DID - Aug. 21, 2009 Issue

Vol. 8 No. 163

U.S. Supreme Court Asked to Take Patent Decision Out of Juries’ Hands

The U.S. Supreme Court has been asked to take juries out of the decisionmaking process when the court is deciding whether a patent should be invalidated because of obviousness.

The precedent was set on patent cases that center on obviousness in the U.S. Court of Appeals for the Federal Circuit. The court took the position that lay juries can render verdicts that preclude independent judicial determination of the ultimate question of patent validity.

In a case that could well apply to drug patents, devicemaker Medela is petitioning the Supreme Court to determine that a judge, not a lay jury, should decide whether a patent is obvious, in an Aug. 13 petition.

“A person accused of patent infringement has no right to independent judicial, as distinct from lay jury, determination of obviousness,” Medela says in its Aug. 13 petition. It holds that this precedent is incorrect.

Dennis Crouch, an associate professor of law at the University of Missouri School of Law, told DID Thursday, “Because obviousness is a question of law, there is a potential that appeals on obviousness could become one of the most frequently appealed issues. This result makes sense in some ways — since nonobviousness is really the core element of invention.”

The Federal Circuit has held that a court review of a jury verdict is limited to “re-creating facts that ‘may have been found’ by the jury” and determining whether there was an allowable legal rationale that the jury might have used in reaching its conclusion. This precedent conflicts with decisions by the 7th and 9th Circuits, which have held that judges must independently decide whether facts lead to a legal conclusion of obviousness, according to the petition.

The company, which makes postnatal supplies, points to a federal study on patent system reform that identifies “excessive reliance on juries as a ‘serious threat to the patent system.” It adds that using juries to determine validity issues “generat[es] the greatest amount of public concern,” according to court documents.

The Federal Circuit’s position conflicts with Supreme Court precedent on obviousness, Medela asserts. “For more than four decades, this Court has held that ‘the ultimate question of patent validity is one of law,’” the company says in its petition. The Supreme Court’s April 2007 decision in KSR International Co. v. Teleflex Inc., et al. underscores this point, stating that an obvious analysis was to be conducted by courts or patent examiners, Medela adds.

However, under Federal Circuit procedures, “the entire ‘analysis’ of obviousness can consist of a jury’s ‘yes’ or ‘no’ answer to the legal question whether an asserted patent claims was ‘proven’ to have encompassed ‘obvious’ subject matter by ‘clear and convincing evidence,” Medela says.

Andrew Berdon, partner at Quinn Emanuel Urquhart told DID in 2007 that obviousness arguments based on the KSR decision are bound to turn up more and more in generic patent challenge suits. “Everyone is looking to see how KSR may improve the law of the land in their invalidity cases,” he said.

If Medela were to prevail in this case, it would have a major impact and likely would tend to favor defendants, Crouch said. 

“Jury deliberations on obviousness tend to be seen as something of a black box,” Crouch added. “Juries return a verdict but provide little or no indication of the process they used to reach the decision, leaving the losing parties little grounds for appeal. The procedural fact that juries decide obviousness also tended to limit the litigation impact of the Supreme Court’s 2007 KSR v. Teleflex decision, which lowered the legal standard for finding a patent obvious.

Crouch added that a win by Medela would lead to more summary judgments on the question of obviousness.

The company filed its petition after the U.S. Court of Appeals for the Federal Circuit upheld a decision that it and co-defendants Richard Weston and Blue Sky Medical Group had infringed the ’643 and ’081 patents owned by Wake Forest University, one of the plaintiffs in the case. These patents relate to treating difficult-to-heal wounds by applying suction, according to court documents.

The Appeals Court found in a 2–1 decision that U.S. District Court for the Western District of Texas Judge W. Royal Furgeson was correct in rejecting the defendant’s request for a new trial.

The Appeals Court made its decision in Kinetic Concepts, Inc. et al. v. Blue Sky Medical Group, Inc., et al. Feb. 2. — Elizabeth Jones


FDA Proposes Mandatory Electronic Adverse Event Reporting

The FDA has proposed a rule requiring that drug and biologic manufacturers submit all reports of adverse events electronically, making formal an option that has been on the books since 2000.

The proposed rule will save time and costs, Gerald Dal Pan, director of CDER’s Office of Surveillance and Epidemiology, said in a Thursday conference call with reporters. The rule is scheduled to be published in the Federal Register Aug. 21 and comments are due Nov. 19.

The proposed rule notes that manufacturers will find the most current information on submitting postmarketing safety reports electronically in a Oct. 19, 2005 draft guidance and another draft guidance June 12, 2008. The agency intends to finalize the draft guidance documents in the near future, according to the rule.

Amendments to electronic reporting requirements in the proposed rule will leave substantive aspects of the requirements mostly unchanged, the FDA says. The technical specifications in the drafts will continue to rely on ICH standards.

The proposed rule would not affect what types of incidents must be reported to the FDA. Manufacturers have been submitting reports to the FDA either through its Electronic Submission Gateway or on CD-ROM, digital tape or floppy disk. International Conference on Harmonisation (ICH) standards for data elements and technical specifications are used for the electronic submissions.

If the new rule is put in place, manufacturers, packers, distributors and holders of NDAs, BLAs and related applications will have to obtain a certificate from the FDA to use the electronic gateway under the ICH standards or use a web portal the FDA is developing.

The web portal, which is part of the FDA’s MedWatch Plus Initiative, is intended for small manufacturers or individuals submitting adverse event reports. If it is not ready by the time the rule goes into effect, the agency “will find some way of working with small manufacturers,” Dal Pan said.

The proposed rule for drugs and biologics reporting does not apply to:

  • Reports filed under an IND application;
  • Annual reports for an approved product;
  • Biologic product deviation reports;
  • Reports of fatal complications in blood transfusion and collection; and
  • Certain reports on human cells, tissues and cellular and tissue-based products.

The FDA is no longer accepting comments submitted by email and asks that electronic comments be submitted by using the Federal eRulemaking Portal.

The proposed rule is available at www.fdanews.com/ext/files/2009-19682_PI.pdf. — Martin Berman-Gorvine


Senators Probe GPO Relationships With Manufacturers

Three Senate committees are questioning the way drugmakers do business with hospitals and other healthcare providers.

At the heart of the inquiry are group purchasing organizations (GPOs), seven of which recently received a letter from Sens. Chuck Grassley (R-Iowa), Herb Kohl (D-Wis.) and Bill Nelson (D-Fla.), requesting information detailing their relationships with medical products industries, such as drugmakers, and healthcare providers since Jan. 1, 2005.

The Aug. 11 letter — sent on behalf of the Senate Finance Committee, the Judiciary Committee’s Antitrust Subcommittee and the Special Committee on Aging — specifically asks for:

  • Details of GPO negotiation and administration of group purchasing agreements and contracts;
  • A description of other activities and services the GPO offers its clients;
  • Sources of funding for each activity, including the extent to which a service is paid for by fees collected from manufacturers;
  • A description of all types of payments received from manufacturers and the purpose of the payments;
  • A description of payments received from GPO clients (healthcare providers);
  • Information about sole-source contracts and the circumstances under which they are awarded;
  • Information about negotiations for “bundled” discounts for clients.

The senators request sample copies of contracts and give the GPOs until Sept. 8 to submit the information.

PhRMA declined Thursday to comment on the matter through a spokeswoman. The Generic Pharmaceutical Association and the Biotechnology Industry Organization weren’t available to comment by press time.

The senators’ letter follows discussions Finance Committee staff had with the Health Industry Group Purchasing Association (HIGPA) and several member GPOs in June.

The GPOs, which started as provider-funded cooperatives, were granted a “safe harbor” more than 20 years ago when Congress exempted them from penalties associated with the Medicare anti-kickback statute. Since that time, they have charged the manufacturers administrative fees.

 “There appears to be limited public information about the additional services and activities performed by GPOs and how they are paid for,” the senators say in the letter. “In addition, there is little information about other fees or payments that GPOs may secure from manufacturers, other vendors and suppliers, and distributors in connection with and outside of group purchasing activities, such as product marketing.”

HIGPA President Curtis Rooney says in a statement that the association is reviewing the letter on behalf of its members and looks forward to providing the requested information. He cites two recent studies that found that GPOs save the nation between $36 billion and $64 billion in healthcare costs each year.

“It is also important to note that the health care GPO industry is among the most transparent,” he adds. The association adopted a Code of Conduct Principles in July 2002.

This is not the first time GPOs have been under the congressional microscope. A 2002 Government Accountability Office report noted an increase in administrative fees charged by GPOs and the subsequent cost to Medicare. In 2006, the Antitrust Subcommittee examined the safe harbor provision. And that year, three bills on GPO reform were proposed. — Mari Serebrov


Topical Ibuprofen Earns FDA Warning Letters for Companies

The FDA has issued warning letters to eight companies accused of selling OTC topical drugs containing ibuprofen.

The painkillers contain ibuprofen in combination with other active ingredients and do not comply with the FDA’s OTC drug monograph system that allows some OTC drugs to be marketed without first obtaining agency approval, the FDA says in a statement Thursday.

The FDA has not reviewed claims that topical ibuprofen is a safer alternative to the oral formulation, nor has the agency evaluated what side effects might be associated with such products, the agency says.

“These companies have an obligation to the public to demonstrate to the FDA that their products are safe and effective, and they have failed to do so,” Deborah Autor, director of the office of compliance at CDER, says in the statement.

The companies must stop marketing their unapproved products and tell the agency within 15 business days how they will correct the violations, the agency says in the letters.

Florida-based Geromatrix Health Products, which received one of the letters, was surprised by the FDA’s allegations, Bob Magedoff, the company’s owner, told DID.

“We’re one of 50 companies that sell the same thing, we buy it from a contract manufacturer,” Magedoff said.

The names of the manufacturers and products that received warning letters are:

  • BioCentric Laboratories’ BioEntopic 15% Ibuprofen Creme;
  • Core Products International’s Ibunex Topical Ibuprofen;
  • Geromatrix Health Products’ LoPain AF 15% Ibuprofen Creme;
  • Progena Professional Formulations’ IbuPRO-10 Plus;
  • Progressive Emu’s Emuprofen;
  • Ridge Medical Products’ Profen HP; and
  • Wonder Laboratories’ IBU-RELIEF 12. — David Belian


Pediatric Hiberix Vaccine Wins FDA Approval

The FDA granted accelerated approval to GlaxoSmithKline’s (GSK) Hiberix vaccine against Haemophilus influenzae type B (Hib), which can cause bacterial meningitis, for children age 15 months to 4 years.

The approval will help alleviate a shortage of the vaccine that began in December 2007 following Merck’s voluntary recall and subsequent production suspension of PedvaxHIB (Haemophilus influenza type B) and Comvax (haemophilus influenza type B), two of four vaccines approved for primary and booster immunization against disease associated with HIB.

Merck’s recall of one million doses was due to a sterilization problem in manufacturing (DID, Dec. 13, 2007). The shortage resulted in a recommendation by the Centers for Disease Control and Prevention to temporarily defer the Hib vaccine booster dose for children who were not at high risk for infection. This deferral was in effect from Dec. 18, 2007, through June 25.

Although current vaccine supply is sufficient to reinstate the booster dose and begin catch-up vaccinations, it is not yet ample enough to support mass vaccination of all children whose boosters were deferred, according to an FDA statement this week.

“The FDA approved Hiberix under the agency’s accelerated approval pathway,” Karen Midthun, acting director of the FDA’s Center for Biologics Evaluation and Research, says in a statement. “This approval will provide an additional safe and effective vaccine to help ensure that there is an adequate Hib vaccine supply during necessary catch-up vaccinations.”

Accelerated approval is granted on the condition that clinical trials are continued during the postapproval marketing of the product to verify the anticipated clinical benefit. GSK will conduct a postmarketing study in the U.S. to evaluate the safety and immunogenicity of primary and booster vaccination with Hiberix. — Elizabeth Jones


EMEA Outlines Safety Surveillance Measures for Vaccines

Manufacturers of vaccines against infectious diseases should investigate safety concerns identified before marketing authorization and address the concerns in a risk management plan, the European Medicines Agency (EMEA) says.

If a specific safety concern associated with the vaccination schedule or the target population can be anticipated based on experience with other vaccines, manufacturers also should consider the use of targeted, post-authorization safety studies, the agency says in a guideline posted on its website this week. The guidance is not intended to replace other relevant guidances, the agency says.

The guideline, which is addressed to marketing authorization holders and competent authorities, primarily covers postmarketing safety issues and offers advice to drugmakers on monitoring of safety signals for vaccines used to prevent infectious diseases before or after exposure to pathogens, the EMEA says.

For combined vaccines — two or more vaccine antigens in one pharmaceutical preparation — manufacturers should be aware of the increased frequency and severity of adverse reactions. The reactions associated with the combined vaccine should be compared with those reported with the precursor product, and if appropriate, risk-minimizing strategies should be developed.

If a particular batch of a vaccine is suspected of being linked to adverse reactions, drugmakers should notify the regulatory authority that granted the vaccine’s approval immediately and provide a full assessment of the possible reason for the incident.

It is essential that complete and accurate records documenting the administration of all vaccines, as well as the date of vaccination, product administered, manufacturer, batch number, site, route of administration and a detailed description of the adverse event be provided to regulatory authorities, the EMEA says.

When reviewing spontaneously reported adverse reactions to vaccines, manufacturers should pay particular attention to serious adverse reactions that have not been reported frequently, the EMEA says. Sponsors also should focus on adverse reactions that:

  • May be signs of an immune response;
  • Reflect the clinical picture of the disease for which immunization has been given; and
  • Are unexpected and for which no causal relationship has been found.

The guideline serves as a companion to Volume 9A of the “Rules Governing Medicinal Products” in the EU. — David Belian

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