Late yesterday, thirty advocacy organizations, representing seniors, labor, providers, patient safety advocates, cancer patients, and consumers joined Community Catalyst in calling for Congressional action to improve the safety of drug manufacturing.  In letters to the Senate HELP and House Energy and Commerce committees, groups urged Congress to make safe drug manufacturing legislation a priority by including new patient safeguards “in the upcoming reauthorization of the Prescription Drug User Fee Authorization Act (PDUFA).” 

Signed by advocacy groups from across the nation and in districts of some key Energy and Commerce committee members, the letters warns that the many recent drug recalls, failed inspections, and manufacturing quality breakdowns by both brand-name and generic manufacturers are likely just “the tip of the iceberg” because most manufacturing problems at overseas facilities go unseen.

The high profile manufacturing problems by Johnson and Johnson, GlaxoSmithKline, and other facilities were discovered primarily by FDA visits to the 2,500 domestic drug manufacturing plants, which are inspected once every two and a half years.  But the number of foreign drug manufacturers has doubled in the last seven years, encompassing approximately 3,800 foreign manufacturers in more than 150 countries.  

This rapid globalization of overseas drug manufacturing has far outstripped the FDA’s capacity to inspect these new facilities, which today are the source of 40 percent of finished drug products taken in the U.S., and 80 percent of active drug ingredients and bulk chemicals used to make drugs domestically.  According to the GAO, under current resources, the FDA can inspect these 3,800 foreign sites only once every nine years.

The letters show that these risks are real, serious, and potentially lethal for vulnerable patients. For instance, the intentional contamination of heparin tragically led to numerous deaths and hundreds of adverse reactions amongst the hundreds of thousands of dialysis or post-operative patients treated with Heparin each year.

We also noted how these risks are not floating under the radar, but are widely known by industry leaders. A 2010 poll of pharmaceutical executives identified “raw materials imported from outside the U.S. as the greatest vulnerability” to the purity and integrity of drug products in the next five years. But progress has been made. Our letter commends how the generic drug industry has “stepped up to the plate” by “agreeing to fund inspections with user fees….” See here and here.

Reform is also widely supported by voters from across the political spectrum. In fact “81 percent of Republicans, 87 percent of Independents, and 97 percent of Democrats support increased FDA authority to issue recalls, destroy contaminated products upon import, and inspect foreign manufacturers” according to a recent poll.

The letter asks Congress to provide FDA with new authority to adequately protect US patients from the increasing risks of counterfeit drugs, a leading black-market enterprise around the world. This would include the ability to issue a recall, or to destroy contaminated, expired, or unsafely manufactured drug products that are seized at the border.

Yesterday, Rep. Michael Burgess, vice chairman of the House Energy and Commerce Subcommittee on Health, announced that reforms to end drug shortages would be included in legislation to renew the system of collecting fees from drug-makers in order to fund FDA review of new drug products. We support efforts to eliminate drug shortages, and improvements to drug manufacturing quality would certainly help. According to the FDA, manufacturing problems were the cause of over half of the drug shortages in 2010. And these problems can be quite serious, with sterile drugs found to be contaminated with “glass shards, metal filings, and fungal or other contamination” according to an FDA report last month. 

Thanks to our partners who joined us in calling for increased safety of drug manufacturing: 

Action for Boston Community Development (ABCD)
AFSCME
Alliance for Retired Americans
Breast Cancer Action
California Alliance for Retired Americans (CARA)
Center for Medical Consumers
Community Catalyst
Connecticut Center for Patient Safety
Consumers Union
Families USA
Florida CHAIN
Health Law Advocates of Louisiana, Inc.
Illinois Public Interest Research Group (Illinois PIRG)
Medicare Rights Center
Mississippi Human Services Coalition
Missouri Alliance for Retired Americans
National Education Association (NEA)
National Labor Alliance of Health Care Coalitions
National Physicians Alliance
National Research Center for Women & Families / Cancer Prevention and Treatment Fund.
National Women’s Health Network
New Hampshire Alliance for Retired Americans
North Carolina Justice Center’s Health Access Coalition
Ohio Alliance for Retired Americans
Pennsylvania Public Interest Research Group (PennPIRG)
TeamstersCare  – Teamsters Union 25 Health Services & Insurance Plan
Texas Alliance for Retired Americans
UHCAN Ohio
USAction
USPirg
Vermont Public Interest Research Group (VPIRG)

In his keynote address to the “After Heparin” convening today, FDA Principal Deputy Commissioner John Taylor said the agency has not made enough progress in transforming its oversight system, but that bills before the last Congress—the Bennet and Dingell bills–could help accelerate that process.

He also laid out a global strategy plan to revamp its monitoring system that would rely more on third-party inspections, improved risk-based intelligence, data-sharing and cooperation with partners in the public and private sectors.

Taylor brought big numbers to illustrate the big gap between the domestic nature of FDA’s founding mission and the new global realities. There are 300,000+ FDA-regulated products coming into the U.S. from 150 countries. By 2008, Taylor said, the U.S. import imbalance on pharma products had increased 10-fold, to $18 billion.

The impressive range of stakeholders around the table today – from chemical manufacturers to consumers representing the patient who takes her medicine – covered a lot of ground and came to some important consensuses around needed policy reforms to close the gaps. Here are some major themes:

Info-sharing/collaboration
One common refrain from Taylor’s keynote to the closing remarks was the need to share information strategically on safety and monitoring systems. Martin VanTrieste, head of Rx-360, a non-profit industry audit-sharing organization, promoted the efficiencies his group has gained in sharing audit info and planning group audits, which offer the potential for more in-depth visits and cuts down on redundancy.

Falsifying drugs is a perfect crime, said Guy Villax, board member of the European Fine Chemicals group and CEO of Hovione, and he proposes to tackle it with info-sharing databases like the one the European Medicines Agency has developed.

Inspectorama
Inspections remain an important piece of the overall quality picture, though everyone agreed there aren’t enough resources to inspect anywhere close to all the sites that make raw materials and substances that go into U.S. drugs. The 2010 GAO update and last night’s 60 Minutes (and the PostScript archives) all have those numbers.

FDA’s Deb Autor said that gaining parity between domestic and foreign inspections are just not feasible, and in some cases, the every two years required for domestic sites would be excessive, even wasteful. But Marcia Hams of Community Catalyst reminded the group that it’s partly that very level of inspection that allowed regulators to find and monitor the flagrant quality problems at Johnson and Johnson’s three domestic factories—and to eventually take them over.

Who’s gonna pay for this?
There was, predictably, less consensus about how to pay for inspections. Though all agree that cost-savings is the major driver in the shift of supply and manufacture to emerging markets, Prabir Basu of the National Institute of Pharmaceutical Technology and Education, said that cost savings is directly linked to the low- or un-regulated climates of those markets, and can’t be accounted for by labor costs alone. But it’s unclear that the greater risk that comes with industry savings is being matched with a willingness to spend on safety and quality systems.

One solution discussed was a user fee that would go toward inspections; right now user fees go to pay for approval. But Mylan President Heather Bresch said that a user-fee system should be holistic – that is, it should support bringing safe, quality products to market and then ensure their safety once they’re on the shelves.

Cheating to the test
The culprits responsible for the adulterated heparin linked to the American death developed a molecule that fooled up more than a dozen different country’s and companies’ tests, including the US Pharmacopeia, which now has an updated heparin assay. USP’s CEO Roger Williams said that a thoughtful updated test is a critical factor in assuring safety and quality, and called for legislative support for such standards.

But physical audits are absolutely key, said Philippe Andre, a China-based auditor whose photos bore that out. Andre and Brant Zell, past chair of the Bulk Pharmaceuticals Task Force, both underscored that when it comes to working with overseas suppliers, knowing what you’re getting ahead of time is critical. Andre said he’s surprised by how many companies contract with suppliers in China without ever visiting the plant. And Zell pointed out the importance of companies doing proactive physical audits. “If you just test, you don’t get all the answers,” he said. “Quality’s built-in, and if you visit, you get an idea about how things are being done.”

National Security Rx
Drug safety is, at its core, a national security issue. An industry in which bad actors are economically motivated and able to infiltrate the legitimate supply chain with a relatively low risk of penalty is ripe for exploitation, and in this way, heparin is a shadow of the bioterrorism threats that captivated the nation a decade ago and caution for the bigger crises inevitable if the system goes unfixed. Attendee Laurie Garrett from Council on Foreign Relations pointed out that one of the lesser-hyped documents in the Wikileaks case was a State Department memo listing of overseas sites of national security interest to the U.S.: more than 30 percent were drug, vaccine and biological manufacturing sites.

Nearly all the parties around the table agreed that the safety gaps in the pharma supply pose a great and growing threat to public health, and that incremental scale-ups won’t solve the sort or scope of risks that the new globalized drug supply chain pose.

This has got to be a paradigm shift. And we fail to make it at the patient’s peril.

“We just need to figure this out, we just need to step it up,” said AARP’s Ahaviah Glaser. “As a consumer rep, I still look to the FDA, but it’s got to be group accountability.”

“If we can’t trust where our drugs are coming from, that’s so fundamental,” said Cleveland Clinic cardiologist Harry Lever. “If my patient isn’t doing well, the first thing I think about now is: maybe it’s a drug.”

Allan Coukell of the Pew Health Group, which hosted the convening, said he was encouraged by the caliber of the discussion: Significant common ground was gained, wide agreement forged on some policy reform proposals, and all with very little finger-pointing.

Hams asked FDA’s Taylor how he saw the role of the consumer: How do we engage the people taking the medicines around safety, and communicate the need to be both vigilant and compliant?

To a degree it’s good, Taylor said, when consumers take the FDA for granted. When their aspirin is safe, and works, then the agency is behind-the-scenes and doing its job. But he agreed of the need to figure out how to engage the public: “We’re going have to explain why we think these changes are necessary…in a way that actually affords consumers an extra level of confidence that the world is changing,” and that the rules must change to meet it.

“We can’t take for granted that folks know that [this] world is changing.”

Tune in tomorrow for Day Two, and follow @SafeRxWatch on Twitter for short, live tweets from tomorrow’s sessions.

–Kate Petersen, PostScript blogger

We’re late out of the gate on this one, but the numbers still bear mentioning – a report from the Center for Public Integrity out last month showed that the pharmaceutical industry’s been getting its money’s worth on K Street. Good news for the industry, because those expenditures totaled $168 million in 2007, up 32 percent in a year.  Bad news for those concerned that pharma’s influence on the Hill and on its own regulation is already too big.

In the win column for the industry in 2007: the reauthorization of the Prescription Drug User Fee Act, and a blocked bill that would have permitted drug reimportation.

The eye-opening stat for PostScript? “More than $6.8 million of the $14.4 million the pharmaceutical and health product industry gave in contributions went to members of three committees that regulate the industry: the House Committee on Energy and Commerce, House Committee on Ways and Means, and Senate Committee on Health, Education, and Labor.”

And while some may still hold out hopes of Karl Rove’s ‘permanent majority’, this report made it clear that pharma isn’t among them – support for candidates by party has swung widely since the Dems’ 2006 takeover, and for the first time in history, Democratic candidates received more funding from the industry than Republicans did. 

Prescription drug problems have hit the presidential radar screen. With an announcement of a plan to rein in the pharmaceutical industry this weekend at a campaign stop in Laconia, NH, John Edwards became the first major 2008 presidential candidate to take on the drug companies.  Here’s coverage in the Associated Press and Concord Monitor. Check out the full Edwards platform here on the campaign website.  Though much of it’s pulled from measures stripped from the FDA reauthorization bill passed earlier this year, Edwards’ proposal, which includes provision for a comparative effectiveness drug-testing center, full disclosure of safety and comparative effectiveness information on drug labeling and ads, empowering the FDA to go after drug companies that run misleading ads, and a two year moratorium on consumer ads for new drugs, is smart, and represents a leap forward in the candidates’ health care conversation.

On one hand, the fact that pharmaceutical marketing and industry reform is showing up in the presidential platforms only now is curious.  After all, talk of health care reform is as ubiquitous on the presidential campaign trail as American flag lapel pins, and the cost of prescription drugs is an issue that has emotional resonance with a pharmacy nation like ours.  Conventional (or perhaps campaign) wisdom has led candidates to focus on coverage, access and Medicare—how to cover more people without charging anyone else—these are the big ticket items. Catch is, conflicts of interest and undue marketing influence on prescribers have the power to affect the cost of those items, and recent reports indicate that they have.

On the other hand, it’s no surprise: health care groups, pharma included, have been some of the most aggressive lobbyists and generous contributors to presidential contenders, according to the Wall Street Journal Health blog, which has done a good job of keeping track.  And today the New York Times reported that health care groups have given $6.5 million to Democratic candidates and $4.8 million to Republicans so far. 

Pfizer has been the pharmaceutical company with the deepest pockets, giving the most to Hillary Clinton ($12,150), followed by Rudy Guiliani ($8,600).  Predictably, Edwards has received the least health care sector contributions to date (the Health blog points to his career as a plaintiff’s lawyer as explanation.)

So far, the headlines have focused on Edward’s DTCA moratorium, and the Monitor piece makes clear why: On the stump, it’s easier to lampoon the endless Flomax ads during the World Series or summon, as Edwards did, goofy images of allergen-free skipping fields. That’s fine—a two-year hold on ads for new drugs certainly won’t hurt matters, and may even decelerate the dubious consumer-marketing machine pharma’s driving.

But voters and the media should remember that DTCA is just a portion of a bigger problem—companies spend nearly twice as much in direct-to-physician marketing each year.  A candidate committed to these issues should address the rough reality that drug ads are just the tip of a really big iceberg: the potential for conflict of interest spills into academic medical centers, university research, continuing medical education, and physician marketing.  We must address those areas, too, if we are to truly tackle our nation’s prescription problem.

A report by the Office of the Inspector General of Health and Human Services released today says that the FDA has shirked its duty to oversee federal clinical trials in this country in a big way. Fewer than 200 inspectors are responsible for auditing more than 350,000 trial sites, and central tracking and follow up to inspections is largely absent. According to a report in the New York Times, just one percent of all trials for drugs seeking approval are audited. And despite 348 reports of serious problems that were filed by inspectors between 2000 and 2005, the FDA disqualified results just twice and investigators from conducting further trials just 26 times. Follow-up warnings were issued years after the research subject complained and the inspectors visited.

Alarming stuff, especially in light of the recent report that showed up on Pharmalot. Conducted by the Center for Congressional and Presidential Studies at American University (and underwritten by Pfizer) the survey showed that 82 percent of the public trusted the FDA to oversee medications, 67 percent trusted the drugmakers, and 53 percent trusted Congress. Just eight percent had heard of the FDA reform bill (the Prescription Drug User Fee Act reauthorization, or PDUFA) that President Bush signed yesterday.

So what to make of all this?

On the surface, PDUFA:The Next Generation is no cops-and-robbers story made for primetime news. But at its heart, the bill touches on some very cops and robbers issues—like how are clinical trials conducted, and who’s watching out for the safety of the subjects and accuracy of the data? Who knew about the dangers of Vioxx, and when did they know? Was trial data suppressed or ignored? Were doctors under the influence of an especially aggressive Vioxx campaign blitz from drug marketers? Should a regulatory agency be sponsored by the very companies seeking its approval? And there are one hundred more.

Every prescription drug we pick up at the pharmacy has been reviewed and approved by the FDA (54 percent of us knew this). What that means and how safe we are is a very public issue. But there isn’t always a direct translation from what the general public should know about and what it can change. In the case of medical care, public awareness can be eclipsed the long chain of decision-makers in play: patients, doctors, pharmacists, pharmacy benefit managers, providers, regulators, investigators and manufacturers all have a role in what someone takes to feel better.

Patient-prescriber relationships are especially tricky. Unlike a traditional economic relationship where the consumer is also the choosing agent in the market, the physician or nurse in this case acts as an intermediary with the power to choose what drugs a patient pays for and takes. Even if a patient is educated about the issues, knows the ins and outs of treatment guidelines and can find out how much his doctor took from pharmaceutical companies last year, the doctor is still the one making the diagnosis and writing the prescription. The unique nature of this mediated consumer relationship—in which the consumer is not the one wielding the purchasing power—means that the intentions and actions of the prescriber on behalf of the patient must be absolutely clear and free of conflict.

And moving up this chain of medical trust—in the U.S. anyhow—is the FDA, the main gatekeeper and certifier of safety. It has been endowed the power to approve drugs, and to verify and oversee the trials that ultimately test their safety and efficacy. Even the best-intentioned doctors, completely free of conflict with pharmaceutical interests and with their patient’s health first in mind, have to take the FDA’s word—whether it be in the form of an approval or warning—that what they are writing on the script does what the label says it does.

The new FDA reform bill is a step forward. But as Friday’s HHS report shows, we still have a long ways to go.