1.Firms take on do-it-yourself regulating
2.When Regulators Become Enablers
EXTRACT: The acid test for this program will be acceptance by stakeholders, such as venture funds that can't afford to risk investments in firms that might implode by having a technology "leak". (item 1)
1.Firms take on do-it-yourself regulating
By Rachel Melcer ST. LOUIS POST-DISPATCH, 26 July 2007http://www.stltoday.com/stltoday/business/stories.nsf/0/D888B2805DD1D3C186257324000A885C?OpenDocument
Biotech crop makers on Wednesday said they are increasing self-regulation to avoid the accidental spread of genetic material. These incidents can cost companies access to foreign markets, consumer confidence and big legal bills.
The Biotechnology Industry Organization, a Washington-based trade group, will design and administer the program, dubbed "Excellence Through Stewardship."
Member companies - including the world's six largest providers of genetically modified seeds - will adopt quality management standards, then undergo independent third-party audits to verify compliance. The goal is to track and control genetic crop traits in research discovery, through field trials, marketing and eventual phaseout.
No one wants these genes to turn up in places they're not supposed to be - such as last year's surprise finding of unapproved LibertyLink genes in commercially available long-grain rice. Advertisement
Regulators found the trait, developed by Bayer CropScience, was harmless and subsequently approved it for the market. But damage was done: Japan, the European Union and other countries closed to U.S. rice imports. Prices fell, then farmers suffered and filed a class-action lawsuit against Bayer in U.S. District Court in St. Louis.
"The industry is trying its best, in a world that's not 100 percent perfect, to self-regulate and self-police because it's in their best interest," said Marshall Martin, associate director of agricultural research programs at Purdue University.
The stewardship program will roll out in three phases.
Companies will self-certify they have adopted the program in their domestic operations by early next year. At the end of next year, they will have completed audits by independent firms that are trained and certified by BIO, the industry organization. In 2009, BIO member companies will roll out the program to operations abroad.
"Part of our challenge will be - and we look forward to it - making sure that this is the gold standard and that it is understood around the world," said BIO President and Chief Executive Jim Greenwood.
The initiative is not a reaction to the Bayer incident, he said. Rather, "we see the science evolving, we see the use of these products expanding, and we felt our efforts should evolve as well."
Andrew Baum, chairman of BIO's Food and Agricultural Section Governing Body, said companies always have had quality management standards.
"It's not as if (the Bayer incident) took place and we had an epiphany," he said. "We were moving towards this anyway."
What's more, the stewardship program should raise all boats by making the best practices of industry giants available to smaller companies, university researchers and players abroad, BIO said.
"I wish, when we had five employees, we had something like this. It would have saved us a lot of time and effort," said Baum, president and CEO of SemBioSys Inc., a 70-person plant-based pharmaceutical firm in Calgary, Alberta.
The acid test for this program will be acceptance by stakeholders, such as venture funds that can't afford to risk investments in firms that might implode by having a technology "leak," he said.
BIO presented its program to the U.S. Department of Agriculture, Environmental Protection Agency, and Food and Drug Administration - all of which regulate biotech crops.
The federal agencies do not have this type of quality management and stewardship regulation in place - but ag biotech companies say they are not trying to step on government toes.
"The industry supports strong, science-based federal regulation. This is a complement to that, it's not a substitute. Both are really important," said Jerry Steiner, an executive vice president with Creve Coeur-based Monsanto Co., the industry leader.
Participants hope the program will stave off future leaks of biotech traits into conventional crops, which damage consumer acceptance of their products. It's a pivotal time for the industry, as it nears commercialization of a generation of crops engineered with traits that add consumer benefits - healthy-oil and omega-3 enriched soybeans, for example. Shoppers need to trust the safety of the technology for these to succeed.
"I don't think anyone can say this will prevent any particular incident," said Tom West, a vice president with DuPont unit Pioneer Hi-Bred International Inc. "But this is about raising standards all across the board."
2.When Regulators Become Enablers
Inside Bush's FDA
By EVELYN PRINGLE
CounterPunch, July 17 2007
Americans need to stop and consider how many consumers will be killed and injured by dangerous drugs by the time George Bush heads back to Texas at the end of his Presidency, as a direct result of his allowing the interests of the pharmaceutical industry to take control of the FDA.
For nearly 70 years, the common-law tort systems in the individual states have provided a remedy for citizens injured by prescription drugs. However, in one of the most blatant paybacks for political contributions in US history, in January 2006, Bush-appointed officials at the FDA announced that the agency's approval of a drug and its labeling acts to preempt product liability lawsuits filed by patients against the pharmaceutical giants.
On February 23, 2006, Democratic lawmakers Rep Henry Waxman, of the Committee on Government Reform, and Reps John Dingell and Sherrod Brown of the Committee on Energy and Commerce, sent a letter to the Secretary of Health and Human Services, and voiced their outrage.
"The announcement," the lawmakers wrote, "provides unfortunate evidence that the Bush Administration is more committed to protecting drug industry profits than to building a sound system for ensuring drug safety."
"The FDA's preemption announcement," the letter said, "is particularly troubling at a time when FDA's own ability to protect Americans from unsafe drugs has been called into question by a series of cases in which the FDA was slow to warn consumers of significant drug risks."
The new rules went into effect on June 30, 2006, and preemption is now being used in litigation all over the country in an attempt to dismiss lawsuits filed by private citizens against drug companies.
Unbeknownst to average Americans, the administration's gift of preemption is not limited to industries regulated by the FDA. Bush-appointed officials in all federal regulatory agencies are working in concert to ensure that major corporations subject to product liability lawsuits can claim that federal regulation of their products preempts any recovery for consumers harmed, whether the injury involves defective automobiles, pesticides or whatever.
In return, the major corporations are ganging up on private citizens by filing amicus briefs in support of pharmaceutical companies involved in litigation. For instance, the drug giant Wyeth is arguing preemption in a petition currently pending before the US Supreme Court in a case involving one lone woman in Vermont, in an attempt to overturn a jury verdict that was affirmed by the Vermont Supreme Court.
Amicus briefs to support Wyeth's preemption argument are piling up, including one filed by the Product Liability Advisory Council on behalf of just about every major product manufacturer in America.
The plaintiff, Diana Levine, a professional musician, has the support of the Public Citizen Litigation Group. Ms Levine went to the hospital to seek treatment for a headache and left with injuries that led to the amputation of her arm after the drug Phenergan was administered by IV to alleviate the nausea associated with a migraine headache.
Specifically, her arm had to be amputated because the drug reached Ms Levine's arteries, and the lawsuit alleges that Wyeth was aware of the risk of arterial contact when the drug was administered by IV and failed to warn against using a method to administer Phenergan that caused the injury.
In the petition, Wyeth does not dispute that Ms Levine's arm was amputated because the company failed to warn about using this method. Its sole argument is that she is not entitled to damages because the FDA did not require Wyeth to warn about the danger of administering the drug this way.
The Vermont Supreme Court rejected this argument. The agency's claim of conflict with federal law, the Court held, did not warrant deference because it was flatly at odds with both the FDA's regulation permitting manufacturers "to add or strengthen a warning 'to increase the safe use of the drug product' without prior FDA approval," and with Congress' express directive that state law concerning prescription drugs be superseded only when it poses a '"direct and positive conflict' with federal law."
On May 21, 2007, the Supreme Court invited the Solicitor General to file a brief to express the views of the government, which will no doubt add support for a favorable preemption ruling for Wyeth, potentially affecting tens of thousand of private citizens with cases pending all over the country.
A favorable ruling on preemption could provide an escape hatch for GlaxoSmithKline in lawsuits filed by patients injured by the diabetes drug Avandia (rosiglitazone), even though the FDA is aware of the fact that Glaxo concealed the serious cardiovascular risks known to be associated with the drug for years.
Medical experts are now predicting another Vioxx-like disaster with Avandia. In May 2007, prominent cardiologist Dr Steven Nissen, of the Cleveland Clinic, reported a study in the New England Journal of Medicine that found the drug to be associated with a 43% increase in heart attacks and possibly a 64% increase in cardiovascular death.
In a May 26, 2007, speech on the Senate Floor, Senator Charles Grassley (R-Iowa) said that the actual number of heart attacks possibly linked to Avandia may be as high as 20 a day.
Since the drug came on the market about 8 years ago, he said, tens of millions of prescriptions have been written, and Medicare and Medicaid have paid hundreds of millions of dollars for the drug.
At a June 6, 2007, hearing of the House Committee on Oversight and Government Reform to review the FDA's failure to warn the public about Avandia, Chairman Waxman (D-Cal) began the meeting by pointing out: "It is not Congress' role to adjudicate these medical issues."
"But it is our role," he noted, "to ensure that the Food and Drug Administration is taking these concerns seriously and providing doctors and patients with the guidance they need to make informed decisions."
"Although Avandia has been on the market for eight years and has been used by millions of Americans," Rep Waxman said, "the post-market studies have not been done to say conclusively whether Avandia increases or decreases the risk of heart attacks."
"That's a major failure of our system," he said. "And it is what is causing so much confusion and worry among the patients who are taking Avandia today."
Another FDA failure that will surely lead to many lawsuits was allowing Permax (pergolide), a drug used by Parkinson's patients, to remain on the market until March 29, 2007, long after its link to valvular heart damage was known.
Eli Lilly gained approval for Permax in 1988 but, at the time of the recall, the drug was manufactured by Valeant Pharmaceuticals and generics were sold by Par and Teva.
As early as December 2002, doctors at the Mayo Clinic reported that 3 Permax patients had developed heart valve disease similar to that caused by the Fen-Phen diet combination. In 2004, HealthDay News reported that a study had confirmed earlier findings that Permax was linked to heart valve damage which required surgery to correct.
On January 4, 2007, two studies in the New England Journal of Medicine said that the number of patients developing valve damage was higher than expected. One study found moderate to severe valve problems in more than 23% of the patients on Permax, compared to less than 6% in the comparison group.
The second study found Permax users were 5 to 7 times more likely to have leaky heart valves than patients taking other Parkinson's drugs, and patients taking the highest doses of Permax were at a 37 times greater risk.
The FDA's preemption policy has the potential to benefit every major drug company. Johnson & Johnson's SEC filings show that the company is currently facing hundreds of lawsuits over the deaths and injuries linked to the Ortho Evra birth control patch in women all over the country who have suffered blood clots, heart attacks and strokes.
Legal analysts predict that many more lawsuits will be filed due to the wide use of the device and as women realize that their injuries are due to the patch. In 2005 alone, there were more than 9.4 million prescriptions issued for the Ortho Evra patch, according to IMS Health, an industry-tracking firm.
A preemption ruling in this litigation would be especially onerous in light of the fact that the injuries are clearly due to the patch, because blood clots, heart attacks and stroke are almost unheard of in the age group of women who use this device.
This is another case where FDA officials knew of the health risks before the drug was approved. Agency records show that in 2000, the FDA scientist in charge of reviewing the preapproval trials submitted, warned that blood clots could occur and recommended that the information be included in the prescribing information for the patch.
The new drug application for the antibiotic, Ketek, marketed by Sanofi-Aventis, was rejected twice, in 2001 and 2003, before FDA management approved the drug on April 1, 2004, based on fraudulent studies, and over the objections of the FDA's own scientists.
Many patients have been harmed because doctors trusted the FDA's approval of Ketek. According to a review of the FDA's Adverse Event Reporting System, by the staff of the Senate Finance Committee, between July 2005 and September 2005 alone, there were two deaths, 35 liver adverse reactions, 44 cardiac events, and 80 visual events in Ketek patients.
In addition, internal FDA emails obtained by staffers, prove that top FDA officials were aware of the problems with Ketek before it was approved, and that FDA scientists, Dr David Ross, Dr David Graham, Dr Charles Cooper, and Dr Rosemary Johann-Liang, all warned FDA management about the serious adverse effects associated with the drug.
A May 16, 2006, FDA memo authored by safety reviewers said Ketek was linked to 12 reported liver failures including 4 deaths, 23 reports of serious liver injury, and a higher rate of adverse reaction reports than other antibiotics on the market, and the reviewers recommended a black box warning for the Ketek-related liver injury.
However, Sanofi-Aventis and FDA officials disregarded the recommendation and announced that only a new bolded warning would be added.
In addition to the massive Vioxx litigation, Merck is facing a large number of plaintiffs in lawsuits over the osteoporosis drug Fosamax, alleging the drug causes jaw-bone death, which is an extremely rare condition.
Kenneth Hargreaves of the University of Texas, discussed the increasing cases of ONJ in the April 3, 2006 LA Times. "We've uncovered about 1,000 patients in the past six to nine months alone," he said, "so the magnitude of the problem is just starting to be recognized."
Oral surgeon, Dr Salvatore Ruggiero, one of the first doctors to notice the increase in 2001, told the Times, "Even though the chances of getting this are small, considering there are 23 million women taking this drug, we could be talking about a significant number of people."
The FDA approved Fosamax in 1995, and because it is a relatively new drug, unreported cases OJN may be higher than expected because doctors may attribute the pain caused by the condition to osteoporosis, according to Diane Wysowski of the FDA's Office of Drug Safety in the Times.
Here again, the FDA and the drug maker were aware of the link between OJN and Fosamax but failed to warn the public until after the drug was prescribed to tens of millions of patients.
The man most credited for the creation of the preemption policy is the FDA's former Chief Counsel, Daniel Troy, who plays for the opposite team in private practice. Prior to his appointment as Chief Counsel, Mr Troy was a partner at Washington's Wiley Rein & Fielding, where he filed lawsuits against the FDA on behalf of the pharmaceutical industry to loosen restrictions on off-label prescribing and advertising of prescription drugs.
In fact, critics say, it was Mr Troy's loyalty to the industry, demonstrated by years of legal battles against FDA regulations, that earned him the appointment by the Bush administration as the industry's inside legal counsel.
Mr Troy himself bragged about his part in implementing the preemption policy in an article he wrote in the October 9, 2006, Legal Times stating: "I was also at the FDA while January's Physician Labeling Rule, which contains a statement in its preamble about the FDA's pre-emption authority, was written."
"And I now," Mr Troy states, "advise and represent companies confronting state-law claims that implicate the pre-emptive effect of FDA requirements."
But the fact is, Mr Troy was testing the viability of the preemption argument with judges in state and federal courts long before the new policy was announced in January 2006, by filing amicus briefs on behalf of drug companies and against private citizens in cases involving the new class of selective serotonin reuptake inhibitor antidepressants (SSRI's) back in 2002.
Critics say it's a toss-up between Vioxx and the SSRI's when it comes to the number of deaths and injuries that could have been prevented if the information about the serious health risks known to the drug makers had not been concealed.
Over the last 2 decades, SSRI's, which include Paxil, Zoloft, Prozac, Celexa, Luvox and Lexapro, have been prescribed off-label for uses not approved by the FDA more often than any other drugs in history. The Journal of Clinical Psychiatry found that 75% of SSRI prescriptions were written for unapproved uses in June 2005.
Critics say that the profits that have resulted from the massive off-label use of SSRI's, and especially with children, are a direct result of their illegal promotion by the drug makers. The success of the off-label marketing of SSRI's is evidenced by a June 29, 2007, report by Reuters that found the most commonly prescribed drugs in the US are antidepressants.
While most of the focus has remained on the risk of suicide, SSRI's have also been linked to extreme violence, including homicides, several life-threatening birth defects, abnormal uterine or gastrointestinal bleeding, a decrease in bone mineral density, sexual dysfunction, fertility problems and a severe withdrawal syndrome.
In September 2002, Mr Troy filed the FDA's first brief in support of preemption in the Zoloft suicide case of Motus v Pfizer, based on a request by Pfizer attorney Malcolm Wheeler. In the brief, Mr Troy claimed that warnings of a causal relationship between Zoloft and suicide would have misbranded the drug and that "any warning, no matter how worded, that could reasonably have been read as describing or alluding to such a relation would have been false or misleading, and therefore in conflict with federal law."
Baum Hedlund partner, Attorney Karen Barth Menzies, has been battling the SSRI makers in the legal arena for more than a decade in representing plaintiffs with claims involving Prozac, Paxil and Zoloft.
Ms Menzies says Mr Troy's argument is absurd because Wyeth strengthened the warning about suicidality on the label of Effexor in August 2003, without obtaining prior FDA approval, and the FDA did not sanction Wyeth or claim the label was false and misleading.
Ms Menzies has defeated the preemption arguments by Mr Troy offered in support of Pfizer and GlaxoSmithKline in a number of cases. The court never reached the preemption issue in Motus because the case was resolved on other grounds, but in September 2002, Mr Troy tried to use the same argument in a lawsuit that alleged Glaxo had failed to warn about the withdrawal effects of Paxil, and the judge stated the argument "contravenes common sense" and "vitiates, rather than advances, the purpose of protecting the public."
Pfizer also submitted Mr Troy's brief from Motus to support a preemption in the case of Witczak v Pfizer. In rejecting the argument, the court pointed out that: "State consumer-protection law compliments, rather than frustrates, the FDA's protective regime."
"This is especially apparent," the court said, "when one considers that prescription drugs were once marketed primarily to trained health care providers -- sophisticated and discerning intermediaries."
"Today, on the other hand, pill-rolling apothecaries and the mortar and pestle have disappeared," he stated. "They have been replaced by drug manufacturers who urge the use of their drugs in mass-market print and television advertisements targeted directly at the public," he said.
As an example, the judge noted that Glaxo had advertised the drug Paxil, "by personifying it as a happy, bouncing-oval cartoon character."
After effectively allocating the power of FDA to drug companies, in 2004, Mr Troy went back to representing the pharmaceutical industry with the preemption policy tucked in his back pocket.
But his departure did not stop Pfizer from trying to use the FDA preemption argument in the Zoloft suicide case of Cartwright v Pfizer, decided in 2005, in which the court rejected Pfizer's preemption argument, finding that Texas tort law "compliments and is parallel to the FDA's regulations regarding safety warnings and, thus, does not interfere with the objectives of the FDA."
The court further noted that the FDA mandates that "manufacturer[s] issue a warning whenever there is 'reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.'"
The truth is that the FDA knew about the risk of suicidality in children taking Zoloft, because the agency's review of Pfizer's clinical trial data in 1996 showed the risk to be five times that of adults on Zoloft and caused enough concern that FDA reviewer Dr James Knudsen wrote to Pfizer asking for an explanation.
The FDA's new preemption policy also purports to immunize doctors. "Pre-emption would include not only claims against manufacturers," the FDA states, "but also against health-care practitioners for claims related to dissemination of risk information to patients beyond what is included in the labeling."
Critics say this language is absurd because it extends protection to all the doctors who are boosting sales for the drug makers by prescribing drugs off-label, and the FDA labeling carries no prescribing information for an unapproved use and no warnings about the risks that may be associated with a drug in treating patients for an off-label condition.
"The unqualified language of this statement," Mr Waxman's letter states, "would appear to preempt cases against physicians for failure to warn a patient of risks associated with an off-label (unapproved) use, since, by definition, such risks rarely appear in the approved drug label."
However, drug companies have been immunizing doctors who prescribe their drugs off-label for years. For instance, in Eli Lilly's first out-of-court settlement with 8,000 plaintiffs in litigation involving the off-label marketing of the antipsychotic Zyprexa in late 2004, the settlement agreement included a ban on suing the doctors who prescribed Zyprexa off-label, according to a plaintiff involved in the case.
A July 7, 2003, Lilly document entitled, "Diabetes Update," recently made public as a result of litigation, describes a plan to immunize doctors so they would continue to prescribe Zyprexa off-label when Lilly learned that the warning about high blood sugar levels and diabetes was about to be announced by the FDA and the American Diabetes Association.
"We must embrace the fact that many physicians are curtailing their use of Zyprexa (particularly in the moderately-ill patient and in the maintenance phase)," the Lilly memo states, "solely on the basis of personal fear (of being sued)."
"Indemnification," the document notes, "represents the most meaningful demonstration of confidence in Zyprexa--both with our customers and with our employees."
The memo brags about the success of the scheme when used with doctors prescribing the company's SSRI. "Our experience with Prozac," it states, "confirms the impact and goodwill of such an initiative."
The drug makers are well aware that the steady flow of profits from off-label marketing schemes would come to a screeching halt without the participation of the prescribing doctors. However, the termination date for the immunization coverage extended to the doctors prescribing Zyprexa by Eli Lilly or the FDA is right around the corner, because the fraudulent billings that have resulted from off-label prescribing of the new class of antipsychotics are bankrupting state Medicaid programs all over the US.
Also, state officials are zeroing in on the money paid to the prescribing doctors. On June 26, in the New York Times, Gardiner Harris reported that states are finding that psychiatrists earn more money from drug companies than doctors in any other specialty, and the psychiatrists who receive the most money from antipsychotic makers prescribe antipsychotics like Zyprexa to children most often.
In the Times, Mr Harris noted that Vermont officials reported that drug company payments to Vermont psychiatrists more than doubled last year, from an average of $20,835 in 2005, up to $45,692 in 2006, and that antipsychotics were among the largest expenses for the Vermont Medicaid program.
He also reported a similar pattern in Minnesota where psychiatrists earned the most money, with payments ranging from $51 to $689,000, and the psychiatrists who took the most money from the makers of antipsychotics prescribed the drugs to children most often.
The atypical antipsychotic makers are currently under investigation by congressional committees and federal and state law enforcement agencies for defrauding public health care programs by marketing the drugs off-label to kids as young as toddlers, as well as elderly citizens in nursing homes, and causing serious injury and death to many patients.
However, Lilly recently purchased a new insurance policy of sorts to keep federal regulators at bay, in hiring Alex Azar II, the former Deputy Secretary of the US Health and Human Services Department, who quit his government job in February 2007 and became a senior vice president at Lilly in May 2007.
According to Lilly's press release, Mr Azar formerly supervised all operations at the HHS, and one of the agencies under his direction was the FDA.
When considering the tens of thousands of lawsuits that have been filed by plaintiffs injured by the new antipsychotics, a favorable ruling on preemption could be worth billions of dollars to the drug makers.
Persons seeking legal advice regarding Avandia can contact the Baum Hedlund Law Firm at: (800) 827-0087; http://www.baumhedlundlaw.com/
(Written as part of a series on Avandia sponsored by Baum, Hedlund, Aristei, Goldman & Menzies' Pharmaceutical Litigation Department)
(1) Floor Statement of U.S. Senator Chuck Grassley of Iowa Safety of Avandia Monday, May 21, 2007
(2) Henry Waxman Web site, Avandia Hearing and letters to FDA, Nissen and Glaxo
(3) Avandia Critic Claims FDA Smear Campaign, ABC News, May 30, 2007
(4) Merck Press Release, April 20, 2007, Merck Says Ruling Could Apply to Other Texas Cases
(5) Diane Levine, Brief in Opposition to Wyeth Petition to Supreme Court
(6) Psychiatrists Top List in Drug Maker Gifts, Gardiner Harris, New York Times, June 27, 2007
(7) U.S. hospital, doctor visits balloon, survey finds, Reuters, June 29, 2007
(8) SENATOR SAYS FDA SHOULD STOP CITING A FRAUDULENT KETEK STUDY, SEEKS ACCESS TO INFORMATION, May 16, 2006 Press release, letters and press releases from Senator Grassley's Web site
(9) Ketek documents and articles, The Corporation Citizens For Responsible Care and Research Inc (CIRCARE),
(10) Bone Drugs' Reverse Damage, LA Times, April 3, 2006
Firms take on do-it-yourself regulating
1.Firms take on do-it-yourself regulating