NEWSMAKINGNEWS.COM April 27, 2005
The day serratia bacteria raised its ugly head in Liverpool
and shook up Chiron in Emeryville, California.
On March 2, 2004, about five months before Chiron Corporation intended to market Fluvirin in the United States, Chiron Vaccine’s employees in Liverpool discovered high levels of bacteria in pools of vaccine that had not been fully processed. Chiron scientists knew low levels of bacteria were permissible before final filtration steps occurred, however high levels signaled a serious problem in processing. The ultimate issue, however, would be sterility of the finished product. Then, on July 8 the first batch of finished product – filled vials of vaccine – failed sterility tests. By August 2, Chiron had discovered eight more contaminated batches. A total of 4 million doses were contaminated. (1, 2, 3) The contaminant was later identified as serratia marceans, a reddish brown bacteria.
On July 8, 2004, serratia bacteria took on Chiron and tested the conscience of its executives. Would they try to market a potentially deadly bacteria?
Bernadette Tanley, in the San Francisco Chronicle, October 31, 2004, reported: (4)
Experts say the serratia bacteria can trigger a cascade of life- threatening illnesses, including heart-valve infections, pneumonia and septic shock when injected into vulnerable patients.
"If you injected it, you'd get bacteremia and sepsis," especially in the people most likely to get the vaccine, said Mary York, a Walnut Creek consultant and former director of microbiology at UCSF. "It would be horrible."
People exposed to the bacteria in the air or water are unlikely to become ill. But injecting it into fragile patients is a different matter.
The illnesses that could result would be hard to treat because serratia has a genetic knack for quickly developing resistance to antibiotics, said Dr. Lee Riley, a professor of infectious disease at UC Berkeley.
Besides their consciences, Chiron executives faced a new legal issue on July 8, 2004 when their scientists discovered the vaccine was contaminated in some tests of the finished product: Should Chiron report the contamination of the vaccine to the FDA and to its investors?
Well, as the old timers and new recruits say at the Townhouse bar in Emeryville, “What are we looking at? What are the odds? Shall we first consider the law, at least a little bit?”
Upon finding a contaminated finished product on July 8, 2004 and on every day thereafter, Chiron had two immediate legal duties which are flip sides of the same coin: 1) to accurately inform the FDA and 2) to publicly and accurately inform its investors. What would be the consequences to Chiron if it did not provide this information accurately and immediately? If Chiron’s vaccine manufacturing operations failed to meet the FDA’s current GMPs, (Good Manufacturing Practice) regulations, and also if Chiron concealed this from the FDA, it could face criminal penalties, civil fines, a consent decree or a complete shut down of its vaccine plants. Since 2000 the FDA had warned other companies such as Aventis Pasteur, Parkedale Pharmaceuticals and Wyeth-Ayerst Laboratories about violations of GMPs in the manufacture of their flu vaccines. Parkedale and Wyeth-Ayerst closed their flu vaccine plants. The FDA hit Wyeth Ayerst with a $30 million dollar fine. Only Aventis Pasteur was able to remedy its problems and continue to manufacture flu vaccine. (5)
If, on July 8, 2004 and everyday thereafter, Chiron failed to adequately and publicly disclose to its investors the extent of its problems with contamination of Fluvirin, and instead make materially false and misleading statements, it could also face criminal or civil penalties from the SEC. Chiron’s shareholders could sue for if these misrepresentations deleteriously affected Chiron's stock value.
The penalties were stiff. Lying to federal authorities could put a corporate executive in the big house. In Chiron’s headquarters in Emeryville, California, the CEO and President of Chiron, Howard H. Pien hit at least two forks in road at breakneck speed. One fork was to admit the contamination of the vaccine made it possibly unsafe, shut down the flu vaccine operation and take a loss. The other fork was to try to finesse the facts to try to get the FDA to let Chiron sell the contaminated vaccine anyway and take a profit. It would seem that prison would be the biggest threat to Pien. But Pien had just had an experience with the FDA that showed him the agency was a toothless tiger. On July 7, 2004, just one day before July 8, when the contamination was first discovered in the finished Fluvirin vaccine, Chiron had written a letter to the FDA to request a copy of the Establishment Inspection Report regarding the FDA’s June 2003 inspection of the Liverpool plant. Over a year before, in June 2003, FDA inspectors “found serious problems in 20 areas of vaccine manufacturing and distribution. Several of the problems related directly to the risk of bacterial contamination.” (6, p. 4) The FDA’s inspectors recommended that the FDA issue a “warning letter”, which is a notice of official enforcement action also released to the public. If, after a warning letter and FDA subsequent inspections, Chiron didn’t comply with the cited cGMPS regulations, the FDA could initiate legal action. However, in September 2003, the top brass at the FDA rejected the inspectors’ recommendation and downgraded the warning to a request to Chiron for “voluntary compliance” in September 2003, at which time the inspectors’ report should have also been sent to Chiron to advise what constituted compliance (5, p.7, 9). About a year later, the reason for the FDA’s failure to provide a copy of the Establishment Inspection Report from the June 2003 inspection until Chiron requested in on July 7, 2004 was revealed. On November 17, 2005, after the Government Reform Committee received over 1,000 pages of documents from Chiron, Congressmen Henry A. Waxman reported:
In fact, the report was not provided until after FDA received Chiron’s June 7, 2004, request, well after the start of vaccine manufacturing for the 2004 to 2005 season. 41 According to FDA officials, confusion between FDA’s Center on Biologics, Evaluation and Research and the Office of Regulatory Affairs was responsible for the delay. (5)
On July 8, 2003, when the vaccine first failed to pass sterility tests, Pien had additional justification to ignore the ineffective agency – the FDA. He knew that after the June 2003 inspection, the FDA did not inspect the Liverpool plant again.
As they say with a wink, a blink and a nod in Emeryville, “Well, where were the cops when this was happening?”
So on July 8, 2004, having found contamination of finished Fluvirin, Pien, albeit with one foot on a banana peel and the other foot in the big house, felt confident. FDA enforcement regarding Chiron was not only lax, it was nil. Pien pulled out the old bag of Chiron’s Emeryville tricks, especially those it used to build its world headquarters in Emeryville, namely polluting a vulnerable population and profiteering at their expense. He started with one of the oldest tricks in the book -- to seek a done deal behind closed doors with the highest government official in charge so as to be able to continue the enterprise at all costs. In this case, Pien anticipated a product, contaminated to some degree, hopefully a small degree, would be sold to the public. He would keep his eye on high government officials, especially those who might look the other way in regards to some degree of vaccine contamination. After all, it wouldn’t be the first time a vaccine manufacturer got away with having the government pay any people made ill from a vaccine, while the manufacturer took its profits free and clear.
Pien knew the government could ultimately allow Chiron to limit its liability in litigations brought against it for injuries or wrongful death if persons were inoculated with Fluvirn and developed illnesses from contamination. Many of these persons could be children. Damages from any litigations brought by children would have been almost totally paid by the National Childhood Vaccine Injury Act.
In his book Emerging Viruses, Aids & Ebola, pages 499, 500, Leonard G. Horowitz explained: (7)
In response (to litigations regarding DPT vaccine), in1986 President Reagan signed the National Childhood Vaccine Injury Act. The law was to have created a non-adversarial, no-fault alternative to lawsuits for victims of mandatory vaccinations. It also: including safety provisions such as a centralized vaccine adverse event reporting system; mandatory reporting by doctors of hospitalizations, juries and deaths following vaccinations; mandatory record keeping by doctors of vaccine lot numbers and reactions; and requirements that doctors give patients/parents vaccine benefit/risk information. Punitive damages in lawsuits against vaccine manufacturers or physicians were outlawed, except for cases where criminal negligence would be proven. However Congress did not complete remove all liability in the court system from the vaccine manufacturers and preserved the right of vaccine victims to bring a lawsuit if they were turned down by the federal system or they considered the award to be too small.
Following the law’s passage, the Departments of Justice and Health and Human Services systematically gutted the program and made it highly adversarial. Each claim was fought by taxpayer funded government lawyers and hired physician experts. Compensation was denied to three quarters of all child vaccine victims. What was to have been a fairer, less emotionally draining and less time consuming alternative to litigation, turned into a sham….(6)
Myron Levin, in the Los Angeles Times, (11/29/05) reported (8):
In 1995, the government changed the rules of the vaccine court in a way that made cases more contentious, protracted and harder for petitioners to win.
Officials amended the vaccine injury table, a set of guidelines that had tilted many cases in petitioners' favor. According to the table, if certain symptoms appeared within a specified time after a shot, the vaccine was deemed the culprit unless the government could prove another cause. Many "table injuries" were simply conceded by the government, leaving only the amount of compensation to be determined.
A few amendments changed all that. In one major shift, "seizure disorder" was scratched from the table as a telltale sign of injury from a DPT shot. And a new, more restrictive definition of encephalopathy — or brain dysfunction — meant that many conditions that had been table injuries suddenly were not.….
The Times analyzed a vaccine court database of 10,741 claims filed over 16 years. The analysis showed that in the three years before the changes, the government conceded one-third of all claims. Of cases filed in that period, compensation was awarded in just over half.
But since the changes took effect March 10, 1995, the government has conceded just one claim in seven. About 35% of petitioners have received compensation.
And cases dragging beyond five years have become increasingly common.
Even the court's top judicial officer, Chief Special Master Gary J. Golkiewicz, has lamented the drift toward "full-blown litigation."
"Clearly," he said in one of his rulings, "that is not what Congress intended when it designed the program as an alternative to tort litigation."
Clifford J. Shoemaker, a lawyer for petitioners, said if the government softened its stance, the worst that would happen is that a "family that needs some money to deal with their profoundly injured child is going to get it."
"Is that such a terrible thing?" he asked.
But what would Pien do if Fluvrin vaccine contaminated adults and made them ill?
Pien knew Chiron’s liability could be limited by a future act of Congress in the nature of the Swine Flu Act. In 1976 President Gerald Ford signed this Act guaranteeing the United States would pay all damages resulting from swine flu litigation. Congress had become concerned about a possible swine flu epidemic and passed the act in a state of near emergency. People were told go take the swine flu vaccine even though the drug and insurance industries refused to proceed unless the U.S. government assumed all legal liability for the
Above all, Pien knew that the U.S. government policy under President George W. Bush was to protect vaccine companies from litigation. In the Homeland Security Act, the government assumed all liability for smallpox vaccinations and for the use of thimerosal. Thimerosal is a mercury-containing organic compound (an organomercurial). Many persons in Europe and the U.S. had brought lawsuits against vaccine manufacturers for mercury poisoning allegedly linked to nerve damage and child autism from vaccines using thimerosal. Chiron’s Fluvirin contained thimerosal used to sterilize and preserve the vaccine. On February 14, 2003, pressed by public outrage at the lack of legal remedy for mercury poisoning, the Omnibus Appropriations Bill passed. It completely repealed the thimerosal protection rider contained in the Homeland Security Act. Senators Olympia Snowe, Susan Collins and Lincoln Chafee pushed for the repeal and achieved it by compromising with Senator Bill Frist. Part of the compromise was that the Senate would schedule aspects of the repeal for review within six months of the enactment. (10), (11), (12)
As they say in Emeryville, “Crunch the almighty numbers, shall we!”
Pine crunched the numbers. He looked at the amount of money Chiron would have to pay to defend itself from lawsuits regarding contaminated vaccine brought by adults, and rarely brought by children who were covered by the National Childhood Vaccine Injury Act, and then he deducted the amount of liability the U.S. government might assume. He could weigh that total figure versus the amount of profits Chiron would make. Profits neatly trumped liability concerns. On July 8, 2004, instead of reporting the contamination to the FDA and investors, Pien decided to try to sell the contaminated vaccine.
Pien initiated the strategy of minimizing the extent of the contamination. But would the FDA also minimize it? As Pien kept his eye on high government officials, he was encouraged by a critical fact: Sometimes the United States government has allowed citizens to be injected with contaminated vaccines. Why? The theory is that risks to the public of contaminated vaccine outweighs the risk of no vaccine at all. According to the U.S. Centers for Disease Control and Prevention (CDC), about 10 to 20 percent of the U.S. population gets influenza each year and influenza causes 114,000 hospitalizations and kills 36,000 people, primarily in people 65 and older. The U.S. government would be hard pressed to lose Chiron’s Fluvirin which constituted half of the nation’s flu vaccine supply, just to save some people from the effects of serratia contamination. After all, many flu vaccines used in the past with success had a degree of contamination.
For example, the first Salk inactivated polio vaccines was contaminated with SV40, a simian virus from the African green monkey. In Mary, Ferrie and the Monkey Virus, Edward T. Haslam, alleged that this SV40 contamination later caused cancers in people who were vaccinated. (13) Scientists have also alleged that this SV40 contamination may have undergone some laboratory transformation to cause the AIDS pandemic. (7, 127 to 134). Experimental Hepatitis B vaccines were allegedly contaminated by AIDS virus progenitors that were administered via various agencies to human beings. Populations in Central West Africa received this Hepatitis vaccine along with other vaccines in the 1970s via the U.S. Agency for International Development. In 1972 children residing in the New York Willowbrook State School for the Retarded received Hepatitis vaccine via Dr. Saul Krugman whose work was approved and funded by the U.S. Army’s Armed Forces Epidemiological Board and approved by New York University. Gay men who “volunteered” to participate in a study in New York City in 1976-77 received the Hepatitis vaccine via Dr. Wolf Szmuness, head of the New York City Blood Bank, working with his colleagues of the New York Blood Center and the Division of Epidemiology at Columbia University’s School of Public Health. (7, pps. 237 – 254, 496-498).
Contamination extends beyond vaccines to cell lines. In 2002 the Bush administration restricted federally funded research to 60 pre-existing embryo stem cell lines. Author Katherine Bourzac, citing the 2001 report of the National Academy of Sciences Committee on the Biological and Biomedical Applications of Stem Cell Research, wrote: (14)
“Extant stem cell lines have been cultured in a medium containing cow serum and grown on a layer of mouse embryonic fibroblasts, which secrete growth factors and sustain the stem cells in an undifferentiated state. These cells can be used for some basic research but not for cures. If they were injected into humans, they might spread animal viruses and other infections picked up in the growth medium. Because of mutations and the risk of infection, there is no reason to assume the existing cell lines are optimal.”
In a study published in Nature Medicine (1/23/05), researchers at the University of California, San Diego School of Medicine and the Salk Institute, reported they found that: (15)
Human embryonic stem cells, including those currently approved for study under federal funding in the U.S., contain a non-human, cell-surface sialic acid called N-glycolylneuraminic acid (Neu5Gc), even though human cells are genetically unable to make it. In a related paper published November 29, 2004 by the Journal of Biological Chemistry (JBC), the Varki group has also discovered the exact cellular mechanism by which this occurs.
Pien was and maybe still is a strategic thinker. The history of vaccines in America favored finding vaccine companies not liable for contaminations and a degree of contamination of vaccines was tolerable, at least to some people in high positions of power. So, on July 8, 2004, CEO Pien kept his mouth shut about the contamination and decided Chiron would do its own investigation and internal testing and hope to find that the contamination was just isolated batches.
As the politicians, old and new, say in Emeryville, “Let the spin begin!
On July 23, 2004, even though Pien knew the vaccine was contaminated, Chiron announced it had shipped
1 million doses of vaccine to distributors in the United States. At the time, this appeared to be an amazing marketing triumph for a company that had just entered the flu vaccine market in the United States
A Chiron Vaccines press release (7/23/04) boasted that Chiron “announces today that it has delivered the first one million doses of its Fluvirin influenza vaccine to U.S. distributors in preparation for the upcoming influenza season. (16) The press release detailed the steps of the testing process:
As part of the annual preparation for the influenza season, the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER) tests samples from each batch of influenza vaccine. Upon passing this regulatory testing step, CBER officially releases the vaccine. CBER has begun this process and released the first million doses of Fluvirin. In the coming days, Chiron Vaccines will complete its internal release procedures, allowing distributors to begin shipping the vaccines to customers.
Chiron’s press release raised questions. What type of testing of “samples” had the FDA performed on the first million doses, if any? Was the testing completed? And if the FDA released the vaccine as the press release stated, did the FDA fail to test for serratia, miss the serratia or did it find serratia and release the vaccine anyway? Did Chiron Vaccines complete its internal release procedures and what were they? Did any Americans receive injections from these first million doses? Above all, was the vaccine so contaminated with serratia bacteria that it was dangerous?
If Pien had his way, these questions would never be answered specifically or under oath. In fact, within about a month, Pien would admit there was some contamination, just not enough contamination to stop manufacture and distribution.
On August 25, 2004, Chiron informed the FDA about the contamination which affected 4 million doses of vaccine. However, and this is a big “however”, Chiron executives told the FDA they were optimistic the rest of the vaccine was not contaminated and would be released in the United States in early October, in time for the flu season. (17)
In the Wall Street Journal and Associated Press, Sarah Lueck, Jeanne Whalen, Pui-Wing Tam reported Pien’s version of the facts (11/5/04): (18)
Pien picked his first spin -- only human error in just one manufacturing step – surely not corporate error at the executive level or widespread defects in the manufacturing process.
On Aug. 26, Chiron's Mr. Pien told regulators and the press he believed "human error" in one manufacturing step had most likely caused the problem. The company ordered more tests and delayed shipping its flu shots until October. (18)
On August 26, 2004, Chiron Vaccines pumped up its spin machine to minimize the public’s perception of the amount of contamination by putting out another press release: (17)
CHIRON CORPORATION (NASDAQ: CHIR) today announced that, in conducting final internal release procedures for its Fluvirin ® influenza vaccine, the company’s quality systems have identified a small number of lots that do not meet product sterility specifications. While ongoing internal investigations into the root cause of the variance indicate no widespread issues with the manufacturing process, Chiron has delayed releasing any Fluvirin doses until it has completed additional release tests. Chiron currently expects that the additional tests will delay product release until early October. Because of the delay in shipment, Chiron does not expect to record any sales of Fluvirin in the third quarter of 2004. Assuming timely release of Fluvirin in October, Chiron expects to be within the range of its previous full-year 2004 pro-forma earnings guidance of $1.80-$1.90 per share but at the low end of this range (a range of $1.50-$1.60 per share on a GAAP basis.
“Chiron is committed to protecting people. These extra checks will ensure that the quality, safety of our product meets our rigorous standards,” said John Lambert, President of Chiron Vaccines. “In our role as a key supplier of an important health product, we are working with the FDA, the U.S. Department of Health and Human Services, and the CDC to meet the projected demand for the upcoming influenza season. We currently expect Fluvrin does to be available in early October, in time to meet public health needs for this influenza season, and we expect to provide even more Fluvirin doses this season than last season.
After this press release wherein Chiron first revealed the vaccine contamination to its investors and the public, its stock dropped from $47.49 on August 26, 2004 to $43.41 on August 27, 2004. But this drop in share price was probably minimized by Pien’s bluster that only a small number of lots were contaminated and above all by his concealing that the Liverpool plant was replete with problems. (19, paragraph 44)
Why did Pien spin the facts so hard and fast to keep making a buck for Chiron?
Howard Pien had a personal motivation to maintain Chiron’s optimism and project high flu sales to keep the price of Chiron stock high. According to Forbes-global.com, as of December 2003, Pien’s total cash compensation annually from Chiron was $3,444,714 and he had 710,000 unexercised stock options, then worth $14,460,000. Who is Pien, a man paid about $250,000 per month? Pien had an MBA from Carnegie Mellon and a BS from MIT. His resume was more business manager than scientist. He had worked for 12 years in global management of pharmaceuticals at GlaxoSmithKline before joining Chiron in April 2003 as CEO. He had replaced Sean P. Lance who also had been in a position of global management responsibility at Glaxo Wellcome, which later merged into GlaxoSmithKline. On the surface, his resume reveals that his work at Glaxo and his connections to it must have impressed Chiron’s board of directors. This fact must be noted, because it was GlaxoSmithKline which sponsored experiments from 1995 through 1997 on children treated at the Incarnation Children’s Center in New York. Incarnation specialized in the treatment of HIV sufferers and is run by Catholic Charities. (20) Perhaps Pien and his fellow travelers engaged in a little human experimentation or tolerated it to facilitate their career enhancement.
The last week of August 2004 was a long and hot week in the history of Chiron, but Pien’s crisis-management strategy appeared to be working. Chiron tested the Fluvirin vaccine at the Liverpool plant for contamination with the self-fulfilling prophecy that contamination would be minimal. Chiron deftly defined the contamination as a “product sterility specification problem”, and still anticipated the vaccine would be sold in the U.S. in early October.
Then an unexpected letter arrived.
On September 24, 2004, Britain’s Medicines and Healthcare Products Regulatory Agency (MHRA), sent a letter to Pien in which it requested that no flu vaccine leave the Liverpool plant until its own inspections were completed. (18)
Pien did not publicly disclose the MHRA’s letter of September 24, 2004. (18)
Instead, in an amazing show of chutzpah, on September 28, 2004, while the MHRA was actually inspecting the Livermore plant for serratia contamination on September 28, 29 and 30, Pien testified before the U.S. Senate Special Committee on Aging in Washington, D.C., in a hearing titled, "Combating the Flu: Keeping Seniors Alive." (21, 22) And at that hearing, Pien did not tell the Senate that scientists had found serratia contaminating some vaccine at the plant, nor did he mention the September 24, 2004 letter from MHRA asking that no flu vaccine leave the plant until the its inspection was complete. He also failed to tell the FDA.
Chiron’s press release set forth the gist of Pien’s testimony: (22)
Mr. Pien will also reiterate Chiron's expectation, as stated in the company's August 26, 2004, press release, that it will supply between 46 million and 48 million Fluvirin(R) influenza virus vaccine doses to the U.S. market for the 2004-2005 influenza season, beginning in early October. The planned late-season delivery of 2 million Fluvirin doses for a national stockpile held by the U.S. Centers for Disease Control and Prevention (CDC), not included in the totals above, remains on schedule as well. Since its August announcement, Chiron has worked closely with government agencies to keep them informed of its retesting process. The results of the confirmatory testing to date are consistent with the company's shipping expectations. Following compilation and formal sign-off of its test data, Chiron expects to complete its discussions with regulatory authorities and proceed with releasing Fluvirin to the U.S. market in early October.
Pien had kept a few crucial damning secrets about the status of the Fluvirin vaccine from the United States Congress on September 28, 2004. He was either a fool or thought he could get away with it.
Was Chiron’s bold spin working?
Yes. Not only was the FDA a toothless tiger, it was a “passive” tiger.
On November 17, 2004, Rep. Henry A. Waxman, looking back at Chiron’s conduct and the FDA reaction, reported (6)
FDA remained passive when evidence of actual contamination came to light in August 2004. After Chiron notified FDA on August 25, 2004, that millions of doses of flu vaccine were contaminated, FDA officials relied on weekly conference calls with Chiron, rather than independent inspections, to monitor the company’s progress. These calls included discussion of how FDA officials could dispel fears of a vaccine shortage. By contrast, British regulators launched a series of actions commencing two weeks after receiving the notice from Chiron. These included sending a team of regulators to the facility twice (from September 13 to 15 and from September 28 to 30), reviewing the company’s records and draft investigation report, convening two high- level committees, and ultimately suspending the facility’s license. FDA officials never asked Chiron or the
British regulators about the British activities, and the British regulators were barred by law from informing FDA of their findings absent consent from Chiron.
But on October 5, 2004, all CEO Pien could think was “the British are coming! The British are coming!
Quickly, efficiently and without spin, on October 5, 2004, the British government suspended Chiron's flu vaccine license for three months because its inspectors found that Fluvirn at the Liverpool plant was contaminated. (21)This meant 48 million doses of Fluvirin were automatically withdrawn from the U.S. market --about one half of the nation’s flu supply.
Many Americans panicked. They stood in long lines at clinics and pharmacies in the United States, hoping for shots. Many high-risk individuals were particularly panicky. After all the spin from Chiron and the U.S. government for years was that influenza vaccine shots were essential to prevent an epidemic and that seniors, children and ill persons were at high-risk of influenza infection.
Chiron did not panic. Chiron responded to the British findings, but admitted that it had not found the cause of the bacterial contamination. As of October 5, 2004, Chiron, with all its so-called brilliant scientists, had not yet found the cause of the contamination was serratia. Well, as the hotshots say in Emeryville, “I have a bridge for sale for cheap. It’s called the Golden Gate!”
Then on October 7, 2004, the San Francisco Chronicle dropped a bombshell on Chiron. It reported that Chiron had actually shipped 6 million doses of Fluvirin, 5 million more than the 1 million it reported it had shipped:
In the San Francisco Chronicle, Sabin Russell reported (10/7/04): (23)
Under U.S. Food and Drug Administration rules that place much of the responsibility for product safety in the hands of manufacturers, Chiron Corp. shipped 6 million doses of its now-suspect flu vaccine from its British plant to the United States before the company's own tests uncovered evidence of bacterial contamination.
The Chronicle has learned that vaccine shipped across the Atlantic has been sitting since August in the warehouses of American drug distributors, under a Chiron-imposed "quarantine,'' but outside the direct control of the company or U.S. regulators.
In this case, Chiron employed the little-known quarantine process under which drug makers can ship products to distributors before final safety tests are completed.
Norman Baylor, deputy director for the FDA's vaccine unit, said it was not unusual for manufacturers to ship vaccine under quarantine. The quarantine is lifted by the manufacturer when the company's final tests confirm that the product is safe and the distributor is free to sell it.
"I think the system works,'' Baylor said in an interview in September shortly after Chiron's contamination problem first surfaced. "The system did what it was supposed to do.''
Baylor also confirmed that 27 bulk lots -- nearly half of the 60 produced by the Chiron plant -- had been "released" by the FDA prior to the company's discovery that some finished product was contaminated. The actual number of doses that can be produced from each lot varies.
Although the federal agency does not conduct tests on the final product, companies are liable for the safety of their medicines and have powerful incentive to test them thoroughly before releasing them from quarantine, Baylor explained.
Chiron shipped its first million doses of vaccine to distributors in late July, trumpeting its first-to-market achievement in a July 23 press release. At that time, the company explained that "in the coming days," it would "complete its internal release procedures, allowing distributors to begin shipping vaccines to customers.'' …..
Chiron chief executive Howard Pien said Tuesday that all of the Fluvirin doses "would be destroyed in due course.''
When British regulators suspended the license of Chiron's Liverpool factory Tuesday, they shut down a facility that had been cleared by U.S. inspectors one year earlier, and they apparently have blocked for good the sale of 27 lots of vaccine that had already been released by the FDA.
According to FDA spokeswoman Lenore Gelb, the agency's direct role in the testing of flu shots ends with the production of bulk quantities of vaccine. The final manufacturing steps, such as filling vials and syringes, are regulated through bi-annual inspections to assure that companies are adhering to "good manufacturing practices" that are the basis of their licensure.
Manufacturers are required to conduct their own tests for sterility, and it was one of these quality-control tests by Chiron that spotted the serratia in August.
Had 6 million doses really passed FDA testing or was Chiron operating completely under the FDA’ radar? Chiron’s motivation for lying about the number of flu shots it had actually shipped (it was only off the mark by 5 million) was not publicly explained.
Although the British caught Chiron with 60 million doses of contaminated vaccine in its plant, Chiron still tried to cover-up and convince the U.S. government to allow the vaccine to be injected into Americans.
On October 4, 2004, Britain’s MHRA suspended the Chiron Corporation’s license to manufacture, ship or market its Fluvirin influenza vaccine for three months. The MHRA’s press release (10/6/04) stated: “The suspension was imposed as a result of Chiron's failure to comply with the requirements of Good Manufacturing Practice, leading to concerns of possible microbial contamination of product.” Britain had an interest in the purity of Fluvirin. Although most of it was to be shipped to the U.S., the remainder was to be distributed in Britain and in about 20 other countries. The World Health Organization set the standards for production of inactivated influenza vaccine. Chiron failed.
Pien, however, took the MHRA’s suspension in stride. The United States government’s current policy is not to be too concerned about global standards or “tests” when the interests of US corporations are at stake.
To duck, take cover and fight on, Chiron Vaccines announced in a press release on October 5, 2004, that the MHRA had temporarily suspended Chiron’s’ license to manufacture Fluvirin in its Liverpool facility for three months. And Chiron stated it had slashed its expected earnings by more than half. But most importantly, Chiron did not give up on selling its vaccine to U.S. consumers for the upcoming flu season. It stated: “Chiron has initiated discussions with the MHRA to determine the appropriate corrective actions.” (24) In fact the price of Chiron stock dropped from $45.42 on October 4, 2004 to $37.98 on October 5, 2004, a drop of 16.3 percent in heavy trading 25 million shares. (19)
Pien’s new mantra was the possibility of “appropriate corrective actions”. Pien still minimized Chiron’s vaccine contamination. The FDA had not yet determined if it would allow the vaccine to be sold. Besides, Pien had kept the lid on the deep nature of its problems at the Livermore plant. Pien knew that the FDA would have to be critical of its own conduct if it found vaccine contamination at the plant. The FDA had given Chiron and the preceding owners of the Liverpool plant a virtual pass on contamination since about 1999 through at least July 2003.
Chiron was not new to the flu vaccine business. In May 2003, Chiron acquired PowderJect, the prior owner of the Liverpool plant, and suddenly became the second largest vaccine maker in the world, second only to Aventis Pasteur. Chiron would be able to jump into the United States flu vaccine market as a major contender. Since its founding Chiron was committed to developing vaccines through the use of genetic engineering. Chiron acquired the Italian vaccine company Sclavo in 1992 and five years later bought the German company Behringwerke. Chiron uses European subsidiaries to make about two dozen vaccines from mump to polio to yellow fever. These vaccines, with the exception of Fluvrin and a rabies vaccine are not sold in the United States. Chiron’s plan regarding Fluvirin and other vaccines paid off well in 2004 when vaccines accounted for about a third of Chiron's $1.8 billion in revenue, including $322 million from worldwide sales of Fluvirin. (23)
Chiron, however, did not purchase a first class vaccine factory in Liverpool. It purchased a mess. Chiron did not publicly disclose this fact. The FDA on the other hand was fully aware of the plant’s problems since 1999 and deftly looked the other way so many times that Chiron could feel reasonably assured the FDA would do so again.
According to Sara Lueck, Wall Street Journal, Jeanne Whalen, Pui-Wing Tam, Associated Press, (11/5/04): (18)
The FDA, which is responsible for ensuring the safety of medicines entering the nation, says it relied on updates from the company, rather than inspecting the plant itself.…..
As it did with Chiron, the FDA typically relies on the companies it regulates to let it know when problems arise. The agency also does safety testing and monitors patients' reactions to drugs. Companies are required to report manufacturing troubles to the FDA and can face prosecution if they don't..….
Chiron, a biotechnology company with annual revenue of about $1.8 billion, acquired the Liverpool plant when it bought British vaccine-maker PowderJect Pharmaceuticals in May 2003.
The Liverpool factory had a history of problems by the time Chiron acquired it. After a 1999 inspection, the FDA sent the factory's previous owners a warning letter saying it found "significant deviations" from FDA standards, including failure to clean, maintain and sanitize equipment and utensils often enough. Dr. Crawford said there was a "clean-up of the plant" after that warning letter.
In 2000, British regulators ordered the recall of a polio vaccine produced at the factory, concerned it could be contaminated with mad-cow disease because it had been made with materials from British cows. The factory's owner at the time, Celltech Group PLC, was quoted in British press reports as saying there was no evidence that the materials came from infected cows.
On an inspection in June 2003, just as Chiron took over, the FDA found problems similar to those that led to the recent shutdown, including high levels of bacteria in unfinished vaccine, according to John Taylor, head of the FDA's inspection branch. Some in the FDA thought the findings were enough to warrant an official action, such as a public warning letter, recalls a person familiar with the inspection. An "official action indicated" frequently comes with a quick re-inspection of the plant. But the agency, finding no contamination in finished vaccine, decided on a less-severe ruling: "voluntary action indicated."
Chiron gave the FDA a plan to fix the issues, and the agency deemed the company's response adequate, Dr. Crawford says. This year's batch of vaccine, he says, "was not affected by what happened in 2003."
Chiron quickly ramped up production at the plant, committing $100 million to upgrade the facility, replace old equipment and expand. The results were almost immediate: The company was on track to boost its output of Fluvirin to 52 million flu shots in 2004, up by a third from 2003, with the majority slated to go to the U.S.
In late August, when Chiron carried out final tests on Fluvirin, it found a big problem: four million doses were contaminated with a bacteria the company later identified as serratia. On Aug. 26, Chiron's Mr. Pien told regulators and the press he believed "human error" in one manufacturing step had most likely caused the problem. The company ordered more tests and delayed shipping its flu shots until October.
FDA officials happened to be at the plant that day, to review its expansion plans. When notified of the contamination problem, they looked at some records and made a few suggestions but didn't conduct a full inspection. Dr. Crawford says Chiron was conducting its own investigation and would be reporting back to the agency. "Our understanding ... was that this could be overcome," he says.
At the time, U.S. officials believed there would simply be a delay in getting the flu shots and sought to reassure the public. "Ultimately, all people who need flu vaccine should be able to get their shots," said Julie Gerberding, head of the Centers for Disease Control and Prevention, in a conference call with reporters Aug. 27.
The FDA relied solely on Chiron to provide updates on progress with the problem, a step one former FDA chief criticizes. "You've got to act like a public-health agency, and that's what was not done," says former FDA Commissioner David Kessler, who left the agency in 1997 for academia. He says the FDA should have returned to inspect the Chiron plant sooner than it did. Dr. Crawford says inspecting sooner wouldn't have done any good. The FDA needed Chiron's report and finished batches of vaccine, he says.
The FDA began holding conference calls with Chiron at least every week to monitor progress. Throughout August and September, Chiron "appeared to be making progress," Dr. Crawford says. "Then the progress stopped." ….
In their September review, half a dozen British experts on biochemical engineering scoured the Chiron plant and determined the "whole production process" needed to be overhauled, says Kent Woods, chief executive of the U.K.'s Medicines and Healthcare products Regulatory Agency. He said the agency was concerned the plant lacked safeguards to ensure the vaccine was safe.
Unable to pinpoint the root of the problem, Chiron executives say they prepared a draft press release in September, saying the company might not be able to ship the vaccine to the U.S. But the press release was never sent. The company says its retesting convinced Chiron the vaccine was safe.
U.S. health officials say Chiron portrayed the British review as a routine matter. On Sept. 28, in a private meeting at the Department of Health and Human Services, U.S. officials asked Mr. Pien whether he expected any trouble from British regulators. He said he didn't, according to people who were there. Chiron declined to comment.
On Oct. 5, just as flu season was about to hit, British regulators suspended the Liverpool factory's manufacturing license for three months. The suspension, which can be lifted only after the company meets British standards, blocked all vaccine shipments.
Chiron's U.K. executives used a previously scheduled conference call with Mr. Pien and other Chiron executives before dawn in California to deliver the news. Mr. Pien then called U.S. health officials to tell them. A fax from British regulators announcing the suspension arrived at FDA offices just before 6 a.m.
The FDA had previously scheduled an 8:45 a.m. call with Chiron, when officials had expected to hear final results of the company's testing. Instead, they were in crisis mode. Mr. Pien asked whether the FDA could do anything to change the British regulators' decision, says a person who participated in the call.
Dr. Crawford says the FDA never discussed the possibility of trying to change the British regulators' decision. FDA officials say the discussion was focused on getting an FDA team to England to inspect the plant and touched on whether the FDA or the British regulators had authority over the plant.
Later that day, Health and Human Services Secretary Tommy Thompson tracked down Britain's health minister, John Reid, who was on vacation in France, and pressed him to allow an FDA team into the factory as soon as possible. Mr. Thompson urged FDA officials going to Liverpool to do whatever they could to salvage at least some of the vaccine, if it could be done safely.
On Oct. 10, the FDA team arrived at the Liverpool plant in a black minivan. Five days later, they came to the same conclusion the British had -- the vaccine was unusable. The FDA did random-sample testing of the vaccine, Dr. Crawford says, and decided it couldn't guarantee all the vaccine was safe.
After its inspection, the FDA said it believes the contamination occurred at the stage in which the vaccine is poured into vials. Chiron and the British regulators decline to detail what went wrong.
On November 7, 2004, Mike McGraw of the Kansas City Star wrote an article based on newly discovered documents showing Chiron never came clean about the contamination at the Liverpool plant: (26)
The Kansas City Star obtained a copy of the FDA's 1999 inspection of the plant last week. The report was part of a lawsuit filed on behalf of a woman who allegedly became paralyzed as a result of a 1998 flu shot manufactured at the Liverpool plant.
Chiron settled the case earlier this year, but the details are sealed, said the attorney in the case. ….
Documents obtained by The Kansas City Star show the Food and Drug Administration five years ago noted that the plant, then owned by the British firm Medeva, had failed to correct longstanding problems. But the agency continued to allow the plant to supply the U.S. market despite clear departures from what the agency calls "Good Manufacturing Practices."….
The Kansas City Star determined that the Liverpool plant’s manufacturing process had not been validated, that is certified by the company as effective since the early 1990s. In fact, the FDA had found problems in the Fluviron manufacturing process in June 2003 but didn’t take formal action. Chiron was allowed to supply flu vaccine in America for the 2003-2004 flu season.
On November 7, 2004, the San Jose Mercury News reported:
On Jan. 28, as Chiron was preparing to start production of this year's Fluvirin shots, its top vaccine executive, John A. Lambert, said he was ``fairly confident'' the plant would be able to produce 50 million doses, 12 million more than ever before. He also said the Food and Drug Administration had inspected the plant the previous June and pronounced the facilities ``in very good order.''
Chiron planned to ramp up the factory's production using existing staff and ``a lot of the old Chiron expertise,'' Lambert said.
But Lambert's assurances glossed over the results of that June 2003 inspection. He did not reveal that inspectors had uncovered numerous problems at the Liverpool plant, some of them substantial.
The inspection took place as the plant was producing vaccine for the 2003 flu season and before Chiron in July had completed its purchase of PowderJect, the British company that owned and operated the facility.
Acting FDA Commissioner Lester Crawford has said the problems this year were different from those uncovered in June 2003.'
Despite his knowledge of all the problems at the Liverpool plant, Pien still looked for the FDA to approve the Fluvirin vaccine for use in the United States in the fall of 2004. Pein had high hopes. Lester Crawford, the FDA Commissioner, nominated by President George W. Bush seemed to be singing Chiron’s tune in that he was saying the problems in 2004 were different from the problems the FDA uncovered in 2003, implying that Chiron must have corrected at least some of these old problems. Any good word from Crawford about the Liverpool plant, was, to Pien, a reassurance that Fluvirin could still be marketed in the fall 2004 in the United States.
In fact, until October 8, 2004, Chiron maintained the contamination of the Fluvirin was confined to a limited number of lots identified by Chiron’s own testing and that the vaccine was safe to be used in the United States.
According to a later online release by the FDA: (21)
On October 8, the FDA team met with senior leadership of Chiron. Chiron presented the key results of their investigation, including negative retesting of all other lots, and indicated that they believed that the results, which they had planned to submit to the FDA, supported their conclusion that the contamination problem was confined to a limited number of lots identified by their testing.
When would the FDA even inspect the Liverpool plant, was the question on Pien’s mind.
On October 9, 2004, the FDA inspection team arrived in Liverpool and met with 2 MHRA inspectors who would act as observers on the team. Finally, on October 10, 2005, for the first time since June 2003, the FDA inspection team initiated the inspection at the Chiron facility in Liverpool. (21)
Still CEO Pien anticipated the FDA would agree with the results of Chiron’s own investigation – that the contamination problem was confined to a limited number of lots identified by their testing. The FDA did not agree. In what must have been a total shock to Pien, on October 15, 2004 the FDA shut down Chiron’s flu vaccine operation in Liverpool, and then issued a damning timeline showing that Chiron wiggled around the facts as it tried for weeks to convince the FDA to give its vaccine a pass. The FDA stated online in a timeline: (21)
FDA's inspection found significant deficiencies in quality control and concerns regarding the test results. Although Chiron's retesting of the unaffected lots of vaccine has been negative for contamination, FDA has determined that it cannot adequately assure the sterility of these lots to our safety standards.
The gig was up for Pien and Chiron -- but only regarding the 2003-2004 flu season. Pien was already anticipating the next flu vaccine season. Could Pien handle the pesky legal problems? Could his executive cohorts David D. Smith, Vice President and Chief Financial Officer and John Lambert, Vice President of Chiron and President of Chiron Vaccines of Liverpool, England, handle the pesky legal problems.
As the guys who get got in Emeryville say, “Let the mea culpas begin!”
According to the Wall Street Journal, (11/5/04): (18)
Mr. Pien has apologized to Congress and pledged to work with regulators to resolve problems. The suspension on the Liverpool plant is scheduled to lift in January, pending approval by British authorities. Dr. Crawford says the FDA is "working lockstep" with British regulators "on getting the plant up and running." Still, in a recent conference call with analysts, Chiron identified a list of items that still need to be fixed before next year's flu season, including overhauling its manufacturing process and improving its quality-control systems.
For Chiron’s executives, it was a time to lawyer up and shut up and call in the
chits from the local judges and people in the Department of Justice Chiron had
come to know and love.
CEO Pien still put his head on his pillow at night without too much concern. Chiron had not fired him and was still cutting him a fat paycheck. How could that be? His future looked like a walk through landmines.
The pesky legal problems only got peskier.
On October 12, 2004, the U.S. Attorneys office for the Southern District of New York issued a grand jury subpoena to Chiron seeking documents and materials relating to Chiron’s Fluvirin and UK regulators decision so suspend manufacture of the vaccine. (19 Par. 50).
On October 13, 2004, the Wall Street Journal reported that the SEC initiated an informal investigation of Chiron “to determine if the company failed to adequately disclose the extent of problems at the Liverpool, England facility that made its influenza vaccines.” (19, Par. 51) (Later in February 2005, that SEC investigation was elevated from informal to formal.)
On October 19, 2004 the Los Angeles Times reported Chiron hired Washington, D.C., defense attorney Robert S. Bennett to coordinate its legal strategy. Bennett is said to be concentrating on a criminal probe of Chiron by the Justice Department and an inquiry by the SEC. Bennett was the attorney for President Bill Clinton during impeachment proceedings.
On Oct. 20, Chiron announced a $91 million write-off on its 2004 inventory of the Fluvirin.
What was CEO Pien’s reaction to this series of legal attacks?
Facing the Congress, New York prosecutors, lawsuits and the SEC, Pien worked on selling the next season’s flu vaccine. Pien promoted Chiron’s new method of vaccine preparation using dog kidney cells to accelerate the preparation process from five months (the current chicken egg process) to two months. According to Zina Moukheiber, Forbes.com (11/1/04): (27)
Chiron is racing to finish late-stage trials of a method that grows strains within clones of 1980s-era dog kidney cell. It expects to seek regulatory approval by the end of the decade
In the late 1990s scientists at Chiron’s laboratory in Marburg, Germany were looking for a more predictable flexible incubation medium. They settled on dog kidney cells. With the proper cocktail of chemical nutrients, a cell line fermenting in a cylindrical vat at about 98.6 degrees Fahrenheit can generate millions of cells growing in suspension. One strain of virus then infects all cells, producing a soup full of virus. Scientists inactivate the virus with formaldehyde and purify the liquid of cellular debris.
In 1999, Chiron signed an agreement with Aventis to jointly develop and fund the technique. Aventis had the rights to sell it in the U.S. anted Chiron in the rest of the world. But this past January Agnates broke off its deal with Chiron to pursue a different approach using human retinal cells. Chiron regained U.S. rights, and Agentis had to step a few years back in the race.
Michael De Wilde, who heads research and development at Aventis’ Pasteur division, says his firm’s work with human cells allows for more precise documentation of cell-line genetic traits, which is important in case something goes awry, such as cancer. “The perception of safety is better,” says DeWilde, who claims that scientists are more in the dark with dog cell lines. DeWilde also disagree with Pien’s assertion that the use of animal cell cultures can cut production time significantly. “It is an illusion,” he said. Testing the vaccine in ferrets before moving on to humans will take six to eight weeks, eliminating any head start over the traditional egg method.
Pien disputes Aventis’ interpretation. Chiron plans to invest more than $100 million to refurbish the lab over the next three years, but one little bacterium has laid waste to its plans for now.
Pien was courageous in the face of SEC action, Congressional investigation, and the calling of a grand jury in New York. Despite the fiasco of the shutdown of its 2004-2005 flu vaccine program, Chiron had better plans for the Liverpool lab – to grows strains within clones of 1980s-era dog kidney cell. The question is inevitable: Did Chiron really not care much about the Liverpool plant in regard to its production of vaccine from eggs because in fact Chiron wanted to renovate that plant to produce vaccine from dog kidney cells?
As the old timers say in Emeryville, “The mob has the best lawyers and judges money can buy.”
In October 2004, the first of several derivative shareholder lawsuits were filed in U.S. District Court, San Francisco. The Judge “randomly” assigned to the first of these lawsuits was Vaughn R. Walker, and subsequently he took over subsequent related filings.
Also, in October 2004, several lawsuits were filed against Chiron in Alameda County, which were eventually consolidated into one case, In Re Chiron Corporation Derivative Litigation, before Judge Ronald M. Sabraw.
Pien looked at his fortress Chiron, firmly ensconced in Emeryville, and sighed the sigh of total relief – Vaughn Walker and Ronald Sabraw were two judge who had a long history in Emeryville, and were not known to have stood in Chiron’s way over the years. FBI Director Robert Mueller, had served as the U.S. Attorney in San Francisco, prior to his elevation to FBI director and he had not stood in Chiron’s way over the years. And as for that pesky grand jury summoned by the U.S. attorney in New York, the same prosecutor who put Martha Stewart into Camp Cupcake and fastened a telltale bracelet around her ankle, didn’t he know that that the venue for cases against Chiron was the Northern District of California?
So what kind of a past have Judge Vaughn R. Walker, Judge Ronald Sabraw and their associates and FBI director Mueller have in common with Chiron and its cronies in Emeryville?
Next, the story about Chiron’s contamination of Emeryville itself and its citizens and the conduct of those characters, high and low, who killed a federal litigation adverse to Chiron’s interest in building its world headquarters, will be told.
by Kathryn Joanne Dixon © 4/27/05
Click. CHIRON CORPORATION GAMBLES ITS OLD EMERYVILLE CHIPS TO
WIN THE POT AND BEAT THE RAP (Part 1)
1. Sabin Russell, “Early Flu-Shot Contamination Revealed. Chiron Knew Sometime In March That Vaccine Was Failing Sterility Tests”, San Francisco Chronicle, November 21, 2004, Url: http://sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2004/11/21/MNG399V9V81.DTL
2. Paul Jacobs. “Problems Found A Year Ago At Vaccine Plant, But Chiron Wasn’t Ordered By The FDA T Make Repairs, San Jose Mercury News, November 18, 2004, Url: http://www.mercurynews.com/mld/mercurynews/business/10212317.htm
3. Paul Jacobs. “Bacteria Detected Long Ago by Chiron. How Flu Vaccine Was contaminated” and “What Chiron Knew”, San Jose Mercury News, November 20, 2004, Url: http://www.mercurynews.com/mld/mercurynews/business/10231662.htm
4. Bernadette Tansey, “Tainted Flu Vaccine Could Have Been A Health Nightmare. Same Bacteria Was Used In 1950 Bay Area Germ-Warfare Test—And High-Risk Groups For Shots Would Be Most Vulnerable”, San Francisco Chronicle, October 31, 2004, Url: http://sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2004/10/31/MNG5O9JIJQ1.DTL
7. Leonard G. Horowitz, Emerging Viruses, Aids & Ebola, Rockport, MA, Tetrahedron, Inc., 1997 pps. 499, 500, pps. 127 to 134, pps. 237 – 254, 496-498.
8. Myron Levin, “Vaccine Injury Claims Face Grueling Fight, Los Angeles Times, November 29, 2004.
9. 1976, Pub. L. 94-380; 42 U.S.C. 247b(j)-(l) (1976) (Swine Flu Act). http://biotech.law.lsu.edu/cases/vaccines/Unthank.htm
10. Chiron Corporation, website, Information about its product Fluvirin, “Thimerosal”: (As of October 24, 2004) http://www.chiron.com/products/vaccines/fluvaccines/fluvirin.html
11. Homeland Security Act Of 2002 Amendments. Sec. 102.Non-Prejucial Repeal Of Sections 1714 Through 1717 Of The Homeland Security Act Of 2002.
12. Kathi Williams, “Benefits for Thimerosal Manufacturer”, Braytonlaw.com, December 13, 2002.
13. Edward T. Haslam, Mary, Ferrie and the Monkey Virus, Wordsworth Communications, Brandenton, FL, 1999.
14. Katherine Bourzac, “Stem Cells and Public Funding: Moral Controversies and Scientific Issues”, Biology and Comparative Literature, University of Southern California Journal of Young Investigators, Url: http://www.jyi.org/volumes/volume5/issue3/features/bourzac.html
15. Sue Pondrom, “Current Human Embryonic Stem Cell Lines Contaminated UCSD/Salk Team Finds”, University Of California, San Diego Press Release, January 23,, 2005, Url: http://www.eurekalert.org/pub_releases/2005-01/uoc--che011805.php
16. Chiron Corporation, Press Release dated July 23, 2004.
18. Sarah Lueck, The Wall Street Journal, Jeanne Whalen, Pui-Wing Tam, Associated Press, San Francisco Chronicle: “Behind flu-vaccine shortage: Struggle to police drug industry globally”, November 5, 2004, Url: http://sfgate.com/cgi-bin/article.cgi?file=/news/archive/2004/11/05/financial0931EST0037.DTL
19. Milberg, Weiss Bershad & Schulman LLP, “Complaint”, Case No. C-04-4293 VRW, United States District Court, Northern District of California, Paragraphs 44, 47, 50, 51.
20. “Young Children and Babies Used as Lab Rats in Drug Trials”, London Observer, April 4, 2004.
21. Food and Drug Administration, “2004 Flu Vaccine Chronology”, FDA website,
October 16, 2004, Url: http://www.fda.gov/oc/opacom/hottopics/chronology1016.html
22. Chiron Corporation, Press Release dated September 28, 2004.
23. Sabin Russell, “6 Million Doses Of Suspect Vaccine In U.S. Warehouses. Quarantined Since August Pending Tests” San Francisco Chronicle, October 7, 2004, Url: http://sfgate.com/cgi-bin/article.cgi?file=/c/a/2004/10/07/MNG31952VC1.DTL
24. Chiron Corporation, Press Release dated October 5, 2004.
25. Paul Jacobs, Deborah Lohse, Lisa Krieger, “Evidence of Bacteria Was Seen Long Before Flu-Shot Shortage”, San Jose Mercury News, November 7, 2004.
26. Mike McGraw, FDA Knew Problems at Vaccine Plant Were Pervasive, Documents Show, Kansas City Star, November 7, 2004.
27. Zina Moukheiber, “Broken Eggs”, Forbes.com, November 1, 2004.