In the Field

REGULATION

Patent Reform Moving Ahead, Industry Impact Expected

The United States House of Representatives passed its version of the Patent Reform Act of 2007 (H.R. 1908) in September in a 220-175 vote. Although the bill aims to fix current flaws in the US patent system and to bring it in line with those of other countries' systems, the biopharmaceutical industry is largely unhappy with the news, arguing that it will reduce patent protection.

"BIO appreciates the continued efforts by the House to improve the Patent Reform Act, but unfortunately cannot support the legislation passed today as it threatens continued biotechnological innovation," said Jim Greenwood, president and CEO of the Biotechnology Industry Organization (BIO), in a Sept. 7 statement. "We welcome improvements to the US patent system, particularly those that increase patent quality, increase public participation, and provide additional resources to the Patent and Trademark Office. However, the legislation that passed and the legislation currently pending in the Senate [S. 1145] do far more harm than good to our nation's patent system."

Some companies claim the legislation may impose some of the most significant changes to the US patent system in 50 years. Specifically, the Patent Reform Act of 2007 would grant patents to the first to file, rather than the first to invent. Currently, the US is the only country that grants patents to the first to invent.

The bill would also change how damages are calculated—including no longer considering the full value of a product. The biopharmaceutical industry is concerned that this change, along with the bill's post-grant review policy—which allows only one opportunity to challenge a patent, will make it more difficult for inventors to prove willful infringement on patent claims, according to a Sept. 7 Associated Press article.

This change would open the door to "an endless loop of legal challenges after patents are awarded," according to United Steelworkers, a union that includes 15,000 US workers in the pharmaceutical industry. The AFL-CIO union federation is also opposed to the legislation and sent a letter to Congressional representatives, arguing that the reforms, as they were written, would damage the industry.

Additional patent changes announced by the US Patent and Trademark Office (USPTO) on Aug. 21 will go into effect Nov. 1. The new rules limit the number of continuation applications and the number of claims an applicant can file in a single application. They also state that certain multiple applications may be treated as a single application. According to USPTO, the changes will provide for "better and more thorough and reliable examination of patent applications."

Both the USPTO changes and the Patent Reform Act changes are nothing to brush under the table. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), pharmaceutical member companies invested $43 billion to research and develop new medicines last year. And it's no secret that Big Pharma depends on full patent periods (17 to 20 years) to make a profit on their drugs, considering that discovery and development can easily take 10 to 15 years and cost an average of $1 billion, according to PhRMA. In fact, according to an August report by World Growth, a nonprofit nongovernmental organization, two-thirds of the value of America's large businesses reside in intellectual property, especially patents and trademarks.

Part of the reason for the proposed changes is to reduce the burden on USPTO, which reviews 450,000 national patent applications each year. The office hired an additional 1,000 examiners during the past two years, according to a Sept. 3 Reuters article, but patents can still take as long as six years to be processed.

At press time, the Patent Reform Act of 2007 was heading to the Senate for review, with revisions expected. –Angie Drakulich

LABELING

The US Food and Drug Administration approved updated labeling for "Coumadin," a common blood-thinning drug, that explains that patients' genetic composition may influence their response to the drug. On Aug. 16, the agency directed manufacturers of warfarin, the active ingredient in Coumadin, to add similar information to their products' labeling.

The labeling change encourages healthcare providers to use genetic tests before prescribing warfarin. The agency believes the tests would help physicians better determine the reasonable warfarin dose for individual patients, optimize the use of warfarin, and lower the risk of bleeding complications from the drug. The labeling changes result from an analysis of recent studies that found that certain genetic variations influence the way people respond to the drug.

"Today's approved labeling change is one step in our commitment to personalized medicine. By using modern science to get the right drug in the right dose for the right patient, FDA will further enhance the safety and effectiveness of the medicines Americans depend on," FDA Commissioner Andrew C. von Eschenbach said in an agency press release. The agency's personalized medicine initiative is based on pharmacogenomics, the science that predicts a response to drugs based upon a person's genetic makeup. –Erik Greb

STRATEGY

Working Group Releases Strategy to Ensure Import Safety

The US Food and Drug Administration's Interagency Working Group on Import Safety released a Strategic Framework on Sept. 10, based on a cost-effective, risk-based approach for ensuring the safety of products exported to the United States. Instead of assessing products at the border, the strategy recommends examining products' entire life cycles. The strategy requires cooperation with foreign manufacturers to identify and mitigate risk during crucial parts of the production and distribution process.

The Strategic Framework follows several months of scandals involving contaminated products manufactured in China. The problems prompted the US government to send a fact-finding team to China to address concerns about food and drug safety.

The Working Group aims to achieve continuous improvement in import safety by using the following six building blocks:

• Advance a common vision

• Increase accountability, enforcement, and deterrence

• Focus on risk over the life cycle of an imported product

• Build interoperable systems

• Foster a culture of collaboration

• Promote technological innovation and new science.

The building blocks recommend changes to the oversight process, including shared goals among federal agencies that promote import safety, better communication between parties in the global supply chain, and collaboration between government and industry.

The Framework says FDA has made 34 confidential arrangements with agencies in 17 countries to share approval, inspection, adverse-event, and emergency information about products manufactured in a partners' territories. FDA currently has more than two such exchanges each day.

In a public statement, FDA Commissioner Andrew von Eschenbach strongly endorsed the Strategic Framework, commending Health and Human Services Secretary Michael Leavitt for leading the Working Group and developing the Framework. President Bush established the Working Group in July to develop better ways to work with importers, manufacturers, and other governments to ensure the safety of imported products. -Erik Greb

PHARMACEUTICAL MARKETING

FDA Proposes Study of DTC Advertising

The US Food and Drug Administration is seeking public comments on a study designed to investigate the impact of visual distraction and the interplay of different sensory modalities (e.g., verbal, visual) used to present risk and benefit information during a television prescription-drug advertisement. Data from this study will provide useful information to help improve how broadcast ads present a prescription drug's risks and benefits. Notice of the study was published in Federal Register 72 (162), 47051–47053 on Aug. 22.

The purpose of the proposed study is, in part, to determine whether the use of competing, compelling visual information about potential drug benefits interferes with viewers' processing and comprehension of risk information about drugs in direct-to-consumer (DTC) advertising or with their cognitive representations of the drugs, according to the notice. "Positive visual images could influence the processing of risk-related information and the final representation of the advertised drug in multiple ways," says the notice.

Both healthcare providers and consumers have expressed concerns to FDA about the effectiveness of its regulation of manufacturers' DTC prescription-drug advertising, especially as it relates to assuring balanced communication of risks compared with benefits, specified the notice. One characteristic of DTC television broadcast ads is the use of compelling visuals. Many assert that the visuals present during the product-risk presentation are virtually always positive in tone and often depict product benefits. A consistently raised question is whether advertising visuals of benefits interferes with consumers' understanding and processing of the risk information in the ad's audio or text. Comments are due Oct. 22, 2007. -Patricia Van Arnum

COMPANY NOTE

In an Aug. 31 press release, Boehringer Ingelheim (Ingelheim, Germany) decided to voluntarily withdraw its "Silomat" drug, which contains clobutinol hydrochloride, in all countries where it is available. The company advised consumers to stop using the drug. Boehringer recently analyzed new findings from a clinical study it performed in healthy subjects that suggest that clobutinol hydrochloride carries the potential risk of cardiac arrhythmia. Although the risk might be low, the company decided to recall the drug in the interest of patients' safety. Boehringer described the recall as a precautionary measure and noted that therapeutic alternatives to the product are available.

NEW DRAFT GUIDANCE

FDA Issues Draft Guidance for Pharmacogenomic Data Submissions

The US Food and Drug Administration issued a draft guidance, Pharmacogenomic Data Submissions Companion Guidance, on Aug. 29, to be used as a companion to an earlier guidance, Pharmacogenomic Data Submissions, which was issued in March 2005. The draft guidance explains the procedure for voluntary genomic data submissions and marketing submissions containing genomics data. These submissions can be part of investigational new drug applications, new drug applications, or biologics license applications. The recommendations are intended to facilitate progress in pharmacogenomics and pharmacogenomic data use in drug development. The draft guidance addresses methodological issues that should be considered when submitting gene expression data from microarrays, including:

• RNA isolation, handling, and characterization

• Labeling systems

• Hybridizations for microarrays

• Fluorescence reader settings for microarrays

• Differentially expressed genes

• Genotyping

• Proficiency testing.

Comments about the draft guidance are due Nov. 27, 2007. -Patricia Van Arnum

BIOLOGICS

FDA Finalizes Guidance on Biologics Manufacturing Using Spore-Formers Microogranisms

The US Food and Drug Administration issued a final guidance, Manufacturing Biological Intermediates and Biological Drug Substances Using Spore-Forming Microorganisms, on Sept. 7, which provides recommendations that allow for greater flexibility when manufacturing biological products with spore-formers. The guidance finalizes a draft guidance issued Feb. 24, 2005, and addresses revised regulations that went into effect June 1, 2004.

Under the revised regulation, FDA no longer requires the use of permanently dedicated buildings and equipment for spore-formers, if certain controls and precautions are applied. "We recognize that advances in facility, system, equipment design, testing, and sterilization technologies have increased the ability of manufacturers to control and analyze the manufacture of biological products," FDA specified in the guidance. "[We] found that manufacturers could evaluate aspects of a biological product's safety and purity with testing. The use of appropriate procedural controls, validated processes, and enhanced testing capability provides the manufacturer with a degree of confidence that their biological product achieves the expected levels of safety and purity. Areas of special concern, such as process containment, contamination with pathogenic and/or toxic agents, sterilization, and disinfection can be addressed using currently available procedures and processes." FDA also said that it encourages alternatives to spore-forming microorganisms for producing future biological products. These alternatives include using sporulation-deficient strains or recombinant proteins expressed in nonspore-forming microorganisms.

For the purposes of the guidance, "spore-forming microorganism" or "spore-former" includes both the spore and vegetative forms of the organism. The guidance applies to the manufacturing of biological intermediates and biological drug substances. -Patricia Van Arnum

FACILITIES

Amgen to Cut Staff, Close Facilities

Amgen (Thousand Oaks, CA) announced on Aug. 15 that it would cut 2200–2600 jobs as part of a plan to increase operational efficiencies. The job cuts are the first ever for the company and will result in a 12–14% staff reduction. Amgen's plan also includes closing certain production operations and reducing planned capital expenditures by approximately $1.9 billion during 2007–2008.

"Recent changes in coverage rules and adjustments to Amgen's FDA-approved labels for 'Epogen' and 'Aranesp' have and will adversely affect Amgen's revenue," explained Chairman and Chief Executive Officer Kevin Sharer in a release.

The company also changed its adjusted earnings per share guidance for 2007 from $4.28 to $4.13–4.23, excluding restructuring charges. The change results from low sales of Amgen's "Aranesp" drug.

Amgen expects its initiatives to be completed by 2008 and to generate $1.0–1.3 billion in pretax savings. The cumulative pretax restructuring charges associated with these changes are expected to be $600–700 million in 2007 and 2008, including $289 million for asset impairment and related costs reported in the second quarter of 2008.

The company said it would implement the initiatives in a way that maintains its responsiveness to customers and patients. Amgen also stated it would treat its staff fairly and minimize the workforce reduction's impact on its employees by using attrition, hiring freezes, and a voluntary transition program. Affected staff will receive career counseling assistance in securing new employment. -Erik Greb

DRUG DELIVERY

Protein-Coated Nanowires Developed for Drug Delivery

A team of researchers from the University of Idaho and Seoul National University have designed a potential drug delivery system by coating silica nanowires with the protein fibronectin. Their study, released Sept. 4 in Moscow, Idaho, found that the protein coating enabled the nanowires to enter cultured human cells and deliver a lethal dose of toxin (called StxA1).

The nanowires reportedly could be coated with antibodies or other materials to deliver low doses of drug to targeted cells without compromising healthy cells.

At press time, the study was scheduled for publication in the Sept. 12 issue of Nano Letters by the American Chemical Society. -Maribel Rios