Many biological medicines draw safety warnings

Why does follow-on monitoring for safety seem like such a strange idea?...

WASHINGTON, Oct 21 (Reuters) - About a quarter of biological medicines approved in the United States and Europe since 1995 have triggered safety warnings in the years after entering the market, Dutch researchers said on Tuesday.

Immune system disorders, infusion reactions, infections and cancer concerns were among the reasons for safety warnings for biological medicines, which are made with proteins derived from living cells rather than the chemicals used in typical drugs.

These medicines, called biologics or biologicals, are typically injected and treat a range of conditions including anemia, rheumatoid arthritis, hepatitis and cancer.

Thijs Giezen of Utrecht University in the Netherlands and colleagues tracked safety-related regulatory actions involving 174 biological medicines approved in the United States or the European Union between January 1995 and June 2007.

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Counterfeiters can get life in jail under new US Act

US President George W Bush has signed a bill under which counterfeiters can be sentenced to life imprisonment if their crime causes the death of an individual.


The passing of the Prioritizing Resources and Organization for Intellectual Property Act of 2007 (PRO IP) strengthens the US court’s power to punish those convicted of counterfeiting; a measure big pharma has been calling for.

By increasing its maximum penalty the US has brought its punishment more closely into line with China, which sentenced a man to life in prison for causing 14 deaths by using a fake ingredient in human immunoglobulin.

The sentence for inflicting serious bodily harm as a result of counterfeit products has also been increased and can now result in up to 20 years in jail. Both sentences can also carry a fine.

In addition to increasing the punishments for trafficking counterfeit goods the new legislation also ramps up US preventative powers.

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US proposes country-of-origin labelling

A good start...we have to start protecting ourselves...

A bill has been introduced to the US Senate that would require the country-of-origin of APIs and excipients to be labeled on finished dosage forms.


This proposal covers both active pharmaceutical ingredients (APIs) and excipients present in prescription or over-the-counter (OTC) products.

Including excipients under the bill differentiates it from the proposal in the draft of the US Food and Drug Administration (FDA) Globalization Act, which was released in April.

Under the proposal the country-of-origin of each active and inactive ingredient would be listed in descending order based upon the quantity in the finished dose.

It appears that it will not be necessary to include the country of origin of all raw materials and intermediates, or the nation in which every step in the synthesis process occurs.

This would provide a more comprehensive view of the origins of an API or excipient but is not mentioned in the bill, probably due to the complexity of implementing such a measure.

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Rest of Sanofi's contaminated Lovenox recalled

The heparin saga continues...

PARIS, Sept 23 (Reuters) - French drugmaker Sanofi-Aventis (SASY.PA: Quote, Profile, Research, Stock Buzz) has recalled remaining batches of contaminated blood thinner Lovenox, a heparin, which were distributed before May 2008, French drug regulator Afssaps said.

Earlier this year, high levels of contamination with an oversulphated chondroitin sulphate in different types of heparin -- derived from pig intestines and used to prevent and treat blood clots -- were linked with serious side effects and deaths.

No such side effects were observed with Sanofi's Lovenox and the European Medicines Agency said in June doctors in Europe could continue to use the drug despite low levels of contamination found in some batches of the product.

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FDA to List Drugs Being Investigated

Talk about "Direct to Consumer" marketing...this sound like "do it yourself" drug safety review...

The Food and Drug Administration will begin posting every three months a list of drugs whose safety is under investigation because of complaints brought to the agency's attention by drug companies, physicians and patients.

The FDA will name the drug and the nature of the "adverse events" but will not describe their seriousness or the number of complaints received, officials said yesterday. Being on the list does not mean the drug is unsafe, only that the FDA is looking into that possibility.

FDA officials said they realize that the new policy, required by changes to federal law enacted last year, may unintentionally alarm some patients.

The agency's Adverse Event Reporting System (AERS) last year received 482,154 unsolicited reports of potential reactions to drugs. The vast majority were false alarms, with the reported problem having nothing to do with the medication a patient was taking.

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Producing heparin without the heartache

or without the Chinese deliberatley substtituing chemical contamination in lieu of actually producing the product they were paid to produce...but, hey, who's quiblling over details...

US researchers have developed a chemoenzymatic strategy to synthesise the anticoagulant drug heparin and avoid the contaminant that has killed more than 80 people.


The breakthrough was presented at the ACS (American Chemical Society) National Meeting and Exposition in Philadelphia, US, earlier this week and described how Escherichia coli (E. coli) bacteria could be harnessed to synthesise the widely-used anticoagulant that has global annual sales of around $4bn (€2.7bn).

Heparin is produced by extraction from pig intestines and contaminated batches of the drug have been linked by the US FDA (Food and Drug Administration) to more than 80 deaths and hundreds of allergic reactions among patients treated with the drug during heart surgery and kidney dialysis.

The contaminated heparin was traced by the FDA to various batches imported from small, family-run workshops in China which supply about 70 per cent of the world’s supply.

While regulators called for greater cooperation and joint inspections of overseas active pharmaceutical ingredient (API) manufacturing plants, Professor Robert Linhardt of the Rensselaer Polytechnic Institute, US, and Associate Professor Jian Liu of the University of North Carolina, US, to search for an alternative method of production.

Prof. Linhardt was part of the team that identified the suspected contaminant as a structurally similar carbohydrate called oversulfated chondroitin sulfate.

"When we found the contamination, it was another sign that the way we currently manufacture heparin is simply unsafe," said Prof. Linhardt.

Researchers have been trying for years to develop a synthetic production method for the drug, however the first total synthesis described in 2003 by researchers from the Massachusetts Institute of Technology (MIT), US, produced only minute batches at a time and could not be economically scaled-up for commercial production.

The synthesis developed by Prof. Linhardt’s team uses a patented biosynthesis that uses enzymes expressed in E. coli bacteria to replicate the normal biosynthesis of natural heparin.

While the team has only used the technique to create the drug on a laboratory scale, scaling the process up should prove no more difficult than scaling-up the production of any other biological drug.

The group plans to begin the necessary preclinical and clinical trials needed to bring the synthetic heparin to market. If successful, the new heparin could be on the market in two to five years.

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FDA seizes drugs worth $74,000

How come we can't get this level of enforcement on real drugs??...

The US Food and Drug Administration (FDA) has ordered the seizure of $74,000 worth of Xiadafil VIP tablets after SEI Pharmaceuticals refused to withdraw them from the market.

A formal request for the recall of the erectile dysfunction dietary supplement was issued by the FDA after it discovered batches contained an undeclared active pharmaceutical ingredient (API).

SEI refused to recall the products leading to the FDA enlisting US Marshals to seize the batches to prevent more illegal Xiadafil from being sold.

Margaret Glavin, associate commissioner of the FDA’s Office of Regulatory Affairs, said: “Today’s seizure action shows that the FDA will take enforcement action to protect the public from dietary supplements that contain prescription drug ingredients that are potentially harmful to consumers.

“The FDA will not tolerate a company’s failure to take voluntary action to protect the public health after being given the opportunity by the FDA to do so.”

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Budget Juggling...

Maybe everybody who lose's their job at the NIH...Slowdown In National Institutes of Health (NIH) Funding Creates 'Quiet Crisis'

Can get a job with the FDA...Agency To Add More Than 1,300 Scientists

Heparin taint tied to deaths

FDA: 3 fatalities linked to material in Baxter product

The U.S. Food and Drug Administration, for the first time, has conclusively linked deaths of patients infused with the blood thinner heparin to a foreign substance found in specific lots of the drug made by Deerfield-based Baxter International Inc.

In an interview Tuesday with the Tribune, the FDA said it completed its review of 93 death reports related to heparin that the agency received from Jan. 1 to March 31, a period when there was a dramatic spike in potentially deadly allergic reactions from patients who had been injected with heparin. The popular blood thinner is used widely in large dosages, often before patients have dialysis or heart surgery.

Of 10 reports of death from severe shock known as anaphylaxis or hypotension, three of those could be traced to lot numbers of Baxter products that tested positive for an animallike substance known as oversulfated chondroitin sulfate. Heparin lot numbers were not known for the other seven deaths from anaphylaxis or hypotension, so the FDA could not determine whether those 7 patients received heparin contaminated with the substance.

"We have what looks like a cause and effect in some patients," Dr. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, said in an interview, referring to the three deaths linked to contaminated heparin. "We know that they got contaminated heparin, and they died subsequently. This is one of the final links in the chain."

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Microbix Chinese vaccine plant boosts global capacity by 20%

Now all we need to do is make a product without contaminations...

Canada-based Microbix has pulled off a coup in sealing a deal with the Chinese government for construction of a facility that will increase the world's vaccine supply by 20 per cent.

Construction of the $198m plant is to be jointly funded by Microbix and the Hunan provincial government, with the site due to become operational in 2013.

A more unusual aspect of the deal will see Microbix construct a replica of the childhood home of Dr Norman Bethune, a Canadian physician who is revered in China for his medical work assisting Chinese communists in resisting the Japanese in the late 1930s.

William Gastle, CEO of Microbix, said: "We've been working for a number of years to bring our technology to market, so today we're delighted to be partnering with the Province of Hunan in building and ultimately operating the most modern and efficient flu vaccine manufacturing facility on the planet.

"This will make China a leader in the production of flu vaccines, and Virusmax the technology of choice in helping other manufacturers in other countries expand their capacity to meet the needs of their populations."

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FDA: 11 Deaths In Medical Devices Tied To Heparin

Unfortunately, we are now moving on to medical devices...

WASHINGTON -(Dow Jones)- The U.S. Food and Drug Administration has received reports of 11 deaths and other adverse events associated with medical devices that contain heparin, a widely used blood thinner that has sparked Congressional inquiries about the agency's oversight of drug manufacturing.

The FDA, in documents posted on its Web site Thursday, said it can't determine at this time whether the devices cited in the reports contain contaminated heparin.

Most of deaths were reported by families. As a result, FDA spokeswoman Karen Riley said, the agency in many cases can't identify the manufacturer or from which lots the heparin came. The FDA is working to contact the families to try to find more information.

Riley said the FDA was able to trace back two of the death reports to conclude that the heparin wasn't contaminated in those cases.

Contaminated heparin from China had previously been linked to 81 deaths in the U.S. and hundreds of allergic reactions. Baxter International Inc. (BAX) is the largest supplier of heparin.

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and Here We Go...

The Chinese start the "active evasion" portion of this tragedy...asking if people who were taking a drug used in dialysis had kidney disease...

China accuses US of shoddy probe into tainted heparin

BEIJING - China's drug safety agency accused the United States on Tuesday of blocking Beijing's inquiry into a blood thinner linked to 81 deaths by refusing to provide details on victims and specifics about production.

Two Chinese experts who attended a conference on the drug, heparin, in suburban Washington, D.C., last month said the U.S. determined a contaminant was likely to blame without considering other possible factors.

"We need to resolve this in a scientific matter, not just by blaming a contaminant," said Jin Shaohong, a member of the drug evaluation committee of China's Food and Drug Administration. "I think it is too early to say that."

Besides the deaths, hundreds of patients have suffered severe allergic reactions to large doses of heparin, which is used in dialysis and other treatments.

The U.S. Food and Drug Administration said it suspects the problems stem from a contaminant the agency discovered in supplies of raw heparin coming from China — a compound derived from animal cartilage that so closely mimics heparin that routine tests can't detect it.

The Chinese experts said U.S. officials and Baxter International refused to give them information to probe the possibility that drug interactions, patients' medical histories or safety issues after the raw material left China may have played a role.

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Report: Risky tests of blood substitutes allowed

The products in question here are very different from each other...

Pooling data would make almost no sense...safety trials would be a good idea, which the FDA strongly recommended, and they enforced their own recommendation...check the timing of Biopure's stock dropping several years ago as compared with the FDA response letter...

other details gets washed over in this article as well...

FDA permitted human testing despite warning signs, report charges

CHICAGO - Experimental blood substitutes raised the risk of heart attack and death, yet U.S. regulators allowed human testing to continue despite warning signs, says a scathing new report.

The U.S. Food and Drug Administration fell short, the report contends, even as red flags popped up during studies by five biotech companies. Rules barred the agency from releasing company trade secrets, and that kept some information hidden and may have led to unnecessary heart attacks and deaths, wrote the authors, who are government scientists and consumer advocates.

“There shouldn’t be secret science,” said the lead author of the report, Dr. Charles Natanson, of the National Institutes of Health Clinical Center. Safety data need “to be made public expeditiously so science can build on the mistakes” of previous research, he said.

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Heparin Recall Update

The Chinese delegation visited the Baxter site in Cherry Hill last week...and there hasn't been much follow-up in the press...

It was heard that that the Chinese requested samples of the product in question in order that they can do their own testing in China...and that these samples were provided to them...

Anybody want to guess what the Chinese will report?

At an embassy news conference in Washington, Chinese officials said the problems
linked to heparin could have occurred in the United States, or that chronic
conditions in some patients led to severe reactions.

This is not the statement of a scientific team focussed on identifying the root cause of an adverse event...which is a demanding, difficult task which requires good research, scientific judgement and caution...these things need to be right...

No, this is the type of waffling statement made by organizations trying to duck out on their responsibility...they will say anything in order to shift the blame or to avoid being held accountable...exactly the sort of behavior that can not possibly result in identifying and correcting the current problem...

Lung cancer warning a death knell for inhaled insulin?

You know all those jokes about drugs where the side effectes are worse than the symptoms the product is supposed to help with?

Pfizer has updated the US product labeling of its inhaled insulin treatment Exubera to include a warning of increased risk of lung cancer among those using it.

Warning labels were issued as a consequence of a clinical trial in which 6 of the 4,740 Exubera-treated patients developed lung cancer, as opposed to 1 of the 4,292 patients not treated with Exubera.

The move is the latest twist in the downwards spiral of Exubera, which appears to have taken the whole inhaled insulin market down with it.

Exubera launched as the world's first inhalable insulin and was touted as a potential $2bn a year blockbuster. However, it was dogged by safety concerns, as well as complaints that the device was too expensive and cumbersome, leading to Pfizer abandoning the treatment.

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FDA Product Safety Alert for Heparin

the Heparin saga continues...

Braun Heparin Sodium in 5% Dextrose and 0.9% Sodium Chloride Injection Solution

The Heparin Saga expands...

B. Braun Medical issues recall of heparin

B. Braun Medical Inc. recalled heparin blood thinner in the U.S. and Canada after learning that it contained a "heparin-like contaminant" from a supplier linked to deaths and allergic reactions in another company's product.

The contaminant was supplied by Scientific Protein Laboratories, Irvine-based B. Braun Medical said Friday. Scientific Protein also supplied Baxter International Inc. with heparin containing a cheaper ingredient from China.

Baxter's heparin has been linked to serious allergic reactions and 19 U.S. deaths. The heparin recalled by Braun is sold to hospitals as a premixed solution in intravenous drip bags, a Food and Drug Administration spokeswoman said.

Neither Braun nor the FDA was aware of anyone sickened by the recalled heparin.

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Contaminant found in heparin

WASHINGTON - U.S. health officials have identified a contaminant in batches of the blood thinner heparin associated with 19 deaths and are trying to determine how the chemical got into the drug.

The lots of heparin, whose key ingredient was imported from China, were recalled Feb. 28, and Food and Drug Administration officials said Wednesday that no new deaths have been reported since that time.

Dr. Janet Woodcock, head of the FDA's Center for Drug Evaluation and Research, said the contaminant is oversulfated condroitin sulfate, a chemical that does not occur naturally.

Condroitin sulfate is a natural compound that occurs widely and is used as a dietary supplement but the oversulfated version has not been widely studied.

"We cannot rule in or out whether this was accidentally or deliberately introduced into the product," Woodcock said, "We are investigating how it got in."

The FDA has also initiated testing of imported heparin entering this country and Woodcock said the agency feels "doctors and patients now can be confident that the product on the market has been tested and is safe."

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The Baxter Heparin Saga...pick your spin...

There are a lot of different ways to look at this issue...

- Writer's Scare Tatics..."Tampering possible in China"

- Troubleshooting drug safety is scientific challenge...heparin-like molecules

- FDA and manufacturer cooperate to maintain drug supply...Earlier this month, the firm stopped production, but the FDA wanted to keep the existing Baxter heparin in doctors' hands because it did not want to cause a shortage of the life-saving drug. Agency officials said increased production by the other heparin manufacturer can now satisfy the demand.

- FDA doesn't inspect overseas manufacturing sites...The FDA has averaged just 15 inspections in China in each of the last five years

- Lack of FDA oversight on imports...Flood of drugs, little oversight by regulators

- Outsourcing causes quality problems...Baxter’s Heparin Problems May Have China Connection

- Chinese quality control...Baxter tests point to Chinese problem

- Realtime crisis management...Call to action at Baxter

Manufacturer intitiates recall...Baxter Issues Urgent Nationwide Voluntary Recall of Heparin

Before you decide on which drum you think should be beat on, just remeber that these issues are harder to solve than you might think...

Operation Jupiter rains on fake antimalarials

anti-counterfeiting operations...sounds exciting...

A multinational, multidisciplinary initiative involving scientists, public health workers, police and government officials could provide a cogent model for rooting out and stamping out counterfeiting of essential and lifesaving drugs.

But replicating 'Operation Jupiter', which employed a battery of forensic tests ranging from mass spectrometry to palynology (pollen analysis) to track down a source of fake artesunate in southern China, would require technical capacity and resources as well as collaborative efforts that at present are sorely lacking in the countries most affected by counterfeiting.

In the developed countries where fake pharmaceuticals are still at a relatively low ebb, counterfeiting can infiltrate a wide range of drugs, but in particular lifestyle products such as the erectile dysfunction treatments Viagra (sildenafil citrate, Pfizer) and Cialis (tadalafil, Eli Lilly).

The focus of the operation co-ordinated by the World Heath Organization's (WHO) Western Pacific Regional Office, the International Criminal Police Organisation (INTERPOL) and the Wellcome Trust-University of Oxford South-east Asian Tropical Medicine Research Programme, in close co-operation with the Chinese authorities, was a generic medicine for a tropical disease that threatens some 40 per cent of the world's population and still claims over a million lives a year.

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