Drug Injury Watch

The FDA Is Not Ready For Federal Preemption Of Lawsuits Involving Drugs And Medical Devices

2008-07-18T14:03:00-04:00

Something Old And Something New: Two Items From July 3, 2008 NEJM Show Why Preemption Applied In These Types Of Cases Is Bad Public Policy

(Posted by Tom Lamb at DrugInjuryWatch.com)

We start with the something "old", which only goes back in time a few months.

In March 2008 William H. Maisel, M.D., M.P.H., wrote a "Perspective" piece The New England Journal of Medicine (NEJM), "Semper Fidelis — Consumer Protection for Patients with Implanted Medical Devices", in which this expert on medical device safety at Boston's Beth Israel Deaconess Medical Center said that the Medtronic Sprint Fidelis recall was a prime example of how medical device companies and the FDA failed to provide the public with timely information about device malfunctions.

In the July 3, 2008 edition of the NEJM there was a Correspondence exchange between Daniel G. Schultz, of the FDA, and Dr. Maisel about this Sprint Fidelis recall piece.

For those interested in how the FDA is doing as regards its oversight of medical devices you may want to read this brief July 2008 exchange, entitled "Medical-Device Safety and the FDA".

Now we move on to the "new" and more obvious item from the July 3 NEJM, simply titled "Why Doctors Should Worry about Preemption", a Perspective piece by Gregory D. Curfman, M.D., Stephen Morrissey, Ph.D., and Jeffrey M. Drazen, M.D.

This July 3 NEJM Perspective article starts by setting the stage:

A leading drug company may be poised to win a landmark legal victory next fall. If the drug manufacturer, Wyeth, prevails in a case soon to be argued before the U.S. Supreme Court (Wyeth v. Levine), drug companies could effectively be immunized against state-level tort litigation if their products that have been approved by the Food and Drug Administration (FDA) are later found to be defective.

A medical-device company won such a victory in April. In Riegel v. Medtronic, the Supreme Court determined that a product-liability lawsuit against Medtronic in a state court was preempted because the device had received FDA approval. Preemption is a legal doctrine based on the supremacy clause of the U.S. Constitution, which states that when federal and state laws are at odds, federal law takes precedence. Its application to state tort litigation is a radical extension of its original meaning. (footnotes omitted)

And as for the answer to the issue raised by Curfman, Morrissey, and Drazen in the title of their piece:

Why should doctors be concerned about preemption? In stripping patients of their right to seek redress through due process of law, preemption of common-law tort actions is not only unjust but will also result in the reduced safety of drugs and medical devices for the American people. Preemption will undermine the confidence that doctors and patients have in the safety of drugs and devices. If injured patients are unable to seek legal redress from manufacturers of defective products, they may instead turn elsewhere.

In addition to the well-reasoned text, there is an interactive graphic "Timeline of Safety Problems Associated with Four Drugs"which accompanies this July 3 NEJM Perspective article.

My position before and after reading this NEJM article by Curfman, Morrissey, and Drazen is that application of the federal preemption doctrine to personal injury or wrongful death lawsuits concerning unsafe drugs and defective medical devices is bad public policy.

What do you think?

FDA Needs To Assure Us That There Is Quality Control For Generic Medications Sold In U.S.

2008-07-15T12:33:05-04:00

In Wake of "Double-Dose" Digitek Pills And ETHEX Morphine Tablets Being Recalled, Drugmaker Ranbaxy Faces Allegations About Fake Data As Regards Quality Of Its Generic Drugs

(Posted by Tom Lamb at DrugInjuryWatch.com)

A July 15, 2008 article, "Ranbaxy denies any misconduct", published by The Star-Ledger put scrutiny on one generic drug manufacturer and raises the concern, more generally, that the FDA has not been monitoring the quality control of generic medications that are used daily by an increasing number of Americans.

We start with the recent allegations being made against the Indian pharmaceutical giant Ranbaxy Laboratories, which manufactures drugs at 11 sites around the globe and had global sales of $1.6 billion last year. From the July 15 Star-Ledgerarticle we get these points regarding this Ranbaxy generic drug investigation:

In a July 3 court filing, prosecutors said "reliable sources and supporting documents" show Ranbaxy systematically lied about the makeup of its generic drugs, which include a cheaper version of Merck's blockbuster cholesterol pill Zocor. The government alleged Ranbaxy used unapproved ingredients and diluted amounts of ingredients in its drugs.

Prosecutors alleged a "pattern of systemic fraudulent conduct" by Ranbaxy, including the fabrication of test data at a plant in northern India and the destruction of documents in an attempt to conceal the ruse from FDA inspectors.

Ranbaxy said its internal audits "will demonstrate that no data manipulation, fraud, or dishonesty occurred" in its regulatory filings with the FDA, according to a response filed late yesterday in U.S. District Court in Maryland.

To show how this Ranbaxy investigation fits in the larger picture when it comes to generic drugs, Star-Ledger staff reporter George E. Jordan developed this background for his July 15 article:

"The most important question is credibility. Once that's lost, its hard to get it back," said Steve Brozak, senior analysts at WBB Securities in Westerfield. "This is a systemic flaw. I'm not picking on Ranbaxy, but if you have one unethical player, it brings into question to entire system."

Ranbaxy denied wrongdoing, but the probe highlights growing concerns about generic drugs around the world.

Earlier this year, Actavis Totowa, the U.S. headquarters of the Icelandic generic drugmaker, recalled the heart medication Digitek because it contained "twice the active ingredient." Actavis and FDA have not explained how the pills landed on the market.

For those of you not familiar with the "double-dose" Digitek pills that were recalled by Actavis Totowa in April 2008, here are some of our past posts about that still-evolving story:

Digitek Digoxin Recall: Tablets May Be Double The Normal Dose

Digitek Update May 2008: When Old News Is Better Than No News At All

Another "Double-Dose" Pill Problem Demonstrates How And Why The Digitek Recall Is So Unusual

Mylan's Corporate Motto, Actavis On The Meaning Of GMP, And Who Is Ultimately Responsible For The Digitek Fiasco

As you can see from that list, there was not just one but two instances where generic pills were mis-manufactured by different drug company, the first being Digitek by Actavis Totowa and the second being ETHEX Corporation's June 2008 recall of its generic morphine sulfate extended release tablets. In both instances those defective pills were dispensed to unsuspecting patients in the U.S. instead of being found upon inspection and destroyed by the company or the FDA.

With a criminal investigation of Ranbaxy underway, one wonders whether federal prosecutors are looking at the conduct of Actavis as regards Digitek and ETHEX for its morphine tablets. Further, perhaps the existence of such an investigation by prosecutors is the reason why we have heard little in terms follow-up from Actavis and ETHEX about the extent of their "double-dose" pill manufacturing problems in terms of date ranges and estimated number of pills involved.

Given this Ranbaxy - ETHEX - Actavis trilogy, one must ask: Where is the FDA on taking steps to ascertain that Good Manufacturing Practices (GMP) are being adhered to so that our nation's supply of FDA-approved generic drugs is safe?

Will There Be An Avelox - Liver Toxicity Warning Letter From Bayer Coming Soon In The U.S., Or Not?

2008-07-10T17:40:00-04:00

In July 2008 FDA Said Avelox, With Other Antibiotics In Fluoroquinolone Class, Would Add A "Black-Box" Warning For Tendinitis And Tendon Ruptures

(Posted by Tom Lamb at DrugInjuryWatch.com)

On July 8, 2008 the FDA announced that a so-called "black-box" warning would be added to the Avelox (moxifloxacin) package insert, or label, to strengthen existing warnings about the increased risk of developing tendinitis and tendon rupture. At the same time, the FDA announced similar action for these other antibiotics in the fluoroquinolone class of drugs:

Ciprofloxacin (marketed as Cipro and generic ciprofloxacin)
Ciprofloxacin extended release (marketed as Cipro XR and Proquin XR)
Gemifloxacin (marketed as Factive)
Levofloxacin (marketed as Levaquin)
Norfloxacin (marketed as Noroxin)
Ofloxacin (marketed as Floxin and generic ofloxacin)

While reading through some of the material that the FDA made available online in connection with this July 2008 label change for these fluoroquinolone antimicrobial drugs, I found the following:

Fluoroquinolones, like any drug, have possible side effects associated with their use. Rarely, some side effects may be serious or even fatal; however, most of the risks are mild. Some of the most serious side effects include seizures, hallucinations, depression, heart rhythm changes (QTc prolongation and torsade de points), and intestine infection with diarrhea. Rarely, damage to the liver, kidneys or bone marrow, and changes to blood sugar may occur. (Emphasis added.)

This last sentence brought to mind the February 2008 "Dear Doctor" letter about Avelox / Avalox that Bayer sent out in Europe, which was reportedly intended to emphasize a 2007 label change Bayer made in Europe about, in part, severe and possibly fatal liver toxicity.

I concluded my February 2008 article about this Avelox letter that Bayer sent to doctors in Europe, only with this remark:

We will watch for any similar Avelox "Dear Doctor" letter from Bayer here in the U.S.

So where is the corresponding letter to health care providers in the U.S. from Bayer about Avelox and its association with liver toxicity?

Further, is the FDA looking at Avelox specifically for serious side effects such as drug-induced hepatitis and liver failure, which seem to be unique to this antibiotic among the fluoroquinolones?

If you have any insight concerning what is going on with Bayer or the FDA about serious adverse reactions to Avelox involving liver toxicity -- ranging from hepatitis to liver transplant -- there are some of us who are curious.

I would like to hear about what you know regarding this Avelox safety issue. Of course, I will share that information with our readers; our "source" can choose, however, to remain anonymous (like over at the Cafepharma Message Boards) or not. Send me an email or submit a Comment, below. Thanks.

New York Doctors Find One Type Of Femoral Stress Fracture Is Possible Fosamax Side Effect

2008-07-08T11:31:16-04:00

Irish Doctors, Meanwhile, Dispute Warnings About Bisphosphonate-Induced Osteonecrosis Of Jaw (BONJ) Being Linked To Fosamax

(Posted by Tom Lamb at DrugInjuryWatch.com)

In late June 2008 we learned about a new bone-related side effect that may be caused by long term use of the popular bisphosphonate Fosamax.

From a June 26, 2008 press release, "Some Patients Using Fosamax Over the Long-Term May Be at Risk for One Type of Fracture", issued by NewYork-Presbyterian/Weill Cornell Medical Center, we get this summary of the new Fosamax study and its results:

The preliminary study followed 70 patients, 25 of whom were taking alendronate (Fosamax) for an average of five years. Among those receiving the therapy, 19 patients (76 percent) presented with one type of femoral stress fracture (simple, transverse) that resulted from little or no trauma. By comparison, the fracture type was only evident in one patient (2 percent) not receiving the therapy.

This newest Fosamax study and its findings are reported by Drs. Dean G. Lorich and Joseph M. Lane of NewYork-Presbyterian Hospital/Weill Cornell Medical Center in the latest issue of the Journal of Orthopaedic Trauma.

This observation comes from Dr. Lorich, the study's senior author:

While bisphosphonates like Fosamax have been proven to successfully treat osteoporosis and other metabolic bone disease, we believe long-term use of these drugs may suppress the ability of bones to heal in some patients. As a consequence, patients with routine stress fractures are unable to properly heal, and minor damage can worsen until a serious fracture occurs.

And some practical guidance from Dr. Lane, the study's corresponding author:

While more research is necessary to confirm our results, physicians prescribing bisphosphonates for longer durations should monitor patients for indications of bone regeneration. In situations where a blood test reveals low bone turnover, a holiday from the bisphosphonates would be recommended until these markers return to an acceptable level.

Meanwhile, what seemed to be a generally accepted association between osteonecrosis of the jaw (ONJ) and oral bisphosponates like Fosamax is being contested by some Irish doctors.

A July 8, 2008 article, "Specialists play down risk of jaw condition", published by The Irish Times, reports about an editorial in the current issue of the Irish Medical Journalwhich asserts that the risk of developing bisphosphonate-induced osteonecrosis of the jaw (BONJ) as a side effect of taking bisphosphonates is "very small".

To start, the July 8 Irish Times article gives us this background information:

The Irish Medicines Board (IMB) issued a warning last January about the drug. "Osteonecrosis of the jaw continues to be reported as a suspected adverse drug reaction associated with bisphosphonates and the number of reports appear to be increasing, particularly for the most potent bisphosphonates," it said in a statement.

Next, the Irish newspaper article provides us with some points raised in this Irish Medical Journaleditorial about the ONJ - bisphosphonate link:

Dr John Carey, consultant rheumatologist at University Hospital Galway (UHG) and his colleagues say: "The weight of evidence from randomised control trials, and large observational studies with appropriate control groups does not support an increased risk of osteonecrosis of the jaw in persons treated with bisphosphonates for osteoporosis. This implies that there is either no increased risk, or if there is, it is likely very small."...

Dr Carey and his colleagues say doctors should reassure patients that the risk is small. "As with everything we do, risk should be put in perspective: the risk of developing the condition would seem to be much less than the lifetime risk of dying on a plane (1:5,000) . . ."

According to this Irish Times article, the various bisphosphonates available in Ireland are marketed under the brand names Fosamax, Osteomel, Bonefos, Didronel, Bonviva, Actonel, and Aclasta.

We will continue to watch for developments concerning the safety of Fosamax as well as other bisphosphonates, and report any significant findings.

Sprint Fidelis Litigation Update: 225 Lawsuits Filed In State Courts And Federal MDL As Of June 2008

2008-07-03T10:20:04-04:00

Medtronic Wants Court To Reject All Injury And Death Cases Based On Riegel Preemption Ruling; Federal MDL Motion To Dismiss Hearing Scheduled For November 2008

(Posted by Tom Lamb at DrugInjuryWatch.com)

A July 3, 2008 online article, "MEDTRONIC: Faces Pending 225 Suits Over Recall of Fidelis Leads", published by Lloyd's Corporate Litigation Reporter, gives us this update on the number of Sprint Fidelis lawsuits that have been filed, and where:

Approximately 225 lawsuits in relation to Medtronic Inc.'s Oct. 15, 2007 voluntarily suspension of the worldwide distribution of its Sprint Fidelis family of defibrillation leads have been filed
against the Company, as of June 19, 2008.

About 33 of the lawsuits are putative class action suits reflecting a total of approximately 600 individual personal injury cases....

Approximately 73 of the lawsuits have been filed in state court, generally alleging similar causes of action. Of those state court actions, approximately 65 are consolidated before a single judge in Minnesota state court. The federal court cases have been consolidated for pretrial proceedings before a single federal judge in the U.S. District Court for the District of Minnesota pursuant to the MDL rules. The MDL court held its first appearance on May 28, 2008, and the Court has since entered an Order staying all discovery pending the outcome of a Nov. 4, 2008 hearing on Medtronic's motion to dismiss the complaints.

The November 4 hearing has to do with Medtronic's motion to dismiss based on the U.S. Supreme Court's ruling in the Riegel v. Medtronic case, wherein the medical device manufacturer was granted immunity against legal liability for any injury or death caused by another Medtronic product based on the doctrine of preemption.

There is proposed legislation which would serve to reverse the Riegel decision that has been introduced in the House of Represenatives and is expected to be introduced in the Senate after the July 4th recess.

We will watch for legislative developments regarding these two new federal bills that would protect the legal rights of patients who have been injured or killed by a defective and unsafe medical device, such as the Medtronic Sprint Fidelis lead wires, which were the subject of an FDA Class 1 recall in October 2007.

Permax Update: Two June 2008 Medical Journal Articles Link Permax To Valvular Heart Disease, Again

2008-06-30T18:01:00-04:00

Reports Of Heart Valve Damage In 2007 Gave Rise To Permax Recalls In U.S. And, Later, In Canada; What About Dostinex, Which Had Similar Reports?

(Posted by Tom Lamb at DrugInjuryWatch.com)

In January 2007 the New England Journal of Medicine (NEJM) reported on studies that showed Permax and Dostinex significantly increased the risk of developing heart-valve damage.

Several months afterwards, in March 2007, the FDA was able to get the drug company responsible for Permax to issue a voluntary recall of Permax, a Parkinson's disease drug.

A bit later, in August 2007, Permax was ordered off the market by Health Canada.

Since then, with the drug being withdrawn in the U.S. and Canada, we have not heard much about Permax.

In June 2008, however, two new medical journal articles about Permax and and its connection to valvular heart disease were published.

One new article about Permax and valvular heart disease was published in the June 16, 2008 edition of the Journal of Neurology. It was written by several French doctors who wanted to further develop the association between Permax (pergolide) and heart-valve damage by conducting a case-control study intended to estimate the frequency and severity of Permax-induced valvular heart abnormality and the possible reversibility of that abnormality after the Permax was withdrawn.

We get these study results from an Abstract for this first June 2008 article, "Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.":

RESULTS : Compared to controls, aortic regurgitation (OR: 3.1; 95 % IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95 % IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n = 2.4 +/- 0.7) and the sum of regurgitation grades (n = 2.8 +/- 1.09) were higher (p = 0.008 and p = 0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40 %) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p = 0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.

A second new Permax report, this one out of Australia, is about a woman who developed moderate to severe mitral and aortic valve insufficiency, which required semi-urgent double-valve replacement, after taking a low-dose of Permax for about five years.

The Abstract for this June 2008 article, "Valvular heart disease associated with taking low-dose pergolide for restless legs syndrome.", includes this remark:

Valvular heart disease is associated with the use of dopamine agonists for the treatment of Parkinson's disease and obesity, typically at much higher doses.

Meanwhile, Pfizer's Dostinex (cabergoline) remains on the market despite the January 2007 NEJM reports that Dostinex, like Permax, was linked to valvular heart disease.

We are interested in hearing about, or from, patients who developed any valvular heart abnormality while using Dostinex.

Newly Introduced Legislation Would Protect Legal Rights of Patients Harmed By Defective Medical Devices

2008-06-27T14:54:27-04:00

Bills Sponsored By Waxman And Pallone In The House As Well As Kennedy And Leahy In The Senate Would Right The Wrong Of Riegel Decision By U.S. Supreme Court

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 26, 2008 Congressmen Henry Waxman (D-Calif.) and Frank Pallone (D-N.J.) along with 62 bipartisan supporters introduced HR 6381, the Medical Device Safety Act of 2008.

We previewed this new Congressional bill regarding preemption in our post, "Court's Riegel Preemption Ruling Would Be Negated With Bill Sponsored By Democrats In Congress", a couple of weeks ago.

Further, it is expected that soon after the upcoming July 4th Congressional recess there will be a companion bill introduced by Senators Ted Kennedy (D-Mass.) and Patrick Leahy (D-Vt.).

The same day that this Waxman-Pallone preemption bill was announced, the consumer advocacy group Public Citizen issued a press release, "Bills Would Restore Rights Of Patients Injured By Faulty Medical Devices", from which we get this perspective:

The Medical Device Safety Act of 2008 would overrule the U.S. Supreme Court's February decision in Riegel v. Medtronic, which held that the 1976 federal law that gives the Food and Drug Administration (FDA) authority to regulate medical devices also severely limits the right of injured patients to sue device manufacturers....

"The possibility of being held liable for injuries their products cause creates an invaluable incentive for manufacturers to make their products as safe as they can, to revise labels as soon as they become aware that they are inadequate and to remove unsafe products from the market," said Public Citizen lawyer Allison Zieve, who argued on behalf of the Riegels in Riegel v. Medtronic. "By eliminating this possibility, the Supreme Court decision removed a significant layer of consumer protection, which makes passage of the Medical Device Safety Act of 2008 so essential."...

"Given the FDA's failure to prevent numerous medical device tragedies in recent years, the continued availability of common-law remedies is essential," Public Citizen President Joan Claybrook said.

The thoughts expressed by Ms. Zieve and Ms. Claybrook in the June 26 Public Citizen press release were similar to some testimony that the House Committee on Oversight and Government Reform heard at a May 14, 2008 hearing, where the main issue was whether FDA regulations should preempt, and thereby prohibit, state law product liability claims involving prescription drugs and medical devices approved by the FDA.

At that May 2008 Congressional hearing David Vladeck, a professor at the Georgetown University Law Center, said the Riegel decision "takes away the manufacturer's incentive to protect the public by preventing or correcting errors as soon as they become manifest." Professor Vladeck went on to state that patients who were implanted with defective Guidant Corporation defibrillators, for example, would not be allowed to file any claim for legal compensation due to the Riegel decision -- a situation about which Vladeck said, "That just isn't right. That's not the way we do things in this country."

We will monitor developments in the House concerning this Medical Device Safety Act of 2008 (HR 6381) and watch for the companioin bill expected to be introduced soon in the Senate by Senators Kennedy and Leahy.

As always, we welcome any and all opinions about this issue of federal preemption in the context of drug injury and medical device litigation. You can submit your Comment, below.

P.S. We have learned that Congressman Waxman wrote a June 26, 2008 letter to FDA Commissioner Andrew von Eschenbach, requesting certain agency documents about preemption written since January 20, 2001, including those documents related to the FDA’s intervention in specific drug injury product liability cases. (6/28/08)

Mylan's Corporate Motto, Actavis On The Meaning Of GMP, And Who Is Ultimately Responsible For The Digitek Fiasco

2008-06-23T07:55:00-04:00

FDA Statement Suggests Actavis Will Be Held Accountable For The Defective Digitek Pills, And Mylan Maintains That This Is Not My(lan) Problem

(Posted by Tom Lamb at DrugInjuryWatch.com)

When considering where things stand with the Digitek recall, there are a few items that seem noteworthy for various reasons.

We'll set the stage with an April 25, 2008 press release from Actavis which first announced and explained the Digitek recall:

Morristown, NJ, 25 April, 2008 - Actavis Totowa LLC, a United States manufacturing division of the international generic pharmaceutical company Actavis Group, is initiating a Class 1 nationwide recall of Digitek (digoxin tablets, USP, all strengths) for oral use. The products are distributed by Mylan Pharmaceuticals, Inc. under a "Bertek" label and by UDL Laboratories, Inc. under a "UDL" label.

The voluntary all-lot recall is due to the possibility that tablets with double the appropriate thickness may have been commercially released. These tablets may contain twice the approved level of active ingredient than is appropriate.

From there we provide a hint about Mylan Pharmaceuticals' position on the defective "double-dose" Digitek pills, which could be based on this corporate motto found on their web site (PDF image no. 4):

The company's success can be attributed to... upholding its founding corporate motto: "We either do it right or we don't do it at all."

Next comes Actavis, which manufactured the Digitek "tablets with double the appropriate thickness". On their web site Actavis tells us how drugs like Digitek should be made with this Q-and-A about the industry standards for manufacturing prescription drugs:

What does “Good Manufacturing Practices” (GMP) mean?

GMP is a regulatory guideline imposed on all manufacturers of pharmaceuticals in order to ensure compliance with quality standards such as the pharmacopeia standards, the marketing authorisation and other applicable regulatory requirements in order to ensure the quality, efficacy and safety of pharmaceuticals.

Now let's look at a more serious issue, that of accountability and liability for those defective Digitek pills. Who is the responsible party, Actavis or Mylan or both?

According to a June 12, 2008 article, "Families Suing Mylan For Medication Mistake", published by The State Journalin Charleston, West Virginia, Mylan is pointing the finger at Actavis:

Mylan Spokesman Michael Laffin said the company has a policy to not comment on pending litigation. However, following Actavis' recall announcement, he said Mylan released the following statement:

"Patient safety has always been of utmost concern for us at Mylan. We have been working with the FDA to ensure that our customers are aware of Actavis Totowa's recall of Digitek. Digitek is manufactured by Actavis and distributed by Mylan. Actavis, as the manufacturer, initiated the recall, and our expectation is that Actavis is responsible for all costs associated with it, including litigation costs. Digitek represents a very small portion of Mylan's global product portfolio."

Mylan's current position may or may not prove to be true as regards liability in civil lawsuits filed on behalf of people injured by the defective Digitek. There are indications, however, that the FDA agrees with Mylan as regards accountability in the regulatory arena.

The following is taken from "CDER’s Compliance Office Highlights Manufacturer Accountability", which was part of the June 17, 2008 FDAnews Drug Daily Bulletin:

As the FDA prepares its response to a senator’s question on how best to hold drugmakers accountable for drug quality, CDER’s Office of Compliance is highlighting the agency’s efforts to examine the drug supply chain, reiterating regulations that the NDA holder is responsible.

“Ultimately the dosage form manufacturer with its name on the label is responsible,” the Office of Compliance said. “Our regulatory structure under the [Food, Drug and Cosmetic] Act, and implementing regulations, provide for the identity, strength, quality and purity of the drug and the prohibited acts provide for civil sanctions and criminal penalties for failure to do so.” ...

Sen. Sherrod Brown (D-Ohio) asked CDER Director Janet Woodcock how best to hold pharmaceutical manufacturers accountable for lapses in drug quality as a follow-up to a Senate hearing on the heparin contamination. During that hearing, Woodcock testified that the best means for ensuring product quality is to hold industry accountable for selling contaminated product.

Since the time when this Digitek recall was announced in late April 2008 there has been not much, if any, information released by Actavis, Mylan, nor the FDA about what went wrong, and when, at the Actavis Totowa manufacturing plant in New Jersey.

Once the cause and extent of the Digitek manufacturing problem are determined the Actavis, Mylan, and the FDA, that information should be made public. Likewise, the FDA should tell us when it takes regulatory action -- civil sanctions and/or criminal penalties? -- concerning this Digitek recall and whether it is against Actavis or Mylan or both.

FDA Staff Wants Amgen To Add Stronger Warning About Enbrel Side Effects In Children

2008-06-18T10:53:31-04:00

June 2008 Staff Report Cites Cancers, Infections, And Neurological Problems Similar To Serious Side Effects In Adults

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 16, 2008 the FDA released a staff report, "Enbrel (etanercept) for the Treatment of Pediatric Plaque Psoriasis", which was prepared for the Dermatologic and Ophthalmic Drugs Advisory Committee's June 18, 2008 meeting.

In part, that FDA advisory committee will consider whether or not Amgen Inc. -- which markets Enbrel with Wyeth -- should be permitted to promote Enbrel for use by children with moderate to severe forms of the skin condition psoriasis. At present, Enbrel is prescribed to treat psoriasis in children on an "off-label" basis, which means that the FDA has not approved Enbrel for that type of use but doctors are allowed to prescribe it to children with psoriasis when using their medical judgment.

According to a June 16, 2008 Reuters article, "UPDATE 2-Amgen's Enbrel in kids 'concerning'-FDA staff", by reporter Susan Heavey:

Regardless of whether the regulators approve the new use, FDA staff reviewers recommended the agency strengthen the drug's label to include reports of serious side effects in children that could lead to deaths or hospitalizations....

FDA safety reviewers looked at 949 reports of serious complications in children ages 4 to 17 taking Enbrel, or etanercept, for psoriasis as well as arthritis.

Among them, 61 reports were for psoriasis patients, according to the documents. No deaths were reported, but five patients were hospitalized.

Overall, the FDA found 14 deaths and 76 other life-threatening cases. Complications included serious infections as well as seizures and anemia.

"Given that the drug usage in pediatric population is estimated to be fairly small at this time, the numbers and types of post-marketing adverse events reported are concerning," the reviewers wrote.

The FDA staff who prepared this June 2008 report will present their findings to the Dermatologic and Ophthalmic Drugs Advisory Committee which, in turn, will make a recommendation to the FDA about whether or not Enbrel should be approved for the treatment of psoriasis in children.

As we reported recently, the FDA also is investigating whether Enbrel, along with rival products Johnson & Johnson's Remicade and Abbott Laboratories Inc's Humira, are linked to cancer in children.

According to the June 16 Reuters news article:

FDA reviewers found seven cases of cancer in children taking Enbrel, and two cases were reported in an Amgen study, according to the documents released on Monday.

We will watch for the advisory panel's recommendation about whether Enbrel should be used for pediatric psoriasis and for developments in the FDA's investigation about whether Enbrel, Humira, and/or Remicade are linked to cancer in children.

ETHEX Corporation Expands Its Voluntary June 2008 Recall Of Morphine Sulfate Extended Release Tablets

2008-06-16T09:58:24-04:00

Recall Now Covers 30 mg And 60 mg Tablets Made During June 2006 To May 2008 Period Due To The Potential For Oversized Tablets

(Posted by Tom Lamb at DrugInjuryWatch.com)

As we reported recently, on June 10, 2008 the FDA issued a MedWatch Email Alert, "Morphine Sulfate 60 mg Extended Release Tablets - Recall of a Single Lot Due to a Report of a Tablet With Twice the Appropriate Thickness". At that time, the ETHEX Corporation seemed to think that its manufacturing problem was limited to the period April 16 to April 27, 2008 and restricted to 60 mg tablets, only.

A few days later, however, ETHEX greatly expanded their morphine pill recall as detailed in the company's June 13 Press Release:

ETHEX Corporation announced today that it has voluntarily recalled specific additional lots of morphine sulfate 60 mg extended release tablets, and specific lots of morphine sulfate 30 mg extended release tablets, as a precaution, due to the possible presence of oversized tablets. Oversized tablets may contain as much as two times the labeled level of active morphine sulfate. The recalled lots were distributed by ETHEX Corporation under an “ETHEX” label between June 2006 and May 2008. The lot numbers involved in the recall are:

Morphine Sulfate ER 30mg Tablet/NDC # 58177-320-04: Lots 75090, 77846, 77847, 80048, 83320, 89661, 89665, 90252 through 90258, and 93284

Morphine Sulfate ER 60mg Tablet/NDC # 58177-330-04: Lots 91762 (previously reported), 75091, 75092, 77848 through 77851, 82517, 82518, 83333, 83817, 83862, 84111, 84112, 84315, 84900, 85326, 85335, 85807, 86270 through 86276, 87723, 87939, 88007, 89083, 89668, 89669, 89821, 90260 through 90272, and 91763 through 91765.

Whereas previously this ETHEX morphine pill recall seemed to be narrow and specific, it now appears that the ETHEX recall may be more like the Digitek problem, where Actavis issued a recall for all lots of its generic digoxin pills manufactured from March 2006 to April 2008.

Returning to the ETHEX June 13 Press Release, there are indications that the drug company is still struggling to determine how and when the manufacturing process was such that oversized tablets were being produced and released:

The voluntary recall follows a report that a tablet with as much as double the appropriate thickness was identified in a previously recalled lot. No oversized tablets have been identified in any additional distributed lot of these products and, based on our investigation, there are likely to be few, if any, oversized tablets in the recalled lots. The decision to recall the additional lots listed above has been taken as a responsible precaution because of the possibility that there may be oversized tablets in those lots.

If any patients or their families have questions about this June 2008 morphine sulfate tablet recall, they can call ETHEX Customer Service (800-321-1705) or, if more appropriate, they can contact their doctor, the dispensing pharmacy / pharmacist, or some other health care provider.

We will continue to monitor developments concerning this ETHEX recall of morphine pills.