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 October, the FDA and manufacturers of finished generic drugs and ingredients (Active Pharmaceutical Ingredients or APIs) reached a ground breaking agreement that can (1) ensure the safety of generic drugs and APIs wherever they are produced globally and (2) ensure that new generic drugs become available to patients more quickly.

The drumbeat of manufacturing safety problems occurring in domestic and foreign plants that produce both brand name and generic pharmaceuticals continues must be addressed. In the last week, FDA has cited generic drug maker Mylan and German manufacturer Jenahexal for manufacturing problems, while Ranbaxy settled longstanding concerns in time to launch their generic version of the block-buster drug Lipitor.

Manufacturing failures can create obstacles to the ongoing availability of affordable generic drugs, or even serious risks to patient safety. Thus this new agreement (the Generic Drug User Fee Act or GDUFA) is critical. Addressing the lag in foreign inspections is especially significant, since 80 percent of active ingredients and bulk chemicals used in U.S. medicines now come from foreign countries. Currently, the FDA does not have the authority or resources to inspect all foreign suppliers of drug ingredients. Domestic plants are inspected by FDA on average every 2.7 years. The New York Times recently reported that at its current pace, the FDA would need 13 years to inspect every foreign drug plant exporting to the United States. 

The draft GDUFA agreement is a major commitment by the industry to solve this problem by “ensuring that industry participants, foreign or domestic, who participate in the U.S. generic drug system are held to consistent high quality standards and are inspected biannually, using a risk-based approach, with foreign and domestic parity.” The industry has backed up this commitment by agreeing to provide $300M annually in user fees to provide FDA with the resources to increase inspections and to speed the review of new generic drugs. The fees would supplement FDA annual funding. 
 
Guaranteeing the availability and safe manufacturing of generics is not only critical to patient safety, but also to access to care and to the financial stability of families, health plans and public programs. Today 78 percent of all prescriptions dispensed in the U.S. are generics. In 2008, the average cost of a generic drug was nearly four times less than the brand name equivalent ($35.22 vs. $137.90). Thus, while 78 percent of prescriptions are generics, the total spending on generics accounts for just 25 percent of the total U.S. drug spending, and generics drugs have saved more than $824B over the last decade.

GDUFA can play a role in solving the problem of drug shortages, as well. Shortages can be catastrophic for patient safety, and often affect generics since they account for 78 percent of prescribed drugs. Stepped up inspections at foreign plants can prevent manufacturing problems that can lead to shortages of medically necessary drugs. Health system pharmacists, who confront these problems every day, point out that “user fees can result in faster approval processes for generic drugs” while not sacrificing  patient safety concerns. 

The FDA-industry draft agreement is now being reviewed by the Office of Management and Budget. When approved, it will be sent to Congress for action, probably to be included in the renewal of the Prescription Drug User Fee Act (PDUFA), which deals with user fees for brand-name drug approvals.

- Marcia Hams, Director of Prescription Access & Quality

In less than a month, the FDA will convene a scientific panel to evaluate emerging evidence that some of the most commonly used contraceptives – Beyaz,Gianvi, Loryna, Ocella, Safyral, Syeda, Yasmin, Yaz, Zarah, — have greater risks than other similar products. Patients and their advocates are seeking court permission to have drugmaker’s internal studies released so that FDA can see the full picture.

These drugs all contain the hormone drospirenone, while other contraceptives use a different active ingredient — progestin levonorgestrel. The FDA reports that “all birth control pills pose a risk of blood clots” but a recent British Medical Journal (BMJ) study found that contraceptives containing drospirenone were “associated with a threefold higher risk of non-fatal [deep vein blood clots]” compared to women who do not use hormonal contraception, and twice the risk of competing drugs using a hormone other than drospirenone.

On December 8, an FDA panel will likely look at the body of evidence concerning this BMJ study, and other studies listed on the FDA website. This review might tip the scales enough to add warnings to the drug’s label. Yet it remains to be seen if FDA will see all the documents it should before making a decision.

About 10,000 patients who took Yaz or Yasmin are suing the drug’s manufacturer Bayer for failing to disclose an increased risk of blood clots, and their lawyers have asked the court’s permission to submit to the FDA hearing approximately 50 documents unearthed in that litigation. The lawyers describe these documents as “internal and candid memoranda of clinical trial data and adverse event data not [before] shared with the FDA [by Bayer]”, according to a brief filed in one lawsuit.

Many readers may recall that documents concerning the safety and illegal marketing of the drug Zyprexa, the widely used antipsychotic drug, were released a couple years ago, both by a doctor retained as an expert witness, and later by the Court. This information was invaluable in alerting the public to the increased risks of death when Zyprexa is used to treat vulnerable seniors suffering from dementia. Following the pattern we saw with the pain drug, Vioxx, in 2004 and the diabetes drug, Avandia, in 2010, the Zyprexa documents showed that in the interest of maintaining the sales of their block-buster drugs, drugmakers withheld critical information from the FDA and the public — causing the deaths of tens of thousands of patients, while leaving tens of millions at risk.

The hearing on December 8 is less than a month away. We hope FDA will make sure it sees any studies that Bayer’s scientists and expert consultants did concerning the risks of drospirenone before making a decision on how to best protect the public health.

And there’s a potential conflict-of-interest issue as well. Lawyers for the injured women are concerned that some of the 13 scientific experts on the FDA panel have financial relationships with Bayer. Under the FDA rules, members of scientific advisory panels must disclose their conflicts to the FDA, and must receive a waiver in order to participate. The advisory panel could recommend that the FDA add warnings to the labels, implement other safety protocols, or even to withdraw them from the market—it should be free of industry influence.

The FDA needs complete information to do a good job, and the public needs to know who ultimately participates or votes on the FDA panel to be sure we can trust their final decision. Every day women are barraged with slick TV ads for Yaz and other contraceptives. We deserve more than marketing buzz – we need an unbiased, transparent and scientific evaluation of the drugs that makes sure women are not knowingly put risk.

(Hat tip to Pharmalot)

– Wells Wilkinson, Project Director Prescription Access and Litigation &
Marcia Hams, Director, Prescription Access and Quality

Things are getting colder here in New England, and we’d been hoping for a little more Sunshine in October. That’s when HHS was supposed to issue rules implementing the Physician Payment Sunshine provisions of health reform.

The urgency was summed up by co-sponsor Sen. Chuck Grassley (R-Iowa) back in 2009: “Transparency fosters accountability, and the public has a right to know about financial relationships. Patients rely on their doctors’ advice. Taxpayers spend billions every year on prescription drugs and medical devices through Medicare and Medicaid. They also fund tens of billions of dollars of medical research each year, and the doctors conducting that research have a big influence on the practice of medicine.” For the last several months, Senators Grassley and Kohl (D-Wisconsin) have been urging HHS to issue regulations as quickly as possible to meet this need.

The Sunshine provisions require drug, device, biologics and medical supply makers to start submitting information to HHS on their payments to physicians, teaching hospitals and group purchasing organizations (GPOs) this January. That information must be available to the public on September 30, 2013 through a searchable online database.

We are increasingly worried that HHS delays could interfere with the process of collecting the most accurate, consistent and understandable reports from manufacturers, and that we and other interested parties will not have time to weigh in on the reporting framework that HHS proposes. Because of these concerns, we submitted a letter on October 20 to HHS Secretary Sebelius, along with Consumers Union, the Pew Health Group and industry itself – PhRMA, BIO and AdvaMed.

Early this spring, Community Catalyst shared our informal recommendations with HHS on how the systems could be set up to be most effective. We based our thinking on our experience with state disclosure laws and industry disclosures resulting from lawsuits and government investigations. Our top concerns are that:

• Reporting categories be defined in a specific, unambiguous, and mutually exclusive manner, so that data tells a clear picture of what these financial relationships are
• The public disclosure website be useful to all users, including lay consumers, physicians whose payments are being reported, and researchers interested in studying trends and impacts of financial relationships with industry

The Sunshine statute itself is much more specific than the state disclosure laws that it will replace. (Note: states can still collect other information not required by Sunshine, such as payments to nurse practitioners.) For instance, the Sunshine provisions lay out 14 descriptors for the “nature” of a payment, including, in brief: consulting fee; compensation other than consulting; honoraria; gift; entertainment; food; travel; education; research; charitable contribution; grant; royalty or license; ownership interest; and speaking for serving as faculty. States and industry data bases use many fewer, often ambiguous categories.

However, we have urged HHS to refine these definitions in regulation so that there is no confusion over how a company should report its payments. And physicians and teaching hospitals deserve to have the payment categories carefully described so they aren’t misinterpreted. The public needs clarity to assess whether certain payments might or might not affect the care they are receiving.

There are concerns by some over how the Sunshine disclosures will relate to other public sources of information on industry payments. These types of issues were front and center last week at a conference we attended on conflicts of interest, put on by the American Society of Law, Medicine and Ethics. The Sunshine law requires industry to report their payments to physicians and teaching hospitals, but physicians themselves must make disclosures about their industry financial ties to many sources, including academic medical centers, medical journals, NIH and FDA panels. There is the potential for confusion and misinterpretation of the data. Despite the challenges, Robert Steinbrook, MD from Dartmouth, and former deputy editor of NEJM, concluded in his presentation on COI and medical journals, that with the Sunshine provisions, “there should be additional opportunities to better control conflicts of interest in Medicine.”

Indeed, we believe the Sunshine provisions can set a national standard that will help in harmonizing all disclosure requirements and provide a useful cross check for physician self-reports.

– Marcia Hams, Director, Prescription Access and Quality
Community Catalyst