John Dingell Blasts FDA’s Closed Culture at Today’s Committee Hearing on Drug Safety

If FDA’s CMO Dr. Janet Woodcock’s goal is to create an atmosphere at FDA in which scientific debate is encouraged, she appears to  have her work cut out for her.

This morning, Congressman John Dingell had some harsh criticism for FDA and its Commissioner at the House Energy and Commerce Committe hearing on FDA and Drug Safety. 

Citing recent whistleblower cases, he suggested that Dr. von Eschenbach has made it clear that the Agency “does not tolerate public dissent from FDA employees,” but that “private dissent doesn’t work, either,” referring to recent Ketek incident.  Written testimony is not archived or available yet.

However, a live videotape will soon be  available via this link.

Below, Congressman Dingell’s warm introduction:  

Mr. Chairman, thank you for holding the second hearing in this Committee’s investigation of the handling of drug safety issues by the Food and Drug Administration (FDA). I welcome the FDA Commissioner, Dr. von Eschenbach, to the Committee.

The Commissioner should know that the FDA’s response to this Committee’s inquiries has been less than acceptable. Responses have been slow to our document requests regarding food safety, drug safety, and conflicts of interest. We do intend to see that all of our questions are answered fully.

The Commissioner’s appearance today was preceded a month ago by former FDA staff members who testified that they were forced to flee the FDA because they feared retaliation from their superiors. These are good doctors and scientists that exposed bad decisions — decisions that appear to have needlessly cost American lives.

Both private statements and public quotes attributed to the Commissioner indicate that he does not tolerate public dissent from FDA employees. Private protests within the FDA do not appear to work either. For example, in the case of the drug Ketek, only after Congress was informed by FDA former employees of the confused dictates of senior FDA officials did the Agency finally rectify its mistakes. We have heard testimony that the Commissioner told these same employees that anyone not willing to be a “team player” would be traded.

Given that their protests went to Congressional offices, including this Committee, I must remind the Commissioner that threatening FDA employees with retaliation for talking to Congress is not only unacceptable, it is illegal. My concern is echoed in a letter dated March 9, 2007, from Senator Chuck Grassley to Commissioner von Eschenbach, which I believe my colleagues should review. I ask that the letter be placed in the hearing record.

Dr. von Eschenbach has been invited to tell us why the Agency’s new Drug Safety Initiative will adequately address the “cultural problems” identified by a number of experts on FDA drug safety policies. That “cultural” problem comes down to what Senator Grassley calls having grown “too cozy” with industry – preferring drug approvals over swift action when clear safety signals manifest post-market problems.

At our last hearing, Dr. David Graham framed the question for today’s hearing as “What in the FDA proposals would prevent another Vioxx?”

For example, what in the new FDA proposal would ensure that FDA reviewers would not negotiate for more than 14 months on label changes, even after receiving substantial evidence of serious cardiac side effects as they apparently did with Vioxx?

Would the newly proposed Office of New Drugs act any differently upon the clear warnings regarding Vioxx from the epidemiological work performed in the Office of Drug Safety?

Under the new proposal, would the FDA medical officers in the Anti-Infectives Division been allowed to present their findings to the Advisory Committee?

Under the new proposal, are the Advisory Committees more likely to hear about potential fraud or errors in pivotal safety studies?

Moreover, where in the new FDA proposal is there any provision to fully inform the public of the case risks and benefits prior to a drug’s approval?

I, for one, do not see anything in the new FDA proposal that effectively responds to the many problems identified by this Committee over the last few years. None of these “reforms” impose structural guarantees to stop the cultural bias that has skewed the Agency’s judgment.

In the end, what the Administration proposal really boils down to is “trust us.” That would be easier to accept if the FDA and the Department of Health and Human Services were not resisting Congressional oversight and threatening whistle blowers.

Regardless, drug safety continues to be the central concern of this Committee as the reauthorization of the Prescription Drug User Fee Act (PUDUFA) goes forward. And you can trust us that, with the strong support of my colleagues across the aisle, we will come up with legislative changes to ensure against another Vioxx.
I thank both Chairman Stupak and Ranking Member Whitfield for holding this hearing, and I look forward to the testimony of today’s witnesses.

Avian Flu: Not If, But When - Immunologist Dr. Douglas Powell on New Vaccine Development

Play Video

Avian Flu Pandemic: It’s Not a Question of If, But When: Dr. Douglas Powell, Director of Immunology, Antigen Express - Bloomberg Bloomberg - (BLOOM) Mar. 19, 2007. 06:12 PM EST The number of cases of avian flu is approaching 300 and solutions are needed. Immunologist Dr. Douglas Powell discussed novel vaccine developments with Bloomberg yesterday.

Dr. Powell is speaking at the World Vaccine Congress in Washington, D.C.  this week. Here’s a summary of what he has been working on lately.

Dr Douglas Powell,
Director of Immunology,
Antigen Express

As an H5N1 virologist and immunologist, Antigen Express Director of Immunobiology Doug Powell studies the immune response H5N1 influenza vaccines and infection. The antibody response in humans vaccinated with inactivated H5N1 virus produced in chicken eggs or by recombinant H5 is relatively weak to when compared to seasonal H1N1 and H3N1 vaccines. This suggests that the H5 hemagglutinin molecule is poorly immunogenic. It is generally accepted that egg-based or recombinant H5 vaccines will play little role during the first wave of a pandemic, therefore it is essential to develop novel vaccination strategies for H5N1. The virus-specific CD4+ T cell response is critical in providing help to B cells for optimal generation of neutralizing antibodies. We have mapped several MHC Class II epitopes in H5 and have demonstrated that immunization with defined epitopes greatly enhances the CD4+ T cell responses to recombinant H5 protein.

Something Missing From InnerState Drama? Cleaning Union Dishes Dirt on Pricing, Safety in Centocor Shareholder Letter, Plans Physician Letter Next

Could the controversial Centocor film, InnerState, have had more dramatic impact by including courtroom scenes or addressing an issue near and dear to some of the patients who take Remicaid: Pricing?

One group, CentocorWatch.org, appears to think so. The group represents the “largest property service workers’ union in the country, ” or some 85,000 janitors, cleaning people, concierges and other workers in six states. Today it has just issued a newsletter to Centocor/J&J shareholders, highlighting pricing practices  and potential safety issues with Remicaid. The group plans to contact physicians next.

The union launched a class action lawsuit against J&J four years ago over its pricing practices (particularly its use of the “Average Wholesale Price,” which, they say, means that they end up paying 30% more for Remicaid than physicians). The group had already distributed leaflets outside the New York premieres of the film InnerState.

Download the Centocor Watch newsletter here.

Below, unedited text of a press release they sent out today.

Newsletter to J&J Shareholders Highlights Potential Financial Troubles

    PHILADELPHIA, March 19 /PRNewswire-USNewswire/ — Local 32BJ today issued the first in a series of newsletters detailing concerns about a court case that charges Johnson & Johnson (J&J) and other drug companies with deceptive drug pricing. The newsletter, which has been mailed to thousands of shareholders in advance of their annual meeting in April, also discussed safety concerns with Remicade, a biologic produced by J&J subsidiary Centocor. The content of the newsletter can be viewed online at http://www.CentocorWatch.org.

    The plaintiffs in the court case about drug pricing charge J&J and others with using pricing and marketing practices that lead to excessive reimbursements by Medicare, private insurers, and patients. In documents filed in connection with the case, J&J admitted to publishing “average wholesale prices” that are above the real cost of medications.

    The newsletter informs readers that, “Ending these higher payments, coupled with greater awareness of the safety concerns about Remicade, could significantly impact Johnson & Johnson’s bottom line.”

    On February 21, representatives from Local 32BJ distributed information about the class action suit against J&J outside of the movie premier of the film INNERSTATE, a ‘documentary’ produced by Centocor that follows the lives of three patients affected by diseases treatable by Remicade.

    Remicade, which generated $3 billion in revenues for J&J last year, also faces scrutiny over safety concerns. Due to increased risk of infections and cancer, the U.S. Food and Drug Administration has issued two black box warnings for Remicade — its strongest safety warning. Humira, a comparable drug produced by J&J’s competitor Abbott, carries only one black box warning, while Enbrel, produced by Amgem, carries no black box warning.

    Future 32BJ publications may include a mailing to physicians about Remicade.

   

Dora Akunyili Stresses the Need for Pharmacovigilance, Wins Awards from BBC and Locally

More news from the front lines of drug anticounterfeiting.  In Onitsa, Nigeria, men sent by NAFDAC to close down dangerous operations were greeted with violence. For more, click here. Dr. Dora Akunyili, head of NAFDAC, recently stressed the need for public health programs in Nigeria to share drug safety data with the national pharmacovigilance authority, before making them public at international conferences.  For more, click here. The doctor won awards recently from BBC, where she was called to judge a competition for excellence in broadcasting, and, more recently, as “most dedicated public servant” in the Giant Strides award.

Just discovered global pharmacovigilance updates from the WHO’s Uppsala Monitoring Center that might be of interest. UN/WHO Upsala report on global pharmacovigilance activities

RhinoMax Recalled

Don’t know how many of you would buy a medicine from a company named Cosmos Trading (no offense to the company, which appears to have cooperated fully with FDA, but it doesn’t sound like a dedicated drug supplier)but just received an FDA notice of a recall of a supplement called RhinoMax, which contained an undeclared ingredient, aminotadalafil, which can react with nitrates from other drugs (like nitroglyercin) to lower blood pressure to dangerous levels.

Silly me, from the “rhino” I thought it was a nasal decongestant, but, it is instead a treatment for that killer disease, “ED.”  Below, the notice from FDA including a link to the full safety report. How can one avoid declaring an active ingredient like that?  All of which points to the need for far better testing of raw materials, and use of better technology, including PAT. Lives are at stake here.

MedWatch - The FDA Safety Information and Adverse Event Reporting
Program

Cosmos Trading, Inc. and FDA notified consumers and healthcare
professionals of a voluntary nationwide recall of a supplement product
sold under the name Rhino Max (Rhino V Max) in 5-tablet boxes or
15-tablet boxes. Lab analysis by FDA of product samples found the
product contains Aminotadalafil, an analogue of Tadalafil, an
FDA-approved drug used to treat Erectile Dysfunction (ED). FDA advised
that this poses a threat to consumers because Aminotadalafil may
interact with nitrates found in some prescription drugs (such as
nitroglycerin) and may lower blood pressure to dangerous levels.
Consumers with diabetes, high blood pressure, high cholesterol, or heart
disease often take nitrates. Consumers who have Rhino Max (Rhino V Max)
in their possession should stop using it immediately and contact their
physician if they experienced any problem that may be related to taking
this product.

Read the complete MedWatch 2007 Safety summary, including a link to the
firm’s press release, at:

http://www.fda.gov/medwatch/safety/2007/safety07.htm#Rhino

_________________________________________________________________

To ensure delivery of these timely alerts to your in-box and prevent
rejection of the notice by a spam filter, please add our MedWatch
address, MEDWATCH@LIST.NIH.GOV, to your address book.

Thank you for using FDA MedWatch as a trusted source for timely safety
information on drugs, devices and diagnostics regulated by the U.S. Food
and Drug Administration. If you find this e-mail notification helpful,
please consider telling colleagues and friends about MedWatch and this
e-mail notification process.  They can learn more and subscribe to the
e-list at http://www.fda.gov/medwatch.

Because One Can’t Live on RFID Alone, AstraZeneca Banks On Unit Serialization for Nexium

Next quarter, AstraZeneca will be using a new security feature for its Nexium product, based on serialized 2-D bar codes using Authentix technology.  However, the platform will be flexible enough to work with RFID, when that technology is sufficiently mature.  Below, the press release.  We’ll be covering this in depth in April’s issue of Pharmaceutical Manufacturing, so stay tuned.

Next quarter, AstraZeneca and Authentix plan to roll out unit-level serialised tamper evident security seals (TESS) combined with unique carton numbers (UCN) for AZ’s Nexium product. When the Serialised Authentication Program launches next quarter, AstraZeneca will become one of the first pharmaceutical companies to implement a comprehensive system to serialise and authenticate its pharmaceutical products down to the unit-level.

The Serialised Authentication Programme for NEXIUM assigns unique serialised codes to each tablet blister pack via the carton and the associated tamper evident seal. Once a serialised code is assigned, it is activated, validated, and entered into a database where it can be cross-checked against all serialised codes throughout the AstraZeneca supply chain.

In November 2006, the European Federation of Pharmaceutical Industries and Associations (EFPIA) endorsed serialisation as the most promising solution to fight counterfeiting and illegal diversion threats in Europe and globally. The EFPIA maintains that serialisation offers greater security, enhances tracking, and will work easily with Radio Frequency Identification (RFID) technologies when RFID matures.

“The Serialised Authentication Programme gives AstraZeneca the potential to monitor our supply chain. Furthermore, working with other pharma companies, industry bodies and government agencies, the system will eventually help facilitate the identification or verification of products across the entire supply chain, from the point of manufacture to the point of dispensing,” says David Teale, Director of Product Security, AstraZeneca. “In addition, the programme can be combined with other brand protection requirements for field authentication and tamper evidence.”

“By becoming one of the first pharmaceutical companies to employ large-scale mass serialisation, AstraZeneca is leading the way” says Jim Rittenburg, Vice President of Healthcare and Life Sciences, Authentix. “AstraZeneca is showing patients that they are committed to being at the forefront of the fight against pharmaceutical counterfeiting.”

The Serialised Authentication Programme is the result of several years of collaborative work between Authentix and AstraZeneca which has resulted in a number of diverse regional authentication and serialisation solutions that help safeguard AstraZeneca products, and ultimately, the patients who depend on them.

ABOUT AUTHENTIX

First Oncology Drug Supplier Establishes e-Pedigree

U.S. Oncology is using SupplyScape. Click here for their news release.

FDA’s Adverse Drug Reaction System Blasted in a Report that FDA Commissioned, WSJ Reports

The Wall Street Journal  (click to access the article—subscription required) here) has just reported on a report that has not yet been released to the public, that finds serious problems with FDA’s Adverse Drug Reaction reporting system. 

Disturbing, since the Agency needs new IT platforms, and has requested an increase in user fees to pay for more IT work.  On the other hand, it has just hired a new CIO.

Let he who has never suffered from a botched IT project or been burned by an IT consultant, cast the first stone.

Below, an excerpt from the WSJ article.  

The Food and Drug Administration has bungled its effort to build a new system for detecting the side effects of medicines after they go on the market, delaying its implementation by at least four years, according to a report commissioned by the agency itself.

As a result, the agency must continue to rely on its existing “dysfunctional” computer system as a primary tool for tracking the safety of medications sold in the U.S., according to the November 2006 report, which hasn’t been made public.

The situation is “frustrating and undermining…the post-marketing drug safety work” of its staff “because they lack some of the basic tools they need to perform their jobs, e.g. a computing system that meets their requirements,” says the report. It was prepared by the Breckenridge Institute, a research and consulting firm in Breckenridge, Colo.

Pfizer’s Getting Ready for its ePedigree Trial; Update on Drug Counterfeiting and Diversion

Counterfeiting has become a huge business, accounting for nearly 3% of the world’s GDP, and, if pharmaceutical counterfeiting, already a $35-billion global business, according to WHO, continues at its current pace, in 10 years, one in five consumers of drugs will take a fake drug.  This overview by legal policy experts Mark Mutterperl, Jessica Parise and Chehrzade Chemcham and published in the U.K.’s The Manufacturer, looks the global trend and summarizes discussion at the Global Anticounterfeiting Congress, which took place in late January.

But RFID Journal recently reported on Pfizer’s upcoming test of its e-Pedigree system (to download the article, click here)….for a recent update on e-Pedigrees from PharmaManufacturing.com, click here).

 In the meantime, this week brought news of a successful drug diversion ring bust in India.  Leading the ring were seemingly “ordinary” businessmen.  It’s always nice to see some dent made, however small, in this huge grey menace. This was reported recently by a local newspaper in Mumbai, India….

Traders held for smuggling
  
Three city-based businessmen have been arrested by the Directorate of Revenue Intelligence (DRI) for allegedly involving in smuggling high-value pharmaceutical drugs worth Rs 7 crore.

Manish Bhavishi, Tajdin Charania and Kamlesh Bhalani acted in connivance with another key accused, Sajid Malik Nazir, a Hong Kong-based Pakistani.  

DRI sources said, “Bhavishi was remanded in judicial custody till March 7 while Charnia and Bhalani were remanded in judicial custody till March 15.”

In his remand application, investigating officer Jayant Nair said, “Acting on specific information, DRI officials intercepted businessmen Bhavishi and Najarali Charania who arrived from London by Emirates Airways on February 20 at Sahar International airport. During a search of their baggage, high-value pharmaceutical drugs worth Rs 2 lakh were found.

When questioned, the two businessmen could not produce documents in support of the drug possession. Later, storage premises of Bhavishi on the first floor of Jyoti Chambers, Narsi Natha street in South Mumbai was searched on February 20, resulted in the recovery of 85 sealed bags each stated to contain one kg each of  Miglitol, a drug of Chinese origin and another sealed bag contained another pharmaceutical drug one kg of Ethynal Estradiol.

DRI officials also allegedly seized rubber stamps of M/s Venus Pharma, M/S B.V.Sales Corporation & Bhavna Traders, blank letter heads, a blank bill of M/s Saino Impex and a bag-sealing machine collectively worth Rs 50 lakh from the premises. The DRI officials further searched the office of M/s Balaji Pharmachem at Ashoka Shopping centre in South Mumbai, belonging to Charania on February 20 and seized import documents pertaining to M/s Palam Pharma, rubber stamps of firms like M/s D.D. Raw Pharma, M/s Reliable Agencies and M/s Swiss Parneteruls Pvt. Ltd, a lap-top, and certain other documents  pertaining to purchase and sale of pharmaceutical drugs.

DRI sources said, “During interrogation, main accused Bhavishi said he was organising large-scale smuggling of high-value pharmaceutical drugs through carriers. He also reportedly admitted selling Ketamine to local traders. He imported pharmaceutical drugs from China in the name of other firms like M/s Palam Pharma and sold the same in local market. He has contacts with a Hong-Kong based Pakistani national Sajid Malik Nazir who procures pharmaceutical drugs at Hong Kong. He had recruited 16 to 17 persons who have been travelling to Hong Kong & Bangladesh regularly for the same purpose.

The accused would pack the smuggled items and sell it in local market.
 

More Drug Safety Transparency: New Open-Access, Peer-Reviewed Journal to Post Clinical Trial Information

I hardly recognize science publishers today….so many mergers have taken place so quickly.  But just got word of a new, free and open-access journal that should be a must-read for anyone in the industry.  Its goal is to disseminate results of clinical trials, but also results of drug-drug- interaction studies as well as pharmacokinetic studies.  For more information, here is the news release that “Wiley-Blackwell” issued today.

Wiley-Blackwell to Launch Archives of Drug Information
Journal to Increase Public Access to Latest Research from Pharmaceutical Industry
 
Hoboken, New Jersey–March 5, 2007 — Wiley-Blackwell announced the launch of Archives of Drug Information (ADI), a new open access, freely available peer-reviewed journal, dedicated to publishing the results of drug studies. This journal will help to address requests for transparency voiced by societies, health care practioners, patients, media, and the government to disclose clinical trial information.
 
ADI is unique because it will publish not only results of clinical trials and drug studies, but also articles on inconclusive and/or negative clinical trials, early drug development, routine drug-drug interaction, pharmacokinetic studies, and other low-profile areas that are traditionally overlooked. The first articles will be published online April 2007.
 
“ADI will provide an unbiased, scientific home for high-quality information that should be in the public domain but currently resides on file somewhere,” says Dr. C. Michael Stein, Editor of Archives of Drug Information. “It will also help prevent scientists in drug development from repeating mistakes or following the same blind alleys others have explored because that information has never been published.” ADI will publish a broad range of research, including cellular, animal, and human studies.
 
While some government and pharmaceutical companies provide repositories to register clinical data and public databases to post clinical trial results, sources for independent publication are very limited.  As a result, the findings of many drug development studies and clinical trials remain unpublished. Archives of Drug Information will bridge this gap by publishing data from clinical trials thereby disclosing results promptly to the researcher, clinician and the public. With ADI, it will be possible for everyone to freely search every published article to locate specific trials, methods, and experimental results.
 
“This new journal is an exciting opportunity for Wiley-Blackwell to help the medical and pharmaceutical communities advance the innovative work of drug discovery and to help patients and their families understand the risks and benefits of prescription medicines,” says Sue Corbett, Vice President and Managing Director, Medicine, Wiley-Blackwell. “Archives of Drug Information will become a resource for scientists, physicians, patients, and students worldwide by providing free access to information that has previously been inaccessible.”
 
For more information on submitting papers, contact ADI@bos.blackwellpublishing.com.-AMS