FDA panel recommends approval of combined HC2 HPV and PAP test for primary screening over age 30

Digene Corporation of Gaithersburg, Md., has announced that the U.S. Food and Drug Administration’s (FDA) Microbiology Devices Panel recommended approval, with conditions, of its Pre-Market Approval Supplement (PMAS) application for the DNA Pap (HPV testing in conjunction with the Pap test). FDA approval would enable Digene to market its Hybrid Capture 2 HPV DNA Test, in conjunction with the Pap test, as a primary screening test for cervical cancer and its precursors in women 30 years of age and older.

The conditions recommended are that Digene provide specific recommendations for using the combined test in clinical management, and that the company furnish the FDA with demonstration of the positive clinical outcomes that the DNA Pap provides. The panel also recommended that Digene provide educational data to laboratories and physicians explaining the meaning of a positive HPV test. The panel further recommended that following receipt of approval, Digene should conduct post-marketing research to confirm the added clinical benefit of the DNA Pap. Digene anticipates providing the requested information and receiving FDA approval during calendar 2002.

Evan Jones, Digene’s Chairman and Chief Executive Officer, commented, “We believe the combination of our HC2 HPV test and the Pap test, called the DNA Pap, will enable physicians to better determine the risk of cervical cancer in women age 30 and older and provide appropriate follow-up care, while also reducing patient anxiety associated with repeat Pap testing and the need for unnecessary invasive procedures. Ultimately, we believe such earlier detection can help reduce deaths from cervical cancer, which is highly treatable when detected early.”In the United States, approximately 12,900 women are diagnosed with cervical cancer, with approximately 4,400 deaths each year. Worldwide, cervical cancer affects over 400,000 women each year and, after breast cancer, is the second most common malignancy found in women.

PAPStat assay assures adequacy of collected sample during office visit

Invirion Inc., of Frankfort, Mich., has announced the introduction of its patented PAPStat, a specimen adequacy assay that enables physicians to determine, at the point of care, whether or not an adequate patient sample has been collected with the liquid-based Pap test.

Liquid-based Pap tests currently account for 50 percent of the Paps performed in the U.S., a proportion that is expected to rise in the coming years. Currently, 50 million women in the U.S. receive a Pap test. Of these, anywhere from five to twenty five percent will have a Pap result read as “unsatisfactory” or “satisfactory but limited”. Many of these results are due to too few cells or to the inability to identify endocervical cells within the sample. Tests with “unsatisfactory” samples must be repeated, while those with “satisfactory but limited” samples are not always re-done, but threaten missed disease for lack of endocervical cells.

Invirion Inc. developed PAPStat to enable physicians to determine, at the time of sampling, whether a Pap test has an adequate number of cells for examination by a cytopathologist. Invirion CEO, Dr. Bruce Patterson, explained, “Up to 4 million women each year will learn, following a visit to their clinician, that their Pap sample was not of the best quality. With PAPStat, women will know before they leave the doctor’s office.”

This can save women, and the healthcare industry, the time and money currently spent on returning to a clinician for a repeat Pap. In addition, the immediate quantification of endocervical cells will improve the rate of discovery of glandular cell abnormalities. “The PAPStat potentially eliminates the only problem noted with the liquid-based Pap test, and that is the increase that some have noted in ‘satisfactory but limited’ results due to a lack of identifiable endocervical cells.” With this assay, the number of polymorphonuclear neutrophils (PMNs), endocervical (columnar) cells, ectocervical (squamous) cells and debris in liquid-based cervical cytology samples are quantified in less than 3 minutes. According to Dr. Patterson, “The number of women with glandular cell abnormalities, in particular adenocarcinoma in situ, is increasing. Currently, there is concern that Pap tests lacking endocervical cells may not be as successful in detecting these glandular lesions.”

Protein patterns in blood may identify stage I ovarian cancer

Scientists from the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) reported in The Lancet that they were able to identify patterns of proteins in blood serum that indicate the presence of ovarian cancer. The scientists used a sophisticated artificial intelligence computer program to search for patterns in samples that look like identified patterns from cancer patients. The researchers hope this diagnostic concept will be applicable to any type of disease.

This testing method can be completed in 30 minutes with a blood sample from a finger stick. Researchers used mass spectroscopy to differentiate between serum samples taken from patients with ovarian cancer and those from unaffected individuals. “The idea that rather than a single biomarker, an entire pattern of proteins contains important diagnostic information, is an exciting new paradigm,” said J. Carl Barrett, Ph.D., director of the NCI’s Center for Cancer Research, which oversees the Institute’s proteomics program. This testing method also unites proteomics with artificial intelligence, two fields that are emerging in importance. The researchers correctly identified 50 out of 50 cancers and 63 of 66 non-cancer samples.

An important finding was the ability to correctly identify, in a small sample of patients, all stage I ovarian cancer cases. Currently, more than 80 percent of ovarian cancer patients are diagnosed at a late clinical stage and have a 20 percent or less chance of survival at five years. In contrast, women diagnosed with early-stage disease have an excellent prognosis, with over 95 percent alive at five years after diagnosis. The results of this study indicate that proteomic technology may help clinicians diagnose the disease much earlier than current methods.

The investigators hope that combining the proteomic approach with other methods of ovarian cancer diagnosis, such as ultrasound, can further improve the accuracy of testing. As with mammograms, the false positive rate is of concern. This may be addressed by a combination of biomarker and imaging techniques.

Two major hospital buying groups accused of making tainted product decisions

As part of an ongoing series of articles in the New York Times on “Medicine’s Middleman,” a March 4, 2002 article reports on conflict-of-interest issues regarding Premier Inc. of San Diego, Calif. and Novation of Irving, Texas, buying groups that negotiated contracts for an estimated $34 billion in hospital supplies in 2001. The two groups act as middlemen for approximately half of the nation’s non-profit hospitals.

Questions are raised as to whether the Group Purchasing Organization (GPO) mission to find the best medical products at lower prices is being compromised by the fact that these groups are financed by the companies that sell the products, rather than the hospitals that buy them. GPOs, which are exempt from federal antikickback laws, receive a fee from manufacturers for purchases made by member hospitals. According to the article, at Novation, 30 percent of contracts include fees that exceed 3 percent of product sales, and some negotiated fees may be in the teens. Premier does not accept fees over 3 percent, but the company and some of its officials have received stocks or options from companies with which they have negotiated contracts. Premier has also invested in a number of medical suppliers. The New York Times reporters cite these financial ties to question the objectivity with which Premier and Novation evaluate products to recommend for purchase by their member hospitals.

As examples in the article demonstrate, some manufacturers complain of competitive disadvantage, claiming that contracts between hospitals and these organizations effectively block entry into that market segment in favor of competitors who generate more financial reward to the buying group. Products may be blocked from hospitals, which can be charged penalties for buying outside the group. The article cites an example in which an expert panel was convened to review a product, which it unanimously recommended as a breakthrough technology. Nonetheless, the better product was not recommended by Premier, who reported to its contracting committee that the panel had found only a “theoretical breakthrough potential,” prompting one committee member to ask, “Was it just going through the motions to say you had an expert panel so then you can do what you want?”

Hospitals receive an annual check from their buying group as a portion of the fees manufacturers have paid. This welcome check may forestall some complaints. In addition, for hospitals that have reduced their purchasing staffs, the buying groups represent an important way to find products and negotiate pricing. While other buying groups also accept manufacturers fees, this article points out that they may return a higher proportion of their revenue to their member hospitals, and may also avoid investment in companies whose products they are supposed to evaluate objectively.

New method promises to extend shelf life of blood platelets

Blood Cell Storage, Inc. (BCSI), a spin-off company of BioPore, Inc., of State College, Pa., has patented a new container technology, which the company claims will increase the useful life of stored platelets by at least 20 percent.

The new technology utilizes gated-pore membranes in containers that are initially impervious to liquids and can contain cell suspensions. According to BCSI, the novel feature of a gated-pore membrane is that, under defined conditions, the “gates” in the membrane open to provide small pores of pre-selected diameter, allowing controlled transfer of molecules across the membrane while cells are retained in the container without dilution.

In conventional platelet storage bags, cells are placed in the container with nutrients for the period of storage. Gas exchange may occur through the bag walls, but toxic wastes accumulate as nutrients are depleted. Cell aggregation is disturbed by rocking of the bag. In contrast, the gated-pore system approach uses an upward flow of fresh nutrients through the gated-pore membrane system to satisfy nutrient needs, remove toxins and suspend cells within the container. Platelets are placed in the container and by virtue of gated-pore technology are kept in suspension, rather than allowed to settle down on the plastic bag. Further, the medium around the cells is refreshed to maintain desired concentrations of oxygen, nutrients, and metabolites.

Successful implementation of these technologies should prolong the useful life of platelets. The current FDA mandated five-day storage period results in disposal of up to 15 percent of platelets collected.

Ortho-Clinical Diagnostics acquires Micro Typing Systems

Ortho-Clinical Diagnostics, Inc. of Raritan, N.J. (OCD), a Johnson & Johnson company, has acquired Micro Typing Systems, Inc. of Pompano Beach, Fla. (MTS), a leading manufacturer of blood bank serology tests for the North American market. MTS, now a wholly owned subsidiary of Ortho-Clinical Diagnostics, manufactures the ID-Micro Typing System (ID-MTS) used in hospitals and donor centers to help to ensure safe and effective blood transfusions.

OCD, a leader in the development and marketing of instrumentation and reagent systems for transfusion medicine, has sold the Ortho BioVue System internationally and has been the exclusive distributor of MTS Gel Technology in North America for over six years. These two technologies enable customers to realize full automation for blood bank laboratories.

Catherine M. Burzik, President, Ortho-Clinical Diagnostics, Inc., said, “OCD has a 60-year heritage in immunohematology and transfusion medicine. We are committed to playing a central role in helping to ensure the safety and availability of the nation’s blood supply. Acquiring MTS positions OCD to expand new product offerings more rapidly in the important North American market, where hospitals and donor centers need to transition to more efficient and cost-effective automation platforms.”

OCD is one of two remaining manufacturers providing blood banking serology products and services to North American blood banks. The company recently spearheaded a program in the United States to raise awareness of the severely fragile state of the nation’s blood supply. The effort led to the passage of the Benefits Improvement and Protection Act in December 2000. This act restored $11.5 billion in Medicare funding and includes additional blood reimbursement provisions. Burzik said that the company would continue efforts to bring long overdue recognition to the state of the nation’s blood supply with policymakers and in industry councils.

Fujirebio Diagnostics will market microtiter cancer assays outside the U.S.

Fujirebio Diagnostics, Inc. (FDI), of Malvern, Pa., will begin marketing a new line of six enzyme immunoassays (EIAs) in microtiter format for the detection of life-threatening cancers. The new EIAs will be based on the same antibodies utilized in the Fujirebio Diagnostics radioimmunoassays (RIA), but without reliance on radioactive elements. The assays will be launched in Southeast Asia in the first quarter of 2002, and later in Latin America, the Middle East, and Eastern Europe.

The new EIAs will target ovarian cancer (CA 125II), breast cancer (CA15-3), pancreatic cancer (CA19-9), gastric cancer (CA72-4), and prostate cancer (Total PSA and Free PSA). The markers will be available in 96-well microtiter format, utilizing coated microwell strips, to provide laboratories with manual or automated options for greater flexibility.

“The additions to our product line will provide the medical community with more flexibility for choosing between assay formats,” said Aris Petropoulos, president and chief operating officer of FDI. He noted that the EIA assays provide the same important clinical attributes associated with FDI’s RIA product line, but the new assays extend cancer detection capabilities to laboratories that in the past could not use RIAs. “In many parts of the world, RIAs for these life-threatening cancers are not available because their radioactive elements cannot be shipped or because local laboratories cannot run them,” Mr. Petropoulos said. “By offering the microtiter format, we are making early detection of recurrent cancer available to people around the world, even in remote localities.”

New blood test to aid heart attack diagnosis receives approval in Europe

A new blood test to detect the early signs of a heart attack is now approved for sale by the Conformité Européen (CE). The Albumin Cobalt Binding (ACB) test, developed by Ischemia Technologies of Denver, Colo., detects a protein in blood known as Ischemia Modified Albumin (IMA). This test will be marketed for use in conjunction with the cardiac marker troponin to aid in the diagnosis of heart attack in patients presenting to emergency departments with chest pain.

“With CE marking, we have started selling the ACB Test to European hospitals and physicians interested in improving the speed and accuracy of managing patients with chest pain,” state Peter Crosby, president and CEO of Ischemia Technologies. “A multicenter clinical study showed that the combination of IMA and cardiac troponin identified 50 percent of all heart attack patients at the first blood draw, compared to 20 percent of such patients using cardiac troponin alone.”

Clinical studies have shown that IMA is an early rising marker in patients with acute myocardial infarction, and is elevated during cardiac ischemia. Cardiac ischemia is an imbalance between oxygen supply and demand to the heart, usually as a result of restricted blood flow from occluded coronary arteries. Each year, about 6 million people present at U.S. emergency departments with symptoms of acute cardiac ischemia, and of those, approximately one-fifth are ultimately determined to have the condition.