Senate status. On the Senate side, the HELP committee put a two-year old bipartisan FOB compromise into its health reform bill. As noted, it is much closer to the Eshoo position than to Waxman. However, the HELP-passed version of FOB may not be the final word in the Senate.

Senator Schumer has introduced the Waxman bill in the Senate (S 726). His bill (and its seven bi-partisan co-sponsors) assures that the HELP bill will not move forward without visible dissent on FOB. The HELP version is also subject to modification when the Senate Finance and Senate HELP committees merge their two versions of health reform.

The health reform factor. Without enactment of health reform, the Eshoo bill and the Senate compromise bill may be dead for this year and, maybe, for this Congress. Short of an equally-compelling, must-pass health vehicle, Chairman Waxman, as chairman, is unlikely to give Representative Eshoo a second chance to offer her FOB amendment. Without passage of health reform, any future House action on FOB is likely to require Waxman's input.

The Senate situation is likely to be similar. If FOB is not in the final health reform bill, then it will be difficult to sustain the Senate FOB compromise version, especially without Senator Ted Kennedy to advocate for it.

The fate of FOB also becomes uncertain if the health reform bills are substantially narrowed in scope. For example, if the final legislation focuses on insurance reform, then FOB might not be in it.

FOB: the substance is important and the politics are fascinating. Stay tuned!

Steven

Prior columns on follow-on biologics:

Health Reform and Follow-on Biologics September 6th, 2009

The Best Little Chess Game in Town August 3rd, 2009

Follow-on Biologics and the Dance of Legislation July 5th, 2009

The Follow-on Biologics Market June 23rd, 2009

Off-Label Promotion and Whistleblowing

Whistleblowing and off-label promotion of drugs and devices have become hot topics because of the September 2 Pfizer settlement with the federal government. For those who were on vacation: Pfizer is paying $2.3 billion to settle criminal and civil complaints dealing with its marketing and sales practices on four drugs. They have also had to accept a stringent corporate integrity agreement with regard to pre-review and audit of its future marketing and sales activities.

While none of my views are specific to Pfizer, the company's settlement provides an opportunity to comment on off-label promotion….and to encourage bio-pharma and medical device companies to engage in deeper soul-searching.

Marketing departments should be able to do better. Even if the clinical trial data is ambiguous, FDA is usually precise in the indications it approves. That limits the scope of claims that can be made by a company. The FDA's promotion rules are far from perfect, but they are clear on most points. For virtually all medical products, it should not be hard for the sponsor to identify promotional claims and activities that are permitted.

Product marketing is a centralized function that requires employees to work together to develop programs and oversee initiatives. It is not an ad-hoc activity. I assume there are multiple sign-offs before any action is taken. Why are these safeguards failing? When things go wrong--which happens remarkably often--is it because everyone in the marketing department is drinking the same fatal Kool-Aid that sales are more important than laws and profits larger than penalties?

Sales practices are harder to control and will always leave companies vulnerable. I have often observed that there are three types of people: those who are shy, those who get over being shy, and salesmen. Medical products companies train sales staffs rigorously, re-train them often, and make them sign documents that attest to their knowledge of the marketing and sales restrictions on bio-pharmaceuticals and medical devices.

However, tens of thousands of sales reps have millions of interactions with prescribers. No matter how well trained and cautioned they are…there will be days when some reps cannot restrain their "inner salesman." How do you guard against that?

Whistleblowers serve a societal function that might not be served any other way. This is painful for me to admit, since I believe so strongly in working within an organization to make things right. I worry that "running to Uncle Sam" might be perceived as a better option than having a candid and concerned conversation with your boss.

However, in many situations, there may be no other way to document certain types of corporate wrong-doing. For that reason, whistleblowing and the resulting qui tam lawsuits are encouraged as a matter of public policy.

My conclusion: it is difficult for bio-pharma and medical device companies to conduct business in a way that makes whistleblowing unnecessary. Nonetheless, FDA-regulated industry can do better than they are presently. We should expect medical product companies to serve patients, prescribers, and shareholders without breaking the law. For those who think the promotion rules are illogical or counterproductive, the remedy is to work for policy changes, not to ignore FDA rules.

I believe that leaders and staff of medical products companies are well-meaning and committed to improving the health of patients. It is detrimental to see off-label promotional activities that can be interpreted as blatant bad faith.

Am I missing factors that might lead to a different conclusion? I encourage readers to post constructive comments to set me straight.

Steven

Notes on the news:

• My September 6^th comments on President Obama's options leading into tonight's speech to Congress on health care reform and how that might affect FDA: http://www.fdamatters.com/?p=471
  
• Senator Dodd has decided not to take the HELP chairmanship. Here are my August 30^th comments on the other contenders and the trade-offs involved: http://www.fdamatters.com/?p=459
  

Health Reform and Follow-on Biologics

When FDA stakeholders discuss health reform, they usually focus on finance rather than regulation. They have strong interests in Medicaid rebates, formularies, adequate reimbursement to support innovation, and who is for/against the President's plan. None of these finance issues affects FDA, although they will certainly have an impact on FDA-regulated industries.

Less often discussed in this larger debate is that some health reform bills include provisions that would alter or expand FDA's responsibilities. The best known and most far-reaching provision would create a regulatory pathway for follow-on biologics (FOB). The fate of FOB, as well as other FDA provisions in the House Energy and Commerce and Senate HELP bills, will be determined by how health reform unfolds this fall.

This Wednesday night (September 9), the President will address Congress, hoping to create a working majority for a set of initiatives that will add up to health reform.

The President has several options. He can find a way to pull together Democratic ranks by bridging liberal and conservative demands. He can warn Democrats of the potential political consequences if they can't pass health reform. These seem to be his likely direction based on this morning's New York Times.

Alternatively or in addition, he can add in a "game-changer," a new proposal that shifts alliances. Former Senator Bill Bradley suggested one yesterday in a NY Times opinion editorial: medical malpractice and tort reform. Arguably, this would appeal to some Republicans and conservative Democrats and expand and intensify support from within the medical and hospital communities.

Finally, he can narrow the scope of health reform, accepting that some steps toward his goals are better than none. Artfully played, this can be turned into a victory rather than a defeat.

The fate of FOB legislation depends on whether President Obama chooses a successful strategy in his speech to Congress and, ultimately, can guide health care reform into law.

Without enactment of health reform, the biotech industry-backed FOB legislation must be considered dead for this year and, maybe, for this Congress. Short of an equally-compelling, must-pass health vehicle, House Energy and Commerce Committee Chairman Henry Waxman will not give Representative Anna Eshoo a second chance to offer her amendment on follow-on biologics. Any future action on FOB will require Waxman's imprimatur.

The Senate situation is likely to be much the same. If FOB is not in the final health reform bill, the likelihood of reviving the Senate FOB compromise--without Senator Ted Kennedy--must be considered slim.

The fate of FOB becomes uncertain if the President calls for narrowing the scope of health reform. Presumably, a slimmed-down health reform bill will be tailored to be in budgetary balance and to provoke minimal controversy. It might be hard to argue that the reform package requires the quite modest cost savings associated with FOB. Further, with AARP and Congressman Waxman as opponents, FOB will probably not be considered non-controversial.

If a large part of the biotechnology industry is rooting for President Obama on Wednesday night, it should be no surprise.

Steven

Prior columns on follow-on biologics (FOB):

The Best Little Chess Game in Town

August 3rd, 2009

One of the reigning champions of political chess, Representative Henry Waxman, has found himself in an endgame on follow-on biologics (FOB). His three decades of success have been built on extraordinary mastery of Congressional procedure, artful compromise and strategic alliances. His defeat seems unavoidable, but no one should assume that he can't yet win or draw this game. Read the rest of this entry »

Follow-on Biologics and the Dance of Legislation

July 5th, 2009

Political scientists love to watch the dance of legislation. FDA watchers are eager to see how thorny agency issues will be decided by Congress. Both will be fascinated by the latest moves and turns in Congressional consideration of legislation on follow-on biologics (FOB).

I can't recollect an instance in which a House chairman faced such massive bipartisan opposition. But never count House Energy and Commerce (E&C) Committee Chairman Henry Waxman out. He has made a career of not having enough votes… and winning, anyway. Read the rest of this entry »

The Follow-on Biologics Market

June 23rd, 2009

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. In my opinion, 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 »

In Praise of Predictability

FDA has always found it challenging to make its actions predictable. This problem will worsen for a number of months while Dr. Hamburg redefines the agency's mission, policies, actions and working assumptions. Once this has been accomplished, the agency will become dramatically more predictable to stakeholders, including Congress.

I have written how Drs. Hamburg and Sharfstein's public health backgrounds make them different from their predecessor over the last 35 years--who were mostly researchers, teachers and clinicians from academic health centers. "Public health" as practiced in a big city health department has a gritty immediacy that shapes every activity. In contrast, academic health centers are devoted to providing clinical services to patients and educating students and house staff. Public health is a valuable by-product, but rarely a primary mission.

"Predictability" also means something different in city government than it does at a university. Public health departments are on the frontlines for all public health decisions--from the availability of flu vaccine to monitoring restaurants for sanitary conditions. Leadership must persevere in the chaotic environment of a big city. Every day brings unpredictable events generated by external forces. Success is achieved by having a tight organizational structure and "standard operating procedures" (SOPs) that cover nearly every potential challenge. In most situations, employees, stakeholders, mayors, and councilmen know what to expect. .

Unpredictable external events play a much smaller role in the life of an academic medical center. The combination of a medical school, a teaching hospital, and biomedical research labs is considered one of the most complex systems in our society. Leadership is more inwardly focused, trying to make the different components work together….and work well. Organizational predictability almost always take a backseat to people management, work flow and revenue generation.

My point is that Drs. Hamburg and Sharfstein have been schooled in the value of creating predictability. Generally speaking, their predecessors were not.

Predictability is in short supply at FDA currently--because the new leadership team is identifying the agency's internal and external problems and constructing appropriate solutions. The "new normal" that eventually emerges will be: more focused in the face of a broadening mission; more committed to serious enforcement; and more dedicated to innovation that is consistent with public health and science.

In the process, agency policies and actions will be increasingly based on SOPs, public and industry guidances, and clear articulation of scientific and legal positions. These will be implemented by a larger, tighter organization that will be more consistent in its decisions.

Although some of this evolution will be painful for FDA-regulated industries….they will eventually benefit from greater predictability and less ad hoc decisionmaking at FDA. And all stakeholders benefit from the increased public credibility that FDA will earn when its decisions are easier to understand, better grounded in science and public health and more predictable.

Steven

After Kennedy, Who Will Lead the Senate HELP Committee?

We mourn the passing of Senator Kennedy. He had something others admire, but can rarely duplicate. He was--often simultaneously—a formidable ideologue and the first to create a bipartisan bridge over troubled Senate waters. The health reform debate has suffered greatly from the absence of his commanding personality and his sense of how to make a deal (and make it stick).

Sadly, we are already involved in the game of guessing who will be the new chairman of the Senate Health, Education, Labor and Pension (HELP) Committee. I have also started to think about the possible impact on the FDA.

No one knows who will be the new chairman, despite a lot of instant analysis. Seniority on the committee is fixed, but every potential successor would have to give up something important.

Senator Chris Dodd has "right of first refusal" and has enjoyed his role leading the HELP committee on health care reform. He would certainly want to be chairman, except he would have to give up his chairmanship of the Senate Banking Committee, of obvious importance to his home state of Connecticut. Facing a very rough re-election campaign, commentators have been divided over whether he benefits from leaving the Banking committee and distancing himself from the near-collapse of the financial industries...or whether he should stay chairman and be the leader on re-regulating them.

Senator Tom Harkin is next in seniority. To take over HELP, he would have to give up the chairmanship of the Senate Agriculture Committee, of obvious importance to his home state of Iowa. He already heads the Appropriations subcommittee responsible for much of the labor and health care programs within the HELP jurisdiction. To have both positions would be incredibly powerful. Some commentators have said that Harkin isn't interested, but the better view is that he will need to assess the political consequences of changing chairmanships.

If Dodd and Harkin say "no," Senator Barbara Mikulski (MD) is next in line. She is also the most senior member of the Democratic Caucus who is not a full committee chair. It is widely assumed that she would happily take over the HELP committee. I think this is right, but at least one commentator has suggested that this might make it more difficult for her to eventually chair the appropriations committee, where she is fifth in seniority.

If this goes past Senator Mikulski, the next most senior member would be Senator Jeff Bingaman (NM), who would have to give up his chairmanship of the Energy and Natural Resources Committee. There are other Senators on the list after that, but the Majority Leader, Senator Harry Reid (NV), might step in first to assure leadership positions for more senior members within the Senate.

Not being discussed at all by commentators is a brokered deal for interim leadership. The chairmanship would then be decided in the next Congress (January 2011).

None of these potential chairs present any problems for FDA. They would all be expected to support the agency. That said, priorities for FDA will eventually change with new leadership of the HELP committee. Before that occurs, the new chair will have to evolve out of Senator Kennedy's enormous shadow and into their own agenda and style. That will happen, but slowly.

Steven

Re-evaluating the Medical Device Approval Process

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.

Whether FDA acts or Congress makes changes in law, I believe that the overall device approval process will change. Yet, it will still be recognizable to those who have worked with the 1976 Medical Devices Amendments, as further amended in 1990. During the re-evaluation process, every aspect of medical device regulation is going to be scrutinized as never before.

The stakeholders are likely to divide into two camps:

• those who think the system is fine with a few tweaks, and
  

• those who think a substantial set of changes are needed.
  

The final result is likely to be somewhere in between: more than a few tweaks, less than an overhaul.

There are multiple issues to address, such as device classification, post-market studies and surveillance, safety of devices, inspections, etc.

Setting the appropriate level of premarket review for a medical device is likely to be the most contentious issue. Under the Federal Food, Drug and Cosmetics Act (FDC Act), as amended, a device can be considered a class III device if it presents a high risk to patients and society or if it is based on a new technology. Class III devices are required to submit data on safety and efficacy to FDA. The sponsor can only market the product if FDA grants a Premarket Approval (PMA).

The vast majority of devices—including some class III devices--do not have a PMA. Some devices placed in class III under the FDC Act are based on a new technology and may not represent a high risk. In these cases, FDA may down-classify the device to class II, which are devices that represent a moderate risk.

Class II devices generally require a 510(k) Premarket Notification. Under the 510(k) process, a sponsor must show that a device is "substantially equivalent" to a device already marketed. The 510(k) is significantly less rigorous than a PMA and "substantial equivalence" has been broadly interpreted.

In April, the FDA responded to the GAO report by announcing that 25 types of class III medical devices will undergo safety and effectiveness review. After receiving information from sponsors, the agency will evaluate the risk level for each device type. Some of these devices are likely to become class II. Those devices found by the FDA to be of high risk to consumers will be required to submit PMA applications.

This makes me wonder: does FDA currently have the statutory authority to resolve most of the issues that surround the medical device approval process?

If so, FDA should evaluate issues, then act to solve any problems themselves. This would provide better assurances about the safety and effectiveness of medical devices, while avoiding the delays and drama that are inherent in the Congressional process.

This column is dedicated to the memory of Senator Ted Kennedy,

who was a champion of an effective FDA over many decades.

Steven