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 »

Deficit Hawks in the New Congress Threaten FDA Funding

FDA Matters doesn't know who the majority party in the House and Senate will be next year. There seem to be a very large number of races where incumbents are vulnerable or are too close to call. The fate of FDA will be driven by the post-election tone of Congress, more than by the fates of individual Members or who holds the majority.

Looking around the country, nearly every candidate is running "against Washington." The major themes--among Democrats and Republicans alike--are the need to create more jobs and the need to reduce the burgeoning government deficit and the national debt.

Congress may be stymied in the jobs area, since it is unclear how to intentionally create more jobs in our current economic situation. In any case, Congress will have to work through divergent views about how to approach this task. If creating jobs proves difficult, then Members will be working extra hard to show the electorate that the deficit is being tamed.

This year's first continuing resolution only provides FY 11 funds for the federal government through December 3. It has to be seen for what it is: a placeholder for more severe cutting that might occur later this year or early in the next Congress. Regardless of the outcome of the election, there will be a working majority of Republicans and Democrats in the House and Senate in 2011 that are deeply committed to substantial deficit reduction.

While it may surprise many, President Obama has a strong commitment to deficit reduction and will be working with newly-empowered deficit-cutters in Congress.

The White House clearly sees what the campaigns see: nearly across the political spectrum, voters want the federal government to spend less…or at least dramatically slow the increases that are already built into budget projections. The White House is likely to disagree with Congress on some budget items, but the focus will be on very specific items or on how far and fast to cut. Philsophically, President Obama sees himself as a deficit-cutter.

None of this sounds good for FDA. And it isn't. The Alliance for a Stronger FDA anticipated a year ago that future increases would be harder to get for FDA. Throughout 2010, the Alliance has been building on the theme that FDA needs to be an exception to whatever budget cutting occurs.

The Alliance's focus has been to show how a well-resourced FDA creates jobs in the American economy, which is a particularly potent argument with nearly 10% unemployment. The Alliance has also focused on the extraordinary demands being placed on the agency, be it growing responsibilities for medical product reviews and food imports or unexpected items such as pandemic flu and contaminated eggs.

The case for FDA "exceptionalism" has been effective in at least two recent years when most of the federal government received flat funding and FDA received an increase. No one knows if it will work in 2011 and 2012. FDA Matters does know that the agency will find it hard to function if it is caught in an "across the board" 5% or 10% cut in domestic discretionary spending.

It could be even worse. At least one proposal being discussed would roll the Federal Government's funding levels back to the FY 08 base. For FDA, this would mean reducing funding from $2.345 billion in FY 10 to the FY 08 level of $1.713 billion. A quarter of the agency might disappear.

Can I imagine things going that badly? Frankly, no. But so many things happen that we don't believe possible that I worry for the agency and hope readers will lend their voices to those advocating for increased FDA funding.

Steven

For purposes of disclosure: I am a founder and Deputy Executive Director of the Alliance for a Stronger FDA. It is the only multi-stakeholder group devoted to education and advocacy to increase the appropriated resources available to FDA. Members include patient and consumer groups, professional societies, research advocacy groups, associations, companies, consultants and individuals. For more information about the Alliance, go to www.StrengthenFDA.org or write to me at sgrossman@StrengthenFDA.org.

FDA Funding for FY 11: Back to the Future
October 3rd, 2010

Not so long ago, FDA appropriations barely budged from year-to-year. A good year was a 2% to 3% increase. This changed four years ago, after the formation of the Alliance for a Stronger FDA. The agency's case for more resources—always a good one—finally had an independent, multi-stakeholder voice. Champions on the Hill and in the Executive Branch emerged.

The agency appropriation has grown 50% in the last three fiscal years. So far, FY 11 looks more like the past than it does the last few years. FDA Matters believes that the consequences could be severe. 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 Funding for FY 11: Back to the Future

Not so long ago, FDA's appropriation barely budged from year-to-year. A good year was a 2% to 3% increase. This changed four years ago, after the formation of the Alliance for a Stronger FDA. The agency's case for more resources—always a good one—finally had an independent, multi-stakeholder voice. Champions on the Hill and in the Executive Branch emerged.

The agency appropriation has grown 50% in the last three fiscal years. So far, FY 11 looks more like the past than it does the last few years. FDA Matters believes that the consequences could be severe.

For the new fiscal year (FY 11) starting on October 1, Congress passed a Continuing Resolution (CR) that funds the government until December 3. As a result, the government is open, but no agency received new funding. For the next 2 months, government agencies (including FDA) will only be able to spend the amount they were appropriated in fiscal year 2010.

One of this year's Alliance themes has been the need for FDA to be an exception to the overall dismal federal budget situation. The agency must receive funding increases to do its job, which grows larger every day. There is strong support for this in Congress. The Alliance expects FDA to receive serious attention anytime Congress debates funding priorities.

This didn't happen for this first round of the CR for a fairly simple reason: Congress put this CR together without acknowledging any funding priorities. The Alliance believes FDA can win the debate to get increased funding, but only if that debate occurs.

When Congress returns in mid-November and looks at FY 11 funding again, there will be an opportunity to make the case that FDA should receive more funds. However, it is only a guess that this debate will occur before December 3. Congress may decide to pass the same CR to cover the period from December 3 to February 4.  If so, the pain of level funding will only become more intense for FDA.

Funding FDA at last year's levels is a particularly acute problem because over 80% of the agency's budget is people-related costs: salary, benefits, rent, IT, travel, support services. FDA cannot delay spending, as NIH might, by waiting a few extra months to disburse grant funds.

FDA management is reviewing contingency plans to preserve its priorities and maximize output. Retaining the fiscal 2010 spending levels will impact FDA's ability to hire medical product reviewers and food inspectors and personnel for other areas of growing need. The agency must use its CR funding to pay for October 1 raises and rent increases, which obviously are not reflected in the FY 10 appropriations level.

The overall situation, as well as these new costs, restricts FDA's ability to make commitments in hiring, new programming, better IT, and contracts. They will also not want to create obligations now that they may not be able to fund later in the year.

Congress will eventually be ready to address the nation's funding priorities, hopefully in November. Regardless of when this debate occurs, all of FDA's supporters will need to rise up as one to convince Congress that more monies are needed.

Steven

For purposes of disclosure: I am a founder and Deputy Executive Director of the Alliance for a Stronger FDA. It is the only multi-stakeholder group devoted to education and advocacy to increase the appropriated resources available to FDA. Members include patient and consumer groups, professional societies, research advocacy groups, associations, companies, consultants and individuals. For more information about the Alliance, go to www.StrengthenFDA.org or write to me at sgrossman@StrengthenFDA.org.

FDA's Yearly Appropriations Growth Since FY 2003

FY 03 (base year):         $1.390 billion

FY 04 ($11M increase):    $1.401 billion

FY 05 ($51M increase):    $1.452 billion

FY 06 ($41M increase):     $1.493 billion

FY 07 ($77M increase):    $1.569 billion (most domestic programs received no increase)

FY 08 ($145M increase):    $1.714 billion (plus $150M one-time supplemental, non-add)

FY 09 ($325M increase):    $2.039 billion

FY 10 ($306M increase):     $2.345 billion

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 and Quran Burning: Trouble Can Start With a Tweet

Bravo! Florida Pastor Terry Jones has decided not to burn a copy of the Quran. The next danger is that the Pastor's "success" will be seen narrowly as the unique confluence of 9/11, the Ground Zero mosque, and the readiness of millions to take to the streets at signs of American intolerance toward Muslims.

FDA Matters thinks the lessons are larger and urges FDA to pay attention to how this reflects changes in the way crises develop and decisions are made.

According to the Washington Post, on July 12 the Pastor sent a simple message on Twitter: "9/11/2010 Int Burn a Koran Day." From that beginning, he became the focus of international concern and one of the most watched people on the planet. All news sources—print, television and internet—were filled with stories about his intended actions. The situation most resembled a dramatic, high-stakes hostage negotiation. In a sense, it was, with Pastor Jones'copy of the Quran as hostage.

If we are imaginative, there is much more to concern us than Pastor Jones. We now know that one man's temper tantrum (or cause?)—distributed via Internet, Twitter, YouTube, 24/7 news outlets, etc.—can leave the world's leaders pleading for a favorable outcome. The power to capture the public eye, move public sentiment and galvanize the world...now belongs to all us. As Pastor Jones demonstrated, not everyone has the restraint to use that power responsibly.

In the late 1980's, AIDS activists staged a large demonstration that caused a multi-day lock-down situation at FDA. Patients and their friends were expressing their desperate need for access to drugs in development. It was a scary time at the FDA. No one wanted to create the precedent that FDA "would bend to a mob," but there also was a lot of sympathy for the plight of HIV patients.

Soon thereafter and over the next few years, FDA made a number of significant changes to the drug approval process. For example, the demonstrations eventually led to an accelerated approval process and "fast-tracking" of certain new drug applications. FDA began to treat surrogate endpoints seriously (e.g. CD4 viral load count rather than HIV disease progression). Most of these changes have been judged "good" with the passage of time, but there was a lot of uncertainty at the time.

With all the new avenues for communication, this scenario could easily repeat itself today on behalf of any number of diseases that are life-threatening or crippling. Could a group of parents with dying children try to force FDA to grant compassionate use access to a drug in pre-clinical (animal) testing? To make their point, the parents could create a vigil for the children with countdown clocks, while posting daily video showing their deterioration.

Yet another scenario might blend the skills of the Tylenol poisoner with the long-term persistence of the Unabomber. Every three months, anonymous videos might be posted that show gloved hands adulterating some additional batches of a food, drug or device. This would be a corporate nightmare that would also bring all FDA-regulated products under suspicion. FDA would be at the center of an enormous public health crisis.

I know I have not reflected the depth or breadth of challenges FDA could face. Hopefully, these few make the point that FDA is increasingly vulnerable as an agency. It must prepare for risks well beyond those faced by most federal agencies.

Commissioner Hamburg ought to meet soon with senior staff to review, extend, and refresh FDA's crisis plans. Even if they met two weeks ago, they should do it again because Pastor Jones has proven that the world has changed.

And while senior staff is having this discussion, they should also plan some simulations and practice drills. A crisis plan is only as good as the ability to implement it.

Steven

The Washington Post story describing the escalation after the tweet is at: http://www.washingtonpost.com/wp-dyn/content/article/2010/09/10/AR2010091007033.html?hpid=topnews

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 »

FDA’s Pivotal Role Fighting Bioterrorism and Emerging Infectious Diseases

With Congress out of session until September 13, the Executive Branch has the opportunity to gain extra column inches and media bandwidth. Thus, last week's report on medical countermeasures (MCM), released by HHS Secretary Sebelius, drew a lot of interest and a minimum of Congressional comment.

The Secretary released the findings and recommendations from a top-to-bottom review of the Department's efforts with regard to the development of MCM. In the view of FDA Matters, the report thrusts FDA back into its rightful place as a key agency deserving more resources and respect for its national security responsibilities.

MCM are products that will decrease morbidity and mortality from a bioterror attack or from naturally occurring emerging infectious diseases. Think anthrax or radioactivity from an improvised nuclear device for the first, think H1N1 influenza for the second.

Scientifically and medically, these are difficult products to discover and develop. Financially, they won't ever be developed without:

• federal assistance to promising research; and
  
• a strategic national stockpile and government contracts that will buy proven MCM's.
  

As with the larger promise of moving medical therapies from "bench to bedside," there is no progress without FDA. The agency encourages companies by helping them to define appropriate safety and efficacy endpoints for their particular MCM and works with them to resolve questions of animal models, lab standards, statistical plans, quality manufacturing, etc.  

Then, the agency evaluates the testing results and determines whether to approve the product. This work has an additional wrinkle. With most MCM's (maybe all) it is unethical to do human efficacy trials (e.g. intentionally expose a human being to anthrax to see if the MCM works). Instead, the agency (and the company) must make the difficult evaluation as to whether efficacy in animals is a sufficient surrogate for efficacy in humans.

The Secretary (and the underlying report) found that FDA's efforts in this area are insufficiently funded. Perhaps for the first time, there was a more global recognition of FDA's central role in making us safer from bioterrorism and naturally occurring emerging infectious diseases. The Secretary also recognized that FDA needs resources above its current level to do this job well.

The Administration placed a price tag--$170 million in funds to be available until expended--on the size and scope of the monies needed to upgrade FDA's efforts in this area.  The monies will come from dollars previously appropriated to HHS to combat pandemic flu. HHS and OMB have agreed that the monies can be transferred administratively as long as they retain their original purpose of helping to deal with pandemic flu.

However, the Secretary's recommendation is for the transferred funds to also be used for non-pandemic medical countermeasures. This requires a budget amendment to be sent to Congress to broaden the permitted uses of these funds. How likely is Congress to approve this? We probably won't know until after September 13.

What we do know for sure is that FDA can use the additional resources and America will ultimately be safer as a result.

Steven

FDA Matters' most recent (and still accurate) assessment of FDA and the FY 2011 appropriations process:

Update on FDA's Appropriation for FY 11 July 18th, 2010

On July 1, the House Appropriations Agriculture/FDA Subcommittee marked up it FY 11 bill. The bottomline was good for FDA: $2.571 billion, a $214 million increase over FY 10, about 9%. No further details will be released until the full committee marks up.

On July 15, the Senate Appropriations Committee marked up its version of the Agriculture/FDA funding bill. The good news is that the Senate agreed that FDA needs better funding….and provided $2.516 billion, a $158 million in new monies. This is a bit more than 6%. Here is FDA Matters' analysis of this critical budget battle. 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 »

For Twenty-Five Million Zebras: New Hope for Therapies

Several generations of North American trained doctors were taught: if you hear hoofbeats, think horses not zebras. This graphic image reinforced an important aspect of medicine for young physicians seeing mostly severely ill patients in tertiary care hospitals: if an otherwise healthy patient is coughing, it is most likely a bad cold. It is almost certainly not pneumonic plague.

What Congress, FDA, and NIH have learned over the last 30 years is that there are many more medical zebras in the United States than anyone imagined. NIH has catalogued nearly 7,000 rare diseases. More are being discovered all the time. Altogether, it is estimated that 25 to 30 million Americans are affected by rare diseases.

When I first became involved in health policymaking in the mid-1970's, the "war on cancer" was in its first, high-growth phase and cardiovascular disease was rampant. An "orphan drug" was one that would help third world diseases. During that decade, there were less than a dozen therapies developed for diseases that were rare in the US and elsewhere in the world.

The realization that there could be political strength in unity among those with rare diseases led to the creation of the National Organization for Rare Disorders (NORD) and the passage of the Orphan Drug Act of 1983 (ODA). A rare disease was defined as one that affects fewer than 200,000 Americans. Many rare disease populations are above 100,000, but far more are under a few thousand.

As a result of the ODA, more than 350 orphan products have been approved. The growth of biotechnology and the growth of orphan drugs have been closely aligned. Likewise, knowledge gained through orphan drug development has returned benefits for patients with more prevalent diseases.

More aggressive efforts are being undertaken to stimulate the development of orphan products. Just this year, FDA has been involved in:

• Helping to develop and work with NIH's Therapeutics for Rare and Neglected Diseases program (TRND), which is intended to move promising orphan drugs forward in the drug development pipeline until they meet FDA requirements for an Investigational New Drug (IND) application.
  
• Creating a new position, Associate Director for Rare Diseases in the Center for Drug Evaluation and Research, who will assist stakeholders and developers of drug and biologic products in navigating the complex regulatory requirements for approval of therapies for rare diseases.
  
• Developing the Rare Disease Repurposing Database that identifies drugs that are deemed promising for rare diseases and are already approved by FDA for another disease.
  
• Stepping up its training of medical product reviewers to devote more time and focus to the construction and analysis of small clinical trials.
  

These efforts have been welcomed by the rare disease community as important steps. Deservedly so.

But will these actions prompt a change in thinking at FDA? FDA claims that orphan drugs are reviewed with the same standards for safety and effectiveness as other drugs. This has become a barrier rather than an advantage.

When reviewing medical product applications for rare diseases, FDA needs to apply a somewhat difference set of rules to account for the special challenges of developing treatments for very small patient populations. Simply put, you can't expect a 500-person safety database in a disease that only affects 500 people.

With more than 25 million "zebras" roaming the United States, such special considerations seem the least we can do. It is imperative that we advance the scientific and regulatory knowledge that provides these patients with hope and, ultimately, with therapies.

Steven

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 »

Update on FDA’s Appropriation for FY 11

On July 1, the House Appropriations Agriculture/FDA Subcommittee marked up it FY 11 bill. The bottomline was good for FDA: $2.571 billion, a $214 million increase over FY 10, about 9%. No further details will be released until the full committee marks up, possibly later this month.

On July 15, the Senate Appropriations Committee marked up its version of the Agriculture/FDA funding bill. The good news is that the Senate agreed that FDA needs better funding….and provided $2.516 billion, a $158 million in new monies. This is a bit more than 6%. Here is FDA Matters' analysis of this critical budget battle.

The Senate's funding level for FDA is the same as the Administration's request. There was hope that the Senate could find the $55 million more to reach the House level. Even the House's proposed funding is not nearly enough to meet FDA's responsibilities in the coming year and the Senate is clearly even further behind with its number. Even so, the Senate's 6% increase is more than what most domestic federal agencies will receive.

The Senate mark-up proved one important point. Both the Senate and the House agree that FDA needs to be an exception to this year's tough round of budget-cutting.

There is still a ways to go. The House full committee needs to mark up its bill, and then both bodies will need to consider and approve these appropriations bills. This presumably would occur in September, although it may occur in late July. It looks like the Agriculture/FDA legislation might be one of the first appropriations bills to move through the pipeline. Hopefully it will be enacted into law before the Congress has to pass a Continuing Resolution (September 30 in advance of the new fiscal year, which starts on October 1).

The primary advocacy group for FDA resources, the Alliance for a Stronger FDA, continues to work for the House level or higher.  It is difficult for any agency in this appropriations cycle. Hill deliberations are already sharply skewed by the upcoming 2010 elections. Despite this environment, the FDA's friends in the Administration, the House and the Senate are still trying hard to get the agency more money for FY 11.  The Alliance is working with them to preserve FDA gains and to raise awareness that FDA is still under-resourced relative to the agency's responsibilities.

In past years, it would have been safe to assume FDA would receive an increase of $158 million to $214 million. However, none of the current numbers can be relied upon until the House and the Senate reach some understanding about total spending for FY 11.

The Senate is considering proposals that would reduce domestic discretionary spending by either $4 billion or $20 billion. If it is the latter, a large number of domestic programs will face deeper cuts than currently planned. Those who are doing comparatively better may find their gains wiped away. This macro-budgetary risk means the case for FDA must continue to be made and that numbers being discussed now cannot be relied upon.

Below I have provided links to prior columns that discuss why FDA's needs grow each year and why the agency must be an exception to budget cuts. Also below is a chart comparing FY 10 to the levels proposed by the Alliance, the Administration, the House and the Senate.

For information about adding your voice to those advocating for more FDA resources, go to www.strengthenfda.org or send me a note at sgrossman@strengthenfda.org.

Steven

For purposes of disclosure, I am one of the founders of the Alliance for a Stronger FDA and serve as its deputy executive director. FDA Matters is not affiliated in any way with the Alliance.

FDA: A Bargain at Two Cents Per Day Per American
March 28th, 2010

FDA touches every American many times each day. Today's investment (2 cents per day per American) is a pittance compared to the benefit of a strong FDA and the risk of an underfunded FDA. There cannot be many agencies in the US government that have such a vast scope of responsibilities and so few dollars to get the job done.

This is the powerful message that the Alliance for a Stronger FDA has been delivering to Capitol Hill. Even still, it will be a difficult year for any federal agency whose mission and responsibilities are growing. Read the rest of this entry »

FDA Needs at Least a $250 Million Increase in FY 2011
March 7th, 2010

The President's proposal to freeze domestic discretionary programs in FY 2011 (and beyond) will force painful cuts across government and in programs that millions of American rely upon. Even some traditionally-favored agencies, such as NIH, are looking at only small increases. With a proposed 6% increase (about $150 million), FDA would seem to be doing far better than most.

FDA Matters feels strongly that this is not nearly enough. By my calculations, at least a $250 million increase for FDA would be needed, just to achieve the program levels anticipated in the President's budget request. The Alliance for a Stronger FDA has asked for a $495 million increase, which could be put to good use by the agency. Why is 6% not enough? Read the rest of this entry »

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

Status of FY 11 Appropriations for the FDA

Compared to the Alliance for a Stronger FDA's FY 11 Request

Updated July 16, 2010

Budget Authority Appropriations (does not include user fees)

Function Note: budget authority only, by center	FY 10 Final (October 2009)		FY 11 Alliance Request	FY 11 President's Request Feb. 2010	FY 11 House Subcommittee 7/1/10	FY 11 Senate Committee 7/15/10
Food	$   784 million		$ 955 million	$ 856 million		$856 million
Human Drugs	$    465 million		$ 580 million	$ 484 million		$489 million
Biologics	$    206 million		$ 255 million	$ 215 million		$215 million
Animal Drugs/Feed	$    135 million		$ 165 million	$ 141 million		$141 million
Devices & Radiological Health	$    315 million		$ 385 million	$ 326 million		$326 million
Natl. Ctr. For Toxicological Research	$     59 million		$ 72 million	$ 61 million		$61 million
HQ, Office of Commissioner and Other	$    144 million		$ 183 million	$ 162 million		$157 million
Rent & Facilities Cost	$    237 million		$ 250 million	$ 259 million		$259 million
SUBTOTAL, Salaries and Expenses	$ 2.346 billion		$ 2.845 billion	$2.504 billion		$2.504 billion
Building and Facilities Repair	$ 12 million		$ 12 million	$ 12 million		$ 12 million
TOTAL, ALL Budget Authority Appropriations (no user fees)	$ 2.358 billion +$307M over FY 09		$ 2.857 billion Proposes $499 million over FY10	$2.516 billion Proposes $158 million over FY 10	$2.571 billion Proposes $214 million over FY 10	$2.516 billion Proposes $158 million over FY 10

Some columns may not add due to rounding.

The House has released the total for the FDA, but does not release the allocation until full committee mark-up expected later this month.

For more information about the Alliance for a Stronger FDA:

Ladd Wiley, phone: (202) 887-4083 email:  lwiley@StrengthenFDA.org

Steven Grossman, phone: 1- (301) 539-9660 email:  sgrossman@StrengthenFDA.org

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, Female Sexual Desire and the Media

This week's hottest bio-pharmaceutical story was the June 18 FDA advisory committee's review of a drug to treat hypoactive sexual desire disorder (HSDD). The committee did not recommend approval of the drug, but encouraged the sponsoring company and others to continue working in this area.

What struck me most was the contrast between the seriousness of the advisory committee in deciding whether the treatment was safe and effective in treating a genuine medical disorder and the inability of the American media to report the story objectively or sympathetically.

The New York Times had at least four articles—two news stories and two commentaries. The coverage in three of them gives focus and space to whether HSDD is a disease, whether biopharma companies create diseases, and the legacy of Victorian beliefs about sex. These were not part of the advisory committee meeting or issues raised by FDA.

The New York Times gave credence to the views that HSDD is primarily caused by bad lovers and high expectations and that the primary remedies are talk therapy, ending relationships and lower expectations. In short, they featured "experts" dueling on tangential, almost ideological, issues reflecting their professional self-interests.

Other than speculation on the number of women affected, there was little space devoted to the unmet medical need. Of most concern, there was no apparent attempt to provide a patient's perspective or interview a patient. Yet, this would seem routine for a news story concerning drugs being reviewed by FDA---especially where the drug treats a condition for which there is no approved therapy.

To find source material on patient perspectives, NY Times writers needed to look no further than a thoughtful NY Times magazine article from November 2009. Need to talk to a patient? Call the article's author or one of the researchers he mentions.

Fortunately for patients, FDA had long-ago decided the answers to the questions that the media deemed to be hot topics. In May 2000, the Division of Reproductive/Urologic Drug Products (DRUP) issued a draft guidance for industry entitled, Female Sexual Dysfunction: Clinical Development of Drug Products for Treatment. The guidance deals with the difficulties of proving safety and efficacy. It raises no concerns about whether female sexual dysfunction exists nor does it question the value of products being developed to treat the condition.

There is a solid history of FDA playing a critical, but totally unheralded role, in shaping and reshaping our society's understanding of disease.

For example, homosexuality was long treated as a disease or mental disorder. For at least the last two decades, it would be unthinkable for FDA to consider an "anti-homosexuality pill." For hundreds of years, obesity has been a symbol of wealth and well-being. Today, it is being redefined as a disease, complete with claims that it is an epidemic. FDA decided obesity was a "disease" years ago and has considered a number of "anti-obesity pills."

Other diseases reflect new thinking about what constitutes illness. Examples would include post-traumatic stress disorder, attention-deficit hyperactivity disorder and restless leg syndrome. FDA has approved drugs treating each of these.

FDA seems to make these judgments without any fanfare. The question "is this a disease" doesn't come up every day at the agency. When FDA does make these judgments, it appears a routine part of the process and not a notable event.

Maybe in the future, the media will have a better grasp of why this is so and respect FDA authority and good judgment about such matters. Meantime, for the benefit of women with HSDD, FDA's role and earlier decisions are a very good thing.

Steven

Disclosure: Since I don't usually write about specific drugs, it may be useful to state that I am not working on HSDD for any of my clients nor am I doing any work for the company whose drug was reviewed.

The origins of my views are in a November 2009 column, entitled: "FDA: Invisible Arbiter of What Constitutes Disease," at http://www.fdamatters.com/?p=646. I have re-used some of the examples from that article, which was focused on whether FDA issues would ever approve an "anti-aging" drug.

Here are the four recent New York Times articles:

http://www.nytimes.com/2010/06/17/business/17sexpill.html

http://www.nytimes.com/2010/06/19/business/19sexpill.html

http://www.nytimes.com/2010/06/27/business/27stream.html?fta=y

http://www.nytimes.com/2010/06/27/opinion/27Paglia.html?th&emc=th

Here is the earlier New York Times Magazine article:

http://www.nytimes.com/2009/11/29/magazine/29sex-t.html

Prioritizing patient needs is not just a media issue. I have previously criticized industry for not acknowledging that "Patients Come First." http://www.fdamatters.com/?p=632

I have also questioned FDA when it went astray in "One Disease + Two Concerns = FDA's Need to Communicate Better and Modernize Standards." http://www.fdamatters.com/?p=430

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 »