DID - May 15, 2008 Issue

Vol. 7 No. 96

Von Eschenbach Details Immediate Funding Needs

FDA Commissioner Andrew von Eschenbach says the agency needs an immediate $275 million infusion, including $100 million for drugs, biologics and medical devices, in a May 5 letter to a ranking Senate Republican.

The funding assessment was in response to a request by Sen. Arlen Specter (R-Penn.), ranking member of the Senate Appropriations Subcommittee on Labor. The Senate Appropriations Committee is scheduled Thursday to mark up fiscal 2008 emergency supplemental legislation that, among other measures, includes $265 million in funding that would be available to the FDA through the end of fiscal 2009.

The bill, which has not been introduced, includes $48.5 million for CDER operations and related field activities of the Office of Regulatory Affairs (ORA), and $23.5 million is earmarked for CBER and related ORA activities.

An additional $6 million is slated for the National Center for Toxicological Research, and $21.8 million is dedicated to the FDA Office of the Commissioner, Office of Operations, Office of Scientific and Medical Programs, Office of International and Special Programs, and Office of Policy, Planning and Preparedness.

Von Eschenbach’s funding assessment identified needs for the following appropriations:

  • $45 million for FDA field operations, including inspections;
  • $17 million for obligations under the FDA Amendments Act, including requirements for labeling, clinical trials, active drug surveillance and postmarket study commitments;
  • $15 million for data access and analysis for active postmarketing surveillance and to develop data mining tools to detect safety signals; and
  • $15 million for building a “regulated Product Information Data Warehouse” to enable intelligence sharing with other regulatory agencies.

The commissioner told Specter that the assessment was developed independent of competing budget priorities in the Bush administration.
The FDA told DID that, if authorized, the funding needs identified in von Eschenbach’s assessment would not all be spent during fiscal 2008 and would enable the agency to implement HHS’ Import Safety Action Plan (DID, Nov. 8, 2007).

“These resources will also allow FDA to strengthen its information technology to improve threat assessment, conduct product safety research and analysis, detect product safety and integrity problems and allow more effective targeting of FDA inspection teams,” the FDA told DID.

The letter can be accessed at www.fdanews.com/ext/files/Drug_Industry_Daily/vonEschenbachSpector.pdf.  — Christopher Hollis


Pallone: The FDA Needs User Fees to Ensure Import Safety

Although the pharmaceutical and other industries are concerned about increased user fees included in a draft bill to enhance the FDA’s ability and authority to ensure the safety of imported products, Rep. Frank Pallone (D-N.J.) said the fees would be necessary.

The FDA’s “need is so great, there is going to be a need for user fees in addition to whatever is appropriated,” Pallone, one of the bill’s sponsors and chair of the House Energy and Commerce Committee’s Health Subcommittee, said at Wednesday’s hearing.

The draft bill, co-sponsored by Reps. John Dingell (D-Mich.) and Bart Stupak D-Mich.), is aimed at preventing imports of such unsafe products as the tainted heparin from China that was linked to 81 deaths in the U.S. The draft requires the FDA to inspect all overseas drug-manufacturing plants once every two years instead of continuing its current risk-based approach.

At an earlier hearing on the bill, CDER Director Janet Woodcock said the FDA would need at least $225 million to inspect foreign facilities as frequently as it does domestic sites (DID, May 2).

FDA Commissioner Andrew von Eschenbach recently told lawmakers in a letter obtained by DID that the agency could use $275 million more in fiscal 2008 to allow the agency to implement plans for safer imports, modernize its IT systems and meet other goals (see related story).

Dingell said the hearing was the third and final one on the discussion draft of the Food and Drug Administration Globalization Act of 2008. Pallone said the bill is expected to move to markup in the near future, but he could not specify an exact date.

The text of the bill is available online at energycommerce.house.gov/FDAGlobalAct-08/Dingel_60AXML.pdf. — April Astor


Preemption ‘Will Harm Drug Safety,’ House Committee Told

Allowing unchecked federal preemption of state drug and device liability laws “will harm drug safety,” former FDA Commissioner David Kessler told the House Committee on Oversight and Government Reform Wednesday.

Preemption has been an issue for lawmakers since the Supreme Court’s Feb. 20 ruling in Riegel v. Medtronic, which limits devicemakers’ liability under state laws for products with FDA premarket approval (DID, Feb. 21). A similar drug-related case — Wyeth v. Levine — is scheduled for the court’s term beginning in October (DID, Jan. 22).

Kessler’s view was contradicted by Randall Lutter, deputy commissioner for policy at the FDA, who told the committee that state product liability lawsuits can harm public health by limiting patient and doctor choices, decreasing patient access to beneficial products and increasing confusion over warnings, except where such lawsuits claim the drug or devicemaker failed to meet the conditions of FDA approval.

When questioned by committee Chairman Henry Waxman (D-Calif.) and Rep. Bruce Braley (D-Iowa), Lutter said the FDA has had the same position on preemption since the 1970s.

The problem with the model of preemption the FDA now backs is that the agency cannot comprehensively protect drug and device safety on its own, and removing the threat of state-based lawsuits would reduce pressure on drug- and devicemakers to ensure their products are safe, Kessler said.

The hearing produced sharp partisan exchanges between members of the committee as well as high-profile testimony from actor Dennis Quaid, whose lawsuit against Baxter Healthcare over a heparin overdose his twin children suffered has been challenged on preemption grounds.

Quaid testified that his twin infants were mistakenly given 10,000 units of Heparin instead of 10 units of Baxter’s Hep-Lock product on two occasions in November 2007 due to the similar color and appearance of the labels, a medication error that nearly killed them. Similar errors killed three other infants and severely injured three more in Indianapolis in September 2006.

In his opening statement, Waxman slammed preemption as a “radical legal doctrine being advocated by the pharmaceutical and device industries and the FDA” that would deprive injured patients of the right to seek compensation and would remove “one of the most powerful incentives for safety — the threat of liability.”

Ranking committee member Tom Davis (R-Va.) countered with a call for balance “between total federal preemption and unrestrained litigation of medical claims in 50 state court systems. … Total preemption means dangerous and defective products could hide behind narrowly based FDA findings of safety and effectiveness. Total litigation would raise medical costs, stifle drug and device development and subject both companies and patients to an endless labyrinth of conflicting standards.”

Kessler said he is “not opposed to federal preemption in certain cases, but I think there should be specific criteria governing when it is deemed appropriate.” FDA regulation should preempt state law in any given case only if the agency has taken substantive and definitive action. There is a direct conflict between state and FDA action that would thwart the agency’s ability to achieve its statutory goals and there is a public health reason to favor it, he said.

Preemption’s Effect on Postmarket

“My greatest concern with preemption is that it would, I believe, dramatically reduce the incentives for manufacturers to act quickly and responsibly to detect, analyze, investigate and take action on potentially serious and life-threatening adverse reactions once a drug is on the market,” he added.

This view was backed by most of the other witnesses, including Gregory Curfman, executive editor of the New England Journal of Medicine, who said that “preemption of common-law tort actions against drug and medical device companies is ill advised and will result in less safe medical products for the American people.”

Rep. Mark Souder (R-Ind.) complained that the Democratic majority on the committee had stacked the hearing with eight witnesses opposing preemption while only two backed the Republican view.

Supporting the FDA’s current view was John Calfee of the American Enterprise Institute, who argued that state lawsuits to compensate injured patients amount to using the tort system as if it were an insurance system, “driving up drug prices,” and that counter to the claims of its backers, litigation will not improve information for patients and physicians. — Martin Gidron


Mylan Launches Generic Paxil

Mylan has started marketing its generic version of GlaxoSmithKline’s (GSK) antidepressant Paxil CR, roughly seven months after the firms entered a settlement related to the drug.

Mylan was the first company to file an ANDA containing Paragraph IV certifications for Paxil CR (paroxetine hydrochloride) in 12.5- and 25-mg strengths and has 180 days of marketing exclusivity. It also has the right to market a 37.5-mg version.

After Mylan submitted its ANDA for the drug, GSK initially did not sue. The FDA granted approval for the application last June after the expiration of the pediatric exclusivity associated with the ’723 patent.

But the U.S. Patent and Trademark Office granted GSK a new patent for Paxil CR, the ’640 patent, which was added to the Orange Book. Mylan amended its ANDA to include a Paragraph IV certification for the ’640 patent, prompting GSK to file suit in the U.S. District Court for the District of New Jersey.

The ’640 patent expires in 2016 and covers a controlled-release composition of paroxetine “that reduces the incidence of nausea and vomiting,” according to court records. Under the settlement, the case was dismissed with prejudice (DID, Oct. 24, 2007).

Paroxetine HCl extended-release tablets had U.S. sales of approximately $301 million for the 12 months ending March 31, according to Mylan. — Elizabeth Jones


AstraZeneca Gets One of Five New Indications for Seroquel

The FDA’s approval of AstraZeneca’s Seroquel as an adjunct to lithium or divalproex for the maintenance treatment of patients with bipolar I disorder gives the company one of five potential U.S. approvals for new indications for the product.

The Seroquel (quetiapine fumarate) approval is based on two multicenter, randomized, double-blind, placebo-controlled trials that included a 12–36 week stabilization phase followed by up to two years of randomized, double-blind treatment, according to the company. The primary endpoint was time to recurrence of a depressive, manic or mixed mood event.

Pooled study results indicate that patients treated with Seroquel experienced a reduction of 70 percent for time to recurrence of a mood event compared with those taking placebo. The proportion of patients who relapsed after taking Seroquel was 19.3 percent compared with 50.4 percent of those on placebo, AstraZeneca said.

Earlier this month, AstraZeneca submitted an sNDA for Seroquel XR tablets to treat generalized anxiety disorder, including maintenance of the anti-anxiety effect (DID, May 9).

In January, the company filed two separate sNDAs to the FDA for Seroquel XR to treat manic and depressive episodes associated with bipolar disorder. The following month, it filed an sNDA seeking approval for the treatment of major depressive disorder with the drug as monotherapy, adjunct therapy and maintenance therapy. The FDA is reviewing those submissions.

Global sales of Seroquel in 2007 were $4.02 billion, the company said. — Elizabeth Jones


Sanofi Dealt Another Blow in Lovenox Case

A federal court has upheld a ruling that patents covering sanofi-aventis’ blood thinner Lovenox are unenforceable due to inequitable conduct.

The decision stems from the ruling in the U.S. District Court for the Central District of California that Aventis intended to deceive the U.S. Patent and Trademark Office (PTO) by withholding information when it filed an application for the ’618 patent covering Lovenox (enoxaparin sodium injection).

Aventis owns two patents covering Lovenox, the ’743 and the ’618 patents, both of which cover a composition comprising low molecular weight heparins. The ’618 patent was surrendered when the other patent, which expires in 2012, was issued. (Aventis later became part of sanofi-aventis, which markets the drug.)

Amphastar Pharmaceuticals and Teva Pharmaceuticals each filed ANDAs with Paragraph IV certifications to gain approval for generic versions of Lovenox. Aventis subsequently sued both drugmakers in the California district court.

After the court found against Aventis, the drugmaker appealed to the U.S. Federal Court of Appeals for the Federal Circuit, which concluded that the withheld information prevented the examiner from considering information relevant to the patent in question. It also ruled that the district court erred in finding intent to deceive on summary judgment and remanded the case, according to court documents.

The district court held a bench trial limited to the issue of intent and found that the  ’743 and the ’618 patents were unenforceable due to inequitable conduct. Sanofi-aventis again appealed to the U.S. Federal Court of Appeals for the Federal Circuit, which affirmed the lower court’s decision. 

In his dissent, Judge Randall Rader, says, “My reading of our case law restricts a finding of inequitable conduct to only the most extreme cases of fraud and deception.”

Lovenox had sales of approximately $4 billion last year, according to sanofi.— Elizabeth Jones

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