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The almost two-year manufacturing woes of orphan drug manufacturer Genzyme have been well documented and publicized. Despite these problems and an FDA consent decreed, it was not enough to stop Sanofi-Aventis from doggedly pursuing Genzyme as a take over target for the past year.

As you may recall, production shortages of several of Genyzme’s key products, most notably Fabrazyme, a treatment for Fabry disease (a rare genetically inherited lysosomal enzyme storage disease) forced Genzyme to ration Fabrazyme to patients. Fabrazyme is the only approved treatment for Fabry disease and the rationing plan called for patients already taking Fabrazyme to receive half the approved dosage while newly diagnosed patients were prevented from receiving the drug at all!

A post on the Pharmalot blog last week revealed that at least half a dozen patients with Fabry disease who were taking Fabrazyme filed a lawsuit against Genzyme and New York’s Mt. Sinai Medical School for the ongoing shortages and the ill-conceived rationing plan. According to the lawsuit, as many as three patients with Fabry disease have died as a result of the Genzyme rationing plan. Mt. Sinai was named as a co-defendant in the case because it licensed Fabrazyme to Genzyme and went along with the company’s rationing program. Further, the lawsuit contends that neither Genzyme nor Mt. Sinai had adequately tested whether or not the reduced dosage was effective as a treatment for Fabry disease. Obviously, the FDA approved Fabrazyme as a treatment for Fabry disease based on the dosage information that Genzyme determined to be optimal in it BLA.

The lawsuit will likely never make it to trial (Genzyme will undoubtedly settle) and therefore have little or no impact on the impending acquisition of Genzyme by Sanofi-Aventis. Companies that are being acquired or merging don’t like it much when there is outstanding litigation that may interfere with the transaction.

Nevertheless, Genzyme’s manufacturing problems highlights one of the weaknesses of the US Orphan Drug Act. For those of you who may not know companies granted approval of drugs for orphan indications (< 200,000 patients) are guaranteed seven years of market exclusively (along with tax credits, grants and less onerous clinical trials). This means that no other company (aside from the innovator company) will be granted regulatory approval for a similar orphan product for seven years from the approval date of the first product. Not surprisingly, this forces patients with orphan diseases to exclusively rely on a single drug that is manufactured by a single company i.e. there is no backup. And, if an orphan drug manufacturer has regulatory compliance issues or goes out of business etc the patients that rely on the drug are SOL (as it is said in the vernacular). Unfortunately, this was exactly what happen with Fabrazyme when Genzyme’s chronic manufacturing problems resulted in shortages of the drug.

While many people take drug companies to task for developing so-called “me too” drugs there is a reason why FDA and other regulatory agencies approve them. That is: when there is more than one manufacturer of drugs that treat a particular indication then there will be alternate treatments available to patients if something goes awry with one or another of the products. Although I am a strong proponent of the Orphan Drug Act, the recent entry of several major pharmaceutical companies like Pfizer, GlaxoSmithKline and others into the orphan drug development space suggests that the seven years of market exclusivity offered by the Act may no longer be necessary. Further, shortening or eliminated the market exclusivity term would like help to increase competition among orphan drug developers. Increased competition would, in turn, and then help to drive down the price of orphan drugs which are currently exorbitantly expensive and sometimes not covered by insurers. Changing the orphan drug act would primarily benefit patients with rare diseases and not drug makers. And, in the end, helping patients is admittedly all that matters!

Until next time...

Good Luck and Good Job Hunting!!!!!!!!

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Can things get any worse at Genzyme? First there were the manufacturing problems that result in plummeting stock share prices and a proxy battle by Carl Icahn and company. Next up was a $175 million consent decree judgment levied by the US Food and Drug Administration for the manufacturing problems. Then came the $18 billion takeover bid from Sanofi Aventis. Now, patients affected by shortages of the drugs Fabrazyme three patients have petitioned the US Department of Health and Human Services (HHS) to disregard Genzyme’s patent for the medicine to overcome the drug shortages.

Because of the manufacturing problems, Genzyme rationed its supplies of Fabrazyme to one-third of the normal dose for Fabry disease patients. Some of these patients reported increased pain and no newly diagnosed patients could receive the drug. Meanwhile, Shire Pharmaceuticals has been trying to obtain FDA approval of its Fabry disease treatment, Replagal which is approved in Europe.

The patients who petitioned HHS contend that HHS can override the patents because the National Institutes of Health paid for research at the Mount Sinai School of Medicine, which exclusively licensed Fabrazyme to Genzyme. The goal of the action is to induce another company to produce the drug in case Genzyme is unable to deliver adequate quantities to new and existing patients. Provisions in the Bayh-Dole Act suggest that this action may not be unreasonable if ‘a licensee cannot reasonably meet the public health and safety needs of the American public.’

Stay tuned for the next installment of the continuing Genzyme saga!

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Genzyme announced yesterday that it expects to be fined roughly $175 million in fines and penalties related to the manufacturing troubles at its Allston Landing, MA manufacturing plant that resulted in severe shortages of two of its best selling products, Cerezyme (Gaucher disease) and Fabrazyme (Fabry disease) 

The fines and penalties are part of a consent decree that the US Food and Drug Administration (FDA) intends to levy against the company for the manufacturing infractions. A substantial portion of the penalties included a disgorgement settlement, a process that allows FDA to collect a certain percentage of the sales of products made at the troubled Genzyme production facility.

According to an article in today’s New York Times business section, Genzyme representatives said that patients using Cerezyme would continue getting half a dose for two or three more months. It previously said full supplies would be restored May.

Patients who use Fabrazyme would continue to be allocated a third of their usual dose at least through the third quarter. The company had previously hoped to resolve the Fabrazyme shortage in the third quarter.

The highly publicized manufacturing problems at Genzyme, has shaken both physician and patient confidence in the company’s ability to safely manufacture and supply sufficient quantities of Cerezyme and Fabrazyme; two orphan drugs designed to treat patients with debilitating genetically-inherited diseases. 

Several physicians and patients who were previously loyal and ardent supporters of Genzyme, have indicated that they may switch to recently approved and new treatments being developed by Genzyme’s competitors that include Shire.

The lack of commitment to quality manufacturing by Genzyme executives has seriously tarnished the image of a once highly respected and reputable orphan drug developer.

Until next time…

Good Luck and Good Job Hunting!!!!!

Until next time…

Good Luck and Good Job Hunting!!!!!!!   

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The recent manufacturing woes of orphan drug manufacturer Genzyme have been well documented and widely publicized. These problems resulted in massive shortages of some of its top selling drugs Cerezyme (Gaucher disease) and Fabrazyme (Fabry disease) causing many of the patients who depend on these drugs to maintain their quality of life to go without reduced or no treatments for months. 

Because both drugs were approved by the US Food and Drug Administration (FDA) as orphan drugs they enjoy seven years of market exclusivity from the date of regulatory approval which prohibits other companies from seeking approval and selling similar drugs in the US. Consequently, Genzyme is the only commercially-available source for the drugs. Genzyme’s ongoing biomanufacturing created massive shortages of both drugs last summer. Because of this, FDA allowed two other companies, Shire and Protolix Biotherapeutics (both have treatments for Gaucher (Protalix) and Fabry (Shire) disease in late stage clinical development), to make their drugs available (at no charge) to patients prior to regulatory approval. This was a relatively rare and bold move by the agency. But, to be fair, they had little choice because so many patients were suffering.  

In case you may be wondering there are approximately 1500 Cerezyme users and fewer than 1000 Fabrazyme users in the US. Despite the small numbers of patients, the cost of the treatments are extraordinarily high; costing patients as much as $200,000 per year for treatment.

According to an article in today’s NY Times as many a 15 percent of American Cerezyme users have switched to a different drug. Fewer patients with Fabry disease have switched mostly because Shire’s drug for Fabry disease Replagal was less widely available. The almost year-long shortages of both drugs have seriously tarnished Genzyme’s reputation. And previously loyal patients are questioning their almost decade long allegiance to the company. This, coupled with a 26 per cent decline in Genzyme’s stock price last year suggest that Genzyme’s standing as one of the top five biotechnology companies in the world may be in serious jeopardy. 

Despite calls for his resignation (and an attempt by Carl Icahn to wrest control of the company), CEO Henri A. Termeer, who has led Genzyme for over 20 years has vowed not to resign. While manufacturing problems are not uncommon in the biotechnology industry, the severity and ongoing nature of the manufacturing problems at Genzyme’s Allston Landing, MA production facility are unacceptable; especially for a company that specializes and prides itself in developing treatment for orphan disease indications. The FDA recently announced that it would fine Genzyme and place its manufacturing operations under a consent degree for an indefinite period of time.

Genzyme representatives now contend full supplies of Cerezyme will be available after May 1 and those for Fabrazyme possible in the third quarter of this year.

While so-called “copycat” or “me too” drugs developed by pharmaceutical companies tend to be vilified by consumers and patient advocacy groups, the agency prefers to approve more than one treatment option for a given disease indication in case one medication doesn’t deliver the intended therapeutic benefits or induces untoward adverse events. Unfortunately, the seven years of market exclusivity awarded to orphan drugs manufacturers that garner regulatory approval for their products prohibits this. The biomanufacturing fiasco at Genzyme suggests that it may be time to reexamine the Orphan Drug Act and modify some of the financial and regulatory terms that were included to induce drug companies to develop new treatments for orphan disease indications.

Until next time…

Good Luck and Good Job Hunting!!!!!!!

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Orphan drug manufacturer Genzyme today issued a press release that the US Food and Drug Administration (FDA) notified the company that it intends to take enforcement action to ensure that products manufactured at its troubled biomanufacturing facility in Allston Landing, MA are made in compliance with good manufacturing practice regulations.

The agency’s enforcement action will likely result in a consent decree under which a third party would inspect and review the plant’s operation for an extended period and certify compliance with FDA regulations. Under a consent decree, Genzyme also would be required to make payments to the government and could incur other costs.

The Allston Landing facility was experiencing product quality problems for some time before FDA intervened and threatened regulatory action and sanctions against the orphan drug producer. According to the press release Genzyme will:

work cooperatively with the FDA to restore the agency’s confidence in its ability to operate the Allston plant at the highest standards, building on the progress it has made over the past year to address the manufacturing deficiencies at the Allston plant. This progress includes:

• Retaining a leading quality assurance advisory firm to help develop a comprehensive strategy and risk mitigation plan. More than 30 expert consultants from this firm are currently working at the Allston plant or at other Genzyme manufacturing facilities.
• Naming a new site head and reorganizing and strengthening the management team at the facility.
• Hiring two highly regarded industry veterans to serve as President of Global Manufacturing and Corporate Operations and Senior Vice President of Global Product Quality.

While this is not good news for Genzyme, it is great news for patients who rely on Genzyme’s medicines to manage their oft times devastating and potentially life threatening genetically-inherited diseases.

Until next time…

Good Luck and Good Job Hunting!!!!!!!

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Genzyme announced in a Securities and Exchange Commission filing on Monday that it inked a "fill and finish manufacturing services" deal with Hospira for several of its top selling drugs including Cerezyme (Gaucher disease), Fabrazyme (Fabry disease, Myozyme (Pompe disease) and Thyrogen (thryroid cancer). The move follows a series of highly publicized manufacturing problems at the company’s Allston Landing, MA biomanufacturing facility in 2009.

Beginning in March, Genzyme received a warning letter from the US Food and Drug Administration (FDA) detailing "significant objectionable conditions" at the Allston facility. The agency identified deviation and violations of current Good Manufacturing Practice (GMP) in four areas including: 1) maintenance of equipment, 2) computerized systems, 3) production controls and 4) the failure to follow procedures aimed at preventing microbiological contamination.

In June, Genzyme shut down the biomanufacturing plant to clean up viral contamination that had been slowing down production of Cerezyme and Fabrazyme. The virus, Vesivirus 2117, is known to interfere with the growth of Chinese hamster ovary (CHO) cells and is believed to have been introduced through a cell culture nutrient. The virus doesn’t infect humans, but the shutdown cost the company millions in revenue and caused shortages of Cerezyme and Fabrazyme. Production restarted at the plant in September.

Meanwhile, in November, the Food and Drug Administration said it found tiny particles of steel, rubber and fiber in finished vials of Cerezyme, Fabrazyme, Myozyme, Aldurazyme (mucopolysaccharidosis I) and Thyrogen. These and other violations are outlined in a 483 that was issued by FDA following inspection of the troubled facility.

The deal with Hospira, which makes drug and medication delivery systems,calls for the initial term to expire on Dec. 31, 2015. There are options for a two-year extension. The financial terms of the agreement were not disclosed. The deal is still subject to regulatory approval for manufacturing the products.

While GMP deviations and warning letters are common place at many biotechnology companies, Genzyme’s ongoing manufacturing problems had potentially grave medical implications. This is because, unlike most of its competitors, Genzyme focuses almost exclusively on the development of orphan drugs. Orphan drugs are used to treat diseases like Gaucher, Fabry and Pompe disease which are rare, afflict relatively small numbers of patient and usually result from genetic mutations. Generally speaking, there is usually only a single manufacturer of orphan drugs. Consequently, manufacturing problems can result in drug shortages which may inhibit access to these life saving drugs. As corny as it may sound, patients with orphan diseases have literally placed their lives in the hands of the drug companies that manufacture these orphan drugs.

Until last year, Genzyme had an outstanding and impeccable reputation and was regularly lauded by the orphan drug community. Unfortunately, its management team lost sight of its original to commitment to quality—a sign that changes may be necessary in the executive suite. Hopefully, the new fill and finish deal with Hospira will eliminate many of the company’s manufacturing problems and Genzyme can restore confidence in its brand!

Until next time....

Good Luck and Good Manufacturing !!!

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