German heparin supplies recalled

Janet Woodcock, the deputy commissioner of The Food and Drugs Administration (FDA) has announced that 5 - 20 % of samples of the blood thinning agent , essential for people having dialysis, sold in the US by Baxter's was contaminated. (see previous posts)

There is , as yet, no direct causal link" between the drug and the 785 adverse reactions which have been reported so far. The number of recorded deaths has increased from 4 to 19. Nor can they say this was an "error , by some biological process, or if this occurred deliberately."

The FDA says the contaminant is present in the active pharmaceutical ingredient originating from Baxter's US supplier, Scientific Protein Laboratories of Waunakee, Wis. plant in China - who extract the basic product from pig intestines. However, the FDA said that it is also possible that the "heparin-like" substance could have been introduced at Scientific Protein's facility in Wisconsin. Baxter indicated that its New Jersey plant, which produces heparin in its final form, is not the cause of the problem.

The New York Times reports that the FDA have asked all U.S. companies that produce heparin to test it with nuclear magnetic resonance spectroscopy and capillary electrophoresis, the only tests that can uncover a possibly counterfeit ingredient.

German heparin product recalled.

Now Rotexmedica GmbH Arzneimittelwerk (owned since 1999 by Groupe Panpharma of Fougeres, France) has announced a product recall of its heparin product in Germany after receiving an increase in reports of adverse events (less than 100) in patients similiar to those recorded in the US but no deaths have been reported.

Axel Thiele, a spokesman for the Federal Institute for Drugs and Medical Devices, (BfArM) said the drug, was pulled from the market after 80 patients suffered shortness of breath, low blood pressure and episodes of rapid heartbeat. Press Release

Rotexmedica's heparin is made using an active ingredient from China, similar to Baxter's recalled product.

The company has written to doctors and pharmacists notifying them of the problem and claim "it can't be ruled out that the quality of the batches has been compromised."

The FDA state that heparin active ingredient used by Rotexmedica in their product was not obtained from" Scientific Protein Laboratories.

Scientific Protein may have obtained raw ingredients from the same source as the supplier for the German heparin, said Sidney Wolfe, director of Public Citizen's Health Research Group

In Switzerland the national medical authority Swissmedic is investigating heparin medication , but there have been no reports of complications.

How Heparin Maker in China Tackles Risks

This is the title of an article in the Wall Street Journal today about Shenzhen Hepalink Pharmaceutical Co.'s high-tech factory in the southern China boomtown of Shenzen who supply APP the competitors of Baxter in the US.

The Shenzhen Hepalink plant has been inspected and approved 9 times in recent years by government health authorities, including the U.S. Food and Drug Administration, China's drug watchdog and German regulators. Buyers have done their own audits 25 times.

Changzhou SPL the suppliers to SPL and thus to Baxters registered itself in China as a chemical manufacturer rather than a drug company. As such, it doesn't fall under the jurisdiction of China's State Food and Drug Agency. The U.S. FDA, in an oversight, also failed to inspect the facility when it began making the active ingredient for the U.S. market.

When FDA officials last month toured the Changzhou SPL factory at the center of Baxter's heparin recall, they described findings that indicated flaws in record-keeping and a lack of evidence that appropriate steps were being taken to effectively rid crude heparin of possible contaminants.

Baxter audited Changzhou SPL in September, Baxter spokeswoman Deborah Spak says. Baxter officials made "several observations," including "a few touching on the same areas" as those identified by the FDA.

Ms. Spak says Baxter approved the Changzhou SPL factory for heparin production "pending satisfactory responses" to the concerns its officials raised. Changzhou SPL provided those responses in January, she says, and Baxter continued to buy its heparin.

China's SFDA approved the two Chinese companies that made the active ingredient for the heparin now recalled in Germany: Changzhou Qianhong Bio-Pharma Co. and Yantai Dongcheng Biochemicals Co.

The U.S. and Europe stopped using heparin extracted from sheep and cow organs more than a decade ago after scientists became concerned about bovine spongiform encephalitis, or mad-cow disease, and the associated sheep disorder called scrapie.

This is a good article at the medical site Seeking Alpha Baxter's Recalled Heparin: The FDA Can't Keep Up - that details the problems the FDA have had in following up the production processes at Changzhou SPL suppliers to SPL > Baxters.

UPDATE 11th March 2008 10.00 pm GMT
Changzhou Qianhong Bio-pharma Co., Ltd. in Jiangsu province with total investment of RMB 120,000,000, covers an area of over 90,000 square meters with construction area of about 31000 square meters including comprehensive production building, office building, R&D center, and analysis and test center. The whole factory was designed and built according to national GMP standard. The company mainly produces lyophilized powder, injections, tablets, capsules and API etc. The annual production of preparations amounts to 1.2 billion pieces and that of API is 150tons. Typical products are Kallidinogenase, Elastase, L-Asparaginase, Urokinase, Heparin and LMM heparin and so on.

In business for 2 decades preparing Kallidinogenase, Elastase, L-Asparaginase, Multi-enzyme capsule etc. Especially we primarily use Kallidinogenase to cure chronic complications in diabetes.

Baxter Healthcare Heparin crisis grows - active ingredient traced to Chinese production plant that was not inspected by the FDA

Deerfield, Illinois-based Baxter Healthcare

Baxter Issues Urgent Nationwide Voluntary Recall of Heparin 1,000 Units/ML 10 and 30mL Multi-Dose Vials
NDC NUMBERS 0641-2440-45, 0641-2440-41, 0641-2450-45 and 0641-2450-41; LOTS: 107054, 117085, 047056, 097081, 107024, 107064, 107066, 107074, 107111

January 25, 2008 – Baxter Healthcare Corporation has announced the voluntary recall of nine lots of heparin sodium injection 1000 units/mL 10mL and 30mL multi-dose vials. The company began recalling the lots on January 17, 2008 as a precautionary measure due to an increase in the number of reports of adverse patient reactions that may be associated with the product. Baxter is conducting a thorough investigation of these reports to identify the cause of the increase in allergic-type reactions.

Heparin, (Baxter Data Sheet)which has been in widespread clinical use since the 1930s, is administered in operating rooms and other critical care areas to prevent blood clots and is crucial in hemodialysis and heart surgery, it is derived from pigs intestines although was first extracted from livers (hepar =Gk liver) . Millions of patients worldwide each year receive the product intravenously and Baxter sells 100,000 vials a day.

The company sells about $30 million of heparin injections annually, compared with $11.2 billion in corporate sales in 2007.

Baxter suspends multi-dose heparin vial production Guradian / Reuters Monday February 11 2008 By Susan Kelly

CHICAGO, Feb 11 (Reuters) - Baxter International Inc on Monday said it has temporarily stopped making the blood-thinner heparin in multi-dose vials after four patients who took the drug died and hundreds of others became ill.

The U.S. Food and Drug Administration said it had received about 350 reports of health problems associated with Baxter's injectable heparin product since the end of 2007. Four patients died, but the relationship to the drug is unclear, an FDA statement said.

Since the recall, Baxter has received reports of similar adverse reactions occurring in other lots of 1,000 units/mL, 10 and 30mL multi-dose vials; 5,000 units/mL and 10,000 units/mL multi-dose vials; and 5,000 units/mL single-dose vials when single doses were combined to create a larger bolus dose.

FDA Never Inspected Chinese Facililty Where Ingredient in Heparin Is Made
By Anna Wilde Mathews and Thomas M. Burton WSJ 13th february 2007

A Chinese facility that has never been inspected by the U.S. Food and Drug Administration made the active ingredient of a Baxter International Inc. blood-thinner that is under investigation after reports of hundreds of allergic reactions and four deaths among its users, the agency said yesterday.

An FDA spokeswoman said the plant making the active ingredient for the drug heparin "was supposed to be inspected" but "due to human error, and inadequate information-technology systems, a pre-approval inspection, which would normally be conducted, was not." Currently, she said, "preparations are being made to perform an inspection as soon as possible."

Both the FDA and Baxter have specified that it is not clear the allergic reactions are linked to the product from the Chinese facility.

Market watch Feb 13th
Baxter heparin ingredient made in uninspected plant: report By Wallace Witkowski

SAN FRANCISCO (MarketWatch) -- Active ingredients used in the recently recalled blood thinner heparin made by Baxter International Inc. have been traced back to a Chinese plant that had never been inspected by the Food and Drug Administration. In January, Baxter issued an "urgent" recall of batches of heparin after reports it caused severe allergic reactions in hundreds of recipients that included four deaths.

The Chicago Tribune report that Baxter's Heparin is manufactured at a plant in Cherry Hill, N.J. where the product is finished, (and is currently stopped) the Deerfield-based company uses a U.S. based-supplier that makes the "active pharmaceutical ingredient" in plants in China. Baxter would not name the supplier.

The U.S. Food and Drug Administration could not be reached for comment.."We have worked with this supplier for over 20 years and we have been making Heparin for over 30 years," said Baxter spokeswoman Erin Gardiner.

UPDATE : 14th February 6.15 EST.

Those interested in this and related issues might like to visit Eagle Forum ..."sole supplier to the United States of the abortion pill, mifepristone, known as RU-486. Our FDA had previously concealed the source of RU-486, and its U.S. distributor, Danco Laboratories, does not list a street address on its website or return press calls. " (The website is actually http://www.earlyoptionpill.com/)

Abortion Pill maker Revealed CBS Shanghai-based Hua Lian Pharmaceutical Co. will make the raw compound for RU-486, but the FDA refused at the time to discuss the manufacturing arrangement for RU-486. Hua Lian got help from the U.S.-based Rockefeller Foundation in winning the production license for RU-486 under FDA specifications, said Gao Ersheng, a research director at the Shanghai Family Planning Commission.

A statement from Danco said the plant that will make RU-486 for the U.S. market meets "both Danco's drug specifications and the current good manufacturing practices of the FDA."

Danco Laboratories is an LLC which was incorporated in the Cayman Islands in 1995. Danco has a license from the Population Council to distribute the drug mifepristone, under the brand name Mifeprex. Mifeprex is the only drug distributed by Danco. The offices of Danco are in New York City, and are under an unlisted phone number and a post office box for security purposes.

There are many who will query the concern that the FDA have that production facilities of RU-486 meet current good manufacturing practices of the FDA yet there are problems over Heparin used daily by haemodialysis patients.

Heparin - APP doubles prices, triples production - the fascinating life of Dr Soon-Shiong and cures for cancer and diabetes

Recalls of heparin around the world and a tainted Chinese supply of its raw ingredient are triggering a spike in prices of the blood thinner to hospitals and dialysis centers amid tight supplies.

Direct consumers are unlikely to feel the impact because heparin is cheap, costing $1 dollar per vial by most estimates. The drug is administered during dialysis and heart surgeries and therefore would be a fraction of the overall procedure's cost, hospitals say.

APP Pharmaceuticals Inc. (previously known as Abraxis BioScience ) said it will increase the price of heparin in what (they claim) amounts to 6 cents per 1000 units of heparin, or about "48 cents per dialysis treatment," the company said. APP would not disclose specific prices or future increases saying they are "proprietary" and vary by dosage and customer.

Following the withdrawal of supplies of heparin from the US market due to contamination of their Chinese supplies with low cost oversulfated chondroitin sulfate.

Subsequently APP Pharmaceuticals Inc. (NASDAQ : APPX) have become the principal US supplier.

Heparin is a blood thinning agent required prior to dialysis and heart surgery and is a relatively low cost drug. It is also used to thin blood in the tiny catheters required when dealing with premature baies in IC units.

APP have now increased prices (without discolosing what they say are proprietary pricing structures) which they say amounts to about 50 cents per dialysis procedure. According to the Stanford and Fresenius Research report of May 2, 2008, the reimbursement for managed care dialysis treatment is approximately $614, with an average reimbursement per dialysis treatment of $325, taking into consideration the Medicare reimbursement rate of $237 per dialysis treatment. APP Press release.

The U.S. Food and Drug Administration has so far identified more than 80 deaths and more than 1,000 adverse events associated with patients in the U.S. Contaminated heparin has now been identified in the U.S. and 10 other countries and at least a dozen Chinese sources.

APP said it had been absorbing huge increases in raw materials costs last year. Now they need to raise prices this year due to increasing security of its supply chain, additional testing required by the FDA and hiring additional staff to handle new security procedures. APP say they have had to triple production to meet domestic US demand.

USA Today report that 2 major dialysis centres using APP product have seen heparin prices double since mid April. Angela Newman, vice president of Brentwood, Tennessee based Renal Advantage's 90 dialysis centers, says price have risen twice and spokeswoman Stephanie Horn of DaVita with 1,300 dialysis centers, says they have seen a similar jump in prices.

Renal Advantage can't pass increased heparin costs on because most dialysis patients are treated under government-based Medicare and heparin is included in the base rate it pays for treatments, Newman says. While she says she's glad APP stepped up production, the 100% jump is "a little extreme."

The same article also quotes APP Chairman Patrick Soon-Shiong that APP's China-sourced heparin for the USA has tested clean, thanks to a tightly controlled supply chain. Adding that Soon-Shiong says APP, a generic-drug maker, had heparin sales of about $40 million last year and revenue of $647 million. He owns more than 80% of APP's shares. They closed Thursday at $11.81, down 11%. APP said 2008 profit may be flat vs. last year. Mr SS is a man with a fascinating history in the supply of pharmaceuticals courced in China SEE FOOTNOTE

APP issued a Press release on Thursday which says ""Because of the steps that we have been taking since early 2000 to ensure a safe, traceable supply chain and are continuing to take with regard to the production of heparin, we have been able to provide a product of the highest quality standards," said Patrick Soon-Shiong, M.D., chairman of APP Pharmaceuticals. "

U.S. Health and Human Services secretary Mike Leavitt said this week that , "We have put in place processes that we believe can ensure the safety of the heparin supply within the United States," but added, "We believe the system that we have for ensuring safety is a good one but completely inadequate for the future,"

He also acknowledged that the heparin scare had seen the need to change supervsory procedures."What you'll see from the United States is a substantial change in our strategy," he added, noting Washington's plans to station Food and Drug Administration inspectors in China and other countries.

Meanwhile inquisitive members of Congress are still bering blocked by the FDA who continue withholding a list of Chinese heparin suppliers requested by congressional investigators looking into problems with hepqrin. The FDA say that confidentiality agreements prevent release of the companies' names.

Members of Congress also are concerned that Chinese heparin manufacturers and their raw-material suppliers didn't fully cooperate with an FDA inspection team in February, after the problems of contaminated heparin became known.

"The FDA thinks they have it under control, but they really don't," said the congressman leading the investigation, Rep. Bart Stupak (D., Mich.). The FDA's reluctance to release the Chinese companies' names is a red flag, he said. "If I was the FDA director, I'd shut down every drug coming in from China" until they were deemed safe, he said. (WSJ10/5/08)

FOOTNOTE on the interesting career of Mr Soon Shiong

Patrick Soon Shiong was born in South Africa, his parents fled China during WWII.
Online Journal April 20th 2007. Did Abraxis BioScience instruct AstraZeneca to use illegal marketing in their quest to increase sales? By Peter Rost, M.D.

"In a February 2007 press release, Abraxis BioScience (AKA APP Paharmaceuticals) reported record revenue of $765 million in 2006 versus $521 million for 2005. They made that money selling a new version of an old cancer drug at $4,200 per dose.

That new drug is called Abraxane and it has pushed Abraxis BioScience stock from $5 in 2002 to $27 in 2007. The lofty stock price has made Abraxis CEO and Chairman, Dr. Patrick Soon-Shiong a billionaire; Dr. Soon-Shiong owns 84 percent of the stock, today worth about $3.8 billion. "

Peter Rost, M.D., is a former Vice President of Pfizer. He is the author of “The Whistleblower, Confessions of a Healthcare Hitman.” He also writes the daily Dr. Peter Rost blog. See also Counterpoint article on the ethically confused billionaire by same author.

Feb 22nd 2008 Pathophilia APP's Soon-Shiong: No Stranger to Suspect Chinese Suppliers

In VIVO Blog Thursday, February 21, 2008
Heparin Investigation Takes an Ugly Turn for Baxter, Industry

...."Soon-Shiong has been in the news before. APP was the subject of a front page story in the New York Times in 2002 because of its relationship with the group purchasing organization Premier; that was during a time when Congress was looking into GPO practices following allegations by small device manufacturers that they were being shut out of the market.

Before that, Soon-Shiong played a part in the controversy surrounding generic launches of Bristol-Myers Squibb's paclitaxel (Taxol). APP asserted that a patent it held on a cremaphor free formulation of paclitaxel should block generics of the Bristol product. The issue briefly delayed generic launches and prompted a Federal Trade Commission inquiry. (Bristol ultimately settled a series of antitrust claims regarding its patent defense strategies for several brands; APP was never charged.)

One last thing: APP also has first-hand experience with the challenges of global supply chain management. The company acquired its injectable generic product line from Fujisawa USA in the 1990s. Shortly after the acquisition, APP had to recall injectable gentamicin due to endotoxin contamination. The culprit? A Chinese raw material supplier.

Soon-Shiong should make an interesting witness..."

Diabetes health Dr. Soon-Shiong Sued by Mylan Laboratories - Melissa Sattley1 August 1998

"Mylan Laboratories Inc. (3rd largest generic drug supplier in the world now called Mylan Inc.) has filed suit in a Los Angeles court against Patrick Soon-Shiong, MD, the well publicized islet cell transplant researcher at VivoRX.

Mylan claimed that Soon-Shiong diverted some of the US$46 million it had invested for islet cell transplant research into other non-diabetes related companies which directly profited Soon-Shiong. "

(In early 1999 the case went to an arbitrator, who examined 17,000 pages of documents--and cleared Soon-Shiong of any wrongdoing but the litigation simmered for more than a year until Soon Shiong agreed to pay US$32 million for the balance of Mylan's American Bioscience shares .)

Islet Foundation May 1998 Can Dr. Soon-Shiong Perform Miracles?by Scott. M. King.

"Soon-Shiong performed the first whole pancreas transplant in 1987 at UCLA." ..."After hearing Dr. Soon-Shiong's glowing report of his work, some in the audience in Palm Springs wondered if it was a giant hoax. However, if Soon-Shiong is right, it could be a real cure for diabetes. "

"Is there any truth behind Dr. Soon-Shiong's dramatic claims of expanding human islets? Sadly, I can find no one who believes it."

Forbes 10th June 2003 , has an interesting article on Dr Soon Shiong and his apparent breakthrough on cancer treatment.


Keep an eye open for more interesting information about this very interesting man and his very interesting career. Meanwhile the results of Dr Soon-Shiong's 2 "transplants" of islet cells are .. the first, Steven Craig died at the age of 43 in 1998 , he took his own life.The second Clarissa Hooper. said that this procedure was not effective for her. She subsequently had both legs amputated, and a kidney transplant. She passed away in Livingston, Montana at the age of 47 on January 16, 2006 from heart failure.

How very odd that none of this has appeared in the mainstream press.

European Medicines Agency recalls heparin batches in France, Italy and Denmark

Concern is spreading in Europe about the extent of contamination of injectable heparin which has been sourced in China. To date the FDA have identified 19 deaths in the USA 19 patients who have died after taking heparin, apparently from allergic reactions.

London based European Medicines Agency spokesman Martin Harvey-Allchurch said that France, Italy and Denmark have recalled batches of the blood thinner heparin, although no adverse effects have been reported in any of those countries.

In Italy and Denmark, the raw material for heparin has been pulled from the market, while in Germany and France, it's the finished medicine that was removed, Harvey-Allchurch said. The ingredient has been traced to four Chinese manufacturers.

Germany's Rotexmedica GmbH said it recalled ``several batches'' of the blood thinner earlier this month after patients experienced allergic reactions. Switzerland's regulator asked G. Bichsel AG and B. Braun Medical AG last week to remove two heparin products from the Swiss market. German heparin supplies recalled (March 10th)

The EMEA presumes (but does not yet know definitely) that the contaminant in the three countries is over-sulphated chondroitin sulphate, the same substance found in lots of heparin recalled in the US and a deliberately modified form of the popular diet supplement for joint pains, chondroitin sulphate.

The Wall Street Journal reports that Italian company Opocrin SpA. said it bought some ingredients from Shenzhen Hepalink Pharmaceutical Co., in China that turned out to be contaminated.

APP Pharmaceuticals Inc. -- currently the sole supplier of large-dose heparin for surgery and kidney dialysis in the U.S. have also been supplied by the same company,

However APP spokeswoman Maili Bergman said yesterday that Opacrin heparin was sourced from a different slaughterhouse than the source of APP material. APP heparin has consistently tested contaminant-free in its own and in U.S. Food and Drug Administration testing.

Boston.com
iht
Previous posts on heparin contamination

Lawyers start to sue Baxter over tainted heparin supplies

Regular readers will be aware of regular posts on the effect of deliberate substitution of oversulfated chondroitin sulfate, or OSCS--that is derived from animal cartilage -- in supplies of heparin -- derived from pig intestines -- in China which first showed up in deaths and illness in users of Baxters heparin in the US during twice weekly kidney dialyisis sessions earlier this year. (see Wednesday, February 13, 2008 Baxter Healthcare Heparin crisis grows - active ingredient traced to Chinese production plant that was not inspected by the FDA )

This week's Time magazine has helpful update detailing some of the personal tragedies this has caused - Heparin's Deadly Side Effects By Bill Powell/Shanghai Thursday, Nov. 13, 2008

The article claims that (as many have suspected) that OSCS's key benfit is -- as a Baxter spokeswoman is quoted by Time, a "virtual mimic of heparin" in most tests and, according to a congressional investigator, costs only $20 per kg, vs. $2,000 for crude heparin. The suppliers, investigators believe, colluded to substitute OSCS in the crude heparin they passed along for the standard price and pocketed the $1,980 difference for each kilogram they sold.

Naturally in the land of the lawyers , plaintiff attorneys have filed 60 suits to date against Baxter and their Chinese based heparin suppliers, Scientific Protein Laboratories LLC (SPL), in federal courts. (Pic of Changzou SPL factory outside Shanghai)

SPL CEO Strunce can claim his company's heparin met Chinese standards, but that's probably a meaningless defense in a U.S. trial. For American drug companies using sources in China, quality control is not just China's problem--it's also their problem.

It is of interest that Waunakee, Wis., based SPL was started in 1976 by Oscar Meyer (now part of Kraft Foods) , top hot dog merchants throughout the USA. SPL have no connection now and are an independent company - " As a truly independent company, SPL is extremely nimble, entrepreneurial and customer-focused .... While we retain the levels of quality and compliance from our “Big-Pharma” roots.." (website)

Time points out that the gruesome connection is that half the world's pigs are to be found in China and Oscar Meyer handles a lot of them and so set up the company to manufacture and trade the many proteins used in the world wide pharmaceutical industry.

Thos interested in the further story of how Baxter's competitors in the USA , APP was taken over by dailysis speciaists Fresenius (FREG_p.DE: Quote) and the fascinating career of their fascinating Chinese born founder Patrick Soon Shong - Wednesday, July 09, 2008 who is till busy counting the US$3 Bn. he collected on selling out. Heparin -another chapter in the tale APP taken over by Fresenius - Patrick Soon Shong trousers US$3 Billion

Food and Drug Administration underesourced to monitor overseas drug manufacture - heparin problems become global.

The worldwide effects of Chinese heparin blood thinner products deliberately contaminated with low cost over sulphated Chondoitin Sulphate becames more apparent every day.

Dr. Janet Woodcock, director of the Food and Drug Administration's drug center, has announced that German regulators have uncovered a cluster of illnesses among dialysis patients who took contaminated heparin.To date the contaminated product is directly related to 81 deaths and a large number of severe reactions in many patients.

Woodcock also claimed that Chinese officials had conceded that heparin produced in their country contained a contaminant, though they deny its connection to the reported problems and insist that Chinese inspectors be allowed to inspect the American plant where the finished heparin vials were made.

"We don't have a strong evidence to show that it is heparin or its contaminant that caused the problem," said the official, Ning Chen, second secretary at the Chinese Embassy.

This dispute, resulting in human fatalaties comes on top of poisonous toothpaste, lead-painted toys, toxic pet food laced with melamine, and tainted fish.

The FDA sent a warning letter on Monday to Changzhou SPL, the Chinese plant identified as the source of contaminated heparin made by Baxter International in the United States. It warned that the plant used unclean tanks to make heparin, that it accepted raw materials from an unacceptable vendor and that it had no adequate way to remove impurities.

The FDA has identified 12 Chinese companies that have supplied contaminated heparin to 11 countries — Australia, Canada, China, Denmark, France, Germany, Italy, Japan, the Netherlands, New Zealand and the United States. Deborah Autor, director of compliance at the FDA's drug center, said the agency did not know the original source of all the contamination or the points in the supply chain at which it was added.

Lots of heparin going back to 2006 have been found to be contaminated. The current spike in illness and death first became apparent in November 2007 and continued for several months as the product was withdrawn and substituted.The severe reactions seem to be related to patients who were given high doses of the drug, Woodcock said.

She said she would not detail the suspected problems with the contaminant in heparin until the information is published in scientific literature and other researchers have had a chance to contribute to the results.

"We are not able to rule out the fact that there could be other problems leading to these adverse events," Woodcock said.She did tell Reuters that "We have data in vitro, in test tube ... as well as animal data that shows that this contaminant can trigger events that would lead to these type of reactions. That doesn't tell us everything or the whole story but it establishes a link."

The Government Accountability Office (GAO)is to release a report showing that the FDA will need to spend at least US$56 million more in 2009 to begin full inspections of foreign plants. It would need to spend at least $15 million annually to inspect China's drug plants every two years, which is the required minimum standard for drug manufacturers in the US.

The FDA could spend the next 27 years at the current rate inspecting every foreign medical device plant that exports to the United States, 13 years to check every foreign drug plant and 1,900 years to examine every foreign food plant, GAO say.

US Heparin production boosted by APP as Baxter and FDA still need to identify their problem with Chinese sourced drug component

It's an ill wind.

Schaumberg, IIlinois based APP Pharmaceuticals (formerly known as Abraxis Bioscience Inc. ) and Baxter each supplied roughly 50/50 o fthe heparin for the US market which is essential for haemodialysis. Now that Baxter have of heparin , APP have ramped up production to meet demand and have arranged new production lines at its Grand Island, N.Y., plant.

APP source the heparin product from several sources inspected and approved by both the FDA and the Chinese regulatory body SFDA.

APP shares rose 79 cents to $11.30 in trading on the Nasdaq on the news which was also affected by the University of Chicago Medical Center, announcing that it switched last month to APP product. A chain of 1,600 U.S. kidney-dialysis centers run by Fresenius Medical Care North America, a unit of Germany's Fresenius Medical Care AG, already have announced switching to buying exclusively from APP. Fresenius has 120,000 dialysis patients who get esential life saving treatments three times a week.

Shares of APP are still nearly 20 percent off a 52-week high of $15.25 the stock price hit in April of last year.

Baxter note that heparin makes up less than 1% of Baxter's corporate sales and are working with the FDA who are examining the Cherry Hill, N.J., Baxter facility and the Waunakee, Wis., plant of Baxter's supplier, Scientific Protein Laboratories LLC. Scientific Protein's Chinese joint venture, Changzhou SPL in Changzhou, China, is to be examined closely by a team that will include manufacturing experts and a Chinese-speaking chemist.

The FDA is still puzzling over the cause of the heparin reactions potentially tied to Baxter's version of heparin and they are also facing Congessional scrutiny about their failure to examine and approve Changzhou SPL which they claim was due to a mix up over similiar names of companies on their database.

Joseph Famulare, deputy director of the FDA drug center's office of compliance, said the name of the operation "that was sent to the office of compliance for evaluation was not the correct firm. It was another firm with a similar name," which had been inspected and found to be in compliance.

This problem has highlighted concern in the U.S. over the mounting number of foreign-sourced drug ingredients (unkown to many consumers) and the FDA's questionable ability to effectively monitor quality control.

Such Congressional concern might spill over into other practices outsourced to China - testing on animals, humans etc.,

Heparin -another chapter in the tale APP taken over by Fresenius - Patrick Soon Shong trousers US$3 Billion

German medical group Fresenius (FREG_p.DE: Quote) the biggest worldwide provider of dialysis services have bid a remarkable US$3.7 Bn. for APP Pharmaceuticals (APPX.O: Quote, ) who have, since problems with Chinese supplies of heparin pre cursor, become the dominant US supplier of heparin for dialysis , which hit competitor Baxter International Inc (BAX.N: Quote)

The high price saw Fresenius stock declining as they intend to finance part part of the deal through a capital increase. The deal will not only help Fresenius control costs (heparin from APPX has more than doubled in price) but provide an edge on competitor , dialysis services group DaVita Inc. (DVA.N: Quote, )

Fresenius will pay a 29% premium to the market price on Monday of US$23 per share and a possible US $6 a share in the second quarter of 2011 if APP beats a core profit target. Fresenius will also take on APP's net debt of about $940 million. It expects to close the deal at the end of 2008 or start of 2009 after regulatory approval when AP will become part of the Fresenius ' Kabi unit, its infusion drug therapy and nutrition division.

"With the APP platform, Fresenius Kabi will be able to market its product range in the U.S. Fresenius Kabi's international marketing and sales network will allow us to sell APP's products globally," Fresenius Chief Executive Ulf Schneider said.

Fresenius plans to finance the purchase with a mix of debt and equity aimed at minimizing the impact on Fresenius SE's credit ratings, with the largest portion through debt.

Colourful and controversial Patrick Soon-Shiong, APP founder and holder of over 80% of the APP outstanding stock, had given his written consent and a voting agreement and will pick up US$3 Bn. see Saturday, May 17, 2008 see Heparin - APP doubles prices, triples production - the fascinating life of Dr Soon-Shiong and cures for cancer and diabetes

We said at the time "Keep an eye open for more interesting information about this very interesting man and his very interesting career." .. which probably explains why a lot of interest has been shown in the last 2 days in the above post by folks at JP Morgan and Lehman Bros.... amomgst others.

Well maybe Baxter International just got unlucky with their suppliers of heparin from China enabling APP to snuck in, take over the dialysis market, double prices ... Patrick must have had good contacts in China to ensure supplies were not contaminated.

UPDATE WED 4.45 BST Here is soemthing very interesting about this very intersting company run by the very intersting Dr Patrick Soon Shiong. Footnoted.org notes an 8K SEC filing at around 2-30 on July 2nd ...there was Footnoted noted ..."sudden uptick in the company’s stock on Wednesday afternoon, someone seems to have picked up on the filing, or at least used it as a convenient excuse to buy."

"But it’s not just the stock that bounced. A short time ago, I spoke with Ryan Dietrick, a senior technical strategist at Schaeffer’s Research who said the options activity late last week looked unusual, given that normal open interest for APPX options had been “very light”. But on Thursday, someone made a pretty bold bet and bought 540 August call options @ 17.50 a share, which Dietrick says likely went for $1.30 to $1.40. Right now, those options are going for $6.30 a share, which makes whomever bought those options on Thursday either very smart or unusually lucky."

A Commentator posts ...."Hmmm, looks suspicious. I wonder if someone got the call first…"

Heparin contaminant is a modified cheap diet supplement for joint pain - "it didn't come straight from the pig"

The Food and Drug Administration stated yesterday that a contaminant - over-sulfated chondroitin sulfate, a substance derived from animal cartilage, found in recalled batches of the blood-thinner heparin was deliberately altered in a way that mimicked the real substance.

Janet Woodcock, head of the FDA's drug division, said the substamce was not medically approved ***and was a lower cost product than heparin. Chondroitin sulfate is sold as a cheap and widely used dietary supplement in it's unmodified form to relieve joint pain or osteoarthritis - often with glucosamine.

"It does not appear to be a natural contaminant that got in there. We don't know how it was introduced or why," she said. Woodcock noted that the over-sulfated substance was deliberately processed and chemically modified so it would act like heparin - "It didn't come straight from the pig".

In some samples of Baxter's active ingredient, the contaminant made up between 2% and 50% of the total material, Dr. Woodcock said.It is heparin sold by Baxter that has resulted in the reports of over 700 adverse reactions and 19 deaths.

The FDA could not say whether iot was added by mistake or to lower costs.

Lord Patel's favourite Senator, Iowan Republican Charles Grassley, ever alert to the malign forces at work in commerce , said the investigation has "provided additional evidence of the need for a robust foreign inspection program within the Food and Drug Administration."

In fiscal 2007, there were a total of 714 Chinese facilities making drugs or drug ingredients for the U.S. market.

Charles Hubbard who was head of the FDA intil 2005 is reported in WAPO saying , "I have no doubt that there are other contaminated or counterfeit drugs like heparin coming into the country, because there's really no system in place to stop them,"

This case mirrors the discovery last year that Chinese suppliers had put low cost melamine into gluten used by American pet food manufacturers to make animal food appear more nutritious. Thousands of American pets became sick or died as a result. Which as far as Lord Patel is concerned is good. The only good dog is a dead dog - 4 legged shit machines.

*** Chondritin sulphate is approved for use in Europe as a symptomatic slow-acting drug for ostearthritis (SYSADOA) with evidenced efficacy and safety demonstrated by clinical trials in osteoarthritic patients. This also provides reference for chemical purity.

The bioavailability of chondroitin sulfate ranges from 15% to 24% of the orally administered dose.

The rationale behind the use of chondroitin sulfate is based on the belief that osteoarthritis is associated with a local deficiency in some natural substances, including chondroitin sulfate.

There is no proof that either glucosamine or Chondritin sulphate , taken singly or in combination, will actually slow the degenerative process or restore cartilage in arthritic joints. A recent a recent study by ConsumerLab.com in the US showed that almost half of the glucosamine/ chondroitin supplements tested did not contain the labelled amounts of ingredients.

Heparin - B Braun issue nationwide product recall after supplier notifies contaminated suuples

B. Braun Medical Inc. (est.1839) began recalling 23 lots of pre- mixed injectable Heparin Sodium in 5% Dextrose and 0.9% Sodium Chloride injection solution on March 21st , 2008 from the US and Canada. This is a precautionary measure as their supplier, Scientific Protein Laboratories (SPL), disclosed that one lot of Heparin Sodium, USP Active Pharmaceutical Ingredient acquired by B. Braun Medical Inc. had a heparin-like contaminant.

To date, B. Braun Medical Inc. has not received any adverse event reports related to this issue. B Braun recall FDA recall notice

US borders safe from illegal importation of incorrectly labelled Penis Pumps - Democracy is safe.

This is one of those arcane, grubby, but nonetheless delightful internet web cyber HOT STORIES that amuse juveniles and like minded souls - The FDA have put out an alert IA #78-01 - 8/20/08, REVISION TO IMPORT ALERT #78-01, "DETENTION WITHOUT PHYSICAL EXAMINATION OF PENIS ENLARGERS AND ERECTION MAINTAINING RINGS"

We need to thank the sharp eyed souls at Texas Star Telegram who picked up this from the FDA website.

Apparently the FDA have identified a problem with penis enlargement devices as there are inadequate instructions for use "The article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a device, the label of which fails to bear adequate directions for use [Misbranding, Section 502(f)(1)]." (Makes you wonder how that contaminated heparin got through these hard working guys at the FDA ?)see Wednesday, February 13, 2008
Baxter Healthcare Heparin crisis grows - active ingredient traced to Chinese production plant that was not inspected by the FDA

Helpfully, in their alert the problems that arise from incorrect use are detailed in somewhat grim and startling detail :The use of penis enlargers and erection maintaining rings may have harmful effects. They may aggravate existing medical conditions such a Pegronies disease, priapism, and urethral stricture. They may contuse or cause rupture of the subcutaneous blood vessels, which may produce hemorrhage and hematoma formation. Additionally, frequent use of erection maintaining rings may result in ecchymosis of the proximal portion of the penis and scrotum, and the lymphatic stasis of the penis.

Perhaps most alarming (if this hasn't already put you off the use of penile rings for a lifetime) : Prolonged use of the rings may cause gangrene of the penis.

Even more helpfully they add that :Basically, the labelling of these devices falsely states or implies they will treat impotence, prolong erection, and increase the dimensions of the penis.

We will hold off on further details of and harm that may result, from the use of : Erection Maintaining Devices, Penis Enlargers, and Supportive Devices - Click here if you need help.

If not already awed by the burly boys and girls of the extraordinarily polite and helpful Transportation Security Administration (TSA) officers when emerging Stateside - the message is clear - should you have brought along your penis pump .... remember to keep the instructions handy. Or this could happen.

Toni Fabuloso's TOP TIP for TRAVELLERS : TSA Federal Flight Deck Officers are trained by the Federal Air Marshal Service on the use of firearms, use of force, legal issues, defensive tactics etc., so it would be unwise to even think about using such devices whilst in flight.

Israeli company Teva to acquire US company Barr to take global lead in generic drugs supply

We posted about American generic manufacturer IVAX being taken over by Teva, Israel's biggest in April 2006. This made Teva the worlds biggest generic company with combined sales to the US market of 330 drugs and sales of US$7 Bn - of which US$1.2 Mn is MS treatment Copaxone - (Glatiramer Acetate ) The first innovative drug to be developed in Israel (at the Weizmann Institute of Science ) and to receive FDA approval, . The US HQ is in Kansas City.

Teva is now to acquire Barr of the US in a $7.5bn deal that will sharply reinforce its position as the largest seller of off-patent medicines. Teva closed at at $45.80 - a dividend yield of 1%.

The agreed takeover, at an agreed 32% premium to the US company's average share price over the past year, will create a group with US$12bn in annual sales, 500 marketed products and more than 200 applications for new drugs filed with US regulators alone. The combined company would be a generic powerhouse employing about 37,000 people globally and operating directly in more than 60 countries.

Teva had a knock-back when clinical trials failed to show a significant benefit for a new dosage of Copaxone, that accounts for one-third of profits and which will be subject to growing competitive pressure in the next few years.

This follow other generic deals recently, with Daiichi-Sankyo of Japan offering up to US $4.6bn for Ranbaxy of India. Fresenius of Germany bidding US$3.7bn for APP of the US - see post Wednesday, July 09, 2008 Heparin -another chapter in the tale APP taken over by Fresenius - Patrick Soon Shong trousers US$3 Billion .

Sanofi-Aventis of France is also tendering US $1.9bn for Czech-based Zentiva although they have rejected the bid as far too low - Bid Fails to Reflect the Company’s Underlying Value and Future Prospects . They have a major position in Czech, Turkish, Romanian and Slovak markets .

Shlomo Yanai, CEO at Teva for less than 18 months ago,sees this as another step in a 5 year plan for Teva double sales by 2012 with a net margin of at least 20 %. Buying Barr would also boost Teva's generic franchise in Central and Eastern Europe as well as Italy and Spain. Barr jumped into the international market when it acquired Croatia's Pliva based in Zagreb in 2006.

For each Barr share, investors will receive US$39.90 in cash and 0.6272 Teva American Depositary Receipts, and Teva will assume $1.5bn of net debt. If the Barr board reject the deal Lehman Bros have negotiated a US$200 Mn break fee .

Teva Q1 Profits shine

On July 29th Teva revaled Q1 figures - Revenue of US$2.823 billion, up 18%, and EPS of 65 cents was ahead of expectations. Teva, saw Europe, 30% of sales, rise 25%, while sales Latin America and other parts of the developing world, were up 37%. Sales in the US rose 12%.

The company attributed a large part of the sales growth to generics in Europe.

The company say the R&D budget from 5.7% to 7% of sales, for improved development of generic drugs. Full year forecast EPS are $2.69 to $2.75.